Serum interferon-gamma is associated with longitudinal decline in lung function among asthmatic patients: the Normative Aging Study.
BACKGROUND
Cytokines are important mediators of the asthmatic response. A retrospective pilot study showed that serum levels of interleukin (IL)-5 and interferon (IFN)-gamma were related to lung function decline among asthmatic patients over the preceding 3 years. To confirm these findings, we tested the hypothesis that serum cytokines are associated with longitudinal lung function decline.


METHODS
We conducted a prospective, longitudinal study of 25 asthmatic and 50 nonasthmatic men (median age, 63 years; range, 45 to 80 years) participating in the Normative Aging Study. All study subjects completed two consecutive triennial examinations, including spirometry, methacholine challenge testing, allergy skin testing, and phlebotomy. Serum levels were measured for IL-4, IL-5, IL-6, IL-8, IL-10, and IFN-gamma.


RESULTS
Among asthmatic patients, a higher initial serum level of IFN-gamma was associated with a greater rate of decline of forced expiratory volume in 1 second (FEV1; beta = -67 mL/year per log increase in serum IFN-gamma, P = 0.04) and, to a lesser extent, of FEV1/forced vital capacity ratio (beta = -0.91%/year per log increase in serum IFN-gamma, P = 0.07) after adjusting for age, smoking status, and baseline level of lung function. Serum IL-5 level was associated with a rate of decline in FEV1 of borderline significance (beta = -61 mL/year per log increase in serum IL-5, P = 0.08) among asthmatic patients. These relationshipswere not observed among nonasthmatic patients.


CONCLUSIONS
Serum levels of IFN-gamma are associated with subsequent rate of change in lung function among asthmatic patients in this cohort of middle-aged and older men, and may be useful as biologic markers of risk for accelerated lung function decline in population studies.
Litonjua
Augusto A
AA
Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. augusto.litonjua@channing.harvard.edu
Sparrow
David
D
Guevarra
Lucille
L
O'Connor
George T
GT
Weiss
Scott T
ST
Tollerud
David J
DJ
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D001249:Asthma / Q000503:physiopathology*; D001900:Boston / Q000453:epidemiology; D001985:Bronchial Provocation Tests; D015331:Cohort Studies; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D015848:Interleukin-5 / Q000097:blood; D007378:Interleukins / Q000097:blood; D008137:Longitudinal Studies; D008168:Lung / Q000503:physiopathology*; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D011446:Prospective Studies; D012882:Skin Tests; D012907:Smoking / Q000503:physiopathology; D013147:Spirometry; D011795:Surveys and Questionnaires; D014797:Vital Capacity
D015848:Interleukin-5; D007378:Interleukins; D016210:Methacholine Chloride; D007371:Interferon-gamma