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Donald A Mahler,1,2 Henrik Watz,3 Rachel Emerson-Stadler,4 John Ritz,5 Asparuh Gardev,4 Asif Shaikh,6 M Bradley Drummond7 1Geisel School of Medicine at Dartmouth, Hanover, NH, USA; 2Valley Regional Hospital, Claremont, NH, USA; 3Pulmonary Research Institute at LungenClinic Grosshansdorf, Grosshansdorf, Germany; 4Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany; 5Syneos Health, Somerset, NJ, USA; 6Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 7Pulmonary Diseases and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USACorrespondence: Donald A Mahler, Tel +1 603 542-6777, Email mahlerdonald@gmail.comBackground: In patients with COPD, inhalation ability should be assessed when considering inhaler choice. To evaluate whether the soft mist inhaler (SMI) is suitable for COPD patients irrespective of inhalation ability, the TRONARTO study investigated the efficacy of dual long-acting bronchodilator therapy delivered via the Respimat® SMI on lung function in patients with COPD stratified by inhalation ability. Tiotropium/olodaterol delivered via the SMI was effective both in patients with peak inspiratory flow (PIF) < 60 L/min and PIF ≥ 60 L/min, measured against medium-low resistance.Methods: This congress compilation summarizes post hoc analyses from the TRONARTO study presented at the annual American Thoracic Society 2022 and European Respiratory Society 2022 meetings. These analyses evaluated PIF in over 200 patients, with PIF measurements taken daily at home for 4 weeks, and in the clinic at baseline, Weeks 2 and 4.Results: Overall, 57.9% of patients had a PIF range (difference between lowest and highest PIF measurements) < 20 L/min (12.4% of patients had PIF range < 10 L/min). At-home PIF range decreased over the study period, suggesting that inhaler training/repeated PIF measurements may help to make patients’ inspiratory

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)

Jill A Ohar,1 Gary T Ferguson,2 Donald A Mahler,3 M Bradley Drummond,4 Rajiv Dhand,5 Roy A Pleasants,4,6 Antonio Anzueto,7 David MG Halpin,8 David B Price,9,10 Gail S Drescher,11 Haley M Hoy,12 John Haughney,9 Michael W Hess,13 Omar S Usmani14 1Section of Pulmonary, Critical Care, Allergy, and Immunology, School of Medicine, Wake Forest University, Winston-Salem, NC, USA; 2Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, USA; 3Geisel School of Medicine at Dartmouth, Hanover, NH, USA; 4Division of Pulmonary Diseases and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 5Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN, USA; 6Department of Quality, University of Michigan, Ann Arbor, MI, USA; 7Pulmonology Section, University of Texas Health, and South Texas Veterans Health Care System, San Antonio, TX, USA; 8University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, UK; 9Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 10Observational and Pragmatic Research Institute, Singapore; 11Pulmonary Services Department, MedStar Washington Hospital Center, Washington, DC, USA; 12Transplant Center, Vanderbilt University Medical Center, Nashville, TN, USA; 13COPD Foundation, Kalamazoo, MI, USA; 14National Heart and Lung Institute, Imperial College London and Royal Brompton Hospital, London, UKCorrespondence: Jill A OharSection of Pulmonary, Critical Care, Allergy, and Immunology, School of Medicine, Wake Forest University, 1834 Wake Forest Road, Winston-Salem, NC 27109, USATel +1 336-716-8426Fax +1 336-716-7277Email johar@wakehealth.eduAbstract: Dry powder inhalers (DPIs) are breath actuated, and patients using DPIs need to generate an optimal inspiratory flow during the inhalation maneuver for effective drug delivery to the lungs. Howeve

Donald A Mahler,1,2 Andrea Ludwig-Sengpiel,3 Gary T Ferguson,4 Alberto de la Hoz,5 John Ritz,6 Asif Shaikh,7 Henrik Watz8 1Geisel School of Medicine at Dartmouth, Hanover, NH, USA; 2Section of Pulmonary Medicine, Valley Regional Hospital, Claremont, NH, USA; 3KLB Gesundheitsforschung Lübeck GmbH, Lübeck, Germany; 4Department of Medicine, Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, USA; 5Cardio-Metabolism and Respiratory, Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany; 6Biostatistics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 7Clinical Development & Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 8Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, GermanyCorrespondence: Donald A MahlerMedicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USATel +1 603 542-6777Fax +1 603 543-5613Email mahlerdonald@gmail.comBackground: Inhaled bronchodilator therapy is currently the mainstay of treatment for patients with chronic obstructive pulmonary disease (COPD). Some inhalers require patients to achieve certain inhalation efforts either to activate the device or to deliver medication to the site of action. For dry powder inhalers, low peak inspiratory flow (PIF) can result in poor medication delivery but the clinical significance of this is not well understood.Methods: TRONARTO was a 4-week, randomized, double-blind, placebo-controlled, multicenter, parallel-group study which stratified patients with moderate-to-severe COPD according to their PIF against medium-low resistance at screening. Patients were randomized to receive tiotropium/olodaterol (5 μg/5 μg) or matched placebo delivered via the Respimat® Soft Mist™ inhaler (SMI). After 4 weeks of treatment, we assessed change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve

