This Week in Pulmonary — Sep 8, 2026

Welcome to This Week in Pulmonary. This week we're covering 10 notable papers spanning thoracic oncology, guideline updates in pulmonary hypertension and tobacco treatment, two negative randomised trials that should change what we offer patients, and a cluster of work on lung transplantation and palliative care. Let's dive in.

Let's start with thoracic oncology, where two papers pull in opposite directions. In The Lancet, the SWOG/NRG S1914 trial asked whether adding atezolizumab to stereotactic body radiation therapy improves survival in medically inoperable early-stage non-small-cell lung cancer with high-risk features. Daly and colleagues randomised just over 400 eligible patients across 146 institutions to radiation alone or radiation plus neoadjuvant, concurrent and adjuvant atezolizumab. Accrual was stopped at the first interim analysis for futility, and the updated analysis showed no survival benefit whatsoever — two-year overall survival was 82 percent in both arms — while grade 3 or higher adverse events rose from about 3 percent to about 12 percent with immunotherapy, including two fatal respiratory events [1]. This is a clean negative result in a population where the temptation to extrapolate from stage 3 chemoradiation data has been considerable. For now, stereotactic radiation alone remains the standard, and adding checkpoint blockade outside a trial adds toxicity without measurable gain. Contrast that with the New England Journal of Medicine, where Arbour and colleagues report the phase 1-2 experience with daraxonrasib, an oral multiselective inhibitor that targets the active, GTP-bound form of both mutant and wild-type RAS. Among 136 previously treated patients with advanced RAS-mutant lung cancer, objective responses occurred in more than 30 percent across dose levels, with about 37 percent responding at the 300 milligram dose [2]. RAS mutations drive roughly 30 percent of non-small-cell lung cancer, and until now only specific KRAS G12C alterations were druggable, so a pan-RAS agent with activity across isoforms is clinically meaningful. The cost is real toxicity: rash, diarrhoea, nausea and mucositis were common, just over half of patients had grade 3 or higher events, pneumonia occurred in one in ten, and there were four fatal events. This is early-phase data, not a comparative trial, but it is worth knowing about when counselling patients on molecular testing and trial referral. Rounding out the oncology theme, the New England Journal also published a review of pulmonary nodules by Callister and Silvestri, a practical reminder that solid nodules stable for two years can be called benign whereas subsolid nodules need longer surveillance, that subsolid nodules are slower growing but carry a higher malignancy risk — especially when a solid component appears or enlarges — and that risk prediction models should be driving whether a patient gets surveillance imaging, PET-CT, biopsy, or resection [3].

Next, guidelines. The European Respiratory Journal has published the European Respiratory Society clinical practice guidelines update for pulmonary arterial hypertension, and the headline is sotatercept. Kovacs and colleagues, using GRADE methodology, recommend add-on sotatercept — an activin signalling inhibitor working through an entirely new pathway — for patients already on background pulmonary arterial hypertension therapy who remain at intermediate-low, intermediate-high, or high risk of death on follow-up assessment. That recommendation rests on high-certainty randomised trial evidence [4]. For low-risk patients, the task force explicitly declined to make a recommendation, because those patients were barely represented in the trials. The guideline also asks us to be less shy about repeat right heart catheterisation during follow-up in that same intermediate-to-high-risk group, when the result would actually change management, and it stresses that sotatercept should be initiated and monitored in pulmonary hypertension centres. Practically, this reinforces risk stratification at every follow-up visit as the trigger for escalation. Chest, meanwhile, published the American College of Chest Physicians clinical practice guideline on tobacco treatment in the inpatient setting. Kathuria and colleagues screened more than 9,000 abstracts and included 142 studies to generate eight recommendations, and the honest framing is that none rests on high-certainty inpatient-specific evidence — four are moderate certainty and the rest lower [5]. The central operational recommendation is an opt-out, population-based model: every hospitalised patient who smokes gets counselling and pharmacotherapy proactively unless they explicitly decline, with the counselling continued after discharge. That last point matters, because the post-discharge tail is where most of the cessation benefit accrues. If your hospital still relies on a referral-based, opt-in consult service, this guideline is an argument for redesigning the default.

