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Dupilumab for patients with COPD and blood eosinophilia reduces exacerbation frequency
There is increasing interest in phenotypes of patients with COPD that may indicate different response to treatments. Patients with COPD and type 2 inflammation have been shown to have a different response to glucocorticoids and so may also respond to other anti-inflammatory medications. The BOREAS trial (NEJM 2023: DOI 10.1056/NEJMoa2303951) was a phase 3, international, multicentre, randomised, double-blind, placebo-controlled study designed to investigate the safety and the efficacy of dupilumab (a fully human monoclonal antibody that blocks a shared receptor component for interleukin-4 and interleukin-13) in this subset of COPD patients that were already under triple inhaled therapy over 52 weeks. A total of 939 patients across 275 sites from 24 countries were randomised 1:1 (dupilumab group 468 and placebo group 471). The Dupilumab treated group had a lower annualised rate of moderate or severe exacerbations compared with placebo group (0.78, 95%confidence interval 0.64 to 0.93 vs 1.10, 95%confidence interval 0.93 to 1.30; rate ratio 0.70, 95%confidence interval 0.58 to 0.86). There was also evidence for improvement in lung function (160 mL, 95%confidence interval 126 to 195 vs 77 mL, 95%confidence interval 42 to 112, p<0.001 at week 12) and quality of life (percentage at week 52 with increase above MCID in St George’s Respiratory Questionnaire 52% vs 43%, p=0.009). Treatment with dupilumab improves important clinical and patient relevant outcomes in patients with COPD and evidence of type two inflammation.
Bronchiectasis in Europe: data on disease characteristics from the European bronchiectasis registry (EMBARC)
Bronchiectasis is a commonly encountered clinical condition but due to the heterogeneity there are few large multicentre studies to direct clinical care. Chalmers and colleagues (Lancet Respir Med 2023: DOI 10.1016/S2213-2600(23)00093-0) report an observational, prospective cohort of 16 963 adult patients with bronchiectasis, conducted between 2015 and 2022, across 27 European countries and Israel. Patients with cystic fibrosis and traction bronchiectasis due to interstitial lung diseases were not included. The median age was of 67 years (IQR 57–74) and female patients were predominant (60.9%). The most frequent causes of bronchiectasis were idiopathic (38.1%) and post-infective (21.2%), with important differences in aetiologies, like the higher prevalence of idiopathic disease in the United Kingdom (UK) and southern Europe. Allergic bronchopulmonary aspergillosis (ABPA) was also more common in the UK and in the north and western Europe. As well as differences in aetiology of bronchiectasis there were important regional variation in lung function, exacerbation frequency, microbiology and treatment were noted. In particular patients in central and eastern Europe had more severe bronchiectasis (Bronchiectasis severity index 51.3% vs 35.1% in the whole cohort) and more frequent exacerbations (adjusted rate ratio 1.12, 95%confidence interval 1.01 to 1.25). Interestingly normal spirometry (31.2%) was almost as common as obstructive pattern (34.9%). The study demonstrates clinically important differences across Europe and Israel which will support the pursuit for improved therapeutical strategies.
Improving physical activity after hospitalisation for an exacerbation of COPD: motivational techniques increase step count
Acute exacerbations in COPD are associated with reduced physical activity that may not return to pre-morbid baseline. Interventions such as pulmonary rehabilitation after an exacerbation can improve clinical outcomes but may not improve overall physical activity. Valerio et al (Respirology 2023;28:357) present a multicentre randomised clinical trial aimed to reduce sedentary behaviour using a 12 week, patient tailored, pedometer-based, progressive and target-driven programme following hospitalisation due to an COPD exacerbation. 46 patients admitted to hospital with an exacerbation of COPD were randomised and 43 (20 intervention, 23 control) were analysed. Important exclusion criteria included a hospital exacerbation within the previous 12 months or admission to the ICU. All patients received the Dynaport accelerometer to objectively measure physical activity. The intervention comprised three components: a motivational interview, a personalised physical activity programme with a pedometer and a printed calendar and weekly telephone calls assessed progression. The mean age was 66 years (SD 10) and 74% of patients were male. Only the intervention group had a significant increase in the number of steps per day after the 12 week programme comparing to the baseline (mean difference 2932 steps, 95%confidence interval 1069 to 4795). However, high levels of sedentary behaviour persisted in both groups. This might be explained by the primary focus on increasing physical activity (steps per day) without targeted goals on sedentary behaviour. Since patients were blind to the purpose of the pedometer, the trial results are optimistic in the pursuit for a more active lifestyle in COPD patients following an exacerbation which could result in a more favourable long-term outcome.
Inhaled anti-TSLP antibody fragment (ecleralimab) for allergic asthma reduces type 2 inflammation with good safety profile
Thymic stromal lymphopoietin (TSLP) is an important regulator of the type 2 inflammatory response and is associated with atopic diseases, including asthma. Ecleralimab is the first inhaled neutralising antibody fragment against human TSLP. Gauvreau and colleagues (Eur Respir J 2023;61:2201193) report a multicentre, randomised, double-blind, placebo-controlled, parallel-design, allergen inhalation challenge (AIC) study that was performed between 2017 and 2019 including 10 centres in Canada and Germany. 28 adult patients (18–60 years) with stable mild atopic asthma requiring no chronic asthma medications were recruited and 27 (14 ecleralimab, 13 placebo) completed the 12 weeks of the study. One patient in the treatment group dropped out with uncontrolled asthma prior to evaluation. Ecleralimab was delivered via a dry powder inhaler at a dose of 4 mg. At day 84 there was a significant attenuated allergen-induced late asthmatic response in the ecleralimab group compared with placebo (48% reduction p=0.029). Sputum eosinophilia (day 84: 64% vs 52% reduction) and FENO (day 17: 27% vs 7% reduction) were significantly reduced compared with the placebo group. Treatment with inhaled ecleralimab was safe and well tolerated with only mild adverse event reported in both groups (ecleralimab 51 events in 10 patients; placebo 42 events in 12 patients). While ecleralimab was effective at reducing the late phase allergic response the clinical relevance remains unclear, however further studies in patients with severe asthma are underway.
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Twitter @joaorodri24
Contributors JOR is the sole author of the paper.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.