Do small airway abnormalities characterize asthma phenotypes? In search of proof

Abstract

The role of small airway abnormalities in asthma pathogenesis has been extensively studied and debated for several decades. However, whether or not small airway abnormalities play a relevant role in specific phenotypes of asthmatic patients and contribute to clinical presentation is largely unknown. In the present review, we evaluated available data on the role of small airways in severe asthma, with a further focus on asthma in smokers and asthma in the elderly. These phenotypes are characterized by a poor response to treatment and they can represent a model of greater small airway impairment. In severe asthmatics, small airway involvement has been shown through evidence of both distal inflammation and of increased air trapping. The few available data on asthmatics who smoke, and elderly asthmatics, similarly suggests that small airway abnormalities contribute to the pathogenesis of the disease. In this perspective, there could be a rationale for specifically assessing small airway impairment in these patients and for clinical studies evaluating whether pharmacological approaches targeting the more peripheral airways result in clinical benefits beyond conventional therapy.

Leukotriene receptor antagonists pranlukast and montelukast for treating asthma

“…Recent findings support the concept that not only central, but peripheral airways are involved in allergic airway inflammation and obstruction, especially in severe asthma [76,77]. Furthermore, the density of inflammatory cells is greater in the outer, than in the inner airway walls of asthmatic peripheral airways [78].…”

Assessing small airway impairment in mild-to-moderate smoking asthmatic patients

“…In asthma, small airway alterations are associated with poor clinical outcomes [1]. Cigarette smoke is known to induce peripheral airway abnormalities, asthmatic smokers exhibit a more rapid lung function decline, experience more frequent exacerbations and are more likely to be uncontrolled, even when the disease is managed as recommended [2].…”

Assessing and accessing the small airways; implications for asthma management

“…There is abundant evidence that inflammatory and functional abnormalities of the lung periphery occur in all stages of the disease from the mildest [10,11] to the most severe form [12,13]. Interestingly, a correlation between disease severity and the magnitude of small airway impairment has been documented [14]. The question arises as to whether peripheral airways are a site of structural and functional alterations in asthma irrespective of the clinical manifestation or does the involvement of the peripheral airways in asthma represent a specific phenotype of the disease that leads to more severe manifestations, poor clinical control and/or poor response to treatment.…”