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[Display omitted] The response to inhaled corticosteroids (ICS) in asthma is affected by the interplay of several factors. Among these, the role of the upper-airway microbiome has been scarcely investigated. We aimed to evaluate the association between the salivary, pharyngeal, and nasal microbiome with asthma exacerbations despite receipt of ICS. Samples from 250 asthma patients from the Genomics and Metagenomics of Asthma Severity (GEMAS) study treated with ICS were analyzed. Control/case subjects were defined by the absence/presence of asthma exacerbations in the past 6 months despite being treated with ICS. The bacterial microbiota was profiled by sequencing the V3-V4 region of the 16S rRNA gene. Differences between groups were assessed by PERMANOVA and regression models adjusted for potential confounders. A false discovery rate (FDR) of 5% was used to correct for multiple comparisons. Classification models of asthma exacerbations despite ICS treatment were built with machine learning approaches based on clinical, genetic, and microbiome data. In nasal and saliva samples, case subjects had lower bacterial diversity (Richness, Shannon, and Faith indices) than control subjects (.007 ≤ P ≤.037). Asthma exacerbations accounted for 8% to 9% of the interindividual variation of the salivary and nasal microbiomes (.003 ≤ P ≤.046). Three, 4, and 11 bacterial genera from the salivary, pharyngeal, and nasal microbiomes were differentially abundant between groups (4.09 × 10−12 ≤ FDR ≤ 0.047). Integrating clinical, genetic, and microbiome data showed good discrimination for the development of asthma exacerbations despite receipt of ICS (AUC training : 0.82 and AUC validation : 0.77). The diversity and composition of the upper-airway microbiome are associated with asthma exacerbations despite ICS treatment. The salivary microbiome has a potential application as a biomarker of asthma exacerbations despite receipt of ICS. [ABSTRACT FROM AUTHOR]

Background: Exacerbations are the strongest risk factor for future exacerbations for patients living with chronic obstructive pulmonary disease (COPD). The period immediately following exacerbation is a high-risk period for recurrence and hospital admission, and is a critical time to intervene. GPs are ideally positioned to deliver this care. Aim: To explore perceptions of GPs regarding the care of patients following exacerbations of COPD and to identify factors affecting the provision of evidence-based care. Design and setting: A descriptive qualitative study was undertaken involving semi-structured, in-depth interviews with Australian GPs who volunteered to participate following a national survey of general practice care for COPD patients following exacerbations. Method: Interviews were conducted via the Zoom video conference platform, which were audio-recorded and transcribed verbatim. QSR NVivo was used to support data management, coding, and inductive thematic analysis. Results: Eighteen GPs completed interviews. Six key themes were identified: 1) GPs' perceptions and knowledge in the management of COPD patients following exacerbation and admission to hospital; 2) pharmacological management; 3) consultation time; 4) communication between healthcare professionals; 5) access to other health services; and 6) patient compliance. Conclusion: Delivery of post-exacerbation care to COPD patients is affected by GPs, patients, and health service-related factors. The care of COPD patients may be further improved by supporting GPs to overcome identified barriers. [ABSTRACT FROM AUTHOR]

(1) Background: We have previously shown that sputum rheology can discriminate between patients with COPD and other muco-obstructive lung diseases, and that it is correlated with mucin content and sputum eosinophilia. We now hypothesize that it could be a more-accurate guide than clinical evaluation for the prescription of azithromycin to prevent exacerbations of COPD and to reduce exposure to antibiotics; (2) Methods: "COPD CaRhe" is a multicentric, randomized, controlled trial comparing outcomes in two parallel arms (36 vs. 36 patients). Patients will be recruited in the university hospitals of Montpellier, Bordeaux, and Toulouse, in France, and they should have a diagnosis of COPD with frequent exacerbations (≥3/year). Enrollment will occur during a routine visit to a respiratory department, and follow-up visits will occur every 3 months for a period of 1 year. At each visit, a 3-month prescription of azithromycin will be provided to those patients who obtain a score of <70 on the Cough and Sputum Assessment Questionnaire (CASA-Q) or a critical stress score of σc > 39 on a rheological assessment of sputum, depending upon their randomization group. The primary outcome will be the number of exacerbations of COPD; (3) Discussion: By using sputum rheology, the COPD CaRhe study may provide clinicians with an objective biomarker to guide the prescription of azithromycin while reducing the cumulative exposure to macrolides. [ABSTRACT FROM AUTHOR]

Different ages of asthma onset can lead to similar clinical symptoms but have different underlying mechanisms that may influence treatment response. This post-hoc analysis assessed response to omalizumab in relation to the age of asthma onset. Using pooled data from two phase III studies (patients 12–75 years), changes in exacerbation rates, forced expiratory volume in 1 second (FEV1) and inhaled corticosteroids (ICS) were assessed by age of asthma onset (<18 [n = 574], 18– 40 [n = 360], >40 years [n = 136]). Exacerbations (week 16) were reduced with omalizumab versus placebo in all subgroups (relative rate reduction [95% confidence interval]: <18, (53.1% [–73.6,–16.6]; 18–40, (68.3% [–85.5,–31.0]; >40, (38.4% [–77.3,67.4]). FEV1 increased with omalizumab in all subgroups; increases were sustained in <18 and 18–40 years subgroups, but not in >40 years subgroup. ICS dose reductions (week 28) were greater with omalizumab versus placebo, regardless of age of asthma onset, as were percentages of patients with ICS doses reduced by at least 50% and 100%. In conclusion, omalizumab-treated patients had lower exacerbation rates and were more frequently able to reduce/ discontinue ICS versus placebo, regardless of age of asthma onset, therefore omalizumab may be beneficial to all eligible patients with allergic asthma. [ABSTRACT FROM AUTHOR]

Background: The small airway disease has been recognized as a central feature of chronic obstructive pulmonary disease (COPD). Triple fixed combination beclomethasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) is provided as a pressurized single-dose inhaler based on an extra-fine formulation, which has been approved for patients with COPD experiencing frequent disease exacerbations. Methods: The aim of our real-life single-center observational study was to investigate, in 22 patients with COPD, the effects of BDP/FF/G on lung function, respiratory symptoms, health status, and exacerbation rate. Several clinical and lung functional parameters were evaluated at baseline and after 12 months of treatment with combined inhaled triple therapy. Results: With respect to baseline, after 12 months of treatment with BDP/FF/G, significant changes were recorded with regard to forced expiratory flow at 75% of forced vital capacity (FVC) (p < 0.01), forced expiratory flow at 50% of FVC (p < 0.01), forced expiratory flow at 25% of FVC (p < 0.05), and forced mid-expiratory flow between 25% and 75% of FVC (p < 0.01). Moreover, we observed reductions of total resistance (p < 0.01), effective resistance (p < 0.01), and effective specific resistance (p < 0.01). In the same period, residual volume diminished (p < 0.01) and forced expiratory volume in 1 s increased (p < 0.01). Moreover, in a subgroup of 16 patients, an enhancement of diffusion lung capacity (p < 0.01) was also detected. These functional results were paralleled by concomitant clinical effects, as evidenced by the improvements of modified British Medical Research Council (mMRC) dyspnea scale (p < 0.001), COPD Assessment Test (CAT) score (p < 0.0001), and COPD exacerbations (p < 0.0001). Conclusion: In conclusion, the valuable findings of our observational study consist in the corroboration in a real-life context of the therapeutic effects evidenced by randomized controlled trials with regard to the use of the triple inhaled BDP/FF/G therapy in patients with COPD. [ABSTRACT FROM AUTHOR]

Whereas exacerbation action plans to self-manage Chronic Obstructive Pulmonary Disease (COPD) significantly improve health outcomes, patients’ adherence to those action plans is often poor. This study aimed to identify facilitators and barriers of adherence to tailored multi-disease exacerbation action plans. We also explored patients’ perspectives toward disease management roles. Individual semi-structured interviews were conducted with a sample of COPD patients who completed a Dutch-Australian self-management intervention evaluating tailored exacerbation action plans for COPD and relevant comorbidities. Interviews were thematically analyzed using a deductive approach guided by the Capability, Opportunity and Motivation of Behavior (COM-B) model. In 2016, ten patients (5 Australian; 5 Dutch; 6 men; age 59-83 years) were interviewed at the end of their one-year follow-up. Facilitators of adherence included improved patients’ comprehension of disease and treatment, positive feelings about the intervention, improved self-confidence, and professional support. Barriers included difficulties to recognize symptoms, dislike toward daily symptom monitoring, negative feelings about the intervention, negative mood state, and complexity of symptom diaries and action plans. Patients indicated three distinctive perspectives of their own and their healthcare professional’s role in their disease management: 1) patients felt mainly responsible; 2) patients felt shared responsibility with their healthcare professional; and 3) patients felt not responsible as they perceived their healthcare professional to be mainly responsible. We successfully used the COM-B model as a guide to identify facilitators and barriers of patients’ adherence to multi-disease exacerbation action plans. Improving patients’ adherence in future self-management interventions by targeting specific facilitators or barriers should be considered. [ABSTRACT FROM AUTHOR]

The purpose of this study was to establish a nomogram for predicting community-acquired pneumonia (CAP) in hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The retrospective cohort study included 1249 hospitalized patients with AECOPD between January 2012 and December 2019. The patients were divided into pneumonia-complicating AECOPD (pAECOPD) and non-pneumonic AECOPD (npAECOPD) groups. The least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were utilized to identify prognostic factors. A prognostic nomogram model was established, and the bootstrap method was used for internal validation. Discrimination and calibration of the nomogram model were evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Logistic and LASSO regression analysis showed that C-reactive protein (CRP) >10 mg/L, albumin (Alb) <40 g/L, alanine transferase (ALT) >50 U/L, fever, bronchiectasis, asthma, previous hospitalization for pAECOPD in the past year (Pre-H for pAECOPD), and age-adjusted Charlson score (aCCI) ≥6 were independent predictors of pAECOPD. The area under the ROC curve (AUC) of the nomogram model was 0.712 (95% CI: 0.682–0.741). The corrected AUC of internal validation was 0.700. The model had well-fitted calibration curves and good clinical usability DCA curve. A nomogram model was developed to assist clinicians in predicting the risk of pAECOPD. China Clinical Trials Registry: ChiCTR2000039959 [ABSTRACT FROM AUTHOR]

