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Background: Guidelines advise minimizing asthma exacerbation risk, which is achieved partially through good clinical practice activities, including scheduled asthma reviews, inhaler technique checks, and asthma management plans. We assessed how frequently these activities are provided and how effective they are in clinical practice., Research Question: Do guideline-recommended activities such as asthma reviews, inhaler technique checks, and asthma management plans prevent asthma exacerbations?, Study Design and Methods: This retrospective chart review used United Kingdom primary care medical records between 2004 and 2021, linked to hospital records. Children were eligible from asthma diagnosis until age 16 years. Annual implementation of asthma review, inhaler technique check, and asthma management plan was measured. Risk factors for these activities not being undertaken were determined by using multivariable logistic regression. Self-controlled case series was adopted to assess the effectiveness of each activity over 12 months; this was divided into two 6-month periods., Results: A total of 126,483 children were eligible; 30% to 45% received each annual activity, and 8% received all 3 together. Risk factors for not receiving activities included younger age, more socioeconomic deprivation, and higher or no BMI measurement. Management plans and asthma reviews, as standalone activities, were associated with an approximately 15% exacerbation reduction over 12 months and 8% over 6 months, respectively (asthma management plan, n = 4,624; 0-6 months [incidence rate ratio (95% CI)]: 0.87 [0.79-0.96]; 6-12 months: 0.83 [0.73-0.95]; asthma review, n = 6,948; 0-6 months: 0.92 [0.85-0.99]; 6-12 months: 0.93 [0.83-1.03]). Standalone inhaler technique checks were not associated with exacerbations. Provision of all activities together was associated with an approximately 30% exacerbation reduction over 12 months (n = 3,643; 0-6 months: incidence rate ratio, 0.76 [0.68-0.85]; 6-12 months: incidence rate ratio, 0.69 [95% CI, 0.60-0.81])., Interpretation: Most children in the United Kingdom do not receive the guideline-recommended activities to monitor their asthma. This study suggests that these activities, if implemented, are effective in clinical practice and maximally effective when combined in the same visit., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The varied treatment response to inhaled corticosteroids (ICS) in patients with COPD and the associated increased risk of pneumonia necessitate a personalized ICS therapeutic approach. This is informed by blood eosinophil count (BEC), which predicts ICS treatment response. However, BEC appears to change in response to ICS treatment., Research Question: Does (1) BEC measured on ICS treatment (2) BEC measured off ICS treatment, or (3) the change in BEC during ICS treatment best predict treatment response to ICS in COPD?, Study Design and Methods: The Fluticasone Salmeterol on COPD Exacerbations Trial (FLAME), a 52-week, double-blind randomized controlled trial compared long-acting beta-2 agonists (LABAs)/long-acting muscarinic antagonists (LAMAs) with LABA/ICS. Corticosteroids were prohibited during a 4-week run-in period. We chose patients previously on ICS, thereby allowing BEC before and after the run-in period to represent BEC on and off ICS, respectively. In this post hoc analysis, we revisited outcome data, exploring how the three BEC biomarkers interacted with treatment response to the ICS-containing regimen., Results: Our study showed that LABA/LAMA combination was superior, or at least noninferior, to LABA/ICS in curbing exacerbations for most FLAME participants. However, higher BEC off ICS, higher BEC on ICS, and significant BEC suppression during ICS treatment corresponded to superior response to LABA/ICS in terms of exacerbation rate, time to first exacerbation, and time to first pneumonia. In a subgroup, including 9% of participants, BEC changed significantly during ICS treatment (≥ 200 cells/μL), and higher BEC on ICS did not predict ICS treatment response. For these patients, BEC off ICS and BEC change proved more predictive. Excess pneumonia risk associated with ICS appeared to be confined to patients who do not benefit from this treatment. BEC was not predictive of treatment effects on lung function and health status., Interpretation: This exploratory analysis advocates preferentially using BEC off ICS or BEC change during ICS treatment for guiding ICS treatment decisions. BEC measured on ICS is less predictive of treatment response., Clinical Trial Registration: ClinicalTrials.gov; No.: NCT01782326; URL: www., Clinicaltrials: gov., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: A. G. M. reports honoraria for presenting from GSK, not related to this work. D. S. reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Glenmark, Menarini, Mundipharma, Novartis, Pfizer, Pulmatrix, Theravance, and Verona; and personal fees from Cipla, Genentech, and Peptinnovate, not related to this work. J. V. reports honoraria for consulting and/or presenting from ALK, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, and Teva, not related to this work. None declared (S. B., P. S., J.-U. S. J.)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: N. R. reports grants and personal fees from Boehringer Ingelheim, Novartis, Pfizer, and GSK, and personal fees from AstraZeneca, Austral, Biosency, Chiesi, MSD, Sanofi & Zambon, outside the submitted work. O. S. U. reports grants and personal fees from Astra Zeneca, Boehringer Ingelheim, Chiesi, Deva, and Glaxosmithkline; grants from Edmond Pharma; and personal frees from Cipla, Covis, Kyorin, Lambda, Menarini, Mereo Biopharma, Mundipharma, Napp, Novartis, Orion, Sandoz, Takeda, Trudell Medical & UCB outside the submitted work. None declared (G. L., S. B. A.).

Background: The 2023 International Pediatric Ventilator Liberation Clinical Practice Guidelines provided evidence-based recommendations to guide pediatric critical care providers on how to perform daily aspects of ventilator liberation. However, because of the lack of high-quality pediatric studies, most recommendations were conditional based on very low to low certainty of evidence., Research Question: What are the research gaps related to pediatric ventilator liberation that can be studied to strengthen the evidence for future updates of the guidelines?, Study Design and Methods: We conducted systematic reviews of the literature in eight predefined Population, Intervention, Comparator, Outcome (PICO) areas related to pediatric ventilator liberation to generate recommendations. Subgroups responsible for each PICO question subsequently identified major research gaps by synthesizing the literature. These gaps were presented at an international symposium at the Pediatric Acute Lung Injury and Sepsis Investigators meeting in spring 2022 for open discussion. Feedback was incorporated, and final evaluation of research gaps are summarized herein. Although randomized controlled trials (RCTs) represent the highest level of evidence, the panel sought to highlight areas where alternative study designs also may be appropriate, given challenges with conducting large multicenter RCTs in children., Results: Significant research gaps were identified in six broad areas related to pediatric ventilator liberation. Several of these areas necessitate multicenter RCTs to provide definitive results, whereas other gaps can be addressed with multicenter observational studies or quality improvement initiatives. Furthermore, a need for some physiologic studies in several areas remains, particularly regarding newer diagnostic methods to improve identification of patients at high risk of extubation failure., Interpretation: Although pediatric ventilator liberation guidelines have been created, the certainty of evidence remains low and multiple research gaps exist that should be bridged through high-quality RCTs, multicenter observational studies, and quality improvement initiatives., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by the malfunction of motile cilia and a specific etiology of adult bronchiectasis of unknown prevalence. A better understanding of the clinical phenotype of adults with PCD is needed to identify individuals for referral to diagnostic testing., Research Question: What is the frequency of PCD among adults with bronchiectasis; how do people with PCD differ from those with other etiologies; and which clinical characteristics are independently associated with PCD?, Study Design and Methods: We investigated the proportion of PCD among the participants of the Prospective German Non-CF-Bronchiectasis Registry (PROGNOSIS) study; applied multiple imputation to account for missing data in 64 (FEV 1 ), 58 (breathlessness), 26 (pulmonary exacerbations), and two patients (BMI), respectively; and identified predictive variables from baseline data using multivariate logistic regression analysis., Results: We consecutively recruited 1,000 patients from 38 centers across all levels of the German health care system. Overall, PCD was the fifth most common etiology of bronchiectasis in 87 patients (9%) after idiopathic, postinfective, COPD, and asthma. People with PCD showed a distinct clinical phenotype. In multivariate regression analysis, the chance of PCD being the etiology of bronchiectasis increased with the presence of upper airway disease (chronic rhinosinusitis and/or nasal polyps; adjusted OR [aOR], 6.3; 95% CI, 3.3-11.9; P < .001), age < 53 years (aOR, 5.3; 95% CI, 2.7-10.4; P < .001), radiologic involvement of any middle and lower lobe (aOR, 3.7; 95% CI, 1.3-10.8; P = .016), duration of bronchiectasis > 15 years (aOR, 3.6; 95% CI, 1.9-6.9; P < .001), and a history of Pseudomonas aeruginosa isolation from respiratory specimen (aOR, 2.4; 95% CI, 1.3-4.5; P = .007)., Interpretation: Within our nationally representative cohort, PCD was a common etiology of bronchiectasis. We identified few easy-to-assess phenotypic features, which may promote awareness for PCD among adults with bronchiectasis., Clinical Trial Registration: ClinicalTrials.gov; No.: NCT02574143; URL: www., Clinicaltrials: gov., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: I. P. reports grants from COFONI-2FF4 and COFONI-6LZF23 by the Ministry of Science and Culture of Lower Saxony paid to her institution and personal lecture fees from AstraZeneca and Boehringer Ingelheim. S. S. reports fees for clinical trial participation from Celtaxsys, Corbus, Galapagos, Insmed, Proteostasis, and Vertex Pharmaceuticals paid to his institution; and personal fees for consulting and lectures from Boehringer Ingelheim, Insmed, and Vertex Pharmaceuticals. S. P. A. reports personal consulting fees from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, and