Association between asthma and COPD: A longitudinal evaluation of the Dutch hypothesis

This Ph.D. dissertation presents results that shed light into the fundamental question of whether there is an epidemiological association between asthma and the subsequent development of chronic obstructive pulmonary disease (COPD). This question is investigated in the context of a longitudinal study that establishes asthma as a predictor for the future development of characteristics consistent with COPD. Asthmatic subjects without chronic bronchitis or emphysema diagnoses were identified at the initial survey and followed longitudinally to assess the development of COPD. Longstanding asthma has been proposed as a possible contributing factor to the risk of developing COPD. To evaluate this hypothesis, a question concerning the association between asthma duration and asthma persistence with lower lung function and odds of cough and sputum in the elderly is also investigated. This second question is addressed by means of comparative analyses of immunologic and pulmonary characteristics of elderly versus younger non-smoking asthmatics. In addition, this work investigates the role of genetic factors that may predispose to the development of COPD, in particular, the association between alpha 1-antitrypsin deficiency (PiMZ and PiMS) and rapid decline in pulmonary function. This work utilizes data derived from the Tucson Epidemiologic Study of Airways Obstructive Diseases (TESAOD), initiated in 1971. Results show a significant association between an active asthma diagnosis at initial survey and subsequent development of signs and symptoms consistent with COPD. Results show as well, that longstanding asthma is associated with lower pulmonary function, and that this association is stronger for older persistent asthmatics compared to younger asthmatics. In addition, subjects with shorter asthma duration have higher risk for cough and sputum than non-asthmatics or those with longer asthma duration. Furthermore, no association between rapid decline in pulmonary function and the PiMZ or PiMS phenotypes is seen. These results support the implied relationship of asthma with COPD proposed in the Dutch hypothesis, where despite the known differences between asthma and COPD at initial diagnosis, over time the two diseases develop signs and symptoms that overlap. However, the proposed involvement in this association of heterozygous forms of alpha1-antitrypsin by other studies was not supported in the present research