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Jovica Veljanovski,1 Daniel R Ouellette2 1Internal Medicine, Henry Ford Hospital, Detroit, MI, USA; 2Division of Pulmonary and Critical Care Medicine, Henry Ford Hospital, Detroit, MI, USA Purpose: The purpose of this study was to examine differences between patients clinically diagnosed with COPD with and without obstruction by spirometry and to identify risk factors for respiratory hospitalizations. Materials and methods: This is a retrospective analysis of all patients diagnosed with COPD at a large academic Internal Medicine Clinic in 2014, who had spirometry performed during the period 2013–2014. Two groups existed: one with obstruction termed classical COPD and another without obstruction. Demographics, comorbidities, prescribed medications, spirometry, respiratory hospitalization, and eosinophilia among other variables were compared between patients with and without obstruction. Risk factors for two or more respiratory hospitalizations during the period 2014–2015 were sought for both populations by both univariate and multivariate analyses. Subsequently, we studied the population without obstruction for risk factors for one or more respiratory hospitalizations first by univariate analysis and then by multivariate analysis. Results: Among 657 patients, 210 met inclusion criteria, with 157 having obstruction on spirometry and 53 without obstruction. There was no difference between those with and without obstruction on the rate of respiratory hospitalization when using two or more respiratory hospitalizations (p=0.397) or one or more respiratory hospitalizations (p=0.467). Nontreatment risk factors associated with two or more respiratory hospitalizations by multivariate analysis included a maximum eosinophil count above the threshold of 0.5 K/µL (maximum eosinophil number threshold [MENT]; p=0.001, OR =3.792, 95% CI =1.676–8.582) and % predicted forced expiratory volume in the first second (p=0.031, OR =0.978, 95% CI =0.959–0.998). In patients without obstruction, MENT above the threshold of 0.5 K/µL (p=0.032, OR =5.087, 95% CI =1.147–22.557) was the only risk factor associated with one or more respiratory hospitalizations. Conclusion: In a clinically diagnosed COPD population who had spirometry performed, the presence of airflow obstruction was not a risk factor for respiratory hospitalizations. The most significantly associated nontreatment factor associated with respiratory hospitalization, both in the study population as a whole and in the cohort without obstruction, was MENT above the threshold of 0.5 K/µL. Keywords: chronic obstructive pulmonary disease, airflow obstruction, spirometry, eosinophilia

Daniel R Ouellette,1 Kim L Lavoie2 1Department of Pulmonary and Critical Care Medicine, Henry Ford Hospital, Detroit, MI, USA; 2Montreal Behavioral Medicine Center (MBMC), Research Center, Integrated University Health and Social Services Center – Sacred Heart Hospital of Montreal, Montreal, QC, Canada Abstract: COPD is highly prevalent and associated with substantial morbidity and mortality. Clinicians have long been aware that patients with COPD have problems with cognition and are susceptible to mood (depression) and anxiety disorders. With the increasing awareness of COPD as a multisystem disorder, many studies have evaluated the prevalence of neuropsychiatric conditions in patients with COPD. This review presents evidence regarding the prevalence of neuropsychiatric conditions (cognitive disorders/impairment, depression/anxiety) in COPD, their risk factors, and their impact on relevant outcomes. It also discusses both assessment and treatment of neuropsychiatric conditions and makes recommendations for improved screening and treatment. The findings suggest that clinicians caring for patients with COPD must become familiar with diagnosing these comorbid conditions and that future treatment has the potential to impact these patients and thereby improve COPD outcomes. Keywords: COPD, cognitive impairment, mood disorders, anxiety disorders, hypoxemia, pulmonary rehabilitation

Background: Blood products frequently are administered to critically ill patients. Considering recent trials and practice variability, a comprehensive review of current evidence was deemed essential to offer pertinent guidance to critical care practitioners. This American College of Chest Physicians (CHEST) guidelines panel examined the literature on RBC transfusions among critically ill patients overall and specific subgroups, including patients with gastrointestinal bleeding, acute coronary syndrome (ACS), cardiac surgery, isolated troponin elevation, and septic shock, to provide evidence-based recommendations., Study Design and Methods: A panel of experts developed six Population, Intervention, Comparator, and Outcome questions addressing RBC transfusions in critically ill patients and performed a comprehensive evidence review. The panel applied the Grading of Recommendations, Assessment, Development, and Evaluations approach to assess the certainty of evidence and to formulate and grade recommendations. A modified Delphi technique was used to reach consensus on the recommendations., Results: The initial search identified a total of 3,082 studies, and after the initial screening, 38 articles were reviewed. Among them, 23 studies met inclusion criteria, comprising 22 randomized controlled trials and one cohort study. Based on the analysis of these studies, the panel formulated two strong and four conditional recommendations. The overall quality of evidence for recommendations ranged from very low to moderate., Conclusions: In most critically ill patients, a restrictive strategy was preferable to a permissive approach because it does not increase the risk of death or complications, but does decrease RBC use significantly. Data from critically ill subpopulations also supported a restrictive approach, except in patients with ACS, for whom favoring a restrictive approach could increase adverse outcomes., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Over the past decade, therapeutic monoclonal antibodies (mAbs) have established their role as valuable agents in the treatment of various diseases ranging from cancers to infectious, cardiovascular and autoimmune diseases. Reactive groups of the amino acids within these proteins make them susceptible to many kinds of chemical modifications during manufacturing, storage and in vivo circulation. Among these reactions, the oxidation of methionine residues to their sulfoxide form is a commonly observed chemical modification in mAbs. When the oxidized methionine is in the complementarity-determining region (CDR), this modification can affect antigen binding and thus abrogate biological activity. For these reasons, it is essential to identify oxidation liabilities during the antibody discovery and development phases. Here, we present an in silico method, based on protein modeling and molecular dynamics simulations, to predict the oxidation-liable residues in the variable region of therapeutic antibodies. Previous studies have used the 2-shell water coordination number descriptor (WCN) to identify methionine residues susceptible to oxidation. Although the WCN descriptor successfully predicted oxidation liabilities when the residue was solvent exposed, the method was much less accurate for partially buried methionine residues. Consequently, we introduce a new descriptor, WCN-OH, that improves the accuracy of prediction of methionine oxidation susceptibility by extending the theoretical framework of the water coordination number to incorporate the effects of polar amino acids side chains in close proximity to the methionine of interest., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Tavella et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Rhabdomyolysis is a common cause of admission to the intensive care unit. However, recurrent rhabdomyolysis remains a rare encounter for intensivists and presents a challenge in terms of identifying its etiology. Considerations of metabolic myopathies as a culprit remain underexplored. We present a case of a patient with recurrent rhabdomyolysis with extreme elevation of creatine kinase., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Al Bizri et al.)

