Clinical Burden of Chronic Obstructive Pulmonary Disease in Patients with Suboptimal Peak Inspiratory Flow.

Introduction: Many patients with chronic obstructive pulmonary disease (COPD) may derive inadequate benefit from dry powder inhalers (DPIs) because of suboptimal peak inspiratory flow (sPIF). Objectives: To assess the clinical burden of COPD by characterizing the clinical characteristics of participants with sPIF against medium-low resistance DPIs versus those with optimal PIF (oPIF) from two phase 3 clinical trials. Methods: Baseline data were collected from two randomized, controlled, phase 3 trials (NCT03095456; NCT02518139) in participants with moderate-to-severe COPD. oPIF (60 L/min) against the medium-low resistance DPIs was used as the threshold for defining the PIF subgroups (<60 L/min (sPIF) vs ≥60 L/min (oPIF)). Results: Most participants included in this analysis were White (92%) and male (63%); the mean (range) age was 65 (43-87) years. Participants with sPIF had significantly greater dyspnea than those with oPIF as measured using the modified Medical Research Council scoring (mean (95% CI): 2.1 (2.0-2.2) vs 1.6 (1.4-1.7); P < 0.001) and baseline dyspnea index (mean (95% CI): 5.1 (4.9-5.4) vs 6.1 (5.8-6.3); P < 0.001). Based on COPD Assessment Test scores, participants with sPIF had a higher COPD symptom burden than those with oPIF (mean (95% CI): 21.5 (19.7-23.3) vs 19.5 (18.6-20.4); P = 0.05). Conclusion: In these trials, participants with COPD who had sPIF against the medium-low resistance DPIs had more dyspnea and worse health status than those with oPIF. These results demonstrate that sPIF is associated with a higher clinical burden as measured by patient-reported outcomes.

Utility of peak inspiratory flow measurement for dry powder inhaler use in chronic obstructive pulmonary disease.

PURPOSE OF REVIEW: Every type of dry powder inhaler (DPI) device has its own intrinsic resistance. A patient's inspiratory effort produces a pressure drop that determines the inspiratory flow, depending on the inhaler's specific internal resistance. Optimal peak inspiratory flow (PIF) is needed for effective release of dry powder, disaggregation of drug-carrier agglomerates, and optimal deposition of respirable drug particles, particularly generation of a high fine-particle fraction to reach the small airways of the lungs. However, standardized recommendations for PIF measurements are lacking and instructions appeared vague in many instances. RECENT FINDINGS: Suboptimal PIFs are common in outpatient chronic obstructive pulmonary disease (COPD) patients and during acute exacerbations of COPD, and are associated with increased healthcare resource utilization. There is significant variation in the results of studies which is in part related to different definitions of optimal flow rates, and considerable variation in how PIF is measured in clinical and real-life studies. SUMMARY: Standardization of technique will facilitate comparisons among studies. Specific recommendations for PIF measurement have been proposed to standardize the process and better ensure accurate and reliable PIF values in clinical trials and clinical practice. Clinicians can then select and personalize the most appropriate inhaler for their patients and help them achieve the optimal PIF needed for effective drug dispersion.

Improvements in health status with revefenacin, a once-daily, nebulized, long-acting muscarinic antagonist for chronic obstructive pulmonary disease.

BACKGROUND: Replicate, 12-week, phase 3 trials (0126 and 0127) of once-daily nebulized revefenacin 175 µg vs placebo demonstrated significant bronchodilation and improvements in health status in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). This post hoc analysis evaluated improvement in patient-reported outcomes (PROs), including the St. George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT), and Clinical COPD Questionnaire (CCQ) in both women and men. METHODS: Participants were pooled from the two 12-week studies (411 [51%] women and 401 [49%] men). Changes in PROs were assessed overall and separately in men and women. RESULTS: Revefenacin improved SGRQ and CAT total scores from baseline in both studies; improvement in CCQ total score reached significance only in 0126. In pooled data, a greater proportion of patients achieved clinically meaningful response in SGRQ score (≥4-unit decrease from baseline) with revefenacin vs placebo (odds ratio, 1.5; 95% confidence interval, 1.1-2.1; P = 0.012). Clinically meaningful responses were also seen in CAT (≥2-unit decrease from baseline) and CCQ (≥0.4-unit decrease from baseline) scores with revefenacin vs placebo. When stratified by sex, improvements from baseline in SGRQ, CAT, and CCQ scores following revefenacin vs placebo reached statistical significance only in women. CONCLUSIONS: Maintenance treatment with revefenacin improved health status in patients with moderate to very severe COPD; however, the effect was more pronounced for women than men. CLINICALTRIALS: GOV: NCT02459080; NCT02512510.

