Background:The balance between matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) may be critical in extracellular matrix remodelling, a characteristic of asthmatic airways. An excess of TIMP-1 over MMP-9 has been associated with chronic airflow obstruction but the mechanisms underlying this association remain unknown. Recent computed tomographic (CT) studies indicate that airway wall thickening is associated with chronic airflow obstruction. Methods: Sputum levels of MMP-9, TIMP-1, and their molar ratio were examined in 26 patients with stable asthma and their relationship with pulmonary function and airway wall thickness, assessed by a validated CT technique which measured wall area corrected by body surface area (WA/BSA), the ratio of WA to outer wall area (WA%), and the absolute wall thickness corrected by !BSA of a segmental bronchus (T/ !BSA), was examined. Results: Sputum MMP-9 levels were inversely correlated with WA% and TIMP-1 levels were positively correlated with WA/BSA and T/!BSA. The MMP-9/TIMP-1 molar ratio was inversely correlated with WA% and T/!BSA and positively correlated with post-bronchodilator values of mid-forced expiratory flow and maximum expiratory flow at the quartile of lung volume. Conclusion: Excess TIMP-1 may have a pathogenetic role in airway wall thickening in asthmatic patients which may result in chronic airflow obstruction.

Patients with cough variant asthma, a common cause of chronic cough, may develop wheezing. We examined the determinants of this phenomenon and achievement of remission in 42 patients. During 4 years after diagnosis, wheezing developed in 13 of the patients. Early inhaled corticosteroid treatment was inhibitory against the development of wheezing by univariate analysis and by multivariate analysis with an odds ratio of 0.12 (95% confidence interval, 0.02 to 0.87, p = 0.037). Remission was achieved in 7 patients, who were younger than those without remission by univariate analysis (p = 0.048). Early treatment with inhaled corticosteroid may prevent the progression of cough variant asthma to classic asthma.

Four patients with sarcoidosis presented as hypothalamic-hypophyseal syndrome including diabetes insipidus (DI) were followed up for more than 8 years from the onset of clinical manifestation. The mean age was 26 years, male : female ratio was 3 : 1 and the mean disease duration of 10 years. All patients had hypogonadism, hyperprolactinemia.

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Several cough triggers may reflect the pathophysiology of prolonged or chronic cough.