This Week in Pulmonary — Aug 11, 2026

Welcome to This Week in Pulmonary. This week we're covering 10 notable papers spanning thoracic oncology and lung cancer screening, sleep-disordered breathing and cardiovascular risk, and a mixed bag of results in obstructive and interstitial lung disease. Let's dive in.

We start in thoracic oncology, where two papers push in the direction of more targeted, more individualised treatment. In JAMA, a multicentre phase 3 randomised trial from 17 sites in China asked whether patients with EGFR-mutated advanced non-small cell lung cancer who also carry a concurrent TP53 mutation — a group known to do worse on tyrosine kinase inhibitor monotherapy — benefit from adding chemotherapy to first-line osimertinib. Two hundred and ninety-four treatment-naive patients with stage four or recurrent nonsquamous disease were randomised to osimertinib plus pemetrexed and carboplatin, or osimertinib alone. At a median follow-up of about two years, median progression-free survival was 34 months with the combination versus 15.6 months with monotherapy — a difference of more than 18 months, and roughly a 56 percent reduction in the risk of progression or death [1]. The benefit held in prespecified subgroups including patients with brain metastases and those with L858R mutations. Two caveats matter: overall survival data are only about 30 percent mature, so we have a trend but not proof of a survival benefit, and grade 3 or higher treatment-related adverse events were more common with combination therapy, though no new safety signals emerged. Practically, this is the strongest prospective evidence yet that TP53 co-mutation status — which many of us already have on next-generation sequencing panels — can be used to select which EGFR-mutant patients should be offered upfront chemotherapy rather than osimertinib alone. Alongside that, the Journal of Thoracic Oncology reports a small single-centre case series of 11 patients with metastatic DLL3-high pulmonary carcinoid treated with the bispecific T-cell engager tarlatamab, a drug we currently associate with small cell lung cancer. Eight of 11 responded, all 11 had some tumour shrinkage, and disease control was universal, including one patient with central nervous system-only disease [6]. Cytokine release syndrome occurred in cycle one in nine of 11, two at grade 3. Eleven patients is not a trial, but for a tumour where systemic options rarely produce responses, this is a signal worth acting on by checking DLL3 expression and seeking trial enrolment.

Staying with lung cancer but moving upstream to screening, JAMA Internal Medicine published a pragmatic two-by-two factorial randomised trial in nearly 1,900 patients at Kaiser Permanente Washington who had completed a low-dose CT with normal findings. The two interventions were a patient-facing health communication package of print and video messaging, and a Stepped Reminders strategy in which the follow-up scan order was pended for the primary care physician and the patient was contacted to schedule it. The results diverged sharply. Stepped Reminders raised adherence to the annual scan from 47 percent to 76 percent — a 28 percentage point absolute gain — with the largest effect in patients who were currently smoking, where adherence rose from 41 to 73 percent [4]. The health communication intervention, by contrast, was associated with adherence about 5 percentage points lower than in those who did not receive it, a statistically significant negative finding. The message is uncomfortable but useful: more patient education material did not help and may have hurt, whereas building the order and the reminder into the workflow moved adherence substantially. If your screening programme is struggling with the second and third annual scans, invest in pended orders and coordinator-driven outreach, not brochures.

Turning to sleep medicine, where the central unresolved question remains whether treating obstructive sleep apnoea reduces cardiovascular events. The European Respiratory Journal reports a French sleep-clinic cohort of 3,370 positive airway pressure-treated patients with moderate-to-severe apnoea, linked to national health claims data and followed for a median of nine years, during which 740 had a major adverse cardiovascular event. Patients were stratified as high risk using two physiological biomarkers — sleep apnoea-specific hypoxic burden and event-related heart rate response. Adherence, defined as at least four hours per night, was associated with roughly a 47 percent lower risk of major cardiovascular events overall, and importantly the association was significantly stronger in the high-risk group, with a significant interaction [2]. The same pattern held using simplified versions of both biomarkers derived from oximetry alone, and appeared stronger in non-sleepy patients — precisely the group that randomised trials have struggled to show benefit in. This is observational, so adherence remains a marker of healthier behaviour as well as of treatment, but it offers a plausible explanation for why unselected trials have been neutral, and it suggests hypoxic burden and autonomic response deserve a place in how we counsel patients about cardiovascular benefit. Complementing that, Chest published a patient-centred narrative review on mask selection, noting that the larger comparative studies — all observational and potentially selection-biased — favour nasal over oronasal masks for both objective and patient-reported outcomes, and emphasising that distinguishing mouth leak from mask leak lets you correct the actual problem rather than cycling through new masks [8]. Three-dimensional facial scanning and artificial intelligence-assisted fitting are emerging, but the practical takeaway is that leak troubleshooting and structured follow-up, in person or by telehealth, are where adherence is won.

