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.
Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. augusto.litonjua@channing.harvard.edu
Augusto A
AA
Litonjua
David
D
Sparrow
Lucille
L
Guevarra
George T
GT
O'Connor
Scott T
ST
Weiss
David J
DJ
Tollerud
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