GlaxoSmithKline. A. G. reports personal fees for consulting, advisory board participation, and lectures from Boehringer Ingelheim and GlaxoSmithKline. A. S. reports personal fees for consulting and lectures from Ethris, Insmed, Spirovant, and Translate Bio; and is involved in the European Respiratory Society (ERS) Clinical Research Collaborations AMR-Lung, BEAT-PCD, and EMBARC. S. W. reports fees for clinical trial participation from Insmed paid to her institution and personal honoraria from Vertex Pharmaceuticals. P. M. reports fees for clinical trial participation from Boehringer Ingelheim and Insmed paid to his institution; reports personal fees for lectures from AstraZeneca, MAÄF eV, ResMed, and streamedup! GmbH; reports travel support from the German Society for Internal Medicine (DGIM), CSL Behring, and Insmed; and is honorary co-chair of the German Bronchiectasis Registry PROGNOSIS. J. R. reports grants from the German Center for Lung Research (DZL), the German Center for Infection Research (DZIF), the Federal Ministry of Education and Research (BMBF), the Federal Ministry of Health (BMG), Novartis, and Insmed paid to her institution; reports personal fees for consulting or advisory board participation and honoraria for lectures from AstraZeneca, Brahms GmbH, ERS, Grifols, Insmed, MedUpdate, MSD, Pfizer, Shionogi, and streamedup! GmbH; and is honorary co-chair of the German Bronchiectasis Registry PROGNOSIS and chair of the Respiratory Infections and Tuberculosis Assembly of the German Respiratory Society (DGP). F. C. R. reports grants from the German Center for Lung Research (DZL), the German Center for Infection Research (DZIF), IMI (EU/EFPIA), and the Innovative Medicines Initiative (IMI) and EFPIA companies under the European Commission funded project, iABC [Grant 115721], Novartis, and Insmed Germany paid to his institution; reports personal fees for consulting or advisory board participation and honoraria for lectures from Parion, Grifols, Zambon, Insmed, Helmholtz-Zentrum für Infektionsforschung, i!DE Werbeagentur GmbH, Interkongress GmbH, streamedup! GmbH, AstraZeneca, Insmed, Shionogi, and Grifols; reports travel support from the German Kartagener Syndrome and Primary Ciliary Dyskinesia patient advocacy group, which he serves as the unpaid co-speaker of its medical advisory board; and is honorary co-chair of the German Bronchiectasis Registry PROGNOSIS, a member of the steering committee of the European Bronchiectasis Registry EMBARC, and a member of the Protocol Review Committee of the PCD-Clinical Trials Network. None declared (R. E., U. S., B. O. S.)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The serum antiglycopeptidolipid core IgA antibody test has been proposed as a diagnostic tool for Mycobacterium avium complex pulmonary diseases. Cross-reactivity with other nontuberculous mycobacteria (NTM), including Mycobacterium abscessus, indicates that it may have a role as a broader screening test for nontuberculous mycobacterial pulmonary disease (NTM-PD). NTM-PD is believed to be underdiagnosed in patients with bronchiectasis., Research Question: Can the serum antiglycopeptidolipid core IgA antibody test be used to screen for NTM-PD in bronchiectasis?, Study Design and Methods: Patients from the prospective European Bronchiectasis Registry (European Multicentre Bronchiectasis Audit and Research Collaboration-Bronchiectasis Research Involving Databases, Genomics and Endotyping; ClinicalTrails.gov Identifier: NCT03791086) were enrolled. Patients from the United Kingdom, Italy, Spain, Belgium, The Netherlands, and Germany were included. A control cohort of patients without any underlying lung disease also was recruited. The levels of serum IgA antibodies against the glycopeptidolipid core were measured using an enzyme immunoassay kit, and receiver operating characteristics curve analysis was conducted to evaluate the accuracy of the antibody level in screening for NTM-PD., Results: Two hundred eighty-two patients were enrolled (151 female patients [53.6%]; median age, 68 years). Median antiglycopeptidolipid core IgA antibody levels were 0.2 U/mL (interquartile range [IQR], 0.1-0.3 U/mL) in patients without NTM isolation and NTM-PD (n = 238), 0.3 U/mL (IQR, 0.2-0.4 U/mL) in patients with NTM isolation that was incompatible with the diagnosis of NTM-PD (n = 18), and 1.5 U/mL (IQR, 0.4-6.2 U/mL) in patients with NTM-PD (n = 26; P = .0001). Antibody levels showed excellent accuracy in identifying patients with NTM-PD (area under the receiver operating characteristic curve, 0.886; 95% CI, 0.800-0.973) in the bronchiectasis cohort and also showed excellent discrimination of patients with NTM-PD from those with NTM isolation who did not meet the diagnostic criteria for NTM-PD (0.816; 95% CI, 0.687-0.945)., Interpretation: The antiglycopeptidolipid core IgA antibody demonstrated excellent efficacy in screening for NTM-PD in a large cohort of patients with bronchiectasis., Clinical Trial Registry: ClinicalTrials.gov; No.: NCT03791086; URL: www., Clinicaltrials: gov., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: H. C. reports grant from the Basic Science Research Program of the Korean Ministry of Education (grant no. 2021R1I1A3052416); and lecture fees from Boryung Pharmaceutical Co. and Kolon Pharma and Abbott. M. Shteinberg reports consulting fees from GSK, Boehringer Ingelheim, Kamada, Medison, and Zambon; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Insmed, Boehringer Ingelheim, GSK, AstraZeneca, Teva, Novartis, Kamada, and Sanofi; support for attending meetings, travel, or both from Novartis, Actelion, Boehringer Ingelheim, GSK, and Rafa; participation on a data safety monitoring board or advisory board for Bonus Therapeutics, Israel; leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid for EMBARC Management, Israel Pulmonology Society Board, Israel Society for TB and Mycobacterial Diseases; receipt of equipment, materials, drugs, medical writing, gifts, or other services from Trudell Medical Int.; and other financial or nonfinancial interests including associate editor, American Journal of Respiratory and Critical Care Medicine. E. P. reports grants or contracts from any entity from Grifols; consulting fees from Insmed, Bayer, Chiesi, and Zambon; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bayer, Chiesi, Grifols, GlaxoSmithKline, Insmed, Menarini, and Zambon; and support for attending meetings, travel, or both from Insmed, Pfizer, and Moderna. P. C. G. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Insmed, GSK, and Chiesi; support for attending meetings, travel, or both from Chiesi; and participation in a data safety monitoring board or advisory board for Boehringer, GSK, and Pfizer. F. B. reports grants or contracts from any entity from AstraZeneca, Chiesi, and Insmed; consulting fees from Menarini; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Chiesi, GSK, Guidotti, Grifols, Insmed, Menarini, Novartis, OM Pharma, Pfizer, Sanofi, Viatris, Vertex, and Zambon. A. S. reports consulting fees from Spirovant and Translate Bio; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Translate Bio, Ethris, and Insmed; leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid for European Respiratory Society Clinical Research Collaborations (EMBARC, BEATPCD, AMR). S. A. reports grants or contracts from any entity from Insmed Incorporated, Chiesi, Fisher and Paykel, and GSK; royalties or licences from McGraw Hill; consulting fees from Insmed Incorporated, Insmed Italy, Insmed Ireland Ltd, Zambon Spa, AstraZeneca UK Ltd., AstraZeneca Pharmaceutical LP, CSL Behring GmbH, Grifols, Fondazione Internazionale Menarini, Moderna, Chiesi, MCD Italis SrL, Brahms, Physioassist SAS, and GlaxoSmithKline Spa; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from GlaxoSmithKline Spa, Thermofisher Scientific, Insmed Italy, Insmed Ireland, Zambon, and Fondazione Internazionale Menarini; participation on a data safety monitoring board or advisory board from Insmed Incorporated, Insmed Italy, AstraZeneca UK Ltd., and MSD Italia Srl. C. S. H. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from 30 Technology, CSL Behring, Chisi, Insmed, Janssen, LifeArc, Meiji, Mylan, Pneumagen, Shionogi, Vertex, and Zambon. F. C. R. reports grants or contracts from any entity from German Center for Lung Research (DZL), German Center for Infection Research (DZIF), IMI (EU / EFPIA), and iABC Consortium (incl. Alaxia, Basilea, Novartis, and Polyphor), Mukoviszidose Institute, Novartis, Insmed Germany, Grifols, Bayer, and InfectoPharm; consulting fees from Parion, Grifols, Zambon, Insmed, and Helmholtz-Zentrum für Infektionsforschung; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from I!DE Werbeagentur GmbH, Interkongress GmbH, AstraZeneca, Insmed, Grifols, and Universitätsklinikum Frankfurt am Main; payment for expert testimony from Social Court Cologne; support for attending meetings, travel, or both from German Kartagener Syndrome and Primary Ciliary Dyskinesia Patient Advocacy Group Mukoviszidose e.V.; participation on a data safety monitoring board or advisory board for Insmed, Grifols and Shionogi; leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, as coordinator of the ERN-LUNG Bronchiectasis Core Network, chair of the German Bronchiectasis Registry PROGNOSIS, member of the SteerCo of the European Bronchiectasis Registry EMBARC, member of the SteerCo of the European Nontuberculous Mycobacterial Pulmonary Disease Registry EMBARC-NTM, cospeaker for the Medical Advisory Board of the German Kartagener Syndrome and PCD Patient Advocacy Group, speaker of the Respiratory Infections and TB Group of the German Respiratory Society, speaker of the Cystic Fibrosis Group of German Respiratory Society (DGP), primary investigator of the German Center for Lung Research, member of the Protocol Review Committee of the PCD-CTN, and member of Physician Association of the German Cystic Fibrosis Patient Advocacy Group; and other financial or nonfinancial interests with AstraZeneca, Boehringer Ingelheim, Celtaxsys, Corbus, Insmed, Novartis, Parion, University of Dundee, Vertex, and Zambon. M. R. L. reports consulting fees from Armata, 30T, AstraZeneca, Parion, Insmed, Chiesi, Zambon, Electromed, Recode, AN2, and Boehringer Ingelheim; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Insmed; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, as ERS Infection Group Chair. N. L. reports leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, as a founder and chair of the Belgian NTM Clinical Advisory Board and a chair of NTM-NET. J. D. C. reports grants or contracts from any entity from AstraZeneca, Boehringer Ingelheim, Genentech, Gilead Sciences, GlaxoSmithKline, Grifols, Insmed, LifeArc, and Novartis; and consulting fees from AstraZeneca, Chiesi, GlaxoSmithKline, Insmed, Grifols, Novartis, Boehringer Ingelheim, Pfizer, Janssen, Antabio, and Zambon. None declared (C. H., Z. E., M. Shuttleworth, T. W., M. B. L.)