The use of inhaled corticosteroids (ICS) for the maintenance of bronchodilator treatment in patients with chronic obstructive pulmonary disease (COPD) is controversial. While some patients achieve clinical benefits, such as fewer exacerbations and improved symptoms, others do not, and some experience undesired side effects, such as pneumonia. Thus, we reviewed the evidence related to predictors of ICS therapy treatment response in patients with COPD. The first priority clinical markers when considering the efficacy of ICS are type 2 inflammatory biomarkers, followed by a history of suspected asthma and recurrent exacerbations. It is also necessary to consider any potential infection risk associated with ICS, and several risk factors for pneumonia when using ICS have been clarified in recent years. In this article, based on the evidence supporting the selection of ICS for COPD, we propose an ICS composite that can be added to the COPD (ICO) chart for use in clinical practice. The chart divided the type 2 biomarkers into three ranges and provided recommendations (recommend, consider, and against) by combining the history of suspected asthma, history of exacerbations, and risk of infection. [ABSTRACT FROM AUTHOR]

Introduction: Awareness of risk factors for asthma exacerbation can reduce the morbidity and mortality of the disease. The current study aimed to investigate the risk factors associated with current asthma exacerbations in school-age children. Methods: This study enrolled children who were admitted to a tertiary outpatient paediatric allergy and asthma department and were diagnosed with asthma. Patients and their caregivers underwent an interviewer-administered questionnaire, which obtained information regarding the demographic features and parameters to determine environmental exposures along with previous disease history. Laboratory examinations, including complete blood count with differential, total IgE levels, skin prick tests, and pulmonary function tests, were also performed. Results: A total of 431 children (288 male, 66.8%) with a median age (interquartile range) of 8.1 (6.3–11.2) years were included, among whom 265 (61.5%) had aeroallergen sensitization. Asthma was controlled, partially controlled, and uncontrolled in 154 (35.7%), 53 (12.3%), and 143 (33.2%) patients, respectively. A total of 81 patients (18.8%) experienced asthma exacerbation. Multivariate logistic regression analysis revealed that a history of asthma exacerbation within the last year (odds ratio [confidence interval]) (20.73 [9.95–43.20]; p < 0.001), a shorter asthma duration (<2.5 years) (2.58 [1.44–4.61]; p = 0.001), and a lack of regular controller therapy (4.12 [1.54–10.98]; p = 0.005) were associated with current asthma exacerbation. Discussion/Conclusion: Awareness of risk factors for asthma exacerbation may help physicians treat school-age children with asthma by providing prompt and rational interventions in order to prevent asthma exacerbations. [ABSTRACT FROM AUTHOR]

Purpose: Asthma is a common comorbidity in patients with bronchiectasis and has been shown to increase the risk of bronchiectasis exacerbations. This paper explores the impact of comorbid asthma on patients receiving intravenous antibiotic treatment for bronchiectasis exacerbations. Methods: This was a post hoc analysis of the Meropenem randomised controlled trial of 90 patients that had intravenous antibiotic treatment for bronchiectasis exacerbations. The participants were split into two groups: group 1 (asthma and bronchiectasis) and group 2 (bronchiectasis). The authors assessed response to treatment and time to next exacerbation. Results: There were 38 participants in group 1 and 34 participants in group 2. The groups were found to be comparable in terms of age, sex, and bronchiectasis severity (median (95% CI) group 1 and then group 2 data): age 64.0(59.3, 68.6) and 63.6(57.9, 69.4) years old, p = 0.8; 57.9% and 64.7% female, p = 0.6; Bronchiectasis Severity Index 11.1(9.8, 12.4) and 10.1(8.2, 12.0), p = 0.3. There was a similar response to treatment between the groups, but group 1 were found to relapse early by day 14, 31.6% in group 1 and 11.8% in group 2, p = 0.03. In the Cox proportional hazards model, asthma was the only independent risk factor for early relapse by day 14 (odds ratio (95% CI) 3.16 (1.02–9.79), p = 0.047). Conclusion: The clinical response to treatment was similar but patients with coexisting asthma were at increased risk of early relapse within 14 days of stopping intravenous antibiotic therapy. Clinical Trial Registration: NCT02047773. [ABSTRACT FROM AUTHOR]

Introduction: A twice-daily single inhaler triple therapy consisting of budesonide/glycopyrrolate/formoterol fumarate (BGF) was approved by the US Food and Drug Administration (FDA) in July 2020 as a maintenance treatment for patients with chronic obstructive pulmonary disease (COPD). The objective of this AURA study is to describe patient characteristics, exacerbation and treatment history, and healthcare resource utilization (HCRU) before BGF initiation to better inform treatment decisions for prescribers. Methods: This retrospective cohort study leveraged data of all payer types from IQVIA's Longitudinal Prescription Data (LRx) linked to Medical Data (Dx). Patients with COPD who had ⩾1 LRx claim for BGF between 1 October 2020 and 30 September 2021 were included. The date of first BGF claim was the index date. Patient demographic and clinical characteristics, history of COPD exacerbation or related event, treatment history, and HCRU were assessed during the 12 months before index (baseline). Results: We identified 30,339 patients with COPD initiating BGF (mean age: 68.2 years; 57.1% female; 67.6% Medicare). Unspecified COPD (J44.9; 74.0%) was the most commonly coded COPD phenotype. The most prevalent respiratory conditions/symptoms were dyspnea (50.8%), lower respiratory tract infection (25.3%), and sleep apnea (19.0%). Uncomplicated hypertension (58.8%), dyslipidemia (43.9%), cardiovascular disease (41.4%), and heart failure (19.9%) were the most prevalent nonrespiratory conditions. During the 12-month baseline, 57.9% of patients had evidence of a COPD exacerbation or related event, and 14.9% had ⩾1 COPD-related emergency department (ED) visit; 21.0% of patients had evidence of prior triple therapy use, while 54.3% had ⩾1 oral corticosteroid (OCS) fill. Among OCS users, 29.9% had cumulative exposures >1000 mg [median [Q1-Q3] exposure: 520 (260-1183) mg]. Conclusion: This real-world data analysis indicates that BGF is being initiated in patients with COPD experiencing symptoms and exacerbations despite current therapy, and among patients who have various chronic comorbidities, most often cardiopulmonary-related. [ABSTRACT FROM AUTHOR]

Background: Asthma is the most common non-communicable chronic airway disease worldwide. Obesity and cigarette use independently increase asthma morbidity and mortality. Current literature suggests that obesity and smoking synergistically increase asthma-related wheezing. Objective: To assess whether increased serum cotinine and obesity act synergistically to increase the likelihood of having an asthma exacerbation, emergency department (ED) visit, or hospitalization. Methods: A cross-sectional analysis of the 2011–2015 iterations of NHANES database was performed. Patients aged 18 years or greater with asthma were included. Serum cotinine was utilized as an accurate measurement of cigarette use. Logistic regression models were constructed to determine whether elevated serum cotinine and obesity were associated with self-reported asthma exacerbations, asthma-specific ED usage, and hospitalizations for any reason in the past year. Odds ratios were adjusted for age, gender, race, and ethnicity. Interactions were assessed by multiplying the adjusted effect sizes for elevated cotinine and obesity. Results: We identified 2179 (N = 32,839,290) patients with asthma, of which 32.2% were active smokers and 42.7% were obese. Patients with an elevated cotinine and asthma were significantly more likely to have had an asthma-related ED visit in the past year (adjusted odds ratio [AOR] 1.82; 95% CI 1.19–2.79), have a physician-prescribed asthma medication (AOR 2.04; 95% CI 1.11–3.74), and have a hospitalization for any reason (AOR 3.65; 95% CI 1.88–7.07) compared to those with low cotinine. Patients with asthma and obesity were more likely to have an asthma-related ED visit (AOR 1.67; 95% CI 1.06–2.62) or hospitalization for any reason in the past year compared to non-obese patients (AOR 2.76; 95% CI 1.69–4.5). However, a statistically significant interaction between obesity and cotinine was only identified in patients who currently have asthma compared to a previous asthma diagnosis (AOR 1.76; 95% CI 1.10–2.82). There were no synergistic interactions among ED usage or asthma exacerbations. Conclusion: Nearly one-third of patients with asthma were current smokers, and almost half were obese. This study identified elevated serum cotinine, a metabolite of cigarette use, and obesity as key risk factors for asthma exacerbations, asthma-related ED visits, and hospitalizations for any reason. Elevated serum cotinine and obesity were not found to act synergistically in increasing asthma exacerbations or ED visits. However, the presence of both risk factors increased the risk of currently having asthma (compared to a previous diagnosis) by 76%. Serum cotinine may be useful in predicting asthma outcomes. [ABSTRACT FROM AUTHOR]

Background: In this study, we will derive and validate a prognostic tool to predict in-hospital death based on Chinese acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients. Methods: Independent predictors of in-hospital death were identified by logistic regression analysis and incorporated into a clinical prediction tool. Results: The clinical prediction model was developed with data from 1121 patients and validated with data from 245 patients. The five predictors of in-hospital death from the development cohort (Arrival ward requiring help by wheelchair or medical cart, Arterial oxygenation index, Age, Albumin and Neutrophil count) were combined to form the AAAAN Score. The AAAAN Score achieved good discrimination (AUC = 0.85, 95% CI 0.81-0.89) and calibration (Hosmer-Lemeshow chi-square value was 3.33, p = 0.65). The AAAAN Score, which underwent internal bootstrap validation, also showed excellent discrimination for mortality (AUC = 0.85, 95% CI 0.81 to 0.89) and performed more strongly than other clinical prediction tools. Patients were categorized into 3 risk groups based on the scores: low risk (0-2 points, 0.7% in-hospital mortality), intermediate risk (3-4 points, 4.1% in-hospital mortality), and high risk (5-7 points, 23.4% in-hospital mortality). Predictive performance was confirmed by external validation. Conclusions: The AAAAN Score is a prognostic tool to predict in-hospital death in Chinese AECOPD patients. [ABSTRACT FROM AUTHOR]

