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  1. Lucy Searle
  1. Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
  1. Correspondence to Dr Lucy Searle, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF, UK; lucy.searle5{at}nhs.net

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Effects of prematurity on lung function: impact can be measured well into adult life

Prematurity has been linked to reduced lung function up to the age of 33, and the rates of COPD and prematurity are increasing in parallel. Bui et al (Lancet Respir Med 2022;10:478) investigated the effect of prematurity on fixed obstructive lung function deficits in a prospective cohort study. The cohort comprised 1445 participants from the Tasmanian Longitudinal Health Study, initially recruited in 1968, who were stratified by gestational age and grouped into very-to-moderate preterm (n=46), late preterm (n=172) and term (n=1227) births. Lung function tests performed at age 53 showed that very-to-moderate preterm birth was significantly associated with increased risk of COPD compared with term birth (OR 2.9, 95% CI 1.1 to 7.7), as well as lower post-bronchodilator FEV1/FVC ratio (beta-coefficient −2.9% (95% CI −4.9 to −0.81); FEV1 (−190 mL, 95% CI −339 to −40) and diffusing capacity for carbon monoxide (DLCO) (−0.55 mmol/min/kPa, 95% CI −0.97 to −0.13). Furthermore, this association was amplified by active smoking status (p=0.0082), suggesting opportunity for early public health intervention. This study acknowledges the limitations in the generalisability of these data given the changes in neonatal care, in particular the introduction of surfactant and antenatal corticosteroids but provides an insight into the important association between COPD and prematurity.

Fractional exhaled nitrous oxide to support decision making in childhood asthma: no role yet

Fractional exhaled nitrous oxide (FeNO) test correlates with eosinophilic airway inflammation and is responsive to asthma treatment. Recent studies suggest it may have scope in supporting symptom-guided asthma treatment decisions. Turner et al (Lancet Respir Med 2022;10:478) present this multicentre, randomised, controlled, phase III trial, which evaluated the role of FeNO in addition to symptoms to guide stepping up or down asthma preventative treatment to reduce exacerbations. Five hundred and fifteen children with asthma were randomised to FeNO plus symptom-guided treatment (intervention group) or symptom-guided treatment alone (standard care). Baseline Asthma Control Test (ACT) or Childhood ACT (CACT) and measurement of FeNO were recorded, and patients were followed up at 3-month intervals, with treatment decisions recommended by a guideline-based algorithm. The primary outcome of asthma exacerbation treated with oral steroids occurred in 123/255 (48.2%) patients in the intervention group and 129/251 patients in the standard care group (intention-to-treat adjusted OR 0.88, 95% CI 0.61 to 1.27, p=0.49). There was no statistically significant difference between treatment groups for any of the secondary outcomes, including time to first exacerbation (adjusted HR 0.92, 95% CI 0.71 to 1.18). While the algorithm treatment recommendation was not followed in 377/1771 (21.3%) assessments, analysis to account for treatment adherence difference showed a similar outcome (OR 0.82, 95% CI 0.48 to 1.41). The heterogeneity of these data when compared with previous studies suggests that the study design needs further optimisation before reliable conclusions are drawn. The frequent occurrence of the primary outcome in the 12-month period stresses the need for improvements to asthma management decisions.

Long-term treatment of severe eosinophilic asthma with mepolizumab: if it ain’t broke…

Mepolizumab is an anti-IL-5 monoclonal antibody which suppresses eosinophilic airway inflammation in severe eosinophilic asthma and improves asthma control in short-term clinical trials. Whether long-term treatment is required for sustained disease control is currently unknown. Moore et al (Eur Respir J 2022;59:2100396) evaluated the clinical impact of stopping mepolizumab 100 mg subcutaneously following long-term (>3 years) exposure in patients with severe eosinophilic asthma. Patients were recruited from previous mepolizumab trials and were randomised to continue mepolizumab 100 mg subcutaneously at 4-weekly intervals (n=144), or stop mepolizumab and switch to placebo (n=151), for a 52-week period. Recruited patients were mainly female (59%), white (81%) and aged 56±11 years old. The primary end point of time to first clinically significant exacerbation was significantly shorter in the placebo group compared with the mepolizumab group (HR 1.61, 95% CI 1.17 to 2.22, p=0.004). Furthermore, the placebo group had a 52% increased risk of decrease in asthma control over 12 months, as measured by Asthma Control Questionnaire-5 score (HR 1.52, 95% CI 1.13 to 2.02, p=0.005). Interestingly, the post hoc analysis showed that the treatment effect was attenuated in patients with two or more exacerbations in the year prior to enrolment raising the potential that the risk:benefit of continuation may be different in this group. The findings support the continued use of mepolizumab for long-term disease control in successfully treated patients.

Disease progression in pulmonary hypertension-interstitial lung disease: inhaled treprostinil still conveys some clinical benefits

Pulmonary hypertension (PH) frequently complicates the disease course in interstitial lung disease (ILD) and results in increased mortality. Treprostinil is a synthetic analogue of prostacyclin which promotes vasodilation of the pulmonary and systemic arterial circulation. This post hoc analysis presented by Nathan et al (Am J Respir Crit Care Med 2022;205:198) investigated multiple disease progression events (DPEs) over the 16-week INCREASE trial, during which 326 patients with PH-ILD were randomised to receive inhaled treprostinil (n=163) or placebo (n=163). DPEs were defined as ≥15% reduction in 6 minute walk distance, cardiopulmonary hospitalisation, lung transplant, death, 10% decline in FVC and exacerbation of underlying lung disease. Compared with the placebo group, patients who received inhaled treprostinil had a significantly lower risk of experiencing a single DPE (HR 0.71, 95% CI 0.54 to 0.94, p=0.019) and a second DPE (HR 0.53, 95% CI 0.35 to 0.81, p=0.003). Death after ≥1 DPE occurred less frequently in the inhaled treprostinil group (5/163, 3%) than the placebo group (12/163, 7%) but this failed to reach statistical significance (p=0.081). Subgroup analysis demonstrated a reduced risk of multiple DPEs in the idiopathic interstitial pneumonia (n=146, p=0.036) and connective tissue disease-associated ILD (n=72, p=0.014) groups but significance was not reached in the idiopathic pulmonary fibrosis (n=92, p=0.269) or combined pulmonary fibrosis and emphysema (n=82, p=0.187) groups. Although of limited duration, this post hoc analysis demonstrates ongoing impact of inhaled treprostinil in PH-ILD even after an initial DPE. Large-scale studies over longer study periods are needed to accurately identify the patient subgroups who will sustain the greatest clinical benefit.

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Footnotes

  • 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.