Monitoring airway inflammation in asthma by induced sputum
Authors: H. Magnussen, O. Holz
Journal: European Respiratory Journal (1999)

In the past, airway inflammation has been detected by the study of the cellular and biochemical composition of bronchial lavage fluid and biopsies. Owing to its invasive nature, however, bronchoscopy is not an appropriate method for repeated measurements. Therefore, a noninvasive method, such as sputum induction, is needed to understand better the role of airway inflammation in the natural course of asthma, in determining the consequences of therapeutic interventions, and in studying cellular mechanisms during exacerbation and improvement of the disease. Sputum has been used for more than a hundred years to characterize airway diseases and in 1992 PIN et al. [1] proposed inducing sputum by the inhalation of hypertonic saline in those subjects and patients with airway diseases not complaining of spontaneous sputum production. Today, the method is considered to be reliable, valid, responsive and reproducible [2, 3]. Although the procedure is noninvasive, the inhalation of hypertonic saline by hyperresponsive subjects is often followed by an obstructive airway response; therefore, sputum induction should always be preceded by inhalation of bronchodilators (e.g. b2-agonist) and frequent measurements of lung function should be performed during the induction procedure to avoid significant bronchoconstriction. Experience in many laboratories has shown that when these precautions are taken into account, sputum induction with hypertonic saline is a method with acceptable side-effects [4]. In patients with more severe asthma it is even feasible to use isotonic saline and shorter inhalation periods to minimize further the risk of developing airway obstruction during the procedure. This modification has recently been proposed by PIZZICHINI et al .[ 5]. In this issue of the Journal, PIZZICHINI et al. [6] report the use of their modified technique of sputum induction to study eight prednisone-dependent patients with asthma during a programmed reduction of prednisone. The measurements of sputum, blood and clinical parameters were started after 1 week of high-dose prednisone treatment, during the programmed reduction, at clinical exacerbation and again after a high-dose of prednisone treatment for 1 week, and detailed data are presented for the last two time points. Although only a small number of patients were studied, the authors found that the time course of sputum eosinophilia differs from the time course of blood eosinophilia and clinical parameters and, in particular, that sputum eosinophilia precedes clinical exacerbation by several weeks. These results are in line with observations made in a similar study by the same group in which changes in sputum eosinophils, blood and clinical parameters in a group of nonprednisone-dependent asthmatics were examined after an exacerbation. Sputum eosinophils decreased later as a result of prednisone treatment compared with blood eosinophils and clinical parameters [5]. In both studies the treatment was accompanied by changes in the concentration of eosinophil cationic protein, similar to changes in eosinophil number, while the responses of fibrinogen and interleukin-5 were more pronounced in the nonprednisone-dependent asthmatics in the first study. The results of these studies in patients with severe asthma suggest that the degree of sputum eosinophilia as a marker of airway inflammation can be used to monitor the effect of treatment more accurately than blood or clinical parameters. Clearly, this information would have substantial consequences for the understanding of the course of asthma and the timing of therapy. Stimulated by the observations of PIZZICHINI et al. [5, 6], we would like to address four points: the methodological aspect, the time course of events, the target of therapy and the need for early intervention.