Low Peak Inspiratory Flow Rates are Common Among COPD Inpatients and are Associated with Increased Healthcare Resource Utilization: A Retrospective Cohort Study.

Background: 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.

Measuring Peak Inspiratory Flow in Patients with Chronic Obstructive Pulmonary Disease.

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.

Will Remotely Based Pulmonary Rehabilitation Water Down Its Effectiveness?

Despite numerous benefits, traditional Pulmonary Rehabilitation (PR) as a resource remains underutilized in chronic lung disease. Less than 3% of eligible candidates for PR attend one or more sessions after hospitalization due to many barriers, including the ongoing COVID-19 pandemic. Emerging alternative models of PR delivery such as home-based PR, tele-rehabilitation, web-based PR, or hybrid models could help address these barriers. Numerous studies have tested the feasibility, safety, and efficacy of these methods, but there is wide variability across studies and methods. We conducted a literature review to help determine if these alternative delivery methods watered down the effectiveness of PR. To evaluate the effectiveness of remotely based PR, the authors performed a literature search for randomized controlled trials (RCTs), cohort studies, and case series using PubMed, CINAHL, and Medline to identify relevant articles through 1 May 2021. Twenty-six applicable studies were found in which 11 compared tele-rehabilitation to conventional clinic-based PR; 11 evaluated tele-rehabilitation using the patient's baseline status as control; and four compared tele-rehabilitation to no rehabilitation. Despite the different technologies used across studies, tele-rehabilitation was found to be both a feasible and an efficacious option for select patients with lung disease. Outcomes across these studies demonstrated similar benefits to traditional PR programs. Thus the existing data does not show that remotely based PR waters down the effectiveness of conventional PR. Use of remotely based PR is a feasible and effective option to deliver PR, especially for patients with significant barriers to conventional clinic-based PR. Additional, well-conducted RCTs are needed to answer the questions regarding its efficacy, safety, cost-effectiveness and who, among patients with COPD and other lung diseases, will derive the maximum benefit.

Novel LRRK2 mutations and other rare, non-BAP1-related candidate tumor predisposition gene variants in high-risk cancer families with mesothelioma and other tumors.

There is irrefutable evidence that germline BRCA1-associated protein 1 gene (BAP1) mutations contribute to malignant mesothelioma (MM) susceptibility. However, BAP1 mutations are not found in all cases with evidence of familial MM or in other high-risk cancer families affected by various cancers, including MM. The goal of this study was to use whole genome sequencing (WGS) to determine the frequency and types of germline gene variants occurring in 12 MM patients who were selected from a series of 141 asbestos-exposed MM patients with a family history of cancer but without a germline BAP1 mutation. WGS was also performed on two MM cases, a proband and sibling, from a previously reported family with multiple cases of MM without the inheritance of a predisposing BAP1 mutation. Altogether, germline DNA sequencing variants were identified in 21 cancer-related genes in 10 of the 13 probands. Germline indel, splice site and missense mutations and two large deletions were identified. Among the 13 MM index cases, 6 (46%) exhibited one or more predicted pathogenic mutations. Affected genes encode proteins involved in DNA repair (ATM, ATR, BRCA2, BRIP1, CHEK2, MLH3, MUTYH, POLE, POLE4, POLQ and XRCC1), chromatin modification (ARID1B, DNMT3A, JARID2 and SETD1B) or other cellular pathways: leucine-rich repeat kinase 2 gene (LRRK2) (two cases) and MSH4. Notably, somatic truncating mutation or deletions of LRRK2 were occasionally found in MMs in The Cancer Genome Atlas, and the expression of LRRK2 was undetectable or downregulated in a majority of primary MMs and MM cell lines we examined, implying that loss of LRRK2 expression is a newly recognized tumor suppressor alteration in MM.

The Role of ICS/LABA Fixed-Dose Combinations in the Treatment of Asthma and COPD: Bioequivalence of a Generic Fluticasone Propionate-Salmeterol Device.

