Seven Pillars of Small Airways Disease in Asthma and COPD – Supporting Opportunities for Novel Therapies.

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Identification of pathological changes in early and mild obstructive lung disease has revealed the importance of the small airways and their contribution to symptoms. Indeed, significant small airways dysfunction has been found before any overt airway obstruction is detectable by conventional spirometry techniques. However, most therapies for the treatment of obstructive lung disease target the physiological changes and associated symptoms that result from chronic lung disease, rather than directly targeting the specific underlying causes of airflow disruption or the drivers of disease progression. In addition, while spirometry is the current standard for diagnosis and monitoring of response to therapy, the most widely used measure, forced expiratory volume in 1 second, does not align with the pathological changes in early or mild disease and may not align with symptoms or exacerbation frequency in individual patient. Newer functional and imaging techniques allow more effective assessment of small airways dysfunction; however, significant gaps in our understanding remain. Improving our knowledge of the role of small airways dysfunction in early disease in the airways, along with the identification of novel endpoints to measure sub-clinical changes in this region, i.e. those not captured as symptoms or identified through standard FEV1, may lead to the development of novel therapies that directly combat early airways disease processes with a view to slowing disease progression and reversing damage. This expert opinion paper will discuss small airways disease in the context of asthma and COPD and highlight gaps in current knowledge that impede earlier identification of obstructive lung disease and the development and standardization of novel small airways-specific endpoints for use in clinical trials.

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Authors: Omar S Usmani, MeiLan K Han, David A Kaminsky, James Hogg, Josephine Hjoberg, Naimish Patel, Megan Hardin, Christina Keen, Stephen Rennard, François-Xavier Blé, Mary N Brown