Abstract Background Over-reliance on short-acting β2-agonists (SABAs) is associated with poor asthma outcomes. However, the extent of SABA use in Turkey is unclear owing to a lack of comprehensive healthcare databases. Here, we describe the demographics, disease characteristics and treatment patterns from the Turkish cohort of the SABA use IN Asthma (SABINA) III study. Methods This observational, cross-sectional study included patients aged ≥ 12 years with asthma from 24 centres across Turkey. Data on sociodemographics, disease characteristics and asthma treatments were collected using electronic case report forms. Patients were classified by investigator-defined asthma severity (guided by the 2017 Global Initiative for Asthma [GINA]) and practice type (primary/specialist care). The primary objective was to describe SABA prescription patterns in the 12 months prior to the study visit. Results Overall, 579 patients were included (mean age [standard deviation; SD]: 47.4 [16.1] years; 74.3% female), all of whom were treated by specialists. Most patients had moderate-to-severe asthma (82.7%, GINA steps 3–5), were overweight or obese (70.5%), had high school or university/post-graduate education (51.8%) and reported fully reimbursed healthcare (97.1%). The mean (SD) asthma duration was 12.0 (9.9) years. Asthma was partly controlled/uncontrolled in 56.3% of patients, and 46.5% experienced ≥ 1 severe exacerbation in the preceding 12 months. Overall, 23.9% of patients were prescribed ≥ 3 SABA canisters in the previous 12 months (considered over-prescription); 42.9% received no SABA prescriptions. As few patients had mild asthma, only 5.7% were prescribed SABA monotherapy. Therefore, most patients (61.5%) were prescribed SABA in addition to maintenance therapy, with 42.8% receiving ≥ 3 SABA canisters in the previous 12 months. Inhaled corticosteroids (ICS), ICS + a long-acting β-agonist fixed-dose combination and oral corticosteroids were prescribed to 14.5%, 88.3% and 28.5% of all patients, respectively. Additionally, 10.2% of patients purchased SABA over the counter, of whom 27.1% purchased ≥ 3 canisters in the preceding 12 months. Conclusions Despite all patients being treated by specialists and most receiving fully reimbursed healthcare, nearly a quarter of patients received prescriptions for ≥ 3 SABA canisters in the previous 12 months. This highlights a public health concern and emphasizes the need to align clinical practices with the latest evidence-based recommendations.

Evgeni Mekov,1 Nikolay Yanev,2 Nedelina Kurtelova,2 Teodora Mihalova,2 Adelina Tsakova,3 Yordanka Yamakova,4 Marc Miravitlles,5 Rosen Petkov2 1Department of Occupational Diseases, Medical University Sofia, Sofia, Bulgaria; 2Department of Pulmonary Diseases, Medical University Sofia, Sofia, Bulgaria; 3Central Clinical Laboratory, Medical University Sofia, Sofia, Bulgaria; 4Department of Anesthesiology and Intensive Care, Medical University Sofia, Sofia, Bulgaria; 5Pneumology Department, Hospital Universitari Vall d´Hebron/Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Campus; CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, SpainCorrespondence: Marc Miravitlles, Pneumology Department, Hospital Universitari Vall d´Hebron, Pg. Vall d’Hebron 119-129, Barcelona, 08035, Spain, Email marcm@separ.esIntroduction: Diaphragmatic dysfunction is common in patients with chronic obstructive pulmonary disease (COPD). This study aimed to assess the prognostic significance of impaired diaphragmatic movement at rest and after exercise.Methods: This was a prospective study of patients with stable COPD. Diaphragmatic movements were examined at rest and after a 6-minute walking test (6MWT) with a convex transducer with a frequency of 3.5-5-7.5 MHz. Maximal movement of the diaphragm was measured in both right and left diaphragm, and the side with higher amplitude was selected for further analysis. Measurements obtained were evaluated for their prognostic value for a composite endpoint of moderate and severe COPD exacerbations and death in 1 year time period was assessed. In addition, postbronchodilator spirometry, symptoms, quality of life, and demographic and clinical information were collected.Results: A total of 96 patients were analyzed (62.5% male, mean age 65.1 years (standard deviation (SD): 8.1), mean FEV1 (% predicted): 55.8%, SD: 18.3%, mean CAT: 15.6 units, SD: 9.2). Sixty-four patients (67%) presented the composite endpoint. In the multivariate Cox analysis, FVC (HR = 0.944, p = 0.005), CAT score (HR = 1.133, p = 0.011), previous severe exacerbations (HR = 5.446, p = 0.004) and diaphragmatic movement at rest (HR = 0.932, p = 0.033) were found to be predictors of the composite endpoint. This model correctly classified 86.5% (83/96) of the patients.Conclusion: Non-invasive assessment of diaphragmatic movement by ultrasound measurement both at rest and after exercise could contribute to the assessment of disease severity and prognosis of COPD.Keywords: COPD, diaphragmatic dysfunction, comorbidities, thoracic ultrasound, exacerbations

Fernando González-Torralba,1 Adolfo Baloira,2 Araceli Abad,3 Antonia Fuster,4 Juan Luis García-Rivero,5 Patricia García-Sidro,6 Eduardo Márquez-Martín,7 Marta Palop,8 Néstor Soler,9 José Luis Velasco10 1Respiratory Department, University Hospital of Aranjuez, Madrid, Spain; 2Respiratory Department, University Hospital of Pontevedra, Pontevedra, Spain; 3Respiratory Department, University Hospital of Getafe, Madrid, Spain; 4Respiratory Department, University Hospital Son Llatzer, Palma de Mallorca, Spain; 5Respiratory Department, University Hospital Marqués de Valdecilla, Santander, Spain; 6Respiratory Department, University Hospital of La Plana, Castellón, Spain; 7Respiratory Department, University Hospital Virgen del Rocío, Sevilla, Spain; 8Respiratory Department, Hospital of Sagunto, Valencia, Spain; 9Respiratory Department, Hospital Clinic, Barcelona, Spain; 10Respiratory Department, University Hospital Virgen de la Victoria, Málaga, SpainCorrespondence: Adolfo Baloira, Email adolfo.baloira.villar@sergas.esPurpose: The pharmacological treatment of chronic obstructive pulmonary disease (COPD) is largely based on inhaled bronchodilators. Inspiratory flow and lung deposition are key parameters to be considered in inhaled therapy; however, the relationship between these two parameters, the patient specificities, and the suitability of the inhaler type for COPD management has not been fully addressed. The present study follows a Delphi Panel methodology to find expert consensus on the role of inspiratory flow and lung deposition as key decision factors in COPD inhaled therapy.Methods: A two-round Delphi Panel, consisting of 38 statements (items) and completed by 57 Spanish pulmonologists, was carried out to measure the experts’ consensus degree with each item.Results: A high degree of consensus was reached on most of the items consulted, among these inspiratory flow or inspiratory capacity should be periodically considered when choosing an inhalation device and to ensure the suitability of the inhaler used; the outflow velocity and particle size of the different devices should be considered to ensure adequate lung deposition; an active device (pressurized metered-dose inhalers (pMDI) or soft mist inhalers (SMI)) should be used in patients with low inspiratory flow to achieve adequate lung deposition; and, the use of dry powder inhalers (DPI) should be re-evaluated in patients with severe obstruction and severe exacerbations.Conclusion: This study shows the relevance of inspiratory flow and the degree of particle deposition in the lung in the choice of an inhalation device for COPD management, as well as the convenience of an SMI type device in cases of low inspiratory flow. Moreover, it highlights the scarcity of information on the specific features of inhalation devices in COPD guidelines.Keywords: dry powder inhalers, pressurized metered-dose inhalers, soft mist inhaler, inhaled therapy device, exacerbations

Yi Li, Hongyu Qian, Kewei Yu, Ying Huang Department of Respiratory and Critical Care Medicine, Tianjin Chest Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Yi Li, Department of Respiratory and Critical Care Medicine, Tianjin Chest Hospital, Tianjin, People’s Republic of China, Email lisalie5252@hotmail.comBackground: Although the benefits of conventional pulmonary rehabilitation (PR) maintenance are well documented, it is challenged by many difficulties. We investigated whether remote home-based PR maintenance strategy via social media (WeChat) is effective on clinical improvements and reducing the risk for acute exacerbation of chronic obstructive pulmonary disease (COPD).Methods: The eligible stable COPD patients completing an initial 8-week PR were allocated into three groups randomly. Group A: PR maintenance via social media supervision at home. Group B: PR maintenance at hospital. Group C: Usual care. During a 12-month follow-up, the frequency of acute exacerbation of COPD (AECOPD), 6 minutes walking test (6MWT), COPD assessment test (CAT), and modified Medical Research Council scale (mMRC) were evaluated every 3 months.Results: At the end of the follow-up, compared to the decline in the usual care group (n = 49), the clinical improvements of 6MWD, CAT, and mMRC were sustained in both the home-based group (n = 47) and the hospital-based maintenance group (n = 44) (p < 0.001), no difference was observed between these two groups (p > 0.05). In multivariate analysis, the home-based PR maintenance and hospital-based PR maintenance were independent predictors of lower risk for AECOPD (incidence rate ratio (IRR) 0.712, 95% CI 0.595– 0.841, p < 0.001 and IRR 0.799, 95% CI 0.683– 0.927, p = 0.002), respectively.Conclusion: Remote PR maintenance via social media is effective in reducing the risk for AECOPD and keeping the clinical improvement from decline. Remote PR maintenance via social media might be used to deliver alternatives to conventional PR.Keywords: chronic obstructive pulmonary disease, pulmonary rehabilitation, maintenance, exacerbations, home monitoring

Abstract Background Although it is generally accepted that physical activity and flares of low back pain (LBP) are related, evidence for the directionality of this association is mixed. The Flares of Low back pain with Activity Research Study (FLAReS) takes a novel approach to distinguish the short-term effects of specific physical activities on LBP flares from the cumulative effects of such activities, by conducting a longitudinal case-crossover study nested within a cohort study. The first aim is to estimate the short-term effects (≤ 24 h) of specific physical activities on LBP flares among Veterans in primary care in the Veterans Affairs healthcare system. The second aim is to estimate the cumulative effects of specific activities on LBP-related functional limitations at 1-year follow-up. Methods Up to 550 adults of working age (18—65 years) seen for LBP in primary care complete up to 36 “Scheduled” surveys over 1-year follow-up, and also complete unscheduled “Flare Window” surveys after the onset of new flares. Each survey asks about current flares and other factors associated with LBP. Surveys also inquire about activity exposures over the 24 h, and 2 h, prior to the time of survey completion (during non-flare periods) or prior to the time of flare onset (during flares). Other questions evaluate the number, intensity, duration, and/or other characteristics of activity exposures. Other exposures include factors related to mood, lifestyle, exercise, concurrent treatments, and injuries. Some participants wear actigraphy devices for weeks 1–4 of the study. The first aim will examine associations between 10 specific activity categories and participant-reported flares over 1-year follow-up. The second aim will examine associations between the frequency of exposure to 10 activity categories over weeks 1–4 of follow-up and long-term functional limitations at 12 months. All analyses will use a biopsychosocial framework accounting for potential confounders and effect modifiers. Discussion FLAReS will provide empirically derived estimates of both the short-term and cumulative effects of specific physical activities for Veterans with LBP, helping to better understand the role of physical activities in those with LBP. Trial Registration ClinicalTrials.gov NCT04828330 , registered April 2, 2021.

