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1. Treatment patterns in patients with newly diagnosed COPD in the USA

Author

Antonio Anzueto, Sheri Rogers, Bonnie Donato, Beverly Jones, Kushal Modi, Abisola Olopoenia, and Robert Wise

Subjects
COPD, Exacerbations, Newly diagnosed, Treatment patterns, Maintenance therapy, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Prompt and effective management with maintenance therapy (single or dual bronchodilator therapy) is recommended after the initial diagnosis of chronic obstructive pulmonary disease (COPD) to maintain lung function and prevent exacerbations. Contrary to guideline-based recommendations, most patients are not prescribed maintenance treatment at initial diagnosis. The current study assessed the pharmacologic treatment patterns and outcomes of newly diagnosed patients with COPD in the USA. Methods This retrospective, noninterventional study used de-identified data from the Inovalon Insights’ database (Commercial, Medicaid Managed Care, and Medicare Advantage–insured individuals) between January 1, 2015, and December 31, 2021. The “patient journey” from initial diagnosis was followed over a 4-year period. The primary outcome measure was the number of moderate or severe exacerbations. Secondary outcome measures included the cumulative incidence of exacerbations, mean cumulative count of moderate and severe exacerbations, rates of moderate and severe exacerbations in patients who remained untreated after diagnosis in 12-month time periods for 4 years, sociodemographic and clinical characteristics, and pharmacologic treatment patterns. Results The cohort consisted of 238,158 newly diagnosed patients with COPD (female [52.9%]; mean age 63.8 years). The majority of patients with COPD had Medicaid as their primary insurance (46.2%). Overall, during the 4-year follow-up period, 32.9% of the patients had at least one moderate or severe exacerbation, and 25.8% and 13.8% experienced moderate and severe exacerbations, respectively. At diagnosis, 86.2% of the patients were untreated and most remained untreated by the end of the follow-up (63.8%). Most patients (62.0%) received long-acting beta-agonist (LABA)/inhaled corticosteroids (ICS) as their initial treatment at diagnosis, and LABA/ICS continued to be the most common initial treatment during the 4-year period (64.0% at year 1; 58.0% at year 4). Conclusions Most patients with COPD were not treated at initial diagnosis and remained untreated during follow-up. Our data highlight a lack of adherence to recommendations for clinical practice.

Published
2024
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2. Long-acting muscarinic antagonist and long-acting β-agonist combination for the treatment of maintenance therapy–naïve patients with chronic obstructive pulmonary disease: a narrative review

Author

Roland Buhl, Marc Miravitlles, Antonio Anzueto, and Stephen Brunton

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Faster lung function impairment occurs earlier in the disease, particularly in mild-to-moderate COPD, highlighting the need for early and effective targeted interventions. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2024 report recommends initial pharmacologic treatment with a long-acting muscarinic antagonist (LAMA) and long-acting β 2 -agonist (LABA) combination in group B (0 or 1 moderate exacerbation not leading to hospitalization, modified Medical Research Council score of ⩾2, and COPD Assessment Test™ score of ⩾10) and E (⩾2 moderate exacerbations or ⩾1 exacerbation leading to hospitalization and blood eosinophil count

Published
2024
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3. Delphi Consensus on Clinical Applications of GOLD 2023 Recommendations in COPD Management: How Aligned are Recommendations with Clinical Practice?

Author

Antonio Anzueto, Mark Cohen, Andres L. Echazarreta, Gehan Elassal, Irma Godoy, Rafael Paramo, Abdullah Sayiner, Carlos A. Torres-Duque, Sudeep Acharya, Bhumika Aggarwal, Hakan Erkus, and Gur Levy

Subjects
Clinical practice, COPD, Delphi procedure, GOLD 2023, Diseases of the respiratory system, RC705-779
Abstract

Abstract Introduction The objective of this Delphi study was to understand and assess the level of consensus among respiratory experts on the clinical application of GOLD 2023 recommendations in management of patients with chronic obstructive pulmonary disease (COPD). Methods The study comprised two online surveys and a participant meeting with 34 respiratory experts from 16 countries. Responses of 73 questions were recorded using a Likert scale ranging from 0 (disagreement) to 9 (agreement). The consensus threshold was 75%. Results Survey 1 and survey 2 had 34 and 32 participants, respectively; and 25 attended the participant meeting. Consensus was reached on survey 1: 28/42; survey 2: 18/30 close-ended questions. A consensus was reached on the clinical relevance of most updates in definitions and diagnosis of COPD. Mixed results for the treatment recommendations by GOLD were noted: 74% agreed with the recommendation to initiate treatment with dual bronchodilators for group E patients; 63% agreed for including inhaled corticosteroids (ICS)/long-acting β2 agonist(LABA)/ Long-acting muscarinic receptor antagonists (LAMA) as a treatment option for GOLD B patients. Also, consensus lacked on removing ICS + LABA as an initial therapeutic option, in countries with challenges in access to other treatment option;. 88% agreed that they use GOLD recommendations in their daily clinical practice. Conclusions This Delphi study demonstrated a high level of consensus regarding key concepts of GOLD 2023 report, with most participants favoring recent updates in definitions, diagnosis, management, and prevention of COPD. More evidence on the etiotype based management and treatment options for group B and E are required which could further strengthen clinical application of the GOLD report.

Published
2023
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4. Returning incidentally discovered Hepatitis C RNA-seq results to COPDGene study participants

Author

Edwin K. Silverman, Arthur Y. Kim, Barry J. Make, Elizabeth A. Regan, Jarrett D. Morrow, Craig P. Hersh, James O’Brien, James D. Crapo, Nadia N. Hansel, Gerard Criner, Eric L. Flenaugh, Douglas Conrad, Richard Casaburi, Russell P. Bowler, Nicola A. Hanania, R. Graham Barr, Surya P. Bhatt, Frank C. Sciurba, Antonio Anzueto, MeiLan K. Han, Charlene E. McEvoy, Alejandro P. Comellas, Dawn L. DeMeo, Richard Rosiello, Jeffrey L. Curtis, Tricia Uchida, Carla Wilson, and P. Pearl O’Rourke

Subjects
Medicine, Genetics, QH426-470
Abstract

Abstract The consequences of returning infectious pathogen test results identified incidentally in research studies have not been well-studied. Concerns include identification of an important health issue for individuals, accuracy of research test results, public health impact, potential emotional distress for participants, and need for IRB permissions. Blood RNA-sequencing analysis for non-human RNA in 3984 participants from the COPDGene study identified 228 participants with evidence suggestive for hepatitis C virus (HCV) infection. We hypothesized that incidentally discovered HCV results could be effectively returned to COPDGene participants with attention to the identified concerns. In conjunction with a COPDGene Participant Advisory Panel, we developed and obtained IRB approval for a process of returning HCV research results and an HCV Follow-Up Study questionnaire to capture information about previous HCV diagnosis and treatment information and participant reactions to return of HCV results. During phone calls following the initial HCV notification letter, 84 of 124 participants who could be contacted (67.7%) volunteered that they had been previously diagnosed with HCV infection. Thirty-one of these 124 COPDGene participants were enrolled in the HCV Follow-Up Study. Five of the 31 HCV Follow-Up Study participants did not report a previous diagnosis of HCV. For four of these participants, subsequent clinical HCV testing confirmed HCV infection. Thus, 30/31 Follow-Up Study participants had confirmed HCV diagnoses, supporting the accuracy of the HCV research test results. However, the limited number of participants in the Follow-Up Study precludes an accurate assessment of the false-positive and false-negative rates of the research RNA sequencing evidence for HCV. Most HCV Follow-Up Study participants (29/31) were supportive of returning HCV research results, and most participants found the process for returning HCV results to be informative and not upsetting. Newly diagnosed participants were more likely to be pleased to learn about a potentially curable infection (p = 0.027) and showed a trend toward being more frightened by the potential health risks of HCV (p = 0.11). We conclude that HCV results identified incidentally during transcriptomic research studies can be successfully returned to research study participants with a carefully designed process.

Published
2023
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5. Use of thiols and implications for the use of inhaled corticosteroids in the presence of oxidative stress in COPD

Author

Mario Cazzola, Clive P. Page, Jadwiga A. Wedzicha, Bartolome R. Celli, Antonio Anzueto, and Maria Gabriella Matera

Subjects
Antioxidant, Chronic obstructive pulmonary disease, Glutathione, Inhaled corticosteroids, Inflammation, Oxidative stress, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Oxidative stress and persistent airway inflammation are thought to be important contributors to the development of chronic obstructive pulmonary disease (COPD). This review summarizes the evidence for targeting oxidative stress and inflammation in patients with COPD with mucolytic/antioxidant thiols and inhaled corticosteroids (ICS), either alone or in combination. Main body Oxidative stress is increased in COPD, particularly during acute exacerbations. It can be triggered by oxidant air pollutants and cigarette smoke and/or by endogenous reactive oxygen species (ROS) released from mitochondria and activated inflammatory, immune and epithelial cells in the airways, together with a reduction in endogenous antioxidants such as glutathione (GSH). Oxidative stress also drives chronic inflammation and disease progression in the airways by activating intracellular signalling pathways and the release of further inflammatory mediators. ICS are anti-inflammatory agents currently recommended for use with long-acting bronchodilators to prevent exacerbations in patients with moderate-to-severe COPD, especially those with eosinophilic airway inflammation. However, corticosteroids can also increase oxidative stress, which may in turn reduce corticosteroid sensitivity in patients by several mechanisms. Thiol-based agents such as erdosteine, N-acetyl L-cysteine (NAC) and S-carboxymethylcysteine (S-CMC) are mucolytic agents that also act as antioxidants. These agents may reduce oxidative stress directly through the free sulfhydryl groups, serving as a source of reducing equivalents and indirectly though intracellular GSH replenishment. Few studies have compared the effects of corticosteroids and thiol agents on oxidative stress, but there is some evidence for greater antioxidant effects when they are administered together. The current Global Initiative for Chronic Obstructive Lung Disease (GOLD) report supports treatment with antioxidants (erdosteine, NAC, S-CMC) in addition to standard-of-care therapy as they have been demonstrated to reduce COPD exacerbations. However, such studies have demonstrated that NAC and S-CMC reduced the exacerbation risk only in patients not treated with ICS, whereas erdosteine reduced COPD exacerbations irrespective of concomitant ICS use suggesting that erdosteine has additional pharmacological actions to ICS. Conclusions Further clinical trials of antioxidant agents with and without ICS are needed to better understand the place of thiol-based drugs in the treatment of patients with COPD.

Published
2023
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6. Immune resilience despite inflammatory stress promotes longevity and favorable health outcomes including resistance to infection

Author

Sunil K. Ahuja, Muthu Saravanan Manoharan, Grace C. Lee, Lyle R. McKinnon, Justin A. Meunier, Maristella Steri, Nathan Harper, Edoardo Fiorillo, Alisha M. Smith, Marcos I. Restrepo, Anne P. Branum, Matthew J. Bottomley, Valeria Orrù, Fabio Jimenez, Andrew Carrillo, Lavanya Pandranki, Caitlyn A. Winter, Lauryn A. Winter, Alvaro A. Gaitan, Alvaro G. Moreira, Elizabeth A. Walter, Guido Silvestri, Christopher L. King, Yong-Tang Zheng, Hong-Yi Zheng, Joshua Kimani, T. Blake Ball, Francis A. Plummer, Keith R. Fowke, Paul N. Harden, Kathryn J. Wood, Martin T. Ferris, Jennifer M. Lund, Mark T. Heise, Nigel Garrett, Kristen R. Canady, Salim S. Abdool Karim, Susan J. Little, Sara Gianella, Davey M. Smith, Scott Letendre, Douglas D. Richman, Francesco Cucca, Hanh Trinh, Sandra Sanchez-Reilly, Joan M. Hecht, Jose A. Cadena Zuluaga, Antonio Anzueto, Jacqueline A. Pugh, South Texas Veterans Health Care System COVID-19 team, Brian K. Agan, Robert Root-Bernstein, Robert A. Clark, Jason F. Okulicz, and Weijing He

Subjects
Science
Abstract

Abstract Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammation in infectious diseases as well as other causes of inflammatory stress. We gauge IR levels with two distinct peripheral blood metrics that quantify the balance between (i) CD8+ and CD4+ T-cell levels and (ii) gene expression signatures tracking longevity-associated immunocompetence and mortality-associated inflammation. Profiles of IR metrics in ~48,500 individuals collectively indicate that some persons resist degradation of IR both during aging and when challenged with varied inflammatory stressors. With this resistance, preservation of optimal IR tracked (i) a lower risk of HIV acquisition, AIDS development, symptomatic influenza infection, and recurrent skin cancer; (ii) survival during COVID-19 and sepsis; and (iii) longevity. IR degradation is potentially reversible by decreasing inflammatory stress. Overall, we show that optimal IR is a trait observed across the age spectrum, more common in females, and aligned with a specific immunocompetence-inflammation balance linked to favorable immunity-dependent health outcomes. IR metrics and mechanisms have utility both as biomarkers for measuring immune health and for improving health outcomes.

Published
2023
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7. Nine controversial questions about augmentation therapy for alpha-1 antitrypsin deficiency: a viewpoint

Author

Marc Miravitlles, Antonio Anzueto, and Miriam Barrecheguren

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Augmentation therapy with intravenous alpha-1 antitrypsin is the only specific treatment for alpha-1 antitrypsin deficiency (AATD)-associated emphysema. This treatment has been available and remained basically unchanged for more than 35 years, but many questions persist regarding its indications, regimen of administration and efficacy. Because AATD is a rare disease, it has not been possible to conduct randomised, placebo-controlled trials that are adequately powered for the usual outcomes analysed in non-AATD-related COPD, such as lung function decline, exacerbations, symptoms or quality of life. New outcomes such as lung densitometry measured by computed tomography are more sensitive for identifying emphysema progression but are not widely accepted by regulatory agencies. In addition, clinical manifestations, severity and the natural history of lung disease associated with AATD are very heterogeneous, which means that individual prediction of prognosis is challenging. Therefore, the indication for augmentation is sometimes a dilemma between initiating treatment in individuals who may not develop significant lung disease or in whom disease will not progress and delaying it in patients who will otherwise rapidly and irreversibly progress. Other areas of debate are the possible indication for augmentation in patients with severe AATD and respiratory diseases other than emphysema, such as bronchiectasis or asthma, and the use of therapy after lung transplant in AATD patients. All these uncertainties imply that the indication for treatment must be personalised in expert reference centres after in-depth discussion of the pros and cons of augmentation with the patient.

Published
2023
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8. Machine learning predicts mortality based on analysis of ventilation parameters of critically ill patients: multi-centre validation

Author

Behrooz Mamandipoor, Fernando Frutos-Vivar, Oscar Peñuelas, Richard Rezar, Konstantinos Raymondos, Alfonso Muriel, Bin Du, Arnaud W. Thille, Fernando Ríos, Marco González, Lorenzo del-Sorbo, Maria del Carmen Marín, Bruno Valle Pinheiro, Marco Antonio Soares, Nicolas Nin, Salvatore M. Maggiore, Andrew Bersten, Malte Kelm, Raphael Romano Bruno, Pravin Amin, Nahit Cakar, Gee Young Suh, Fekri Abroug, Manuel Jibaja, Dimitros Matamis, Amine Ali Zeggwagh, Yuda Sutherasan, Antonio Anzueto, Bernhard Wernly, Andrés Esteban, Christian Jung, and Venet Osmani

Subjects
Critical care medicine, Machine learning, ICU, Risk stratification, Mechanical ventilation, Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Abstract Background Mechanical Ventilation (MV) is a complex and central treatment process in the care of critically ill patients. It influences acid–base balance and can also cause prognostically relevant biotrauma by generating forces and liberating reactive oxygen species, negatively affecting outcomes. In this work we evaluate the use of a Recurrent Neural Network (RNN) modelling to predict outcomes of mechanically ventilated patients, using standard mechanical ventilation parameters. Methods We performed our analysis on VENTILA dataset, an observational, prospective, international, multi-centre study, performed to investigate the effect of baseline characteristics and management changes over time on the all-cause mortality rate in mechanically ventilated patients in ICU. Our cohort includes 12,596 adult patients older than 18, associated with 12,755 distinct admissions in ICUs across 37 countries and receiving invasive and non-invasive mechanical ventilation. We carry out four different analysis. Initially we select typical mechanical ventilation parameters and evaluate the machine learning model on both, the overall cohort and a subgroup of patients admitted with respiratory disorders. Furthermore, we carry out sensitivity analysis to evaluate whether inclusion of variables related to the function of other organs, improve the predictive performance of the model for both the overall cohort as well as the subgroup of patients with respiratory disorders. Results Predictive performance of RNN-based model was higher with Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) of 0.72 (± 0.01) and Average Precision (AP) of 0.57 (± 0.01) in comparison to RF and LR for the overall patient dataset. Higher predictive performance was recorded in the subgroup of patients admitted with respiratory disorders with AUC of 0.75 (± 0.02) and AP of 0.65 (± 0.03). Inclusion of function of other organs further improved the performance to AUC of 0.79 (± 0.01) and AP 0.68 (± 0.02) for the overall patient dataset and AUC of 0.79 (± 0.01) and AP 0.72 (± 0.02) for the subgroup with respiratory disorders. Conclusion The RNN-based model demonstrated better performance than RF and LR in patients in mechanical ventilation and its subgroup admitted with respiratory disorders. Clinical studies are needed to evaluate whether it impacts decision-making and patient outcomes. Trial registration: NCT02731898 ( https://clinicaltrials.gov/ct2/show/NCT02731898 ), prospectively registered on April 8, 2016.

Published
2021
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9. Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus tiotropium monotherapy in patients with COPD

Author

Sandeep Bansal, Martin Anderson, Antonio Anzueto, Nicola Brown, Chris Compton, Thomas C. Corbridge, David Erb, Catherine Harvey, Morrys C. Kaisermann, Mitchell Kaye, David A. Lipson, Neil Martin, Chang-Qing Zhu, and Alberto Papi

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Abstract Chronic obstructive pulmonary disease (COPD) treatment guidelines do not currently include recommendations for escalation directly from monotherapy to triple therapy. This 12-week, double-blind, double-dummy study randomized 800 symptomatic moderate-to-very-severe COPD patients receiving tiotropium (TIO) for ≥3 months to once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 mcg via ELLIPTA (n = 400) or TIO 18 mcg via HandiHaler (n = 400) plus matched placebo. Study endpoints included change from baseline in trough forced expiratory volume in 1 s (FEV1) at Days 85 (primary), 28 and 84 (secondary), health status (St George’s Respiratory Questionnaire [SGRQ] and COPD Assessment Test [CAT]) and safety. FF/UMEC/VI significantly improved trough FEV1 at all timepoints (Day 85 treatment difference [95% CI] 95 mL [62–128]; P

Published
2021
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10. Tiotropium in chronic obstructive pulmonary disease – a review of clinical development

Author

Antonio Anzueto and Marc Miravitlles

Subjects
Chronic obstructive pulmonary disease, Dry-powder inhaler, Dyspnea, Exacerbations, HandiHaler®, Long-acting muscarinic antagonist, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Bronchodilators are the mainstay of pharmacological treatment in chronic obstructive pulmonary disease (COPD), and long-acting muscarinic antagonist (LAMA) monotherapy is recommended as initial treatment for Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups B, C, and D. Main body Tiotropium bromide was the first LAMA available for COPD in clinical practice and, because of its long duration of action, is administered once daily. Tiotropium was initially available as an inhalation powder delivered via a dry-powder inhaler (DPI). Later, tiotropium also became available as an inhalation spray delivered via a soft mist inhaler (SMI). The SMI was designed to overcome or minimize some of the issues associated with other inhaler types (eg, the need for strong inspiratory airflow with DPIs). Results of short- and long-term randomized, controlled clinical trials of tiotropium in patients with COPD indicated tiotropium was safe and significantly improved lung function, health-related quality of life, and exercise endurance, and reduced dyspnea, lung hyperinflation, exacerbations, and use of rescue medication compared with placebo or active comparators. These positive efficacy findings triggered the evaluation of tiotropium in fixed-dose combination with olodaterol (a long-acting β2-agonist). In this review, we provide an overview of studies of tiotropium for the treatment of COPD, with a focus on pivotal studies. Conclusion Tiotropium is safe and efficacious as a long-term, once-daily LAMA for the maintenance treatment of COPD and for reducing COPD exacerbations. The SMI generates a low-velocity, long-duration aerosol spray with a high fine-particle fraction, which results in marked lung drug deposition. In addition, high inspiratory flow rates are not required.

