Longitudinal Study of Spatially Heterogeneous Emphysema Progression in Current Smokers with Chronic Obstructive Pulmonary Disease

Background Cigarette smoke is the main risk factor for emphysema, which is a key pathology in chronic obstructive pulmonary disease (COPD). Low attenuation areas (LAA) in computed tomography (CT) images reflect emphysema, and the cumulative size distribution of LAA clusters follows a power law characterized by the exponent D. This property of LAA clusters can be explained by model simulation, where mechanical force breaks alveolar walls causing local heterogeneous lung tissue destruction. However, a longitudinal CT study has not investigated whether continuous smoking causes the spatially heterogeneous progression of emphysema. Methods We measured annual changes in ratios of LAA (LAA%), D and numbers of LAA clusters (LAN) in CT images acquired at intervals of ≥3 years from 22 current and 31 former smokers with COPD to assess emphysema progression. We constructed model simulations using CT images to morphologically interpret changes in current smokers. Results D was decreased in current and former smokers, whereas LAA% and LAN were increased only in current smokers. The annual changes in LAA%, D, and LAN were greater in current, than in former smokers (1.03 vs. 0.37%, p = 0.008; −0.045 vs. −0.01, p = 0.004; 13.9 vs. 1.1, p = 0.007, respectively). When LAA% increased in model simulations, the coalescence of neighboring LAA clusters decreased D, but the combination of changes in D and LAN in current smokers could not be explained by the homogeneous emphysema progression model despite cluster coalescence. Conversely, a model in which LAAs heterogeneously increased and LAA clusters merged somewhat in relatively advanced emphysematous regions could reflect actual changes. Conclusions Susceptibility to parenchymal destruction induced by continuous smoking is not uniform over the lung, but might be higher in local regions of relatively advanced emphysema. These could result in the spatially heterogeneous progression of emphysema in current smokers.

[1]  I. Rahman.  Oxidative stress in pathogenesis of chronic obstructive pulmonary disease , 2007, Cell Biochemistry and Biophysics.

[2]  A. Majumdar,et al.  Early emphysema in the tight skin and pallid mice: roles of microfibril-associated glycoproteins, collagen, and mechanical forces. , 2006, American journal of respiratory cell and molecular biology.

[3]  J. Crapo,et al.  Cellular and connective tissue changes in alveolar septal walls in emphysema. , 1999, American journal of respiratory and critical care medicine.

[4]  Kunihiro Yagihashi,et al.  Morphological Progression of Emphysema on Thin-section CT: Analysis of Longitudinal Change in the Number and Size of Low-Attenuation Clusters , 2006, Journal of computer assisted tomography.

[5]  S. Muro,et al.  Relationship between pulmonary emphysema and osteoporosis assessed by CT in patients with COPD. , 2008, Chest.

[6]  W. Bailey,et al.  Editorial: Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 Guidelines for COPD, Including COVID-19, Climate Change, and Air Pollution , 2023, Medical science monitor : international medical journal of experimental and clinical research.

[7]  A Gefen,et al.  Analysis of stress distribution in the alveolar septa of normal and simulated emphysematic lungs. , 1999, Journal of biomechanics.

[8]  P. Paré,et al.  Computed tomographic measurements of airway dimensions and emphysema in smokers. Correlation with lung function. , 2000, American journal of respiratory and critical care medicine.

[9]  J. Hogg,et al.  Quantification of lung surface area using computed tomography , 2010, Respiratory research.

[10]  J. Boreham,et al.  Carbon monoxide in breath in relation to smoking and carboxyhaemoglobin levels. , 1981, Thorax.

[11]  Stefano Diciotti,et al.  Changes in Volume-corrected Whole-lung Density in Smokers and Former Smokers During the ITALUNG Screening Trial , 2012, Journal of thoracic imaging.

[12]  Béla Suki,et al.  On the progressive nature of emphysema: roles of proteases, inflammation, and mechanical forces. , 2003, American journal of respiratory and critical care medicine.

[13]  The definition of emphysema. Report of a National Heart, Lung, and Blood Institute, Division of Lung Diseases workshop. , 1985, The American review of respiratory disease.

[14]  Yasutaka Nakano,et al.  CT scan findings of emphysema predict mortality in COPD. , 2010, Chest.

[15]  P. Gevenois,et al.  Pulmonary emphysema: objective quantification at multi-detector row CT--comparison with macroscopic and microscopic morphometry. , 2006, Radiology.

[16]  J. Wedzicha,et al.  Susceptibility to exacerbation in chronic obstructive pulmonary disease. , 2010, The New England journal of medicine.

[17]  B Suki,et al.  Roles of mechanical forces and collagen failure in the development of elastase-induced emphysema. , 2001, American journal of respiratory and critical care medicine.

[18]  E Kohda,et al.  Longitudinal follow-up study of smoking-induced lung density changes by high-resolution computed tomography. , 2000, American journal of respiratory and critical care medicine.

[19]  G. Joos,et al.  Role of apoptosis in the pathogenesis of COPD and pulmonary emphysema , 2006, Respiratory research.

[20]  A. Majumdar,et al.  Mechanical forces regulate elastase activity and binding site availability in lung elastin. , 2010, Biophysical journal.

[21]  P. Friedman,et al.  Persistent airway inflammation and emphysema progression on CT scan in ex-smokers observed for 4 years. , 2011, Chest.

[22]  Johan H C Reiber,et al.  Volume correction in computed tomography densitometry for follow-up studies on pulmonary emphysema. , 2008, Proceedings of the American Thoracic Society.

[23]  S. Muro,et al.  Impact of exacerbations on emphysema progression in chronic obstructive pulmonary disease. , 2011, American journal of respiratory and critical care medicine.

[24]  N. Müller,et al.  "Density mask". An objective method to quantitate emphysema using computed tomography. , 1988, Chest.

[25]  Marleen de Bruijne,et al.  Short-term effect of changes in smoking behaviour on emphysema quantification by CT , 2010, Thorax.

[26]  A. Dirksen,et al.  Exploring the role of CT densitometry: a randomised study of augmentation therapy in α1-antitrypsin deficiency , 2009, European Respiratory Journal.

[27]  Tilo Winkler,et al.  Emergent structure-function relations in emphysema and asthma. , 2011, Critical reviews in biomedical engineering.

[28]  N H Holstein-Rathlou,et al.  Volume adjustment of lung density by computed tomography scans in patients with emphysema , 2004, Acta radiologica.

[29]  P De Vuyst,et al.  Comparison of computed density and macroscopic morphometry in pulmonary emphysema. , 1995, American journal of respiratory and critical care medicine.

[30]  B Suki,et al.  Complexity of terminal airspace geometry assessed by lung computed tomography in normal subjects and patients with chronic obstructive pulmonary disease. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[31]  B. Stoel,et al.  Detection of emphysema progression in alpha 1-antitrypsin deficiency using CT densitometry; Methodological advances , 2008, Respiratory research.

[32]  Jason C Woods,et al.  Effects of CT section thickness and reconstruction kernel on emphysema quantification relationship to the magnitude of the CT emphysema index. , 2010, Academic radiology.