Background: The major reasons to treat sarcoidosis are to lower the morbidity and mortality risk or to improve quality of life (QoL). The indication for treatment varies depending on which manifestation is the cause of symptoms: lungs, heart, brain, skin or other manifestations. While glucocorticoids remain the first choice for initial treatment of symptomatic disease, prolonged use is associated with significant toxicity. Glucocorticoid-sparing alternatives are available. The presented treatment guidelines aim to provide guidance to physicians treating the very heterogenous sarcoidosis manifestations., Methods: A European Respiratory Society Task Force committee composed of clinicians, methodologists and patients with experience in sarcoidosis developed recommendations based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology. The committee developed eight PICO (Patients, Intervention, Comparison, Outcomes) questions and these were used to make specific evidence-based recommendations., Results: The Task Force committee delivered 12 recommendations for seven PICOs. These included treatment of pulmonary, cutaneous, cardiac and neurologic disease as well as fatigue. One PICO question regarding small-fibre neuropathy had insufficient evidence to support a recommendation. In addition to the recommendations, the committee provided information on how they use alternative treatments, when there was insufficient evidence to support a recommendation., Conclusions: There are many treatments available to treat sarcoidosis. Given the diverse nature of the disease, treatment decisions require an assessment of organ involvement, risk for significant morbidity, and impact on QoL of the disease and treatment., Competing Interests: Conflict of interest: R.P. Baughman reports grants from Gilead, Genentech, Bayer, aTyr and Bellephron, grants and personal fees for consultancy from Novartis, personal fees for consultancy from Methial, grants and personal fees for consultancy and lectures from Mallinckrodt, grants and personal fees for lectures from Boehringer Ingelheim, outside the submitted work. Conflict of interest: D. Valeyre reports personal fees for advisory board work from Boehringer Ingelheim and Roche, outside the submitted work. Conflict of interest: P. Korsten reports grants and personal fees from GlaxoSmithKline, personal fees from AbbVie, Pfizer, Chugai, Novartis Pharma, Sanofi-Aventis, Lilly and Gilead, outside the submitted work. Conflict of interest: A.G. Mathioudakis reports grants from Boehringer Ingelheim, outside the submitted work. Conflict of interest: W.A. Wuyts has nothing to disclose. Conflict of interest: A. Wells reports personal fees for lectures and advisory board work from Boehringer Ingelheim and Roche, during the conduct of the study. Conflict of interest: P. Rottoli has nothing to disclose. Conflict of interest: H. Nunes has nothing to disclose. Conflict of interest: E.E. Lower reports grants from Gilead, Genentech, Bayer and aTYR, grants and personal fees for consultancy from Novartis, outside the submitted work. Conflict of interest: M.A. Judson received grant support for his institution from Mallickrodt. Conflict of interest: D. Israël-Biet has nothing to disclose. Conflict of interest: J.C. Grutters has nothing to disclose. Conflict of interest: M. Drent has nothing to disclose. Conflict of interest: D.A. Culver reports grants and personal fees from aTyr, Mallinckrodt, Boehringer Ingelheim and Foundation for Sarcoidosis Research, personal fees from Roche, outside the submitted work. Conflict of interest: F. Bonella reports personal fees and non-financial support from Boehringer Ingelheim, Roche, Galapagos, BMS and Savara Pharma, outside the submitted work. Conflict of interest: K. Antoniou has nothing to disclose. Conflict of interest: F. Martone has nothing to disclose. Conflict of interest: B. Quadder has nothing to disclose. Conflict of interest: G. Spitzer has nothing to disclose. Conflict of interest: B. Nagavci acts as an ERS methodologist. Conflict of interest: T. Tonia acts as an ERS methodologist. Conflict of interest: D. Rigau acts as an ERS methodologist. Conflict of interest: D.R. Oullette reports grants from PCORI (Patient-Centred Outcomes Research Institute, US Federal) and Sanofi, outside the submitted work; and has provided expert witness work for venous thromboembolic disease., (Copyright ©The authors 2021. For reproduction rights and permissions contact permissions@ersnet.org.)

