Paggiaro P, Bacci E, Paoletti P, Bernard P, Dente F L, Marchetti G, Talini D, Menconi G F, Giuntini C
Second Medical Clinic, University of Pisa, Italy.
Chest. 1990 Sep;98(3):536-42. doi: 10.1378/chest.98.3.536.
To evaluate the morphologic basis of the different outcomes of toluene diisocyanate (TDI) asthma after quitting occupational exposure, we examined ten patients with TDI asthma who showed, at diagnosis, a positive TDI challenge test and nonspecific bronchial hyperresponsiveness (NSBH) to methacholine. After diagnosis, all patients ceased work and a 4- to 40-month follow-up was obtained with three to eight determinations of the cumulative dose producing a 15 percent fall in FEV1 (PD15FEV1) methacholine in each patient. Bronchoalveolar lavage (BAL) and biopsy of bronchial muscosa were performed 3 to 39 months after cessation of work, in the absence of acute exacerbations of the disease. Total cell count in BAL fluid was moderately increased in four of ten patients, eosinophils were increased in five of ten patients, and neutrophils were increased in eight of ten patients. Mucosal biopsy specimens of main or lobar bronchi were available in eight of ten patients; epithelial damage and thickening of basement membrane was observed in almost all patients, as well as a mild-to-moderate inflammatory reaction in the submucosa, mainly represented by lymphocytes, eosinophils, and neutrophils. No relationship was observed between the cellularity of BAL and the degree of NSBH at the time of BAL; mean values of total cells and differential count were not different between patients with presence or absence of the different histologic findings. Mucosal biopsy and BAL were performed also in four subjects exposed to dusts without respiratory symptoms or NSBH; similar findings were obtained except for the absence of eosinophils in BAL and a lesser degree of basement membrane thickening and inflammatory reaction in the submucosa. The study of the changes in NSBH after quitting exposure showed that five of ten patients had a significant improvement in NSBH to methacholine, as evaluated by a positive significant linear regression between months of work cessation and PD15FEV1 methacholine; only one of these five patients had an increased number of eosinophils in BAL fluid. By contrast, four of the five patients with persistent NSBH after quitting exposure had an increased number of eosinophils in BAL. We suggest that persistent NSBH in TDI asthma after cessation of work may be related to an inflammatory reaction in which eosinophil infiltration seems to be a major determinant.
为了评估停止职业接触后甲苯二异氰酸酯（TDI）哮喘不同转归的形态学基础，我们检查了10例TDI哮喘患者，这些患者在诊断时TDI激发试验呈阳性，对乙酰甲胆碱有非特异性支气管高反应性（NSBH）。诊断后，所有患者停止工作，并对每位患者进行了4至40个月的随访，期间对导致第1秒用力呼气容积（FEV1）下降15%的乙酰甲胆碱累积剂量（PD15FEV1）进行了3至8次测定。在停止工作3至39个月后，且在疾病无急性加重的情况下，进行了支气管肺泡灌洗（BAL）和支气管黏膜活检。10例患者中有4例BAL液中的总细胞数中度增加，10例中有5例嗜酸性粒细胞增多，10例中有8例中性粒细胞增多。10例患者中有8例获得了主支气管或叶支气管的黏膜活检标本；几乎所有患者均观察到上皮损伤和基底膜增厚，以及黏膜下层轻度至中度炎症反应，主要由淋巴细胞、嗜酸性粒细胞和中性粒细胞构成。在进行BAL时，未观察到BAL中的细胞成分与NSBH程度之间存在关联；存在或不存在不同组织学表现的患者之间，总细胞数和分类计数的平均值并无差异。我们还对4例接触粉尘但无呼吸道症状或NSBH的受试者进行了黏膜活检和BAL；除BAL中无嗜酸性粒细胞以及黏膜下层基底膜增厚和炎症反应程度较轻外，获得了相似的结果。对停止接触后NSBH变化的研究表明，10例患者中有5例对乙酰甲胆碱的NSBH有显著改善，这通过停止工作月数与乙酰甲胆碱PD15FEV1之间呈显著正线性回归得以评估；这5例患者中只有1例BAL液中的嗜酸性粒细胞数量增加。相比之下，停止接触后仍有持续性NSBH的5例患者中有4例BAL中的嗜酸性粒细胞数量增加。我们认为，停止工作后TDI哮喘患者的持续性NSBH可能与一种炎症反应有关，在这种炎症反应中，嗜酸性粒细胞浸润似乎是一个主要决定因素。