In obstructive and interstitial lung disease, the week brings one clear negative trial and several refinements. The European Respiratory Journal reports a phase 2a, double-blind, placebo-controlled trial of mitiperstat, a myeloperoxidase inhibitor, in 381 patients with moderate-to-severe chronic obstructive pulmonary disease at high exacerbation risk on dual or triple inhaled therapy. Time to first composite exacerbation event was not improved — around two thirds of patients in both arms had an event — nor was time to first moderate-to-severe exacerbation, lung function, symptoms, or disease impact, and there were seven pneumonias on drug versus two on placebo [5]. The authors conclude the risks outweigh the benefits, which closes the door on this compound and is a reminder that targeting neutrophilic inflammation in chronic obstructive pulmonary disease remains unproven. On the diagnostic side, Respiratory Medicine reports quantitative CT analysis in 2,579 participants from the Swedish CArdioPulmonary bioImage Study, of whom 430 had chronic airflow limitation. Expiratory CT measures discriminated airflow limitation better than inspiratory measures; combining both raised the area under the curve from 0.66 to 0.77, and adding deep-learning lobar analysis reached 0.81, with 94 percent negative predictive value but a positive predictive value of only 34 percent [9]. That profile makes it useful for ruling out rather than diagnosing airflow limitation opportunistically on chest CT. In Thorax, a prospective study of 100 patients with idiopathic pulmonary fibrosis on nintedanib found that 46 percent developed diarrhoea and that lower standardised body surface area was an independent predictor, with a model discriminating well; reassuringly, dose adjustment controlled symptoms without compromising forced vital capacity or diffusing capacity trajectories over 12 months [7]. So for your smaller-framed patients, warn early, plan for dose reduction, and don't fear that reduction costs efficacy. Also in the European Respiratory Journal, the global TOPP-2 registry of 445 children with newly diagnosed Group 1 pulmonary arterial hypertension found that children started on dual therapy upfront had markedly lower risk of death or transplant than those started on monotherapy and escalated to dual within a year, and the same held for upfront triple therapy including parenteral prostanoid versus delayed escalation [3] — observational, and confounding by indication is a real concern, but it aligns with the adult paradigm favouring upfront combination therapy. Finally, a single-centre retrospective Chinese cohort of 267 COVID-19 patients needing advanced respiratory support found that antifungal prophylaxis reduced COVID-19-associated pulmonary aspergillosis from about 23 percent to under 4 percent, with preemptive therapy showing a similar trend, but in-hospital mortality was essentially identical across groups at around 45 to 50 percent [10]. Fewer fungal diagnoses, no survival gain, small numbers — not yet a reason to prophylax routinely.

If you only have time for one paper this week, make it the JAMA trial of osimertinib with or without chemotherapy in EGFR-mutant lung cancer with concurrent TP53 mutations [1]. It converts a molecular marker most of us already receive on our sequencing reports into an actionable treatment decision at the very first line, which is where it matters most.

Here are the key takeaways from this week in Pulmonary. First, in EGFR-mutant advanced non-small cell lung cancer, look for a concurrent TP53 mutation, because adding chemotherapy to first-line osimertinib more than doubled progression-free survival in that group, at the cost of more high-grade toxicity and with survival data still immature. Second, DLL3-high pulmonary carcinoid may respond to tarlatamab, based on a very small series with frequent cytokine release syndrome — worth testing for and referring, not yet standard care. Third, to fix lung cancer screening adherence, change the workflow: pended orders plus coordinated reminders raised annual scan completion by nearly 30 percentage points, while patient education material alone performed worse than usual care. Fourth, positive airway pressure adherence was associated with fewer cardiovascular events, and most strongly in patients with high hypoxic burden or a large heart rate response, suggesting these biomarkers can help identify who stands to gain. And fifth, mitiperstat failed on every endpoint in chronic obstructive pulmonary disease, while in idiopathic pulmonary fibrosis, small body size predicts nintedanib-related diarrhoea and dose reduction preserved lung function over a year.

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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