Objectives: To investigate the differences in clinical course, ventilator mechanics, and outcomes of patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection compared with a historical cohort of acute respiratory distress syndrome., Design: Comparative case-control study., Setting: Multicenter, comprehensive tertiary healthcare facility in Detroit, MI., Patients/subjects: Adult patients hospitalized with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection were compared with patients hospitalized with acute respiratory distress syndrome prior to the coronavirus disease 2019 pandemic (control)., Interventions: None., Measurements and Main Results: We included 384 patients in the analysis. Inpatient mortality was significantly higher in patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection compared with controls (64% vs 49%; p = 0.007). Despite both groups demonstrating similar ventilatory function and Sequential Organ Failure Assessment score on day 1 of intubation, with similar lung compliance throughout the study period, patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection demonstrated progressive hypoxia compared with controls across the study period. Similarly, higher positive end-expiratory pressure levels and increased use of paralytics were observed in the patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection group. On univariate analysis of the entire cohort, significant risk factors for inpatient mortality included coronavirus disease 2019 infection ( p = 0.007), older age ( p < 0.001), high Sequential Organ Failure Assessment score ( p = 0.003), vasopressor use ( p = 0.039), paralytic use ( p < 0.001), higher positive end-expiratory pressure levels on day 3 ( p = 0.027) and day 7 ( p < 0.001), in addition to acute respiratory distress syndrome severity on both days 3 ( p = 0.008) and 7 ( p < 0.001). Multivariate analysis identified coronavirus disease 2019 infection (odds ratio, 1.939; p = 0.021), older age (odds ratio, 1.042; p < 0.001), paralytic use (odds ratio, 3.366; p < 0.001), and higher Sequential Organ Failure Assessment score (odds ratio, 1.152; p = 0.027) as significant predictors of mortality across the entire cohort., Conclusions: Patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection demonstrated higher mortality compared with control patients hospitalized with acute respiratory distress syndrome prior to the pandemic, with progressive hypoxia throughout the study period, despite similar lung mechanics and initial Sequential Organ Failure Assessment score. Coronavirus disease 2019 infection, older age, paralytic use, and higher Sequential Organ Failure Assessment scores were independent risk factors for 28-day mortality across the entire cohort., Competing Interests: Dr. Ouellette receives grant support for research from a Patient-Centered Outcomes Research Institute grant (U.S. Federal Government) for research concerning oral agents to prevent chronic obstructive pulmonary disease (COPD) exacerbations. He also receives grant support from Sanofi Pharmaceutical for research involving a novel biologic agent to treat patients with COPD and eosinophilia. All funds go to the institution, and this investigator does not receive salary support from this project. The remaining authors have disclosed that they do not have any conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

The 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group was coordinated and supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health. It is designed to improve patient care and support informed decision making about asthma management in the clinical setting. This update addresses six priority topic areas as determined by the state of the science at the time of a needs assessment, and input from multiple stakeholders:A rigorous process was undertaken to develop these evidence-based guidelines. The Agency for Healthcare Research and Quality's (AHRQ) Evidence-Based Practice Centers conducted systematic reviews on these topics, which were used by the Expert Panel Working Group as a basis for developing recommendations and guidance. The Expert Panel used GRADE (Grading of Recommendations, Assessment, Development and Evaluation), an internationally accepted framework, in consultation with an experienced methodology team for determining the certainty of evidence and the direction and strength of recommendations based on the evidence. Practical implementation guidance for each recommendation incorporates findings from NHLBI-led patient, caregiver, and clinician focus groups. To assist clincians in implementing these recommendations into patient care, the new recommendations have been integrated into the existing Expert Panel Report-3 (EPR-3) asthma management step diagram format., (Published by Elsevier Inc.)