The negative-trial theme continues in paediatric respiratory prevention. In The Lancet, the ORBEX trial led by Morgan tested the oral bacterial lysate OM-85 for the primary prevention of wheezing lower respiratory illness in 822 children aged 6 to 18 months at high risk of asthma because of atopic dermatitis or family history. Children took OM-85 or placebo for ten days each month for two years and were then followed for three more years off drug. There was no difference in time to first wheezing illness — around a fifth of children in each group had at least one event, with numerically slightly more in the treatment arm — and no signal of benefit on any timescale [6]. Adverse events were comparable. The authors conclude plainly that bacterial lysates are not efficacious for primary prevention of asthma-like symptoms in the preschool years, which should settle a question that has attracted considerable off-label enthusiasm in some countries. Also in Chest, a randomised physiological study by Grad and colleagues delivers a caution about a feature most of us barely think about: expiratory pressure alleviation on CPAP devices, the comfort algorithms that drop pressure during exhalation. In 29 adults with severe obstructive sleep apnoea, activating expiratory pressure alleviation roughly halved peak inspiratory flow during flow limitation, pushed the manually titrated therapeutic pressure up by more than 2 centimetres of water, and left a higher residual apnoea-hypopnoea index both on fixed and on auto-CPAP [7]. Crucially, adherence was identical at about seven hours a night either way. So the comfort feature bought no adherence benefit while measurably degrading upper airway patency and disease control. If a patient has persistent residual events on apparently adequate pressure, checking whether expiratory relief is switched on is now a concrete troubleshooting step.

Finally, two papers on lung transplantation and one on palliative care, all speaking to what we tell patients about the road ahead. In Chest, El Kik and colleagues applied the days-alive-and-out-of-hospital metric to all 1,222 patients transplanted in France between 2020 and 2023. In the year before transplant, patients were alive and out of hospital about 95 percent of days; in the first year after transplant that fell to about 80 percent, then recovered to nearly 99 percent in the second year [8]. Connective tissue disease and single-lung transplantation were each independently associated with worse first-year figures. That is a genuinely useful counselling frame — the first year is harder than the year of waiting, and the second year is substantially better than either. Alongside it, the European Respiratory Journal published a broad review by Goda and colleagues on the modern transplant continuum, covering extended-criteria and donation-after-circulatory-death donors, ex vivo lung perfusion, the United States composite allocation score, frailty and nutritional assessment of candidates, and emerging tools including donor-derived cell-free DNA immunomonitoring and xenotransplantation, while underlining that chronic lung allograft dysfunction remains the reason lung survival lags other solid organs [9]. And in Chest, Guerreiro and colleagues describe a nurse-led, interdisciplinary outpatient palliative care model for advanced chronic respiratory disease, built and refined through Plan-Do-Study-Act cycles, with referral triggered by symptom burden, respiratory decline, frailty, treatment decision-making needs, or caregiver strain [10]. It is a service-design paper rather than a trial, but it addresses a persistent gap: patients with chronic respiratory disease carry a heavier symptom load than patients with lung cancer yet reach palliative care later, often only at the very end.

If you only have time for one paper this week, make it the European Respiratory Society pulmonary arterial hypertension guideline update [4]. It converts sotatercept from trial result into a high-certainty, risk-stratified recommendation and tells you exactly which patients in your clinic qualify for escalation.

Here are the key takeaways from this week in Pulmonary. First, adding atezolizumab to stereotactic radiation in inoperable early-stage lung cancer failed for futility and increased serious toxicity — do not do it off trial. Second, sotatercept now has a high-certainty add-on recommendation for pulmonary arterial hypertension patients who remain at intermediate-low risk or worse, which makes systematic risk reassessment at every visit essential. Third, bacterial lysates do not prevent preschool wheeze in high-risk children, so that conversation can now be closed. Fourth, CPAP expiratory relief algorithms worsened airway patency and residual events without improving adherence — consider switching them off in patients with persistent events. And fifth, hospitalisation should default to opt-out tobacco treatment with post-discharge follow-up, and for advanced chronic respiratory disease, nurse-led palliative care and realistic days-out-of-hospital counselling around transplant are both practical ways to improve the lived experience of our patients.

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

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