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

Respiratory Research

Wim Janssens²  Marc Decramer²  Daniel Berckmans³  Karl Janssens⁴  Pieter Slagmolen¹  Martijn Hemeryck¹  Walter Dewever⁵  Johan Coolen⁵  Anneleen Peeters²  Vasileios Exadaktylos³  Marko Topalovic² 

[1] Medical Imaging Research Center, KU Leuven & UZ Leuven, Leuven, Belgium;Respiratory Division, University Hospital Leuven, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium;Department of Biosystems, Measure, Model and Manage Bioresponses (M3 BIORES), KU Leuven, Leuven, Belgium;Research and Development, LMS International, Leuven, Belgium;Department of Radiology, University Hospital Leuven, Leuven, Belgium

关键词: Lung collapse;    Chronic obstructive pulmonary disease;    Flow-volume loops;    Pulmonary emphysema;    Spirometry;   

Others  :  792292
DOI  :  10.1186/1465-9921-14-131

 received in 2013-06-17, accepted in 2013-11-18,  发布年份 2013

【 摘 要 】

Background

Spirometric 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.

Methods

A 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.

Results

AC 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 K_CO, %predicted and FEV_1, %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.

Conclusions

Airway 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.

【 授权许可】

   
2013 Topalovic et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Decramer M, Janssens W, Miravitlles M: Chronic obstructive pulmonary disease. Lancet 2012, 379:1341-1351.
• [2]Mathers CD, Loncar D: Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006, 3:e442.
• [3]Murray CJ, Lopez AD: Alternative projections of mortality and disability by cause 1990-2020: global burden of disease study. Lancet 1997, 349:1498-1504.
• [4]WHO: World health statistics. 2008. http://www.who.int/whosis/whostat/EN_WHS08_Full.pdf webcite . 2012
• [5]Mannino DM, Buist AS: Global burden of COPD: risk factors, prevalence, and future trends. Lancet 2007, 370:765-773.
• [6]Agusti A, Calverley PM, Celli B, Coxson HO, Edwards LD, Lomas DA, MacNee W, Miller BE, Rennard S, Silverman EK, et al.: Characterisation of COPD heterogeneity in the ECLIPSE cohort. Respir Res 2010, 11:122.
• [7]Miravitlles M, Jose Soler-Cataluna J, Calle M, Soriano JB: Treatment of COPD by clinical phenotypes. Putting old evidence into clinical practice. Eur Respir J 2012, 41:1252-1256.
• [8]Boschetto P, Quintavalle S, Zeni E, Leprotti S, Potena A, Ballerin L, Papi A, Palladini G, Luisetti M, Annovazzi L, et al.: Association between markers of emphysema and more severe chronic obstructive pulmonary disease. Thorax 2006, 61:1037-1042.
• [9]Bon J, Fuhrman CR, Weissfeld JL, Duncan SR, Branch RA, Chang CC, Zhang Y, Leader JK, Gur D, Greenspan SL, et al.: Radiographic emphysema predicts low bone mineral density in a tobacco-exposed cohort. Am J Respir Crit Care Med 2011, 183:885-890.
• [10]Makita H, Nasuhara Y, Nagai K, Ito Y, Hasegawa M, Betsuyaku T, Onodera Y, Hizawa N, Nishimura M: Characterisation of phenotypes based on severity of emphysema in chronic obstructive pulmonary disease. Thorax 2007, 62:932-937.
• [11]Martinez CH, Chen YH, Westgate PM, Liu LX, Murray S, Curtis JL, Make BJ, Kazerooni EA, Lynch DA, Marchetti N, et al.: Relationship between quantitative CT metrics and health status and BODE in chronic obstructive pulmonary disease. Thorax 2012, 67:399-406.
• [12]Ohara T, Hirai T, Muro S, Haruna A, Terada K, Kinose D, Marumo S, Ogawa E, Hoshino Y, Niimi A, et al.: Relationship between pulmonary emphysema and osteoporosis assessed by CT in patients with COPD. Chest 2008, 134:1244-1249.
• [13]Wilson DO, Weissfeld JL, Balkan A, Schragin JG, Fuhrman CR, Fisher SN, Wilson J, Leader JK, Siegfried JM, Shapiro SD, et al.: Association of radiographic emphysema and airflow obstruction with lung cancer. Am J Respir Crit Care Med 2008, 178:738-744.
• [14]de Torres JP, Marin JM, Casanova C, Cote C, Carrizo S, Cordoba-Lanus E, Baz-Davila R, Zulueta JJ, Aguirre-Jaime A, Saetta M, et al.: Lung cancer in patients with chronic obstructive pulmonary disease– incidence and predicting factors. Am J Respir Crit Care Med 2011, 184:913-919.
• [15]Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD: Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011, 365:395-409.
• [16]Chang J, Mosenifar Z: Differentiating COPD from asthma in clinical practice. J Intensive Care Med 2007, 22:300-309.
• [17]Baldi S, Miniati M, Bellina CR, Battolla L, Catapano G, Begliomini E, Giustini D, Giuntini C: Relationship between extent of pulmonary emphysema by high-resolution computed tomography and lung elastic recoil in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001, 164:585-589.
• [18]Gimeno F, Postma DS, van AR: Plethysmographic parameters in the assessment of reversibility of airways obstruction in patients with clinical emphysema. Chest 1993, 104:467-470.
• [19]Chan ED, Irvin CG: The detection of collapsible airways contributing to airflow limitation. Chest 1995, 107:856-859.
• [20]Saltzman HP, Ciulla EM, Kuperman AS: The spirographic “kink”. A sign of emphysema. Chest 1976, 69:51-55.