Francesco Menzella,1 Matteo Fontana,1 Marco Contoli,2 Patrizia Ruggiero,1 Carla Galeone,1 Silvia Capobelli,1 Anna Simonazzi,1 Chiara Catellani,1 Chiara Scelfo,1 Claudia Castagnetti,1 Francesco Livrieri,1 Nicola Facciolongo1 1Pulmonology Unit, Arcispedale Santa Maria Nuova, Azienda USL – IRCCS di Reggio Emilia, Reggio Emilia, Italy; 2Respiratory Section, Department of Translational Medicine, University of Ferrara, Ferrara, ItalyCorrespondence: Francesco Menzella, Pulmonology Unit, Arcispedale Santa Maria Nuova, Azienda USL – IRCCS di Reggio Emilia, Reggio Emilia, Italy, Tel +39 0522 296073, Email fmenzella@gmail.comPurpose: Treatment of severe asthma has made great strides thanks to rapid progress in understanding immune response and inflammatory pathways. This led to the advent of the first biologic for severe allergic asthma (SAA), omalizumab. Although the long-term efficacy and safety of omalizumab has been confirmed, increasingly longer follow-up data can further reinforce this evidence and potentially provide new ones, for example on any loss of efficacy or the appearance of unexpected side effects. This study reports omalizumab treatment-related outcomes after 16 years of follow-up.Patients and Methods: In this real-life retrospective study, an extension of a previous 9-year follow-up study on patients initially recruited in a clinical trial, we enrolled 8 adult patients with SAA followed-up from November 2005 to December 2021. Study subjects were selected based on omalizumab eligibility criteria.Results: Exacerbation rate significantly decreased from 3.6 ± 2.1 events in year before index date to 0.1 ± 0.4 after 32 weeks of treatment (p < 0.0001). Mean annual number of mild-to-moderate exacerbations at 16 years was 0.88 compared with 1.8 in the year before the index date and 1.1 at 32 weeks. No hospitalizations were documented during the 16-year follow-up compared to 0.3 hospitalizations/patient in the year before the index date. Respiratory function also progressively and significantly improved. Regarding patient-reported outcomes (PROs), The AQLQ and ACT significantly improved from baseline throughout the follow-up, particularly up to 9 years of follow-up. During the study, an overall reduction in doses of asthma medications was observed, with a significant OCS-sparing effect.Conclusion: Our study, the longest clinical follow-up on patients treated with anti-IgE, confirms and amplifies the results of the studies carried out so far, as they are maintained over a very long interval of time without drops in efficacy without any type of side effect.Keywords: severe allergic asthma, biologics, omalizumab, exacerbations, side effects, oral corticosteroids

Bassam Mahboub,1 Ahmed Mohy,2 Islam El-Amir,2 Tamara Luki&cacute;,3 Raef Gouhar,4 Saeed Noibi5 1Pulmonary Medicine Department, Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates; 2Medical Affairs Department, GSK, Jeddah, Kingdom of Saudi Arabia; 3GSK Research and Development, Dubai, United Arab Emirates; 4Medical Affairs Department, GSK, Dubai, United Arab Emirates; 5Medical Excellence and Value Access, Emerging Markets Region, GSK, Jeddah, Kingdom of Saudi ArabiaCorrespondence: Raef Gouhar, Medical Affairs Department, GSK, Dubai, United Arab Emirates, Email raef.a.gouhar@gsk.comPurpose: To estimate 5-years budgetary impact of introducing mepolizumab to eligible patients with uncontrolled severe eosinophilic asthma treated at a tertiary care hospital within Dubai Health Authority (DHA).Patients and Methods: A budget impact analysis (BIA) model was adapted to the setting of Rashid Hospital, DHA to estimate the budgetary implications of introducing first-in-class anti-IL5 (mepolizumab) as add-on therapy for eligible patients with severe eosinophilic asthma. The eligible patient population (n=60) was estimated from aggregate data provided by the clinic. Patients were eligible to treatment with mepolizumab if they had ≥ 2 exacerbation in the previous year and eosinophil count ≥ 150 cell/μL. The analysis compared the cost of treating patients in two alternative scenarios; a scenario where patients are treated with optimized usual care or with available biologic as add-on therapy, and a second scenario where mepolizumab is fully accessible to eligible patients.Results: Administration of mepolizumab to eligible patients at Rashid Hospital is predicted to result in overall savings estimated at £ 270,545 over a 5-year time horizon. Exacerbation rates could not be indirectly compared for mepolizumab and omalizumab, since treatment continuation rules were defined differently. Therefore, these parameters were directly taken from the clinical trials for mepolizumab and omalizumab. The savings were estimated due to drug acquisition costs (£ 269,900) and estimated reduction in exacerbation (n=15). One-way sensitivity analysis showed that the model results was most sensitive to changing the method of calculating omalizumab dose and varying the drug acquisition cost of omalizumab by ± 20%.Conclusion: The BIA showed that full accessibility of mepolizumab to eligible severe asthma patients is predicted to be budget saving in the Dubai Health Authority. This evaluation is relevant to healthcare decision making as it demonstrates that mepolizumab is budget saving for eligible patients, while reducing burden by improving their control and symptoms.Keywords: asthma phenotypes, eosinophil count, exacerbations, anti-IL5, treatment cost

Introduction: Adding LAMA to LABA/ICS is recommended to improve control in patients with persistent asthma. Methods: This observational, retrospective, before-and-after study considered patients diagnosed with asthma who started LABA/ICS + LAMA treatment (triple therapy, TT) between 1 January 2017 and 31 December 2018 and had been treated with LABA/ICS (dual therapy, DT) in the year before. Changes in lung function and exacerbation rates, healthcare resource utilization, and healthcare and non-healthcare costs (€2019) were estimated in patients with asthma in clinical practices in Spain. Data from computerized medical records from seven Spanish regions were collected ±1 year of LAMA addition. Results: 4740 patients (64.1 years old [SD: 16.3]) were included. TT reduced the incidence of exacerbations by 16.7% (p < 0.044) and the number of patients with exacerbations by 8.5% (p < 0.001) compared to previous DT. The rate of patients with severe exacerbations requiring systemic corticosteroids and their hospitalization rates significantly decreased by 22.5% and 29.5%. TT significantly improved FEV1, FVC, and FEV1/FVC, saving €571/patient for society. Younger patients with asthma (18–44 years old) and patients with severe asthma (FEV1 < 60%) performed better upon the initiation of TT. Conclusions: TT reduced asthma exacerbations, improved lung function and reduced healthcare costs vs. DT, particularly in patients requiring systemic corticosteroids to treat severe exacerbations.

INTRODUCTION: Smoke exposure of COPD (Chronic Obstructive Pulmonary Disease) patients increases the frequency of exacerbations and affects the quality of life. However, most patients still continue to active/passive smoking exposure after being diagnosed with COPD. In this study, the effects of active/passive smoking exposure on symptoms exacerbation/pulmonary functions in COPD patients were investigated. METHODS: Totally 151 COPD patients were included in the study. Patient data on active/passive smoking exposure and exacerbation frequency, and COPD Assessment Test(CAT), modified Medical Research Council dyspnea scale(m-MRC), and pulmonary function tests(PFT) were recorded. As well as active smoking exposure, these parameters were especially evaluated in ex-smoker COPD patients according to passive smoking exposure. The data were evaluated in SPSS 22.0 program; X2 and student t-tests were applied. RESULTS: Active/passive exposure was determined (26.49% and 43.05%, respectively). Total cigarette consumption was 1.5 times higher in men, and passive smoking exposure (69.56%) was higher in women. In addition, it was determined that the m-MRC score increased statistically significantly as exposure to passive cigarettes increased. It was observed that the number of exacerbations increased in ex-smoker COPD patients with passive exposure. Another finding in the study; was determined that the increase in each standard deviation in cigarette consumption caused a 19% decrease in pulmonary function capacity and an increase in m-MRC, CAT scores. DISCUSSION AND CONCLUSION: Active/passive smoking exposure was detected in most COPD patients. It was determined that continuous smoking exposure in patients caused an increase in the number of exacerbations and a deterioration in the quality of life. Therefore, it is necessary to increase awareness of passive smoking exposure in the management of COPD patients.

Leah B Sansbury,1 David A Lipson,2,3 Chanchal Bains,4 Glenn A Anley,5 Kieran J Rothnie,4 Afisi S Ismaila6,7 1Value Evidence and Outcomes, Epidemiology, R&D Global Medical, GlaxoSmithKline, Research Triangle Park, NC, USA; 2Respiratory Clinical Sciences, GlaxoSmithKline, Collegeville, PA, USA; 3Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 4Value Evidence and Outcomes, R&D Global Medical, GlaxoSmithKline, Uxbridge, UK; 5UK Health Outcomes, GlaxoSmithKline, Uxbridge, UK; 6Value Evidence and Outcomes, GlaxoSmithKline, Collegeville, PA, USA; 7Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, CanadaCorrespondence: Afisi S Ismaila, Value Evidence and Outcomes, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA, 19426-0989, USA, Tel +1 919 315 8229, Email afisi.s.ismaila@gsk.comPurpose: Clinical guidelines for COPD management suggest pharmacologic treatment algorithms based on symptoms and exacerbation history. As previous research has suggested that prescribing patterns are not always aligned with these recommendations, this study investigated the burden of disease in patients with COPD receiving, and persisting on, new inhaled maintenance therapy.Patients and Methods: This was a retrospective observational study using two linked electronic databases containing health records of patients in England. Patients aged ≥ 35 years with a confirmed diagnosis of COPD, and who initiated a new inhaled respiratory pharmacologic maintenance regimen between January 1, 2014 and December 31, 2016 (index date) were eligible for inclusion. New treatments could be long-acting muscarinic antagonist (LAMA) or long-acting β2-agonist (LABA) monotherapy, inhaled corticosteroid (ICS)/LABA or LAMA/LABA dual therapy, or a multiple-inhaler triple therapy (MITT; LAMA/LABA/ICS). Patients were required to have 12 months of available medical history prior to, and after, the index date.Results: In total, 25,350 eligible patients were identified, of these 8282 (mean age: 70.9 years; 51.5% male) persisted with their newly prescribed inhaled therapy for ≥ 12 months and were included in the analysis. In the 12 months prior to index, 54% of patients had moderate or severe dyspnea (Medical Research Council score ≥ 3). The most common therapy initiated at index was MITT (42%), followed by ICS/LABA dual therapy (31.2%). The proportion of patients with moderate or severe dyspnea in the post-index period ranged from 29.0% of patients receiving ICS to 64.2% of patients receiving MITT. In the post-index period, 48.1% of patients experienced ≥ 1 exacerbation and 54.9% had ≥ 5 general practitioner visits.Conclusion: Many of the patients with COPD in our study continued to experience symptoms and exacerbations, despite persisting on the same treatment for ≥ 12 months. This suggests that some patients may benefit from treatment modification in accordance with guideline recommendations.Keywords: chronic obstructive pulmonary disease, exacerbations, healthcare utilization, maintenance therapy, general practice

