Population-based studies on COPD : from a gender perspective

Men are different, women too. A concept which has long been neglected in biomedical research. Except for reproductive differences women were regarded as smaller men, clinical guidelines did not differentiate between men and women. There are, however, further differences. Every cell has a sex, which might influence regulation of gene expression, disease phenotype and drug toxicity. In drug research it is important to understand the pathomechanism and clinical presentation of a disease as well as the mechanism of action of a drug. Information on drug safety and efficacy are collected in preclinical and clinical studies. Natural history of disease studies provide valuable information on the clinical presentation of a disease. It is important to provide this information gender stratified to be able to offer best care to future patients. Chronic obstructive pulmonary disease (COPD) has traditionally been regarded as a disease of white men but today almost as many women are affected by the disease as men. The burden of COPD is still projected to increase, particularly in women. Despite this there are few studies comparing the clinical manifestation and clinical course in men and women with COPD. It was the aim of this thesis to contribute new data to the natural history of COPD with a special focus on the effect of gender.
The studies of this thesis were conducted with data from the General Practice Research Database (GPRD), a large population-based database in the United Kingdom. The GPRD provides anonymized medical information on a 5% representative sample of the UK population. This thesis presents six studies focussing on a population of 35,772 COPD patients, aged 40-79 years, who received their incident COPD diagnosis between 1995 and 2005 and the same number of randomly matched COPD-free patients for comparison. In a case-control analysis we compared the prevalence of co-morbidities and respiratory drug utilization in men and women with COPD. In nested case control analyses COPD and COPD-free patients were compared with respect to their risk to develop cardiovascular or gastrointestinal outcomes, depression or cancer.
The first study described the COPD population with respect to co-morbidities, drug use and survival. Patients with COPD had more co-morbidities and a lower survival than COPD-free patients. In COPD patients the prevalence of diabetes, myocardial infarction, stroke / transient ischemic attack (TIA), arrhythmia and peptic ulcer were higher in men than in women while depression and osteoporosis were more prevalent in women. We observed small but significant gender differences in drug utilization and survival. The second study analysed in more detail the association between COPD and the prevalence of diabetes. The prevalence of diabetes was lower in the COPD group than in the COPD-free comparison group. This association was significant in men but not women and mainly seen in users of sulfonylurea. Studies 3-6 were follow-up and nested case control analyses evaluating the risk of the cardiovascular outcomes (arrhythmia, pulmonary embolism, deep vein thrombosis, myocardial infarction and stroke / TIA), gastro-oesophageal reflux disease, peptic ulcer, depression and cancer risk in the population of COPD patients and compared it to a COPD-free population. The incidence of most cardiovascular diseases was higher in patients with COPD. COPD had a stronger impact on the risk of MI and stroke / TIA in women than in men. Relative risks of PE, DVT and arrhythmia were similar in men and women. Severe COPD materially increased the risk of MI and PE in both men and women. The incidence rates of GORD were slightly higher in men than in women while peptic ulcer incidence rates were higher in men. COPD did not materially alter the risk of GORD or peptic ulcer. Current use of long-acting beta agonists was associated with a decreased risk of peptic ulcer. Patients with COPD had a higher risk of cancer than COPD-free patients. The increased risk was mainly driven by a high lung cancer risk among COPD patients, which was higher in women than in men. This effect was seen independent of smoking status. Many patients with COPD developed depression during follow-up, particularly patients with severe COPD. The risk of depression was higher in women than in men but COPD seemed to have a greater impact in men than in women.
The studies of this thesis provide further evidence that patients with COPD are at an increased risk of depression, most cardiovascular diseases and lung cancer. They also demonstrate that gender-stratified analyses are important to adequately address the risk for a disease.