Comparison of Plethysmographic and Helium Dilution Lung Volumes: Which is Best in COPD? C. R. O’Donnell, A. A. Bankier, L. Stiebellehner, J. D. Reilly, R. Brown, S. H. Loring (Chest 2009 [Epub ahead of print]).
Background. Theoretical considerations and limited scientific evidence suggest that whole body plethysmography overestimates lung volume in patients with severe airflow obstruction. We sought to compare plethysmographic-, helium dilution- and CT-derived lung volume measurements in a sample containing many patients with severe airflow obstruction.
Methods. We measured total lung capacity (TLC) in 132 patients at 3 hospitals, with monitored application of recommended techniques for plethysmographic and helium dilution (He) measurements of lung volume and by thoracic CT scans obtained during breath hold at full inspiration.
Results. Average TLC among 132 subjects was 6.18L (± 1.69L) by plethysmography, 5.55L (±1.39L) by helium dilution, and 5.31L (±1.47) by CT. Plethysmographic TLC was significantly greater than either He- or CT-TLC (p ≤ 0.001) while there was no significant difference between He and CT values. When examined separately, there were significant within subject differences in TLC by measurement technique among subjects with airflow obstruction, but not among those without airflow obstruction. Plethysmographic overestimation of TLC was greatest among subjects with FEV(1) less than 30% of predicted.
Conclusions. In the setting of airflow obstruction, plethysmography systematically overestimates lung volume relative to helium dilution or thoracic imaging despite adherence to current recommendations for proper measurement technique.
Comments: The conventional wisdom has been that Helium dilution techniques may underestimate lung volumes due to the Helium gas failing to equilibrate in areas that are poorly ventilated. This study lends credence to the alternative concern that plythysmography may overestimate lung volumes in those with severe airflow obstruction. Given that there is really no gold standard for establishing lung volumes and there are questions about whether individuals with severe airflow obstruction lying on their back for a CT scan can achieve maximum inspiratory breath holds means that it could be possible that Helium dilution techniques and CT estimates both underestimate lung volumes. More study is required before we abandon plethysmography as the better estimate of lung volumes even in subjects with severe airflow limitation.
Increased Risk of Myocardial Infarction and Stroke following Exacerbation of Chronic Obstructive Pulmonary Disease; G. C. Donaldson, J. R. Hurst, C. J. Smith, R. B. Hubbard, J. A. Wedzicha (Chest 2009 Dec 18. [Epub ahead of print]).
Objective. Patients with chronic obstructive pulmonary disease (COPD) are at risk of cardiovascular events. This has been attributed to increased systemic inflammation. The course of COPD is punctuated by exacerbations, which further increase systemic inflammation, but the risk of vascular events in the post-exacerbation period has never been defined.
Design. We analysed data from 25,857 COPD patients entered in The Health Improvement Network (THIN) database over a 2-year period. Exacerbations were defined using a health care utilization definition of prescription of oral corticosteroids >20 mg/day and/or selected oral antibiotics. The risk of myocardial infarction (MI) and stroke in the post-exacerbation period was calculated relative to the patient's baseline risk using the self-controlled case series approach.
Results. We identified 524 MI in 426 patients and 633 ischaemic strokes in 482 patients. The incidence rates of MI and stroke were 1.1 and 1.4 per 100 patient years, respectively. There was a 2.27-fold (95% CI 1.1–4.7; P = 0.03) increased risk of MI 1–5 days after exacerbation (defined by prescription of both steroids and antibiotics). This relative risk diminished progressively over time and was not significantly different from the baseline MI risk at any other post-exacerbation time interval. One in 2,513 exacerbations was associated with MI within 1–5 days. There was a 1.26-fold (95% CI 1.0–1.6; P = 0.05) increased risk of stroke 1–49 days after exacerbation. CONCLUSION: The results suggest that exacerbations of COPD increase the risk of myocardial infarction and stroke. This may have implications for therapy in both stable and exacerbated COPD.
Comments: This paper like others illustrates that patients with COPD are at greater risk of cardiovascular events during times of exacerbations, but goes further to demonstrate that this is particularly the case within the first 5 days of the exacerbation. It supports the notion that the inflammatory or tissue injury response to air pollution or infections in the lung may lead to responses in the cardiovascular system that increase the risk of MI and stroke. Exploring the mechanisms for this association are critical to our understanding as to whether the increase in cardiovascular events is a direct result of an inflammatory response during an exacerbation extending into the systemic circulation, is it a result of the oxidative stress response or the result of a relative reduction in oxygen delivery to these vital tissues that leads to such events. It certainly reinforces the need to see COPD as a systemic disease and the need for greater research into these extra pulmonary manifestations.
What Drives the peripheral Lung-Remodeling Process in Chronic Obstructive Pulmonary Disease? J. C. Hogg, J. E. McDonough, J. V. Gosselink, S. Hayashi (Proc Am Thorac Soc. 2009 Dec; 6(8):668–672).
The smaller airways (<2 mm in diameter) offer little resistance in normal lungs but become the major site of obstruction in chronic obstructive pulmonary disease (COPD). We examined bronchiolar remodeling in COPD by combining quantitative histology, micro-computed tomography (CT), and gene expression studies. Volumes of bronchiolar tissue, total collagen, collagen-1, and collagen-3 were measured in lung tissue from 52 patients with different levels of COPD severity. Micro-CT was used to measure the number and lumen area of terminal bronchioles in 4 lungs removed before lung transplantation and in 4 donor lungs that served as controls. Laser capture microdissection provided 136 paired samples of bronchiolar and surrounding lung tissue from 63 patients and the gene expression of a cluster of tissue repair genes was compared.
This study shows that total bronchiolar tissue decreased with progression of COPD and was associated with a reduction in total collagen and relative increase in collagen-3 over collagen-1. The micro-CT studies showed a 10-fold reduction in terminal bronchiolar number and a 100-fold reduction in lumen area. Interestingly, most genes associated with tissue accumulation during repair decreased their expression in both airways and in the surrounding lung as FEV1 declined, but 8 genes previously associated with COPD increased expression in the surrounding lung tissue. Our study shows that small airway remodeling is associated with narrowing and obliteration of the terminal bronchioles that begins before emphysematous destruction in COPD and in relation to differential expression of tissue repair genes in the airways and surrounding lung.
Comments: This study demonstrates that the small airways show changes in advance of emphysematous destruction of the lung parenchyma. Linking the study of the histological characteristics of tissue samples from patients with different stages of COPD with gene expression is one of the most powerful and elegant methods for advancing our understanding of the basic pathogenesis and also the heterogeneity of responses to tobacco smoke exposure. Perhaps it is possible that very early in the pathogenesis of COPD, changes in the small airways occur before significant changes are noted in larger airways. Developing genetic screening tools, better techniques to measure small airway function and/or biomarkers of tissue injury response may lead to criteria used to diagnose COPD before reductions in the FEV1/FVC ratio are evident. This could improve the efficacy of our interventions geared to secondary prevention.