This week in Pulmonary

This AudioScholar briefing is generated by artificial intelligence for healthcare professionals and trainees. It is not medical advice.

Welcome to This Week in Pulmonary. This week we're covering 10 notable papers spanning critical care and transplant, airway disease and its infections, and thoracic oncology and care delivery. Let's dive in.

We begin in the intensive care unit, where this week's evidence mostly tells us what does not move the needle. The largest paper of the week, published in The Lancet, is PROSpect, led by Curley and colleagues, an international factorial trial across 75 paediatric intensive care units in 18 countries testing prone positioning and high-frequency oscillatory ventilation in children with early, moderate-to-severe paediatric ARDS [1]. Children were randomised to one of four combinations of supine or prone positioning with conventional or oscillatory ventilation. The trial stopped early for futility and slow enrolment after 424 of a planned 600 patients, and neither intervention changed ventilator-free days through day 28, with medians sitting around 17 to 18 days in every arm. About one in ten children had died by day 28, with no group differences. The harms, however, were measurable: prone positioning was associated with roughly five times the rate of artificial airway plugging or obstruction and about six times the risk of stage 2 or worse pressure injuries, while oscillatory ventilation brought more haemodynamic instability. For paediatric intensivists, this is the most rigorous data yet that routine early proning and oscillation do not improve ventilator-free days in this population, although the early stop means smaller effects cannot be fully excluded. In adults, Respiratory Medicine published a four-centre retrospective cohort from Hou and colleagues looking at 117 patients with suspected high-risk pulmonary embolism too unstable for CT pulmonary angiography [2]. In-hospital mortality was about 42 percent with ECMO-first management versus about 58 percent with thrombolysis, a difference that was not statistically significant on crude comparison; only after multivariable adjustment was ECMO associated with roughly halving the risk of death. With a small sample, a nonrandomised design and an unadjusted result that missed significance, this is hypothesis-generating, as the authors themselves acknowledge. Rounding out the theme, the American Journal of Respiratory and Critical Care Medicine published an analysis by Pandya and colleagues from the eight-centre Lung Transplant Outcomes Group cohort of 2,419 recipients [3]. Primary graft dysfunction was associated with a maximum achievable FEV1 about 300 millilitres lower and a lower chance of reaching predicted lung function, yet it was not associated with chronic lung allograft dysfunction, either obstructive or restrictive, over a median of almost six years. That separates two ideas often bundled together: early graft injury appears to cap lung function, but this prospective cohort does not support it as a driver of chronic rejection.

Our second theme is chronic airway disease and the drugs and infections that travel with it. In the American Journal of Respiratory and Critical Care Medicine, Han and colleagues pooled the BOREAS and NOTUS trials, nearly 1,900 patients with COPD and type 2 inflammation, for a post hoc look at lung function on dupilumab [4]. Compared with placebo, dupilumab raised pre-bronchodilator FEV1 by about 80 millilitres, with gains across FVC and small-airway flows appearing by week 12 and holding to week 52. The benefit was seen regardless of smoking status or coexisting emphysema and was larger in patients with higher eosinophil counts or exhaled nitric oxide. As a post hoc analysis from industry-sponsored trials, it refines rather than establishes the case, but it adds spirometric depth to the existing exacerbation data in this phenotype. Biomarker-guided care is also the subject of a narrative review by Li and Li in the International Journal of COPD, focused on acute exacerbations [5]. Their framing is useful: blood eosinophils carry the most developed trial evidence for guiding or shortening corticosteroids, C-reactive protein supports antibiotic stewardship most clearly in primary care, and procalcitonin reduces antibiotic use in selected non-intensive-care inpatients but failed to establish non-inferiority for mortality in the intensive care trial. The authors stress that each result is tied to a specific population, threshold and treatment rule.

