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First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan
Correspondence and requests for reprints should be addressed to Masaharu Nishimura, First Dept. of Medicine, Hokkaido University School of Medicine, North 15, West 7, Kita-ku, Sapporo, JAPAN 060-8638. E-mail: ma-nishi{at}med.hokudai.ac.jp
The Hokkaido COPD cohort study was primarily designed to examine the natural history of chronic obstructive pulmonary disease (COPD) according to the phenotype based upon high-resolution computed tomography (HRCT) findings and is currently ongoing. Two-hundred twenty-three patients with COPD, excluding clinically diagnosed bronchial asthma, were enrolled until the end of 2004; they received detailed interviews on clinical symptoms, blood tests, pulmonary function tests before and after 0.4 mg of inhaled salbutamol, and underwent lung HRCT. The presence of emphysema, which was scaled visually and/or by computerized analysis, was highly varied among the subjects with the same degree of airflow limitation. When the subjects were classified according to emphysema severity (mild, n = 88; moderate, n = 104; severe, n = 37), there were no significant differences in age, sex, body mass index, and smoking history among the three groups. Those subjects who had only mild emphysema were not necessarily patients with bronchitis, because the prevalence of chronic cough and/or phlegm was as low as 24% overall, regardless of emphysema severity. Unexpectedly, the bronchodilator response by salbutamol was not significantly different among the three groups, and it hold true if we chose only the subjects with moderate and severe COPD according to the GOLD criteria (
FEV1, 179 ± 18 ml [n = 61]; 188 ± 17 [n = 76]; 160 ± 21 [n = 30]).
We then examined determinants for the reversibility of airflow limitation, including ß2-adrenergic receptor (ß2AR) gene polymorphism (Arg16Gly and Gln27Glu in particular). The presence of reversibility was defined as an increase in FEV1 that is both greater than 200 ml and 12% above the prebronchodilator FEV1. Thirty-one percent of all the subjects were considered to have airway reversibility. The presence of reversibility had a significant association with lower prebronchodilator %FEV1 (45.6 ± 1.8% vs. 61.8 ± 1.8%, p < 0.01) and the Gly/Gly genotype (adjusted odds ratio, 2.75; 95% confidence interval, 1.2–3.4; p = 0.014), but not with log (IgE) or log (eosinophils). Compared with the subjects carrying the Arg allele (n = 142), the subjects with the Gly/Gly genotype (n = 48) had a greater percentage increase in FEV1 (p = 0.014) and a greater increase in FEV1 (p = 0.028) after salbutamol inhalation.
In conclusion, the COPD based upon HRCT findings is different from the traditional phenotype, that is, pink puffers and blue bloaters. The airway reversibility in COPD is, in part, determined by lower prebronchodilator %FEV1 and ß2AR gene polymorphism. Further studies are ongoing to examine the possible difference in natural history according to the phenotype of COPD.
FOOTNOTES
During the presentation at the 2005 Aspen Conference, the authors mistakenly named the Arg allele for the Gly allele.
Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.
(Received in original form March 16, 2006; accepted in final form March 23, 2006)
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