Patients with ME are at increased risk for severe exacerbation despite more intensive maintenance anti-inflammatory treatment. Persistent irreversible airflow limitation and complications of chronic sinusitis and/or NSAIDs intolerance are characteristics to this subpopulation.

Background: The 72 kDa matrix metalloproteinase 2 (MMP-2) and the 92 kDa matrix metalloproteinase 9 (MMP-9) are type IV collagenases implicated in various aspects of inflammation including accumulation of inflammatory cells, tissue injury, and development of remodelling. The role of these enzymes in the pathogenesis of asthma exacerbations is unknown. Methods: Circulating levels of MMP-2 and MMP-9 proteins and the expression of their inhibitor, tissue inhibitor of metalloproteinase 1 (TIMP-1), were measured in 21 patients experiencing an asthma exacerbation and 21 age matched patients with stable asthma. Circulating gelatinolytic activity was compared during the asthma exacerbation and during subsequent convalescence by gelatin zymography in the same individuals. In addition, MMP-9 specific activity was quantified with a colorimetric assay which uses an artificial proenzyme containing a specific domain recognised by MMP-9 in the same paired samples. Results: A significant increase in the circulating level of MMP-9 was seen in patients with an asthma exacerbation compared with patients with stable asthma (202.9 (22.0) v 107.7 (9.9) ng/ml, p=0.0003). There were no significant differences in the circulating levels of MMP-2 or TIMP-1. Gelatin zymography identified two major circulating gelatinolytic activities corresponding to MMP-2 and MMP-9, and showed that asthma exacerbations are characterised by markedly increased MMP-9 activity with no significant change in MMP-2 activity compared with the activities during convalescence in the same individuals. Direct measurement showed that MMP-9 specific activity is significantly increased during asthma exacerbations compared with subsequent convalescence (269.6 (31.7) v 170.4 (12.6) ng/ml, p=0.0099). Conclusions: Asthma exacerbations are characterised by increased circulating MMP-9 activity. This increased activity may be related to exaggerated airway inflammation and airway remodelling. It is generally accepted that chronic inflammation leads to airway remodelling in patients with asthma 1 and that this may contribute to irreversible airflow obstruction in affected individuals.2 The role of inflammation in the pathophysiology of asthma is related to the fact that the intensity of inflammation is associated with the degree of airway remodelling, 2 as well as with the severity of disease. 3 The inflammatory processes underlying asthma involve a complex interaction of cell communications that result in increases in airway wall thickness. These alterations include an increase in vascularity, the development of oedema, smooth muscle hypertrophy and hyperplasia, and hyperplasia of mucus glands. 4 Increases in the thickness of the basement membrane and subepithelial fibrosis 4 5 also occur and are currently recognised as the hallmarks of remodelled asthmatic airways. 6 These changes are believed to be related to the severity of the disease.7 Several lines of evidence suggest that these changes are part of the repair process designed to restore tissue integrity in response to inf...

A 54-year-old female presented with an exacerbation of right middle lobe bronchiectasis. A bronchoscopic bronchial washing and repeated trials of sputum culture consistently recovered no other infectious agent except Exophiala dermatitidis. Her illness was improved by administrations of intravenous miconazole and nebulized amphotericin B when sputum cultures yielded no fungi, demonstrating a pathogenic role of the fungi. The present case illustrates E. dermatitidis as a pathogenic agent in non-cystic fibrosis bronchiectasis.

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Summary:Lung parenchymal disease is associated with reduced pulmonary function in patients with sarcoidosis, however, the underlying pathophysiology of the condition is unclear. The present study was conducted to characterize the association between pulmonary function and bronchoalveolar lavage (BAL) findings in patients with sarcoidosis. Twenty-three patients with lung parenchymal disease (stage 2) and twenty-five patients without lung parenchymal disease (stage 1) underwent pulmonary function tests, including blood gas analysis, spirometry and diffusing capacity for carbon monoxide (DLco) and BAL, to determine the number of inflammatory cells, matrix metalloproteinase (MMP) 9 activity and tissue inhibitor of metalloproteinase (TIMP) 1 concentration in the lower airway. Vital capacity (VC) to its reference value (%VC) and %DLco were significantly reduced in patients with stage 2 disease in comparison with those with stage 1 disease. BAL fluid analysis revealed that the numbers of total inflammatory and CD8 cells, and TIMP-1 concentration were significantly higher in patients with stage 2 disease in comparison with those in patients with stage 1 disease. There were significant correlations between %VC and the numbers of inflammatory cells and TIMP-1 in the BAL fluid. These results suggest that inflammation and enhanced TIMP-1 concentration in the lower airway play critical roles in the impaired pulmonary function in patients with lung parenchymal sarcoidosis. Key words sarcoidosis, lung parenchymal diseaseCorrespondence to: Dr Koga, Asakura Medical Association Hospital, Raiharu 422-1, Asakura 838-0069, Japan. Tel: +81-946-23-0077 Fax: +81-946-23-0076 E-mail: koga.tk@asakura-med.or.jp Abbreviations: BAL, bronchoalveolar lavage; BHL, bilateral hilar lymphadenopathy; DLco, diffusing capacity for carbon monoxide; ECM, extracellular matrix; MMP, matrix metalloproteinase; TIMP, tissue inhibitor of metalloproteinase; VC, vital capacity.