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Aspergillus species cause diverse clinical manifestations in bronchiectasis including allergic bronchopulmonary aspergillosis (ABPA), Aspergillus sensitization (AS), and raised IgG indicating exposure to or infection with Aspergillus., Research Question: What are the prevalence and clinical significance of Aspergillus-associated conditions in individuals with bronchiectasis?, Study Design and Methods: Patients with bronchiectasis enrolled into the European Bronchiectasis Registry from 2015 through 2022 with laboratory testing for Aspergillus lung disease (total IgE, IgE specific to Aspergillus or Aspergillus skin test, or IgG specific to Aspergillus and blood eosinophil counts) were included for analysis. Modified International Society for Human and Anima Mycology ABPA working group criteria (2021) were used to define ABPA., Results: Nine thousand nine hundred fifty-three patients were included. Six hundred eight patients (6.1%) were classified as having ABPA, 570 patients (5.7%) showed AS, 806 patients (8.1%) showed raised Aspergillus-specific IgG without AS, 184 patients (1.8%) showed both AS and had raised Aspergillus-specific IgG levels, and 619 patients (6.2%) demonstrated eosinophilic bronchiectasis (elevated eosinophil counts without evidence of Aspergillus lung disease). The remaining 72% showed negative Aspergillus serologic findings. Patients with ABPA, AS, or raised Aspergillus-specific IgG demonstrated more severe disease, with worse lung function and more frequent exacerbations at baseline. During long-term follow-up, patients with raised Aspergillus-specific IgG experienced higher exacerbation frequency and more severe exacerbations. AS was associated with increased exacerbations and hospitalizations only in patients not receiving inhaled corticosteroids (ICS)., Interpretation: Aspergillus lung disease is common in bronchiectasis. Raised IgG levels to Aspergillus are associated with significantly worse outcomes, whereas ABPA and AS are associated with severe disease and exacerbations with a risk that is attenuated by ICS use., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: J. P. reports support for attending meetings, travel, or both from the European Respiratory Society, Asthma + Lung UK, American Thoracic Society, and British Association for Lung Research (BALR). P. C. G. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Insmed, GSK, and Chiesi; support for attending meetings, travel, or both from Chiesi; and participation on a data safety monitoring board or advisory board for Boehringer, GSK, and Pfizer. S. A. reports grants or contracts from any entity from Insmed Incorporated, Chiesi, Fisher and Paykel, and GSK; royalties or licences from McGraw Hill; consulting fees from Insmed, Inc, Insmed Italy, Insmed Ireland Ltd, Zambon Spa, AstraZeneca UK Ltd., AstraZeneca Pharmaceutical LP, CSL Behring GmbH, Grifols, Fondazione Internazionale Menarini, Moderna, Chiesi, MCD Italis SrL, Brahms, Physioassist SAS, and GlaxoSmithKline Spa; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from GlaxoSmithKline Spa, Thermofisher Scientific, Insmed Italy, Insmed Ireland, Zambon, and Fondazione Internazionale Menarini; and participation on a data safety monitoring board or advisory board from Insmed Incorporated, Insmed Italy, AstraZeneca UK Ltd, and MSD Italia Srl. E. P. reports grants or contracts from any entity from Grifols; consulting fees from Insmed, Bayer, Chiesi, and Zambon; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bayer, Chiesi, Grifols, GlaxoSmithKline, Insmed, Menarini, and Zambon; and support for attending meetings, travel, or both from Insmed, Pfizer, and Moderna. M. L. C. reports consulting fees from Boxer Capital LLC. F. C. R. reports grants or contracts from any entity from German Center for Lung Research (DZL), German Center for Infection Research (DZIF), IMI (EU/EFPIA), and iABC Consortium (incl. Alaxia, Basilea, Novartis, and Polyphor), Mukoviszidose Institute, Novartis, Insmed Germany, Grifols, Bayer, InfectoPharm; consulting fees from Parion, Grifols, Zambon, Insmed, and Helmholtz-Zentrum für Infektionsforschung; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from I!DE Werbeagentur GmbH, Interkongress GmbH, AstraZeneca, Insmed, Grifols, and Universitätsklinikum Frankfurt am Main; payment for expert testimony from Social Court Cologne; support for attending meetings, travel, both from German Kartagener Syndrome and Primary Ciliary Dyskinesia Patient Advocacy Group Mukoviszidose e.V.; participation on a data safety monitoring board or advisory board for Insmed, Grifols, and Shionogi; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, as coordinator of the ERN-LUNG Bronchiectasis Core Network, chair of the German Bronchiectasis Registry PROGNOSIS, member of the steering committee of the European Bronchiectasis Registry EMBARC, member of the steering committee of the European Nontuberculous Mycobacterial Pulmonary Disease Registry EMBARC-NTM, cospeaker of the medical advisory board of the German Kartagener Syndrome and Primary Ciliary Dyskinesia Patient Advocacy Group, speaker of the respiratory infections and TB group of the German Respiratory Society, speaker of the cystic fibrosis group of German Respiratory Society (DGP), primary investigator of the German Center for Lung Research, member of the protocol review committee of the PCD-CTN, member of physician association of the German Cystic Fibrosis Patient Advocacy Group; and other financial or nonfinancial interests with AstraZeneca, Boehringer Ingelheim, Celtaxsys, Corbus, Insmed, Novartis, Parion, University of Dundee, Vertex, and Zambon. R. D. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from LUPIN, CIPLA, and Glenmark. M. V. reports grants or contracts from any entity from Chiesi; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Insmed and Publi Creation; support for attending meetings, travel, or both from Zambon, Chiesi, Novartis, Behring, and Gebro; participation on a data safety monitoring board or advisory board for Insmed; and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Insmed and Novartis. P.-R. B. reports grants or contracts from any entity from GSK and Vertex; consulting fees from AstraZeneca, Chiesi, GSK, Insmed, MSD, Vertex, Viatris, and Zambon; and support for attending meetings, travel, or both from AstraZeneca and Chiesi. C. S. H. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from 30 Technology, CSL Behring, Chiesi, Insmed, Janssen, LifeArc, Meiji, Mylan, Pneumagen, Shionogi, Vertex, and Zambon. A. D. reports grants or contracts from AstraZeneca, Pfizer, GSK, and Novartis; consulting fees from AstraZeneca, Insmed, GSK, Boehringer, 30T, and Bayer; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Pfizer, GSK, and Novartis. A. B. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Chiesi; leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, for Head of Assembly 5 (airway diseases, asthma, COPD and chronic cough) of the European Respiratory Society, vice-chair of the Nordic Severe Asthma Network (NSAN)-NORDSTAR, and steering committee of European Respiratory Society CRC severe asthma, SHARP. J. R. reports payment or honoraria for lectures, presentations, speakers bureaus, or educational events from CSL Seqirus, Berlin-Chemie, GlaxoSmithKline, AstraZeneca, Chiesi, ThermoFisher, Boehringer Ingelheim, Pfizer, Shionogi, and INSMED; and participation on a data safety monitoring board or advisory board from GlaxoSmithKline, GILEAD, ThermoFischer, Shionogi, and INSMED. D. S. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from CSL Behring, Berlin-Chemie, Menarini, Novartis, GlaxoSmithKline, AstraZeneca, Vifor, Merck, Chiesi, and Sanofi; and participation on a data safety monitoring board or advisory board from GlaxoSmithKline and CSL Behring. P. K. reports support for attending meetings, travel, or both from Nordic Respiratory Academy; participation on a data safety monitoring board or advisory board from Swedish Orphan Biovitrium; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, from Finnish Respiratory Society and Finnish Tuberculosis Foundation Grant Committee; and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Theravance. A. A. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Zambon Group; and support for attending meetings, travel, or both from Zambon Group, Boehringer Ingelheim, and Novartis Farma. F. B. reports grants or contracts from any entity from AstraZeneca, Chiesi, and Insmed; consulting fees from Menarini; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Chiesi, GSK, Guidotti, Grifols, Insmed, Menarini, Novartis, OM Pharma, Pfizer, Sanofi, Viatris, Vertex, and Zambon. M. S. reports consulting fees from GKS, Boehringer Ingelheim, Kamada, and Zambon; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Insmed, Boehringer Ingelheim, GSK, AstraZeneca, Teva, Novartis, Kamada, and Sanofi; support for attending meetings, travel, or both from Novartis, Actelion, Boehringer Ingelheim, GSK, and Rafa; participation on a data safety monitoring board or advisory board for Bonus Therapeutics, Israel; leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, for EMBARC Management, Israel Pulmonology Society Board, and the Israel Society for TB and mycobacterial diseases; receipt of equipment, materials, drugs, medical writing, gifts, or other services from Trudell Medical International; and other financial or nonfinancial interests as the associate editor of American Journal of Respiratory Critical Care Medicine. K. D. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Novartis, Boehringer Ingelheim, GSK, Norma Hellas, Chiesi, AstraZeneca, and Zambon; support for attending meetings, travel, or both from Novartis, Boehringer Ingelheim, GSK, Norma Hellas, Chiesi, AstraZeneca, and Menarini; and participation on a data safety monitoring board or advisory board from Novartis, GSK, and Chiesi. J. D. C. reports grants or contracts from any entity from AstraZeneca, Boehringer Ingelheim, Genentech, Gilead Sciences, GlaxoSmithKline, Grifols, Insmed, LifeArc, and Novartis; and consulting fees from AstraZeneca, Chiesi, GlaxoSmithKline, Insmed, Grifols, Novartis, Boehringer Ingelheim, Pfizer, Janssen, Antabio, and Zambon. M. R. L. reports consulting fees from Armata, 30T, AstraZeneca, Parion, Insmed, Chiesi, Zambon, Electromed, Recode, AN2, Mannkind, and Boehringer Ingelheim; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Insmed; Leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, for the European Respiratory Society Infection Group (chair). None declared (J. D, A. G, M. M, O. S, M. v. d. E, A. T. H, R. W, O. M, R. M, A. T, T. W, W. B, J. S. E.)., (Copyright © 2024. Published by Elsevier Inc.)

