Computer quantification of airway collapse on forced expiration to predict the presence of emphysema

BackgroundSpirometric parameters are the mainstay for diagnosis of COPD, but cannot distinguish airway obstruction from emphysema. We aimed to develop a computer model that quantifies airway collapse on forced expiratory flow–volume loops. We then explored and validated the relationship of airway collapse with computed tomography (CT) diagnosed emphysema in two large independent cohorts.MethodsA computer model was developed in 513 Caucasian individuals with ≥15 pack-years who performed spirometry, diffusion capacity and CT scans to quantify emphysema presence. The model computed the two best fitting regression lines on the expiratory phase of the flow-volume loop and calculated the angle between them. The collapse was expressed as an Angle of collapse (AC) which was then correlated with the presence of emphysema. Findings were validated in an independent group of 340 individuals.ResultsAC in emphysema subjects (N = 251) was significantly lower (131° ± 14°) compared to AC in subjects without emphysema (N = 223), (152° ± 10°) (p < 0.0001). Multivariate regression analysis revealed AC as best indicator of visually scored emphysema (R2 = 0.505, p < 0.0001) with little significant contribution of KCO, %predicted and FEV1, %predicted to the total model (total R2 = 0.626, p < 0.0001). Similar associations were obtained when using CT-automated density scores for emphysema assessment. Receiver operating characteristic (ROC) curves pointed to 131° as the best cut-off for emphysema (95.5% positive predictive value, 97% specificity and 51% sensitivity). Validation in a second group confirmed the significant difference in mean AC between emphysema and non-emphysema subjects. When applying the 131° cut-off, a positive predictive value of 95.6%, a specificity of 96% and a sensitivity of 59% were demonstrated.ConclusionsAirway collapse on forced expiration quantified by a computer model correlates with emphysema. An AC below 131° can be considered as a specific cut-off for predicting the presence of emphysema in heavy smokers.

[1]  J E Cotes,et al.  Lung volumes and forced ventilatory flows , 1993, European Respiratory Journal.

[2]  J E Cotes,et al.  [Lung volumes and forced ventilatory flows. Work Group on Standardization of Respiratory Function Tests. European Community for Coal and Steel. Official position of the European Respiratory Society]. , 1994, Revue des maladies respiratoires.

[3]  D. Postma,et al.  Plethysmographic parameters in the assessment of reversibility of airways obstruction in patients with clinical emphysema. , 1993, Chest.

[4]  D. Gossot,et al.  [Thoracic surgery: progression to surgical endoscopy]. , 1994, Revue des maladies respiratoires.

[5]  D. Postma,et al.  Lung function decline in male heavy smokers relates to baseline airflow obstruction severity. , 2012, Chest.

[6]  M. Cosio,et al.  Loss of alveolar attachments in smokers. A morphometric correlate of lung function impairment. , 1985, The American review of respiratory disease.

[7]  C. Mathers,et al.  Projections of Global Mortality and Burden of Disease from 2002 to 2030 , 2006, PLoS medicine.

[8]  L. Fabbri,et al.  Association between markers of emphysema and more severe chronic obstructive pulmonary disease , 2006, Thorax.

[9]  R. Stockley,et al.  Radiologic and clinical features of COPD patients with discordant pulmonary physiology: lessons from alpha1-antitrypsin deficiency. , 2007, Chest.

[10]  L Battolla,et al.  Relationship between extent of pulmonary emphysema by high-resolution computed tomography and lung elastic recoil in patients with chronic obstructive pulmonary disease. , 2001, American journal of respiratory and critical care medicine.

[11]  E. Chan,et al.  The detection of collapsible airways contributing to airflow limitation. , 1995, Chest.

[12]  M. Hasegawa,et al.  Characterisation of phenotypes based on severity of emphysema in chronic obstructive pulmonary disease , 2007, Thorax.

[13]  A. Kuperman,et al.  The spirographic "kink". A sign of emphysema. , 1976, Chest.

[14]  Stephen Lam,et al.  The effects of radiation dose and CT manufacturer on measurements of lung densitometry. , 2007, Chest.

[15]  H. Anderson,et al.  Single breath diffusing capacity in a representative sample of the population of Michigan, a large industrial state. Predicted values, lower limits of normal, and frequencies of abnormality by smoking history. , 1983, The American review of respiratory disease.

[16]  A. Gulsvik,et al.  Quantitative CT measures of emphysema and airway wall thickness are related to D(L)CO. , 2011, Respiratory medicine.

