Background: The severity of COPD is commonly assessed by the reduction in forced expiratory volume at one second (FEV1), although more recently prognostic factors influencing survival have also incorporated functional capacity, degree of breathlessness on exertion, and body mass index. Increasingly, the reliability of physiological parameters such as FEV1 to predict patient-centered outcomes has been brought into question. Objectives: To evaluate the relationship between dyspnea as assessed by the Modified Medical Council Dyspnea (MMRC) scale, the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2014) staging and indices of lung hyperinflation and spirometry. Methods: Data were retrospectively analyzed at a 600-bed tertiary care center including spirometry, plethysmographic lung volumes, single breath carbon monoxide diffusion capacity and dyspnea graded according to MMRC, and GOLD staging. Results: Data for 331 patients were analyzed. Differences amongst FEV1, IC, IC/TLC, FRC and RV/TLC were significant between GOLD I/II and GOLD III/IV groups. The closest relationship to GOLD staging was seen with FEV1, FVC and slow vital capacity (SVC). FEV1/FVC, IC, and IC/TLC were inversely associated with MMRC score, while RV/TLC exhibited a positive relation with MMRC score. Conclusions: Indices of lung hyperinflation are closely associated, with dyspnea as assessed by MMRC grading with TLC, RV/TLC and IC exhibiting the closest relations, more so than FEV1. GOLD staging also shows strong correlations with lung volume subdivisions (weakly with TLC), more so than with FEV1. That TLC changed little between GOLD stages can be explained by the presence of collateral interalveolar channels and population characteristics different from those of other studies. These findings further support the concept that more than a reduction in FEV1, lung hyperinflation contributes to the sensation of dyspnea in airflow limitation.
References
[1]
Pauwels, R.A., Buist, A.S., Calverley, P.M., Jenkins, C.R. and Hurd, S.S. (2001) Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop Summary. American Journal of Respiratory and Critical Care Medicine, 163, 1256-1276.
https://doi.org/10.1164/ajrccm.163.5.2101039
[2]
Casanova, C., de Torres, J.P., Aguirre-Jaíme, A., Pinto-Plata, V., Marin, J.M., Cordoba, E., Baz, R., Cote, C. and Celli, B.R. (2011) The Progression of Chronic Obstructive Pulmonary Disease Is Heterogeneous: The Experience of the BODE Cohort. American Journal of Respiratory and Critical Care Medicine, 184, 1015-1021.
https://doi.org/10.1164/rccm.201105-0831OC
[3]
Celli, B.R., Cote, C.G., Marin, J.M., Casanova, C., Montes de Oca, M., Mendez, R.A., Pinto Plata, V. and Cabral, H.J. (2004) The Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity Index in Chronic Obstructive Pulmonary Disease. The New England Journal of Medicine, 350, 1005-1012.
https://doi.org/10.1056/NEJMoa021322
[4]
Celli, B.R., Decramer, M., Wedzicha, J.A., et al. (2015) ATS/ERS Task Force for COPD Research. An Official American Thoracic Society/European Respiratory Society Statement: Research Questions in COPD. European Respiratory Review, 24, 159-172. https://doi.org/10.1183/16000617.00000315
[5]
Jones, P., Miravitlles, M., van der Molen, T. and Kulich, K. (2012) Beyond FEV1 in COPD: A Review of Patient-Reported Outcomes and Their Measurement. International Journal of Chronic Obstructive Pulmonary Disease, 7, 697-709.
https://doi.org/10.2147/COPD.S32675
[6]
Vogelmeier, C.F., Criner, G.J., Martinez, F.J., et al. (2017) Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary. American Journal of Respiratory and Critical Care Medicine, 195, 557-582. https://doi.org/10.1164/rccm.201701-0218PP
[7]
Pellegrino, R., Viegi, G., Brusasco, V., et al. (2005) Interpretative Strategies for Lung Function Tests. American Journal of Respiratory and Critical Care Medicine, 26, 948-968. https://doi.org/10.1183/09031936.05.00035205
[8]
Schoenberg, J.B., Beck, G.J. and Bouhuys, A. (1978) Growth and Decay of Pulmonary Function in Healthy Blacks and Whites. Respiration Physiology, 33, 367-393.
https://doi.org/10.1016/0034-5687(78)90063-4
[9]
Crapo, R.O., Morris, A.H., Clayton, P.D. and Nixon, C.R. (1982) Lung Volumes in Healthy Nonsmoking adults. Bulletin Européen de Physiopathologie Respiratoire, 18, 419-425.