Background: The coronavirus disease 2019 (COVID-19) has swept the globe and is causing significant morbidity and mortality. Given that the virus is transmitted via droplets, open airway procedures such as bronchoscopy pose a significant risk to health-care workers (HCWs). The goal of this guideline was to examine the current evidence on the role of bronchoscopy during the COVID-19 pandemic and the optimal protection of patients and HCWs., Study Design and Methods: A group of approved panelists developed key clinical questions by using the Population, Intervention, Comparator, and Outcome (PICO) format that addressed specific topics on bronchoscopy related to COVID-19 infection and transmission. MEDLINE (via PubMed) was systematically searched for relevant literature and references were screened for inclusion. Validated evaluation tools were used to assess the quality of studies and to grade the level of evidence to support each recommendation. When evidence did not exist, suggestions were developed based on consensus using the modified Delphi process., Results: The systematic review and critical analysis of the literature based on six PICO questions resulted in six statements: one evidence-based graded recommendation and 5 ungraded consensus-based statements., Interpretation: The evidence on the role of bronchoscopy during the COVID-19 pandemic is sparse. To maximize protection of patients and HCWs, bronchoscopy should be used sparingly in the evaluation and management of patients with suspected or confirmed COVID-19 infections. In an area where community transmission of COVID-19 infection is present, bronchoscopy should be deferred for nonurgent indications, and if necessary to perform, HCWs should wear personal protective equipment while performing the procedure even on asymptomatic patients., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objective This guideline provides evidence-based recommendations on treating patients presenting with dysphonia, which is characterized by altered vocal quality, pitch, loudness, or vocal effort that impairs communication and/or quality of life. Dysphonia affects nearly one-third of the population at some point in its life. This guideline applies to all age groups evaluated in a setting where dysphonia would be identified or managed. It is intended for all clinicians who are likely to diagnose and treat patients with dysphonia. Purpose The primary purpose of this guideline is to improve the quality of care for patients with dysphonia, based on current best evidence. Expert consensus to fill evidence gaps, when used, is explicitly stated and supported with a detailed evidence profile for transparency. Specific objectives of the guideline are to reduce inappropriate variations in care, produce optimal health outcomes, and minimize harm. For this guideline update, the American Academy of Otolaryngology-Head and Neck Surgery Foundation selected a panel representing the fields of advanced practice nursing, bronchoesophagology, consumer advocacy, family medicine, geriatric medicine, internal medicine, laryngology, neurology, otolaryngology-head and neck surgery, pediatrics, professional voice, pulmonology, and speech-language pathology. Action Statements The guideline update group made strong recommendations for the following key action statements (KASs): (1) Clinicians should assess the patient with dysphonia by history and physical examination to identify factors where expedited laryngeal evaluation is indicated. These include but are not limited to recent surgical procedures involving the head, neck, or chest; recent endotracheal intubation; presence of concomitant neck mass; respiratory distress or stridor; history of tobacco abuse; and whether the patient is a professional voice user. (2) Clinicians should advocate voice therapy for patients with dysphonia from a cause amenable to voice therapy. The guideline update group made recommendations for the following KASs: (1) Clinicians should identify dysphonia in a patient with altered voice quality, pitch, loudness, or vocal effort that impairs communication or reduces quality of life (QOL). (2) Clinicians should assess the patient with dysphonia by history and physical examination for underlying causes of dysphonia and factors that modify management. (3) Clinicians should perform laryngoscopy, or refer to a clinician who can perform laryngoscopy, when dysphonia fails to resolve or improve within 4 weeks or irrespective of duration if a serious underlying cause is suspected. (4) Clinicians should perform diagnostic laryngoscopy, or refer to a clinician who can perform diagnostic laryngoscopy, before prescribing voice therapy and document/communicate the results to the speech-language pathologist (SLP). (5) Clinicians should advocate for surgery as a therapeutic option for patients with dysphonia with conditions amenable to surgical intervention, such as suspected malignancy, symptomatic benign vocal fold lesions that do not respond to conservative management, or glottic insufficiency. (6) Clinicians should offer, or refer to a clinician who can offer, botulinum toxin injections for the treatment of dysphonia caused by spasmodic dysphonia and other types of laryngeal dystonia. (7) Clinicians should inform patients with dysphonia about control/preventive measures. (8) Clinicians should document resolution, improvement or worsened symptoms of dysphonia, or change in QOL of patients with dysphonia after treatment or observation. The guideline update group made a strong recommendation against 1 action: (1) Clinicians should not routinely prescribe antibiotics to treat dysphonia. The guideline update group made recommendations against other actions: (1) Clinicians should not obtain computed tomography (CT) or magnetic resonance imaging (MRI) for patients with a primary voice complaint prior to visualization of the larynx. (2) Clinicians should not prescribe antireflux medications to treat isolated dysphonia, based on symptoms alone attributed to suspected gastroesophageal reflux disease (GERD) or laryngopharyngeal reflux (LPR), without visualization of the larynx. (3) Clinicians should not routinely prescribe corticosteroids in patients with dysphonia prior to visualization of the larynx. The policy level for the following recommendation about laryngoscopy at any time was an option: (1) Clinicians may perform diagnostic laryngoscopy at any time in a patient with dysphonia. Differences from Prior Guideline (1) Incorporating new evidence profiles to include the role of patient preferences, confidence in the evidence, differences of opinion, quality improvement opportunities, and any exclusion to which the action statement does not apply (2) Inclusion of 3 new guidelines, 16 new systematic reviews, and 4 new randomized controlled trials (3) Inclusion of a consumer advocate on the guideline update group (4) Changes to 9 KASs from the original guideline (5) New KAS 3 (escalation of care) and KAS 13 (outcomes) (6) Addition of an algorithm outlining KASs for patients with dysphonia.

The American College of Chest Physicians (CHEST) has been at the forefront of evidence-based clinical practice guideline development for more than 2 decades. In 2006, CHEST adopted a modified system of Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to support their rigorous guideline development methodology. The evolution of CHEST's Living Guidelines Model, as well as their collaborative efforts with other organizations, has necessitated improvements in their guideline development methodology. CHEST has made the decision to transition to the standard GRADE method for rating the certainty of evidence and grading recommendations in their evidence-based clinical practice guidelines, a deviation from the modified approach that was adopted in 2006. The standard GRADE approach will be used to grade recommendations in all CHEST guidelines, including updates to previously published guidelines. CHEST's adoption of a standard GRADE approach will ensure that its guideline development methodology is more consistent with that used by other organizations, will better align evidence synthesis methods, and will result in more explicit and easy to understand recommendations., (Copyright © 2016 American College of Chest Physicians. All rights reserved.)