Published
2020
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11. Efficacy and safety of two doses of budesonide/formoterol fumarate metered dose inhaler in COPD

Author

Nicola A. Hanania, Alberto Papi, Antonio Anzueto, Fernando J. Martinez, Kimberly A. Rossman, Christy S. Cappelletti, Elizabeth A. Duncan, Jack S. Nyberg, and Paul M. Dorinsky

Subjects
Medicine
Abstract

Inhaled corticosteroid/long-acting β2-agonist combination therapy is a recommended treatment option for patients with chronic obstructive pulmonary disease (COPD) and increased exacerbation risk, particularly those with elevated blood eosinophil levels. SOPHOS (NCT02727660) evaluated the efficacy and safety of two doses of budesonide/formoterol fumarate dihydrate metered dose inhaler (BFF MDI) versus formoterol fumarate dihydrate (FF) MDI, each delivered using co-suspension delivery technology, in patients with moderate-to-very severe COPD and a history of exacerbations. In this phase 3, randomised, double-blind, parallel-group, 12–52-week, variable length study, patients received twice-daily BFF MDI 320/10 µg or 160/10 µg, or FF MDI 10 µg. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) at week 12. Secondary and other endpoints included assessments of moderate/severe COPD exacerbations and safety. The primary analysis (modified intent-to-treat) population included 1843 patients (BFF MDI 320/10 µg, n=619; BFF MDI 160/10 µg, n=617; and FF MDI, n=607). BFF MDI 320/10 µg and 160/10 µg improved morning pre-dose trough FEV1 at week 12 versus FF MDI (least squares mean differences 34 mL [p=0.0081] and 32 mL [p=0.0134], respectively), increased time to first exacerbation (hazard ratios 0.827 [p=0.0441] and 0.803 [p=0.0198], respectively) and reduced exacerbation rate (rate ratios 0.67 [p=0.0001] and 0.71 [p=0.0010], respectively). Lung function and exacerbation benefits were driven by patients with blood eosinophil counts ≥150 cells·mm−3. The incidence of adverse events was similar, and pneumonia rates were low (≤2.4%) across treatments. SOPHOS demonstrated the efficacy and tolerability of BFF MDI 320/10 µg and 160/10 µg in patients with moderate-to-very severe COPD at increased risk of exacerbations.

Published
2020
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12. Concomitant inhaled corticosteroid use and the risk of pneumonia in COPD: a matched-subgroup post hoc analysis of the UPLIFT® trial

Author

Donald P. Tashkin, Marc Miravitlles, Bartolomé R. Celli, Norbert Metzdorf, Achim Mueller, David M. G. Halpin, and Antonio Anzueto

Subjects
COPD, Pneumonia, Inhaled corticosteroids, Fluticasone propionate, UPLIFT®, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Use of inhaled corticosteroids (ICS) increases the risk of pneumonia in chronic obstructive pulmonary disease (COPD), but the magnitude of risk with different ICS remains unclear. Methods A post hoc analysis of the 4-year UPLIFT® trial to assess whether pneumonia risk differed by type of ICS (fluticasone propionate [FP], other ICS, or no ICS) in permanent users (defined by use until end of study) or in users at baseline (sensitivity analysis). Results For the permanent-users analysis, 825 patients receiving FP throughout the trial, 825 patients receiving other ICS and 825 patients not receiving ICS were matched on relevant baseline features 1:1:1. A significantly greater risk of pneumonia was observed for FP versus no ICS: the hazard ratio (HR) for risk of pneumonia was 1.33 (95% confidence interval [CI] 1.00, 1.75; p = 0.046) and the rate ratio (RR) was 1.58 (95% CI 1.05, 2.37; p = 0.028). A greater risk was also found for FP versus other ICS: HR 1.28 (95% CI 0.97, 1.68; p = 0.078) and RR 1.48 (95% CI 1.00, 2.19; p = 0.049). A higher proportion of patients on FP were hospitalized with pneumonia (7.9%) versus other ICS (6.7%) or no ICS (5.9%). Whilst other ICS use was associated with the highest number of fatal pneumonia events, the total number of fatal pneumonia incidents was low. A similar pattern was observed in the sensitivity analyses, which included 4002 patients on different treatments at baseline (FP, other ICS, and no ICS) and considered potential switches during the study. Conclusion The results support existing evidence of an increased pneumonia risk with FP use compared with other ICS and no ICS use in patients with COPD. Healthcare professionals should evaluate the risk–benefit ratio of using ICS when making treatment decisions with their patients. Trial registration Post hoc analysis of UPLIFT®. ClinicalTrials.gov number: NCT00144339. Retrospectively registered September 2, 2005.

Published
2018
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13. Pneumonia in Patients with Chronic Obstructive Pulmonary Disease

Author

Marcos I. Restrepo, M.D., M.Sc., Oriol Sibila, M.D., Ph.D.,, and Antonio Anzueto, M.D.

Subjects
pneumonia, pulmonary disease, chronic obstructive, vaccines, adrenal cortex hormones, Diseases of the respiratory system, RC705-779
Abstract

Chronic obstructive pulmonary disease (COPD) is a frequent comorbid condition associated with increased morbidity and mortality. Pneumonia is the most common infectious disease condition. The purpose of this review is to evaluate the impact of pneumonia in patients with COPD. We will evaluate the epidemiology and factors associated with pneumonia. We are discussing the clinical characteristics of COPD that may favor the development of infections conditions such as pneumonia. Over the last 10 years, there is an increased evidence that COPD patients treated with inhaled corticosteroids are at increased risk to develp pneumonia. We will review the avaialbe information as well as the possible mechanism for this events. We also discuss the impact of influenza and pneumococcal vaccination in the prevention of pneumonia in COPD patients.

Published
2018
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14. Optimizing bronchodilation in the prevention of COPD exacerbations

Author

Marc Miravitlles, Antonio Anzueto, and José R. Jardim

Subjects
Dual bronchodilation, ICS, LABA, LAMA, Treatment guidelines, Triple therapy, Diseases of the respiratory system, RC705-779
Abstract

Abstract The natural disease course of chronic obstructive pulmonary disease (COPD) is often punctuated by exacerbations: acute events of symptom worsening associated with significant morbidity and healthcare resource utilization; reduced quality of life; and increased risk of hospitalization and death. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommend that patients at risk of exacerbations (GOLD Groups C and D) receive a long-acting muscarinic antagonist (LAMA) or a long-acting β2-agonist (LABA)/LAMA combination, respectively, as preferred initial treatments. The latter recommendation is based on recent trial evidence demonstrating the superior efficacy of a fixed-dose LABA/LAMA over an inhaled corticosteroid (ICS)/LABA in exacerbation prevention. ICS in combination with a LABA is also indicated for prevention of exacerbations, but the use of ICS is associated with an increased risk of adverse events such as pneumonia, and offers limited benefits beyond those provided by LABA or LAMA monotherapy. In this review, we examine evidence from a number of pivotal studies of LABAs and LAMAs, administered as monotherapy or as part of dual or triple combination therapy, with a specific focus on their effect on exacerbations. We also discuss a new proposed treatment paradigm for the management of COPD that takes into account this recent evidence and adopts a more cautious approach to the use of ICS. In alignment with GOLD 2017, we suggest that ICS should be reserved for patients with concomitant asthma or in whom exacerbations persist despite treatment with LABA/LAMA.

Published
2017
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15. Association of atypical antipsychotics and mortality for patients hospitalised with pneumonia

Author

Zachary Boivin, Mario F. Perez, Nkiruka C. Atuegwu, Mark Metersky, Carlos A. Alvarez, Antonio Anzueto, and Eric M. Mortensen

Subjects
Medicine
Abstract

Introduction Atypical antipsychotics are commonly used in patients with psychiatric conditions and dementia. They are also frequently used in patients being admitted with pneumonia; however, there are few safety data. The purpose of this study was to examine whether atypical antipsychotic use prior to admission is associated with increased mortality in patients with pneumonia. Methods We conducted a retrospective cohort study of hospitalised patients with pneumonia over a 10-year period. We included patients 65 years or older and hospitalised with pneumonia. For our primary analysis, we used propensity score matching to balance confounders between atypical antipsychotic users and nonusers. Results There were 102 897 patients and 5977 were taking atypical antipsychotics. After matching there were 5513 users and 5513 nonusers. Atypical antipsychotic use was associated with increased odds of 30-day (OR 1.20, 95% CI 1.11–1.31) and 90-day mortality (1.19, 1.09–1.30). Conclusion In patients 65 years or older that are hospitalised with pneumonia, we found an association between atypical antipsychotic use and increased odds of mortality. This was particularly pronounced for patients with pre-existing psychiatric or cardiac conditions. We suggest closely monitoring patients who use these medications and minimising their use in older adult patients.

Published
2019
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16. Microbiological testing of adults hospitalised with community-acquired pneumonia: an international study

Author

Manuela Carugati, Stefano Aliberti, Luis Felipe Reyes, Ricardo Franco Sadud, Muhammad Irfan, Cristina Prat, Nilam J. Soni, Paola Faverio, Andrea Gori, Francesco Blasi, Marcos I. Restrepo, Patricia Karina Aruj, Silvia Attorri, Enrique Barimboim, Juan Pablo Caeiro, María I. Garzón, Victor Hugo Cambursano, Adrian Ceccato, Julio Chertcoff, Florencia Lascar, Fernando Di Tulio, Ariel Cordon Díaz, Lautaro de Vedia, Maria Cristina Ganaha, Sandra Lambert, Gustavo Lopardo, Carlos M. Luna, Alessio Gerardo Malberti, Nora Morcillo, Silvina Tartara, Claudia Pensotti, Betiana Pereyra, Pablo Gustavo Scapellato, Juan Pablo Stagnaro, Florencio Varela, Sonali Shah, Felix Lötsch, Florian Thalhammer, Kurt Anseeuw, Camille A. Francois, Eva Van Braeckel, Jean Louis Vincent, Marcel Zannou Djimon, Jules Bashi, Roger Dodo, Simone Aranha Nouér, Peter Chipev, Milena Encheva, Darina Miteva, Diana Petkova, Adamou Dodo Balkissou, Eric Walter Pefura Yone, Bertrand Hugo Mbatchou Ngahane, Ning Shen, Jin-fu Xu, Carlos Andres Bustamante Rico, Ricardo Buitrago, Fernando Jose Pereira Paternina, Jean-Marie Kayembe Ntumba, Vesna Vladic Carevic, Marko Jakopovic, Mateja Jankovic, Zinka Matkovic, Ivan Mitrecic, Marie-Laure Bouchy Jacobsson, Anette Bro Christensen, Uffe Christian Heitmann Bødtger, Christian Niels Meyer, Andreas Vestergaard Jensen, Gertrud Baunbæk-Knudsen, Pelle Trier Petersen, Stine Andersen, Ibrahim El-Said Abd El-Wahhab, Nesreen Elsayed Morsy, Hanaa Shafiek, Eman Sobh, Kedir Abdella Abdulsemed, Fabrice Bertrand, Christian Brun-Buisson, Etienne de Montmollin, Muriel Fartoukh, Jonathan Messika, Pierre Tattevin, Abdo Khoury, Bernard Ebruke, Michael Dreher, Martin Kolditz, Matthias Meisinger, Mathias W. Pletz, Stefan Hagel, Jan Rupp, Tom Schaberg, Marc Spielmanns, Petra Creutz, Norton Suttorp, Beatrice Siaw-Lartey, Katerina Dimakou, Dimosthenis Papapetrou, Evdoxia Tsigou, Dimitrios Ampazis, Evangelos Kaimakamis, Mina Gaga, Mohit Bhatia, Raja Dhar, George D'Souza, Rajiv Garg, Parvaiz A. Koul, P.A. Mahesh, B.S. Jayaraj, Kiran Vishnu Narayan, Hirennappa B. Udnur, Shashi Bhaskara Krishnamurthy, Surya Kant, Rajesh Swarnakar, Sneha Limaye, Sundeep Salvi, Keihan Golshani, Vera M. Keatings, Ignacio Martin-Loeches, Yasmin Maor, Jacob Strahilevitz, Salvatore Battaglia, Maria Carrabba, Piero Ceriana, Marco Confalonieri, Antonella d'Arminio Monforte, Bruno Del Prato, Marino De Rosa, Riccardo Fantini, Giuseppe Fiorentino, Maria Antonia Gammino, Francesco Menzella, Giuseppe Milani, Stefano Nava, Gerardo Palmiero, Roberta Petrino, Barbra Gabrielli, Paolo Rossi, Claudio Sorino, Gundi Steinhilber, Alessandro Zanforlin, Fabio Franzetti, Manuela Morosi, Elisa Monge, Mauro Carone, Vincenzo Patella, Simone Scarlata, Andrea Comel, Kiyoyasu Kurahashi, Zeina Aoun Bacha, Daniel Barajas Ugalde, Omar Ceballos Zuñiga, José F. Villegas, Milic Medenica, E.M.W. van de Garde, Deebya Raj Mihsra, Poojan Shrestha, Elliott Ridgeon, Babatunde Ishola Awokola, Ogonna N.O. Nwankwo, Adefuye Bolanle Olufunlola, Segaolu Olumide, Kingsley N. Ukwaja, Lukasz Minarowski, Skoczyński Szymon, Felipe Froes, Pedro Leuschner, Mariana Meireles, Sofia B Ravara, Victoria Brocovschii, Chesov Ion, Doina Rusu, Cristina Toma, Daniela Chirita, Carmen Mihaela Dorobat, Alexei Birkun, Anna Kaluzhenina, Abdullah Almotairi, Zakeya Abdulbaqi Ali Bukhary, Jameela Edathodu, Amal Fathy, Abdullah Mushira Abdulaziz Enani, Nazik Eltayeb Mohamed, Jawed Ulhadi Memon, Abdelhaleem Bella, Nada Bogdanović, Branislava Milenkovic, Dragica Pesut, Charles Feldman, Ho Kee Yum, Luis Borderìas, Noel Manuel Bordon Garcia, Hugo Cabello Alarcón, Catia Cilloniz, Antoni Torres, Vicens Diaz-Brito, Xavier Casas, Alicia Encabo González, Maria Luisa Fernández-Almira, Miguel Gallego, Inmaculada Gaspar-GarcÍa, Juan González del Castillo, Patricia Javaloyes Victoria, Elena Laserna Martínez, Rosa Malo de Molina, Pedro J. Marcos, Rosario Menéndez, Ana Pando-Sandoval, Cristina Prat Aymerich, Jordi Rello, Silvia Moyano, Francisco Sanz, Oriol Sibila, Ana Rodrigo-Troyano, Jordi Solé-Violán, Ane Uranga, Job F.M. van Boven, Ester Vendrell Torra, Jordi Almirall Pujol, Arnauld Attannon Fiogbe, Ferdaous Yangui, Semra Bilaceroglu, Levent Dalar, Ufuk Yilmaz, Artemii Bogomolov, Naheed Elahi, Devesh J. Dhasmana, Andrew Feneley, Rhiannon Ions, Julie Skeemer, Gerrit Woltmann, Carole Hancock, Adam T. Hill, Banu Rudran, Silvia Ruiz-Buitrago, Marion Campbell, Paul Whitaker, Alexander Youzguin, Anika Singanayagam, Karen S. Allen, Veronica Brito, Jessica Dietz, Claire E. Dysart, Susan M. Kellie, Ricardo A. Franco-Sadud, Garnet Meier, Thomas L. Holland, Stephen P. Bergin, Fayez Kheir, Mark Landmeier, Manuel Lois, Girish B. Nair, Hemali Patel, Katherine Reyes, William Rodriguez-Cintron, Shigeki Saito, Julio Noda, Cecilia I. Hinojosa, Stephanie M. Levine, Luis F. Angel, Antonio Anzueto, K. Scott Whitlow, John Hipskind, Kunal Sukhija, Vicken Totten, Richard G. Wunderink, Ray D. Shah, Kondwelani John Mateyo, Lorena Noriega, Ezequiel Alvarado, Mohamed Aman, and Lucía Labra

Subjects
Medicine
Abstract

This study aimed to describe real-life microbiological testing of adults hospitalised with community-acquired pneumonia (CAP) and to assess concordance with the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) and 2011 European Respiratory Society (ERS) CAP guidelines. This was a cohort study based on the Global Initiative for Methicillin-resistant Staphylococcus aureus Pneumonia (GLIMP) database, which contains point-prevalence data on adults hospitalised with CAP across 54 countries during 2015. In total, 3702 patients were included. Testing was performed in 3217 patients, and included blood culture (71.1%), sputum culture (61.8%), Legionella urinary antigen test (30.1%), pneumococcal urinary antigen test (30.0%), viral testing (14.9%), acute-phase serology (8.8%), bronchoalveolar lavage culture (8.4%) and pleural fluid culture (3.2%). A pathogen was detected in 1173 (36.5%) patients. Testing attitudes varied significantly according to geography and disease severity. Testing was concordant with IDSA/ATS and ERS guidelines in 16.7% and 23.9% of patients, respectively. IDSA/ATS concordance was higher in Europe than in North America (21.5% versus 9.8%; p

Published
2018
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17. An official American Thoracic Society/European Respiratory Society statement: research questions in COPD

Author

Bartolome R. Celli, Marc Decramer, Jadwiga A. Wedzicha, Kevin C. Wilson, Alvar A. Agustí, Gerard J. Criner, William MacNee, Barry J. Make, Stephen I. Rennard, Robert A. Stockley, Claus Vogelmeier, Antonio Anzueto, David H. Au, Peter J. Barnes, Pierre-Regis Burgel, Peter M. Calverley, Ciro Casanova, Enrico M. Clini, Christopher B. Cooper, Harvey O. Coxson, Daniel J. Dusser, Leonardo M. Fabbri, Bonnie Fahy, Gary T. Ferguson, Andrew Fisher, Monica J. Fletcher, Maurice Hayot, John R. Hurst, Paul W. Jones, Donald A. Mahler, François Maltais, David M. Mannino, Fernando J. Martinez, Marc Miravitlles, Paula M. Meek, Alberto Papi, Klaus F. Rabe, Nicolas Roche, Frank C. Sciurba, Sanjay Sethi, Nikos Siafakas, Don D. Sin, Joan B. Soriano, James K. Stoller, Donald P. Tashkin, Thierry Troosters, Geert M. Verleden, Johny Verschakelen, Jorgen Vestbo, John W. Walsh, George R. Washko, Robert A. Wise, Emiel F.M. Wouters, and Richard L. ZuWallack

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality and resource use worldwide. The goal of this official American Thoracic Society (ATS)/European Respiratory Society (ERS) Research Statement is to describe evidence related to diagnosis, assessment, and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management. Clinicians, researchers and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarised, and then salient knowledge gaps were identified. Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus. Great strides have been made in the diagnosis, assessment and management of COPD, as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS research statement highlights the types of research that leading clinicians, researchers and patient advocates believe will have the greatest impact on patient-centred outcomes.

