This Week in Pulmonary — Sep 15, 2026

Welcome to This Week in Pulmonary. This week we're covering 10 notable papers spanning thoracic oncology, airways disease and respiratory infection risk, interstitial lung disease from genetics to rehabilitation, and the pulmonary vasculature. Let's dive in.

We start with thoracic oncology, where two trials extend the reach of systemic therapy at opposite ends of the disease spectrum. In the New England Journal of Medicine, Zhao and colleagues report the interim analysis of a phase 3, open-label trial of tambotatug pelitecan, an antibody-drug conjugate targeting B7-H3, against topotecan in relapsed small-cell lung cancer after platinum-based therapy [1]. Four hundred and fifty-one patients were randomised. Median overall survival was 13.3 months with the antibody-drug conjugate against 9.4 months with topotecan, cutting the risk of death by roughly half, and progression-free survival more than doubled. Confirmed objective responses occurred in about six in ten patients on the new agent compared with roughly one in ten on topotecan — an extraordinary gap in a setting where second-line response rates have historically been dismal. Just as notable, severe adverse events were less common with the antibody-drug conjugate, affecting just over half of patients versus close to four in five on topotecan. This is an interim analysis in a largely Chinese trial population and the drug is not yet widely available, but it signals that B7-H3 targeting is likely to reshape relapsed small-cell disease. At the other end, the Journal of Thoracic Oncology publishes an exploratory 8-year landmark update from ADAURA, led by Wu, on adjuvant osimertinib in resected EGFR-mutated stage IB to IIIA non-small cell lung cancer [2]. In the stage II to IIIA group, 8-year overall survival was 74 percent with osimertinib versus 58 percent with placebo; across stage IB to IIIA, 79 percent versus 64 percent. The benefit held across subgroups, and appeared larger for exon 19 deletions than for L858R, where the difference was not statistically robust. This is post hoc, with incomplete follow-up in a subset of patients, but for the pulmonologist doing the diagnostic workup, the message is that molecular testing on a resected early-stage specimen now carries an eight-year survival consequence.

Turning to airways disease and infection risk, three papers each argue for acting earlier. In Chest, Canonica and colleagues pooled more than nine thousand patients with severe asthma from the International Severe Asthma Registry, the CHRONICLE registry in the United States, and the United Kingdom Optimum Patient Care Research Database — 26 countries in all — to ask whether the timing of biologic initiation matters [3]. It does. For every additional ten years of asthma before a biologic was started, the odds of achieving clinical remission at twelve months fell by about 14 percent. Pre-existing lung function impairment was the strongest penalty, cutting the odds of remission to roughly a quarter of what they otherwise would be, and every ten grams of lifetime cumulative oral corticosteroid nearly halved those odds. Longer duration of potential severe asthma before biologic also meant higher post-biologic exacerbation rates and less lung function recovery. This is observational and vulnerable to confounding by indication, but the authors' framing is memorable: move from a reserve approach to a preserve approach, treating before the airway remodels rather than after. In the American Journal of Respiratory and Critical Care Medicine, Narayana and colleagues analysed sputum metagenomes from 600 people with bronchiectasis across ten countries to explain why Pseudomonas behaves so differently between patients [4]. They identified four abundance-based subgroups, which tracked with disease severity, symptoms and lung function, and separately four interaction-based subgroups defined by how Pseudomonas relates to other organisms, which tracked with exacerbation risk. Two of those interaction groups carried roughly 45 percent higher exacerbation rates, while the group characterised by Pseudomonas–Streptococcus interactions was lowest risk. In a small longitudinal subset, abundance patterns stayed stable through exacerbations while interaction patterns shifted. This is hypothesis-generating and not yet a clinical test, but it reframes Pseudomonas from a binary culture result into an ecological trait. And in Thorax, Maitre and colleagues interrogated the World Health Organization VigiBase pharmacovigilance database for tuberculosis reported with JAK inhibitors compared with TNF-alpha inhibitors [5]. A disproportionality signal was present for both, stronger for TNF blockers but clearly significant for ruxolitinib, baricitinib, tofacitinib and upadacitinib. Among 695 tuberculosis cases occurring on JAK inhibitor therapy, extrathoracic involvement was common, and about 6 percent of patients died with active disease. Disproportionality analyses cannot give incidence and are prone to reporting bias, but the practical implication is concrete: screen for latent tuberculosis and consider preventive therapy before starting a JAK inhibitor, including in low-incidence countries.