Background: An update of evidence-based guidelines concerning liberation from mechanical ventilation is needed as new evidence has become available. The American College of Chest Physicians (CHEST) and the American Thoracic Society (ATS) have collaborated to provide recommendations to clinicians concerning liberation from the ventilator., Methods: Comprehensive evidence syntheses, including meta-analyses, were performed to summarize all available evidence relevant to the guideline panel's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, and the results were summarized in evidence profiles. The evidence syntheses were discussed and recommendations developed and approved by a multidisciplinary committee of experts in mechanical ventilation., Results: Recommendations for three population, intervention, comparator, outcome (PICO) questions concerning ventilator liberation are presented in this document. The guideline panel considered the balance of desirable (benefits) and undesirable (burdens, adverse effects, costs) consequences, quality of evidence, feasibility, and acceptability of various interventions with respect to the selected questions. Conditional (weak) recommendations were made to use inspiratory pressure augmentation in the initial spontaneous breathing trial (SBT) and to use protocols to minimize sedation for patients ventilated for more than 24 h. A strong recommendation was made to use preventive noninvasive ventilation (NIV) for high-risk patients ventilated for more than 24 h immediately after extubation to improve selected outcomes. The recommendations were limited by the quality of the available evidence., Conclusions: The guideline panel provided recommendations for inspiratory pressure augmentation during an initial SBT, protocols minimizing sedation, and preventative NIV, in relation to ventilator liberation., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: This clinical practice guideline addresses six questions related to liberation from mechanical ventilation in critically ill adults. It is the result of a collaborative effort between the American Thoracic Society (ATS) and the American College of Chest Physicians (CHEST)., Methods: A multidisciplinary panel posed six clinical questions in a population, intervention, comparator, outcomes (PICO) format. A comprehensive literature search and evidence synthesis was performed for each question, which included appraising the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The Evidence-to-Decision framework was applied to each question, requiring the panel to evaluate and weigh the importance of the problem, confidence in the evidence, certainty about how much the public values the main outcomes, magnitude and balance of desirable and undesirable outcomes, resources and costs associated with the intervention, impact on health disparities, and acceptability and feasibility of the intervention., Results: Evidence-based recommendations were formulated and graded initially by subcommittees and then modified following full panel discussions. The recommendations were confirmed by confidential electronic voting; approval required that at least 80% of the panel members agree with the recommendation., Conclusions: The panel provides recommendations regarding liberation from mechanical ventilation. The details regarding the evidence and rationale for each recommendation are presented in the American Journal of Respiratory and Critical Care Medicine and CHEST., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Interventions that lead to earlier liberation from mechanical ventilation can improve patient outcomes. This guideline, a collaborative effort between the American Thoracic Society and the American College of Chest Physicians, provides evidence-based recommendations to optimize liberation from mechanical ventilation in critically ill adults., Methods: Two methodologists performed evidence syntheses to summarize available evidence relevant to key questions about liberation from mechanical ventilation. The methodologists appraised the certainty in the evidence (i.e., the quality of evidence) using the Grading of Recommendations, Assessment, Development, and Evaluation approach and summarized the results in evidence profiles. The guideline panel then formulated recommendations after considering the balance of desirable consequences (benefits) versus undesirable consequences (burdens, adverse effects, and costs), the certainty in the evidence, and the feasibility and acceptability of various interventions. Recommendations were rated as strong or conditional., Results: The guideline panel made four conditional recommendations related to rehabilitation protocols, ventilator liberation protocols, and cuff leak tests. The recommendations were for acutely hospitalized adults mechanically ventilated for more than 24 hours to receive protocolized rehabilitation directed toward early mobilization, be managed with a ventilator liberation protocol, be assessed with a cuff leak test if they meet extubation criteria but are deemed high risk for postextubation stridor, and be administered systemic steroids for at least 4 hours before extubation if they fail the cuff leak test., Conclusions: The American Thoracic Society/American College of Chest Physicians recommendations are intended to support healthcare professionals in their decisions related to liberating critically ill adults from mechanical ventilation.

Background: This clinical practice guideline addresses six questions related to liberation from mechanical ventilation in critically ill adults. It is the result of a collaborative effort between the American Thoracic Society and the American College of Chest Physicians., Methods: A multidisciplinary panel posed six clinical questions in a Population, Intervention, Comparator, and Outcomes format. A comprehensive literature search and evidence synthesis was performed for each question, which included appraising the certainty in the evidence (i.e., the quality of evidence) using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The Evidence-to-Decision framework was applied to each question, requiring the panel to evaluate and weigh the importance of the problem, the confidence in the evidence, the certainty about how much the public values the main outcomes, the magnitude and balance of desirable and undesirable outcomes, the resources and costs associated with the intervention, the impact on health disparities, and the acceptability and feasibility of the intervention., Results: Evidence-based recommendations were formulated and graded initially by subcommittees and then modified after full-panel discussions. The recommendations were confirmed by confidential electronic voting; approval required that at least 80% of the panel members agree with the recommendation., Conclusions: The panel provides recommendations regarding liberation from mechanical ventilation. The details regarding the evidence and rationale for each recommendation are presented in the American Journal of Respiratory and Critical Care Medicine and Chest.

Background: The purpose of this study is to compare the in-hospital mortality rates between septic patients receiving statins and those that did not prior to developing sepsis. We compared subgroups receiving atorvastatin and simvastatin because these two drugs differ in their pharmacologic properties., Methods: This study was a retrospective analysis of patients selected from an institutional data base of patients hospitalized with sepsis. The study patients were drawn from a data base of 1,961 hospitalized patients with sepsis and included patients who met selection criteria and who were studied for HMG-CoA reductase inhibitor (statin) use both prior to and during hospitalization. The in-hospital mortality rates of patients receiving statins and those that did not prior to developing sepsis were compared. In-hospital mortality rates of patient subgroups receiving atorvastatin and simvastatin were also compared. A multivariable analysis was conducted with in-hospital mortality as the outcome variable and with multiple risk factors to include atorvastatin and simvastatin use., Results: The mortality rate for 359 patients receiving statins prior to hospitalization for sepsis was not significantly different than that for 1,302 patients who did not receive pre-hospital statins (26.5% versus 30.4%, p > 0.05). The mortality rate for 92 patients who had received atorvastatin prior to hospitalization was significantly less than that of 253 patients who received simvastatin (18.5% versus 30.0%, p = 0.032). The use of atorvastatin prior to sepsis was independently associated with lower in-hospital mortality in a multivariable analysis of sepsis risk factors (p = 0.021, OR = 0.455). Patients who received atorvastatin prior to hospitalization for sepsis and had statins continued in hospital had a very low mortality rate that was significantly less than that of those patients who never received statins (15.7% versus 30.8%, p = 0.007)., Conclusions: Pre-hospital atorvastatin use was associated with improved in-hospital mortality in septic patients when compared with pre-hospital simvastatin use and was independently associated with an improved outcome when compared to other sepsis risk factors. The effect of statins in patients with sepsis may be different for individual statins.