Both asthma and chronic obstructive pulmonary disease (COPD) are inflammatory chronic respiratory conditions with high rates of morbidity and mortality worldwide. The objectives of this review are to briefly describe the pathophysiology and epidemiology of asthma and COPD, discuss guideline recommendations for uncontrolled disease, and review a new generic option for the treatment of asthma and COPD. Although mild forms of these diseases may be controlled with as-needed pharmacotherapy, uncontrolled or persistent asthma and moderate or severe COPD uncontrolled by bronchodilators with elevated eosinophilia or frequent exacerbations may require intervention with combination therapy with inhaled corticosteroids (ICS) and long-acting beta agonists (LABAs), according to international guidelines. Fixed-dose combinations of ICS/LABA are commonly prescribed for both conditions, with fluticasone propionate (FP) and salmeterol forming a cornerstone of many treatment plans. An oral inhalation powder containing the combination of FP and salmeterol has been available as Advair Diskus® in the United States for almost 20 years, and the first and only substitutable generic version of this product has recently been approved for use: Wixela™ Inhub™. Bioequivalence of Wixela Inhub and Advair Diskus has been established. Furthermore, the Inhub inhaler was shown to be robust and easy to use, suggesting that Wixela Inhub may provide an alternative option to Advair Diskus for patients with asthma or COPD requiring intervention with an ICS/LABA.

Long-Term Noninvasive Ventilation in Chronic Stable Hypercapnic Chronic Obstructive Pulmonary Disease. An Official American Thoracic Society Clinical Practice Guideline.

Background: Noninvasive ventilation (NIV) is used for patients with chronic obstructive pulmonary disease (COPD) and chronic hypercapnia. However, evidence for clinical efficacy and optimal management of therapy is limited.Target Audience: Patients with COPD, clinicians who care for them, and policy makers.Methods: We summarized evidence addressing five PICO (patients, intervention, comparator, and outcome) questions. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to evaluate the certainty in evidence and generate actionable recommendations. Recommendations were formulated by a panel of pulmonary and sleep physicians, respiratory therapists, and methodologists using the Evidence-to-Decision framework.Recommendations:1) We suggest the use of nocturnal NIV in addition to usual care for patients with chronic stable hypercapnic COPD (conditional recommendation, moderate certainty); 2) we suggest that patients with chronic stable hypercapnic COPD undergo screening for obstructive sleep apnea before initiation of long-term NIV (conditional recommendation, very low certainty); 3) we suggest not initiating long-term NIV during an admission for acute-on-chronic hypercapnic respiratory failure, favoring instead reassessment for NIV at 2-4 weeks after resolution (conditional recommendation, low certainty); 4) we suggest not using an in-laboratory overnight polysomnogram to titrate NIV in patients with chronic stable hypercapnic COPD who are initiating NIV (conditional recommendation, very low certainty); and 5) we suggest NIV with targeted normalization of PaCO2 in patients with hypercapnic COPD on long-term NIV (conditional recommendation, low certainty).Conclusions: This expert panel provides evidence-based recommendations addressing the use of NIV in patients with COPD and chronic stable hypercapnic respiratory failure.

In Vitro Effect of Different Airflow Rates on the Aerosol Properties of Nebulized Glycopyrrolate in the eFlow® Closed System and Tiotropium Delivered in the HandiHaler®.

INTRODUCTION: Personalized therapy for patients with COPD requires appropriate choice of drug and delivery device. Inhalers and nebulizers vary in their drug delivery characteristics, particularly the need for passive or active patient inhalation for appropriate drug dispersal and delivery. In this in vitro analysis, we assessed the aerosol performance and drug delivery of two long-acting muscarinic antagonists, glycopyrrolate (GLY; 25 µg solution; 1 ml) and tiotropium (TIO; 18 µg powder) through their respective delivery systems: the eFlow® Closed System (CS) vibrating membrane nebulizer and the HandiHaler® dry-powder inhaler (DPI). METHODS: The aerosol performances of the eFlow® CS nebulizer and the HandiHaler® were determined using the Next Generation cascade Impactor. The delivered dose of GLY and TIO was determined using different breathing patterns, which varied in tidal volume and peak inspiratory flow rate, respectively, to simulate breathing conditions ranging from normal to severe obstruction. RESULTS: Aerodynamic particle analysis showed generally similar mass median aerodynamic diameter (MMAD, range, 3.6-4.6 µm) and fine particle fraction (FPF, range, 48.2%-63.7%) with GLY delivered using the eFlow® CS nebulizer under all breathing patterns tested. TIO, delivered via the HandiHaler®, showed variations in MMAD (range, 3.8-5.8 µm) and FPF (range, 16.1%-32.4%) under different inspiratory flow rates. The majority of GLY was deposited in stages 2-5 of the impactor, which corresponds with particle sizes in the respirable range (< 5 µm), whereas a large proportion of TIO was deposited in the throat/mouthpiece pre-separator, irrespective of test conditions. The median residual dose of GLY with eFlow® CS was notably lower compared to that of TIO with HandiHaler® (2.4%-4.4% vs. 40%-67%, respectively). CONCLUSIONS: These simulation results highlight the different deposition patterns generated by a DPI device and a vibrating membrane nebulizer, which may help inform device selection and treatment decision in COPD management.