Background: Obesity-associated asthma results in increased morbidity and mortality. We report 1-year asthma outcomes with a weight management regimen, the Counterweight-Plus Programme (CWP), compared with usual care (UC) in a single-center, randomized controlled trial in patients with difficult-to-treat asthma and obesity., Research Question: Can use of the CWP result in improved asthma control and quality of life compared with UC at 1 year in patients with difficult-to-treat asthma and obesity?, Study Design and Methods: Adults with difficult-to-treat asthma and BMI ≥ 30 kg/m 2 were randomized (1:1 CWP:UC) to treatment. The CWP, with dietitian support, included a 12-week total diet replacement phase (850 kcal/d low-energy formula), and then subsequent food reintroduction and maintenance phases up to 1 year. Outcomes include results of the 6-item Asthma Control Questionnaire (ACQ-6) and Asthma Quality of Life Questionnaire (AQLQ), as well as health care usage. A minimal clinically important difference (MCID) is 0.5 for ACQ-6 and AQLQ., Results: Of 36 patients recruited, 29 attended visits at 52 weeks (13 CWP and 16 UC). The CWP resulted in greater weight change (median, -14 kg [interquartile range (IQR), -15 to -9 kg]) compared with UC (median, 2 kg [IQR, -7 to 8 kg]; P = .015) at 52 weeks. A greater proportion achieved MCID with the CWP vs UC in AQLQ (71% vs 6%, respectively; P < .001). No between-group differences were observed in ACQ-6. Median exacerbation frequency was reduced over 52 weeks with the CWP from 4 (IQR, 2 to 5) to 0 (IQR, 0 to 2) (P < .001), although no between-group difference was observed. Seventy percent of the CWP group lost ≥ 10% body weight and had improvement in ACQ-6 (mean difference, -1.1; 95% CI, -1.9 to -0.3; P = .018) and AQLQ (mean difference, 1.2; 95% CI, 0.4, 2.1; P = .011) across 52 weeks., Interpretation: Use of a dietitian-supported weight management program resulted in sustained weight loss and is a potential treatment for obesity in asthma. The CWP resulted in a higher proportion achieving MCID improvements in AQLQ compared with UC. Within-group differences in AQLQ and exacerbation frequency suggest potential with the CWP. These encouraging signals justify a larger sample study to further assess asthma-related outcomes., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: V. S. and H. C. R. have received travel awards to attend conferences. V. S. has received fees for presentations from AstraZeneca. N. B. has received funding from Cambridge Weight Plan for PhD and conference and travel expenses and has shares in and is an employee of Counterweight Ltd. D. S. B. has received a CSO grant unrelated to this study. R. C. has received funding from AstraZeneca for a study within a Medical Research Council project as investigator lead; has received payment for lectures from GSK, AstraZeneca, Teva, Chiesi, Sanofi, and Novartis; has received funding to attend conferences from Chiesi, Sanofi, and GSK; and has participated on advisory board meetings for GSK, AstraZeneca, Teva, Chiesi, and Novartis. M. E. J. L. has received grants from the National Institute for Health and Care Research, Diabetes UK, All Saints Educational Trust, Novo Nordisk, and MJ Smith Trust for the study; has received consulting fees from Novo Nordisk and Nestle; has received payment for lectures from Oviva, Merck, Sanofi, and Roche; and is a medical advisor for Counterweight Ltd. None declared (L. M., L. C., L. S., A. G., F. S., D. C. C.)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: Financial/Nonfinancial Disclosures None declared.

Background: Pulmonary hypertension (PH) is a key complication in interstitial lung disease (ILD), with recent therapeutic advances., Research Question: What are the diagnostic evaluation, epidemiologic features, associated factors, prognostic significance, and outcome measures in interventional trials for PH in patients with ILD in the current literature?, Study Design and Methods: The Ovid MEDLINE, Embase, and CENTRAL databases were searched for original research evaluating PH in participants with ILD of any cause. The definition of PH was based on the investigators' criteria., Results: Three hundred two studies were included, with varying diagnostic evaluations used to define PH. Commonly used diagnostic tests were right heart catheterization (56%) and transthoracic echocardiography (50%). The pooled prevalence for PH in general populations with ILD was 36% (95% CI, 30%-42%) using right heart catheterization and 34% (95% CI, 29%-38%) using transthoracic echocardiography. Lower diffusion capacity of the lungs for carbon monoxide, worse oxygenation status, reduced exercise capacity, increased pulmonary artery to aorta ratio and pulmonary artery diameter, and elevated serum brain natriuretic peptide consistently were associated with the presence of PH in at least 60% of reported studies. The presence of PH was associated with increased symptom burden and worse prognosis. Outcome measures in interventional trials of PH in ILD focused on changes in pulmonary vascular hemodynamics and 6-min walk distance., Interpretation: PH is a common complication in ILD with significant health impacts. A standardized definition with prospective evaluation of risk-stratified assessments for PH using identified associated risk factors is warranted. Our findings provide an evidence base for validation as surrogate end points in future PH interventional trials in ILD., Trial Registry: International Prospective Register of Systematic Reviews; No.: CRD42021255394; URL: https://www.crd.york.ac.uk/prospero/., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: Y. H. K. reports fellowship support from an NHMRC Investigator Grant, Austin Medical Research Foundation, and Royal Australasian College of Physicians, and grants from Boehringer Ingelheim during the conduct of the study. C. J. R. reports grants from Boehringer Ingelheim during the conduct of the study, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Hoffmann-La Roche, personal fees from Veracyte, personal fees from Pliant Therapeutics, personal fees from Astra Zeneca, and personal fees from Cipla Ltd. outside the submitted work. None declared (H. L. A., M. S., R. K. C., H. H. T., A. H.)., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The 2022 European Society of Cardiology/European Respiratory Society guidelines define pulmonary hypertension (PH) as a resting mean pulmonary artery pressure (mPAP) > 20 mm Hg at right heart catheterization (RHC). Previously, patients with an mPAP between 21 and 24 mm Hg were classified in a "gray zone" of unclear clinical significance., Research Question: What is the diagnostic performance of the main parameters used for PH screening in detecting patients with systemic sclerosis (SSc) with an mPAP of 21 to 24 mm Hg at RHC?, Study Design and Methods: Patients with SSc from the European Scleroderma Trials and Research (EUSTAR) database with available tricuspid annular plane systolic excursion (TAPSE), systolic PAP (sPAP), and mPAP data were included. Patients with mPAP 21 to 24 mm Hg and patients with mPAP ≤ 20 mm Hg were considered for the analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated., Results: TAPSE/sPAP was lower in the group of patients with SSc with mPAP 21 to 24 mm Hg than in the non-PH group (0.58 [0.46-0.72] vs 0.69 [0.57-0.81] mm/mm Hg, respectively; P < .01). No difference was found in other parameters between the two groups. Diffusing capacity of the lungs for carbon monoxide < 80% of the predicted value had the highest sensitivity (88.9%) and NPV (80%), but the lowest specificity (18.2%) and PPV (30.8%) in detecting patients with SSc with mPAP 21 to 24 mm Hg. TAPSE/sPAP < 0.55 mm/mm Hg had the highest specificity (78.9%), PPV (50%), and accuracy (68.1%); its NPV was 75.4%, and its sensitivity was 45.1%., Interpretation: In this study, diffusing capacity of the lungs for carbon monoxide < 80% of the predicted value was the parameter with the highest sensitivity and NPV in detecting patients with SSc with mPAP 21 to 24 mm Hg. TAPSE/sPAP < 0.55 mm/mm Hg had the highest specificity, PPV, and accuracy and, therefore, can be a useful additional parameter to decrease the number of unnecessary RHCs., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: V. S. is senior clinical investigator of the Research Foundation—Flanders (Belgium): (FWO) (1.8.029.20N). This funding source had no role in the literature review and the synthesis and interpretation of the data; in the writing of the report; or in the decision to submit the paper for publication. C. B. received grants from Boehringer-Ingelheim, consulting fees from Janssen, honoraria for lectures from Novartis, and travel grants from Kyverna, which were not related to this project. E. Z. received speaking and lecture fees from Janssen and consulting fees from Janssen and GSK. F. I. received honoraria and speaking fees from AbbVie, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB outside this work. C. P. S. A. received consulting fees and support for attending meetings from Janssen-Cilag SAS, Boehringer Ingelheim Ltd and MSD. None declared (A. C., E. H., C. P., G. R., J. H., D. L., A. M., A. M. G., M.-E. T., S. O., M. V., F. D. G., E. R.)