Published
2015
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18. A Non-Human Primate Model of Severe Pneumococcal Pneumonia.

Author

Luis F Reyes, Marcos I Restrepo, Cecilia A Hinojosa, Nilam J Soni, Anukul T Shenoy, Ryan P Gilley, Norberto Gonzalez-Juarbe, Julio R Noda, Vicki T Winter, Melissa A de la Garza, Robert E Shade, Jacqueline J Coalson, Luis D Giavedoni, Antonio Anzueto, and Carlos J Orihuela

Subjects
Medicine, Science
Abstract

RATIONALE:Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and infectious death in adults worldwide. A non-human primate model is needed to study the molecular mechanisms that underlie the development of severe pneumonia, identify diagnostic tools, explore potential therapeutic targets, and test clinical interventions during pneumococcal pneumonia. OBJECTIVE:To develop a non-human primate model of pneumococcal pneumonia. METHODS:Seven adult baboons (Papio cynocephalus) were surgically tethered to a continuous monitoring system that recorded heart rate, temperature, and electrocardiography. Animals were inoculated with 109 colony-forming units of S. pneumoniae using bronchoscopy. Three baboons were rescued with intravenous ampicillin therapy. Pneumonia was diagnosed using lung ultrasonography and ex vivo confirmation by histopathology and immunodetection of pneumococcal capsule. Organ failure, using serum biomarkers and quantification of bacteremia, was assessed daily. RESULTS:Challenged animals developed signs and symptoms of pneumonia 4 days after infection. Infection was characterized by the presence of cough, tachypnea, dyspnea, tachycardia and fever. All animals developed leukocytosis and bacteremia 24 hours after infection. A severe inflammatory reaction was detected by elevation of serum cytokines, including Interleukin (IL)1Ra, IL-6, and IL-8, after infection. Lung ultrasonography precisely detected the lobes with pneumonia that were later confirmed by pathological analysis. Lung pathology positively correlated with disease severity. Antimicrobial therapy rapidly reversed symptomology and reduced serum cytokines. CONCLUSIONS:We have developed a novel animal model for severe pneumococcal pneumonia that mimics the clinical presentation, inflammatory response, and infection kinetics seen in humans. This is a novel model to test vaccines and treatments, measure biomarkers to diagnose pneumonia, and predict outcomes.

Published
2016
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19. Optimizing management of chronic obstructive pulmonary disease in the upcoming decade

Author

Richard Russell, Antonio Anzueto, and Idelle Weisman

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Richard Russell1, Antonio Anzueto2, Idelle Weisman31Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, UK; 2University of Texas Health Science Center at San Antonio, South Texas Veterans Health Care System, San Antonio, Texas, USA; 3Pfizer Inc, Medical Affairs, Respiratory, Primary Care Business Unit, New York, USAAbstract: Chronic obstructive pulmonary disease (COPD) is a leading cause of disability and mortality. Caring for patients with COPD, particularly those with advanced disease who experience frequent exacerbations, places a significant burden on health care budgets, and there is a global need to reduce the financial and personal burden of COPD. Evolving scientific evidence on the natural history and clinical course of COPD has fuelled a fundamental shift in our approach to the disease. The emergence of data highlighting the heterogeneity in rate of lung function decline has altered our perception of disease progression in COPD and our understanding of appropriate strategies for the management of stable disease. These data have demonstrated that early, effective, and prolonged bronchodilation has the potential to slow the rate of decline in lung function and to reduce the frequency of exacerbations that contribute to functional decline. The goals of therapy for COPD are no longer confined to controlling symptoms, reducing exacerbations, and maintaining quality of life, and slowing disease progression is now becoming an achievable aim. A challenge for the future will be to capitalize on these observations by improving the identification and diagnosis of patients with COPD early in the course of their disease, so that effective interventions can be introduced before the more advanced, disabling, and costly stages of the disease. Here we critically review emerging data that underpin the advances in our understanding of the clinical course and management of COPD, and evaluate both current and emerging pharmacologic options for effective maintenance treatment.Keywords: COPD, chronic obstructive pulmonary disease, long-acting bronchodilator, early treatment

Published
2011

20. 2473 Cardiac injury due to Streptococcus pneumoniae invasion during severe pneumococcal pneumonia in a novel nonhuman primate model

Author

Luis F. Reyes, Cecilia A. Hinojosa, Nilam J. Soni, Julio Noda, Vicki T. Winter, Melissa A. de la Garza, Jacqueline J. Coalson, Luis Giavedoni, Antonio Anzueto, Carlos J. Orihuela, and Marcos I. Restrepo

Subjects
Medicine
Abstract

OBJECTIVES/SPECIFIC AIMS: The aims of this study are (1) to develop and characterize a novel nonhuman primate model of pneumococcal pneumonia that mimics human disease; and (2) determine whether Streptococcus pneumoniae can: (a) translocate to the heart, (b) cause adverse cardiac events, (c) induce cardiomyocyte death, and (d) lead to scar formation during severe pneumonia in baboons. METHODS/STUDY POPULATION: Six adult baboons (Papio cynocephalus) were surgically tethered to a monitoring system to continuously assess their heart rate, temperature, and electrocardiogram (ECG). A baseline transthoracic echocardiogram, 12-lead ECG, serum troponin-I levels, brain natriuretic peptide, and heart-type fatty acid binding protein (HFABP) levels were obtained before infection and at the end of the experiment to determine cardiovascular damage during pneumococcal pneumonia. Animals were challenged with 108 colony-forming units of S. pneumoniae in the right middle lobe using flexible bronchoscopy. Three baboons were rescued with ampicillin therapy (80 mg/kg/d) after the development of pneumonia. Cardiac damage was confirmed by examination of tissue sections using immunohistochemistry as well as electron and fluorescence microscopy. Western-blots and tissue staining were used to determine the presence of necroptosis (RIP3 and pMLKL) and apoptosis (Caspase-3) in the cardiac tissue. Cytokine and chemokine levels in the heart tissue were determined using Luminex technology. RESULTS/ANTICIPATED RESULTS: Four males (57%) and three (43%) females were challenged. The median age of all baboons was 11 (IQR, 10-19) years old, which corresponds to a middle-aged human. Infected baboons consistently developed severe pneumonia. All animals developed systemic inflammatory response syndrome with tachycardia, tachypnea, fever, and leukocytosis. Infection was characterized by initial leukocytosis followed by severe leukopenia on day 3 postinoculation. Non-specific ischemic alterations by ECG (ST segment and T-wave flattering) and in the premortem echocardiogram were observed. The median (IQR) levels of troponin I and HFABP at the end of the experiment were 3550 ng/mL (1717–5383) and 916.9 ng/mL (520.8–1323), respectively. Severe cardiomyopathy was observed using TEM and H&E stains in animals with severe pneumonia. Necroptosis was detected in cardiomyocytes of infected animals by the presence of pMLKL and RIP3 in cardiac tissues. Signs of cardiac remodeling indicated by disorganized collagen deposition was present in rescued animals but not in the other animals. DISCUSSION/SIGNIFICANCE OF IMPACT: We confirmed that baboons experience cardiac injury during severe pneumococcal pneumonia that is characterized by myocardial invasion, activation of necroptosis, and tissue remodeling in animals rescued by antimicrobial therapy. Cardiac damage by invading pneumococci may explain why adverse cardiac events that occur during and after pneumococcal pneumonia in adult human patients.

Published
2018
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21. Insights into interventions in managing COPD patients: lessons from the TORCH and UPLIFT® studies

Author

Marc Miravitlles and Antonio Anzueto

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Marc Miravitlles1, Antonio Anzueto21Fundació Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, Barcelona, Spain; 2Department of Pulmonary/Critical Care, The University of Texas Health Science Center at San Antonio and the South Texas Veterans Health Care System, San Antonio, Texas, USAAbstract: Influencing the progression of COPD has long been an elusive goal of drug therapy. Directly or indirectly, this has again been investigated in two of the largest, long-term drug trials in COPD: Towards a Revolution in COPD Health (TORCH) and Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT®). Neither trial achieved statistical significance in their respective primary outcomes; however, both make considerable contributions to understanding of how the progression of COPD may be influenced. The objective of this article is to review the data from these different trials with a view to what can be learnt about the management of COPD. The long-term improvements in lung function, health-related quality of life, and possibly survival from the use of long-acting bronchodilators in these trials suggest an influence on progression of the disease. With the more optimistic view of benefits from drug treatment of COPD that these trials provide, a review of prescribing practices is warranted. Keywords: bronchodilators, FEV1, fluticasone, inhaled corticosteroids, mortality, salmeterol, tiotropium

Published
2009

22. The association of cardioprotective medications with pneumonia-related outcomes.

Author

Albert Wu, Chester Good, John R Downs, Michael J Fine, Mary Jo V Pugh, Antonio Anzueto, and Eric M Mortensen

Subjects
Medicine, Science
Abstract

Little research has examined whether cardiovascular medications, other than statins, are associated with improved outcomes after pneumonia. Our aim was to examine the association between the use of beta-blockers, statins, angiotensin converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs) with pneumonia-related outcomes.We conducted a retrospective population-based study on male patients ≥ 65 years of age hospitalized with pneumonia and who did not have pre-existing cardiac disease. Our primary analyses were multilevel regression models that examined the association between cardiovascular medication classes and either mortality or cardiovascular events.Our cohort included 21,985 patients: 22% died within 90 days of admission, and 22% had a cardiac event within 90 days. The cardiovascular medications studied that were associated with decreased 90-day mortality included: statins (OR 0.70, 95% CI 0.63-0.77), ACE inhibitors (OR 0.82, 95% CI 0.74-0.91), and ARBs (OR 0.58, 95% CI 0.44-0.77). However, none of the medications were significantly associated with decreased cardiovascular events.While statins, ACE inhibitors, and ARBs, were associated with decreased mortality, there was no significant association with decreased CV events. These results indicate that this decreased mortality is unlikely due to their potential cardioprotective effects.

Published
2014
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23. Impact of prior systemic corticosteroid use in patients admitted with community-acquired pneumonia

Author

Adriel Malave, Elena Laserna, Oriol Sibila, Eric M. Mortensen, Antonio Anzueto, and Marcos I. Restrepo

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Background and objective: Limited information is available regarding the impact of prior outpatient use of systemic corticosteroids (SCS) in patients subsequently developing community-acquired pneumonia (CAP). We investigate the effects of prior SCS on severity of illness, microbiology and clinical outcomes for patients hospitalized with CAP. Methods: A retrospective cohort study of subjects with CAP (according to International Classification of Diseases, 9th edition codes) was conducted over a 3-year period at two tertiary teaching hospitals. Subjects were considered to be SCS users if they received oral corticosteroids prior to admission. Primary outcomes were severity of illness, microbiology and 30-day mortality. Results: Data were abstracted on 698 patients [prior SCS users, 75 (10.7%) versus prior non-SCS users 623 (89.3%)]. Prior SCS users were more likely to have chronic obstructive pulmonary disease. No differences were found in severity of disease at admission, microbiological etiology including opportunistic and drug-resistant pathogens and clinical outcomes, including 30-day mortality, intensive care unit admission, length of hospital stay, need for mechanical ventilation and need for vasopressors. Conclusion: Prior SCS use is not associated with increased 30-day mortality for patients hospitalized with CAP. In addition, no differences were found in either the severity of the disease at the time of presentation or in the presence of the resistant or opportunistic pathogens among groups.

Published
2012
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24. Characterisation of exacerbations of chronic bronchitis and COPD in Europe: the GIANT study

Author

Marc Miravitlles, Antonio Anzueto, Santiago Ewig, Delfino Legnani, and Kathrin Stauch

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Objective: The GIANT study collected information on patients with acute exacerbations of chronic bronchitis (AECB) and chronic obstructive pulmonary disease (COPD) and the effect of treatment with moxifloxacin. Methods: AECB history, concomitant diseases, moxifloxacin treatment, concomitant medication, clinical symptoms and adverse events were recorded. A questionnaire at the end of treatment recorded the impact on patients’ daily lives. Results: Among 9225 patients from eight European countries, marked variation was seen in characteristics including age, smoking history and type of exacerbation. Spirometry use was more common among chest physicians (66.7%) than GPs (15.5%). Patients with Anthonisen type 1 and 2 exacerbations had more frequent exacerbations and these patients experienced a greater impact on daily activities compared with patients with type 3 episodes. Patient symptoms improved with moxifloxacin treatment after a mean (SD) of 3.4 (1.8) days, allowing return to normal daily activities after 5.4 (4.4) days and with full recovery taking 6.5 (3.1) days. Conclusions: Characteristics of patients with AECB and acute exacerbations of COPD differ among European countries. Spirometry is under-used, particularly in primary care and antibiotic treatment does not always follow current guidelines. Results confirm the efficacy of moxifloxacin in the treatment of AECB in real-life conditions.

Published
2009
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25. Efficacy of tiotropium in the prevention of exacerbations of COPD

Author

Antonio Anzueto and Marc Miravitlles

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Exacerbations are the most frequent cause of medical visits, hospital admissions and death among patients with chronic obstructive pulmonary disease (COPD). Tiotropium bromide is a long-acting bronchodilator that has demonstrated clinical efficacy in significantly improving the FEV 1 and health-related quality of life (HRQL) in patients with COPD. The prolonged and persistent bronchodilation achieved with tiotropium may reduce the exacerbation and COPD-related hospitalisation rates. The effect of tiotropium treatment on the incidence of exacerbations has been determined (as a secondary outcome) in registration trials. There are studies designed specifically to demonstrate the effect of tiotropium on the reduction in the frequency of exacerbations. Two of these studies of 6-month and 1-year duration demonstrated an additional significant benefit in the reduction of exacerbations and hospitalisations. The recent UPLIFT trial included 5993 patients followed for 4 years and, compared with control, tiotropium significantly delayed time-to-first exacerbation (16.7 versus 12.5 months) and time-to-first hospitalisation for exacerbations (lower risk of hospitalisation; HR, 0.86 [95% CI = 0.78-0.95]; p = 0.002). Tiotropium also reduced the mean number of exacerbations by 14% (rate per patient-year, 0.73 versus 0.85; HR, 0.86 [95% CI = 0.81-0.91]; p < 0.001). It is important to highlight that the control group in the UPLIFT trial consisted of patients with usual treatment for COPD, which included inhaled corticosteroids and/or long-acting beta-2 agonists in up to 62% of cases at baseline and up to 73% of cases at any time during follow-up. The new clinical trials have demonstrated a significant reduction in exacerbations and hospitalisations, even in patients treated with other drugs that can potentially prevent exacerbations.

Published
2009
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26. Review: Novel targets in the management of pneumonia

Author

Luis A. Díaz, Eric M. Mortensen, Antonio Anzueto, and Marcos I. Restrepo

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Community-acquired pneumonia (CAP) is the leading cause of death from infectious diseases in the US. It accounts each year for 500,000 hospitalizations and 45,000 deaths and represents one of the most common causes of intensive care unit (ICU) admission. The mortality rate due to severe CAP has shown little improvement in the past three decades, remaining between 21% and 58% in patients admitted to the intensive care unit. Antimicrobial agents are the cornerstone of therapy against CAP, but there are some novel antibiotic and nonantibiotic therapies that have been recently tested that may potentially impact outcomes of patients with severe CAP. We will review the most recent data regarding novel therapies in patients with the highest risk of death such as those with severe CAP.

Published
2008
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27. Global initiative for chronic obstructive lung disease 2023 report: gold executive summary

Author

Alvar Agustí, Bartolome R. Celli, Gerard J. Criner, David Halpin, Antonio Anzueto, Peter Barnes, Jean Bourbeau, MeiLan K. Han, Fernando J. Martinez, Maria Montes de Oca, Kevin Mortimer, Alberto Papi, Ian Pavord, Nicolas Roche, Sundeep Salvi, Don D. Sin, Dave Singh, Robert Stockley, M. Victorina López Varela, Jadwiga A. Wedzicha, and Claus F. Vogelmeier

Subjects
Pulmonary and Respiratory Medicine, Critical Care and Intensive Care Medicine
Published
2023

28. Clinical Markers Associated With Risk of Suicide or Drug Overdose Among Individuals With Smoking Exposure

Author

Brigid A. Adviento, Elizabeth A. Regan, Barry J. Make, MeiLan K. Han, Marilyn G. Foreman, Anand S. Iyer, Surya P. Bhatt, Victor Kim, Jessica Bon, Xavier Soler, Gregory L. Kinney, Nicola A. Hanania, Katherine E. Lowe, Kristen E. Holm, Abebaw M. Yohannes, Gen Shinozaki, Karin F. Hoth, Jess G. Fiedorowicz, James D. Crapo, Edwin K. Silverman, Terri H. Beaty, Peter J. Castaldi, Michael H. Cho, Dawn L. DeMeo, Adel El Boueiz, Auyon Ghosh, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Wonji Kim, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Dmitry Prokopenko, Matthew Moll, Jarrett Morrow, Dandi Qiao, Aabida Saferali, Phuwanat Sakornsakolpat, Emily S. Wan, Jeong Yun, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Matthew Strand, Jim Crooks, Katherine Pratte, Aastha Khatiwada, Erin Austin, Gregory Kinney, Kendra A. Young, Alejandro A. Diaz, Barry Make, Susan Murray, Elizabeth Regan, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L. Curtis, Perry G. Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R. Graham Barr, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Eric L. Flenaugh, Hirut Gebrekristos, Mario Ponce, Silanath Terpenning, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Divay Chandra, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, and Harjinder Singh

Subjects
Pulmonary and Respiratory Medicine, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
Published
2023

29. Weaning Outcomes in Patients with Brain Injury

Author

Eva E. Tejerina, Chiara Robba, Laura del Campo-Albendea, Paolo Pelosi, Alfonso Muriel, Oscar Peñuelas, Fernando Frutos-Vivar, Konstantinos Raymondos, Bin Du, Arnaud W. Thille, Fernando Ríos, Marco González, Lorenzo del-Sorbo, Maria del Carmen Marín, Bruno Valle Pinheiro, Marco Antonio Soares, Nicolas Nin, Salvatore M. Maggiore, Andrew Bersten, Pravin Amin, Nahit Cakar, Gee Young Suh, Fekri Abroug, Manuel Jibaja, Dimitros Matamis, Amine Ali Zeggwagh, Yuda Sutherasan, Antonio Anzueto, and Andrés Esteban

Subjects
Adult, Brain Injuries, Airway Extubation, Intubation, Intratracheal, Humans, Prospective Studies, Neurology (clinical), Critical Care and Intensive Care Medicine, Ventilator Weaning, Respiration, Artificial
Abstract

Despite the need for specific weaning strategies in neurological patients, evidence is generally insufficient or lacking. We aimed to describe the evolution over time of weaning and extubation practices in patients with acute brain injury compared with patients who are mechanically ventilated (MV) due to other reasons.We performed a secondary analysis of three prospective, observational, multicenter international studies conducted in 2004, 2010, and 2016 in adults who had need of invasive MV for more than 12 h. We collected data on baseline characteristics, variables related to management ventilator settings, and complications while patients were ventilated or until day 28.Among the 20,929 patients enrolled, we included 12,618 (60%) who started the weaning from MV, of whom 1722 (14%) were patients with acute brain injury. In the acutely brain-injured cohort, 538 patients (31%) did not undergo planned extubation, defined as the need for a tracheostomy without an attempt of extubation, accidental extubation, and death. Among the 1184 planned extubated patients with acute brain injury, 202 required reintubation (17%). Patients with acute brain injury had a higher odds for unplanned extubation (odds ratio [OR] 1.35, confidence interval for 95% [CI 95%] 1.19-1.54; p 0.001), a higher odds of failure after the first attempt of weaning (spontaneous breathing trial or gradual reduction of ventilatory support; OR 1.14 [CI 95% 1.01-1.30; p = 0.03]), and a higher odds for reintubation (OR 1.41 [CI 95% 1.20-1.66; p 0.001]) than patients without brain injury. Patients with hemorrhagic stroke had the highest odds for unplanned extubation (OR 1.47 [CI 95% 1.22-1.77; p 0.001]), of failed extubation after the first attempt of weaning (OR 1.28 [CI 95% 1.06-1.55; p = 0.009]), and for reintubation (OR 1.49 [CI 95% 1.17-1.88; p 0.001]). In relation to weaning evolution over time in patients with acute brain injury, the risk for unplanned extubation showed a downward trend; the risk for reintubation was not associated to time; and there was a significant increase in the percentage of patients who underwent extubation after the first attempt of weaning from MV.Patients with acute brain injury, compared with patients without brain injury, present higher odds of undergoing unplanned extubated after weaning was started, lower odds of being extubated after the first attempt, and a higher risk of reintubation.

