Pulmonology — Weekly Evidence Brief

Recent advancements offer promising tools for personalized diagnostics and treatment optimization in respiratory diseases. A novel support vector machine (SVM) model, incorporating multimodal ultrasound variables such as lung ultrasound scores, diaphragmatic dysfunction, and quadriceps atrophy, achieved excellent diagnostic performance for acute exacerbations of COPD (AECOPD) with an AUC of 0.9302 in a test set, providing a non-invasive, bedside tool 1. For lung transplant recipients, a bronchoalveolar lavage cell pellet (BAL-cp) genomic classifier identified acute cellular rejection (ACR) with an accuracy of 93.1% and predicted chronic lung allograft dysfunction (CLAD) risk, suggesting a less invasive alternative to biopsy 2. Furthermore, a genome-wide association study identified 21 SNPs associated with rapid FEV1 decline in a Korean cohort and developed a genetic risk score (GRS) to predict individuals at higher risk of accelerated lung function decline 3.

Optimizing existing treatments and exploring new therapeutic targets are crucial for improving patient outcomes. A randomized trial demonstrated that a blood eosinophil-guided approach could safely reduce systemic corticosteroid exposure in adults hospitalized for asthma exacerbation, particularly in non-eosinophilic cases, without compromising treatment failure rates 4. In resource-limited settings, implementing a stepped anti-inflammatory reliever (AIR) therapy with budesonide-formoterol significantly reduced the proportion of participants experiencing moderate or severe exacerbations and hospitalizations for undifferentiated obstructive lung disease 5. Beyond existing treatments, preclinical research identified N-phenylquinazolin-4-amine-based EGFR TKIs as suppressors of pulmonary fibrosis in murine models by modulating the alveolar epithelial EGFR/ERBB3 axis, offering a potentially actionable therapeutic strategy for a disease with high unmet needs 6.

Understanding underlying disease mechanisms and patient vulnerabilities can guide more effective interventions. Repression of PDLIM2 in myeloid cells has been identified as a common mechanism across COPD, interstitial lung disease (ILD)/idiopathic pulmonary fibrosis (IPF), and lung cancer, leading to increased susceptibility to infections by exacerbating pro-inflammation and diminishing anti-inflammation signaling 7. Research into IPF also shows variable steady inflammation in normal-appearing and transitional lung areas, with inflammatory markers participating in pro-fibrotic signaling, which might result in dual pro-fibrotic and inflammatory effects during disease progression 8. Additionally, vulnerable subgroups face heightened risk from wildfire smoke exposure, with machine learning models identifying complex heterogeneity in cardio-respiratory health impacts based on individual (age, sex, race/ethnicity) and area-level factors 910.

Lifestyle interventions and comprehensive management strategies continue to demonstrate significant benefits for chronic respiratory conditions. A 12-month pulmonary rehabilitation program in IPF patients significantly enhanced cerebral oxygenation during exercise, improved peak oxygen consumption, increased exercise capacity, and positively impacted psychological health (reduced anxiety/depression) 11. Furthermore, physical activity, even below recommended levels, was associated with reduced all-cause and non-cardiovascular mortality in adults with chronic lower respiratory diseases (CLRD), including COPD. The "weekend warrior" pattern also showed a non-significant, but promising, mortality trend, reinforcing the importance of activity for these patients 12.

In non-small cell lung cancer (NSCLC), molecular subtyping offers avenues for personalized immunotherapy. Unsupervised clustering of pre-treatment tumor transcriptomes from the IMpower150 trial identified four distinct molecular NSCLC subtypes (NMF1-4) with varying tumor PD-L1 expression, immune composition, and responses to atezolizumab-bevacizumab-carboplatin-paclitaxel (ABCP) versus control regimens 13. Notably, the NMF4 subtype, rich in B and T cells and with elevated PD-L1, showed significant progression-free and overall survival benefits with ABCP, while the NMF1 subtype also benefited from ABCP over other regimens 13. These insights are critical for guiding individualized first-line treatment for metastatic NSCLC, moving towards more targeted therapeutic strategies.