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Patients with COPD frequently demonstrate pulmonary hypertension (PH). Severe PH in patients with COPD, identified by pulmonary vascular resistance (PVR) of > 5 Wood units (WU), is closely linked to impaired transplant-free survival. The impact of PH-targeting pharmacotherapy in this context remains unclear., Research Question: Is PH-targeted therapy associated with improved transplant-free survival in patients with COPD and PH?, Study Design and Methods: This study included Pulmonary Vascular Research Institute GoDeep meta-registry patients with COPD and PH and available right heart catheterization at diagnosis. We investigated PH-targeted therapy prevalence and its association with transplant-free survival using diverse statistical methods, including Cox regression and subgroup analyses based on PH severity, comorbidities, and pulmonary function test results. Immortal time bias was addressed through a landmark approach., Results: As of December 2023, the GoDeep meta-registry included 26,981 patients (28% in PH group 1, 13% in PH group 2, 12% in PH group 3, 10% in PH group 4, 2% in PH group 5, 26% undefined, and 9% control participants). Of these, 836 patients had a diagnosis of COPD with PH and were included in this analysis, with median age of 66 years (59-73 years), FEV 1 of 51% predicted (34%-69% predicted), mPAP of 35 mm Hg (28-44 mm Hg), PVR of 5 WU (4-8 WU), cardiac index of 2.5 L/min/m 2 (2.0-2.9 L/min/m 2 ), and mostly World Health Organization functional class III were included. Five-year transplant-free survival was 42%, significantly worse than in group 1 PH. A multivariable Cox proportional hazards model identified PVR, but not FEV 1 , as a major predictor of outcome. Four hundred eighteen patients (50%) received phosphodiesterase 5 inhibitor (PDE5i) therapy, which was associated with significantly reduced mortality: hazard ratio of 0.65 (0.57-0.75) for the entire cohort of patients with COPD and PH and of 0.83 (0.74-0.94) when performing landmark analysis. This PDE5i effect was reproduced robustly when performing subgroup analyses for patients with moderate to severe PH, various comorbidities, and supplemental oxygen requirement and when assessing the impact of unobserved confounders., Interpretation: Patients with COPD and PH exhibit poor transplant-free survival, with PVR being a predictor of mortality. In this meta-registry, PDE5i therapy was associated with a significant reduction in mortality across all tested models., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: K. T. has received personal fees from Bayer, AstraZeneca, and Gossamer. A. Y. has received personal fees from MSD and support for scientific meetings from AOP. D. G. K. reports support from the Sheffield Biomedical Research Centre and consulting fees and other payments from Jansen Pharmaceuticals, Ferrer, Altavant, MSD, and United therapeutics. H. O. reports grants or contracts from Actelion, Bayer, Boehringer-Ingelheim, Janssen, MSD, IQVIA, and Pfizer; consulting fees from Bayer and IQVIA; speaker fees from Actelion, Bayer, Boehringer-Ingelheim, MSD, and Pfizer; support for scientific meetings from Astra Zeneca, Boehringer-Ingelheim, Menarini, and MSD; and participation on data safety board or advisory board for Bayer and IQVIA. G. K. reports consulting and speaker fees from Boehringer-Ingelheim, Janssen, MSD, Astra Zeneca, Chiesi, AOP, and Ferrer and support for scientific meetings from AOP, Vitalaire, MSD, and Boehringer-Ingelheim. P. M. H. reports personal fees from Merck Co. M. R. W. reports personal fees from MorphogenIX, Janssen, Chiesi, and Aerami; grants from British Heart Foundation and NIHR; and personal fees from MSD, Benevolent AI, and Tiakis Biotech outside the submitted work. L. H. reports personal fees and nonfinancial support from Janssen and personal fees from MSD, Gossamer, and Altavant. M. R. has received support from Janssen Pharmaceutica and Bayer Pharma AG, and speaker fees from Janssen Pharmaceutica and OMT. H.-A. G. has received fees from Actelion, AstraZeneca, Bayer, GSK, Janssen-Cilag, Lilly, Novartis, OMT, Pfizer, and United Therapeutics. W. S. has received consultancy fees from United Therapeutics, Tiakis Biotech AG, Liquidia, Pieris Pharmaceuticals, Abivax, Pfizer, and Medspray BV. None declared (R. W. M., A. L., E. B., J. S. A., A. B., Z. K., A. J. S., R. T. Z., A. A., G. G., H. R. C., R. F., P. G. W., M. Frauendorf, K. M., T. A., M. Feunerich, F. G., J. W.)., (Copyright © 2024. Published by Elsevier Inc.)

In this instalment of the How I Do It series on severe asthma, we tackle the clinical conundrum of choosing the right biologic for the right patient with severe asthma. With 6 biologics now approved for use in this area comprising 4 different targeting strategies (anti-Ig E: omalizumab; anti-IL-5 and anti-IL-5-receptor: mepolizumab, reslizumab, and benralizumab; anti-IL-4-receptor: dupilumab; anti-thymic stromal lymphopoietin: tezepelumab), this question is increasingly complex. Recognizing that no head-to-head trial has compared biologics, we based our review on the expected effects of inhibiting different aspects of type 2 airway inflammation, supported whenever possible by clinical trial and real-world data. We use 4 variations of a case of severe uncontrolled asthma to develop concepts and considerations introduced in the previous installment ("Workup of Severe Asthma") and discuss pregnancy-related, biomarker-related, comorbidity-related, and corticosteroid dependency-related considerations when choosing a biologic. The related questions of deciding when, why, and how to switch from one biologic to another also are discussed. Overall, we consider that the choice of biologics should be based on the available clinical trial data for the desired efficacy outcomes, the biomarker profile of the patient, safety profiles (eg, when pregnancy is considered), and opportunities to target 2 comorbidities with 1 biologic. Using systemic and airway biomarkers (blood eosinophils and exhaled nitric oxide) and other phenotypic characteristics, we suggest a framework to facilitate therapeutic decision-making. Post hoc studies and new comparative studies are needed urgently to test this framework and to determine whether it allows us to make other clinically useful predictions., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: S. C. reports nonrestricted research grants from the NIHR Oxford BRC, the Quebec Respiratory Health Research Network, the Fondation Québécoise en Santé Respiratoire, AstraZeneca, bioMérieux, and Sanofi-Genyme-Regeneron; support as the Association Pulmonaire du Québec’s Research Chair in Respiratory Medicine and as a clinical research scholar of the Fonds de Recherche du Québec; speaker honoraria from AstraZeneca, GlaxoSmithKline, Sanofi-Regeneron, and Valeo Pharma; consultancy fees from FirstThought, AstraZeneca, GlaxoSmithKline, Sanofi-Regeneron, Access Biotechnology, and Access Industries; and sponsorship to attend or speak at international scientific meetings by or for AstraZeneca and Sanofi-Regeneron. He is an advisory board member and will have stock options for Biometry, Inc., a company that is developing an Feno device (myBiometry). He advised the Institut National d’Excellence en Santé et Services Sociaux for an update of the asthma general practice information booklet for general practitioners. D. J. J. has received advisory board and speaker’s fees from AstraZeneca, Boehringer Ingelheim, Novartis, Teva, GSK, Sanofi/Regeneron, and Chiesi outside of the submitted work. I. D. P. has received speaker’s honoraria for speaking at sponsored meetings from AstraZeneca, Boehringer Ingelheim, Aerocrine AB, Almirall, Novartis, Teva, Chiesi, Sanofi/Regeneron, Menarini, and GSK in the last 5 years and has received payments for organizing educational events from AstraZeneca, GSK, Sanofi/Regeneron, and Teva. He has received honoraria for attending advisory panels with Genentech, Sanofi/Regeneron, AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Teva, Merck, Circassia, Chiesi, and Knopp and has received payments to support Food and Drug Administration approval meetings from GSK. He has received sponsorship to attend international scientific meetings from Boehringer Ingelheim, GSK, AstraZeneca, Teva, and Chiesi. He has received a grant from Chiesi to support a phase 2 clinical trial in Oxford. He is copatent holder of the rights to the Leicester Cough Questionnaire and has received payments for its use in clinical trials from Merck, Bayer, and Insmed. In 2014-2015 he was an expert witness for a patent dispute involving AstraZeneca and Teva. M. E. W. reports grants and personal fees from Novartis, Sanofi, GSK, and Cohero Health; personal fees from Regeneron, Genentech, Sentien, Restorbio, Equillium, and Genzyme; grants, personal fees, and nonfinancial support from Teva; personal fees and nonfinancial support from Boehringer Ingelheim; and grants, personal fees, and nonfinancial support from AstraZeneca., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Topic Importance: COVID-19 can cause ongoing and persistent symptoms (such as breathlessness and fatigue) that lead to reduced functional capacity. There are parallels in symptoms and functional limitations in adults with post-COVID symptoms and adults with chronic respiratory diseases. Pulmonary rehabilitation is a key treatment for adults with chronic respiratory diseases, with the aims to improve symptom management and increase functional capacity. Given the similarities in presentation and aims, a pulmonary rehabilitation program may be optimal to meet the needs of those with ongoing symptoms after COVID-19., Review Findings: Aerobic and strength training has shown benefit for adults living with long COVID, although there is little evidence on structured education in this population. Breathing pattern disorder is common in adults with long COVID, and considerations on treatment before rehabilitation, or alongside rehabilitation, are necessary. Considerations on postexertional malaise are important in this population, and evidence from the chronic fatigue syndrome literature supports the need for individualization of exercise programs, and considerations for those who have an adverse reaction to activity and/or exercise., Summary: This narrative review summarizes the current evidence on pulmonary rehabilitation programs in a long-COVID population. Where the evidence is lacking in long COVID the supporting evidence of these programs in chronic respiratory diseases has highlighted the importance of aerobic and strength training, considerations for fatigue, potential mechanisms for immunology improvement, and management of breathing pattern disorders in these programs., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: S. J. S. is a National Institute for Health Research Senior Investigator. None declared (E. D., G. M., J. H. H., N. C. B., M. B., C. B., H. J. C. M., N. J. G.)., (Copyright © 2024 American College of Chest Physicians. All rights reserved.)