Published
2022

30. Use of Computed Tomography Lung Densitometry as an Outcome Measure for Emphysema Progression: The Case of Losartan

Author

Marc Miravitlles, Antonio Anzueto, Institut Català de la Salut, [Miravitlles M] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Anzueto A] Pulmonary Disease/Critical Care University of Texas Health and South Texas Veterans Health Care System San Antonio, Texas, USA, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Emphysema, Investigative Techniques::Chemistry Techniques, Analytical::Photometry::Densitometry [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Pulmonary and Respiratory Medicine, diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Otros calificadores::Otros calificadores::/diagnóstico por imagen [Otros calificadores], Respiratory Tract Diseases::Lung Diseases::Lung Diseases, Obstructive::Pulmonary Disease, Chronic Obstructive::Pulmonary Emphysema [DISEASES], enfermedades respiratorias::enfermedades pulmonares::enfermedades pulmonares obstructivas::enfermedad pulmonar obstructiva crónica::enfisema pulmonar [ENFERMEDADES], Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], técnicas de investigación::técnicas de química analítica::fotometría::densitometría [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Critical Care and Intensive Care Medicine, Losartan, Pulmonary Emphysema, Emfisema pulmonar - Imatgeria, Outcome Assessment, Health Care, Densitometria òssia, Avaluació de resultats (Assistència sanitària), Humans, Lung, Tomography, Other subheadings::Other subheadings::/diagnostic imaging [Other subheadings], Densitometry
Abstract

Tomography; Emphysema; Outcomes Tomografía; Enfisema; Resultados Tomografia; Emfisema; Resultats

Published
2022

31. The acute effects of azithromycin use on cardiovascular mortality as compared with <scp>amoxicillin–clavulanate</scp> in US Veterans

Author

Maral, DerSarkissian, Yinong, Young-Xu, Mei Sheng, Duh, Rachel H, Bhak, Niki, Palmetto, Eric, Mortensen, Antonio, Anzueto, Catherine, Nguyen, Mu, Cheng, Vera, Frajzyngier, Suna, Park, Angela, Lax, Lisa B, Weatherby, and Alexander M, Walker

Subjects
Adult, Cardiovascular Diseases, Epidemiology, Humans, Pharmacology (medical), Azithromycin, Middle Aged, Amoxicillin-Potassium Clavulanate Combination, Aged, Anti-Bacterial Agents, Veterans
Abstract

Azithromycin is a common first-line antibiotic for respiratory infection; however, there is conflicting evidence regarding risk of cardiovascular death. We assessed cardiovascular and noncardiovascular mortality associated with azithromycin versus amoxicillin-clavulanate among US Veterans treated for nonear-nose-throat respiratory infection ("respiratory") or ear-nose-throat infection indication.Electronic health record data from the US Veterans Health Administration database were used to identify Veterans (30-74 years) with outpatient dispensings of oral azithromycin versus amoxicillin-clavulanate for respiratory or ear-nose-throat infection (January 01, 2000-December 31, 2014). Outcomes assessed were risk of cardiovascular death and noncardiovascular death within 1-5 and 6-10 days postdispensing. Inverse probability of treatment-weighted proportional hazards models and binomial regression models were used to estimate hazard ratios (HRs) and compute risk differences (RD) per million courses of therapy. Cardiac death (subset of cardiovascular death) was assessed in sensitivity analyses.There were 629 345 azithromycin and 168 429 amoxicillin-clavulanate dispensings for respiratory indications, 143 783 azithromycin, and 203 142 amoxicillin-clavulanate dispensings for ear-nose-throat indications. For respiratory indications, azithromycin was not associated with a significantly different risk of cardiovascular death versus amoxicillin-clavulanate within 1-5 days postdispensing (HR [95% confidence interval (CI)]: 1.12 [0.63, 2.00]; RD [95% CI]: 11 [-43, 64] deaths/million courses of therapy). No elevated risk for azithromycin was found for ear-nose-throat indications. Pooled results for both indications via meta-analysis showed no association between antibiotics and cardiovascular mortality. There was no significant difference in risk of noncardiovascular or cardiac death between antibiotics postdispensing.Azithromycin was not associated with elevated risk of cardiovascular or noncardiovascular death versus amoxicillin-clavulanate among US Veterans.

Published
2022

32. Clinically Significant and Comorbid Anxiety and Depression Symptoms Predict Severe Respiratory Exacerbations in Smokers: A Post Hoc Analysis of the COPDGene and SPIROMICS Cohorts

Author

Anand S. Iyer, Trisha M. Parekh, Jacqueline O’Toole, Surya P. Bhatt, Michelle N. Eakin, Jerry A. Krishnan, Abebaw M. Yohannes, Prescott G. Woodruff, Christopher B. Cooper, Richard E. Kanner, Nicola A. Hanania, Mark T. Dransfield, Elizabeth A. Regan, Karin F. Hoth, Victor Kim, James D. Crapo, Edwin K. Silverman, Barry J. Make, Terri Beaty, Ferdouse Begum, Peter J. Castaldi, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dmitry Prokopenko, Dandi Qiao, Phuwanat Sakornsakolpat, Emily S. Wan, Sungho Won, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, MeiLan K. Han, Eric A. Hoffman, Stephen Huries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San José Estépar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Gregory Kinney, Kendra A. Young, Jessica Bon, Alejandro A. Diaz, Barry Make, Susan Murray, Elizabeth Regan, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L. Curtis, Perry G. Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R. Graham Barr, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Robert Wise, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Los Angeles, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Divay Chandra, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, and Harjinder Singh

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Comorbid anxiety, business.industry, Internal medicine, Post-hoc analysis, Medicine, Respiratory system, business, Depressive symptoms
Published
2022

33. Measuring Peak Inspiratory Flow in Patients with Chronic Obstructive Pulmonary Disease

Author

Jill A Ohar, Gary T Ferguson, Donald A Mahler, M Bradley Drummond, Rajiv Dhand, Roy A Pleasants, Antonio Anzueto, David MG Halpin, David B Price, Gail S Drescher, Haley M Hoy, John Haughney, Michael W Hess, and Omar S Usmani

Subjects
peak inspiratory flow, Pulmonary Disease, Chronic Obstructive, dry powder inhalers, Administration, Inhalation, Humans, General Medicine, Review, Lung, chronic obstructive pulmonary disease
Abstract

Dry powder inhalers (DPIs) are breath actuated, and patients using DPIs need to generate an optimal inspiratory flow during the inhalation maneuver for effective drug delivery to the lungs. However, practical and standardized recommendations for measuring peak inspiratory flow (PIF)—a potential indicator for effective DPI use in chronic obstructive pulmonary disease (COPD)—are lacking. To evaluate recommended PIF assessment approaches, we reviewed the Instructions for Use of the In-Check™ DIAL and the prescribing information for eight DPIs approved for use in the treatment of COPD in the United States. To evaluate applied PIF assessment approaches, we conducted a PubMed search from inception to August 31, 2021, for reports of clinical and real-life studies where PIF was measured using the In-Check™ DIAL or through a DPI in patients with COPD. Evaluation of collective sources, including 47 applicable studies, showed that instructions related to the positioning of the patient with their DPI, instructions for exhalation before the inhalation maneuver, the inhalation maneuver itself, and post-inhalation breath-hold times varied, and in many instances, appeared vague and/or incomplete. We observed considerable variation in how PIF was measured in clinical and real-life studies, underscoring the need for a standardized method of PIF measurement. Standardization of technique will facilitate comparisons among studies. Based on these findings and our clinical and research experience, we propose specific recommendations for PIF measurement to standardize the process and better ensure accurate and reliable PIF values in clinical trials and in daily clinical practice.

Published
2022

34. Immunologic resilience and COVID-19 survival advantage

Author

Grace C. Lee, Marcos I. Restrepo, Nathan Harper, Muthu Saravanan Manoharan, Alisha M. Smith, Justin A. Meunier, Sandra Sanchez-Reilly, Aamir Ehsan, Anne P. Branum, Caitlyn Winter, Lauryn Winter, Fabio Jimenez, Lavanya Pandranki, Andrew Carrillo, Graciela L. Perez, Antonio Anzueto, Hanh Trinh, Monica Lee, Joan M. Hecht, Celida Martinez-Vargas, Raj T. Sehgal, Jose Cadena, Elizabeth A. Walter, Kimberly Oakman, Raymond Benavides, Jacqueline A. Pugh, Scott Letendre, Maristella Steri, Valeria Orrù, Edoardo Fiorillo, Francesco Cucca, Alvaro G. Moreira, Nu Zhang, Elizabeth Leadbetter, Brian K. Agan, Douglas D. Richman, Weijing He, Robert A. Clark, Jason F. Okulicz, Sunil K. Ahuja, Mohamed I. Abdalla, Sandra G. Adams, Joseph Agnew, Saleem Ali, Jennifer Barker, Angela Birdwell, Stephen Bradford, Heather Briggs, Judith Marin Corral, Jennifer J. Dacus, Patrick J. Danaher, Scott A. DePaul, Jill Dickerson, Jollynn Doanne, Samantha Elbel, Corina Escamilla, Robert Farrar, David Feldman, Julianne Flynn, Delvina Ford, Joanna D. Foy, Megan Freeman, Samantha Galley, Maritza Garza, Sherraine Gilman, Jennifer Gomez, Varun K. Goyal, Sally Grassmuck, Joshua Hanson, Brande Harris, Gabrielyd Hastings, Audrey Haywood, Cecilia Hinojosa, Tony T. Ho, Teri Hopkins, Pamela Jewell, Thomas B. Johnson, Vasiliki Kotogiannes, Austin C. Lawler, Chadwick S. Lester, Stephanie M. Levine, Haidee V. Lewis, Angel Louder, Charmaine Mainor, Rachel Maldonado, Yvette Martinez, Neil McElligott, Laura Medlin, Myra Mireles, Kathleen Morneau, Samuel B. Munro, Anoop Nambiar, Daniel Nassery, Robert Nathanson, Jane O’Rorke, Cheryl Padgett, Sergi Pascual-Guardia, Marisa Patterson, Rogelio Perez, Robert E. Phillips, Patrick B. Polk, Michael A. Pomager, Kristy J. Preston, Kevin C. Proud, Michelle Rangel, Temple A. Ratcliffe, Renee L. Reichelderfer, Evan M. Renz, Jeanette Ross, Teresa Rudd, Maria E. Sanchez, Tammy Sanders, Kevin C. Schindler, David Schmit, Claudio Solorzano, Nilam Soni, Win S. Tam, Edward J. Tovar, Anna R. Tyler, Anjuli Vasquez, Maria C. Veloso, Steven G. Venticinque, Jorge A. Villalpando, Melissa Villanueva, Lauren Villegas, Andrew Wallace, Emily Wang, Andreia Williamson, Sadie A. Trammell Velasquez, Andrea Yunes, and Katharine H. Zentner

Subjects
Oncology, medicine.medical_specialty, business.industry, Immunology, Hazard ratio, Odds ratio, medicine.disease, Rate ratio, Framingham Heart Study, Acquired immunodeficiency syndrome (AIDS), Interquartile range, Internal medicine, Cohort, medicine, Immunology and Allergy, Immunocompetence, business
Abstract

Background The risk of severe COVID-19 varies significantly among persons of similar age and is higher in males. Age-independent, sex-biased differences in susceptibility to severe COVID-19 may be ascribable to deficits in a sexually dimorphic protective attribute that we termed immunologic resilience (IR). Objective To examine whether deficits in IR that antedate or are induced by SARS-CoV-2 infection independently predict COVID-19 mortality. Methods IR levels were quantified with two novel metrics: immune health grades (IHG-I [best] to IHG-IV) to gauge CD8+ and CD4+ T-cell count equilibrium, and blood gene expression signatures. IR metrics were examined in a prospective COVID-19 cohort (n=522); primary outcome was 30-day mortality. Associations of IR metrics with outcomes in non-COVID-19 cohorts (n=13,461) provided the framework for linking pre-COVID-19 IR status to IR during COVID-19, as well as to clinical outcomes. Results IHG-I, tracking high-grade equilibrium between CD8+ and CD4+ T-cell counts, was the most common grade (73%) among healthy adults, particularly in females. SARS-CoV-2 infection associated with underrepresentation of IHG-I (21%) vs. overrepresentation (77%) of IHG-II or IHG-IV, especially in males vs. females (P Conclusion Preservation of immunocompetence with controlled inflammation during antigenic challenges is a hallmark of IR and associates with longevity and AIDS resistance. Independent of age, a male-biased proclivity to degrade IR before and/or during SARS-CoV-2 infection predisposes to severe COVID-19. Clinical implications Biomarkers tracking immunologic resilience may have broad prognostic utility, as they associated with longevity, as well as resistance to a progressive disease course during SARS-CoV-2, influenza, or HIV infection.

Published
2021

35. The Association Between Lung Hyperinflation and Coronary Artery Disease in Smokers

Author

Divay Chandra, Aman Gupta, Gregory L. Kinney, Carl R. Fuhrman, Joseph K. Leader, Alejandro A. Diaz, Jessica Bon, R. Graham Barr, George Washko, Matthew Budoff, John Hokanson, Frank C. Sciurba, James D. Crapo, Edwin K. Silverman, Barry J. Make, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Adel R. Boueiz, Peter J. Castaldi, Michael Cho, Dawn L. DeMeo, Marilyn G. Foreman, Eitan Halper-Stromberg, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dmitry Prokopenko, Dandi Qiao, Phuwanat Sakornsakolpat, Emily S. Wan, Sungho Won, Mustafa Al Qaisi, Harvey O. Coxson, Teresa Gray, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Douglas Stinson, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Carla G. Wilson, Robert Jensen, Jim Crooks, Douglas Everett, Camille Moore, null Strand, John Hughes, Gregory Kinney, Katherine Pratte, Kendra A. Young, Surya Bhatt, Carlos Martinez, Susan Murray, Xavier Soler, Farnoush Banaei-Kashani, Russell P. Bowler, Katerina Kechris, Jeffrey L. Curtis, Perry G. Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Michael E. DeBakey, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Eugene Berkowitz, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Surya P. Bhatt, Anand Iyer, Hrudaya Nath, J. Michael Wells, Joe Ramsdell, Paul Friedman, Andrew Yen, Alejandro P. Comellas, Karin F. Hoth, John Newell, Brad Thompson, Ella Kazerooni, Carlos H. Martinez, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, and Mario E. Ruiz

Subjects
Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Coronary Artery Disease, Critical Care and Intensive Care Medicine, COPD: Original Research, Coronary artery disease, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, Functional residual capacity, Risk Factors, Internal medicine, medicine, Humans, Lung volumes, 030212 general & internal medicine, Myocardial infarction, Lung, Subclinical infection, COPD, business.industry, Smoking, Organ Size, Middle Aged, respiratory system, medicine.disease, Coronary Vessels, United States, Respiratory Function Tests, respiratory tract diseases, Airway Obstruction, Plethysmography, Biological Variation, Population, Pulmonary Emphysema, 030228 respiratory system, Asymptomatic Diseases, Cohort, Cardiology, Airway Remodeling, Female, Tomography, X-Ray Computed, Cardiology and Cardiovascular Medicine, business
Abstract

BACKGROUND: Smokers manifest varied phenotypes of pulmonary impairment. RESEARCH QUESTION: Which pulmonary phenotypes are associated with coronary artery disease (CAD) in smokers? STUDY DESIGN AND METHODS: We analyzed data from the University of Pittsburgh COPD Specialized Center for Clinically Oriented Research (SCCOR) cohort (n = 481) and the Genetic Epidemiology of COPD (COPDGene) cohort (n = 2,580). Participants were current and former smokers with > 10 pack-years of tobacco exposure. Data from the two cohorts were analyzed separately because of methodologic differences. Lung hyperinflation was assessed by plethysmography in the SCCOR cohort and by inspiratory and expiratory CT scan lung volumes in the COPDGene cohort. Subclinical CAD was assessed as the coronary artery calcium score, whereas clinical CAD was defined as a self-reported history of CAD or myocardial infarction (MI). Analyses were performed in all smokers and then repeated in those with airflow obstruction (FEV(1) to FVC ratio, < 0.70). RESULTS: Pulmonary phenotypes, including airflow limitation, emphysema, lung hyperinflation, diffusion capacity, and radiographic measures of airway remodeling, showed weak to moderate correlations (r < 0.7) with each other. In multivariate models adjusted for pulmonary phenotypes and CAD risk factors, lung hyperinflation was the only phenotype associated with calcium score, history of clinical CAD, or history of MI (per 0.2 higher expiratory and inspiratory CT scan lung volume; coronary calcium: OR, 1.2; 95% CI, 1.1-1.5; P = .02; clinical CAD: OR, 1.6; 95% CI, 1.1-2.3; P = .01; and MI in COPDGene: OR, 1.7; 95% CI, 1.0-2.8; P = .05). FEV(1) and emphysema were associated with increased risk of CAD (P < .05) in models adjusted for CAD risk factors; however, these associations were attenuated on adjusting for lung hyperinflation. Results were the same in those with airflow obstruction and were present in both cohorts. INTERPRETATION: Lung hyperinflation is associated strongly with clinical and subclinical CAD in smokers, including those with airflow obstruction. After lung hyperinflation was accounted for, FEV(1) and emphysema no longer were associated with CAD. Subsequent studies should consider measuring lung hyperinflation and examining its mechanistic role in CAD in current and former smokers.