Donald A Mahler,1 Xiaoli Niu,2 Kathleen L Deering,3 Carole Dembek2 1Geisel School of Medicine, Dartmouth, Hanover, NH, USA and Valley Regional Hospital, Claremont, NH, USA; 2Sunovion Pharmaceuticals Inc., Marlborough, MA, USA; 3EPI-Q, Inc, Oak Brook, IL, USACorrespondence: Donald A Mahler, Emeritus Professor of Medicine, Geisel School of Medicine, Dartmouth, Director of Respiratory Services, Valley Regional Hospital, 1 Rope Ferry Road, Hanover, NH, 03755, USA, Tel +1 603 542-6777, Fax +1 603 543-5613, Email mahlerdonald@gmail.comPurpose: A suboptimal peak inspiratory flow (PIF) against a dry powder inhaler (DPI) may result in ineffective inhalation of medications, which may affect outcomes. The primary objective of this study was to examine the association between PIF status and COPD exacerbations among outpatients with moderate to very severe COPD.Patients and Methods: This was a prospective, observational study of patients from 7 US outpatient centers. PIF was measured using an inspiratory flow meter (In-Check™ DIAL G16) set to medium low resistance. Patients were classified by suboptimal (< 60 L/min) or optimal PIF (≥ 60 L/min). The primary outcome was the proportion of patients with moderate/severe COPD exacerbations collected by medical record review over 12 months. Secondary outcomes were time to first exacerbation and mortality.Results: Of 474 patients screened, 38.8% had suboptimal PIF, and 71 patients with optimal PIF were excluded from the study. The enrolled sample included 184 and 219 patients with suboptimal and optimal PIF, respectively. Suboptimal PIF was associated with shorter stature (66.6± 4.1 vs 67.8± 3.8 inches, P = 0.002), female sex (45.1 vs 34.7%, P = 0.033), Black race (27.2 vs 11.0%, P < 0.001), and greater symptom burden (CAT: 22.3± 7.7 vs 19.0± 7.0, P < 0.001; mMRC: 2.0± 1.1 vs 1.7± 1.1, P = 0.003). The proportion of patients with COPD exacerbations at 12 months was not significantly different (29.3 vs 27.9%, P = 0.751). Suboptimal PIF was associated with shorter time to first COPD exacerbation (3.8± 2.7 vs 4.9± 3.0 months, P = 0.048). The mortality rate at 12 months was higher in the suboptimal cohort but not significantly different (6.5 vs 2.8%, P = 0.073).Conclusion: Over one-third of outpatients with stable moderate to very severe COPD had a suboptimal PIF against a medium low resistance DPI. The phenotype of suboptimal PIF was short stature, female, and Black. Suboptimal PIF status was associated with shorter time to moderate/severe COPD exacerbations compared with optimal PIF.Keywords: dry powder inhaler, exacerbations, prospective, mortality

Sanjay Sethi,1 Barry J Make,2 Scott B Robinson,3 Shambhavi Kumar,3 Michael Pollack,4 Chad Moretz,5 Jill Dreyfus,5 Ann Xi,5 Dakota Powell,5 Norbert Feigler4 1University at Buffalo, Buffalo, NY, USA; 2National Jewish Health, Denver, CO, USA; 3Avalere, Health Economics and Advanced Analytics, Washington, DC, USA; 4AstraZeneca, Biopharmaceuticals Medical, Wilmington, DE, USA; 5Formerly Avalere, Washington, DC, USACorrespondence: Michael Pollack, Health Economics and Payer Evidence-Global, 1800 Concord Pike, Wilmington, DE, 19850, USA, Tel +1 302-886-1253, Email michael.pollack1@astrazeneca.comPurpose: To quantify the effects of moderate and/or severe chronic obstructive pulmonary disease (COPD) exacerbations on future exacerbations and healthcare costs in Medicare Fee-For-Service beneficiaries.Patients and Methods: A retrospective cohort study of patients ≥ 40 years of age, with continuous enrollment from 2015 to 2018, with an index COPD diagnosis defined as first hospitalization, emergency department visit, or first of two outpatient visits (≥ 30 days apart) in 2015 with a claim for chronic bronchitis, emphysema, or chronic airway obstruction. Patients were stratified by baseline exacerbation categories in year one (YR1) and subsequently evaluated in YR2 and YR3: (A) none; (B) 1 moderate; (C) ≥ 2 moderate; (D) 1 severe; and (E) ≥ 2, one being severe. Moderate exacerbations were defined as COPD-related outpatient/ED visits with a corticosteroid/antibiotic claim within ± 7 days of the visit and severe exacerbations as hospitalizations with a primary COPD diagnosis. Total all-cause costs for Categories B-E were compared to reference Category A using generalized linear models and inflation adjusted to 2019 dollars.Results: A total of 1,492,108 patients met study criteria with a mean (±SD) age of 70.9± 10.9. In YR1, nearly 40% of patients experienced ≥ 1 moderate and/or severe exacerbations. Patients having multiple exacerbations, regardless of severity were 2– 4 times more likely to experience an exacerbation during YR2 and YR3. Adjusted costs ranged between $24,000 and $26,600 for all categories for YR2 and YR3. Adjusted YR2 costs for Category D and E were $1421 and $1548 higher than those without an exacerbation (Category A YR2 $25,084, YR3 $24,282; p< 0.0001). The respective YR3 adjusted costs were $2062 and $2117 higher than those without an exacerbation (Category A; p< 0.0001), representing an increase of 6– 8% and 8– 9% for YR2 and YR3.Conclusion: Medicare patients with recent moderate or severe exacerbations, or at least two exacerbations per year are at significant risk for future exacerbations and incur higher all-cause costs.Keywords: chronic obstructive pulmonary disease, exacerbations, medicare, maintenance therapy, costs

Saad AlShareef,1 Christine F McDonald,2– 4 Joy Lee2,5 1Department of Medicine, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 13317-4233, Saudi Arabia; 2Department of Respiratory and Sleep Medicine, Austin Health, Heidelberg, Australia; 3Institute for Breathing and Sleep, Heidelberg, Australia; 4Faculty of Medicine, University of Melbourne, Melbourne, Australia; 5School of Public Health & Preventive Medicine, Monash University, Melbourne, AustraliaCorrespondence: Saad AlShareef, Email drsaad321@hotmail.comBackground: Although there have been indirect comparisons of the relative efficacy of mepolizumab (anti-IL-5) and benralizumab (anti-IL-5Rα) in severe asthma patients, long-term direct head-to-head comparisons are lacking. Here, we (i) examined the effect of mepolizumab, benralizumab, and omalizumab on symptom control and lung function parameters over time; and (ii) compared the efficacy of mepolizumab and benralizumab on symptom control and lung function outcomes.Methods: This was a retrospective study of patients with severe asthma taking anti-IgE (omalizumab; n = 24), anti-IL5 (mepolizumab, n = 23), or anti-IL-Rα (benralizumab; n = 12) therapy. Data were extracted on (i) Asthma Control Questionnaire (ACQ-5) scores; (ii) forced expiratory volume over 1 second (FEV1); and (iii) peak expiratory flow rate (PEFR) at 4– 6 months and 1 year and documented reductions in exacerbations. Clinical and lung function outcomes were compared between patients taking mepolizumab and benralizumab and over time.Results: There were significant decreases in ACQ-5 scores (3.3 ± 0.93 to 1.7 ± 0.98 for mepolizumab, 3.5 ± 0.72 to 1.6 ± 0.89 for benralizumab, and 3.5 ± 0.95 to 1.7 ± 1.1 for omalizumab; t-test, all p < 0.0001) but not increases in FEV1 and PEFR for all three agents after 4– 6 months of therapy, which persisted but did not decrease further at one year. There were trends toward a greater percentage increase in FEV1 and PEFR from baseline and a decrease in the number of exacerbations in patients taking benralizumab than those taking mepolizumab.Conclusion: Although limited by a small sample size, this real-world, head-to-head comparison of mepolizumab and benralizumab is consistent with comparative data on asthma biologicals and indirect comparisons showing no major difference in efficacy. The study also generates new testable hypotheses about the efficacy of asthma biologicals in different patient populations.Keywords: asthma, benralizumab, exacerbations, omalizumab, mepolizumab, monoclonal antibody

Miguel Angel Martinez-García,1,2 David Rigau,3 Miriam Barrecheguren,2,4 Alberto García-Ortega,1 Alexa Nuñez,2,4 Grace Oscullo Yepez,1 Marc Miravitlles2,4 1Pneumology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain; 2CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain; 3Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; 4Pneumology Department, Hospital Universitari Vall d´Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona, SpainCorrespondence: Marc Miravitlles, University Hospital Vall d’Hebron, Department of Pneumology, Vall d’Hebron Barcelona Hospital Campus, Pg Vall d’Hebron 119-129, Barcelona, 08036, Spain, Email marcm@separ.esBackground: Chronic bronchial infection is frequent in chronic obstructive pulmonary disease (COPD), but the impact of the isolation of pathogenic bacteria, and in particular Pseudomonas aeruginosa (PA) in respiratory samples on the prognosis of COPD is unclear.Methods: We conducted a systematic review of prognostic studies including patients with isolation of PA in sputum in stable state or during exacerbations of COPD. The main outcomes were all-cause mortality, respiratory mortality, and number and severity of future exacerbations. Data were expressed as hazard ratio (HR) (95% confidence interval [CI]) whenever possible.Results: Of 2773 studies, eight were finally included (23,228 individuals). The mean age ranged from 65.5 to 73 years. Six studies reported data for all-cause mortality. The adjusted risk of death was almost double in patients with PA isolation (HR 1.95, 95% CI, 1.34 to 2.84; quality of evidence moderate). Patients with PA isolation showed a three times higher adjusted risk of readmission at 30 days after discharge (OR 3.60, 95% CI, 3.60 to 12.03, 1 study; quality of evidence very low), and more than double adjusted risk of death and hospitalization at two years (HR 2.80, 95% CI, 2.20 to 3.56, 1 study; quality of evidence very low).Conclusion: There is moderate certainty that the isolation of PA in sputum is associated with an adjusted increased risk of death in patients with COPD.Keywords: COPD, prognosis, outcomes, mortality, exacerbations, bronchial infection, bronchial colonization