Background: Pulmonary hypertension (PH) is a heterogeneous disease with a poor prognosis. Accurate risk stratification is essential for guiding treatment decisions in pulmonary arterial hypertension (PAH). Although various risk models have been developed for PAH, their comparative prognostic potential requires further exploration. Additionally, the applicability of risk scores in PH groups beyond group 1 remains to be investigated., Research Question: Are risk scores originally developed for PAH predictive in PH groups 1 through 4?, Study Design and Methods: We conducted a comprehensive analysis of outcomes among patients with incident PH enrolled in the multicenter worldwide Pulmonary Vascular Research Institute GoDeep meta-registry. Analyses were performed across PH groups 1 through 4 and further subgroups to evaluate the predictive value of PAH risk scores, including the Registry to Evaluate Early and Long-Term PAH Disease Mangement (REVEAL) Lite 2, REVEAL 2.0, European Society of Cardiology/European Respiratory Society 2022, Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) 3-strata, and COMPERA 4-strata., Results: Eight thousand five hundred sixty-five patients were included in the study, of whom 3,537 patients were assigned to group 1 PH, whereas 1,807 patients, 1,635 patients, and 1,586 patients were assigned to group 2 PH, group 3 PH, and group 4 PH, respectively. Pulmonary hemodynamics were impaired with median mean pulmonary arterial pressure of 42 mm Hg (interquartile range, 33-52 mm Hg) and pulmonary vascular resistance of 7 Wood units (WU) (interquartile range, 4-11 WU). All risk scores were prognostic in the entire PH population and in each of the PH groups 1 through 4. The REVEAL scores, when used as continuous prediction models, demonstrated the highest statistical prognostic power and granularity; the COMPERA 4-strata risk score provided subdifferentiation of the intermediate-risk group. Similar results were obtained when separately analyzing various subgroups (PH subgroups 1.1, 1.4.1, and 1.4.4; PH subgroups 3.1 and 3.2; group 2 with isolated postcapillary PH vs combined precapillary and postcapillary PH; patients of all groups with concomitant cardiac comorbidities; and severe [> 5 WU] vs nonsevere PH)., Interpretation: This comprehensive study with real-world data from 15 PH centers showed that PAH-designed risk scores possess predictive power in a large PH cohort, whether considered as common to the group or calculated separately for each PH group (1-4) and various subgroups., Trial Registry: ClinicalTrials.gov; No.: NCT05329714; URL: www., Clinicaltrials: gov., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: A. Y. has received personal fees from MSD. H. G. has received personal fees from Actelion, AstraZeneca, Bayer, BMS, GossamerBio, GSK, Janssen-Cilag, Lilly, MSD, Novartis, OMT, Pfizer, and United Therapeutics. M. R. W. reports personal fees from MorphogenIX, Janssen, Chiesi, and Aerami; grants from British Heart Foundation and NIHR; and personal fees from MSD, Benevolent AI, and Tiakis Biotech, outside the submitted work. L. H. reports personal fees and nonfinancial support from Janssen and personal fees from MSD, Gossamer, and Altavant. D. G. K. reports support for the present manuscript from the Sheffield Biomedical Research Centre and consulting fees and other payments from Jansen Pharmaceuticals, Ferrer, Altavant, MSD, and United therapeutics. P. M. H. reports personal fees from Merck Co. S. Y. C. reports personal fees from Janssen, Bayer, Pfizer, United Therapeutics, and Acceleron Pharma and is a director, officer, and shareholder of Synhale Therapeutics. S. O. reports personal fees from MSD, Janssen, and Gallenica-Ferrer. H. A. G. has received fees from Actelion, AstraZeneca, Bayer, GSK, Janssen-Cilag, Lilly, Novartis, OMT, Pfizer, and United Therapeutics. M. J. R. has received support from Janssen Pharmaceutica and Bayer Pharma AG and speaker fees from Janssen Pharmaceutica and OMT. S. S. reports personal fees from Gossamer Bio, Merck, Keros, Janssen, United Therapeutics, and Liquidia. K. T. has received personal fees from Bayer, AstraZeneca, and Gossamer. W. S. has received consultancy fees from United Therapeutics, Tiakis Biotech AG, Liquidia, Pieris Pharmaceuticals, Abivax, Pfitzer, and Medspray BV. None declared (M. Fünderich, A.L., Y. S., O. T., A. J. S., R. T. Z., P. G. W., M. Frauendorf, A. Arvanitaki, G. G., K. S., H. R. C., R. F., I. A. G., E. B., J. S. A., A. P., S. G., A. Anthi, R. W. M., J. W., F. G.), (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: COPD is characterized by reduced exercise tolerance, and improving physical performance is an important therapeutic goal. A variety of exercise tests are commonly used to assess exercise tolerance, including laboratory and field-based tests. The responsiveness of these various tests to common COPD interventions is yet to be compared, but the results may inform test selection in clinical and research settings., Research Question: What exercise test possesses the greatest sensitivity to change from before to after intervention in patients with COPD?, Study Design and Methods: One hundred fifty-four patients with symptomatic COPD were recruited and randomized (2:1:1) to 6 weeks of long-acting muscarinic antagonist (LAMA), pulmonary rehabilitation (PR), or usual care. Before and after intervention, participants performed an incremental cycle exercise test (ICET) and constant work rate cycle test (CWRCT), incremental shuttle walk test (ISWT) and endurance shuttle walk test (ESWT), 6-minute walk test (6MWT), and 4-m gait speed test., Results: One hundred three participants (mean ± SD age, 67 ± 8 years; 75 male participants [73%]; FEV 1 , 50.6 ± 16.8% predicted) completed the study. Significant improvements in the ICET, CWRCT, ISWT, ESWT, and 6MWT results were observed after PR (P < .05), with the greatest improvements seen in the constant work rate protocols (percentages change: CWRCT, 42%; ESWT, 41%)., Interpretation: The ESWT and CWRCT seemed to be the most responsive exercise test protocols to LAMA and PR therapy. The magnitude of change was much greater after a program of rehabilitation compared with bronchodilator therapy., Clinical Trial Registry: International Standard Randomised Controlled Trial Number (ISRCTN): No. 64759523; URL: https://www.isrctn.com/ISRCTN64759523., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: R. T.-S. is a retiree and shareholder of GlaxoSmithKline since 2019. M. A. is a former employee of GlaxoSmithKline. A.H is a former employee of Boehringer Ingelheim (Canada) Ltd. M. C. S reports personal fees and non-financial support from Boehringer Ingelheim and GlaxoSmithKline, outside the submitted work. None declared (T. C.H.-D., M. M. B, M. I. P, M. R, S. A. E, M. D. M, S. J. S)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Albumin is used commonly across a wide range of clinical settings to improve hemodynamics, to facilitate fluid removal, and to manage complications of cirrhosis. The International Collaboration for Transfusion Medicine Guidelines developed guidelines for the use of albumin in patients requiring critical care, undergoing cardiovascular surgery, undergoing kidney replacement therapy, or experiencing complications of cirrhosis., Study Design and Methods: Cochairs oversaw the guideline development process and the panel included researchers, clinicians, methodologists, and a patient representative. The evidence informing this guideline arises from a systematic review of randomized clinical trials and systematic reviews, in which multiple databases were searched (inception through November 23, 2022). The panel reviewed the data and formulated the guideline recommendations using Grading of Recommendations Assessment, Development, and Evaluation methodology. The guidelines were revised after public consultation., Results: The panel made 14 recommendations on albumin use in adult critical care (three recommendations), pediatric critical care (one recommendation), neonatal critical care (two recommendations), cardiovascular surgery (two recommendations), kidney replacement therapy (one recommendation), and complications of cirrhosis (five recommendations). Of the 14 recommendations, two recommendations had moderate certainty of evidence, five recommendations had low certainty of evidence, and seven recommendations had very low certainty of evidence. Two of the 14 recommendations suggested conditional use of albumin for patients with cirrhosis undergoing large-volume paracentesis or with spontaneous bacterial peritonitis. Twelve of 14 recommendations did not suggest albumin use in a wide variety of clinical situations where albumin commonly is transfused., Interpretation: Currently, few evidence-based indications support the routine use of albumin in clinical practice to improve patient outcomes. These guidelines provide clinicians with actionable recommendations on the use of albumin., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: J. C. receives research support from Canadian Blood Services and Octapharma and serves on the board of directors of the Canadian Hematology Society. N. J. S. is a director of the National Board of Echocardiography and receives royalties from Wolters Kluwer. A. B. is an employee of Canadian Blood Services. H. K. is an employee of Canadian Blood Services. E. G. C. receives research funding (related to albumin) from Department of Medicine, The Ottawa Hospital and University of Ottawa, The Ottawa Hospital Academic Medical Organization, Kidney Foundation of Canada, and Physician Services Incorporated Foundation; is an editorial board member of the Canadian Journal of Kidney Health and Disease; and is a member of the Contrast-Associated Acute Kidney Injury guideline panel for the Canadian