Published
2021

36. Driving Pressure Is a Risk Factor for ARDS in Mechanically Ventilated Subjects Without ARDS

Author

Nicolás Nin, Manuel Jibaja, Jordi Riera, César Laborda, Marina García-de-Acilu, Fernando Frutos-Vivar, Salvatore Maurizio Maggiore, Lorenzo del-Sorbo, Pravin Amin, Nahit Cakar, Dimitros Matamis, Fernando Rios, Marco Antonio Soares, Oriol Roca, Alfonso Muriel, Maria del Carmen Marín, Antonio Anzueto, Andrew D. Bersten, Fekri Abroug, Gee Young Suh, Yuda Sutherasan, Oscar Peñuelas, Amine Ali Zeggwagh, Konstantinos Raymondos, Bin Du, Andrés Esteban, Bruno do Valle Pinheiro, Arnaud W. Thille, Marco González, and Judit Sacanell

Subjects
Pulmonary and Respiratory Medicine, Mechanical ventilation, medicine.medical_specialty, ARDS, Potential risk, business.industry, Respiration, Ventilator-Induced Lung Injury, medicine.medical_treatment, General Medicine, Odds ratio, Critical Care and Intensive Care Medicine, Logistic regression, medicine.disease, Internal medicine, Post-hoc analysis, Tidal Volume, medicine, Cardiology, Humans, In patient, Original Research Article, Risk factor, business, Lung
Abstract

BACKGROUND: Driving pressure (ΔP) has been described as a risk factor for mortality in patients with ARDS. However, the role of ΔP in the outcome of patients without ARDS and on mechanical ventilation has received less attention. Our objective was to evaluate the association between ΔP on the first day of mechanical ventilation with the development of ARDS. METHODS: This was a post hoc analysis of a multicenter, prospective, observational, international study that included subjects who were on mechanical ventilation for > 12 h. Our objective was to evaluate the association between ΔP on the first day of mechanical ventilation with the development of ARDS. To assess the effect of ΔP, a logistic regression analysis was performed when adjusting for other potential risk factors. Validation of the results obtained was performed by using a bootstrap method and by repeating the same analyses at day 2. RESULTS: A total of 1,575 subjects were included, of whom 65 (4.1%) developed ARDS. The ΔP was independently associated with ARDS (odds ratio [OR] 1.12, 95% CI 1.07–1.18 for each cm H(2)O of ΔP increase, P < .001). The same results were observed at day 2 (OR 1.14, 95% CI 1.07–1.21; P < .001) and after bootstrap validation (OR 1.13, 95% CI 1.04–1.22; P < .001). When taking the prevalence of ARDS in the lowest quartile of ΔP (≤9 cm H(2)O) as a reference, the subjects with ΔP > 12–15 cm H(2)O and those with ΔP > 15 cm H(2)O presented a higher probability of ARDS (OR 3.65, 95% CI 1.32–10.04 [P = .01] and OR 7.31, 95% CI, 2.89–18.50 [P < .001], respectively). CONCLUSIONS: In the subjects without ARDS, a higher level of ΔP on the first day of mechanical ventilation was associated with later development of ARDS. (ClinicalTrials.gov registration NCT02731898.)

Published
2021

37. Low-dose methylprednisolone treatment in critically ill patients with severe community-acquired pneumonia

Author

G Umberto, Meduri, Mei-Chiung, Shih, Lisa, Bridges, Thomas J, Martin, Ali, El-Solh, Nitin, Seam, Anne, Davis-Karim, Reba, Umberger, Antonio, Anzueto, Peruvemba, Sriram, Charlie, Lan, Marcos I, Restrepo, Juan J, Guardiola, Teresa, Buck, David P, Johnson, Anthony, Suffredini, W Andrew, Bell, Julia, Lin, Lan, Zhao, Lauren, Uyeda, Lori, Nielsen, Grant D, Huang, and Guy Soo, Hoo

Subjects
Adult, Community-acquired pneumonia, Critical Illness, Clinical Trials and Supportive Activities, Clinical Sciences, Methylprednisolone, Clinical Research, Humans, Glucocorticoids, Lung, ESCAPe Study Group, Respiration, Evaluation of treatments and therapeutic interventions, Pneumonia, Respiration, Artificial, Emergency & Critical Care Medicine, Community-Acquired Infections, Treatment Outcome, Good Health and Well Being, Intensive care, 6.1 Pharmaceuticals, Artificial, Pneumonia & Influenza, Respiratory, Public Health and Health Services, Randomized clinical trial
Abstract

PurposeSevere community-acquired pneumonia (CAP) requiring intensive care unit admission is associated with significant acute and long-term morbidity and mortality. We hypothesized that downregulation of systemic and pulmonary inflammation with prolonged low-dose methylprednisolone treatment would accelerate pneumonia resolution and improve clinical outcomes.MethodsThis double-blind, randomized, placebo-controlled clinical trial recruited adult patients within 72-96h of hospital presentation. Patients were randomized in 1:1 ratio; an intravenous 40mg loading bolus was followed by 40mg/day through day 7 and progressive tapering during the 20-day treatment course. Randomization was stratified by site and need for mechanical ventilation (MV) at the time of randomization. Outcomes included a primary endpoint of 60-day all-cause mortality and secondary endpoints of morbidity and mortality up to 1year of follow-up.ResultsBetween January 2012 and April 2016, 586 patients from 42 Veterans Affairs Medical Centers were randomized, short of the 1420 target sample size because of low recruitment. 584 patients were included in the analysis. There was no significant difference in 60-day mortality between the methylprednisolone and placebo arms (16% vs. 18%; adjusted odds ratio 0.90, 95% CI 0.57-1.40). There were no significant differences in secondary outcomes or complications.ConclusionsIn patients with severe CAP, prolonged low-dose methylprednisolone treatment did not significantly reduce 60-day mortality. Treatment was not associated with increased complications.

Published
2022

38. Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus tiotropium monotherapy in patients with COPD

Author

Alberto Papi, Mitchell Kaye, Morrys C. Kaisermann, Chang-Qing Zhu, Antonio Anzueto, Catherine Harvey, Sandeep Bansal, David Erb, Neil Martin, David A. Lipson, Chris Compton, Nicola Brown, Thomas C Corbridge, and Martin Anderson

Subjects
Pulmonary and Respiratory Medicine, Quinuclidines, medicine.medical_specialty, Socio-culturale, Therapeutics, Chlorobenzenes, Placebo, Gastroenterology, Article, Fluticasone propionate, Pulmonary Disease, Chronic Obstructive, tiotropium monotherapy, chemistry.chemical_compound, Diseases of the respiratory system, Medical research, Double-Blind Method, Forced Expiratory Volume, Internal medicine, Administration, Inhalation, medicine, Clinical endpoint, Humans, COPD, In patient, Tiotropium Bromide, Benzyl Alcohols, RC705-779, business.industry, Nebulizers and Vaporizers, Chronic obstructive pulmonary disease, Inhaler, Single-inhaler fluticasone furoate/umeclidinium/vilanterol triple therapy, Public Health, Environmental and Occupational Health, Single-inhaler fluticasone furoate/umeclidinium/vilanterol triple therapy, tiotropium monotherapy, COPD, medicine.disease, Bronchodilator Agents, respiratory tract diseases, Androstadienes, Treatment Outcome, chemistry, UMECLIDINIUM/VILANTEROL, Vilanterol, business, medicine.drug
Abstract

Chronic obstructive pulmonary disease (COPD) treatment guidelines do not currently include recommendations for escalation directly from monotherapy to triple therapy. This 12-week, double-blind, double-dummy study randomized 800 symptomatic moderate-to-very-severe COPD patients receiving tiotropium (TIO) for ≥3 months to once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 mcg via ELLIPTA (n = 400) or TIO 18 mcg via HandiHaler (n = 400) plus matched placebo. Study endpoints included change from baseline in trough forced expiratory volume in 1 s (FEV1) at Days 85 (primary), 28 and 84 (secondary), health status (St George’s Respiratory Questionnaire [SGRQ] and COPD Assessment Test [CAT]) and safety. FF/UMEC/VI significantly improved trough FEV1 at all timepoints (Day 85 treatment difference [95% CI] 95 mL [62–128]; P

Published
2021

39. Air pollution and COPD: GOLD 2023 committee report

Author

Don D. Sin, Dany Doiron, Alvar Agusti, Antonio Anzueto, Peter J. Barnes, Bartolome R. Celli, Gerard J. Criner, David Halpin, MeiLan K. Han, Fernando J. Martinez, Maria Montes de Oca, Alberto Papi, Ian Pavord, Nicolas Roche, Dave Singh, Robert Stockley, M. Victorina Lopez Varlera, Jadwiga Wedzicha, Claus Vogelmeier, and Jean Bourbeau

Subjects
Pulmonary and Respiratory Medicine
Abstract

Exposure to air pollution is a major contributor to the pathogenesis of COPD worldwide. Indeed, most recent estimates suggest that 50% of the total attributable risk of COPD may be related to air pollution. In response, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Scientific Committee performed a comprehensive review on this topic, qualitatively synthesised the evidence to date and proffered recommendations to mitigate the risk. The review found that both gaseous and particulate components of air pollution are likely contributors to COPD. There are no absolutely safe levels of ambient air pollution and the relationship between air pollution levels and respiratory events is supra-linear. Wildfires and extreme weather events such as heat waves, which are becoming more common owing to climate change, are major threats to COPD patients and acutely increase their risk of morbidity and mortality. Exposure to air pollution also impairs lung growth in children and as such may lead to developmental COPD. GOLD recommends strong public health policies around the world to reduce ambient air pollution and for implementation of public warning systems and advisories, including where possible the use of personalised apps, to alert patients when ambient air pollution levels exceed acceptable minimal thresholds. When household particulate content exceeds acceptable thresholds, patients should consider using air cleaners and filters where feasible. Air pollution is a major health threat to patients living with COPD and actions are urgently required to reduce the morbidity and mortality related to poor air quality around the world.

Published
2023

40. Prevalence of abnormal spirometry in individuals with a smoking history and no known obstructive lung disease

Author

Thuonghien V. Tran, Gregory L. Kinney, Alejandro Comellas, Karin F. Hoth, Arianne K. Baldomero, A. James Mamary, Jeffrey L. Curtis, Nicola Hanania, Richard Casaburi, Kendra A. Young, Victor Kim, Barry Make, Emily S. Wan, Alejandro A. Diaz, John Hokanson, James D. Crapo, Edwin K. Silverman, Surya P. Bhatt, Elizabeth Regan, Spyridon Fortis, Barry J. Make, Elizabeth A. Regan, Terri H. Beaty, Peter J. Castaldi, Michael H. Cho, Dawn L. DeMeo, Adel El Boueiz, Marilyn G. Foreman, Auyon Ghosh, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Wonji Kim, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Dmitry Prokopenko, Matthew Moll, Jarrett Morrow, Dandi Qiao, Aabida Saferali, Phuwanat Sakornsakolpat, Jeong Yun, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Erin Austin, Gregory Kinney, Jessica Bon, Susan Murray, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush BanaeiKashani, Perry G. Pernicano, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R. Graham Barr, John Austin, Belinda D'Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Eric L. Flenaugh, Hirut Gebrekristos, Mario Ponce, Silanath Terpenning, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D'Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Divay Chandra, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, and Harjinder Singh

Subjects
Pulmonary and Respiratory Medicine
Published
2023

41. Mechanical ventilation in Spain, 1998–2016: Epidemiology and outcomes

Author

Oscar Peñuelas, J.M. Quiroga, S. Temprano, Alfonso Muriel, R. de Pablo, A. García-Jiménez, Rafael Fernandez, Miquel Ferrer, Fernando Frutos-Vivar, F. Gordo, M. Leon, J. Mancebo, A. Esteban, I. Vallverdú, M. Valledor, and Antonio Anzueto

Subjects
medicine.medical_specialty, Variabilidad clínica, Epidemiology, medicine.medical_treatment, Lung injury, 03 medical and health sciences, Mechanical ventilation, 0302 clinical medicine, Post-hoc analysis, Epidemiología, Medicine, Mortality, Variability, Tidal volume, business.industry, 030208 emergency & critical care medicine, Ventilación mecánica, 030228 respiratory system, SAPS II, Mortalidad, Emergency medicine, Breathing, business, Cohort study
Abstract

PURPOSE: To evaluate changes in the epidemiology of mechanical ventilation in Spain from 1998 to 2016. DESIGN: A post hoc analysis of four cohort studies was carried out. SETTING: A total of 138 Spanish ICUs. PATIENTS: A sample of 4293 patients requiring invasive mechanical ventilation for more than 12h or noninvasive ventilation for more than 1h. INTERVENTIONS: None. VARIABLES OF INTEREST: Demographic variables, reason for mechanical ventilation, variables related to ventilatory support (ventilation mode, tidal volume, PEEP, airway pressures), complications during mechanical ventilation, duration of mechanical ventilation, ICU stay and ICU mortality. RESULTS: There was an increase in severity (SAPSII: 43 points in 1998 vs. 47 points in 2016), changes in the reason for mechanical ventilation (decrease in chronic obstructive pulmonary disease and acute respiratory failure secondary to trauma, and increase in neurological disease and post-cardiac arrest). There was an increase in noninvasive mechanical ventilation as the first mode of ventilatory support (p

Published
2021

42. Treatment of Community-Acquired Pneumonia in Immunocompromised Adults

Author

Stephen Furmanek, Bin Cao, Gustavo Lopardo, Eric M. Mortensen, Mark L. Metersky, Francesco Blasi, Julio Ramirez, Francisco Arancibia, Michael S. Niederman, Yann-Erick Claessens, Patrick G. P. Charles, Scott E. Evans, Brandon J. Webb, Elie Azoulay, Takaya Maruyama, Yuichiro Shindo, Martin Witzenrath, Steven D. Burdette, Antoni Torres, Chadi A. Hage, Richard G. Wunderink, Kristina Crothers, Antonio Anzueto, Jean Chastre, Marcos I. Restrepo, Rodrigo Cavallazzi, Charles Feldman, Mathias W. Pletz, Donna Mildvan, Jordi Rello, Muriel Fartoukh, Carlos M. Luna, Stefano Aliberti, Forest W Arnold, James D. Chalmers, Daniel M. Musher, Thomas M. File, Charles S. Dela Cruz, Filipe Froes, Tobias Welte, Rosario Menéndez, Jose Bordon, Grant W. Waterer, Martin Gnoni, Xavier Duval, and Nathan C. Dean

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, education.field_of_study, business.industry, Population, Delphi method, Immunocompromised patient, Critical Care and Intensive Care Medicine, medicine.disease, Pneumocystis pneumonia, 03 medical and health sciences, Pneumonia, 0302 clinical medicine, 030228 respiratory system, Community-acquired pneumonia, medicine, Initial treatment, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, Intensive care medicine, education, business, Research question
Abstract

Background Community-acquired pneumonia (CAP) guidelines have improved the treatment and outcomes of patients with CAP, primarily by standardization of initial empirical therapy. But current society-published guidelines exclude immunocompromised patients. Research Question There is no consensus regarding the initial treatment of immunocompromised patients with suspected CAP. Study Design and Methods This consensus document was created by a multidisciplinary panel of 45 physicians with experience in the treatment of CAP in immunocompromised patients. The Delphi survey methodology was used to reach consensus. Results The panel focused on 21 questions addressing initial management strategies. The panel achieved consensus in defining the population, site of care, likely pathogens, microbiologic workup, general principles of empirical therapy, and empirical therapy for specific pathogens. Interpretation This document offers general suggestions for the initial treatment of the immunocompromised patient who arrives at the hospital with pneumonia.

Published
2020

43. Inter-country variability over time in the mortality of mechanically ventilated patients

Author

Bruno do Valle Pinheiro, Jordi Mancebo, Marco González, Dimitros Matamis, Marco Antonio Soares, Maria del Carmen Marín, Antonio Anzueto, Fernando Frutos-Vivar, Manuel Jibaja, Nahit Cakar, Víctor Abraira, Andrew D. Bersten, Yuda Sutherasan, Alfonso Muriel, Lorenzo del-Sorbo, Oscar Peñuelas, Andrés Esteban, Amine Ali Zeggwagh, Pravin Amin, Fekri Abroug, Fernando Rios, Salvatore Maurizio Maggiore, Gee Young Suh, Niall D. Ferguson, Konstantinos Raymondos, Bin Du, Arnaud W. Thille, and Nicolás Nin

Subjects
medicine.medical_specialty, Original, Epidemiology, medicine.medical_treatment, Critical Care and Intensive Care Medicine, Hypoxemia, 03 medical and health sciences, 0302 clinical medicine, Mechanical ventilation, Anesthesiology, Internal medicine, medicine, Odds Ratio, Humans, Variability, Mortality, Outcome, business.industry, Confounding, 030208 emergency & critical care medicine, Odds ratio, Respiration, Artificial, Confidence interval, Clinical trial, 030228 respiratory system, medicine.symptom, business
Abstract

Purpose Variations in clinical characteristics and management and in the mortality of mechanically ventilated patients have not been sufficiently evaluated. We hypothesized that mortality shows a variability associated with country after adjustment for clinical characteristics and management. Methods Analysis of four studies carried out at 6-year intervals over an 18-year period. The studies included 26,024 patients (5183 in 1998, 4968 in 2004, 8108 in 2010, and 7765 in 2016) admitted to 1253 units from 38 countries. The primary outcome was 28-day mortality. We performed analyses using multilevel logistic modeling with mixed-random effects, including country as a random variable. To evaluate the effect of management strategies on mortality, a mediation analysis was performed. Results Adjusted 28-day mortality decreased significantly over time (first study as reference): 2004: odds ratio 0.82 (95% confidence interval [CI] 0.72–0.93); 2010: 0.63 (95% CI 0.53–0.75); 2016: 0.49 (95% CI 0.39–0.61). A protective ventilatory strategy and the use of continuous sedation mediated a moderate fraction of the effect of time on mortality in patients with moderate hypoxemia and without hypoxemia, respectively. Logistic multilevel modeling showed a significant effect of country on mortality: median odds ratio (MOR) in 1998: 2.02 (95% CI 1.57–2.48); in 2004: 1.76 (95% CI 1.47–2.06); in 2010: 1.55 (95% CI 1.37–1.74), and in 2016: 1.39 (95% CI 1.25–1.54). Conclusions These findings suggest that country could contribute, independently of confounder variables, to outcome. The magnitude of the effect of country decreased over time. Clinical trials registered with http://www.clinicaltrials.gov (NCT02731898). Electronic supplementary material The online version of this article (10.1007/s00134-019-05867-9) contains supplementary material, which is available to authorized users.

Published
2020

44. Mortality and Exacerbation Risk by Body Mass Index in Patients with COPD in TIOSPIR and UPLIFT

Author

Bartolome R. Celli, Robert A. Wise, Donald P. Tashkin, Peter M.A. Calverley, Nirupama Putcha, Achim Mueller, Antonio Anzueto, and Norbert Metzdorf

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, COPD, Exacerbation, business.industry, Hazard ratio, nutritional and metabolic diseases, Overweight, medicine.disease, Obesity, Confidence interval, Body Mass Index, Pulmonary Disease, Chronic Obstructive, Risk Factors, Internal medicine, medicine, Humans, Female, Underweight, medicine.symptom, Tiotropium Bromide, business, Body mass index
Abstract

Rationale: There is an association between body mass index (BMI) and mortality in chronic obstructive pulmonary disease (COPD), with underweight individuals having higher mortality risk. Mortality and exacerbation risks among individuals with higher BMI are unclear. Objective: To examine the relationship between BMI and adverse outcomes in COPD. Methods: This post hoc analysis included data from Tiotropium Safety and Performance in Respimat® (TIOSPIR®) (N=17,116) and tiotropium-treated patients in Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) (N=2986). BMI classes (underweight [BMI

Published
2022

45. Easy prognostic assessment of concomitant organ failure in critically ill patients undergoing mechanical ventilation

Author

Dimitros Matamis, Lorenzo del-Sorbo, Fekri Abroug, Arnaud W. Thille, Marco Antonio Soares, Konstantinos Raymondos, Bin Du, Amine Ali Zeggwagh, Nahit Cakar, Oscar Peñuelas, Yuda Sutherasan, Pravin Amin, Alfonso Muriel, Fernando Frutos-Vivar, Manuel Jibaja, Michael Lichtenauer, Nicolás Nin, Fernando Rios, Salvatore Maurizio Maggiore, Maria del Carmen Marín, Antonio Anzueto, Andrew D. Bersten, Gee Young Suh, Bernhard Wernly, Christian Jung, Andrés Esteban, Malte Kelm, Bruno do Valle Pinheiro, and Marco González

Subjects
Adult, Male, ARDS, medicine.medical_specialty, Critical Illness, medicine.medical_treatment, Youden's J statistic, 030204 cardiovascular system & hematology, Risk Assessment, Severity of Illness Index, End Stage Liver Disease, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Internal medicine, Internal Medicine, medicine, Humans, Hospital Mortality, International Normalized Ratio, 030212 general & internal medicine, Aged, Retrospective Studies, Mechanical ventilation, Framingham Risk Score, Proportional hazards model, business.industry, Hemodynamics, Middle Aged, Prognosis, medicine.disease, Respiration, Artificial, Survival Analysis, body regions, Concomitant, Multivariate Analysis, Cohort, Female, business
Abstract

Acute respiratory distress syndrome (ARDS) is a life-threatening disease. We evaluated the prognostic utility of Model for End-stage Liver Disease excluding INR (MELD-XI) score for predicting mortality in a cohort of critically ill patients on mechanical ventilation.In total, 11,091 mechanically ventilated patients were included in our post-hoc retrospective analysis, a subgroup of the VENTILA study (NCT02731898). Evaluation of associations with mortality was done by logistic and Cox regression analysis, an optimal cut-off was calculated using the Youden Index. We divided the cohort in two sub-groups based on their MELD-XI score at the optimal cut-off (12 score points).Peak-, plateau- and positive end-expiratory pressure were higher in patients with MELD-XI12. Patients with MELD-XI12 had higher driving pressures (14 ± 6 cmH2O versus 13 ± 6; p 0.001). MELD-XI was associated with 28-day mortality after correction for relevant cofounders including SAPS II and ventilation pressures (HR 1.04 95%CI 1.03-1.05; p 0.001. Patients with MELD-XI12 evidenced both increased hospital (46% versus 27%; p 0.001) and 28-day mortality (39% versus 22%).MELD-XI is independently associated with mortality and constitutes a useful and easily applicable tool for risk stratification in critically ill patients receiving mechanical ventilation.NCT02731898, registered 4 April 2016.

