Asthma is a common, chronic respiratory disease affecting 1–18% of the whole population in different countries and, despite the advances in diagnosis and treatment, it remains a serious global health problem with a great proportion of patients that are still not properly controlled [1].

The lack of asthma control is rarely associated to a real drug-resistant condition, but it is related to different factors regarding the patients (age, comorbidities, and cognitive status), their therapy compliance, the disease phenotypes, the drugs, and their formulations [2,3,4,5,6,7,8,9]. In particular, recent studies have indicated the inflammation in the small airways as a substantial feature associated with bronchial hyper-responsiveness, worsening of asthma symptoms, and increased exacerbations [10,11].

In this review, we focus our interest in the role played by the small airways and their inflammation in the physiopathological and clinical aspects of asthma and in the recent advances in treatment of this airway compartment. We performed a literature review via Pubmed database using the following terms: “asthma”, “small airways”, “inflammation”, “biomarkers”, “treatment”, “extrafine formulations” in different combination. We selected the studies performed on asthmatic patients on the basis of their relevance.