Small Airways: The “Silent Zone” of 2021 GINA Report?

Abstract

Asthma is a chronic disease, affecting approximately 350 million people worldwide. Inflammation and remodeling in asthma involve the large airways, and it is now widely accepted that the small airways (those with an internal diameter <2 mm) are involved in the pathogenesis of asthma and are the major determinant of airflow obstruction in this disease. From a clinical perspective, small airways dysfunction (SAD) is associated with more severe bronchial hyperresponsiveness, worse asthma control and more exacerbations. Unlike the GOLD guidelines which, in their definition, identify COPD as a disease of the small airways, the Global Initiative for Asthma (GINA) guidelines do not refer to the prevalence and role of SAD in asthmatic patients. This decision seems surprising, given the growing body of compelling evidence accumulating pointing out the high prevalence of SAD in asthmatic patients and the importance of SAD in poor asthma control. Furthermore, and remarkably, SAD appears to possess the characteristics of a treatable pulmonary trait, making it certainly appealing for asthma control optimization and exacerbation rate reduction. In this mini-review article, we address the most recent evidence on the role of SAD on asthma control and critically review the possible inclusion of SAD among treatable pulmonary traits in international guidelines on asthma.

Monoclonal antibodies targeting small airways: a new perspective for biological therapies in severe asthma

“…These results are consistent with other published data, in which asthma control was closely related to SAD and clinical phenotypes associated with SAD [ 8 , 11 , 21 – 27 ]. Notably, in the majority of these studies, the IOS is better associated with asthma control than spirometry, supporting the importance of using IOS and more modern tools in addition to spirometry in the evaluation of asthma control.…”

“…Many studies and systematic reviews have suggested that small airway dysfunction (SAD) is associated with more severe bronchial hyper-responsiveness, worse asthma control and a higher number of exacerbations [ 4 – 11 ].…”

“…However, conventional spirometry reflects mostly the variability and/or the reversibility of airway obstruction and is unable to sensitively evaluate the small airways, becoming abnormal only when approximately 75% of small airways are obstructed [ 13 ]. To date, there are numerous diagnostic techniques available to assess SAD, from non-invasive to minimally invasive or invasive, such as spirometry (FEF25–75%, FVC, FVC/SVC), impulse oscillometry (IOS) (R5–R20, X5, ΔX5in-esp, AX, Fres), single breath nitrogen washout (SBNW) or multiple breath nitrogen washout (MBNW) test, body plethysmography (RV, RV/TLC), high-resolution computerized tomography (HRCT), nuclear medicine (scintigraphy, SPECT, PET), 3He-magnetic resonance imaging (MRI), sputum induction, and bronchoscopy [ 11 ].…”

“…From this perspective, SAD appears to possess the characteristics of a treatable pulmonary trait, making it certainly appealing for asthma control optimization and exacerbation rate reduction [ 11 ]. This seems especially important in the perspective of moving toward precision medicine.…”

Repositioning baloxavir marboxil as VISTA agonist that ameliorates experimental asthma

“…Asthma is a frequent long-term respiratory condition that impacts over 350 million individuals globally (Cottini et al 2022 ). Over the past decades, the incidence and prevalence of asthma have increased, especially in children.…”