Effect of inhaled steroids on increased collagen synthesis in asthma.

BACKGROUND: We previously reported that sputum levels of procollagen type I C-terminal peptide (PICP), a marker of ongoing collagen type I deposition, are increased in proportion to airway inflammation in asthma patients. OBJECTIVES: In this study, we examined the effect of inhaled corticosteroids on increased collagen synthesis in step 2-4 asthmatics. METHODS: We compared the sputum PICP concentrations of 25 steroid-naive asthmatics, 25 normal volunteers, and 10 subjects with chronic obstructive pulmonary disease. Asthma subjects were also instructed to start fluticasone propionate treatment, and the percentage of forced expiratory volume in 1 s, sputum eosinophil counts, sputum PICP concentrations, and sputum transforming growth factor-beta-positive cell counts before treatment were compared with those 1 month after treatment. RESULTS: Sputum PICP concentrations were detected in the following order: asthma group >or= chronic obstructive pulmonary disease group > control group. Asthma patients showing high sputum PICP belonged to step 4, although there was no correlation between sputum PICP and asthma severity. Treatment with fluticasone propionate not only significantly improved the mean percentage of forced expiratory volume in 1 s (from 66.7 to 87.2%), but also decreased the mean sputum eosinophil counts (from 13.4 to 5.8%), the mean sputum PICP concentrations (from 30.8 to 10.2 ng/ml), and the mean sputum tumor growth factor-beta-positive cells (from 11.3 to 2.8%). Nevertheless, a significant difference in sputum PICP concentrations was still observed between the control group and the steroid-treated asthma group. CONCLUSIONS: The present results suggest that inhaled corticosteroid treatment might reduce sputum indexes of collagen metabolism and eosinophilic inflammation in asthma patients.

MMP14 gene polymorphisms in chronic obstructive pulmonary disease.

Proteinase/antiproteinase imbalance is a widely accepted theory for the pathogenesis of COPD. Among various proteinases, matrix metalloproteinases (MMPs) digest extracellular matrix of the lung and play significant roles in the development of COPD. Polymorphisms of an MMP that upregulate its activity may result in the degradation of the lung matrix. A case-control study was performed to investigate the association of polymorphisms of the MMP14 gene with COPD. Japanese subjects (96 COPD patients and 61 controls) and Egyptian subjects (106 COPD patients and 72 controls) were recruited. Each subject was genotyped for seven single nucleotide polymorphisms (SNPs) of the MMP14 gene; -165 G/T and -72 G/A in the promoter region, +221 C/T in exon 1, +6727 C/G and +6767 G/A in exon 5, +7096 T/C in exon 6, and +8153 G/A in exon 8. The distributions of the genotype frequencies of these SNPs were not significantly different between the COPD patients and the controls in either ethnic group after correction of multiple comparisons. In the haplotype analysis, however, the haplotype -165 T : +221 T : +6727 C : +7096 C had a significantly higher frequency in the Egyptian COPD group than the control group (pcorr = 0.0063). The haplotype of the MMP14 gene, -165 T : +221 T : +6727 C : +7096 C, might be involved in the pathogenesis of COPD.

The effect of smoking-related hyperhomocysteinemia on spirometric declines in chronic obstructive pulmonary disease in elderly Japanese.

Smoking is implicated in chronic obstructive pulmonary disease (COPD) and hyperhomocysteinemia. To elucidate the role of hyperhomocysteinemia in COPD, we examined the relationship between plasma total homocysteine (tHcy) and spirometric declines in patients with COPD. We recruited 7 male never-smokers, 16 male control smokers, and 24 male patients with COPD. We investigated whether or not smoking might induce hyperhomocysteinemia in subjects predisposed to COPD, and then prospectively examined the relationship between plasma tHcy concentration and annual decline in FEV(1.0) in the COPD group. We found that plasma tHcy concentrations declined among groups in the following order: COPD group > control group > never-smoker group. Furthermore, plasma tHcy concentrations in the COPD group were significantly correlated with %FEV(1.0) (r(s) = 0.46). Also, COPD patients with severe airflow limitation showed a significant decrease in PaO2, which might be involved in the decreased tHcy in those patients. The prospective analysis revealed that plasma tHcy concentration, but not a history of smoking, were significantly correlated with the annual decline in FEV(1.0) calculated by the difference in FEV(1.0) between the first examination and an examination the following year (r(s) = 0.40). The present study suggests that smoking might increase plasma tHcy concentrations, leading to spirometric declines in subjects predisposed to COPD.

Circuit training for elderly patients with chronic obstructive pulmonary disease: a preliminary study.

To examine the efficacy of the circuit training in elderly patients with chronic obstructive pulmonary disease (COPD), we evaluated muscle forces of the upper and lower extremities and respiratory muscles, exercise tolerance and quality of life (QOL) before and after the circuit training in 10 male patients with mild to severe COPD. The circuit training improved muscle forces of the upper and lower extremities and abdominal muscles (P < 0.05), and 6 min walking distance (P < 0.05). Emotional function and mastery in the Chronic Respiratory Disease Questionnaire scores (P < 0.05) were also improved after the circuit training. The circuit training designed in the present study was effective to improve the QOL in elderly COPD patients.