Effect of Gender on Lung Function and Patient-Reported Outcomes in Patients with COPD Receiving Nebulized Glycopyrrolate.

Purpose: 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 ß2-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.

Peak Inspiratory Flows: Defining Repeatability Limits and a Predictive Equation for Different Inhalers.

BACKGROUND: Peak inspiratory flow (PIF) has been proposed as a measure to assess a patient's ability to use dry powder inhalers (DPIs). However, robust quality criteria to determine a repeatability limit for measuring PIF are lacking. RESEARCH QUESTIONS: What are the repeatability limits for measuring PIF? What is the relationship between PIF measured using the In-Check DIAL device at Diskus (GlaxoSmithKline; PIFD) and HandiHaler (Boehringer Ingelheim; PIFHH) resistances? STUDY DESIGN AND METHODS: Data from a randomized, controlled, phase 3 trial (study 0149; see Clinical Trial Registration data) were used to define repeatability limits for PIF. In addition, a model to characterize the relationship between PIF measured with the In-Check DIAL device at PIFD and PIFHH was defined using data from two randomized, controlled, phase 3 trials (studies 0128 and 0149). RESULTS: In study 0128, the mean values (SD) for PIF at zero resistance and PIFHH were 84.6 (33.4) and 57.3 (26.1) L/min, respectively. In study 0149, the mean values (SD) for PIFD and PIFHH were 42.4 (11.2) and 29.0 (8.3) L/min, respectively. At the mean level, the mean difference between measurement attempts for PIFD and PIFHH was small, < 5 and < 3 L/min, respectively. The repeatability limit was determined as 10 and 5 L/min for PIFD and PIFHH, respectively. Modeling the relationship between PIFD and PIFHH, after controlling for significant covariates, demonstrated that a PIFD value of 60 L/min was approximately equivalent to PIFHH of 40 L/min. INTERPRETATIONS: This analysis demonstrated that the two highest values of PIF using the In-Check DIAL device among three inspiratory efforts, met the repeatability limit. Altogether, these data provide guidance for measuring PIF against the simulated resistance of a specific DPI in clinical practice and research studies. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; Nos.: NCT02518139 (study 0128) and NCT03095456 (study 0149); URL: www.clinicaltrials.gov.

The Role of Guaifenesin in the Management of Chronic Mucus Hypersecretion Associated with Stable Chronic Bronchitis: A Comprehensive Review.

Chronic obstructive pulmonary disease is the third leading cause of death and disease burden worldwide. It includes a spectrum of diseases including chronic bronchitis which is characterized by overproduction, hypersecretion and decreased elimination of mucus. Chronic bronchitis has numerous clinical consequences, including predisposition to lower respiratory tract infections, accelerated decline in lung function, increased exacerbation rate and decreased health-related quality of life.Although the inflammatory mechanisms responsible for mucus cell metaplasia in chronic obstructive pulmonary disease and stable chronic bronchitis are poorly understood, the main goals of therapy are to decrease mucus hypersecretion by controlling inflammation and to increase mucus clearance. Non-pharmacological measures include smoking cessation and chest physiotherapy. Pharmacological interventions include expectorants and mucolytics together with long-acting beta2-adrenergic receptor agonists, anticholinergics, glucocorticoids, phosphodiesterase-4 inhibitors, antioxidants, and antibiotics.Guaifenesin is an expectorant that is thought to increase hydration and decrease viscosity of mucus leading to improved clearance of accumulated secretions from the upper and lower airway. Although guaifenesin has a Food and Drug Administration Over-the-Counter (OFC) Monograph indication to "help loosen phlegm (mucus) and thin bronchial secretions in patients with stable chronic bronchitis," there is limited published evidence of either mechanism of action or clinical efficacy in this disease state. Here we review the pathophysiology and consequences of chronic mucus hypersecretion and examine the evidence for the use of guaifenesin in patients with stable chronic bronchitis.