Background: COPD is a major cause of morbidity and mortality in the United States as well as throughout the rest of the world. An exacerbation of COPD (periodic escalations of symptoms of cough, dyspnea, and sputum production) is a major contributor to worsening lung function, impairment in quality of life, need for urgent care or hospitalization, and cost of care in COPD. Research conducted over the past decade has contributed much to our current understanding of the pathogenesis and treatment of COPD. Additionally, an evolving literature has accumulated about the prevention of acute exacerbations., Methods: In recognition of the importance of preventing exacerbations in patients with COPD, the American College of Chest Physicians (CHEST) and Canadian Thoracic Society (CTS) joint evidence-based guideline (AECOPD Guideline) was developed to provide a practical, clinically useful document to describe the current state of knowledge regarding the prevention of acute exacerbations according to major categories of prevention therapies. Three key clinical questions developed using the PICO (population, intervention, comparator, and outcome) format addressed the prevention of acute exacerbations of COPD: nonpharmacologic therapies, inhaled therapies, and oral therapies. We used recognized document evaluation tools to assess and choose the most appropriate studies and to extract meaningful data and grade the level of evidence to support the recommendations in each PICO question in a balanced and unbiased fashion., Results: The AECOPD Guideline is unique not only for its topic, the prevention of acute exacerbations of COPD, but also for the first-in-kind partnership between two of the largest thoracic societies in North America. The CHEST Guidelines Oversight Committee in partnership with the CTS COPD Clinical Assembly launched this project with the objective that a systematic review and critical evaluation of the published literature by clinical experts and researchers in the field of COPD would lead to a series of recommendations to assist clinicians in their management of the patient with COPD., Conclusions: This guideline is unique because it provides an up-to-date, rigorous, evidence-based analysis of current randomized controlled trial data regarding the prevention of COPD exacerbations.

Pneumothorax is divided to primary and secondary. It is a situation that requires immediate treatment, otherwise it could have severe health consequences. Pneumothorax can be treated either by thoracic surgeons, or pulmonary physicians. In our current work, we will focus on unusual cases of pneumothorax. We will provide the etiology and treatment for each case, also a discussion will be made for each situation.

The American Board of Internal Medicine Foundation's Choosing Wisely campaign aims to curb health-care costs and improve patient care by soliciting lists from medical societies of the top five tests or treatments in their specialty that are used too frequently and inappropriately. The American Thoracic Society (ATS) and American College of Chest Physicians created a joint task force, which produced a top five list for adult pulmonary medicine. Our top five recommendations, which were approved by the executive committees of the ATS and American College of Chest Physicians and published by Choosing Wisely in October 2013, are as follows: (1) Do not perform CT scan surveillance for evaluation of indeterminate pulmonary nodules at more frequent intervals or for a longer period of time than recommended by established guidelines; (2) do not routinely offer pharmacologic treatment with advanced vasoactive agents approved only for the management of pulmonary arterial hypertension to patients with pulmonary hypertension resulting from left heart disease or hypoxemic lung diseases (groups II or III pulmonary hypertension); (3) for patients recently discharged on supplemental home oxygen following hospitalization for an acute illness, do not renew the prescription without assessing the patient for ongoing hypoxemia; (4) do not perform chest CT angiography to evaluate for possible pulmonary embolism in patients with a low clinical probability and negative results of a highly sensitive D-dimer assay; (5) do not perform CT scan screening for lung cancer among patients at low risk for lung cancer. We hope pulmonologists will use these recommendations to stimulate frank discussions with patients about when these tests and treatments are indicated--and when they are not.

Introduction: The aim of this study was to determine if there are differences between patients with pre-existing left ventricular dysfunction and those with normal antecedent left ventricular function during a sepsis episode in terms of in-hospital mortality and mortality risk factors when treated in accordance with a sepsis treatment algorithm., Methods: We performed a retrospective case-control analysis of patients selected from a quality improvement database of 1,717 patients hospitalized with sepsis between 1 January 2005 and 30 June 2010. In this study, 197 patients with pre-existing left ventricular systolic dysfunction and sepsis were compared to 197 case-matched patients with normal prior cardiac function and sepsis., Results: In-hospital mortality rates (P = 0.117) and intubation rates at 24 hours (P = 0.687) were not significantly different between cases and controls. There was no correlation between the amount of intravenous fluid administered over the first 24 hours and the PaO2/FiO2 ratio at 24 hours in either cases or controls (r2 = 0.019 and r2 = 0.001, respectively). Mortality risk factors for cases included intubation status (P = 0.016, OR = 0.356 for no intubation), compliance with a sepsis bundle (P = 0.008, OR = 3.516 for failed compliance), a source of infection other than the lung (P = 0.019, OR = 2.782), and the initial mixed venous oxygen saturation (P = 0.004, OR = 0.997). Risk factors for controls were the initial platelet count (P = 0.028, OR = 0.997) and the serum lactate level (P = 0.048, OR = 1.104). Patients with pre-existing left ventricular dysfunction who died had a lower initial mean mixed venous oxygen saturation than those who survived (61 ± 18% versus 70 ± 16%, P = 0.002)., Conclusions: Clinical outcomes were not different between septic patients with pre-existing left ventricular dysfunction and those with no cardiac disease. There was no correlation between fluid administration and oxygenation at 24 hours in either cohort. The mortality risk factor profile of patients with pre-existing left ventricular dysfunction was different when compared with control patients, and may be related to oxygen delivery determinants.

