Genetic and Environmental Influence on Lung Function Impairment in Swedish Twins; J. Hallberg, A. Iliadou, M. Anderson, M. Gerhardsson de Verdier, U. Nihlen, M. Dahlback, N.L. Pedersen, T. Higenbottam, M. Svartengren (Respir Res 2010 Jul 6; 11(1):92 [Epub ahead of print]).
Background. The understanding of the influence of smoking and sex on lung function and symptoms is important for understanding diseases such as COPD. The influence of both genes and environment on lung function, smoking behavior and the presence of respiratory symptoms have previously been demonstrated for each of these separately. Hence, smoking can influence lung function by co-varying not only as an environmental factor, but also by shared genetic pathways. Therefore, the objective was to evaluate heritability for different aspects of lung function, and to investigate how the estimates are affected by adjustments for smoking and respiratory symptoms.
Methods. The current study is based on a selected sample of adult twins from the Swedish Twin Registry. Pairs were selected based on background data on smoking and respiratory symptoms collected by telephone interview. Lung function was measured as FEV1, VC and DLco. Pack-years were quantified, and quantitative genetic analysis was performed on lung function data adjusting stepwise for sex, pack-years and respiratory symptoms.
Results. Fully adjusted heritability for VC was 59% and did not differ by sex, with smoking and symptoms explaining only a small part of the total variance. Heritabilities for FEV1 and DLco were sex specific. Fully adjusted estimates were10 and 15% in men and 46% and 39% in women, respectively. Adjustment for smoking and respiratory symptoms altered the estimates differently in men and women. For FEV1 and DLco, the variance explained by smoking and symptoms was larger in men. Further, smoking and symptoms explained genetic variance in women, but was primarily associated with shared environmental effects in men.
Conclusion. Differences between men and women were found in how smoking and symptoms influence the variation in lung function. Pulmonary gas transfer variation related to the menstrual cycle has been shown before, and the findings regarding DLco in the present study indicates gender specific environmental susceptibility not shown before. As a consequence the results suggest that patients with lung diseases such as COPD could benefit from interventions that are sex specific.
Comment. Evidence continues to emerge that indeed there are gender differences with regard to susceptibility, natural history and prognosis for those who develop COPD. These investigators have a unique cohort of twins that have been studied and characterized clinically. They selected out a group born between 1926–1958. They were able to identify 515 pairs out of 13,258 twin pairs that were included in the cohort. They identified pairs of twins that were symptom concordant or symptom discordant. In all, 392 twins agreed to participate of the 1030 (515 pairs) that were identified. They actually ended up with 176 complete twin pairs, who completed a questionnaire regarding symptoms and smoking data and performed spirometry. Hence, it is a relatively small subset of the total twin pairs and this may have influenced the results. Clearly, further studies such as this will help refine our understanding of gene and environment interactions and gender differences and inform different treatment strategies for men and women.
Decreasing Cardiac Chamber Sizes and Associated Heart Dysfunction in COPD: Role of Hyperinflation; H. Watz, B. Waschki, T. Meyer, G. Kretschmar, A. Kirsten, M. Claussen, H. Magnussen (Chest 2010 Jul; 138(1):32–38. Epub 2010 Feb 26).
Background. Little is known about the role of abnormal lung function in heart size and heart dysfunction in patients with COPD. We studied the relationship of lung function with heart size and heart dysfunction and associated consequences for 6-min walk distance (6MWD) in patients with COPD of different severities.
Methods. In 138 patients with COPD (Global Initiative for Obstructive Lung Disease [GOLD] I-IV), we measured the size of all cardiac chambers, left ventricular diastolic dysfunction (relaxation and filling), and global right ventricular dysfunction (Tei-index) by echocardiography. We also measured lung function (spirometry, body plethysmography, and diffusion capacity) and 6MWD.