Macrolides bring us to mycobacteria. In Chest, Torsheim and colleagues ran two Danish nationwide nested case-control analyses asking whether azithromycin raises the risk of incident nontuberculous mycobacterial isolation in bronchiectasis and COPD [6]. Under the prespecified definition of sustained exposure, azithromycin was not associated with NTM isolation in either disease. Broader definitions did show signals in COPD, but these were not dose-dependent, clustered within 90 days of the culture, faded when only definite isolates were counted, and were matched or exceeded by non-macrolide antibiotics, a pattern the authors read as indication-driven testing rather than a drug effect. They do note one residual association with any exposure in COPD that persisted. For clinicians weighing long-term azithromycin, this is reassuring observational evidence, though not definitive. On the other side of the mycobacterial story, Respiratory Medicine published a single-centre Israeli cohort from Dagan and colleagues on Mycobacterium abscessus in cystic fibrosis [7]. Among 55 patients, those with true pulmonary disease lost roughly a third of their FEV1 percent predicted over follow-up, while colonised patients tracked like controls. After starting elexacaftor, tezacaftor and ivacaftor, about 85 percent of culture-positive patients cleared the organism from sputum. The cohort is small and retrospective, so this is an association, but it suggests modulator therapy may reshape a historically intractable infection.

Our final theme is thoracic oncology and the structures that deliver specialty care. In Chest, Farrand and colleagues studied 6,637 patients with interstitial lung disease within one academic health system [8]. Patients managed outside the subspecialty ILD clinic were more likely to be Black or Latinx, to live in deprived neighbourhoods, and to carry an unspecified ILD label. ILD clinic care was associated with about two and a half times the odds of chest CT and higher odds of antifibrotic therapy, along with roughly half the hazard of hospitalisation and about 40 percent lower mortality. Residual confounding is a real concern in a retrospective design, but the equity signal is striking. In lung cancer, the Journal of Thoracic Oncology published a brief report by Senan and colleagues from the ADRIATIC trial in limited-stage small cell lung cancer, examining where disease recurred after chemoradiotherapy [9]. Intrathoracic-only progression was similar between arms, but extrathoracic progression was lower with consolidation durvalumab, roughly 20 percent versus 30 percent, with brain relapse nearly halved. These are exploratory post hoc data, and the brain finding did not reach statistical significance, but they suggest durvalumab's benefit operates largely against distant spread. Finally, in Nature Medicine, Reck and colleagues report the phase 2 MDT-BRIDGE study of perioperative durvalumab with chemotherapy in resectable and borderline resectable non-small-cell lung cancer, with a pathway to chemoradiotherapy and consolidation durvalumab for patients who became unresectable [10]. Despite more than a third of patients being borderline resectable at baseline, about three quarters underwent resection, nearly all with clear margins, and over 90 percent received curative-intent surgery or chemoradiotherapy. Without a comparator arm, this establishes feasibility of a multidisciplinary bridge strategy rather than superiority.

If you only have time for one paper this week, make it PROSpect in The Lancet [1]. It is the largest randomised test of proning and oscillatory ventilation in paediatric ARDS, and it answers a long-running question about practice variation with a clear null on benefit and a clear signal on harm.

Here is what this week's evidence adds up to in Pulmonary. First, randomised data now show that early prone positioning and high-frequency oscillation do not improve ventilator-free days in moderate-to-severe paediatric ARDS and carry added harms, though the trial stopped early. Second, in COPD with type 2 inflammation, dupilumab's lung function gains appear early and durable across subgroups, but this comes from post hoc analysis. Third, Danish registry data do not link sustained azithromycin use to new NTM isolation, while CF modulator therapy is associated with high rates of Mycobacterium abscessus clearance in a small cohort; both questions still lack prospective confirmation. Fourth, observational signals favouring ECMO-first strategies in unstable suspected pulmonary embolism and subspecialty ILD clinic care are encouraging but vulnerable to confounding. And fifth, primary graft dysfunction appears to limit peak lung function after transplant without raising chronic allograft dysfunction risk, an observation that reframes how early graft injury relates to long-term outcomes.

That's your roundup for This Week in Pulmonary. The full transcript and references are available on the episode page. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.

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