Nebulized Versus Dry Powder Long-Acting Muscarinic Antagonist Bronchodilators in Patients With COPD and Suboptimal Peak Inspiratory Flow Rate.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) and suboptimal peak inspiratory flow rate (sPIFR) may not benefit optimally from dry powder inhalers (DPI) because of inadequate inspiratory flow. Nebulized bronchodilators may provide a better alternative. We compared bronchodilation with the long-acting muscarinic antagonist (LAMA) revefenacin for nebulization versus the DPI LAMA tiotropium, in patients with COPD and sPIFR (< 60 L/min against the resistance of Diskus®). METHODS: This was a randomized, double-blind, double-dummy, 28-day Phase 3b study in patients with COPD enrolled based on sPIFR. The primary endpoint was trough forced expiratory volume in 1 second (FEV1) on Day 29 for revefenacin for nebulization versus tiotropium HandiHaler® DPI. RESULTS: We enrolled 206 patients with mean (standard deviation) age, 65 (8) years; percent predicted FEV1, 37 (16)%; PIFR, 45 (12) L/min. In the intent-to-treat (ITT) population, revefenacin improved trough FEV1 from baseline; however, the difference versus tiotropium was not significant (least squares [LS] mean difference [standard error], 17.0 [22.4] mL, P=0.4461). In a prespecified analysis of patients with FEV1 < 50% predicted, revefenacin produced an LS mean difference (95% confidence interval [CI]), 49.1 (6.3-91.9) mL in trough FEV1 and 103.5 (7.7-199.3) mL in forced vital capacity versus tiotropium. Revefenacin produced >100 mL increase in FEV1 in 41.6% versus 34.4% of patients with tiotropium in ITT and 41.4% versus 25.7% of patients in FEV1 < 50% predicted populations. CONCLUSIONS: Revefenacin did not produce significant improvements in FEV1 versus tiotropium in the ITT population, but increased trough FEV1 in patients with FEV1 < 50% predicted and sPIFR. Clinical Trial Registration (www.Clinicaltrials.gov): Study 0149 (NCT03095456).

Preoperative Sleep Questionnaires Identify Medical Emergency Team Activation in Older Adults.

Patients with obstructive sleep apnea (OSA) have increased postoperative complications that are important for patient safety and healthcare utilization. Questionnaires help identify patients at risk for OSA; however, among older adults who preoperatively self-administered OSA questionnaires, the frequency of postoperative Medical Emergency Team Activation (META), rapid response, code blue, code stroke, is unknown. OBJECTIVES: Identify whether having OSA questionnaires completed by patients is feasible in the preoperative clinic. Determine the frequency of META among older patients at risk for OSA. DESIGN AND INTERVENTION: Cohort of prospective patients independently completed 2 OSA questionnaires in a preoperative clinic, STOP-Bang (SB) and ISNORED (IS). Observers blinded to questionnaire responses recorded incidence of META. SETTING AND PARTICIPANTS: Of the 898 consecutive patients approached in the preoperative assessment clinic and surgical navigation center, 575 (64%) consented and completed the questionnaires in <5 minutes and were included in the analysis. MEASURES: Sleep questionnaire responses and frequency of inpatient postoperative META. RESULTS: With an affirmative response to ≥3 questions on either questionnaire, 65% of patients enrolled were at risk for OSA. Of these, 3.1% sustained an META. In patients at risk for OSA, META occurred in 7.6% (SB+) and 7.2% (IS+) vs 2.5% (SB+) and 1.7% (IS+) for low risk. METAs were disproportionately higher among patients aged ≥65 years (6.3% vs 1.7%; P < .018), American Society of Anesthesiologists (ASA) physical status class ≥3, and IS+. All patients with META positively answered ≥3 of 15 components of the 2 questionnaires. CONCLUSIONS/IMPLICATIONS: Preoperative, self-administration of SB and IS questionnaires is feasible. Overall, 65% of those with affirmative responses to ≥3 questions were at risk for OSA and associated with a disproportionate number of postoperative META in older patients. Additionally, risk of OSA identified by preoperative sleep questionnaires was associated with postoperative META among older adults. Use of clinical tools and OSA questionnaires may improve preoperative identification of META in this population.