James F Donohue,1 Donald A Mahler,2,3 Sanjay Sethi4 1Pulmonary Medicine, UNC School of Medicine, Chapel Hill, NC, USA; 2Geisel School of Medicine at Dartmouth, Hanover, NH, USA; 3Director of Respiratory Services, Valley Regional Hospital, Claremont, NH, USA; 4University at Buffalo, State University of New York, Buffalo, NY, USACorrespondence: James F DonohueUNC School of Medicine, 4125 Bioinformatics Building CB#7020, Chapel Hill, NC 27599-0001, USATel +1 984-974-5703Fax +1 984-974-5737Email James_Donohue@med.unc.eduAbstract: Bronchodilation with muscarinic antagonists, β2-agonists, and inhaled corticosteroids remains the foundation of pharmaceutical treatment for patients with stable COPD. These drugs are delivered from a variety of devices, including dry powder inhalers, pressurized metered-dose inhalers, soft-mist inhalers, or nebulizers. Nebulized delivery is often preferable in patients who are elderly, are cognitively impaired, are unable to generate sufficient inspiratory force to use their inhaler, have difficulty coordinating hand-breath activity, are too dyspneic to hold their breath for a sufficient time, and/or may be acutely ill. Revefenacin, a once-daily long-acting muscarinic antagonist for nebulization recently approved by the US FDA for the treatment of patients with COPD, was discovered and developed using “duration and lung selectivity-by-design.” This strategy selected a molecule with a high lung-selective index to maximize bronchodilation and limit systemic anti-muscarinic side effects. In early-phase clinical studies, revefenacin for nebulization led to a rapid onset of bronchodilation that was sustained for 24 hrs in patients with moderate to severe COPD. Revefenacin also demonstrated minimal systemic exposure and good tolerability in these studies. Statistically and clinically significant improvements in lung function (ie, peak and/or trough FEV1) relative to placebo were observed with revefenacin in Phase III cli

Jean-Bernard Gruenberger,1 Jeffrey Vietri,2 Dorothy L Keininger,1 Donald A Mahler3 1Health Economics and Outcomes Research, Novartis Pharma AG, Basel, Basel-Stadt, Switzerland; 2Health Outcomes Practice, Kantar Health, Horsham, PA, 3Geisel School of Medicine at Dartmouth, Hanover, NH, USA Objective: Dyspnea is a defining symptom in the classification and treatment of chronic obstructive pulmonary disease (COPD). However, the degree of variation in burden among symptomatic COPD patients and the possible correlates of burden remain unclear. This study was conducted to characterize patients in Europe currently being treated for COPD according to the level of dyspnea in terms of sociodemographics, health-related quality of life, work productivity impairment, and health care resource use assessed by patient reports.Methods: Data were derived from the 5-EU 2013 National Health and Wellness Survey (N=62,000). Respondents aged ≥40 years who reported currently using a prescription for COPD were grouped according to their level of dyspnea as per the Global Initiative for Chronic Obstructive Lung Disease guidelines and compared on health status (revised Short Form 36 [SF-36]v2), work impairment (Work Productivity and Activity Impairment questionnaire), and number of health care visits in the past 6 months using generalized linear models with appropriate distributions and link functions.Results: Of the 768 respondents who met the inclusion criteria, 245 (32%) were considered to have higher dyspnea (equivalent to modified Medical Research Council score ≥2). Higher dyspnea was associated with decrements ranging from 3.9 to 8.2 points in all eight domains of the SF-36 health profile after adjustment for sociodemographics, general health characteristics, and length of COPD diagnosis; mental component summary scores and Short Form-6D health utility scores were lower by 3.5 and 0.06 points, respectively. Adjusted mean activity impairment (55% vs 37%, P<0.001) and