Health & Medical Allergies & Asthma

Clinically Relevant Outcomes for New Asthma Therapies

Clinically Relevant Outcomes for New Asthma Therapies

Bronchial Inflammation


Investigation includes invasive and non-invasive methods.

Invasive Measures


Bronchoalveolar lavage (BAL) and endobronchial biopsies sampling by fibreoptic studies have brought valuable information on the pathophysiological aspects of asthma. These techniques have been standardized and allow exploration of the effects of treatment on structural and inflammatory features. They can be applied following allergen challenges or drug interventions but have been used less frequently since the rapid development of noninvasive methods such as sputum or exhaled gases analyses.

Noninvasive Measures


Induced sputum cells and supernatant analysis is a noninvasive way to investigate airway inflammation that has been extensively used in cross-sectional and longitudinal studies. Sputum eosinophil and neutrophil percentages have been used to define inflammatory asthma phenotypes and as predictors of airway asthma exacerbations. Eosinophilia usually suggests steroid-responsiveness, but persistent, uncontrolled eosinophilic asthma may represent a potential target for anti-TH2 mediators biotherapies such as anti-IL5. Nair previously cautioned however that potential agents against eosinophilic or neutrophilic inflammation must be tested in patients with such inflammatory phenotype.

Otherwise, fractional exhaled nitric oxide (FENO) is an easy to measure, reproducible, noninvasive biomarker used to support the diagnosis of asthma. FENO is responsive to ICS and can reflect either treatment nonadherence or uncontrolled/severe asthma. It is however considered an imperfect marker of long-term treatment needs. Cut-off values may vary according to smoking/allergen exposure or in allergic, nonasthmatic individuals, but overall, the changes may be useful in drug interventions. Haccuria et al. recently reported that FENO was also influenced by airway calibre. Otherwise, Hastie et al. suggested that blood eosinophil counts, total serum IgE levels, FENO values and FEV1, despite significant statistical associations, did not accurately predict sputum eosinophil and neutrophil percentages.

Furthermore, exhaled breath condensate (EBC) analysis of its components such as airway pH or oxidative-related mediators may assess airway inflammation, although there are still problems of dilution repeatability and reproducibility that preclude their use in clinical trials. Exhaled breath analysis with a sensor array approach (electronic nose) has been tested to discriminate asthma from other chronic airway disorders. The different volatile organic compounds may reflect asthma pathophysiology, but it requires some refinement and validation, to be used in the setting of randomized control studies in asthma.

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