[17]  D. Mannino,et al.  Global burden of COPD: risk factors, prevalence, and future trends , 2007, The Lancet.

[18]  Marc Decramer,et al.  The 15q24/25 susceptibility variant for lung cancer and chronic obstructive pulmonary disease is associated with emphysema. , 2010, American journal of respiratory and critical care medicine.

[19]  Carla G. Wilson,et al.  Relationships between airflow obstruction and quantitative CT measurements of emphysema, air trapping, and airways in subjects with and without chronic obstructive pulmonary disease. , 2013, AJR. American journal of roentgenology.

[20]  Susan Murray,et al.  Relationship between quantitative CT metrics and health status and BODE in chronic obstructive pulmonary disease , 2012, Thorax.

[21]  Raúl San José Estépar,et al.  Effect of emphysema on CT scan measures of airway dimensions in smokers. , 2013, Chest.

[22]  M. Cosio,et al.  Loss of Alveolar Attachments in Smokers , 2015 .

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

[24]  J Verschakelen,et al.  The TERT-CLPTM1L locus for lung cancer predisposes to bronchial obstruction and emphysema , 2011, European Respiratory Journal.

[25]  Raúl San José Estépar,et al.  Association between airway caliber changes with lung inflation and emphysema assessed by volumetric CT scan in subjects with COPD. , 2012, Chest.

[26]  M. Cosio,et al.  Lung cancer in patients with chronic obstructive pulmonary disease-- incidence and predicting factors. , 2011, American journal of respiratory and critical care medicine.

[27]  Z. Mosenifar,et al.  Differentiating COPD from Asthma in Clinical Practice , 2009, Postgraduate medicine.

[28]  C. Gatsonis,et al.  Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening , 2012 .

[29]  A. C. Bryan,et al.  Transit time analysis of the forced expiratory spirogram in growth. , 1976, Journal of applied physiology.

[30]  Joyce D. Schroeder,et al.  A Combined Pulmonary-Radiology Workshop for Visual Evaluation of COPD: Study Design, Chest CT Findings and Concordance with Quantitative Evaluation , 2012, COPD.

[31]  T. Witek,et al.  Smoking and cotton dust effects in cotton textile workers: an analysis of the shape of the maximum expiratory flow volume curve. , 1986, Environmental health perspectives.

[32]  Joan B. Soriano,et al.  Treatment of COPD by clinical phenotypes: putting old evidence into clinical practice , 2012, European Respiratory Journal.

[33]  David O Wilson,et al.  Association of radiographic emphysema and airflow obstruction with lung cancer. , 2008, American journal of respiratory and critical care medicine.

[34]  A. Wilson,et al.  Physiologic correlates of airway collapse in chronic airflow obstruction. , 1984, Chest.

[35]  Edwin K Silverman,et al.  Characterisation of COPD heterogeneity in the ECLIPSE cohort , 2010, Respiratory research.

[36]  G. Michaud,et al.  Tracheobronchoplasty for severe tracheobronchomalacia: a prospective outcome analysis. , 2007, Chest.

[37]  Analysis of forced expiration--a return to the recording spirometer? , 1979, Thorax.

[38]  N J Morrison,et al.  Quantitation of emphysema by computed tomography using a "density mask" program and correlation with pulmonary function tests. , 1990, Chest.

[39]  H. Gietema,et al.  Nitric oxide diffusing capacity versus spirometry in the early diagnosis of emphysema in smokers. , 2009, Respiratory medicine.

[40]  K. Stowman.  World health statistics. , 1949, The Milbank Memorial Fund quarterly.

[41]  T. Ninan,et al.  Evaluation of mean transit time in children as an indicator of airways obstruction. , 1992, Respiratory medicine.

[42]  J. Stoller,et al.  A review of α1-antitrypsin deficiency. , 2012, American journal of respiratory and critical care medicine.

[43]  F. Martinez,et al.  Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. , 2007, American journal of respiratory and critical care medicine.

[44]  J. Hankinson,et al.  Standardisation of spirometry , 2005, European Respiratory Journal.

[45]  David Gur,et al.  Radiographic emphysema predicts low bone mineral density in a tobacco-exposed cohort. , 2011, American journal of respiratory and critical care medicine.

[46]  D. Postma,et al.  Chronic obstructive pulmonary disease. , 2002, Clinical evidence.

[47]  Alan D. Lopez,et al.  Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study , 1997, The Lancet.