Individuals post stroke often rely more on hip flexors for limb advancement during walking due to distal weakness but the effects of muscle fatigue in this group is not known. The purpose of this study was to quantify how stroke affects the influence of hip flexor fatigue on over ground walking kinematics and performance and muscle activation. Ten individuals with chronic stroke and 10 without stroke (controls) participated in the study. Maximal walking speed, walking distance, muscle electromyograms (EMG), and lower extremity joint kinematics were compared before and after dynamic, submaximal fatiguing contractions of the hip flexors (30% maximal load) performed until failure of the task. Task duration and decline in hip flexion maximal voluntary contraction (MVC) and power were used to assess fatigue. The stroke and control groups had similar task durations and percent reductions in MVC force following fatiguing contractions. Compared with controls, individuals with stroke had larger percent reductions in maximal walking speed, greater decrements in hip range of motion and peak velocity during swing, greater decrements in ankle velocity and lack of modulation of hip flexor EMG following fatiguing dynamic hip flexion contractions. For a given level of fatigue, the impact on walking function was more profound in individuals with stroke than neurologically intact individuals, and a decreased ability to up regulate hip flexor muscle activity may contribute. These data highlight the importance of monitoring the effect of hip flexor muscle activity during exercise or performance of activities of daily living on walking function post stroke., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We describe the clinical course of two cases of neuroinvasive West Nile Virus (WNV) infection in the critical care unit. The first case is a 70-year-old man who presented during summer with mental status changes. Cerebrospinal fluid (CSF) analysis revealed pleocytosis with lymphocyte predominance. WNV serology was positive in the CSF. His condition worsened with development of left-sided weakness and deterioration of mental status requiring intensive care. The patient gradually improved and was discharged with residual left-sided weakness and near-complete improvement in his mental status. The second case is an 81-year-old man who presented with mental status changes, fever, lower extremity weakness, and difficulty in walking. CSF analysis showed pleocytosis with neutrophil predominance. WNV serology was also positive in CSF. During the hospital stay his mentation worsened, eventually requiring intubation for airway protection and critical care support. The patient gradually improved and was discharged with residual upper and lower extremity paresis. Neuroinvasive WNV infection can lead to significant morbidity, especially in the elderly. These cases should be suspected in patients with antecedent outdoor activities during summer. It is important for critical care providers to be aware of and maintain a high clinical suspicion of this disease process.

Introduction: Household products are usually safe to use. Adverse events arising from their use are mostly reported in patients with pre-existing atopy or pulmonary problems and usually only after a prolonged exposure to such products. We report the case of a patient with no prior problems who developed significant side effects from a single exposure to a domestic product., Case Presentation: A 43-year-old Caucasian American man, previously in good health, used a domestic aerosol product called 'Stand N' Seal "Spray-On" Grout Sealer' in an enclosed room in his house. The product contained n-butyl acetate (<5%), propane (10%), isobutane (<5%), C8-C9 petroleum hydrocarbon solvent (80%), a fluoropolymer resin and a solvent. Within a few hours of exposure to the sealant, he developed rapidly progressive shortness of breath and a severe non-productive cough. By the time he reached the emergency room he was severely hypoxic. A diagnosis of chemical pneumonitis was made based on the clinical scenario and the diffuse infiltrates on the computer tomography scan. With supportive therapy, his condition improved and he was discharged from the hospital. However, he continued to have symptoms of intermittent cough and shortness of breath in response to strong odours, fumes, cold air and exertion even after his chest radiograph had normalized. Three months later, bronchial hyper-responsiveness was documented by a methacholine inhalation test and a diagnosis of reactive airways dysfunction syndrome was made. The patient was started on high-dose inhaled steroids and his symptoms improved. The mechanism of toxicity and determination of the exact agent responsible is still under investigation., Conclusion: A household product may still prove unsafe to use even after it has gone through vigorous testing and approval processes. Even healthy individuals are susceptible to adverse outcomes after a brief exposure. Extra precautions should be taken when using any chemical product at home.

Objective: This guideline provides evidence-based recommendations on managing hoarseness (dysphonia), defined as a disorder characterized by altered vocal quality, pitch, loudness, or vocal effort that impairs communication or reduces voice-related quality of life (QOL). Hoarseness affects nearly one-third of the population at some point in their lives. This guideline applies to all age groups evaluated in a setting where hoarseness would be identified or managed. It is intended for all clinicians who are likely to diagnose and manage patients with hoarseness., Purpose: The primary purpose of this guideline is to improve diagnostic accuracy for hoarseness (dysphonia), reduce inappropriate antibiotic use, reduce inappropriate steroid use, reduce inappropriate use of anti-reflux medications, reduce inappropriate use of radiographic imaging, and promote appropriate use of laryngoscopy, voice therapy, and surgery. In creating this guideline the American Academy of Otolaryngology-Head and Neck Surgery Foundation selected a panel representing the fields of neurology, speech-language pathology, professional voice teaching, family medicine, pulmonology, geriatric medicine, nursing, internal medicine, otolaryngology-head and neck surgery, pediatrics, and consumers., Results: The panel made strong recommendations that 1) the clinician should not routinely prescribe antibiotics to treat hoarseness and 2) the clinician should advocate voice therapy for patients diagnosed with hoarseness that reduces voice-related QOL. The panel made recommendations that 1) the clinician should diagnose hoarseness (dysphonia) in a patient with altered voice quality, pitch, loudness, or vocal effort that impairs communication or reduces voice-related QOL; 2) the clinician should assess the patient with hoarseness by history and/or physical examination for factors that modify management, such as one or more of the following: recent surgical procedures involving the neck or affecting the recurrent laryngeal nerve, recent endotracheal intubation, radiation treatment to the neck, a history of tobacco abuse, and occupation as a singer or vocal performer; 3) the clinician should visualize the patient's larynx, or refer the patient to a clinician who can visualize the larynx, when hoarseness fails to resolve by a maximum of three months after onset, or irrespective of duration if a serious underlying cause is suspected; 4) the clinician should not obtain computed tomography or magnetic resonance imaging of the patient with a primary complaint of hoarseness prior to visualizing the larynx; 5) the clinician should not prescribe anti-reflux medications for patients with hoarseness without signs or symptoms of gastroesophageal reflux disease; 6) the clinician should not routinely prescribe oral corticosteroids to treat hoarseness; 7) the clinician should visualize the larynx before prescribing voice therapy and document/communicate the results to the speech-language pathologist; and 8) the clinician should prescribe, or refer the patient to a clinician who can prescribe, botulinum toxin injections for the treatment of hoarseness caused by adductor spasmodic dysphonia. The panel offered as options that 1) the clinician may perform laryngoscopy at any time in a patient with hoarseness, or may refer the patient to a clinician who can visualize the larynx; 2) the clinician may prescribe anti-reflux medication for patients with hoarseness and signs of chronic laryngitis; and 3) the clinician may educate/counsel patients with hoarseness about control/preventive measures., Disclaimer: This clinical practice guideline is not intended as a sole source of guidance in managing hoarseness (dysphonia). Rather, it is designed to assist clinicians by providing an evidence-based framework for decision-making strategies. The guideline is not intended to replace clinical judgment or establish a protocol for all individuals with this condition, and may not provide the only appropriate approach to diagnosing and managing this problem.