Published
2019

46. Evolution Over Time of Ventilatory Management and Outcome of Patients With Neurologic Disease

Author

Tejerina E. E., Pelosi P., Robba C., Penuelas O., Muriel A., Barrios D., Frutos-Vivar F., Raymondos K., Du B., Thille A. W., Rios F., Gonzalez M., Del-Sorbo L., Marin M. D. C., Valle Pinheiro B., Soares M. A., Nin N., Maggiore S. M., Bersten A., Amin P., Cakar N., Young Suh G., Abroug F., Jibaja M., Matamis D., Ali Zeggwagh A., Sutherasan Y., Anzueto A., Esteban A, Fernando Ríos, Damian Violi, Marisol Rodríguez-Goñi, Roger Lamoglie, Fernando Villarejo, Norberto Tiribelli, Santiago Ilutovich, Matías Brizuela, Mariana Monllau, Fernando Saldarini, Silvina Borello, Alberto Marino, Mauricio Vinzio, Karina Bonasegla, Julián Hernández, María Belén Yapur, María Eugenia González, Sebastián E Mare, Judith Sagardía, Marco Bezzi, Cecilia Pereyra, Julian Strati, Daniel Vargas, Claudia Diaz, Pablo Gómez, Marcelo Palavecino, Graciela Elizabeth, Aguilera García, M Eugenia, Luis Pablo Cardonnet, Lisandro Betttini, Hernán Nuñez, Lucas Vallejo, Fernando Fernández, Jorge Arroyo, Daniel Duarte, Gerardo Filippa, Cayetano Galetti, Hernan Nunia, Fernando Lambert, Elisa Estenssoro, Marina Busico, Javier Horacio Álvarez, Alejandro Raimondi, Gustavo Badariotti, Martín Lugaro, Fernando Lipovestky, Alan Javier Zazu, Hugo Capponcelli, Patricia Vogl, Cristina Orlandi, Alejandro Gómez, Gustavo Jannello, Alejandro Risso, Leticia Rapetti, Guillermo Chiappero, Juan Domingo Fernández, Rodrigo E Gómez-Paz, Marcos Juan Zec, Pascual Valdez, Jorgelina Guyon, Ariel Chena, Sergio Lasdica, Martin Deheza, Schimdt Alejandra, Francisco Criado, Norma Beatriz Márquez, Pablo Desmery, José Luis Scapellato, Gonzalo Javier Ríos, Cristian Casabella, Jasmin Board, Andrew Davies, Andrew Bersten, Elisha Matheson, Amy Waters, John Santamaria, Jennifer Holmes, Cartan Costello, Manoj K Saxena, John Myburgh, Ellen Kinkel, Forbes McGain, Claire Cattigan, Allison Bone, Ian Seppelt, Leonie Weisbrodt, Cheryl Cuzner, Christopher MacIsaac, Deborah Barge, Tania Caf, Cameron Knott, Graeme Duke, Imogen Mitchell, Helen Rodgers, Rachel Whyte, Elisha Fulton, Alistair Nichol, Hergen Buscher, Priya Nair, Claire Reynolds, Simon J G Hockley, Ian Moore, Katherine Davidson, David Milliss, Raju Pusapati, Helen Wong, Jason Fletcher, Julie Smith, Paul Goldrick, Dianne Stephens, Jane Thomas, Anders Aneman, Sutrisno Gunawan, Tom Cowlam, George Lukas, Rick McAllister, Minka Springham, Joanne Sutton, Jeff Presneill, Tony Sutherland, Dianne Hill, Howard Connor, Jenny Dennett, Tim Coles, Freddy Sandy, Sando Chavarria, Marcelo Choque, Ronald Pairumani, Juan Guerra, Marco Antônio Soares Reis, José Carlos Versiani, Eduardo Fonseca Sad, Maria Aparecida Braga, Dinalva Aparecida Gomes, Fernando Antônio Botoni, Maurício Meireles Góes, Frederico Costa Val Barros, Rogério de Castro Pereira, Hugo Urbano, Valéria de Carvalho Magela, Aline Camile Yehia, Bruno Bonaccorsi Fernandino, Marco Antônio Ribeiro Leão, Rovílson Lara, Rubens Altair Amaral de Pádua, Janine Dias Alves, Aloísio Marques do Nascimento, Bruno do Valle Pinheiro, Carlos Alberto Studart Gomes, Marcelo Alcântara Holanda, Frederico Rodrigues Anselmo, Niall Ferguson, Neill Adhikari, Robert Fowler, Cheromi Sittambalam, Mehar-Un-Nisa Raja, Nicole Marinoff, Lauralyn McIntryre, Shawna Reddie, Laura Jones, Irene Watpool, Jeffrey Singh, Madison Dennis, Andrea Matte, Marc Lipkus, Ryan Albert, Andrew Steel, Emily Stern, Michael Miletin, Antonio Raso, Robyn Klages, Jan Friedrich, Orla Smith, Laura Wilson, Deborah Cook, Mark Bailey, Sangeeta Mehta, Stephen Lapinsky, Hannah Mathers, Cheryl Ethier, Stephanie Lubchansky, Samer Haj-Bakri, Dietrich Henzler, Lisa Julien, Luis Soto-Román, Juan Carlos Maurelia, César Antonio Maquilon, Luis Soto-Germani, Bin Du, Yan Kang, Bo Wang, Fachun Zhou, Fang Xu, Haibo Qiu, Yi Yang, Qingyuan Zhan, Bing Sun, Zhenjie Hu, Bin Yu, Xi Zhu, Yu Bai, Gang Li, Yi Li, Geng Zhang, Jianbiao Meng, Xiaobo Huang, Hong Pu, Daxing Yu, Chuanyun Qian, Wei Zhang, Yongjie Yin, Debiao Song, Yunxuan Yue, Zhengxuan Lv, Chengmin Yu, Qunmei Yao, Xue Wang, Yuan Xu, Wei He, Mian Chen, Zhihua Hu, Dongpo Jiang, Jian Huang, Wei Yu, Juanxian Gu, Yangong Chao, Zhixiang Li, Zhicheng Zhang, Wanxia Li, Zhenyang He, Jianguo Li, Chang Liu, Tiehe Qin, Shouhong Wang, Feng Li, Jun Jin, Jianhong Fu, Hongyang Xu, Hongyuan Lin, Jianying Guo, Yalin Liu, Jinghua Wang, Maoqin Li, Jiaqiong Li, Lei Chen, Qing Song, Liang Pan, Xianyao Wan, Jiuzhi Zhang, Weihai Yao, Yuhong Guo, Pang Wing Yan, Kelly Choy, Kwan Ming Chit, Patricia Leung, Chau Chin Man, Marco González, Ricardo Buitrago, Marcela Granados, Guillermo Ortiz, Cesar Enciso, Mario Gómez, Bladimir Alejandro Gil, Juan Pablo Sedano, Luis Fernando Castro Castro, Carlo Alberto Acosta, Marco Gonzalez, Francisco Molina, Camilo Pizarro, Mario Villabon, Carmelo Dueñas, Carlos Andrés Díaz, Nelson Fonseca, Rubén Camargo, Juan David Uribe, Hans-Henrik Bülow, Simona Beniczky, Jens Brushoj, Mikkel Præst, Birgitte Viebaek, Sine Wichman, Anette Mortensen, Susanne Andi Iversen, Bo Broberg, Edgard Luna, Manuel Jibaja, Leonardo Pazmiño, Katty Trelles, Fabricio Picoita, Gustavo Paredes, Vanesa Ramírez, Guillermo Falconí, Cristian Cevallos, Boris Villamagua, Marco Escobar, Freddy Sánchez, Miguel Llano, Miguel Lazcano, Ramiro Puetate, José Miguel Guerrero, Mijail Játiva, Myriam Montalvo, Franklin Villegas, Luis González Zambrano, Ronnie Mantilla, Gina Quinde, Andrea Gimenez, Luis Gonzalez Mosquera, Henry Caballero, María Fernanda García, Marcelo Ochoa, Soraya Puertas, Jackeline Coello, Mario Acosta, Medhat Soliman, Arnaud W Thille, Achille Kouatchet, Alain Mercat, Laurent Brochard, François Collet, Guillaume Marcotte, Pascal Beuret, Jean-Christophe M Richard, Gaëtan Bedunaeu, Pierre-Gildas Guitard, Fabien Soulis, Frédéric Bellec, Philippe Berger, Dorothée Carpentier, Benoit Veber, Salem Ould Zein, Géraldine Dessertaine, C Canevet, Fabien Grelon, Konstantinos Raymondos, Rolf Dembinski, Rolf Rossaint, Steffen Weber-Carstens, Christian Putensen, Maximillian Ragaller, Michael Quintel, Winfried Schubert, Thomas Bein, Heinrich Paulus, Walter Brandt, Lutz Pfeiffer, Silke Frenzel, Thoralf Kerner, P Kruska, Leila Eckholt, Joachim Hartung, Harald Fritz, Monika Holler, Johannes Busch, Andreas Viehöfer, Jens Buettner, Jörn Schlechtweg, Achim Lunkeit, Roland Schneider, Maria Wussow, Nils Marquardt, Christian Frenkel, Falk Hildebrandt, Tumbass Volker, Thomas Lipp, Cezar Mihailescu, Thomas Moellhoff, Thomas Steinke, Oliver Franke, Marcus Ruecker, Markus Schappacher, Steffen Appel, Heinz Kerger, Andreas Schwartz, Jan Dittmann, Jörg Haberkorn, Wolfgang Baier, Walter Seyde, Dimitros Matamis, Eleni Antoniadou, Pertsas Evangelos, Maria Giannakou, Zoltan Szentkereszty, Zsolt Molnar, Pravin Amin, Farhad N Kapadia, Nagarajan Ramakrishnan, Deepak Govil, Anitha Shenoy, Umesh G, Samir Sahu, Sheila Nainan Myatra, Subhash Kumar Todi, Sanjay Dhanuka, Mayur Patel, P Samaddar, Dhruva Chaudhry, Vivek Joshi, Srinivas Samavedam, Ankur Devendra Bhavsar, Prachee Sathe, Sujoy Mukherjee, Salvatore Maurizio Maggiore, Francesco Idone, Federica Antonicelli, Paolo Navalesi, Rosanna Vaschetto, Arianna Boggero, Rosalba Tufano, Michele Iannuzzi, Edoardo De Robertis, Romano Tetamo, Andrea Neville Cracchiolo, Antonio Braschi, Francesco Mojoli, Ilaria Curro', Mirko Belliato, Chiara Verga, Marta Ferrari, Erika Mannelli, Valerio Mangani, Giorgio Tulli, Francesca Frigieri, Armando Pedulla', Monica Rocco, Giorgia Citterio, Di Russo, Gaetano Perchiazzi, Loredana Pitagora, Antonio Pesenti, Michela Bombino, Davide Chiumello, Federica Tallarini, Serena Azzari, Antonina Pigna, Ivano Aprile, Marco Adversi, Antonio Corcione, Marianna Esposito, Annunziata Mattei, Vito Marco Ranieri, Rosario Urbino, Ilaria Maria Mastromauro, Antonino Giarratano, Maurizio Raineri Santi, Ambrogio Sansone, Younsuck Koh, Moo Suk Park, Je Hyeong Kim, Kyung Chan Kim, Hye Sook Choi, Yun Seong Kim, Jin Hwa Lee, Myung-Goo Lee, Won-Yeon Lee, Jin Young An, Gee Young Suh, Ki-Suck Jung, Asisclo J Villagómez Ortiz, César Cruz Lozano, Zalatiel Maycotte Luna, José Francisco López Baca, José Elizalde, Guillermo Cueto Robledo, Mario Alonso Treviño Salinas, Ricardo Martinez Zubieta, Claudia Olvera-Guzman, Marco Montes De Oca, Silvio A Ñamendys-Silva, José Salvador Martínez Cano, Jose Angel Baltazar Torres, Gustavo Morales Muñoz, Antonio Villa Delgado, Javier Ladape Martinez, Amine Ali Zeggwagh, Tarek Dendane, Abderrahim Azzouzi, Ahmed Sbihi, Wajdi Maazouzi, Mourad Amor, Charki Haimeur, Michael A Kuiper, Matty Koopmans, Uli Strauch, Dennis Bergmans, Serge Heines, Sylvia den Boer, Bas M Kors, Peter van der Voort, Paul J Dennesen, Bert Beishuizen, Ingrid van den Hul, Erna Alberts, Harry P P M Gelissen, Eduard Bootsma, Auke Reidinga, Kim Heus, Diane Mackle, Paul Young, Rachael Parke, Eileen Gilder, Jodi Brown, Lynette Newby, Catherine Simmonds, Jan Mehrtens, Seton Henderson, Tony Williams, Judi Tai, Chantal Hogan, Mary La Pine, John Durning, Sheree Gare, Troy Browne, Shirley Nelson, Jennifer Goodson, Julio Osorio, Chabu Coronado, Rollin Roldán Mori, Rosa Luz López Martínez, Adam Mikstacki, Barbara Tamowicz, Rui Moreno, Eduardo Almeida, Joana Silvestre, Heloisa Castro, Irene Aragão, Susana Alves Ferreira, Nelson Barros, Filomena Faria, Carlos André Correia Casado, Fausto Fialho Moura, Paulo Marcal, Ricardo Matos, Edward Nicolayenko, Mikhail Kirov, Andrey Yaroshetskiy, Andrei Piontek, Valery Subbotin, Yaseen Arabi, Olivia Dulfo, Chafrina Marie Olay, Edgardo E Tabhan, Nicolas Nin, Alfonso Muñoz, César Aragón, Ana Villagrá, Ainhoa Rosselló, Joan Maria Raurich, María Garitacelaya, Miguel Ángel González-Gallego, Francisco Ortuño, Miguel Fernández-Vivas, David Freire, Francisco Guerrero, Francisco Manzano, Juan Carlos, Alfredo Padrón, Pedro Rosa, Rafael Morales, Liliana Caipe, Maurizio Bottiroli, José María Nicolás, Marta Ugalde, Javier Ruiz, Lucia Capilla, Guillermo Muñiz, Jesús Sánchez-Ruiz, Javier Cebrián, Begoña Balerdi, Elena Parreño, Alvaro van Bommel, César Pérez-Calvo, Irene Dot, Javier Blanco, Raquel Manzanedo, José J Blanco, Daniel Fontaneda, Raúl González, Javier Díaz Domínguez, Alfonso Moreno, Antonio Reyes, Ian Carrasco, Itziar Mintegui, Rosa Sebastián, Javier García-Alonso, Carolina Lorencio, Josep Maria Sirvent, Patricia Jimeno, Miguel León, Pedro Galdos, Nuria Alonso, Julia López-Díaz, María Victoria de la Torre, Jorge Vidal Hernández, Nicolás Zamboschi, Francisco Lucena, Gemma Rialp, Raquel Montoiro, Victoria Goñi, María Ángeles Pena, Antonio Maestre, Marc Fabra, Jacinto Baena, Eva Benveniste, Susana Temprano, Jesús Sánchez, Carmen Campos, Sara Cabañes, María Elena Pérez-Losada, José Claudio Leo, Enrique Piacentini, María Del Carmen de la Torre, Laura Álvarez-Montero, Fernando Sánchez, Antonio Viñuales, Bernabé Álvarez, Javier Castañeda, Ángela Alonso, María Isabel Ruiz, Pedro Jesús Domínguez, Marcos Delgado, Eugenio Palazón, Antonio García-Jiménez, Rosa Álvaro, Clara Laplaza Eva Regidor, Enrique Maraví, José María Quiroga, Amalia Martínez de la Gandara, Cecilia Carbayo, María Luisa Navarrete, Manuel Valledor, Raquel Yano, José María Gutiérrez, Javier González-Robledo, Amparo Ferrandiz, Alberto Belenguer, Lidón Mateu, Laura Sayagues, María José Tolón, Nieves Franco, Elena Gallego, Félix Lacoma, Patricia Albert, Vicente Arraez, Mar Gobernado, Susana Moradillo, Carolina Gímenez-Esparza, Teresa Sánchez de Dios, Carlos Marian Crespo, Cecilia Hermosa, Federico Gordo, Genis Carrasco, María Ángeles Alonso, Alejandro Algora, Raúl de Pablo, Sofía García, Ana Carolina Caballero, José María Montón, Teresa Mut, Eva Manteiga, Alejandro de la Serna, Ana Esther Trujillo, Rafael Blancas, Inmaculada Vallverdú, José Manuel Serrano, Miquel Ferrer, Juan Diego Jiménez, Carlos Gallego, Dolores Vila, Luis Marina, Valentín Parra, Juan Ramón Cortés, Chen Chin-Ming, Ai-Chin Cheng, Fekri Abroug, Besbes Mohamed, Imed Chouchene, Mounir Bouaziz, Stambouli Neji, Islem Ouanes, Ayed Samia, Nahit Cakar, Ismail Kati, Ali Aydım Altunkan, Remzi Iscimen, Zafer Dogan, Bilge Çetin, Tayfun Adanir, Sabriye Guvenc, Unase Büyükkoçak, Antonio Anzueto, Ashley Ellis, Gary Kinasewitz, Allan Walkey, Phil Alkana, Gregory A Schmidt, Susan Gillen, Kathleen Lilli, Jennifer Twombley, Denice Wells, Larry Welder, Alejandro Arroliga, Alfredo Vasquez-Sandoval, Vincent John Scott, Craig Cernosek, Christopher Spradley, Dimple Tejwani, Sindhaghatta Venkatram, Gilda Diaz-Fuentes, Amber Monson, Anthony Saleh, Madhav Gudi, George Liziamma, Mohamed A Saad, Crissie De Spirito, Bryan Beatty, Samir Vermani, Crissie Despirito, Zaza Cohen, Amee Patrawalla, Samir Abdelhadi, Rupesh Vakil, Steven Y Chang, Brian Sherman, Rosanna Del Giudice, John Oropell, Timothy D Girard, Cayce Strength, Joyce Okahashi, Leanne Boehm, Matthew Kirchner, Erwin J Oei, Sebastian Circo, Nelson Medina, Mohammed Al-Jagbeer, V J Cardenas Jr, Smyth Smith, Shelby Sutton, Marcela Canola-Mazo, Tim Houlihan, Yogeet Kaur, Travis Parry, Craig A Piquette, Kerry Canady, Rahul Nanchal, Dana K Soetaert, Maria Del Mar Torres-Perez, Carlos Robles-Arias, William Rodriguez-Cintron, Mark Tidswell, Jennifer Germain, Lori-Ann Kozikowski, Erin Braden, Geneva Tatem, Javier Hurtado, Alberto Deicas, Daniel Weiss, Marta Beron, Román Garrido, Cristina Santos, Mario Cancela, Raúl Lombardi, Pedro Alzugaray, Jorge Gerez, Silvia Mareque, Graciela Franca, Oscar Cluzet, Edgardo Nuñez, Julio Pontet, Sergio Cáceres, Elias Caragna, Alberto Soler, Frank Torres, Gastón Pittini, Gabriel D Empaire, Stevens Salva, Fernando Pérez, Clara Pacheco, Zoraida Parra, Ingrid Von der Osten, Luis Williams, José Salinas, Do Danh Quynh, Pham Thi Van Anh, Nguyen Huu Hoang, Nghuyen Ba Tuan, RS: NUTRIM - R2 - Liver and digestive health, MUMC+: MA Arts Assistenten IC (9), Intensive Care, MUMC+: MA Medische Staf IC (9), Tejerina E.E., Pelosi P., Robba C., Penuelas O., Muriel A., Barrios D., Frutos-Vivar F., Raymondos K., Du B., Thille A.W., Rios F., Gonzalez M., Del-Sorbo L., Marin M.D.C., Valle Pinheiro B., Soares M.A., Nin N., Maggiore S.M., Bersten A., Amin P., Cakar N., Young Suh G., Abroug F., Jibaja M., Matamis D., Ali Zeggwagh A., Sutherasan Y., Anzueto A., Esteban A, and Fernando Ríos, Damian Violi, Marisol Rodríguez-Goñi, Roger Lamoglie, Fernando Villarejo, Norberto Tiribelli, Santiago Ilutovich, Matías Brizuela, Mariana Monllau, Fernando