Association of Radiologists. B. R. is a guideline methodologist for American Thoracic Society, the Society of Critical Care Medicine, and Canadian Blood Services; is the Knowledge Translation director for Canadian Critical Care Society; is the grants and manuscripts chair for Canadian Critical Care Trials Group, and in a guideline group member for multiple guidelines. S. R. B. is the chair of the Clinical Pharmacy and Pharmacology section for the Society of Critical Care Medicine (not albumin use related), is a paid consultant for Wolters Kluwer (Lexicomp), is a Society of Critical Care Medicine Social Media Committee member, is a Surviving Sepsis Campaign Research Committee member, and has received a research grant from the National Institute of General Medicine Sciences. L. C. is a guideline group member for the British Society of Gastroenterology (management of ascites in liver cirrhosis), is involved in peer-reviewed publications (multiple topics including relevant to albumin use), received lecturer honoraria for the Canadian Liver Conference 2022, is a hepatology consultant for the Royal Free Hospital London, and is a Liver Committee member of the British Society of Gastroenterology. M. F. receives consultant fees from Cerus Corporation and Biocogniv, Inc.; has received honoraria from Grifols (none were albumin related); is a board member for Project Santa Fe Foundation and the American Board of Pathology; is the Histocompatibility and Identity Testing Committee Chair for College of American Pathologists; is co-team leader for the Biomedical Excellence for Safer Transfusion (BEST)Collaborative; and is the Editorial Committee co-chair for the ICTMG. R. J. has received fellowship funding from Canadian Blood Services, is an employee of William Osler Health System and the University of Cincinnati Medical Center, and is a panel member for ICTMG Platelet Utilization guideline development group. K. P. serves on the board of directors in North America for International Society for Blood Transfusion (ISBT), is a 2023 Association for the Advancement of Blood and Biotherapies (AABB) Red Blood Cells (RBC) guideline panel member, and is a member of the National Advisory Committee of Blood and Blood Products. P. S. S. is director of the Canadian Neonatal Network, director of the Canadian Preterm Birth Network, director of the International Network to Evaluate Outcomes of Neonates, and an external advisory board member for the Canadian Perinatal Surveillance system (none related to albumin manufacturers). H. S. is a consultant for Terumo and Cerus (not albumin related). Z. M. S. is a consultant and advisory board member of Grifols, Fresenius Kabi, and Novartis; receives research funding from Erydel and Fresenius Kabi; serves on the board of directors for the BEST Collaborative and International Council for Commonality in Blood Banking Automation (ICCBBA), Inc.; is the AABB Committee Chair; is vice chair, treasurer, and committee chair for ICCBBA, Inc.; is treasurer for BEST Collaborative; and has a family member (child) who is a summer intern with Grifols, Inc. T. T. is a paid consultant for Inter-View Partners France, A+A, Bayer HealthCare SAS, BVA, Axess Research, and All Global; has received honoraria from AbbeVie, Gilead Sciences, Advanz Pharma France, and Ipsen Pharma; in the principal investigator of randomized controlled trial Albumin Administration in Cirrhotic Patients With Bacterial Infection and a Systemic Inflammatory Response Syndrome Unrelated to Spontaneous Bacterial Peritonitis (ALB-CIRINF) (ClinicalTrials.gov Identifier, NCT01359813) published in 2015; and is a member of the Liver Cirrhosis-related Complications (LCC)-International Special Interest Group. B. W. is a resident physician at Loma Linda University Medical Center. S. S. is chair of the ICTMG and is an employee of National Health Service Blood and Transplant (NHSBT), a blood service operator in England. However, NHSBT is not a manufacturer of the intervention. N. S. is an employee of Canadian Blood Services; receives research funding from the Canadian Institutes for Health Research (Transfusion Requirements in Younger Patients Undergoing Cardiac Surgery [TRICS-IV] RBC transfusion in young cardiac patients; not related to albumin); is an advisory board member for Fresenius Kabius and Janssen; has received honoraria from the International Financial Corporation of the World Bank, Canadian Blood Services, and Ferring; and serves on the PKD guideline panel and ICTMG guideline panels (Fetal Neonatal Alloimmune Thrombocytopenia [FNAIT], Hemolytic Disease of the Newborn [HDN], platelet transfusion, RBC specifications). None declared (D. F., S. A., M. N., C. P., S. R.). See Appendix 8 for the ICTMG Conflict of Interest Policy., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Inhaled antibiotics are recommended conditionally by international bronchiectasis guidelines for the treatment of patients with bronchiectasis, but results of individual studies are inconsistent. A previous meta-analysis demonstrated promising results regarding the efficacy and safety of inhaled antibiotics in bronchiectasis. Subsequent publications have supplemented the existing body of evidence further in this area., Research Question: To what extent do inhaled antibiotics demonstrate both efficacy and safety as a treatment option for adults with bronchiectasis?, Study Design and Methods: Systematic review and meta-analysis of randomized controlled trials of inhaled antibiotics in adult patients with bronchiectasis. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov for eligible studies. Studies were included if they enrolled adults with bronchiectasis diagnosed by CT imaging and had a treatment duration of at least 4 weeks. The primary end point was exacerbation frequency, with additional key efficacy end points including severe exacerbations, bacterial load, symptoms, quality of life, and FEV 1 . Data were pooled through random-effects meta-analysis., Results: Twenty studies involving 3,468 patients were included. Inhaled antibiotics were associated with reduced number of patients with exacerbations (risk ratio, 0.85; 95% CI, 0.75-0.96), a slight reduction in exacerbation frequency (rate ratio [RR], 0.78; 95% CI, 0.68-0.91), a probable reduction in the frequency of severe exacerbations (RR, 0.48; 95% CI, 0.31-0.74), and a likely slight increase in time to first exacerbation (hazard ratio, 0.80; 95% CI, 0.68-0.94). Inhaled antibiotics likely lead to a slight increase in the Quality of Life Questionnaire-Bronchiectasis respiratory symptom score (mean difference, 2.51; 95% CI, 0.44-4.31) and may reduce scores on the St. George Respiratory Questionnaire (mean difference, -3.13; 95% CI, -5.93 to -0.32). Bacterial load consistently was reduced, but FEV 1 was not changed with treatment. Evidence suggests little to no difference in adverse effects between groups (OR, 0.99; 95% CI, 0.75-1.30). Antibiotic-resistant organisms likely were increased by treatment., Interpretation: In this systematic review and meta-analysis, inhaled antibiotics resulted in a slight reduction in exacerbations, a probable reduction in severe exacerbations, and a likely slight improvement in symptoms and quality of life in adults with bronchiectasis., Trial Registry: International Prospective Register of Systematic Reviews; No.: CRD42023384694; URL: https://www.crd.york.ac.uk/prospero/., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: H. C. reports grants or contracts from the Korean Ministry of Education Basic Science Research Program [Grant 2021R1I1A3052416]; consulting fees from Boryung Pharmaceutical Co., Ltd.; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Boryung Pharmaceutical Co., Ltd. C. S. H. reports consulting fees from 30 Technology, Aradigm, CSL Behring, Chiesi, Gilead, Grifols, GSK, Insmed, Janssen, LifeArc, Meiji, Mylan, Novartis, Pneumagen, Shionogi, Teva, Vertex, and Zambon (personal fees); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Chiesi, Insmed; and payment for expert testimony from Zambon. J. D. C. has received research grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis, Insmed, and Trudell and has received consultancy or speaker fees from Antabio, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Insmed, Janssen, Novartis, Pfizer, Trudell, and Zambon. None declared (R. C.)