[10]
Knudson, R.J., Kaltenborn, W.T., Knudson, D.E. and Burrows, B. (1987) The Single-Breath Carbon Monoxide Diffusing Capacity. Reference Equations Derived from a Healthy Nonsmoking Population and Effects of Hematocrit. The American Review of Respiratory Disease, 135, 805-811.
https://doi.org/10.1164/arrd.1987.135.4.805
[11]
Bates, D.V. (1989) Respiratory Function in Disease. Saunders, Philadelphia, 108-109.
[12]
Fletcher, C.M., Elmes, P.C., Fairbairn, M.B., et al. (1959) The Significance of Respiratory Symptoms and the Diagnosis of Chronic Bronchitis in a Working Population. British Medical Journal, 2, 257-266. https://doi.org/10.1136/bmj.2.5147.257
[13]
Vestbo, J., Hurd, S.S., Agustí, A.G., Jones, P.W., Vogelmeier, C., Anzueto, A., Barnes, P.J., Fabbri, L.M., Martinez, F.J., Nishimura, M., Stockley, R.A., Sin, D.D. and Rodriguez-Roisin, R. (2013) Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: GOLD Executive Summary. American Journal of Respiratory and Critical Care Medicine, 187, 347-365. https://doi.org/10.1164/rccm.201204-0596PP
[14]
Dixon, W.J. and Massey, F.J. (1983) Introduction to Statistical Analysis. 4th Edition, McGraw-Hill, New York, 385-414.
[15]
Woodruff, P.G., Barr, R.G., Bleeker, E., et al. (2016) Clinical Significance of Symptoms in Smokers with Preserved Pulmonary Function. The New England Journal of Medicine, 374, 1811-1812. https://doi.org/10.1056/NEJMoa1505971
[16]
Marin, J.R., Santiago, J.C., Gascon, M., Sanchez, A., Gallego, B. and Celli, B.R. (2001) Inspiratory Capacity, Dynamic Hyperinflation, Breathlessness, and Exercise Performance during the 6-Minute Walk Test in Chronic Obstructive Pulmonary Disease. American Journal of Respiratory and Critical Care Medicine, 163, 1395-1399. https://doi.org/10.1164/ajrccm.163.6.2003172
[17]
Tantucci, C., Donati, C., Nicosia, F., et al. (2008) Inspiratory Capacity Predicts Mortality in Patients with Chronic Obstructive Pulmonary Disease. Respiratory Medicine, 102, 613-619. https://doi.org/10.1016/j.rmed.2007.11.004
[18]
French, A., Balfe, D., Mirocha, J.M., et al. (2015) The Inspiratory/Total Lung Capacity Ratio as a Predictor of Survival in an Emphysematous Phenotype of Chronic Obstructive Pulmonary Disease. International Journal of Chronic Obstructive Pulmonary Disease, 10, 1305-1312. https://doi.org/10.2147/COPD.S76739
[19]
McCarthy, D.S., Spencer, R., Greene, R. and Milic-Emili, J. (1972) Measurement of “Closing Volume” as a Simple and Sensitive Test for Early Detection of Small Airway Disease. The American Journal of Medicine, 52, 747-753.
https://doi.org/10.1016/0002-9343(72)90080-0
[20]
Milic-Emili, J. (2004) Does Mechanical Injury of the Peripheral Airways Play a Role in the Genesis of COPD in Smokers? COPD, 1, 85-92.
https://doi.org/10.1081/COPD-120028700
[21]
Muscadere, J.G., Mullen, J.B., Gan, K., Bryan, C. and Slutsky, A.S. (1994) Tidal Ventilation at Low Airway Pressures Can Augment Lung Injury. American Journal of Respiratory and Critical Care Medicine, 149, 1327-1334.
https://doi.org/10.1164/ajrccm.149.5.8173774
[22]
Saetta, M., Di Stefano, A., Turato, G., Facchini, F.M., Corbino, L., Mapp, C.E., Maestrelli, P., Ciaccia, A. and Fabbbri, L.M. (1998) CD8+ T-Lymphocytes in Peripheral Airways of Smokers with Chronic Obstructive Pulmonary Disease. American Journal of Respiratory and Critical Care Medicine, 15, 822-826.
