Preterm birth has lifelong pulmonary consequences, with many individuals developing prematurity-associated lung disease (PLD). This third paper in the prematurity-associated lung disease Series summarises current evidence for treatment and monitoring of PLD and its phenotypes. Preventive strategies, including maternal and infant vaccination to reduce early life viral exposures, are emerging as key interventions. Pharmacological approaches, such as inhaled corticosteroids, alone or combined with long-acting bronchodilators, show potential benefits in childhood, although there is currently little evidence on phenotype-specific responses. Management should also address extrapulmonary traits, including central airway abnormalities, cardiovascular sequelae, gastro-oesophageal reflux, impaired growth, neurodevelopmental disabilities, reduced physical exercise capacity, and environmental exposures. We discuss monitoring tools for early identification and longitudinal assessment of PLD, evaluation of treatment response, and recommendations for structured follow-up from infancy into adulthood, suitable for both general and specialist respiratory clinicians. Finally, opportunities for repurposing existing drugs and developing new therapies for PLD in children and adults are highlighted.

Exacerbations punctuate the natural course of chronic obstructive pulmonary disease (COPD), posing a substantial burden on patients and health-care systems. Understanding the severity of an acute exacerbation of COPD (AECOPD) is crucial for stratifying mortality risk and guiding treatment decisions. Currently, the severity of an AECOPD is primarily graded on outcomes of health-care use. Given the complex heterogeneity in pathogenesis, clinical presentation, post-event trajectory, and patient perspectives, this approach does not adequately address the causes and extent of clinical deterioration or consider an individual's baseline status, upon which implementation of treatment and prevention of future exacerbations rely. We have conceptualised a multidimensional model to stratify the severity and prognostic risk of an AECOPD, incorporating three distinct domains: baseline functional status (B), the intensity of the event (acuity; A), and the causal trigger (t). The BAt classification for AECOPD could allow for more individualised prognostic and therapeutic implications. The validation process for this model is underway, with preliminary findings supporting its feasibility.

The SOURCE phase 3 oral corticosteroid (OCS)-sparing study of tezepelumab indicated an OCS-sparing effect with tezepelumab versus placebo in patients with OCS-dependent asthma and baseline blood eosinophil counts (BECs) of at least 150 cells per μL. The WAYFINDER study aimed to further evaluate the ability of tezepelumab to reduce or discontinue OCS use in a larger cohort of patients with OCS-dependent severe, uncontrolled asthma.

Endotracheal tubes with subglottic ports and a polyurethane cuff are recommended for reducing microaspiration in patients who are ventilated. However, their long-term safety and efficacy after emergency intubation are uncertain.

Preterm birth is increasingly recognised as a determinant of chronic respiratory disease across the life course. In this Series on prematurity-associated lung disease (PLD), we introduce the concept of PLD as a unifying framework for the diverse pulmonary consequences of preterm birth. Historically, most attention has focused on extremely preterm infants (<28 weeks of gestation) who develop bronchopulmonary dysplasia (BPD), yet not all infants with BPD have long-term morbidity. Conversely, those born very (28-31 weeks), moderate (32-33 weeks), or late (34-36 weeks) preterm also have increased risk for developing lung disease. Multiple factors beyond BPD-including gestational age and intrauterine growth restriction-contribute to PLD development. Recently described PLD phenotypes include prematurity-associated obstructive lung disease, prematurity-associated preserved ratio impaired spirometry, and prematurity-associated dysanapsis. Each phenotype reflects distinct early-life exposures and mechanisms, with differing implications for prognosis. Defining these phenotypes provides a foundation for personalised monitoring and targeted therapeutic strategies.

Monotherapy with KRAS (ie, KRAS Gly12Cys) inhibitors has emerged as a mainstream treatment for patients with KRAS -mutated non-small-cell lung cancer (NSCLC). Synergistic effects have been observed with the combination of a KRAS inhibitor and a SHP2 inhibitor in multiple xenograft models. We aimed to evaluate the safety and efficacy of the KRAS inhibitor glecirasib combined with the SHP2 inhibitor sitneprotafib (JAB-3312; Jacobio Pharmaceuticals, Beijing, China) in patients with KRAS -mutated solid tumours.

Preterm birth is increasingly recognised as adversely influencing lifelong lung function. This Series paper on prematurity-associated lung disease reviews studies reporting longitudinal lung function measurements in individuals who were born preterm. Evidence suggests that preterm birth alters lung function trajectories from early life onwards, with implications for future respiratory morbidity. We propose that this population needs rigorous follow up that should include systematic monitoring of lung function across the lifespan, starting in childhood. Key priorities include understanding risk factors for poor lung function trajectories and moving beyond bronchopulmonary dysplasia alone to establish the phenotype of individuals who were born preterm that are at increased risk of poor trajectory more precisely. Novel approaches, including data-driven analytics and large-scale collaborative studies, will be essential to define phenotypes and trajectories of prematurity-associated lung disease more robustly. Finally, we highlight the need for interventional studies to establish whether adverse lung function trajectories can be stabilised or improved, thereby reducing risk of early chronic obstructive pulmonary disease (ie, diagnosis at age <50 years).