Asthma and COPD: Common Genes, Common Environments?

Am J Respir Crit Care Med. 2011 Feb 4;

Authors: Postma DS, Kerkhof M, Boezen HM, Koppelman GH

Asthma and COPD show similarities and substantial differences. The Dutch hypothesis stipulated that asthma and COPD have common genetic and environmental risk factors (allergens, infections, smoking) in common, which ultimately lead to clinical disease depending on the timing and type of environmental exposures (3). Thus a particular group of shared genetic factors may lead to asthma when combined with specific environmental factors that are met at a certain stage in life, whereas combination with other environmental factors, or similar environmental factors at a different stage in life, this will lead toward COPD. Multiple genes have been found for asthma and COPD. Next to genes unique to these diseases, some shared genetic risk factors exist. Moreover, there are both common host risk factors and environmental risk factors for asthma and COPD. Here we put forward, based on the data available, that genes that affect lung development in utero and lung growth in early childhood in interaction with environmental detrimental stimuli like smoking and air pollution are contributing to asthma in childhood and the ultimate development of COPD. Additional genes and environmental factors then drive specific immunological mechanisms underlying asthma and others may contribute to the ultimate development of specific subtypes of COPD, i.e. airway disease with mucous hypersecretion, small airway disease and emphysema. The genetic predisposition to the derailment of certain pathways may further help to define subgroups of asthma and COPD. In the end this may lead to stratification of patients by their genetic make-up and open new therapeutic prospects.

PMID: 21297068 [PubMed - as supplied by publisher]

Chronic obstructive pulmonary disease (COPD) is an inflammatory systemic disease associated with numerous extrapulmonary manifestations. Amongst these is an increased risk for cardiovascular disease. The mechanisms for this association remain unclear. We sought to examine lipid trends in a well-characterized cohort of patients with severe COPD.

METHODS : We conducted a retrospective prospective analysis of 126 consecutive individuals evaluated for lung transplantation with a diagnosis of COPD in whom lipid values were available. Observed lipid values were compared with a reference population without severe COPD.

RESULTS : Compared with the reference population, mean low-density lipoprotein cholesterol (LDL-C) levels were slightly reduced at 108 ± 44 vs 117 ± 29.5 mg/dl (p = 0.02) in men but were no different in women. Mean high-density lipoprotein cholesterol (HDL-C) levels were significantly elevated at 62 ± 24 vs 45 ± 12 mg/dl (p < 0.0001) in men and at 83 ± 27 vs 59 ± 16 mg/dl in women (p < 0.0001). Prednisone use correlated with higher HDL-C levels but did not fully explain the extent of elevation. Angiographically proven coronary artery disease was found in 61% of individuals and was unrelated to HDL-C levels.

CONCLUSIONS : Severe COPD is associated with increased levels of HDL-C, which is partially attributable to oral steroid use. HDL-C in this population is not associated with reduced risk of angiographically proven coronary artery disease.

Chronic obstructive pulmonary disease (COPD) is a common disease, associated with cardiovascular disease. Many patients use (long-acting) bronchodilators, whilst they continue smoking alongside. We hypothesised an interaction between bronchodilators and smoking that enhances smoke exposure, and hence cardiovascular disease. In this paper, we report our study protocol that explores the fundamental interaction, i.e. smoke retention.

METHOD: The design consists of a double-blinded, placebo-controlled, randomised crossover trial, in which 40 COPD patients smoke cigarettes during both undilated and maximal bronchodilated conditions. Our primary outcome is the retention of cigarette smoke, expressed as tar and nicotine weight. The inhaled tar weights are calculated from the correlated extracted nicotine weights in cigarette filters, whereas the exhaled weights are collected on Cambridge filters. We established the inhaled weight calculations by a pilot study, that included paired measurements from several smoking regimes. Our study protocol is approved by the local accredited medical review ethics committee.

DISCUSSION: Our study is currently in progress. The pilot study revealed valid equations for inhaled tar and nicotine, with an R2 of 0,82 and 0,74 (p< 0,01), respectively. We developed a method to study pulmonary smoke retentions in COPD patients under the influence of bronchodilation which may affect smoking-related disease. This trial will provide fundamental knowledge about the (cardiovascular) safety of bronchodilators in patients with COPD who persist in their habit of cigarette smoking.

Both chronic airway obstruction and obesity are increasing in prevalence but the effect of their combination on pulmonary function parameters across the range of airway obstruction is unknown.

METHODS: We studied the impact of increasing body mass index (BMI) on static lung volumes and airway function in a cohort of 2,265 subjects from a large pulmonary function laboratory database who were 40-80 years of age and met GOLD spirometric criteria for COPD (post-bronchodilator FEV(1)/FVC<0.7). We also evaluated the influence of severity of airway obstruction (by GOLD criteria) on these relationships.

RESULTS: With increasing BMI in the group as a whole: functional residual capacity (FRC), residual volume (RV), expiratory reserve volume (ERV) and specific airway resistance (sRaw) decreased exponentially (all p<0.001); total lung capacity (TLC) decreased linearly (p<0.001); inspiratory capacity (IC) and IC/TLC increased linearly (p<0.001); whereas vital capacity (VC) was not significantly influenced. The effects of increasing BMI on FEV(1)/FVC and sRaw were greatest in GOLD stage III/IV (p<0.05), while increasing BMI had greater effects on IC in GOLD stage I (p<0.001).

CONCLUSION: With increasing BMI, subjects with airway obstruction had consistent reductions in lung hyperinflation, with significant improvements in IC and the FEV(1)/FVC ratio; this effect was greatest in patients with the most severe airway obstruction. These results have important implications for the clinical assessment of patients with combined obesity and airway obstruction.