Familial prevalence of chronic obstructive pulmonary disease in a matched pair study

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      Search for chronic obstructive pulmonary disease (COPD) or chronic bronchitis in 1,441 parents and siblings of 114 index patients and 114 matched control subjects revealed two to three times the frequency of disease among siblings of index patients but no significant difference among parents. Measurement of pulmonary function in closest-aged siblings of the same sex confirmed the higher frequency of COPD reported by index probands on a family questionnaire. Comparison of reported involvement with measured involvement in each closest-aged sibling showed more frequent false-negative reporting by index than by control probands, a phenomenon different from what was expected. Analysis of the distribution of sibship size and frequency of airway disease in relation to size showed no family clustering that would inflate the prevalence of the disease in the index group. There were three PiZ alpha1-antitrypsin phenotypes among the index patients but none among the control subjects. Nine (7.9 per cent) PiMZ phenotypes were seen in the index group and six (5.3 per cent) in the control group. Compared with the phenotype frequency in the general white population (2.3 per cent), the prevalence of the MZ phenotype is significantly higher (P < 0.001) in the group of patients with COPD; compared with the control group, the prevalence is not significantly higher. The occurrence of the Z or MZ phenotypes does not explain the entire difference of prevalence of COPD in the two groups of families. Other genetic or environmental factors must be present to account for the different prevalences in the two groups of siblings.
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