Longitudinal decline of diffusing capacity of the lung for carbon monoxide in community subjects with the PiMZ alpha1-antitrypsin phenotype.
BACKGROUND
It is well known that homozygous deficiency of alpha(1)-antitrypsin, PiZZ, is associated with an increased risk of emphysema. However, studies evaluating associations between the heterozygous form PiMZ with emphysema and impaired lung function have provided conflicting results.


OBJECTIVE
The goal of this study was to determine if the phenotype PiMZ is associated with an accelerated decline in diffusing capacity of the lung for carbon monoxide (Dlco).


METHODS
The Tucson Epidemiologic Study of Airway Obstructive Disease is a prospective, population-based cohort study initiated in 1972. Participants completed standardized questionnaires in up to 12 periodic surveys and Dlco assessments in up to 4 surveys. Random-effects models were used to determine the effects of alpha(1)-antitrypsin phenotypes on percentage of predicted (% predicted) Dlco levels among 1,075 subjects > or = 18 years old.


RESULTS
% predicted Dlco declined more rapidly in subjects who smoked compared to nonsmoking subjects. Additionally, in smokers, the PiMZ phenotype was associated with borderline % predicted Dlco deficits at age 40 years (8.6%; p = 0.075) and significant % predicted Dlco deficits at age 60 years (15.2%; p = 0.001) and 80 years (21.9%; p = 0.003), as compared with the PiMM phenotype.


CONCLUSIONS
Dlco may be a more sensitive indicator of the long-term effects of intermediate levels of alpha(1)-antitrypsin on lung function especially in subjects who smoke.
Silva
Graciela E
GE
College of Nursing and Healthcare Innovation, Arizona State University, 500 N Third St, Phoenix, AZ 85004-0698, USA. graciela.silva@asu.edu
Guerra
Stefano
S
Keim
Sam
S
Barbee
Robert A
RA
Sherrill
Duane L
DL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002248:Carbon Monoxide / Q000494:pharmacology*; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D011446:Prospective Studies; D011653:Pulmonary Diffusing Capacity / Q000187:drug effects* / Q000235:genetics; D011656:Pulmonary Emphysema / Q000453:epidemiology* / Q000209:etiology / Q000503:physiopathology; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D011795:Surveys and Questionnaires; D000515:alpha 1-Antitrypsin / Q000235:genetics* / Q000378:metabolism; D019896:alpha 1-Antitrypsin Deficiency / Q000150:complications* / Q000235:genetics / Q000378:metabolism
D000515:alpha 1-Antitrypsin; D002248:Carbon Monoxide