Bisoprolol in Patients With Chronic Obstructive Pulmonary Disease at High Risk of Exacerbation: The BICS Randomized Clinical Trial.

Importance: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Observational studies report that ß-blocker use may be associated with reduced risk of COPD exacerbations. However, a recent trial reported that metoprolol did not reduce COPD exacerbations and increased COPD exacerbations requiring hospital admission. Objective: To test whether bisoprolol decreased COPD exacerbations in people with COPD at high risk of exacerbations. Design, Setting, and Participants: The Bisoprolol in COPD Study (BICS) was a double-blind placebo-controlled randomized clinical trial conducted in 76 UK sites (45 primary care clinics and 31 secondary clinics). Patients with COPD who had at least moderate airflow obstruction on spirometry (ratio of forced expiratory volume in the first second of expiration [FEV1] to forced vital capacity <0.7; FEV1 <80% predicted) and at least 2 COPD exacerbations treated with oral corticosteroids, antibiotics, or both in the prior 12 months were enrolled from October 17, 2018, to May 31, 2022. Follow-up concluded on April 18, 2023. Interventions: Patients were randomly assigned to bisoprolol (n = 261) or placebo (n = 258). Bisoprolol was started at 1.25 mg orally daily and was titrated as tolerated during 4 sessions to a maximum dose of 5 mg/d, using a standardized protocol. Main Outcomes and Measures: The primary clinical outcome was the number of patient-reported COPD exacerbations treated with oral corticosteroids, antibiotics, or both during the 1-year treatment period. Safety outcomes included serious adverse events and adverse reactions. Results: Although the trial planned to enroll 1574 patients, recruitment was suspended from March 16, 2020, to July 31, 2021, due to the COVID-19 pandemic. Two patients in each group were excluded postrandomization. Among the 515 patients (mean [SD] age, 68 [7.9] years; 274 men [53%]; mean FEV1, 50.1%), primary outcome data were available for 514 patients (99.8%) and 371 (72.0%) continued taking the study drug. The primary outcome of patient-reported COPD exacerbations treated with oral corticosteroids, antibiotics, or both was 526 in the bisoprolol group, with a mean exacerbation rate of 2.03/y, vs 513 exacerbations in the placebo group, with a mean exacerbation rate of 2.01/y. The adjusted incidence rate ratio was 0.97 (95% CI, 0.84-1.13; P = .72). Serious adverse events occurred in 37 of 255 patients in the bisoprolol group (14.5%) vs 36 of 251 in the placebo group (14.3%; relative risk, 1.01; 95% CI, 0.62-1.66; P = .96). Conclusions and Relevance: Among people with COPD at high risk of exacerbation, treatment with bisoprolol did not reduce the number of self-reported COPD exacerbations requiring treatment with oral corticosteroids, antibiotics, or both. Trial Registration: isrctn.org Identifier: ISRCTN10497306.

Oral corticosteroid prescribing practice for chronic rhinosinusitis with nasal polyps among otorhinolaryngologists in Scotland: a nationwide survey.

OBJECTIVE: Oral corticosteroids are used to treat exacerbations of chronic rhinosinusitis with nasal polyps. Oral corticosteroid prescribing practices vary as reported from national surveys in Italy, China, Canada and the USA. METHODS: A nationwide online survey of ENT doctors practicing in Scotland was conducted using Microsoft Forms. RESULTS: There was a 31 per cent response rate. The most common daily doses of oral corticosteroid courses were 25 mg and 40 mg with the lengths being 14 and 7 days, respectively. Seventy-seven per cent of respondents prescribed the same daily dose throughout the course. Rhinologists prescribed longer courses with a smaller daily dose of prednisolone. Only one respondent fully agreed that there were clear guidelines regarding the daily dose and the length of oral corticosteroid course in the treatment of chronic rhinosinusitis with nasal polyps. CONCLUSION: The heterogeneity of oral corticosteroid prescribing practice in different countries, including Scotland, reveals the need for clear guidelines with a specific oral corticosteroid daily dose and length of the course.

Budesonide/Formoterol or Budesonide/Albuterol as Anti-Inflammatory Reliever Therapy for Asthma.