Results. The size of all cardiac chambers decreased with increasing GOLD stage. Overall, moderate relationships existed between variables of lung function and cardiac chamber sizes. Static hyperinflation (inspiratory-to-total lung capacity ratio [IC/TLC], functional residual capacity, and residual volume) showed stronger associations with cardiac chamber sizes than airway obstruction or diffusion capacity. IC/TLC correlated best with cardiac chamber sizes and was an independent predictor of cardiac chamber sizes after adjustment for body surface area. Patients with an IC/TLC < or = 0.25 had a significantly impaired left ventricular diastolic filling pattern and a significantly impaired Tei-index compared with patients with an IC/TLC > 0.25. An impaired left ventricular diastolic filling pattern was independently associated with a reduced GMWD.
Conclusions. An increasing rate of COPD severity is associated with a decreasing heart size. Hyperinflation could play an important role regarding heart size and heart dysfunction in patients with COPD.
Comment. Many patients with COPD have some degree of cardiac dysfunction that may be related to coronary artery disease and/or decreased ventricular function. These authors demonstrate that lung hyperinflation may impair cardiac chamber size and function with the strongest correlations (inverse) being between measures of hyperinflation (residual volume, functional residual capacity and IC/TLC ratio) than measurements such as FEV1 or diffusion capacity. Subjects with an IC/TLC less than 0.25 seemed to be the most affected. Such data suggest that an additional benefit of lung volume reduction surgery may be improvements in cardiac function.
COPD and Chronic Bronchitis Risk of Indoor Air Pollution from Solid Fuel: A Systematic Review and Meta-analysis; O.P. Kurmi, S. Semple, P. Simkhada, W.C. Smith, J.G. Ayres (Thorax 2010 Mar; 65(3): 221–228).
Background. Over half the world is exposed daily to the smoke from combustion of solid fuels. Chronic obstructive pulmonary disease (COPD) is one of the main contributors to the global burden of disease and can be caused by biomass smoke exposure. However, studies of biomass exposure and COPD show a wide range of effect sizes. The aim of this systematic review was to quantify the impact of biomass smoke on the development of COPD and define reasons for differences in the reported effect sizes.
Methods. A systematic review was conducted of studies with sufficient statistical power to calculate the health risk of COPD from the use of solid fuel, which followed standardized criteria for the diagnosis of COPD and which dealt with confounding factors. The results were pooled by fuel type and country to produce summary estimates using a random effects model. Publication bias was also estimated.
Results. There were positive associations between the use of solid fuels and COPD (OR = 2.80, 95% CI 1.85 to 4.0) and chronic bronchitis (OR = 2.32, 95% CI 1.92 to 2.80). Pooled estimates for different types of fuel show that exposure to wood smoke while performing domestic work presents a greater risk of development of COPD and chronic bronchitis than other fuels. CONCLUSION: Despite heterogeneity across the selected studies, exposure to solid fuel smoke is consistently associated with COPD and chronic bronchitis. Efforts should be made to reduce exposure to solid fuel by using either cleaner fuel or relatively cleaner technology while performing domestic work. PMID: 20335290
Comment. There continues to be growing evidence outlining the significant contribution of solid fuels as a cause of COPD globally however many questions remain about whether there are differences between COPD caused by tobacco smoke and that caused by different types of “solid fuels” such as wood or biomass fuels such as cow dung used in many developing countries. There are many pitfalls in performing such meta-analyses that must be addressed including numbers of quality studies available for review, data on exposure dose and accounting for publication bias since studies that did not show an association were less likely to be published. These authors found 23 studies that met the following criteria: English language only, having original data, adjusted for confounding due to tobacco smoking, contained quantitative estimates of the associations between non-exposed and exposed groups to biomass/solid fuel or data sufficient to calculate effect estimates, validated questionnaire tools used to measure respiratory symptoms for chronic bronchitis and lung function measured according to ATS criteria. They also did an analysis for publication bias (did not find any). This systematic review and meta-analysis is highly instructive in that it suggests that exposure to wood smoke may present the highest risk compared to other solid fuels such as biomass fuel. Such a finding may surprise some but more importantly emphasizes the need for increasing awareness and developing education and intervention strategies to reduce the use of all solid fuels for domestic work such as cooking indoors.