Abstract Background Data from phase 3 trials have demonstrated the efficacy and safety of benralizumab in patients with severe eosinophilic asthma (SEA). We conducted a real-world study examining the baseline characteristics of a large SEA population treated with benralizumab in clinical practice and assessed therapy effectiveness. Methods ANANKE is an Italian multi-center, retrospective cohort study including consecutive SEA patients who had started benralizumab therapy ≥ 3 months before enrolment (between December 2019 and July 2020), in a real-world setting. Data collection covered (1) key patient features at baseline, including blood eosinophil count (BEC), number and severity of exacerbations and oral corticosteroid (OCS) use; (2) clinical outcomes during benralizumab therapy. We also conducted two post-hoc analyses in patients grouped by body mass index and allergic status. Analyses were descriptive only. Results Of 218 patients with SEA enrolled in 21 Centers, 205 were evaluable (mean age, 55.8 ± 13.3 years, 61.5% females). At treatment start, the median BEC was 580 cells/mm3 (interquartile range [IQR]: 400–850); all patients were on high-dose inhaled controller therapy and 25.9% were on chronic OCS (median dose: 10 mg/die prednisone-equivalent [IQR: 5–25]); 92.9% experienced ≥ 1 exacerbation within the past 12 months (annualized exacerbation rate [AER] 4.03) and 40.3% reported ≥ 1 severe exacerbation (AER 1.10). During treatment (median duration: 9.8 months [IQR 6.1–13.9]; ≥ 12 months for 34.2% of patients), complete eosinophil depletion was observed; exacerbation-free patients increased to 81% and only 24.3% reported ≥ 1 severe event. AER decreased markedly to 0.27 for exacerbations of any severity (− 93.3%) and to 0.06 for severe exacerbations (− 94.5%). OCS therapy was interrupted in 43.2% of cases and the dose reduced by 56% (median: 4.4 mg/die prednisone-equivalent [IQR: 0.0–10.0]). Lung function and asthma control also improved. The effectiveness of benralizumab was independent of allergic status and body mass index. Conclusions We described the set of characteristics of a large cohort of patients with uncontrolled SEA receiving benralizumab in clinical practice, with a dramatic reduction in exacerbations and significant sparing of OCS. These findings support benralizumab as a key phenotype-specific therapeutic strategy that could help physicians in decision-making when prescribing biologics in patients with SEA. Trial registration ClinicalTrials.gov Identifier: NCT04272463

Ke Zhang, Kangkang Han, Hui Liu, Chunyan Zheng Department of General Practice, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaCorrespondence: Chunyan Zheng, Department of General Practice, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China, Email chyzhengdoc@163.comPurpose: Increasing evidence has shown that the immune response interacts with the chronic inflammatory response and gives rise to the occurrence and development of COPD. Complement component 1q (C1q), as a subcomponent of the C1 complex, could be involved in innate and adaptive immunity. Our study aimed to investigate the relationship between C1q and the clinical characteristics of COPD subjects.Patients and Methods: Serum C1q levels were measured in 203 COPD subjects and 191 non-COPD controls. Correlations between C1q and the characteristics of COPD were analyzed using Spearman’s rho. Receiver operating curve (ROC) analysis was used to evaluate the threshold value in differentiating disease status. All 203 COPD subjects were followed up for 1 year for future acute exacerbations.Results: There were significant reductions in serum C1q levels in COPD subjects compared to non-COPD controls. Moreover, serum C1q levels were obviously positively correlated with the FEV1/FVC ratio and predicted FEV1% but had a weakly negative correlation with the %LAA-950 and the percentage of neutrophils in peripheral blood. Using a cutoff value of 137.150 mg/l as the boundary in ROC analysis, the sensitivity and specificity were 65.9% and 76.0%, respectively. The 1-year follow-up results showed that C1q levels less than 137.150 mg/l were negatively related to the time to the next severe exacerbation and the time to death.Conclusion: Circulating C1q levels may be a novel biomarker not only related to the pulmonary function of COPD but also having great potential to predict the risk of COPD deterioration in the future. However, further prospective trials are needed to clarify the influences of C1q on the pathogenesis of COPD.Keywords: complement component 1q, chronic obstructive pulmonary disease, pulmonary function, exacerbations, future risk

Abstract Background Both allergen-specific IgE and total IgE in serum play a major role in asthma. However, the role of IgE in chronic obstructive pulmonary disease (COPD) is poorly understood. It was the aim of this study to systematically analyze the relationship between serum IgE levels and disease characteristics in large COPD cohorts. Methods COSYCONET is a comprehensively characterized cohort of patients with COPD: total IgE and IgE specific to common aeroallergens were measured in serum of 2280 patients, and related to clinical characteristics of the patients. WISDOM is another large COPD population (2477 patients): this database contains the information whether total IgE in serum was elevated (≥ 100 IU/l) or normal in patients with COPD. Results Both in COSYCONET and WISDOM, total IgE was elevated (≥ 100 IU/l) in > 30% of the patients, higher in men than in women, and higher in currently than in not currently smoking men. In COSYCONET, total IgE was elevated in patients with a history of asthma and/or allergies. Men with at least one exacerbation in the last 12 months (50.6% of all men in COSYCONET) had higher median total IgE (71.3 IU/l) than men without exacerbations (48.3 IU/l): this difference was also observed in the subgroups of not currently smoking men and of men without a history of asthma. Surprisingly, a history of exacerbations did not impact on total IgE in women with COPD. Patients in the highest tertiles of total IgE (> 91.5 IU/ml, adjusted OR: 1.62, 95% CI 1.12–2.34) or allergen-specific IgE (> 0.19 IU/ml, adjusted OR: 2.15, 95% CI 1.32–3.51) were at risk of lung function decline (adjusted by: age, gender, body mass index, initial lung function, smoking status, history of asthma, history of allergy). Conclusion These data suggest that IgE may play a role in specific COPD subgroups. Clinical trials using antibodies targeting the IgE pathway (such as omalizumab), especially in men with recurrent exacerbations and elevated serum IgE, could elucidate potential therapeutic implications of our observations.

Background Bronchiectasis patients with neutrophilic airway inflammation develop symptoms of chronic cough, sputum production, and recurrent exacerbations. Roflumilast has anti-inflammatory actions via decreased neutrophilic airway inflammation. The effectiveness of roflumilast to reduce bronchiectasis exacerbation has never been evaluated. Methods We conducted a double-blinded, randomized, placebo-controlled trial. Our primary objective was to assess the effect of roflumilast compared with that of a placebo in reducing exacerbation rates in bronchiectasis patients. The secondary objectives were the changes in forced expiratory volume in 1 second (FEV1) and St. George’s Respiratory Questionnaire (SGRQ). Bronchiectasis patients older than 18 years who had had two exacerbations during the previous 12 months were randomly assigned to receive either 500 μg of either roflumilast or a placebo once daily for 6 months in a 1:1 ratio. Results Forty bronchiectasis patients who had experienced exacerbations were screened. Thirty patients completed the study after 6 months of treatment: roflumilast group (n=15) and placebo group (n=15). The rates of exacerbations were 0.57 and 0.59 per patient in the roflumilast and placebo groups, respectively. Prebronchodilator FEV1 increased by 0.07 L from baseline in the roflumilast group and decreased by 0.015 L in the placebo group, but the difference was not significant. No significant differences were observed in the change of SGRQ scores between the roflumilast and placebo groups. Roflumilast had significant side effects, including loss of appetite and headache. Conclusion Roflumilast did not significantly affect the rate of exacerbations or quality of life. However, FEV1 tended to improve more in the roflumilast group than in the placebo group.

Paul W Jones,1 Chanzheng Wang,2 Ping Chen,3 Liping Chen,4 Daoxin Wang,5 Junbo Xia,6 Yang Yang,7 Yingyu Wang,7 Qianli Ma2 1Global Medical, Regulatory and Quality, GlaxoSmithKline plc., Brentford, UK; 2Respiratory Department, Chongqing Xinqiao Hospital, Chongqing, People’s Republic of China; 3Respiratory Department, General Hospital of the Northern Theater Command of the People’s Liberation Army, Shenyang, People’s Republic of China; 4Respiratory Department, The Second Affiliated Hospital of Shenyang Medical College, Shenyang, People’s Republic of China; 5Respiratory Department, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 6Respiratory Department, Hangzhou First People’s Hospital, Hangzhou, Zhejiang, People’s Republic of China; 7Research and Development, GlaxoSmithKline plc., Shanghai, People’s Republic of ChinaCorrespondence: Paul W Jones, Global Medical, Regulatory and Quality, GlaxoSmithKline plc., Brentford, UK, Email paul.8.jones@gsk.comIntroduction: Many patients with chronic obstructive pulmonary disease (COPD) do not report exacerbations and may benefit from simple guidance about when to seek medical attention, so we developed a COPD Exacerbation Recognition Tool (CERT).Methods: The study was run across three sites in China in patients who had an exacerbation within the previous year. Step 1: focus group qualitative study (total 48 patients) captured symptoms associated with an exacerbation. Step 2: cognitive debriefing to ensure items were appropriately worded. Step 3: 150 patients (69 years, 21% female, FEV1 63% predicted, CAT 15, 2 exacerbations in previous year) completed a questionnaire composed of the items from Steps 1 and 2 using two response options – severity during an exacerbation and magnitude of change from usual state. Responses were analysed in terms of frequency and tested for influence of demographic factors. Exploratory factor analysis (EFA) identified key domains. Using these results, an expert panel guided choice of items that formed the CERT.Results: Following Steps 1 and 2, 29 candidate items were selected for Step 3. Response rates with the two response options were very similar. There was minimal influence of demographic factors on response to the items. EFA using the 11 items with the highest response rates identified two principal factors, Factor 1: breathlessness and activity limitation (79.1% of variance), Factor 2: cough and sputum (20.9% of variance). Five items were selected for the CERT based on response rate and EFA factor loading: worsening cough, increased sputum volume, shortness of breath, laborious breathing, and limitation of motion. Sensitivity analysis suggested that worsening of two or more symptoms had good sensitivity and specificity for the presence of an exacerbation.Discussion: The CERT is an evidence-based tool to provide patients with simple-to-follow guidance about when to seek medical attention when their COPD symptoms worsen.Keywords: chronic obstructive pulmonary disease, exacerbations, COPD exacerbation tool

