Inflammatory Markers, Respiratory Diseases, Lung Function and Associated Gender Differences

Abstract: Systemic inflammation is associated with impaired lung function. Inflammation is part of asthma and chronic obstructive pulmonary disease (COPD), but the local and systemic inflammatory pattern differs. The overall aim was to evaluate systemic inflammatory markers in obstructive lung diseases and more specifically: To determine if CRP is related to respiratory symptoms, asthma, atopy and bronchial responsiveness (paper I), in a population sample from three countries (paper I and II); to evaluate if CRP is related to COPD, lung function and rate of lung function decline (paper II); to investigate the association of serum MMP-9 and TIMP-1 with lung function in a cross-sectional population based study (paper III); and finally, to study possible gender differences in the longitudinal association between CRP and lung function in a prospective population based study (paper IV). In the first study we reported that CRP was related to non-allergic asthma but not allergic asthma, and that CRP was related to respiratory symptoms such as wheeze, nocturnal cough and breathlessness after effort, but not associated with atopy or bronchial responsiveness. In the second study we found that COPD was more common in subjects in the highest CRP quartiles and higher CRP levels were associated with lower FEV1 values in both men and women, but the negative association between CRP and FEV1 was larger in men than women. The FEV1 decline was larger in men with high CRP levels, whereas no such association was found for women. In the third study we reported that lower FEV1 was associated with higher levels of MMP-9, TIMP-1 and their ratio MMP-9/TIMP-1. After stratification for gender this association was significant in men but not women. In the fourth study we found that CRP levels were associated with change in both FEV1 and FVC in men but not women. This association was found for both baseline CRP and change in CRP, confirming a stronger association between systemic inflammation and lung function decline in men than women. In conclusion, systemic inflammation is associated with non-allergic asthma but not allergic asthma. Our findings of a stronger association between the systemic inflammation and lung function impairment in men, but not women, may indicate a gender difference in the mechanisms of lung function decline.