https://doi.org/10.1164/ajrccm.157.3.9709027
[23]
D’Angelo, E., Pecchiari, M., Baraggia, P., Saetta, M., Balestro, E. and Milic-Emili, J. (2002) Low Volume Ventilation Induces Peripheral Airways Injury and Increased Airways Resistance in Normal Open Chest Rabbits. Journal of Applied Physiology, 92, 949-956. https://doi.org/10.1152/japplphysiol.00776.2001
[24]
Niewoehner, D.E., Kleinerman, J. and Rice, D.B. (1974) Pathologic Changes in the Peripheral Airways of Young Cigarette Smokers. The New England Journal of Medicine, 291, 755-758. https://doi.org/10.1056/NEJM197410102911503
[25]
Hogg, J.C., McDonough, J.E. and Suzuki, M. (2013) Small Airway Obstruction in COPD. New Insights Based on Micro-CT Imaging and MRI Imaging. Chest, 143, 1436-1443. https://doi.org/10.1378/chest.12-1766
[26]
McDonough, J.E., Yuan, R., Suzuki, M., et al. (2011) Small-Airway Obstruction and Emphysema in Chronic Obstructive Pulmonary Disease. The New England Journal of Medicine, 365, 1567-1575. https://doi.org/10.1056/NEJMoa1106955
[27]
Tanabe, N., Vasilescu, D.M., McDonough, J.E., Kinose, D., Suzuki, M., Cooper, J.D., Paré, P.D. and Hogg, J.C. (2017) Micro-Computed Tomography Comparison of Preterminal Bronchioles in Centrilobular and Panlobular Emphysema. American Journal of Respiratory and Critical Care Medicine, 195, 630-638.
https://doi.org/10.1164/rccm.201602-0278OC
[28]
Parameswaran, H., Majumdar, A. and Suki, B. (2011) Linking Microscopic Spatial Patterns of Tissue Destruction in Emphysema to Macroscopic Decline in Stiffness Using a 3D Computational Model. PLOS Computational Biology, 7, e1001125.
https://doi.org/10.1371/journal.pcbi.1001125
[29]
Mondonedo, J.R., Sato, S., Oguma, T., et al. (2019) CT Imaging-Based Low-Attenuation Super Clusters in Three Dimensions and the Progression of Emphysema. Chest, 155, 79-87. https://doi.org/10.1016/j.chest.2018.09.014
[30]
California—Fact Sheet—American FactFinder.
[31]
Metro Vancouver Population by Visible Minority. National Household Survey (NHS) Profile, 2011, Canada.
[32]
Bruse, S., Sood, A., Petersen, H., et al. (2011) New Mexican Hispanic Smokers Have Lower Odds of Chronic Obstructive Pulmonary Disease and Less Decline in Lung Function than Non-Hispanic Whites. American Journal of Respiratory and Critical Care Medicine, 184, 1254-1260. https://doi.org/10.1164/rccm.201103-0568OC
[33]
Akinbami, L.J. and Liu, X. (2011) Chronic Obstructive Pulmonary Disease among Adults Aged 18 and over in the United States, 1998-2009. NCHS Data Brief No. 63. National Center for Health Statistics, Hyattsville.
[34]
Alcaide, A.B., Sanchez-Salcedo, P., Bastarrika, G., et al. (2017) Clinical Features of Smokers with Radiological Emphysema But without Airway Limitation. Chest, 151, 358-365. https://doi.org/10.1016/j.chest.2016.10.044
[35]
Casanova, C., Cote, C., de Torres, J.P., et al. (2005) Inspiratory-to-Total Lung Capacity Ratio Predicts Mortality in Patients with Chronic Obstructive Pulmonary Disease. American Journal of Respiratory and Critical Care Medicine, 171, 591-597.
https://doi.org/10.1164/rccm.200407-867OC
[36]
Klooster, K., Hartman, J.E., ten Hacken, N.H.T. and Slebos, D.-J. (2017) Improved Predictors of Survival after Endobronchial Valve Treatment in Patients with Severe Emphysema. American Journal of Respiratory and Critical Care Medicine, 195, 1272-1274. https://doi.org/10.1164/rccm.201610-1993LE
[37]
Criner, G. (2011) Lung Volume Reduction as an Alternative to Transplantation for COPD. Clinics in Chest Medicine, 32, 379-397.
https://doi.org/10.1016/j.ccm.2011.02.014
[38]
O’Donnell, D.E. (2006) Hyperinflation, Dyspnea, and Exercise Tolerance in Chronic Obstructive Pulmonary Disease. Proceedings of the American Thoracic Society, 3, 180-184. https://doi.org/10.1513/pats.200508-093DO