Saldarini, Silvina Borello, Alberto Marino, Norberto Tiribelli, Mauricio Vinzio, Karina Bonasegla, Julián Hernández, María Belén Yapur, María Eugenia González, Sebastián E Mare, Judith Sagardía, Marco Bezzi, Cecilia Pereyra, Julian Strati, Daniel Vargas, Claudia Diaz, Pablo Gómez, Marcelo Palavecino, Graciela Elizabeth, Aguilera García, M Eugenia, Luis Pablo Cardonnet, Lisandro Betttini, Hernán Nuñez, Lucas Vallejo, Fernando Fernández, Jorge Arroyo, Daniel Duarte, Gerardo Filippa, Cayetano Galetti, Hernan Nunia, Fernando Lambert, Elisa Estenssoro, Marina Busico, Fernando Villarejo, Javier Horacio Álvarez, Alejandro Raimondi, Gustavo Badariotti, Martín Lugaro, Fernando Lipovestky, Alan Javier Zazu, Hugo Capponcelli, Patricia Vogl, Cristina Orlandi, Alejandro Gómez, Gustavo Jannello, Alejandro Risso, Leticia Rapetti, Guillermo Chiappero, Juan Domingo Fernández, Rodrigo E Gómez-Paz, Marcos Juan Zec, Pascual Valdez, Jorgelina Guyon, Ariel Chena, Sergio Lasdica, Martin Deheza, Schimdt Alejandra, Francisco Criado, Norma Beatriz Márquez, Pablo Desmery, José Luis Scapellato, Gonzalo Javier Ríos, Cristian Casabella, Jasmin Board, Andrew Davies, Andrew Bersten, Elisha Matheson, Amy Waters, John Santamaria, Jennifer Holmes, Cartan Costello, Manoj K Saxena, John Myburgh, Ellen Kinkel, Forbes McGain, Claire Cattigan, Allison Bone, Ian Seppelt, Leonie Weisbrodt, Cheryl Cuzner, Christopher MacIsaac, Deborah Barge, Tania Caf, Cameron Knott, Graeme Duke, Imogen Mitchell, Helen Rodgers, Rachel Whyte, Elisha Fulton, Jasmin Board, Andrew Davies, Alistair Nichol, Hergen Buscher, Priya Nair, Claire Reynolds, Simon J G Hockley, Ian Moore, Katherine Davidson, David Milliss, Raju Pusapati, Helen Wong, Jason Fletcher, Julie Smith, Paul Goldrick, Dianne Stephens, Jane Thomas, Anders Aneman, Sutrisno Gunawan, Tom Cowlam, George Lukas, Rick McAllister, Minka Springham, Joanne Sutton, Jeff Presneill, Tony Sutherland, Dianne Hill, Howard Connor, Jenny Dennett, Tim Coles, Freddy Sandy, Sando Chavarria, Marcelo Choque, Ronald Pairumani, Juan Guerra, Marco Antônio Soares Reis, José Carlos Versiani, Eduardo Fonseca Sad, Maria Aparecida Braga, Dinalva Aparecida Gomes, Fernando Antônio Botoni, Maurício Meireles Góes, Frederico Costa Val Barros, Rogério de Castro Pereira, Hugo Urbano, Valéria de Carvalho Magela, Aline Camile Yehia, Bruno Bonaccorsi Fernandino, Marco Antônio Ribeiro Leão, Rovílson Lara, Rovílson Lara, Rubens Altair Amaral de Pádua, Janine Dias Alves, Aloísio Marques do Nascimento, Bruno do Valle Pinheiro, Carlos Alberto Studart Gomes, Marcelo Alcântara Holanda, Frederico Rodrigues Anselmo, Niall Ferguson, Neill Adhikari, Robert Fowler, Cheromi Sittambalam, Mehar-Un-Nisa Raja, Nicole Marinoff, Lauralyn McIntryre, Shawna Reddie, Laura Jones, Irene Watpool, Jeffrey Singh, Madison Dennis, Andrea Matte, Marc Lipkus, Ryan Albert, Andrew Steel, Emily Stern, Michael Miletin, Antonio Raso, Robyn Klages, Jan Friedrich, Orla Smith, Laura Wilson, Deborah Cook, Mark Bailey, Sangeeta Mehta, Stephen Lapinsky, Hannah Mathers, Cheryl Ethier, Stephanie Lubchansky, Samer Haj-Bakri, Dietrich Henzler, Lisa Julien, Luis Soto-Román, Juan Carlos Maurelia, César Antonio Maquilon, Luis Soto-Germani, Bin Du, Yan Kang, Bo Wang, Fachun Zhou, Fang Xu, Haibo Qiu, Yi Yang, Qingyuan Zhan, Bing Sun, Zhenjie Hu, Bin Yu, Xi Zhu, Yu Bai, Gang Li, Yi Li, Geng Zhang, Jianbiao Meng, Xiaobo Huang, Hong Pu, Bin Du, Daxing Yu, Chuanyun Qian, Wei Zhang, Yongjie Yin, Debiao Song, Yunxuan Yue, Zhengxuan Lv, Chengmin Yu, Qunmei Yao, Xue Wang, Yuan Xu, Wei He, Mian Chen, Zhihua Hu, Dongpo Jiang, Jian Huang, Wei Yu, Juanxian Gu, Yangong Chao, Zhixiang Li, Zhicheng Zhang, Wanxia Li, Zhenyang He, Jianguo Li, Chang Liu, Tiehe Qin, Shouhong Wang, Feng Li, Jun Jin, Jianhong Fu, Hongyang Xu, Hongyuan Lin, Jianying Guo, Yalin Liu, Jinghua Wang, Maoqin Li, Jiaqiong Li, Lei Chen, Qing Song, Liang Pan, Xianyao Wan, Jiuzhi Zhang, Weihai Yao, Yuhong Guo, Pang Wing Yan, Kelly Choy, Kwan Ming Chit, Patricia Leung, Chau Chin Man, Marco González, Ricardo Buitrago, Marcela Granados, Guillermo Ortiz, Cesar Enciso, Mario Gómez, Bladimir Alejandro Gil, Juan Pablo Sedano, Luis Fernando Castro Castro, Carlo Alberto Acosta, Marco Gonzalez, Francisco Molina, Camilo Pizarro, Mario Villabon, Carmelo Dueñas, Carlos Andrés Díaz, Nelson Fonseca, Rubén Camargo, Juan David Uribe, Hans-Henrik Bülow, Simona Beniczky, Jens Brushoj, Mikkel Præst, Birgitte Viebaek, Sine Wichman, Anette Mortensen, Susanne Andi Iversen, Bo Broberg, Edgard Luna, Manuel Jibaja, Leonardo Pazmiño, Katty Trelles, Fabricio Picoita, Gustavo Paredes, Vanesa Ramírez, Guillermo Falconí, Cristian Cevallos, Boris Villamagua, Marco Escobar, Freddy Sánchez, Miguel Llano, Miguel Lazcano, Ramiro Puetate, José Miguel Guerrero, Mijail Játiva, Myriam Montalvo, Franklin Villegas, Luis González Zambrano, Ronnie Mantilla, Gina Quinde, Andrea Gimenez, Luis Gonzalez Mosquera, Henry Caballero, María Fernanda García, Marcelo Ochoa, Soraya Puertas, Jackeline Coello, Mario Acosta, Medhat Soliman, Arnaud W Thille, Achille Kouatchet, Alain Mercat, Laurent Brochard, François Collet, Guillaume Marcotte, Pascal Beuret, Jean-Christophe M Richard, Gaëtan Bedunaeu, Pierre-Gildas Guitard, Fabien Soulis, Frédéric Bellec, Philippe Berger, Dorothée Carpentier, Benoit Veber, Salem Ould Zein, Géraldine Dessertaine, C Canevet, Fabien Grelon, Konstantinos Raymondos, Rolf Dembinski, Rolf Rossaint, Steffen Weber-Carstens, Christian Putensen, Maximillian Ragaller, Michael Quintel, Winfried Schubert, Thomas Bein, Heinrich Paulus, Walter Brandt, Lutz Pfeiffer, Silke Frenzel, Thoralf Kerner, P Kruska, Leila Eckholt, Joachim Hartung, Harald Fritz, Monika Holler, Johannes Busch, Andreas Viehöfer, Jens Buettner, Jörn Schlechtweg, Achim Lunkeit, Roland Schneider, Maria Wussow, Nils Marquardt, Christian Frenkel, Falk Hildebrandt, Tumbass Volker, Thomas Lipp, Cezar Mihailescu, Thomas Moellhoff, Thomas Steinke, Oliver Franke, Marcus Ruecker, Markus Schappacher, Steffen Appel, Heinz Kerger, Andreas Schwartz, Jan Dittmann, Jörg Haberkorn, Wolfgang Baier, Walter Seyde, Dimitros Matamis, Eleni Antoniadou, Pertsas Evangelos, Maria Giannakou, Zoltan Szentkereszty, Zsolt Molnar, Pravin Amin, Farhad N Kapadia, Nagarajan Ramakrishnan, Deepak Govil, Anitha Shenoy, Umesh G, Samir Sahu, Sheila Nainan Myatra, Subhash Kumar Todi, Sanjay Dhanuka, Mayur Patel, P Samaddar, Dhruva Chaudhry, Vivek Joshi, Srinivas Samavedam, Ankur Devendra Bhavsar, Prachee Sathe, Sujoy Mukherjee, Salvatore Maurizio Maggiore, Francesco Idone, Federica Antonicelli, Paolo Navalesi, Rosanna Vaschetto, Arianna Boggero, Rosalba Tufano, Michele Iannuzzi, Edoardo De Robertis, Romano Tetamo, Andrea Neville Cracchiolo, Antonio Braschi, Francesco Mojoli, Ilaria Curro', Mirko Belliato, Chiara Verga, Marta Ferrari, Erika Mannelli, Valerio Mangani, Giorgio Tulli, Francesca Frigieri, Armando Pedulla', Monica Rocco, Giorgia Citterio, Di Russo, Gaetano Perchiazzi, Loredana Pitagora, Antonio Pesenti, Michela Bombino, Davide Chiumello, Federica Tallarini, Serena Azzari, Antonina Pigna, Ivano Aprile, Marco Adversi, Antonio Corcione, Marianna Esposito, Annunziata Mattei, Vito Marco Ranieri, Rosario Urbino, Ilaria Maria Mastromauro, Antonino Giarratano, Maurizio Raineri Santi, Ambrogio Sansone, Younsuck Koh, Moo Suk Park, Je Hyeong Kim, Kyung Chan Kim, Hye Sook Choi, Yun Seong Kim, Jin Hwa Lee, Myung-Goo Lee, Won-Yeon Lee, Jin Young An, Gee Young Suh, Ki-Suck Jung, Asisclo J Villagómez Ortiz, César Cruz Lozano, Zalatiel Maycotte Luna, José Francisco López Baca, José Elizalde, Guillermo Cueto Robledo, Mario Alonso Treviño Salinas, Ricardo Martinez Zubieta, Claudia Olvera-Guzman, Marco Montes De Oca, Silvio A Ñamendys-Silva, José Salvador Martínez Cano, Jose Angel Baltazar Torres, Gustavo Morales Muñoz, Antonio Villa Delgado, Javier Ladape Martinez, Amine Ali Zeggwagh, Tarek Dendane, Abderrahim Azzouzi, Ahmed Sbihi, Wajdi Maazouzi, Mourad Amor, Charki Haimeur, Michael A Kuiper, Matty Koopmans, Uli Strauch, Dennis Bergmans, Serge Heines, Sylvia den Boer, Bas M Kors, Peter van der Voort, Paul J Dennesen, Bert Beishuizen, Ingrid van den Hul, Erna Alberts, Harry P P M Gelissen, Eduard Bootsma, Auke Reidinga, Jasmin Board, Andrew Davies, Kim Heus, Diane Mackle, Paul Young, Rachael Parke, Eileen Gilder, Jodi Brown, Lynette Newby, Catherine Simmonds, Jan Mehrtens, Seton Henderson, Tony Williams, Judi Tai, Chantal Hogan, Mary La Pine, John Durning, Sheree Gare, Troy Browne, Shirley Nelson, Jennifer Goodson, Julio Osorio, Chabu Coronado, Rollin Roldán Mori, Rosa Luz López Martínez, Adam Mikstacki, Barbara Tamowicz, Rui Moreno, Eduardo Almeida, Joana Silvestre, Heloisa Castro, Irene Aragão, Susana Alves Ferreira, Nelson Barros, Filomena Faria, Carlos André Correia Casado, Fausto Fialho Moura, Paulo Marcal, Ricardo Matos, Edward Nicolayenko, Mikhail Kirov, Andrey Yaroshetskiy, Andrei Piontek, Valery Subbotin, Yaseen Arabi, Olivia Dulfo, Chafrina Marie Olay, Edgardo E Tabhan, Nicolas Nin, Alfonso Muñoz, César Aragón, Ana Villagrá, Ainhoa Rosselló, Joan Maria Raurich, María Garitacelaya, Miguel Ángel González-Gallego, Francisco Ortuño, Miguel Fernández-Vivas, David Freire, Francisco Guerrero, Francisco Manzano, Juan Carlos, Alfredo Padrón, Pedro Rosa, Rafael Morales, Liliana Caipe, Maurizio Bottiroli, José María Nicolás, Marta Ugalde, Javier Ruiz, Lucia Capilla, Guillermo Muñiz, Jesús Sánchez-Ruiz, Javier Cebrián, Begoña Balerdi, Elena Parreño, Alvaro van Bommel, César Pérez-Calvo, Irene Dot, Javier Blanco, Raquel Manzanedo, José J Blanco, Daniel Fontaneda, Raúl González, Javier Díaz Domínguez, Alfonso Moreno, Antonio Reyes, Ian Carrasco, Itziar Mintegui, Rosa Sebastián, Javier García-Alonso, Carolina Lorencio, Josep Maria Sirvent, Patricia Jimeno, Miguel León, Pedro Galdos, Nuria Alonso, Julia López-Díaz, María Victoria de la Torre, Jorge Vidal Hernández, Nicolás Zamboschi, Francisco Lucena, Gemma Rialp, Raquel Montoiro, Victoria Goñi, María Ángeles Pena, Antonio Maestre, Marc Fabra, Jacinto Baena, Eva Benveniste, Susana Temprano, Jesús Sánchez, Carmen Campos, Sara Cabañes, María Elena Pérez-Losada, José Claudio Leo, Enrique Piacentini, María Del Carmen de la Torre, Laura Álvarez-Montero, Fernando Sánchez, Antonio Viñuales, Bernabé Álvarez, Javier Castañeda, Ángela Alonso, María Isabel Ruiz, Pedro Jesús Domínguez, Marcos Delgado, Eugenio Palazón, Antonio García-Jiménez, Rosa Álvaro, Clara Laplaza Eva Regidor, Enrique Maraví, José María Quiroga, Amalia Martínez de la Gandara, Cecilia Carbayo, María Luisa Navarrete, Manuel Valledor, Raquel Yano, José María Gutiérrez, Javier González-Robledo, Amparo Ferrandiz, Alberto Belenguer, Lidón Mateu, Laura Sayagues, María José Tolón, Nieves Franco, Elena Gallego, Félix Lacoma, Patricia Albert, Vicente Arraez, Mar Gobernado, Susana Moradillo, Carolina Gímenez-Esparza, Teresa Sánchez de Dios, Carlos Marian Crespo, Cecilia Hermosa, Federico Gordo, Genis Carrasco, María Ángeles Alonso, Alejandro Algora, Raúl de Pablo, Sofía García, Ana Carolina Caballero, José María Montón, Teresa Mut, Eva Manteiga, Alejandro de la Serna, Ana Esther Trujillo, Rafael Blancas, Inmaculada Vallverdú, José Manuel Serrano, Miquel Ferrer, Juan Diego Jiménez, Carlos Gallego, Dolores Vila, Luis Marina, Valentín Parra, Juan Ramón Cortés, Chen Chin-Ming, Ai-Chin Cheng, Fekri Abroug, Besbes Mohamed, Imed Chouchene, Mounir Bouaziz, Stambouli Neji, Islem Ouanes, Ayed Samia, Nahit Cakar, Ismail Kati, Ali Aydım Altunkan, Remzi Iscimen, Zafer Dogan, Bilge Çetin, Tayfun Adanir, Sabriye Guvenc, Unase Büyükkoçak, Antonio Anzueto, Ashley Ellis, Gary Kinasewitz, Allan Walkey, Phil Alkana, Gregory A Schmidt, Susan Gillen, Kathleen Lilli, Jennifer Twombley, Denice Wells, Larry Welder, Alejandro Arroliga, Alfredo Vasquez-Sandoval, Vincent John Scott, Craig Cernosek, Christopher Spradley, Dimple Tejwani, Sindhaghatta Venkatram, Gilda Diaz-Fuentes, Amber Monson, Anthony Saleh, Madhav Gudi, George Liziamma, Mohamed A Saad, Crissie De Spirito, Bryan Beatty, Samir Vermani, Crissie Despirito, Zaza Cohen, Amee Patrawalla, Samir Abdelhadi, Rupesh Vakil, Steven Y Chang, Brian Sherman, Rosanna Del Giudice, John Oropell, Timothy D Girard, Cayce Strength, Joyce Okahashi, Leanne Boehm, Matthew Kirchner, Ashley Ellis, Gary Kinasewitz, Erwin J Oei, Sebastian Circo, Nelson Medina, Mohammed Al-Jagbeer, V J Cardenas Jr, Smyth Smith, Shelby Sutton, Marcela Canola-Mazo, Tim Houlihan, Yogeet Kaur, Travis Parry, Craig A Piquette, Kerry Canady, Rahul Nanchal, Dana K Soetaert, Maria Del Mar Torres-Perez, Carlos Robles-Arias, William Rodriguez-Cintron, Mark Tidswell, Jennifer Germain, Lori-Ann Kozikowski, Erin Braden, Geneva Tatem, Javier Hurtado, Alberto Deicas, Daniel Weiss, Marta Beron, Román Garrido, Cristina Santos, Mario Cancela, Raúl Lombardi, Pedro Alzugaray, Jorge Gerez, Silvia Mareque, Graciela Franca, Oscar Cluzet, Edgardo Nuñez, Julio Pontet, Sergio Cáceres, Elias Caragna, Alberto Soler, Frank Torres, Gastón Pittini, Gabriel D Empaire, Stevens Salva, Fernando Pérez, Clara Pacheco, Zoraida Parra, Ingrid Von der Osten, Luis Williams, José Salinas, Do Danh Quynh, Pham Thi Van Anh, Nguyen Huu Hoang, Nghuyen Ba Tuan

Subjects
Male, medicine.medical_treatment, pulmonary complications, RESPIRATORY-DISTRESS-SYNDROME, Critical Care and Intensive Care Medicine, CASE-FATALITY, 0302 clinical medicine, Risk Factors, Brain Injuries, Traumatic, Multicenter Studies as Topic, Hospital Mortality, Prospective Studies, Simplified Acute Physiology Score, Stroke, POPULATION, Age Factors, ANEURYSMAL SUBARACHNOID HEMORRHAGE, Middle Aged, Hemorrhagic Stroke, Intensive Care Units, Observational Studies as Topic, Anesthesia, Breathing, Female, medicine.symptom, Ventilator Weaning, Cohort study, Adult, TRAUMATIC BRAIN-INJURY, Pressure support ventilation, mechanical ventilation, prognosis factors, ACUTE LUNG INJURY, 03 medical and health sciences, medicine, Humans, Aged, Ischemic Stroke, Mechanical ventilation, Noninvasive Ventilation, business.industry, MORTALITY, neurologic patients, Organ dysfunction, 030208 emergency & critical care medicine, Length of Stay, medicine.disease, TRENDS, Respiration, Artificial, 030228 respiratory system, Etiology, NEUROCRITICAL CARE, Nervous System Diseases, Tracheotomy, business
Abstract

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease.