Study Objective: To determine the complication rate from supervised training bronchoscopy in a single pulmonary fellowship program, and to examine the effects of fellow and faculty experience on this complication rate., Design: A retrospective review of preexisting quality improvement data from one center for the time period July 1, 1991, until June 30, 2005, was performed. The data were stratified based on the fellow year group and the staff experience level. The types of complications were recorded., Setting: The study was performed at an accredited pulmonary and critical care fellowship program at a military medical center in the United States., Participants: Fifty-one pulmonary and critical care medicine fellows and 20 staff supervising physicians performed the bronchoscopies that were included in this study., Results: A total of 3,538 training bronchoscopies were performed during the study period with 73 complications for a complication rate of 2.06%. The most common complication was pneumothorax. The overall complication rates for first-year fellows (1stYFs), second-year fellows, and third-year fellows were not significantly different from the total complication rate. Training bronchoscopies supervised by junior staff had a complication rate not significantly different from that of senior staff. The cumulative complication rate for the first trimester for 1stYFs was 3.1%, whereas the cumulative complication rate for the second plus the third trimester for 1stYFs was 1.57% (p < 0.05)., Conclusions: Training bronchoscopy performed during a pulmonary fellowship is a safe procedure in a supervised setting. Patients undergoing bronchoscopy performed by novice bronchoscopists have an increased complication rate during the first trimester of bronchoscopist training.

Healthy individuals are able to tolerate profound, short-term decreases in hemoglobin levels and oxygen saturation without serious consequences, but critically ill patients in respiratory failure lack the necessary reserve capacity to preserve tissue oxygenation. The development of progressive anemia in ICU patients has led to much interest and debate about transfusion practices, yet optimal hemoglobin levels and how they should be achieved remain unclear. Animal and human studies regarding critical oxygen delivery provide the rationale for optimizing hemoglobin levels and supporting cardiovascular function during respiratory failure. Theoretically, the oxygen-carrying benefit of RBCs should hasten recovery from respiratory failure, and transfusions would therefore be expected to shorten the duration of mechanical ventilation. However, evidence to the contrary has been reported. Controversies related to transfusions and their inability to improve outcomes suggest that further research regarding transfusion alternatives is needed, especially in anemic patients with respiratory failure.

Introduction: Anemia is a common problem in critically ill patients. The etiology of anemia of critical illness is often determined to be multifactorial in the clinical setting, but the pathophysiology remains to be elucidated. Erythropoietin (EPO) is an endogenous glycoprotein hormone that serves as the primary stimulus for erythropoiesis. Recent evidence has demonstrated a blunted EPO response as a factor contributing to anemia of critical illness in specific subsets of patients. Critically ill patients requiring mechanical ventilation who exhibit anemia have not been the subject of previous studies. Our goal was to evaluate the erythropoietic response to anemia in the critically ill mechanically ventilated patient., Methods: A prospective observational study was undertaken in the medical intensive care unit of a tertiary care, military hospital. Twenty patients admitted to the medical intensive care unit requiring mechanical ventilation for at least 72 hours were enrolled as study patients. EPO levels and complete blood count were measured 72 hours after admission and initiation of mechanical ventilation. Admission clinical and demographic data were recorded, and patients were followed for the duration of mechanical ventilation. Twenty patients diagnosed with iron deficiency anemia in the outpatient setting were enrolled as a control population. Control patients had baseline complete blood count and iron panel recorded by primary care physicians. EPO levels were measured at the time of enrollment in conjunction with complete blood count., Results: The mean EPO level for the control population was 60.9 mU/ml. The mean EPO level in the mechanically ventilated patient group was 28.7 mU/ml, which was significantly less than in the control group (P = 0.035). The mean hemoglobin value was not significantly different between groups (10.6 g/dl in mechanically ventilated patients versus 10.2 g/dl in control patients; P > 0.05)., Conclusion: Mechanically ventilated patients demonstrate a blunted EPO response to anemia. Further study of therapies directed at treating anemia of critical illness and evaluating its potential impact on mechanical ventilation outcomes and mortality is warranted.

Background: Serum angiotensin-converting enzyme (ACE) level is elevated in a number of disease states and medical conditions. Based on review of the medical literature, we postulated that serum ACE level elevation may occur during infection with the human immunodeficiency virus (HIV)., Methods: In a prospective, controlled study, serum ACE levels of HIV-positive patients were compared with those of an HIV-negative control population., Results: Serum ACE levels were significantly elevated in patients with the acquired immunodeficiency syndrome (55.4 +/- 11.4 U/L) and in patients with an intermediate stage of HIV infection (57.2 +/- 25.3 U/L) when compared with levels in controls (31.9 +/- 14.0 U/L)., Conclusions: Elevated serum ACE levels occur in HIV infection and may be an important marker for this disease.