Search

Jill Ohar,1 Robert Tosiello,2 Thomas Goodin,2 Shahin Sanjar2 1Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA; 2Sunovion Pharmaceuticals Inc., Marlborough, MA, USA Background: The efficacy and safety of nebulized glycopyrrolate inhalation solution (GLY), administered twice daily (BID) via the innovative eFlow® Closed System nebulizer (PARI Pharma GmbH, Starnberg, Germany), were demonstrated in two replicate, placebo-controlled, 12-week Phase III studies (GOLDEN 3 and GOLDEN 4). This report evaluates the efficacy and safety of GLY by baseline disease severity and age in the pooled GOLDEN 3 and GOLDEN 4 patient population (N=1,294). Methods: Patients were grouped by baseline predicted post-bronchodilator FEV1 (

Brendan Clark,1 Brian J Wells,2 Amit K Saha,3 Jessica Franchino-Elder,1 Asif Shaikh,4 Bonnie MK Donato,1 Jill A Ohar5 1Health Economics and Outcomes Research, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA; 2Department of Biostatistics and Data Science, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA; 3Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA; 4Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA; 5Department of Medicine, Section of Pulmonary, Critical Care, Allergy and Immunology, Wake Forest School of Medicine, Winston-Salem, NC, USACorrespondence: Jill A Ohar, Department of Medicine, Section of Pulmonary, Critical Care, Allergy and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA, Tel +1 336-406-6733, Fax +1 336-716-7277, Email johar@wakehealth.eduBackground: Patients with chronic obstructive pulmonary disease (COPD) can have low peak inspiratory flow (PIF), especially after hospitalization for acute exacerbation of COPD (AECOPD).Purpose: To characterize patients hospitalized for AECOPD, and to assess the prevalence of low PIF, changes in PIF after hospitalization, and the association of low PIF with healthcare resource utilization (HRU) outcomes.Patients and Methods: A retrospective cohort study was conducted using electronic health record data of hospitalized COPD patients in the Wake Forest Baptist Health system (01/01/2017 through 06/30/2020). Patients with a first eligible AECOPD hospitalization (index hospitalization) who were discharged before 05/31/2020 were included. PIF was measured using the In-Check DIAL™ at both medium-low resistance (R-2) and high resistance (R-5) during the index hospitalization. For R-2 and R-5, PIF was divided into low PIF (< 60 L/min; < 30 L/min) and high PIF (≥ 60 L/min; ≥ 30 L/min) groups. The primary outcome was the prevalence of low PIF. The stability of PIF after hospitalization was described. Adjusted regression models evaluated associations between low PIF and subsequent 30-day readmissions, 90-day readmissions, and HRU outcomes, including hospitalizations, emergency department visits, inpatient days, and intensive care unit (ICU) days.Results: In total, 743 patients with PIF measured at R-2 and R-5 during a AECOPD hospitalization were included. The prevalence of low PIF was 56.9% at R-2 and 14.7% at R-5. PIF values were relatively stable after hospitalization. Adjusted analyses showed significant increases in HRU (all-cause hospitalizations [31%], COPD hospitalizations [33%], COPD inpatient days [46%], and COPD ICU days [24%]) during the follow-up period among patients with low PIF (< 60 L/min) at R-2. The 30- and 90-day readmission risks were similar between patients with low PIF and high PIF.Conclusion: Low PIF is common among patients hospitalized for AECOPD, relatively stable after hospital discharge, and associated with increased HRU.Keywords: AECOPD, electronic health records, healthcare utilization, PIF

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

Jill A Ohar,1 Ayca Ozol-Godfrey,2 Thomas Goodin,2 Shahin Sanjar2 1Department of Internal Medicine, Wake Forest University, Winston-Salem, NC, USA; 2Sunovion Pharmaceuticals Inc., Marlborough, MA, USACorrespondence: Jill A OharDepartment of Internal Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1054, USATel +1 336 716 7765Email johar@wakehealth.eduPurpose: The clinical manifestation of COPD can differ by gender, with women experiencing worse lung function and health-related quality of life than men. Additionally, women tend to report more symptoms given the same disease severity. Accordingly, the impact of gender on efficacy and safety in patients with moderate-to-very-severe COPD was examined following 12 weeks of nebulized glycopyrrolate (GLY) 25 μg twice daily (BID) or placebo.Patients and Methods: GLY and placebo pooled data from the replicate 12-week GOLDEN 3 and 4 studies (n=861) were grouped by gender. Endpoints reported were change from baseline in trough forced expiratory volume in 1 second (FEV1), St George’s Respiratory Questionnaire (SGRQ) and EXAcerbations of COPD Tool-Respiratory Symptoms (EXACT-RS) total scores. Safety was evaluated by reviewing the incidence of adverse events (AEs) and serious AEs.Results: Men (placebo: 54.7%; GLY: 56.1%) were generally older with a greater proportion of high cardiovascular risk and use of background long-acting β2-agonists or inhaled corticosteroids. GLY treatment resulted in significant, clinically important improvements in trough FEV1, regardless of gender. Patients treated with GLY reported significant improvements in SGRQ total score, irrespective of gender; however, the improvement was numerically higher in women. Although EXACT-RS improved in both genders, only women experienced a significant improvement. Overall, GLY was well tolerated with a numerically lower incidence of AEs in men than women.Conclusion: Treatment with nebulized GLY resulted in lung function, SGRQ total score, and EXACT-RS total score improvements regardless of gender. However, only EXACT-RS showed significantly greater improvements in women compared with men. Treatment with GLY was generally well tolerated across genders. These data support the efficacy and safety of GLY 25 μg BID in patients with moderate-to-very-severe COPD, independent of gender. Gender similarities in airflow improvement and differences in symptom-reporting augment the evidence supporting the consideration of individualized treatment plans for COPD patients.Keywords: COPD, gender, LAMA, nebulized glycopyrrolate

