Update on the roles of distal airways in asthma

Abstract

The present review is the summary of an expert workshop that took place in Vence (France) in 2007 on the role of distal airways in asthma. The evidence showing inflammation and remodelling in distal airways, and their possible involvement in asthma control and natural history, was reviewed. The usefulness and limitations of various techniques used for assessing distal airways were also evaluated, including pulmonary function tests and imaging. Finally, the available data studying the benefit of treatment better targeting distal airways in asthma was examined. It was concluded that both proximal and distal airways were involved in asthma and that distal airways were the major determinant of airflow obstruction. Inflammation in distal airways appeared more intense in severe and uncontrolled asthma. Distal airways were poorly attained by conventional aerosol of asthma medications owing to their granulometry, being composed of 3-5 mm particles. Both proximal and distal airways might be targeted either by delivering medications systemically or by aerosol of extra-fine particles. Extra-fine aerosols of long-acting b-agonists, inhaled corticosteroids or inhaled corticosteroid/long-acting b-agonist combinations have been shown in short-term studies to be not inferior to non-extra-fine aerosols of comparators. However, available studies have not yet demonstrated that extra-fine inhaled medications offer increased benefit compared with usual aerosols in asthmatic patients.

The role of small airways in obstructive airway diseases: Figure 1.

“…This problem can be partly solved by using i.v. gadolinium infusion or by inhalation of 3 He, which allows analysis of ventilation distribution, estimated nonventilated lung volume and percentage diseased lung. The PHIL study evaluated He-MRI findings versus HCRT findings in 29 normal volunteers and in 52 subjects with COPD and performed correlation with FEV1/FVC indicating airway obstruction, and DL,CO indicating alveolar destruction [65].…”

“…Although small airways contribute little to airway resistance in healthy subjects, studies using invasive measurement of airway resistance have shown that small airways are the major site of airflow limitation in both asthma and COPD [2]. Despite their importance, small airways have proven difficult to study [3]. Herein, I will examine current knowledge obtained by pathological and physiological measurements, and their relevance to clinical manifestations and therapeutics in asthma and COPD.…”

Update on the roles of distal airways in COPD

“…Distal airways are usually defined as non-cartilaginous conducting airways with an internal diameter ,2 mm (approximately corresponding to eight generations of airways down to terminal and respiratory bronchioles) and alveoli. A more detailed description of the anatomy of distal airways can be found in a review article by BURGEL et al [7]. Inflammatory changes and structural abnormalities in distal airways of COPD patients have proven difficult to explore due to their localisation deep within the thoracic cavity.…”

Is it really time to look at distal airways to improve asthma phenotyping and treatment?

“…The main difficulty is the lack of reliable and widely available lung function parameters able to detect distal airways involvement in clinical practice. A number of parameters have been proposed but most techniques, and particularly the most specific, remain confined to highly specialised lung function laboratories and none can be considered, at present, as the gold standard [3][4][5].…”