Ves Dimov, MD
Allergist/Immunologist at Cleveland Clinic
Clinical Associate Professor
FAU Charles E. Schmidt College of Medicine
Unmet needs for assessment of small airways dysfunction in asthma will hopefully be met by the ongoing ATLANTIS study
An estimated 300 million people suffer from asthma worldwide. Asthma inflammation affects the entire bronchial tree. The small airways, i.e. less than 2 mm diameter, can be affected by inflammation and remodelling. However, their contribution to asthma control and exacerbations has been minimally investigated. Small airways function can be assessed with invasive and non-invasive techniques, including physiological and radiographic testing, in addition to direct and indirect assessments of inflammation. These tests are usually only available in specialized chest clinics. Unfortunately, there is no gold standard tool, or an easy-to-apply measure, available in which to assess small airways dysfunction (SAD). Thus, there is an unmet need to identify SAD easily and correctly across all severities of asthma, and to assess its role in the control of the disease.
The ATLANTIS study ((AssessmenT of smalL Airways involvemeNT In aSthma) aims to:
- Determine the role of small airways abnormalities in the clinical manifestations of asthma.
- Evaluate which (combination of) clinical methods best assesses the abnormalities of small airways and large airways dysfunction in asthma and best relates to asthma severity, control and future risk of exacerbations, both cross-sectional and longitudinal.
- Further develop and validate the small airways dysfunction tool (SADT).
The ATLANTIS study started in 2014 and the first results are expected in 2016. The data gathered could improve our understanding of small airways pathobiology in asthma and provide a database and sample repository to answer future questions.
Source: Postma DS, Brightling C, Fabbri L, van der Molen T, Nicolini G, Papi A, Rabe KF et al. Unmet needs for the assessment of small airways dysfunction in asthma: introduction to the ATLANTIS study. European Respiratory Journal 2015; 45(6): 1534-1538. (doi:10.1183/09031936.00214314)
Image Source: Flow Chart Graphic, Open Clipart, free to use
Most methods of assessing small airways dysfunction have been largely confined to research purposes
Chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), represent a major social and economic burden. Increasing attention has been directed to the role of small airways in respiratory diseases. Small airways could play a distinct role in specific disease phenotypes. There are limited data on natural history of small airways disease. Most studies have been performed in small population samples, and different techniques to characterize small airways function have been employed. Most methods of assessing small airways dysfunction have been largely confined to research purposes. However, some data are encouraging, and support the utilization of certain techniques into daily clinical practice, particularly for early-stage diseases, when subjects are often asymptomatic and routine pulmonary function tests may normal. Clinical trials and real-life feedback on large populations are highly desirable.
Source: Bonini M and Usmani OS. The role of the small airways in the pathophysiology of asthma and chronic obstructive pulmonary disease. Therapeutic Advances in Respiratory Disease 2015; published online ahead of print, 2 June.
Assessment of Small Airways with Computed Tomography (CT) Leaves More to be Desired
Computed tomography (CT) assessment of air trapping has been considered useful as a measure of small airway disease. Mean lung density (MLD) and the percentage of the lung field occupied by low attenuation area (LAA%) can be evaluated automatically, and their expiratory/inspiratory (E/I) ratios correlate with asthma severity and spirometry parameters. However, mosaic attenuation, another indicator of air trapping, has been assessed visually, and its functional relevance remains controversial.
This retrospective study of 36 nonsmoking patients with stable asthma attempted to correlate mosaic attenuation, which was assessed visually and automatically, and the E/I ratios of MLD and LAA% with clinical and physiological variables, including impulse oscillometry (IOS) indices.
Only the E/I ratios of MLD and LAA% correlated with forced expiratory volume in 1 s/forced vital capacity of spirometry and the IOS indices of resistance from 5 to 20 Hz.
The automatic method for analysis of mosaic attenuation could be useful, but the results themselves may not be reflecting small airway involvement of asthma, unlike the E/I ratios of MLD and LAA%.
Source: Oguma T, Niimi A, Hirai T, Jinnai M, Matsumoto H, Yamaguchi M, Matsuoka H et al. Assessment of small airways with computed tomography: mosaic attenuation or lung density? Respiration 2015; published online before print, April 30.