La suberosis: implicación de los mastocitos broncoalveolares en la génesis de la afectación intersticial

Abstract

Suberosis--the lung disease suffered by cork industry workers--may present in the form of either hypersensitivity pneumonitis (HP) or obstructive pulmonary disease (OPD) with asthma-like symptoms or chronic bronchitis. Mast cells play an important role in pulmonary inflammation and are particularly implicated in the rapid release of mediators in bronchoconstriction and the production of cytokines and mediators of fibroblast activity. Increased numbers of mast cells are present in bronchoalveolar lavage (BAL) fluid in interstitial lung diseases, suggesting that these cells also participate in chronic inflammatory processes and in pulmonary fibrosis. To assess the participation of mas cells in interstitial pulmonary inflammation in cork industry workers by histochemically analyzing their presence in BAL fluid. Foreseeing the possible implication of bronchoalveolar mast cells in the pathogenesis of suberosis, we also studied their relation to various signs and symptoms of the disease, to respiratory function parameters and to degree of alveolitis. Thirty-one cork industry workers with respiratory symptoms related to occupational exposure were enrolled. Occupational and case histories were taken. Physical examinations were complemented by chest X-rays, plethysmography/spirometry, fiberoptic bronchoscopy with BAL, and determination of carbon monoxide diffusing capacity (DLCO) and arterial blood gases at rest. Patient classification (20 with HP and 11 with OPD) was based on clinical and functional criteria and analysis of BAL fluid. Mast cells in cytospinned samples treated with two different stains [May-Grunwald-Giemsa (MGG) and Toluidine Blue (Tol.Bl.)] were counted by two observers and the results were compared. Good correlation between the two staining methods was confirmed (rs = 0.86, p < 0.0001). Correlation between the two observers was also good (MGG rs = 0.86, Yol.Bl. rs = 0.87, p < 0.0001). The number of mast cells in BAL fluid was significantly higher in patients with HP [13.4 +/- 4.5 (x +/- SEM)] than in those with OPD (0.9 +/- 0.3; p < 0.002, Mann Whitney test). The subgroup of eight patients with poorer respiratory function (CV and/or DLCO < 80% of reference value) also had higher mast cell counts in BAL (19.9 +/- 7.7 versus 3.5 +/- 1.7; p = 0.002). We also saw a negative relation between mast cell counts in BAL fluid and lung function parameters: total lung capacity (rs = -0.68, p = 0.005) and DLCO (rs = -0.54, p = 0.008). Mast cell recovery from BAL fluid was positively related to severity of alveolitis in terms of total cell counts (rs = 0.62, p = 0.002), absolute lymphocyte counts (rs = 0.56, p = 0.006) and albumin levels (rs = 0.68, p = 0.003). Our findings suggest that mast cells participate in interstitial lung cell response to the inhalation of organic cork dust, particularly when HP is the form of presentation. Moreover, mas cell recruitment on the alveolar surface seems to be related to the intersity of lymphocytosis and interstitial pulmonary inflammation and to lung function deterioration in affected patients.