Purpose of review: Asthma is a chronic inflammatory airway disorder that can involve the entire bronchial tree. Increasing evidence shows that ventilation heterogeneity and small airway dysfunction are relevant factors in the pathogenesis of asthma and represent a hallmark in adults with persistent asthma. Little is known about the contribution of peripheral airway impairment in paediatric asthma, mainly due to the inaccessibility to evaluation by noninvasive techniques, which have only been widely available in recent years. Recent findings: Emerging evidence suggests that small airways are affected from the early stages of the disease in childhood-onset asthma. Conventional lung function measurement, using spirometry, is unable to sensitively evaluate small airway function and may become abnormal only once there is a significant burden of disease. Recent studies suggest that chronic inflammation and dysfunction in the small airways, as detected with new advanced techniques, are risk factors for asthma persistence, asthma severity, worse asthma control and loss of pulmonary function with age, both in adults and children. Knowing the extent of central and peripheral airway involvement is clinically relevant to achieve asthma control, reduce bronchial hyper-responsiveness and monitor response to asthma treatment. Summary: This review outlines the recent evidence on the role of small airway dysfunction in paediatric asthma development and control, and addresses how the use of new diagnostic techniques available in outpatient clinical settings, namely impulse oscillometry and multiple breath washout, could help in the early detection of small airway impairment in children with preschool wheezing and school-age asthma and potentially guide asthma treatment.

Monoclonal antibodies targeting interleukin (IL)-5 pathways have revolutionized the treatment expectations for eosinophilic-associated conditions, particularly in patients with respiratory involvement. Mepolizumab (IL-5 antagonist monoclonal antibody), benralizumab (IL-5 receptor blocker monoclonal antibody), and reslizumab (IL-5 antagonist monoclonal antibody) have collectively contributed to the overall improvement of the disease burden in various conditions. Eosinophilic asthma currently boasts the most robust evidence across all age groups: all three biologics are approved for adults (aged ≥18 years); mepolizumab is approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) also in children (aged ≥ 6 years), while bernalizumab was recently approved by the FDA for patients aged ≥6 years in the USA. In chronic rhinosinusitis with nasal polyps, subcutaneous mepolizumab is the only anti-IL-5 therapy approved so far and can be used in adult patients (aged ≥18 years). For eosinophilic esophagitis, conflicting evidence surrounds both mepolizumab, reslizumab, and benralizumab, leading to non-approval of these agents by the FDA/EMA. Recently, mepolizumab was approved for eosinophilic granulomatosis with polyangiitis patients aged ≥6 years or older and for hypereosinophilic syndrome adult patients. A phase III trial proving noninferiority of benralizumab versus mepolizumab in eosinophilic granulomatosis with polyangiitis has been recently published, while evidence on reslizumab is scant. Overall, current evidence on anti-IL-5 biologics for eosinophilic-associated disorders is mostly focused on adults, whereas data for individuals aged under 18 years and over 65 years are scarce, resulting in a lack of evidence, particularly regarding efficacy, for the use of anti-IL-5 agents in these specific patient populations. This review addresses high-quality evidence from randomized controlled trials and real-world post-marketing studies regarding the use of anti-IL-5 therapies for eosinophilic-associated disorders across all age groups, spanning childhood, adulthood, and older age.

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.