Sohini Ghosh,1 Roy A Pleasants,2 Jill A Ohar,3 James F Donohue,1 M Bradley Drummond1 1Division of Pulmonary Diseases and Critical Medicine, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 2Durham VA Medical Center, Durham, NC, USA; 3Department of Medicine, Section of Pulmonary, Critical Care, Allergy, and Immunology, School of Medicine, Wake Forest University, Winston-Salem, NC, USA Purpose: Adequate peak inspiratory flow rate (PIFR) is required for drug dispersion with dry powder inhalers (DPIs). Prevalence of PIFR discordance (suboptimal PIFR with prescribed inhalers) and factors influencing device-specific PIFR are unclear in COPD. The objective of this study was to determine the prevalence of PIFR discordance and associated clinical factors in a stable COPD population. Patients and methods: An observational, single-center, cohort study was conducted including 66 outpatients with COPD. PIFR was measured using the In-Check™ Dial with applied resistance of prescribed inhalers. Participants were defined as discordant if measured PIFR was Results: The median age of the COPD participants was 69.4 years, 92% were white and 47% were female. A total of 48% were using low–medium resistance DPIs (Diskus®/Ellipta®) and 76% used high-resistance DPI (Handihaler®). A total of 40% of COPD participants were discordant to prescribed inhalers. Female gender was the only factor consistently associated with lower PIFR. Shorter height was associated with reduced PIFR for low–medium resistance (r=0.44; P=0.01), but not high resistance (r=0.20; P=0.16). There was no correlation between PIFR by In-Check™ dial and PIFR measured by standard spirometer. Conclusion: PIFR is reduced in stable COPD patients, with female gender being the only factor consistently associated with reduced PIFR. Discordance with prescribed inhalers was seen in 40% of COPD patients, suggesting that many COPD patients do not generate adequate inspiratory force to overcome prescribed DPIs resistance in the course of normal use. Keywords: pulmonary disease, chronic obstructive, dry powder inhaler, peak inspiratory flow rate, drug delivery systems

Jill A Ohar,1 Alyssa Bowling,2 Thomas Goodin,2 Barry Price,2 Ayca Ozol-Godfrey,2 Sanjay Sharma,2 Shahin Sanjar2 1Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA; 2Sunovion Pharmaceuticals Inc, Marlborough, MA, USA Purpose: Bronchodilator reversibility has been reported in patients with COPD, although correlations between reversibility and treatment response are unclear. The effect of reversibility on lung function, health status, and dyspnea was assessed in patients with moderate-to-severe COPD receiving glycopyrrolate (GLY) 15.6 µg twice daily vs placebo in the Glycopyrrolate Effect on syMptoms and lung function 1 and 2 (GEM1 and GEM2) replicate, 12-week, placebo-controlled studies. Patients and methods: Reversibility was defined as a post-bronchodilator increase of ≥12% and ≥0.200 L in FEV1. FEV1 area under the curve from 0 to 12 hours (AUC0–12 h), trough FEV1, St George’s Respiratory Questionnaire (SGRQ) total score, COPD Assessment Test (CAT™) score, Transition Dyspnea Index (TDI) focal score, daily symptom scores, and rescue medication use were assessed by reversibility status. Incidences of adverse events and serious adverse events were also assessed. Results: Data from 846 patients enrolled in GEM1 and GEM2 with known reversibility status were pooled for post hoc analysis. GLY significantly improved FEV1 AUC0–12 h, trough FEV1, SGRQ and CAT total scores, and rescue medication use compared with placebo in reversible and nonreversible patients. Significant improvements in TDI focal score and daily symptom scores with GLY over placebo were observed only among reversible patients. Improvements in FEV1 AUC0-12 h (0.165 vs 0.078 L; P

Ohar JA, Ozol-Godfrey A, Goodin T, Sanjar S. Int J Chron Obstruct Pulmon Dis. 2020;15:995–1004. The authors have advised there is an error in Figure 4B on page 1000. For EXACT-RS responder rates, the OR for both genders are shown to be significant at p