Published
2021

47. Alpha-1 Antitrypsin MZ Heterozygosity Is an Endotype of Chronic Obstructive Pulmonary Disease

Author

Auyon J. Ghosh, Brian D. Hobbs, Matthew Moll, Aabida Saferali, Adel Boueiz, Jeong H. Yun, Frank Sciurba, Lucas Barwick, Andrew H. Limper, Kevin Flaherty, Gerard Criner, Kevin K. Brown, Robert Wise, Fernando J. Martinez, David Lomas, Peter J. Castaldi, Vincent J. Carey, Dawn L. DeMeo, Michael H. Cho, Edwin K. Silverman, Craig P. Hersh, James D. Crapo, Barry J. Make, Elizabeth A. Regan, Terri H. Beaty, Adel El-Boueiz, Marilyn G. Foreman, Lystra P. Hayden, Jacqueline Hetmanski, John E. Hokanson, Wonji Kim, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Dmitry Prokopenko, Jarrett Morrow, Dandi Qiao, Phuwanat Sakornsakolpat, Emily S. Wan, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Erin Austin, Gregory Kinney, Kendra A. Young, Surya P. Bhatt, Jessica Bon, Alejandro A. Diaz, Barry Make, Susan Murray, Elizabeth Regan, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L. Curtis, Perry G. Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R. Graham Barr, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Eric L. Flenaugh, Hirut Gebrekristos, Mario Ponce, Silanath Terpenning, Gloria Westney, Richard Rosiello, David Pace, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P. Comellas, Karin F. Hoth, John Newell, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Divay Chandra, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, and Harjinder Singh

Subjects
Male, Endotype, Respiratory System, Critical Care and Intensive Care Medicine, Medical and Health Sciences, Gastroenterology, Loss of heterozygosity, Pulmonary Disease, Chronic Obstructive, Genotype, 80 and over, 2.1 Biological and endogenous factors, Medicine, Longitudinal Studies, Aetiology, Lung, Aged, 80 and over, COPD, RNA sequencing, Middle Aged, Respiratory Function Tests, medicine.anatomical_structure, Phenotype, Meta-analysis, Respiratory, Female, alpha-1 antitrypsin, Genetic Markers, Adult, Pulmonary and Respiratory Medicine, Chronic Obstructive, Heterozygote, medicine.medical_specialty, Chronic Obstructive Pulmonary Disease, Pulmonary disease, Pulmonary Disease, Clinical Research, Internal medicine, alpha 1-Antitrypsin Deficiency, Humans, Allele, Aged, Emphysema, COPDGene Investigators, Whole Genome Sequencing, business.industry, Original Articles, medicine.disease, Survival Analysis, respiratory tract diseases, meta-analysis, alpha 1-Antitrypsin, Case-Control Studies, business
Abstract

RATIONALE: Multiple studies have demonstrated an increased risk of chronic obstructive pulmonary disease (COPD) in heterozygous carriers of the AAT (alpha-1 antitrypsin) Z allele. However, it is not known if MZ subjects with COPD are phenotypically different from noncarriers (MM genotype) with COPD. OBJECTIVES: To assess if MZ subjects with COPD have different clinical features compared with MM subjects with COPD. METHODS: Genotypes of SERPINA1 were ascertained by using whole-genome sequencing data in three independent studies. We compared outcomes between MM subjects with COPD and MZ subjects with COPD in each study and combined the results in a meta-analysis. We performed longitudinal and survival analyses to compare outcomes in MM and MZ subjects with COPD over time. MEASUREMENTS AND MAIN RESULTS: We included 290 MZ subjects with COPD and 6,184 MM subjects with COPD across the three studies. MZ subjects had a lower FEV(1)% predicted and greater quantitative emphysema on chest computed tomography scans compared with MM subjects. In a meta-analysis, the FEV(1) was 3.9% lower (95% confidence interval [CI], −6.55% to −1.26%) and emphysema (the percentage of lung attenuation areas

Published
2021

48. Convalescent Plasma does not improve in-hospital mortality among low SARS-CoV-2-IgG antibodies in COVID-19 hospitalized patients

Author

Felix C. Wangmang, Nilam J. Soni, Marcos I. Restrepo, Sandra Sanchez-Reilly, Antonio Anzueto, and Cadena Jose

Subjects
medicine.medical_specialty, Convalescent plasma, Coronavirus disease 2019 (COVID-19), In hospital mortality, biology, business.industry, Hospitalized patients, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Internal medicine, medicine, biology.protein, Antibody, business
Published
2021

49. Small Airway Disease and Emphysema Are Associated with Future Exacerbations in Smokers with CT-derived Bronchiectasis and COPD: Results from the COPDGene Cohort

Author

Alejandro A. Diaz, Timothy R. Aksamit, Gregory L. Kinney, David A. Lynch, Ashwin Basavaraj, J. Michael Wells, Raúl San José Estépar, Yuka Okajima, Wei Wang, Marcos I. Restrepo, Wojciech R Dolliver, Diego J. Maselli, Christina Mercugliano, Stefano Aliberti, Andrew Yen, Kendra A. Young, and Antonio Anzueto

Subjects
Male, medicine.medical_specialty, Exacerbation, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Interquartile range, Risk Factors, Internal medicine, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Original Research, Aged, COPD, Bronchiectasis, Smokers, business.industry, Middle Aged, medicine.disease, Symptom Flare Up, respiratory tract diseases, Clinical trial, 030220 oncology & carcinogenesis, Relative risk, Cohort, Female, business, Tomography, X-Ray Computed, Body mass index
Abstract

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and bronchiectasis can overlap and share pathologic features, such as small airway disease (SAD). Whether the presence of SAD and emphysema in smokers with CT-derived bronchiectasis is associated with exacerbations is unknown. PURPOSE: To assess whether SAD and emphysema in smokers with CT-derived bronchiectasis are associated with future exacerbations. MATERIALS AND METHODS: SAD and emphysema were quantified using the parametric response map method in former and current heavy smokers with and without bronchiectasis at CT from the COPDGene Study (from July 2009 to July 2018). Exacerbations were prospectively assessed through biannual follow-up. An exacerbation was defined as an increase in or new onset of respiratory symptoms treated with antibiotics and/or corticosteroids. Severe exacerbations were defined as those that required hospitalization. The association of a high burden of SAD (≥15.6%) and high burden of emphysema (≥5%) at CT with exacerbations was assessed with generalized linear mixed models. RESULTS: Of 737 participants, 387 (median age, 64 years [interquartile range, 58–71 years]; 223 women) had CT-derived bronchiectasis. During a 9-year follow-up, after adjustment for age, sex, race, body mass index, current smoking status, pack-years, exacerbations before study entry, forced expiratory volume in 1 second, or FEV(1), and bronchiectasis severity CT score, high burden of SAD and high burden of emphysema were associated with a higher number of exacerbations per year (relative risk [RR], 1.89 [95% CI: 1.54, 2.33] and 1.37 [95% CI: 1.13, 1.66], respectively; P ≤ .001 for both). Results were comparable among participants with bronchiectasis meeting criteria for COPD (n = 197) (RR, 1.67 [95% CI: 1.23, 2.27] for high burden of SAD and 1.51 [95% CI: 1.20, 1.91] for high burden of emphysema; P ≤ .001 for both). CONCLUSION: In smokers with CT-derived bronchiectasis and chronic obstructive pulmonary disease, structural damage to lung parenchyma and small airways was associated with a higher number of exacerbations per year. Clinical trial registration no. NCT00608764 © RSNA, 2021

Published
2021

50. Longitudinal Association Between Muscle Loss and Mortality in Ever Smokers

Author

Stefanie E. Mason, Rafael Moreta-Martinez, Wassim W. Labaki, Matthew J. Strand, Elizabeth A. Regan, Jessica Bon, Ruben San Jose Estepar, Richard Casaburi, Merry-Lynn McDonald, Harry B. Rossiter, Barry Make, Mark T. Dransfield, MeiLan K. Han, Kendra Young, Jeffrey L. Curtis, Kathleen Stringer, Greg Kinney, John E. Hokanson, Raul San Jose Estepar, George R. Washko, James D. Crapo, Edwin K. Silverman, Sara Cummings, Kelley Madden, Barry J. Make, Juliet Nabbosa, Emily Port, Serine Rashdi, Lori Stepp, Shandi Watts, Michael Weaver, Terri Beaty, Russell P. Bowler, David A. Lynch, Gary Anderson, Eugene R. Bleecker, Harvey O. Coxson, Ronald G. Crystal, James C. Hogg, Michael A. Province, Stephen I. Rennard, Thomas Croxton, Weiniu Gan, Lisa A. Postow, Lisa M. Viviano, Corinne Costa-Davis, Elisha Malanga, Delia Prieto, Ruth Tal-Singer, Homayoon Farzadegan, Akila Hadji, Leena Sathe, David Baraghoshi, Grace Chen, James Crooks, Ruthie Knowles, Katherine Pratte, Carla Wilson, Pearlanne T. Zelarney, Katerina J. Kechris, Sonia Leach, Erin E. Austin, Annika Czizik, Gregory Kinney, Yisha Li, Sharon M. Lutz, Margaret F. Ragland, Nicole Richmond, Kendra A. Young, Michael Cho, Peter J. Castaldi, Kimberly Glass, Craig Hersh, Wonji Kim, Yang-Yu Liu, Craig P. Hersh, Jacqueline Bidinger, Michael H. Cho, Douglas Conrad, Dawn L. DeMeo, Adel R. El-Boueiz, Marilyn G. Foreman, Auyon Ghosh, Georg Hahn, Nadia N. Hansel, Lystra P. Hayden, Brian Hobbs, Woori Kim, Christoph Lange, Merry- Lynn McDonald, Michael McGeachie, Matthew Moll, Melody Morris, Nikolaos A. Patsopoulos, Dandi Qiao, Ingo Ruczinski, Emily S. Wan, Jennifer G. Dy, Sean B. Fain, Shoshana Ginsburg, Eric A. Hoffman, Stephen Humphries, Philip F. Judy, Alex Kluiber Stefanie Mason, Andrea Oh, Clare Poynton, Joseph M. Reinhardt, James Ross, Joyce D. Schroeder, Arkadiusz Sitek, Robert M. Steiner, Edwin van Beek, Bram van Ginneken, Eva van Rikxoort, Robert Jensen, Co-Chair: John E. Hokanson, Surya P. Bhatt, Victor Kim, Nirupama Putcha, MeiLan Han, Alejandro A. Diaz, Elizabeth Regan, Antonio Anzueto, William C. Bailey, Gerard J. Criner, Kim Sprenger, Takis Benos, Nicola A. Hanania, Karin F. Hoth, Allison Lambert, Katherine Lowe, Gabriela Oates, Trisha Parekh, Gloria Westney, Aparna Balasubramanian, Aladin Boriek, Ashraf Fawzy, Francine Jacobson, David C. LaFon, Neil MacIntyre, Diego Maselli-Caceres, Meredith C. McCormack, Frank Sciurba, Xavier Soler, Vickram Tejwani, Edwin JR. van Beek, Raymond C. Wade, Mike Wells, Chris H. Wendt, Jeong H. Yun, Jingzhou Zhang, Lucas Gillenwater, Katherine E. Lowe, Katherine A. Pratte, Margaret Ragland, Amy Attaway, Stefanie Mason, Punam Kumar Saha, Ava Wilson, Hannatu Amaza, Adrienne Baldomero, A. James Mamary, James O’Brien, Robert A. Wise, Michelle Eakin, Jess G. Fiedorowicz, Ben Henkle, Kristen Holm, Anand Iyer, Ken M. Kunisaki, Charlene McEvoy, Takudzwa Mkorombindo, Gen Shinozaki, Abebaw Yohannes, Brian D. Hobbs, Bruce E. Miller, Tara Retson, Lisa McCloskey, Perry G. Pernicano, Mustafa Atik, Laura Bertrand, Thomas Monaco, Dharani Narendra, Veronica V. Lenge de Rosen, Kwame Badu-Danso, Francine L. Jacobson, Laura Kaufman, Cherie Maguire, Sophie Struble, Seth Wilson, R. Graham Barr, Casandra Almonte, John H.M. Austin, Maria Lorena Gomez Blum, Belinda M. D’Souza, Emilay Florez, Rodney Martinez, Wendy Curry, H. Page McAdams, Charlotte V. Reikofski, Lacey Washington, Robert Brown, Cheryl Clare, Marie Daniel, Karen Horton, Cheng Ting 'Tony' Lin, Tahira Mirza, Meagan Scott, Becky Shade, Matt Budoff, Robert Calmelat, Deborah Cavanaugh, Chris Dailing, Leticia Diaz, Hans Fischer, Renee Love Indelicato, Janos Porszasz, April Soriano, William Stringer, Miriam Urrutia, Arianne Baldomero, Brian Bell, Miranda Deconcini, Linda Loes, Jonathan Phelan, Camille Robichaux, Cheryl Sasse, Joseph H. Tashjian, Eric L. Flenaugh, Kema Abson, Hirut Gebrekristos, Priscilla Johnson, Jessica Jordan, Mario Ponce, Silanath Terpenning, Derrick Wilson, Grace Broadhurst, Debra Dyer, Elena Engel, Jay Finigan, Andrew Hill, Alex Jones, Ryan Jones, Jordan Owen, Richard Rosiello, Nicole Andries, Mary Charpentier, Diane Kirk, David Pace, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Valena Davis, Parag Desai, Dee Fehrle, Carla Grabianowski, Michael Jacobs, Laurie Jameson, Gayle M. Jones, Steven Kelsen, Nathaniel Marchetti, Francine McGonagle, Aditi Satti, Kartik Shenoy, Regina Sheridan, Maria Vega-Sanchez, Samantha Wallace, Samuel Akinseye-kolapo, Matthew Baker, Arnissa Goggins, Anny McClain, Hrudaya Nath, Satinder P. Singh, Sushil K. Sonavane, Elizabeth Westfall, Marissa Gil, Tarek El Hajjaoui, Albert Hsiao, Amber Martineau, Jenna Mielke, Karl Perez, Gabriel Querido, Tara Reston, Andrew Yen, Alejandro Comellas, Spyridon Fortis, Mauricio Galizia, Eric Garcia, Janet Keating, Archana Laroia, Changhyun Lee, Amber Meyer, Brian Mullan, Prashant Nagpal, Oloigbe Ofori, and Sierra Suiter

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Chronic Obstructive, Clinical Sciences, Respiratory System, Critical Care and Intensive Care Medicine, COPD: Original Research, Body Mass Index, Pectoralis Muscles, Pulmonary Disease, sarcopenia, Pulmonary Disease, Chronic Obstructive, Interquartile range, Clinical Research, Internal medicine, medicine, Tobacco Smoking, COPD, 2.1 Biological and endogenous factors, Humans, Longitudinal Studies, Aetiology, Pectoralis Muscle, Lung, Nutrition, Smokers, COPDGene Investigators, Proportional hazards model, business.industry, Prevention, Smoking, muscle wasting, medicine.disease, mortality, Confidence interval, Good Health and Well Being, Sarcopenia, Cardiology, Body Composition, Cardiology and Cardiovascular Medicine, business, Body mass index, Bioelectrical impedance analysis, Biomarkers
Abstract

BackgroundBody composition measures, specifically low weight or reduced muscle mass, are associated with mortality in COPD, but the effect of longitudinal body composition changes is undefined.Research questionIs the longitudinal loss of fat-free mass (FFM) associated with increased mortality, including in those with initially normal or elevated body composition metrics?Study design and methodsParticipants with complete data for at least one visit in the COPDGene study (n= 9,268) and the ECLIPSE study (n= 1,760) were included and monitored for 12 and 8 years, respectively. Pectoralis muscle area (PMA) was derived from thoracic CT scans and used as a proxy for FFM. A longitudinal mixed submodel for PMA and a Cox proportional hazards submodel for survival were fitted on a joint distribution, using a shared random intercept parameter and Markov chain Monte Carlo parameter estimation.ResultsBoth cohorts demonstrated a left-shifted distribution of baseline FFM, not reflected in BMI, and an increase in all-cause mortality risk associated with longitudinal loss of PMA. For each 1-cm2 PMA loss, mortality increased 3.1%(95%CI, 2.4%-3.7%; P< .001) in COPDGene, and 2.4%(95%CI, 0.9%-4.0%; P< .001) in ECLIPSE. Increased mortality risk was independent of enrollment values for BMI and disease severity [BODE (body mass, airflow obstruction, dyspnea, and exercise capacity) index quartiles] and was significant even in participants with initially greater than average PMA.InterpretationLongitudinal loss of PMA is associated with increased all-cause mortality, regardless of BMI or initial muscle mass. Consideration of novel screening tests and further research into mechanisms contributing to muscle decline may improve risk stratification and identify novel therapeutic targets in ever smokers.

Published
2021

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