Abstract Background: Asthma is the most common non-communicable chronic airway disease worldwide. Obesity and cigarette use independently increase asthma morbidity and mortality. Current literature suggests that obesity and smoking synergistically increase asthma-related wheezing. Objective: To assess whether increased serum cotinine and obesity act synergistically to increase the likelihood of having an asthma exacerbation, emergency department (ED) visit, or hospitalization. Methods: A cross-sectional analysis of the 2011–2015 iterations of NHANES database was performed. Patients aged 18 years or greater with asthma were included. Serum cotinine was utilized as an accurate measurement of cigarette use. Logistic regression models were constructed to determine whether elevated serum cotinine and obesity were associated with self-reported asthma exacerbations, asthma-specific ED usage, and hospitalizations for any reason in the past year. Odds ratios were adjusted for age, gender, race, and ethnicity. Interactions were assessed by multiplying the adjusted effect sizes for elevated cotinine and obesity. Results: We identified 2179 (N = 32,839,290) patients with asthma, of which 32.2% were active smokers and 42.7% were obese. Patients with an elevated cotinine and asthma were significantly more likely to have had an asthma-related ED visit in the past year (adjusted odds ratio [AOR] 1.82; 95% CI 1.19–2.79), have a physician-prescribed asthma medication (AOR 2.04; 95% CI 1.11–3.74), and have a hospitalization for any reason (AOR 3.65; 95% CI 1.88–7.07) compared to those with low cotinine. Patients with asthma and obesity were more likely to have an asthma-related ED visit (AOR 1.67; 95% CI 1.06–2.62) or hospitalization for any reason in the past year compared to non-obese patients (AOR 2.76; 95% CI 1.69–4.5). However, a statistically significant interaction between obesity and cotinine was only identified in patients who currently have asthma compared to a previous asthma diagnosis (AOR 1.76; 95% CI 1.10–2.82). There were no synergistic interactions among ED usage or asthma exacerbations. Conclusion: Nearly one-third of patients with asthma were current smokers, and almost half were obese. This study identified elevated serum cotinine, a metabolite of cigarette use, and obesity as key risk factors for asthma exacerbations, asthma-related ED visits, and hospitalizations for any reason. Elevated serum cotinine and obesity were not found to act synergistically in increasing asthma exacerbations or ED visits. However, the presence of both risk factors increased the risk of currently having asthma (compared to a previous diagnosis) by 76%. Serum cotinine may be useful in predicting asthma outcomes.

The FeNO-guided treatment protocols employed across included studies differed significantly, particularly regarding FeNO cut-offs and selected asthma control measures. Keywords: asthma; biomarkers; exacerbations; FeNO EN asthma biomarkers exacerbations FeNO 791 793 3 08/14/23 20230801 NES 230801 Fractional exhaled nitric oxide (FeNO) testing has emerged as a valuable tool in assessing people with asthma, offering an objective measure of ongoing type 2 cytokine, chemokine and alarmin signalling in the airways.[1] As a non-invasive and easily accessible biomarker, incorporating FeNO testing into asthma management may improve diagnostic accuracy by complementing clinical symptoms and spirometry measures. [Extracted from the article]

Background: Use of long-term tobramycin inhalation solution (TIS) has been shown beneficial in cystic fibrosis (CF) and earlier findings also suggest a benefit in non-CF bronchiectasis. We investigated the efficacy and safety of maintenance TIS once daily (OD) in frequent exacerbating bronchiectasis patients chronically infected by different pathogens sensitive for tobramycin.Objective: The primary outcome was the frequency of exacerbations during the 12-month study period. Secondary outcomes were time to first exacerbation, change in lung function and quality of life (QoL), bacterial analysis and safety.Materials/patients: IN THIS MULTICENTER RCT PATIENTS AGED ≥ 18-YEAR-OLD WERE INCLUDED WITH CONFIRMED BRONCHIECTASIS AND ≥ 2 EXACERBATIONS IN THE PRECEDING YEAR. PATIENTS WERE ASSIGNED (1:1) TO RECEIVE TIS OR PLACEBO OD FOR 1-YEAR.: RESULTS: 58 patients were included of which 52 were analyzed in the mITT analysis. TIS reduced exacerbation frequency with a RR of 0.74 (95% CI 0.49-1.14) (p = 0.15). Within the TIS population a decrease in number of exacerbations was found (2; p = 0.00), which was also seen in the placebo-treated patients (1.5; p = 0.00). In the TIS-treated patients the QoL improved (LRTI-VAS p = 0.02 Leicester Cough p = 0.02) without additional safety concerns. No differences were found for the other secondary outcomes.Conclusion: Long-term TIS OD is a safe treatment modality and showed a non-significant reduced exacerbation frequency of 0.74 as compared to placebo in bronchiectasis patients chronically infected by tobramycin sensitive pathogens. TIS OD may be a potential therapeutic strategy in selected patients with bronchiectasis suffering from a high burden of disease.Trail Registration Number: The BATTLE study was registered at Clinical trials.gov number: NCT02657473 . Date: 13 august 2016. [ABSTRACT FROM AUTHOR]

The microbiome's significance in chronic rhinosinusitis (CRS) is unclear. Antimicrobials are recommended in acute exacerbations of the disease (AECRS). Increasing rates of antibiotic resistance have stimulated research on alternative therapeutic options, including silver nanoparticles (AgNPs). However, there are concerns regarding the safety of silver administration. The aim of this study was to assess the biological activity of tannic acid-prepared AgNPs (TA-AgNPs) towards sinonasal pathogens and nasal epithelial cells (HNEpC). The minimal inhibitory concentration (MIC) for pathogens isolated from patients with AECRS was approximated using the well diffusion method. The cytotoxicity of TA-AgNPswas evaluated using an MTT assay and trypan blue exclusion. A total of 48 clinical isolates and 4 reference strains were included in the study (Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Klebsiellaoxytoca, Acinetobacter baumannii, Serratia marcescens, Enterobacter cloacae). The results of the studies revealed that the MIC values differed between isolates, even within the same species. All the isolates were sensitive to TA-AgNPs in concentrations non-toxic to human cells during 24 h exposition. However, 48 h exposure to TA-AgNPs increased toxicity to HNEpC, narrowing their therapeutic window and enabling 19% of pathogens to resist the TA-AgNPs' biocidal action. It was concluded that TA-AgNPs are non-toxic for the investigated eukaryotic cells after short-term exposure and effective against most pathogens isolated from patients with AECRS, but sensitivity testing may be necessary before application. [ABSTRACT FROM AUTHOR]

Purpose: OSA-COPD overlap is an important and prevalent condition yet remains under-recognised among the vast majority of respiratory health professionals. Patients with OSA-COPD overlap experience more severe respiratory symptoms and worse quality of life, and the relative risk of exacerbations, hospitalisations, and mortality is higher than in either disease state alone. Methods: Electronic databases PUBMED and Google Scholar were searched for studies and academic papers that discussed OSA-COPD overlap. Relevant papers that discussed prevalence, pathophysiology, microbiome studies, treatment regimens and outcomes were included in this paper. Results: High-risk patients with either COPD or OSA should be screened for overlap syndrome as part of routine clinical practice. Screening questionnaires can identify high-risk patients with COPD who may benefit from formal polysomnography. Patients with OSA who are aged over 40 with a significant smoking history or environmental exposures have an increased pre-test probability of obstructive airway disease. The potential roles of gastro-oesophageal reflux disease and lung-gut microbiome are evolving and merit further investigation. A tailored approach to reach a timely diagnosis and thus optimisation of both conditions are key to management. CPAP is the primary therapy for OSA; however, patients with more advanced COPD, with daytime hypercapnia or severe nocturnal desaturations, may benefit from bilevel positive airway pressure. Conclusion: Increased awareness, access to timely investigations and initiation of therapy will improve overall outcomes in OSA-COPD overlap by reducing hospitalisations for exacerbations of COPD and improve mortality rates. [ABSTRACT FROM AUTHOR]

Background: The allergic phenotype is responsible for more than 50% of severe asthma cases. In a stepwise approach, add-on treatments such as anti-IgE are used for severe allergic asthma (SAA). This study was aimed to describe the real-world effectiveness of omalizumab in adult and pediatric patients with SAA in Colombia.Methods: This was an observational, non-interventional, retrospective study. Data from patients with SAA that received at least one month of treatment with omalizumab was obtained from medical records at eight sites in Colombia. Time-zero (t - 0) was defined as the date of initiation of omalizumab, and data was gathered for a 12-month period before t - 0 and a 12-month period after t - 0. Clinical outcomes, including exacerbations, were assessed at 6 and 12 months. Effectiveness of omalizumab was evaluated in terms of the reduction of the risk of exacerbations (annualized rate).Results: We included 143 patients with SAA. There was a decrease of 72.4% of the annualized rate of clinically significant asthma exacerbations during the year after omalizumab (from 1.74 before to 0.48 after) with a substantial reduction of the risk of exacerbations by 56.7% (RR [95% CI] 0.43 [0.30-0.63] p < 0,001).Conclusion: The use of omalizumab in Colombia as a treatment for SAA notably reduced the risk of clinically significant exacerbations. This study is the first to evaluate omalizumab real-life effectiveness in pediatric and adult patients in the country. [ABSTRACT FROM AUTHOR]