The interstitial lung disease papers this week run from genetics to the gym. Thorax publishes a United Kingdom consensus framework from Bowden and colleagues on familial pulmonary fibrosis [6], prompted by the fact that respiratory physicians in England can now order a genetic testing panel directly. The document sets out the history and examination features that should raise suspicion of a telomere biology or surfactant disorder, argues that a genetic diagnosis changes multidisciplinary management and opens the door to family screening, and is candid about the unresolved questions — above all, what to do with an asymptomatic relative who carries a potentially disease-causing variant. If you order these panels, this is the pathway to have on file. Alongside it in the same journal, Csordas and colleagues report proteomic work from the Pulmonary Fibrosis Foundation Patient Registry and an independent validation cohort, curating 79 microvascular-associated proteins [7]. Five — including syndecan-1, MMP10, thrombospondin-2, hepatocyte growth factor and SERPINA5 — were associated with lung function and transplant-free survival in both cohorts, and whole-blood RNA sequencing linked high microvascular risk to immune-mediated pathways. Intriguingly, among patients with a high microvascular risk score, those subsequently started on nintedanib had markedly better three-year transplant-free survival than those who received no antifibrotic — roughly a 44 percent lower risk of death or transplant. That comparison is non-randomised and confounded by whoever gets offered treatment, but it hints at a biomarker-guided approach to antifibrotic timing. Then a clean negative trial, in the American Journal of Respiratory and Critical Care Medicine: Dowman and colleagues randomised 131 participants with fibrotic interstitial lung disease, stratified by exertional desaturation, to high intensity interval training or standard moderate intensity continuous training within an eight-week pulmonary rehabilitation programme [8]. Cycle endurance time improved meaningfully in both arms, with no difference between them, and no difference in six-minute walk distance, symptoms, quality of life, muscle measures or physical activity. There were no adverse events in either group, and completion and progression rates were similar. So interval training is not superior — but it is safe and well tolerated in fibrotic disease, which makes it a legitimate alternative for patients who prefer it or who desaturate on sustained effort.

Finally, two contrasting notes on pulmonary vascular disease. In Thorax, Ghofrani and colleagues report ATMOS, a non-randomised, open-label phase 1b single-dose escalation study of mosliciguat, an inhaled soluble guanylate cyclase activator, in 38 participants with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension [9]. Because it activates heme-free enzyme, it should work where oxidative stress has rendered the nitric oxide pathway unresponsive. Peak pulmonary vascular resistance fell by roughly a fifth at the lowest doses and by around a third at the two highest doses, effects that persisted across a three-hour observation window, with mostly mild adverse events — headache, fatigue, some oxygen desaturation — and no meaningful change in systemic vascular resistance or blood pressure. It is a small, uncontrolled, single-dose study, so treat it as proof of concept. Set against that optimism, Respiratory Medicine carries a case series from Tonelli and colleagues describing malignancies occurring in patients treated with sotatercept [10]. Given activin's dual immunologic role and the already elevated cancer risk in pulmonary arterial hypertension, the authors raise the question of whether activin pathway inhibition could permit progression of preexisting or latent malignancy. They are explicit that these cases do not establish causality — this is a hypothesis, not a signal with a denominator — but it is a reasonable prompt to be attentive to cancer history when selecting patients.

If you only have time for one paper this week, make it the Chest analysis of biologic timing in severe asthma [3]. It applies to patients sitting in your clinic today and it reframes a decision most of us make too slowly — the longer you wait, the less remission you can recover.

Here are the key takeaways from this week in Pulmonary. First, in relapsed small-cell lung cancer, a B7-H3 antibody-drug conjugate beat topotecan on survival, progression and response with fewer severe toxicities. Second, eight-year data continue to support adjuvant osimertinib after resection of EGFR-mutated early-stage disease — so make sure resected specimens get molecularly tested. Third, delay costs remission in severe asthma: preserve lung function rather than reserving biologics. Fourth, screen for latent tuberculosis before starting a JAK inhibitor, even where tuberculosis is uncommon. Fifth, high intensity interval training in fibrotic interstitial lung disease is safe and well tolerated but no better than standard moderate continuous training, so let patient preference guide the prescription.

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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This is an automated summary generated by artificial intelligence, which can make mistakes. Always review the original source materials.