• [21]Lambrechts D, Buysschaert I, Zanen P, Coolen J, Lays N, Cuppens H, Groen HJ, Dewever W, van Klaveren RJ, Verschakelen J, et al.: The 15q24/25 susceptibility variant for lung cancer and chronic obstructive pulmonary disease is associated with emphysema. Am J Respir Crit Care Med 2010, 181:486-493.
• [22]Wauters E, Smeets D, Coolen J, Verschakelen J, De LP, Decramer M, Vansteenkiste J, Janssens W, Lambrechts D: The TERT-CLPTM1L locus for lung cancer predisposes to bronchial obstruction and emphysema. Eur Respir J 2011, 38:924-931.
• [23]Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, et al.: Standardisation of spirometry. Eur Respir J 2005, 26:319-338.
• [24]Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC: [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]. Rev Mal Respir 1994, 11(3):5-40.
• [25]Miller A, Thornton JC, Warshaw R, Anderson H, Teirstein AS, Selikoff IJ: 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. Am Rev Respir Dis 1983, 127:270-277.
• [26]Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, et al.: Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease, GOLD executive summary. Am J Respir Crit Care Med 2012, 187:347-365.
• [27]van dL I, Gietema HA, Zanen P, van Klaveren RJ, Prokop M, Lammers JW, van den Bosch JM: Nitric oxide diffusing capacity versus spirometry in the early diagnosis of emphysema in smokers. Respir Med 2009, 103:1892-1897.
• [28]Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, Fukuchi Y, Jenkins C, Rodriguez-Roisin R, van WC, et al.: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2007, 176:532-555.
• [29]Saetta M, Ghezzo H, Kim WD, King M, Angus GE, Wang NS, Cosio MG: Loss of alveolar attachments in smokers. A morphometric correlate of lung function impairment. Am Rev Respir Dis 1985, 132:894-900.
• [30]Diaz AA, Come CE, Ross JC, San Jose ER, Han MK, Loring SH, Silverman EK, Washko GR: Association between airway caliber changes with lung inflation and emphysema assessed by volumetric CT scan in subjects with COPD. Chest 2012, 141:736-744.
• [31]Diaz AA, Han MK, Come CE, Estepar RS, Ross JC, Kim V, Dransfield MT, Curran-Everett D, Schroeder JD, Lynch DA, et al.: The effect of emphysema on computed tomographic measures of airway dimensions in smokers. Chest 2013, 143:687-693.
• [32]Grydeland TB, Thorsen E, Dirksen A, Jensen R, Coxson HO, Pillai SG, Sharma S, Eide GE, Gulsvik A, Bakke PS: Quantitative CT measures of emphysema and airway wall thickness are related to D(L)CO. Respir Med 2011, 105:343-351.
• [33]Stoller JK, Aboussouan LS: A review of alpha1-antitrypsin deficiency. Am J Respir Crit Care Med 2012, 185:246-259.
• [34]Barr RG, Berkowitz EA, Bigazzi F, Bode F, Bon J, Bowler RP, Chiles C, Crapo JD, Criner GJ, Curtis JL, et al.: A combined pulmonary-radiology workshop for visual evaluation of COPD: study design, chest CT findings and concordance with quantitative evaluation. COPD 2012, 9:151-159.
• [35]Holme J, Stockley RA: Radiologic and clinical features of COPD patients with discordant pulmonary physiology: lessons from alpha1-antitrypsin deficiency. Chest 2007, 132:909-915.
• [36]Schachter EN, Kapp MC, Maunder LR, Beck G, Witek TJ: Smoking and cotton dust effects in cotton textile workers: an analysis of the shape of the maximum expiratory flow volume curve. Environ Health Perspect 1986, 66:145-148.
• [37]Pride NB: Analysis of forced expiration–a return to the recording spirometer? Thorax 1979, 34:144-147.
• [38]Hudson M, Ninan T, Russell G: Evaluation of mean transit time in children as an indicator of airways obstruction. Respir Med 1992, 86:301-304.
• [39]Miller MR: Evaluation of mean transit time. Respir Med 1993, 87:319-320.
• [40]Neuburger N, Levison H, Bryan AC, Kruger K: Transit time analysis of the forced expiratory spirogram in growth. J Appl Physiol 1976, 40:329-332.
• [41]Healy F, Wilson AF, Fairshter RD: Physiologic correlates of airway collapse in chronic airflow obstruction. Chest 1984, 85:476-481.
• [42]Majid A, Guerrero J, Gangadharan S, Feller-Kopman D, Boiselle P, DeCamp M, Ashiku S, Michaud G, Herth F, Ernst A: Tracheobronchoplasty for severe tracheobronchomalacia: a prospective outcome analysis. Chest 2008, 134:801-807.
• [43]Yuan R, Mayo JR, Hogg JC, Pare PD, McWilliams AM, Lam S, Coxson HO: The effects of radiation dose and CT manufacturer on measurements of lung densitometry. Chest 2007, 132:617-623.
• [44]Kinsella M, Muller NL, Abboud RT, Morrison NJ, DyBuncio A: Quantitation of emphysema by computed tomography using a “density mask” program and correlation with pulmonary function tests. Chest 1990, 97:315-321.
• [45]Schroeder JD, McKenzie AS, Zach JA, Wilson CG, Curran-Everett D, Stinson DS, Newell JD Jr, Lynch DA: Relationships between airflow obstruction and quantitative CT measurements of emphysema, air trapping, and airways in subjects with and without chronic obstructive pulmonary disease. AJR Am J Roentgenol 2013, 201:W460-W470.
• [46]Mohamed Hoesein FA, Zanen P, Boezen HM, Groen HJ, Van GB, de Jong PA, Postma DS, Lammers JW: Lung function decline in heavy male smokers relates to baseline airflow obstruction severity. Chest 2012, 142:1530-1538.