Joshua S Cohen,1 Matthew C Miles,2 James F Donohue,3 Jill A Ohar2 1United Lung and Sleep Clinic, Saint Paul, MN, USA; 2Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA; 3University of North Carolina Chapel Hill, Chapel Hill, NC, USA Abstract: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and health care expenditure worldwide. Relaxation of airway smooth muscle with inhaled bronchodilators is the cornerstone of treatment for stable COPD, with inhaled corticosteroids reserved for those with a history of exacerbations. Tiotropium has occupied center stage in COPD treatment for over 10 years and improves lung function, quality of life, exercise endurance, and reduces the risk of COPD exacerbation. Long-acting β2-agonists (LABAs) improve lung function, reduce dynamic hyperinflation, increase exercise tolerance, health-related quality of life, and reduce acute exacerbation of COPD. The combination of long-acting muscarinic antagonists (LAMAs) and LABAs is thought to leverage different pathways to induce bronchodilation using submaximal drug doses, increasing the benefits and minimizing receptor-specific side effects. Umeclidinium/vilanterol is the first combination of LAMA/LABA to be approved for use in stable COPD in USA and Europe. Additionally, indacaterol/glycopyrronium and aclidinium/formoterol have been approved in Europe and in numerous locations outside USA. Several other agents are in the late stages of development, most of which offer once-daily dosing. The benefits of new LAMA/LABA combinations include improved pulmonary function, dyspnea, and health-related quality of life, and in some cases, reduced exacerbations. These evolving treatments will provide new opportunities and challenges in the management of COPD. Keywords: bronchodilator, fixed-dose combination, chronic bronchitis, emphysema, COPD treatment

Yong Liu,1 Roy A Pleasants,2 Janet B Croft,1 Anne G Wheaton,1 Khosrow Heidari,3 Ann M Malarcher,4 Jill A Ohar,5 Monica Kraft,6 David M Mannino,7 Charlie Strange8 1Division of Population Health, Centers for Disease Control and Prevention, Atlanta, GA, 2Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University School of Medicine, Durham, NC, 3Chronic Disease Epidemiology Office, Department of Health and Environmental Control, South Carolina, SC, 4Office of Smoking and Health, Centers for Disease Control and Prevention, Atlanta, GA, 5Section on Pulmonary, Critical Care, Allergy and Immunologic Disease, Wake Forest University, Winston Salem, NC, 6Department of Medicine, University of Arizona, Phoenix, AZ, 7Division of Pulmonary, Critical Care, and Sleep Medicine, Pulmonary Epidemiology Research Laboratory, University of Kentucky, Lexington, KY, 8Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Medical University of South Carolina, Charleston, SC, USA Background: The purpose of this study was to assess the relationship of smoking duration with respiratory symptoms and history of chronic obstructive pulmonary disease (COPD) in the South Carolina Behavioral Risk Factor Surveillance System survey in 2012.Methods: Data from 4,135 adults aged ≥45 years with a smoking history were analyzed using multivariable logistic regression that accounted for sex, age, race/ethnicity, education, and current smoking status, as well as the complex sampling design.Results: The distribution of smoking duration ranged from 19.2% (1–9 years) to 36.2% (≥30 years). Among 1,454 respondents who had smoked for ≥30 years, 58.3% were current smokers, 25.0% had frequent productive cough, 11.2% had frequent shortness of breath, 16.7% strongly agreed that shortness of breath affected physical activity, and 25.6% had been diagnosed with COPD. Prevalence of COPD and each respiratory symptom was lower among former smokers who quit ≥10 years earlier compared with current smokers. Smoking duration had a linear relationship with COPD (P

Abstract Background Variation in ADAM33 has been shown to be important in the development of asthma and altered lung function. This relationship however, has not been investigated in the population susceptible to COPD; long term tobacco smokers. We evaluated the association between polymorphisms in ADAM33 gene with COPD and lung function in long term tobacco smokers. Methods Caucasian subjects, at least 50 year old, who smoked ≥ 20 pack-years (n = 880) were genotyped for 25 single nucleotide polymorphisms (SNPs) in ADAM33. COPD was defined as an FEV1/FVC ratio < 70% and percent-predicted (pp)FEV1 < 75% (n = 287). The control group had an FEV1/FVC ratio ≥ 70% and ppFEV1 ≥ 80% (n = 311) despite ≥ 20 pack years of smoking. Logistic and linear regressions were used for the analysis. Age, sex, and smoking status were considered as potential confounders. Results Five SNPs in ADAM33 were associated with COPD (Q-1, intronic: p < 0.003; S1, Ile → Val: p < 0.003; S2, Gly → Gly: p < 0.04; V-1 intronic: p < 0.002; V4, in 3' untranslated region: p < 0.007). Q-1, S1 and V-1 were also associated with ppFEV1, FEV1/FVC ratio and ppFEF25–75 (p values 0.001 – 0.02). S2 was associated with FEV1/FVC ratio (p < 0.05). The association between S1 and residual volume revealed a trend toward significance (p value < 0.07). Linkage disequilibrium and haplotype analyses suggested that S1 had the strongest degree of association with COPD and pulmonary function abnormalities. Conclusion Five SNPs in ADAM33 were associated with COPD and lung function in long-term smokers. Functional studies will be needed to evaluate the biologic significance of these polymorphisms in the pathogenesis of COPD.