Efficacy of Indacaterol/Glycopyrrolate in Patients with COPD by Airway Reversibility at Baseline: A Pooled Analysis of the FLIGHT1 and FLIGHT2 12-Week Studies.

Bronchodilator reversibility occurs in patients with COPD. Pooled analysis of two 12-week, placebo-controlled randomised studies (FLIGHT1 [NCT01727141]; FLIGHT2 [NCT01712516]) assessed the effect of bronchodilator reversibility on lung function, patient-reported outcomes, and safety in 2,043 patients with moderate-to-severe COPD treated with indacaterol/glycopyrrolate (IND/GLY) 27.5/15.6 µg twice daily. Reversibility was defined as post-bronchodilator increase in forced expiratory volume in one second (FEV1) of ≥12% and ≥0.200 L. Overall, mean reversibility (mean post-bronchodilator FEV1 increase) was 22.8%, and 54.5% of patients met reversibility criteria. IND/GLY resulted in significant (p < 0.05) placebo-adjusted improvements from baseline at Week 12 in reversible and non-reversible patients in FEV1 area under the curve from 0 to 12 hours (0.308 L and 0.170 L, respectively), trough FEV1 (0.260 L and 0.174 L), St. George's Respiratory Questionnaire total score (-6.3 and -3.5), COPD Assessment Test total score (-2.3 and -1.2), daily rescue medication use (-1.52 and -0.79), and daily total symptom score (-0.86 and -0.63); Transition Dyspnoea Index focal score also showed improvements (1.93 and 1.29) at Week 12, irrespective of reversibility status. Improvements in lung function and rescue medication use were significantly (p < 0.05) greater in IND/GLY patients in the reversible subgroup compared with the non-reversible subgroup. The safety profile was similar across treatment groups and reversibility subgroups. Overall, treatment with IND/GLY led to significant improvements in lung function and PROs in patients with moderate-to-severe COPD, regardless of reversibility status, with greater improvements in the reversible subgroup. Safety profile was not affected by reversibility status.

Prevalence and factors associated with suboptimal peak inspiratory flow rates in COPD.

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 <30 L/min and <60 L/min for high and low-medium resistance devices, respectively, using an inspiratory effort the participant normally used with their prescribed DPI. 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.

Efficacy and safety of glycopyrrolate in patients with COPD by reversibility: pooled analysis of GEM1 and GEM2 12-week studies.

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<0.001) and trough FEV1 (0.173 vs 0.070 L; P<0.001) were clinically relevant (based on minimal clinically important differences) and significantly greater in reversible compared with nonreversible patients receiving GLY. The safety profile of GLY was not affected by reversibility status. CONCLUSION: In this post hoc analysis, GLY was associated with significant improvements in lung function and patient-reported outcomes compared with placebo, mostly independent of reversibility status. In patients receiving GLY, improvements in lung function were greater in reversible compared with nonreversible patients. Reversibility status did not meaningfully impact the safety profile of GLY.

The Role of Inhalation Delivery Devices in COPD: Perspectives of Patients and Health Care Providers.

Background: Inhaled medications form the foundation of pharmacologic treatment for chronic obstructive pulmonary disease (COPD).The Delivery Makes a Difference (DMaD) project was conducted to better understand health care provider (HCP) and patient perspectives about the role of inhalation delivery devices in COPD, and to examine the nature of educational efforts between HCPs and patients on proper device technique. Methods: Data were derived from 2 original quantitative, web-based, descriptive, cross-sectional surveys distributed to HCPs who manage COPD (n=513) and patients with COPD (n=499) in the United States. Descriptive statistics were used to assess data across important demographic variables. Inferential statistics were used to assess differences in attitudinal, descriptive, and behavioral measures that were cross-tabulated with demographic data. Results: When prescribing medication for newly diagnosed patients with stable or unstable COPD, only 37% of HCPs considered type of device to be highly important, with only 45% of HCPs assessing device technique in every newly diagnosed patient. Patients with COPD were also relatively unconcerned with proper device technique (64% never concerned), regardless of their COPD severity. Although patients did not identify education as a significant impediment to proper device use, they reported inconsistent educational experiences. Conclusions: We found that HCPs and patients prioritize medication over device when selecting treatments, showing limited concerns about proper device use. These results highlight the need to coordinate professional education with patient-directed educational efforts to further promote proper device selection and use in COPD management.