Overuse of reliever as short-acting beta-agonist and associated underuse of controller as inhaled corticosteroid (ICS) administered via separate inhalers results in worse asthma outcomes. Such discordance can be obviated by combining both controller and reliever in the same inhaler. So-called anti-inflammatory reliever (AIR) therapy comprises the use of a single inhaler containing an ICS such as budesonide (BUD) in conjunction with a reliever as either albuterol (ALB) or formoterol (FORM), to be used on demand, with variable dosing driven by asthma symptoms in a flexible patient-centered regimen. Global guidelines now support the use of BUD-ALB as AIR therapy to reduce exacerbations, either on its own in mild asthma or in conjunction with fixed-dose maintenance ICS-long-acting beta-agonist in moderate to severe asthma. Using BUD-FORM on its own allows patients to seamlessly move in an intuitive flexible fashion between AIR and maintenance and reliever therapy, by stepping up and down the dosing escalator across a spectrum of asthma severities. Head-to-head clinical studies are indicated to compare BUD-FORM versus BUD-ALB as AIR in mild asthma, and also BUD-FORM as maintenance and reliever therapy versus BUD-ALB as AIR plus maintenance ICS-long-acting beta-agonist in moderate to severe asthma. Patients should be encouraged to make an informed decision in conjunction with their health care professional regarding the best therapeutic option tailored to their individual needs, which in turn is likely to result in long-term compliance and associated optimal asthma control.

5-Item sino-nasal outcome test and 22-item sino-nasal outcome test relationship with endoscopic and radiologic scores in chronic rhinosinusitis with nasal polyps.

BACKGROUND: The 22-item sino-nasal outcome test (SNOT-22) is a frequently used patient-recorded outcome measure in patients with chronic rhinosinusitis with nasal polyps (CRSwNPs). Objective findings of nasal polyps and paranasal sinus inflammation are frequently graded using nasal polyp score (NPS) and Lund-Mackay Score (LMS), respectively. OBJECTIVE: To evaluate a novel, abbreviated, rhinology-focused, five-domain SNOT-5 questionnaire because we had anecdotally noticed a relative disconnect between SNOT-22 and endoscopy and imaging scores. METHODS: We performed a retrospective, cross-sectional, single-center review of patients with CRSwNPs who had filled out a SNOT-22, along with post hoc-derived SNOT-5 scores, which were then assessed in relation to NPS and LMS. RESULTS: A total of 129 patients were included in the analysis. SNOT-5 but not SNOT-22 scores significantly correlated vs either NPS (P < .005) and LMS (P < .001), whereas only SNOT-5 differed significantly when comparing the cohort's lowest and highest tertiles for mean LMS: 11.8 vs 16.8 (95% CI, 1.5-8.4; P < .01) and for mean NPS 12.4 vs 15.6 (95% CI, 0.5-5.9; P < .05). CONCLUSION: In a retrospective, real-life cohort study of CRSwNP, there was a relative disconnect between the significant association of SNOT-5 but not SNOT-22 in relation to objective endoscopy and imaging measures. We, therefore, propose that further prospective intervention studies are indicated in CRSwNP to evaluate the SNOT-5 score including establishing the minimal clinically important difference.

Should Airway Hyper-Responsiveness Be Included in the Definition of Clinical Remission With Biologic Therapy in Severe Asthma.

Airway hyper-responsiveness (AHR) is a tenet of the persistent asthma phenotype along with reversible airway obstruction and type 2 (T2) inflammation. Indirect acting challenges such as mannitol are more closely related to the underlying T2 inflammatory process as compared with direct challenges. In this review article, we summarise the current literature and explore the future role of mannitol AHR in clinical remission with biologics.

Medium-term repeatability for airwave oscillometry in patients with severe asthma taking benralizumab.

Background: The effort-independent tidal breathing test used by oscillometry presents a viable alternative for following up patients whose condition is stable while they are receiving biologic therapy. Objective: We aimed to determine intrasession and intersession repeatability values for airwave oscillometry (AOS) and spirometry in patients who were already taking benralizumab. Methods: In all, 21 patients with severe eosinophilic asthma attended the Scottish Centre for Respiratory Research as part of a clinical trial (EudraCT identification number 2019-003763-22). Paired AOS and spirometry values were obtained at 3 separate visits (baseline and days 28 and 56) with no change in asthma therapy. Results: Intrasession agreement between repeated measurements for AOS and spirometry was excellent (intraclass correlation coefficient ≥ 0.90) at all 3 visits. Intersession agreement was also excellent (intraclass correlation coefficient ≥ 0.80). Conclusion: In this study we report medium-term intrasession and intersession repeatability values for airwave oscillometry and spirometry in a cohort of severely asthmatic patients receiving benralizumab therapy. Oscillometry can be used to follow up patients with asthma who are taking biologics.