Revisiting Type 2 Inflammation and Airway Hyper-responsiveness in COPD

Area of Science:

• Pulmonology and Respiratory Medicine
• Clinical Immunology
• Pharmacology

Background:

• Airway hyper-responsiveness (AHR), common in asthma, is under-recognized in chronic obstructive pulmonary disease (COPD).
• Increasing recognition of COPD heterogeneity, including eosinophilic COPD and asthma-COPD overlap, highlights AHR as a marker for type 2 (T2) inflammation.
• This T2-high phenotype affects 20-40% of COPD patients, driving interest in biologics targeting IL-4, IL-5, IL-13, and TSLP.

Purpose of the Study:

• To review current evidence on AHR in COPD.
• To explore the relationship between AHR, inflammatory phenotypes, diagnostic methods, and therapeutic implications in COPD.
• To assess AHR as a potential treatable trait in COPD management.

Main Methods:

• Review of existing literature on AHR in COPD.
• Analysis of diagnostic modalities: direct challenges (e.g., methacholine) assessing airway geometry vs. indirect challenges (e.g., mannitol) reflecting T2 inflammation.
• Correlation of AHR with inflammatory markers like eosinophils and fractional exhaled nitric oxide (FeNO).

Main Results:

• AHR in COPD involves both structural and inflammatory mechanisms.
• Indirect challenges correlate better with T2 inflammation markers (eosinophils, FeNO) than direct challenges.
• Patients with AHR may respond better to inhaled corticosteroids; biologics show promise but require specific COPD trials.

Conclusions:

• AHR is a clinically relevant trait in COPD, especially in T2-high phenotypes.
• Standardized AHR challenges, inflammatory marker integration, and targeted biologic trials are crucial for personalized COPD management.
• AHR represents a promising treatable trait for optimizing COPD therapy.