Asthma and COPD, two of the most prevalent chronic diseases among middle- aged and older Americans, afflict 3% and 11%, respectively, of persons in these age groups. These conditions frequently coexist. COPD is the fourth leading cause of death, the third leading cause of morbidity, and the most rapidly rising cause of death in individuals over 65. The overall goal of this ongoing study is to prospectively identify factors that influence the rate of decline in pulmonary function and to identify predictors of chronic obstructive lung disease (COLD) and asthma in a population sample of older adults. We hypothesize that the development of accelerated decline in FEV1 and the occurrence of respiratory symptoms in older adults are determined by two environmental exposures: tobacco smoke-induced injury and IgE-mediated hypersensitivity to inhaled aeroallergens. The extent to which allergen exposure and airway responsiveness lead to fixed airflow obstruction in older adults is unknown. The primary allergens of interest include: house dust mite (Der p I, Der fI), cockroach (Bla g I, Bla g II), cat (Fel d I), and fungi. Airway hyperresponsiveness to bronchoconstricting stimuli is a physiologic characteristic that may be thought of both as a manifestation of airway disease and as an intrinsic host characteristic which predisposes to the development of airway disease and determines its clinical pattern. We propose to use the extensive longitudinal information on respiratory symptoms and illnesses, cigarette smoking, pulmonary function, airway responsiveness, indices of atopy (skin test, total and antigen-specific IgE), indices of inflammation (eosinophil and leukocyte counts in peripheral blood), and allergen levels in dust and air in NAS participants and their wives to address the following hypotheses. We hypothesize that the association of increased airway responsiveness with accelerated longitudinal decline in pulmonary function is modified by gender, smoking, level of FEV1, and skin test reactivity. We hypothesize that the level of exposure to common indoor allergens affects the rate of longitudinal decline of pulmonary function. We hypothesize that high levels of exposure to common indoor allergens leads to longitudinal increases in airway responsiveness over time. Finally, we hypothesize that settled dust levels of fungi (culturable and countable organisms) and antigens, cockroach (Bla g l, Bla g II], and cat (Fel d I) are correlated with airborne levels of these agents. This proposal will be the first to relate indoor allergen exposure to airway responsiveness and decline in lung function, and should provide important insights into the risk factors and natural history of obstructive airways diseases in adults.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Epidemiology and Disease Control Subcommittee 2 (EDC)
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Ortega, Hector
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Brigham and Women's Hospital
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Litonjua, Augusto A; Silverman, Edwin K; Tantisira, Kelan G et al. (2004) Beta 2-adrenergic receptor polymorphisms and haplotypes are associated with airways hyperresponsiveness among nonsmoking men. Chest 126:66-74
Litonjua, Augusto A; Sparrow, David; Guevarra, Lucille et al. (2003) Serum interferon-gamma is associated with longitudinal decline in lung function among asthmatic patients: the Normative Aging Study. Ann Allergy Asthma Immunol 90:422-8
Weintraub, J M; Sparrow, D; Weiss, S T (2001) Receiver operating characteristics curve analysis of cutaneous skin test reactions to predict hay fever and asthma symptoms in the Normative Aging Study. Allergy 56:243-6
Litonjua, A A; Sparrow, D; Weiss, S T (1999) The FEF25-75/FVC ratio is associated with methacholine airway responsiveness. The normative aging study. Am J Respir Crit Care Med 159:1574-9
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Litonjua, A A; Sparrow, D; Weiss, S T et al. (1997) Sensitization to cat allergen is associated with asthma in older men and predicts new-onset airway hyperresponsiveness. The Normative Aging Study. Am J Respir Crit Care Med 156:23-7
Gottlieb, D J; Sparrow, D; O'Connor, G T et al. (1996) Skin test reactivity to common aeroallergens and decline of lung function. The Normative Aging Study. Am J Respir Crit Care Med 153:561-6
Shadick, N A; Sparrow, D; O'Connor, G T et al. (1996) Relationship of serum IgE concentration to level and rate of decline of pulmonary function: the Normative Aging Study. Thorax 51:787-92
O'Connor, G T; Sparrow, D; Weiss, S T (1995) A prospective longitudinal study of methacholine airway responsiveness as a predictor of pulmonary-function decline: the Normative Aging Study. Am J Respir Crit Care Med 152:87-92

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