Pulmonary Function and Respiratory Diseases in Different Genotypes of Alpha-1 Antitrypsin Deficiency.

OBJECTIVE

Respiratory disease is the major cause of morbidity and mortality in patients with alpha-1 antitrypsin deficiency, mainly in homozygous PI*ZZ individuals. However, this association is uncertain in subjects with other deficiency genotypes. The objective of this study was to assess, in the context of alpha-1 antitrypsin deficiency, the existence of further risk factors that have been associated with respiratory diseases.

MATERIAL AND METHODS

Lung function was assessed by spirometry in a sample of 1334 patients with a known genotype for the SERPINA1 gene whose serum alpha-1 antitrypsin levels had been previously determined. Patients with a normal genotype (PI*MM) were compared to 389 patients carrying a deficiency allele.

RESULTS

Statistically significant associations were detected between (i) PIZZ genotype and abnormal FEV1 values (χ2 = 26.45; P <.0002), FEV1/FVC (χ2 = 14.8; P < .02) or forced mid-expiratory flow 25%-75% (χ2 =22.66; P < .0009); (ii) chronic obstructive pulmonary disease and PIZZ odds ratio: 26.5; 95% CI: (2.6-265.9); P <.005 and or PISS genotype odds ratio: 9; 95% CI: (2-40.1); P < .004; (iii) prevalence of COPD in PIMZ subjects and smoking habit (P < .01), low body weight (P < .01) or older age (P < .0001).

CONCLUSION

The PIZZ and PISS genotypes seem to be associated with the prevalence of chronic obstructive pulmonary disease. Tobacco use, low body weight, and older age are risk factors that increase the probability of prevalence of chronic obstructive pulmonary disease by up to 70% in PI*MZ individuals.