Endotyping Chronic Respiratory Diseases: T2 Inflammation in the United Airways Model

Abstract

Over the past 15 years, the paradigm of viewing the upper and lower airways as a unified system has progressively shifted the approach to chronic respiratory diseases (CRDs). As the global prevalence of CRDs continues to increase, it becomes evident that acknowledging the presence of airway pathology as an integrated entity could profoundly impact healthcare resource allocation and guide the implementation of pharmacological and rehabilitation strategies. In the era of precision medicine, endotyping has emerged as another novel approach to CRDs, whereby pathologies are categorized into distinct subtypes based on specific molecular mechanisms. This has contributed to the growing acknowledgment of a group of conditions that, in both the upper and lower airways, share a common type 2 (T2) inflammatory signature. These diverse pathologies, ranging from allergic rhinitis to severe asthma, frequently coexist and share diagnostic and prognostic biomarkers, as well as therapeutic strategies targeting common molecular pathways. Thus, T2 inflammation may serve as a unifying endotypic trait for the upper and lower airways, reinforcing the practical significance of the united airways model. This review aims to summarize the literature on the role of T2 inflammation in major CRDs, emphasizing the value of common biomarkers and integrated treatment strategies targeting shared molecular mechanisms.

Keywords: asthma; chronic disease; chronic obstructive pulmonary disease; disability; exercise; outcome; rehabilitation.

Figure 1

Innate and adaptive immunity in type 2 (T2) inflammation of upper and lower airways. Th2: T-helper 2 lymphocytes; IgE: immunoglobulins E; TSLP: thymic stromal lympho-proteins; IL: interleukin; ILC2s: non-specific innate lymphoid cells; IL-5Rα: interleukin-5 receptor subunit α.

Figure 2

Eosinophils in nasal lavage (Panel A) and sputum cytology (Panel B).