Conventional inhaler devices have a low efficacy in targeting small airways. Smart nebulizers can be used to increase deposition to small airways by adjusting the flow and depth of each inhalation based on patients 'individual inspiratory capacity. We investigated whether targeting of high dose inhaled corticosteroids (ICS) to small airways with a smart nebulizer could reduce exacerbation rate in children with severe asthma (SA). We conducted a retrospective study in children with SA using a smart nebulizer (Akita® Jet nebulizer) for the administration of high dose ICS in our outpatient clinic at the Erasmus MC — Sophia Children's Hospital. Clinical data before and after start of treatment were collected. The primary outcome was exacerbation rate, defined as: number of asthma exacerbations for which oral corticosteroid courses (OCS) were prescribed. The exacerbation rate 1 year before treatment was compared with the exacerbation rate 1 year after start of treatment. Secondary outcomes were changes in spirometry parameters, hospital admissions and medication use. Data on OCS use was available for 28/31 patients. Median number of asthma exacerbations requiring OCS courses 1 year before decreased from 2 (interquartile range(IQR) 2) to 0.5 (IQR 3) 1 year after treatment (p = 0.021). Hospital admission decreased from 1 (IQR 3) to 0 (IQR 1)(p = 0.028). FEV1, FEF25-75 and FEF75 were not significantly improved after one year of treatment with the smart nebulizer (p = 0.191; p = 0.248; p = 0.572). Targeting small airways with high dose ICS using a smart nebulizer resulted in a significant reduction in exacerbations requiring OCS after one year of treatment. [ABSTRACT FROM AUTHOR]

Background: In adults and adolescents with asthma, use of ≥3 short‐acting β2‐agonist (SABA) canisters/year is associated with increased exacerbation risk. Whether this association is present in younger children remains unknown. In this SABA use IN Asthma (SABINA) Junior study, we assessed the association of SABA collection with exacerbation risk in the general Swedish pediatric asthma population. Methods: This population‐based cohort study utilized linked data from the Swedish national healthcare registries involving patients with asthma (<18 years) treated in secondary care between 2006–2015. Exacerbation risk, by baseline SABA collection (0–2 vs. ≥3 canisters, further examined as ordinal/continuous variable) and stratified on comorbid atopic disease (allergic rhinitis, dermatitis and eczema, and food/other allergies), was assessed for 1‐year follow‐up using negative binomial regression. Results: Of 219,561 patients assessed, 45.4%, 31.7%, and 26.5% of patients aged 0–5, 6–11, and 12–17 years, respectively, collected ≥3 SABA canisters during the baseline year (high use). Collection of ≥3 SABA canisters (vs. 0–2) was associated with increased exacerbation risk during follow‐up (incidence rate ratios [95% confidence interval]: 1.35 [1.29–1.42], 1.22 [1.15–1.29], and 1.26 [1.19–1.34] for 0–5‐, 6–11‐, and 12–17‐year‐olds, respectively); the association persisted with SABA as a continuous variable and was stronger among patients without atopic diseases (32%–44% increased risk versus. 14%–21% for those with atopic disease across groups). Conclusions: High SABA use was associated with increased asthma exacerbation risk in children, particularly in those without comorbid atopic diseases, emphasizing the need for asthma medication reviews and reformative initiatives by caregivers and healthcare providers on SABA use. [ABSTRACT FROM AUTHOR]

Objective: Whether blood eosinophils (bEOS) in chronic obstructive pulmonary disease (COPD) are associated with disease progression is a topic of debate. We aimed to evaluate whether the differential white blood cell (WBC) count, symptoms and treatment may predict lung function decline and exacerbations in COPD patients. Methods: We retrospectively examined stable COPD patients with a minimum follow-up of 3 years at our outpatients’ clinic. We collected information about lung volumes (FEV1, FVC), the total and differential WBC count, acute exacerbations of COPD (number in the 12 months before the beginning of the study=AE-COPD-B, and during the followup= AE-COPD-F), smoking status and treatment. FEV1 decline and AE-COPD-F were described by using a generalized linear model and a 2-level random intercept negative binomial regression, respectively. The models included eosinophil and neutrophil counts as potential predictors and were adjusted by sex, age, smoking status, AE-COPD-B, treatment with bronchodilators and inhaled corticosteroids (ICS). Results: Sixty-eight patients were considered, 36 bEOS- (<170 cells/μL, the median value) and 32 bEOS+ (≥170 cells/μL). ΔFEV1 was higher in bEOS+ than bEOS- (34.86 mL/yr vs 4.49 mL/yr, p=0.029). After adjusting for potential confounders, the eosinophil count was positively (β=19.4; CI 95% 2.8, 36.1; p=0.022) and ICS negatively (β=-57.7; CI 95% -91.5,-23.9; p=0.001) associated with lung function decline. bEOS were not found to be associated with the number of AE-COPD-F. Conclusion: In stable COPD patients, a higher level of blood eosinophils (albeit in the normal range) predicts a greater FEV1 decline, while ICS are associated with a slower progression of airflow obstruction. [ABSTRACT FROM AUTHOR]

Most patients with bronchiectasis have a predominantly neutrophilic inflammatory profile, although other cells such as lymphocytes (as controllers of bronchial inflammation) and eosinophils also play a significant pathophysiological role. Easy-to-interpret blood biomarkers with a discriminative capacity for severity or prognosis are needed. The objective of this study was to assess whether the peripheral neutrophil-to-lymphocyte ratio (NLR) is associated with different outcomes of severity in bronchiectasis. A total of 1369 patients with bronchiectasis from the Spanish Registry of Bronchiectasis were included. To compare groups, the sample was divided into increasing quartiles of NLR ratio. Correlations between quantitative variables were established using Pearson's P test. A simple linear regression (with the value of exacerbations as a quantitative variable) was used to determine the independent relationship between the number and severity of exacerbations and the NLR ratio. The area under the curve (AUC)-ROC was used to determine the predictive capacity of the NLR for severe bronchiectasis, according to the different multidimensional scores. Mean age: 69 (15) years (66.3% of women). The mean NLR was 2.92 (2.03). A higher NLR was associated with more severe bronchiectasis (with an especially significant discriminative power for severe forms) according to the commonly used scores (FACED, E-FACED and BSI), as well as with poorer quality of life (SGRQ), more comorbidities (Charlson index), infection by pathogenic microorganisms, and greater application of treatment. Furthermore, the NLR correlated better with severity scores than other parameters of systemic inflammation. Finally, it was an independent predictor of the incident number and severity of exacerbations. In conclusion, the NLR is an inexpensive and easy-to-measure marker of systemic inflammation for determining severity and predicting exacerbations (especially the most severe) in patients with bronchiectasis. [ABSTRACT FROM AUTHOR]

The study presents trends in the long-term treatment of patients with COPD. For a period of four years, 426 patients diagnosed with COPD were followed. The average duration is 12.56 ± 6.09 years. 46.5% of patients have been diagnosed 10 years ago, and 43.5% lives with COPD between 11 and 20 years. According to the criteria for combined assessment of the disease, 36.5% of patients are in group B and 41.3% – in group D. There is a tendency of exacerbations and hospitalizations in patients with COPD to increase. It was found that the age is not a statistically significant risk factor. The level of treatment satisfaction is 57.73% [ABSTRACT FROM AUTHOR]

Purpose: Acute exacerbations of COPD (AECOPD) are important factors contributing to mortality risk. The rate of exacerbations varies overtime. An inconsistent pattern of exacerbation occurrence is a common finding. The mortality risk associated with such a pattern is not entirely clear. Our objective was to assess the risk of mortality associated with various possible patterns of AECOPD trajectories. Methods: This is a multicenter historical cohort study. Four different exacerbation trajectories were defined according to the incidence of severe AECOPD requiring hospital admission 2 years before and after the date of the first visit to the respiratory clinic—Consistent non-exacerbators (NEx): no AECOPD before or after the index date; consistent exacerbators (Ex): at least one AECOPD both before and after the index date; converters to exacerbators (CONV-Ex): no exacerbations before and at least one AECOPD after the index date; converters to non-exacerbators (CONV-NEx): at least one AECOPD before the index date, and no exacerbations after said date. All-cause mortality risk for these trajectories was assessed. Results: A total of 1713 subjects were included in the study: NEx: 1219 (71.2%), CONV-NEx: 225 (13.1%), CONV-Ex: 148 (8.6%), Ex: 121 (7.1%). After correcting for confounding variables, the group with the highest mortality risk was Ex. The CONV-Ex and CONV-Nex groups had a mortality risk between Ex and NEx, with no significant differences between them. Conclusion: Different possible trajectories of severe AECOPD before and after a first specialized consultation are associated with different mortality risks. An inconsistent pattern of exacerbations has a mortality risk between Ex and NEx, with no clear differences between CONV-Ex and CONV-NEx. [ABSTRACT FROM AUTHOR]

Rationale: The BLOCK COPD (β-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease) study found that metoprolol was associated with a higher risk of severe exacerbation. Objectives: To determine the mechanism underlying these results, we compared changes in lung function over the course of the study between treatment groups and evaluated whether baseline bronchodilator response or early reduction in forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) was associated with exacerbation risk. Methods: We compared changes in lung function (FEV1 and FVC) over the treatment period between treatment groups using linear mixed-effect models. Cox proportional hazards models were used to evaluate the association between baseline bronchodilator responsiveness (FEV1, FVC, and combined FEV1 and FVC), early post-randomization (14 d) change in lung function, and the interaction between treatment assignment and these measures with risk of any or severe or very severe exacerbations. Negative binomial models were used to evaluate the relationship between bronchodilator responsiveness, the interaction between bronchodilator responsiveness and treatment assignment, and exacerbation rate. Results: Over the 336-day treatment period, individuals in the metoprolol group had a significantly greater decrease in logarithmic FEV1 from baseline to visit on Day 28 than individuals in the placebo group. Individuals in the metoprolol group had a significantly greater decrease in FVC from baseline to visits on Days 14 and 28, and also a significantly greater decrease in logarithmic FVC from baseline to visits on Days 42 and 112 than individuals in the placebo group. There were no associations between early lung function reduction or interactions between lung function reduction and treatment assignment and time to any or severe or very severe exacerbations. There were no interactions between treatment arm and baseline bronchodilator responsiveness measures on risk or rate of exacerbations. However, those with baseline FVC bronchodilator responsiveness had a higher rate of severe or very severe exacerbations (adjusted rate ratio, 1.62; 95% confidence interval, 1.04-2.48). Conclusions: Metoprolol was associated with reduced lung function during the early part of the treatment period, but these effects were modest and did not persist. Early lung function reduction and baseline bronchodilator responsiveness did not interact with the treatment arm to predict exacerbations; however, baseline FVC bronchodilator responsiveness was associated with a 60% higher rate of severe or very severe exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT02587351). [ABSTRACT FROM AUTHOR]