Use of inhaled ipratropium bromide to improve exercise-induced laryngeal obstruction cannot be recommended.

Introduction: Exercise-induced laryngeal obstruction (EILO) is a common cause of exertional breathing problems in young adults. Current management generally consists of breathing advice, speech therapy, inspiratory muscle training or supraglottoplasty in highly motivated subjects with supraglottic collapse. Inhaled ipratropium bromide (IB) is a muscarinic receptor antagonist used to treat asthma that is suggested in a few reports to improve EILO symptoms. The aim of the present study was to investigate effects of inhaled IB in EILO diagnosed by continuous laryngoscopy exercise (CLE) test and classified by CLE scores. Methods: A randomised crossover trial was conducted at Haukeland University Hospital, Bergen, Norway, enrolling participants diagnosed with EILO defined by characteristic symptoms and CLE score ≥3 (range 0-12). Two consecutive CLE tests were performed within 2 weeks, one test with and one test without prior administration of inhaled IB in a randomised order. Main outcomes were the CLE score, dyspnoea measured using a modified BORG scale (range 0-10) and cardiopulmonary exercise data provided by the CLE test. Results: 20 participants (14 females) aged 12-25 years participated, and all ran to exhaustion on both tests. Mean CLE score, BORG score and peak oxygen consumption were similar in tests performed with and without IB; mean differences (95% confidence interval) were 0.08 (-0.28-0.43), 0.35 (-0.29-0.99) and -0.4 (-1.9-1.1) mL·kg-1·min-1, respectively. Conclusion: Inhaled IB did not improve CLE score, dyspnoea or exercise capacity in subjects with EILO. The study does not support the use of inhaled IB to treat EILO.

Ethnic Sensitivity Study of the Extrafine, Single-Inhaler, Triple Therapy Beclomethasone Dipropionate, Formoterol Fumarate, and Glycopyrronium Bromide Pressurized Metered Dose Inhaler in Japanese and Caucasian Healthy Individuals: A Randomized, Double-Blind, Single-Dose Crossover Study.

PURPOSE: A number of single-inhaler, fixed-dose, triple combinations are available for the management of chronic obstructive pulmonary disease and/or asthma. One of these is the extrafine formulation beclomethasone dipropionate, formoterol fumarate, glycopyrronium bromide (BDP/FF/GB). Given that differences in ethnicity can result in differences in systemic exposure, we evaluated the relative pharmacokinetic (PK) profiles of BDP/FF/GB in Japanese vs Caucasian healthy volunteers to assess the need for dose adjustment. METHODS: This randomized, double-blind, single-dose, 4-way crossover study recruited healthy men and women 20 to 55 years of age; for each Japanese person a Caucasian was enrolled who matched in terms of sex, age, and weight. Study treatments included BDP/FF/GB 200/12/25 and 400/12/25 µg (therapeutic), 800/48/100 µg (supratherapeutic), and placebo. PK blood samples were taken up to 24 hours for evaluation of BDP, beclomethasone 17-monopropionate (B17MP, an active metabolite of BDP), and formoterol and up to 48 h for GB. The primary objective was to characterize the PK profiles of BDP, FF, and GB after administration of a single dose of BDP/FF/GB in Caucasian and Japanese healthy volunteers in terms of the AUC0-t and Cmax of B17MP, formoterol, and GB. FINDINGS: Of the 32 recruited participants (16 Japanese and 16 Caucasian ), 30 completed the study. A clear plasma exposure dose-response relationship was found for all 4 molecules. B17MP Cmax geometric mean ratios for Japanese vs Caucasian participants for the 3 study treatments ranged from 1.17 to 1.26, and AUC0-t ratios ranged from 1.16 to 1.22; thus, the findings were comparable between the ethnicities. Formoterol exposure was higher in Japanese than Caucasian participants (Cmax, 1.22-1.53; AUC0-t, 1.23-1.40). The GB Cmax with BDP/FF/GB 400/12/25 µg (1.09) and AUC0-t values for all three doses (0.98-1.17) were comparable in the 2 populations, but Cmax with 200/12/25 and 800/48/100 µg were higher in Japanese participants (1.32 and 1.42, respectively). Pharmacodynamic (cortisol, potassium, glucose, blood pressure, heart rate, and QT interval with the Fridericia correction) and safety profile results were similar in the 2 ethnicities, with most patients not experiencing any adverse events. IMPLICATIONS: Exposure to BDP/FF/GB pressurized metered dose inhaler at therapeutic and supratherapeutic doses was associated with higher plasma levels in Japanese versus Caucasian healthy volunteers. These PK differences did not translate into meaningful differences in the safety or pharmacodynamic parameters assessed in this study and were consistent with the results of other long-term (52-week) published studies. Dose adjustments in Japanese people are not deemed necessary. CLINICALTRIALS. GOV IDENTIFIER: NCT03859414.

Patients' perspectives on bronchiectasis: findings from a social media listening study.

Although it is of great importance for healthcare professionals to ensure that patients' needs and concerns are valued and that they feel confident in the quality of the care they receive, there have been few studies specifically addressing the opinions, experiences and needs of patients with bronchiectasis, and more importantly the emotional impact of the disease, diagnosis and treatment. Using enterprise grade social listening tools, a comprehensive search around bronchiectasis was performed in five languages, on different social media platforms between January 2018 and December 2019 to obtain the perspectives of patients and caregivers from nine countries on symptoms, treatments and burden of the disease. Over 27 000 mentions of bronchiectasis were identified on social media channels, 38.8% of which were posted by patients and caregivers. Approximately 1600 posts were found on bronchiectasis symptoms, out of which persistent cough, shortness of breath and mucus production (22%, 20% and 18%, respectively) were the most commonly discussed. The research revealed that existing diagnostic tests often delay diagnosis or provide inaccurate results, leading to multiple rounds of consults and substantial delays in treatment initiation and management of the disease. Misdiagnosis was common across different age groups, especially among patients without severe symptoms, and this was associated with an emotional burden of anger, confusion, frustration and anxiety. Analysis of social media presents a new approach to derive insights on patients' experiences and emotions with bronchiectasis and has the potential to complement more traditional approaches to drive more patient-focused drug development.