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Exacerbation frequency strongly influences treatment choices in patients with severe asthma., Research Question: What is the extent of the variability of exacerbation rate across countries and its implications in disease management?, Study Design and Methods: We retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients aged ≥ 18 years who did not initiate any biologics prior to baseline visit. A severe exacerbation was defined as the use of oral corticosteroids for ≥ 3 days or asthma-related hospitalization/ED visit. A series of negative binomial models were applied to estimate country-specific severe exacerbation rates during 365 days of follow-up, starting from a naive model with country as the only variable to an adjusted model with country as a random-effect term and patient and disease characteristics as independent variables., Results: The final sample included 7,510 patients from 17 countries (56% from the United States), contributing to 1,939 severe exacerbations (0.27/person-year). There was large between-country variation in observed severe exacerbation rate (minimum, 0.04 [Argentina]; maximum, 0.88 [Saudi Arabia]; interquartile range, 0.13-0.54), which remained substantial after adjusting for patient characteristics and sampling variability (interquartile range, 0.16-0.39)., Interpretation: Individuals with similar patient characteristics but coming from different jurisdictions have varied severe exacerbation risks, even after controlling for patient and disease characteristics. This suggests unknown patient factors or system-level variations at play. Disease management guidelines should recognize such between-country variability. Risk prediction models that are calibrated for each jurisdiction will be needed to optimize treatment strategies., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: D. P. has advisory board membership with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals, and Thermofisher; has consultancy agreements with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mylan, Mundipharma, Novartis, Pfizer, Teva Pharmaceuticals, and Theravance; has grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mylan, Mundipharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Respiratory Effectiveness Group, Sanofi Genzyme, Teva Pharmaceuticals, Theravance, and UK National Health Service; has received payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, and Teva Pharmaceuticals; has received payment for the development of educational materials from Mundipharma and Novartis; has received payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Mundipharma, Mylan, Novartis, and Thermofisher; has received funding for patient enrollment or completion of research from Novartis; has stock/stock options from AKL Research and Development Ltd, which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 74% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); has 5% shareholding in Timestamp, which develops adherence monitoring technology; is a peer reviewer for grant committees of the Efficacy and Mechanism Evaluation programme and Health Technology Assessment; and was an expert witness for GlaxoSmithKline. E. W. has received honoraria from AstraZeneca, GlaxoSmithKline, and Genentech; and has been an investigator on studies sponsored by AstraZeneca, GlaxoSmithKline, Genentech, Sanofi, Novartis, and Teva Pharmaceuticals, for which her institution has received funding. M. E. W. reports grants and/or personal fees from Novartis, Sanofi, Regeneron, Genentech, Sentien, Restorbio, Equillium, Genzyme, Cohero Health, Teva Pharmaceuticals, Boehringer Ingelheim, AstraZeneca, Amgen, GlaxoSmithKline, Cytoreason, Cerecor, Sound biologic, Incyte, and Kinaset. D. J. J. has received speaker fees and consultancy fees from AZ, GSK, Sanofi Regeneron, and BI; and research funding from AstraZeneca. J. B. has received research grants from AstraZeneca and personnel fees from NuvoAir, outside the submitted work. L. G. H. has received grant funding, participated in advisory boards, and given lectures at meetings supported by Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Hoffmann la Roche, GlaxoSmithKline, Novartis, Theravance, Evelo Biosciences, Sanofi, and Teva Pharmaceuticals; has received grants from MedImmune, Novartis UK, Roche/Genentech Inc, Amgen, Genentech/Hoffman la Roche, AstraZeneca, MedImmune, Glaxo Smith Kline, Aerocrine, and Vitalograph; has received sponsorship for attending international scientific meetings from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, and Napp Pharmaceuticals; has taken part in asthma clinical trials sponsored by AstraZeneca, Boehringer Ingelheim, Hoffmann la Roche, and GlaxoSmithKline for which his institution received remuneration; and is the academic lead for the Medical Research Council Stratified Medicine UK Consortium in Severe Asthma, which involves industrial partnerships with a number of pharmaceutical companies including Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Hoffmann la Roche, and Janssen. P. E. P. has attended advisory boards for AstraZeneca, GlaxoSmithKline, and Sanofi; has given lectures at meetings supported by AstraZeneca and GlaxoSmithKline; has taken part in clinical trials sponsored by AstraZeneca, GlaxoSmithKline, Novartis, and Sanofi, for which his institution received remuneration; and has a current research grant funded by GlaxoSmithKline. D.-W. P. received sponsorship to attend or speak at international meetings, honoraria for lecturing or attending advisory boards, and research grants from the following companies: AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Daiichi Sankyo, Shionogi, and Orient Pharma. B. G. C. declares grants from Chiesi and GlaxoSmithKline; personal fees for advisory board activities from Chiesi, GlaxoSmithKline, Novartis, Sanofi, Teva Pharmaceuticals, and AstraZeneca; and payment for lectures/speaking engagements from Chiesi, Novartis, GlaxoSmithKline, Menarini, and AstraZeneca, outside the submitted work. L. P.-L. reports grants, personal fees, and nonfinancial support from AstraZeneca, Teva Pharmaceuticals, Sanofi, and FAES; personal fees and nonfinancial support from GlaxoSmithKline and Chiesi; personal fees from MSD, TECHDOW PHARMA, and Leo-Pharma; grants and personal fees from GEBRO; and personal fees from GILEAD, outside the submitted work. R. A.-L. has given lectures at meetings supported by AstraZeneca, Boehringer Ingelheim, Novartis, GlaxoSmithKline, and Sanofi; and participated in advisory board fees from GlaxoSmithKline, AstraZeneca, Novartis, and Abbot. D. L.-L. reports personal fees from ALK-Abelló, AstraZeneca national and global, Bayer, Chiesi, Grunenthal, Grin, GlaxoSmithKline national and global, Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, and Carnot; and grants from Abbvie, Bayer, Lilly, Sanofi, Astrazeneca, Pfizer, Novartis, Circassia, UCB, and GlaxoSmithKline, outside the submitted work. M. A.-A. has received advisory board and speaker fees from AstraZeneca, Sanofi, Novartis, and GlaxoSmithKline; and received a grant from Kuwait Foundation for the Advancement of Sciences (KFAS). C. K. R. received consulting/lecture fees from MSD, AstraZeneca, GlaxoSmithKline, Novartis, Takeda, Mundipharma, Boehringer Ingelheim, Teva Pharmaceuticals, Sanofi, and Bayer. T. I. received lecture fees from Kyorin, GlaxoSmithKline, Novartis, Boehringer Ingelheim, and AstraZeneca. E. H. declares personal fees from Sanofi, Regeneron, GlaxoSmithKline, Novartis, AstraZeneca, Stallergenes, and Circassia. G. W. C. has received research grants and lecture or advisory board fees from A. Menarini, Alk-Albello, Allergy Therapeutics, Anallergo, AstraZeneca, MedImmune, Boehringer Ingelheim, Chiesi Farmaceutici, Circassia, Danone, Faes, Genentech, Guidotti Malesci, GlaxoSmithKline, Hal Allergy, Merck, MSD, Mundipharma, Novartis, Orion, Sanofi Aventis, Sanofi, Genzyme/Regeneron, Stallergenes, UCB Pharma, Uriach Pharma, Teva Pharmaceuticals, Thermo Fisher, and Valeas. R. C. has received honoraria for lectures from Aerogen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Teva Pharmaceuticals; is a member of advisory boards for GlaxoSmithKline and Novartis; has received grant support from GlaxoSmithKline and Aerogen; and has patents in the use of acoustics in the diagnosis of lung disease, assessment of adherence, and prediction of exacerbations. N. G. P. has been a speaker and/or advisory board member for Abbott, Abbvie, ALK, Asit Biotech, AstraZeneca, Biomay, Boehringer Ingelheim, GSK, HAL, Faes Farma, Medscape, Menarini, MSD, Novartis, Nutricia, OM Pharma, Regeneron, Sanofi, Takeda, and Viatris. A. I. P. has received fees and honoraria from Menarini, GSK, Novartis, Elpen, Boehringer Ingelheim, AstraZeneca, and Chiesi. C. M. P. has attended advisory boards for AstraZeneca, Novartis, Teva Pharmaceuticals, and Sanofi-Genzyme; has given lectures at meetings supported by AstraZeneca, Novartis, Teva Pharmaceuticals, Sanofi-Genzyme, and GlaxoSmithKline; has taken part in clinical trials sponsored by AstraZeneca, Novartis, MSD, Sanofi-Genzyme, GlaxoSmithKline, and Novartis; and has received educational and research grants from AstraZeneca, Novartis, Teva Pharmaceuticals, GlaxoSmithKline, ALK, and Sanofi-Genzyme. C. A. T.-D. has received fees as advisory board participant and/or speaker from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Sanofi-Aventis; has taken part in clinical trials from AstraZeneca, Novartis, and Sanofi-Aventis; and has received unrestricted grants for investigator-initiated studies at Fundacion Neumologica Colombiana from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Grifols, and Novartis. T. A. P. declares relevant research support from Novartis and Chiesi Pharma. M. H. declares grants and other advisory board fees (made to his institutional employer) from AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, Teva Pharmaceuticals, and Seqirus, for unrelated projects. M. P. declares personal fees and nonfinancial support from AstraZeneca and GlaxoSmithKline. P. G. G. has received speaker fees and grants to his institution from AstraZeneca, GlaxoSmithKline, and Novartis. J. M. reports speaker fees, grants, or advisory boards for AstraZeneca, Sanofi, GSK, Novartis, Inmunotek, Menarini, and Noucor. C. B. reports advisory boards participation for Sanofi, AstraZeneca, Takeda, and ValeoPharma; honorarium for presentations for GlaxoSmithKline, AstraZeneca, Amgen, Grifols, Sanofi, Regeneron, and ValeoPharma; and clinical trials paid to University of British Columbia sponsored by AstraZeneza, GlaxoSmithKline, BioHaven, and Sanofi. S. C. declares receiving conference fees from Novartis S.A de C.V, Glaxosmithkline Mexico, AstraZeneca Mexico, and Sanofi Mexico. M. S. has received honoraria from AstraZeneca, Boehringer Ingelheim, Teva Pharmaceuticals, and GlaxoSmithKline for purposes unrelated to the content of this manuscript; and has received research funding from AstraZeneza and Boehringer Ingelheim directly into his research account from AstraZeneza for unrelated projects. None declared (T. Y. L., C. P. Y., R. R., L. H. M. L., B. M., G. C. C., E. A. C.-C., W. C.)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)