PURPOSE: Recent data suggests that infection with HIV imparts a risk of accelerated onset and progression of smoking-related emphysema; the etiology and risk factors are unclear. No studies have evaluated the pathophysiologic role of alpha-1 antitrypsin(AAT) in the development of emphysema in these patients. Furthermore, recent data have shown that AAT-activity is markedly reduced in the presence of HIV. If the results of these studies are valid, it is reasonable to hypothesize that decreased serum concentrations and activity of AAT may play a role in the pathophysiology of accelerated emphysema in HIV-positive smokers.
METHODS: Our study is a controlled cross-sectional analysis of 100 HIV-seropositive adult smokers. A “smoker” is defined as more than 15 pack-years. Exclusion criteria include patients with a history of pulmonary complications of AIDS, or other pulmonary diseases. All patients prior to entry were counseled in smoking cessation and filled out a modified ATS questionnaire for symptoms and smoking history. Measurements were made of pulmonary function with initial screening spirometry followed by body plethysmography for FEV1<70%, total AAT-level, AAT-activity level and functionality, AAT-phenotyping and genotyping. Subjects are categorized as HIV-seropositive smokers with criteria for emphysema or HIV-seropositive smokers without emphysema with each group including 50 subjects.
RESULTS: There were a total of 75 patients, 25 diagnosed with emphysema and 50 without emphysema. Although the overall AAT percent functionality was reduced in all subjects(92.4%), with 1/3 having activity <90%, there was no correlation between AAT-functionality and the development of emphysema. There was also no statistical significant difference in the two groups for total AAT level, and AAT-activity level. The prevalence of non-PI*MM phenotypes/genotypes in HIV smokers was the same as the general population(4%).
CONCLUSION: Although the presence of HIV disease reduces active AAT-functionality, this does not appear to impart a risk for developing emphysema. The etiology of early onset emphysema remains unclear and more studies are needed.
CLINICAL IMPLICATIONS: A strategic target for the identification and treatment of emphysema in HIV-positive patients should include efforts aimed at smoking cessation.
DISCLOSURE: Joseph Cicenia, No Product/Research Disclosure Information; Grant monies (from sources other than industry) Alpha-1 Foundation and the CHEST Foundation