The use of induced sputum in clinical trials

As asthma is considered to be an inflammatory disorder of the airways, it seems logical to include an assessment of this inflammatory process as an outcome measure in clinical trials. Biopsy studies illustrate that clinical or lung function characteristics such as symptoms, peak flow variability or degree of airway responsiveness do not consistently correlate with histological alterations. Therefore, these clinical indices cannot be seen as accurate markers of airway inflammation 1–3. Conversely, repeated bronchoscopic sampling is not feasible in large­scale clinical studies. Hence there is interest in a relatively noninvasive but direct marker of airway inflammation. Analysis of induced sputum seems to meet these criteria. Provided proper precautions are taken, induction of sputum is safe, even in patients with more severe asthma 4, 5. In addition, sputum cell counts, particularly eosinophil counts, have been well validated in terms of responsiveness to intervention. It has been argued that, in comparison with other noninvasive markers of inflammation, induced sputum offers the most balanced assessment of the degree of inflammation, being more responsive to intervention than serum eosinophil cationic protein, yet not as oversensitive as exhaled nitric oxide 6–8. As for any outcome measure, when including induced sputum in a clinical trial, specific features of sputum analysis need to be taken into account when designing the study: 1) origin of sputum; 2) methodological aspects; 3) selection of subjects; and 4) power calculations. The induced sputum technique samples the inflammatory cells and soluble markers present in the airway lumen of the bronchial tree, which, although reflective of, does not represent an identical situation to the local inflammatory process in the mucosa. This probably explains the poor correlation between the cellular composition of biopsy samples and sputum, bronchial wash or bronchoalveolar lavage 9–11. Therefore, …