Induced sputum: not only for research but also for better patient management in asthma and COPD.

It has been now twenty years since the first description of induced sputum as a research application in asthma [1, 2]. Since then the research application of this technique has really exploded giving rise to an impressive number of publications in the field of asthma and COPD. Overall it is fair to say that asthma is rather an eosinophilic airway disease while COPD patients usually exhibit a massive neutrophilic inflammation [3]. This view is however simplistic and when asthma becomes more severe, eosinophilic inflammation usually coexists with neutrophilic inflammation [4, 5]. On the other hand, a not negligible contingent of COPD displays an eosinophilic airway inflammation [6]. A lot of studies have measured biochemical compounds in sputum supernatant associated with eosinophilic and neutrophilic inflammation. All these studies can be somehow summarized by saying that eosinophilic airway inflammation is usually associated with raised secretion products from eosinophils like eosinophil cationic prtotein (ECP) and Th2 cytokines like interleukine-5, while neutrophilic inflammation is rather associated with secretion products from neutrophils like myeloperoxidase and the neutrophilic chemokine interleukine-8 [7]. Recent studies have gone further by unravelling the sputum cell gene expression associated with each type of inflammation [8, 9]. Sputum has also made it possible to undertake elegant mechanistic studies looking at cellular pharmacology or at biological properties of supernatant. As an example sputum cells can be cultured for 24h ex vivo and assessed for their capacity to release cytokine or growth factors [10]. Also the fluid phase was shown to contain chemotactic or anti-apoptotic activity for eosinophils or neutrophils that sometimes correlated to disease severity [11-14]. One of the most important features in COPD and severe asthma is the airway and lung remodelling, the latter being essentially seen in COPD. By definition remodelling is measured on piece of tissues usually obtained by bronchial biopsies performed during a bronchoscopy. Alternatively remodelling is more and more assessed by fine lung imaging like thin slice chest CT. There has been early attempt to validate some biochemical compounds from sputum supernatant as markers of airway remodelling. Matrix metalloproteases (MMPs) and their physiological inhibitors (TIMPs) are keys in regulating the metabolism of conjunctive tissue. Among those proteins emphasis has been placed on MMP-9, a matrix metalloprotease with gelatinolytic activity, and TIMP-1, its physiological inhibitor. Both the pro and the activated form of MMP-9 and TIMP-1 were found to be raised in asthmatics and COPD as compared to healthy subjects [15]. Vignola et al. have shown the ratio MMP-9/TIMP-1 to be related airway calibre assessed by FEV1 [16]. In stable asthmatics and patients suffering from chronic bronchitis they showed that the lower the ratio the lower the FEV1 suggesting that an excess of TIMP-1 would favour tissues remodelling [17]. In this issue of the journal Dar et al. confirmed previous results of Vignola et al. by showing raised sputum levels of MMP9 and TIMP-1 in sputum from asthmatics and COPD but a clearly reduced ratio MMP-9/TIMP-1 when disease severity increases [18]. Their study is a further validation of the utility of this ratio as a marker of airway remodelling since they found a relationship between the progression of the remodelling on chest CT and a low ratio value. Conversely high MMP-9/TIMP-1 ratio has been found in acute asthma [19] and following experimental allergenic exposure [20]. This suggests that flare up of airway inflammation is actually associated with an enhanced local gelatinolytic activity. Thus the picture may be different in acute conditions as opposed to the stable state of severe chronic disease. Whether a low MMP-9/TIMP-1 ratio would be predictive of an accelerated lung decline in asthma and COPD is an interesting question that should be addressed in a prospective longitudinal study. Induced sputum has been instrumental in the development of asthma and COPD phenotypes based on the nature of the airway cellular inflammation [21, 22]. Based on our experience in a Monaldi Arch Chest Dis 2012; 77: 1, 5-7.