Cardiopulmonary Exercise Testing in Patients With Interstitial Lung Disease

Yannick Molgat-Seon, Michele R Schaeffer, Christopher J Ryerson, Jordan A Guenette, Yannick Molgat-Seon, Michele R Schaeffer, Christopher J Ryerson, Jordan A Guenette

Abstract

Interstitial lung disease (ILD) is a heterogeneous group of conditions characterized by fibrosis and/or inflammation of the lung parenchyma. The pathogenesis of ILD consistently results in exertional dyspnea and exercise intolerance. Cardiopulmonary exercise testing (CPET) provides important information concerning the pathophysiology of ILD that can help inform patient management. Despite the purported benefits of CPET, its clinical utility in ILD is not well defined; however, there is a growing body of evidence that provides insight into the potential value of CPET in ILD. Characteristic responses to CPET in patients with ILD include exercise-induced arterial hypoxemia, an exaggerated ventilatory response, a rapid and shallow breathing pattern, critically low inspiratory reserve volume, and elevated sensations of dyspnea and leg discomfort. CPET is used in ILD to determine cause(s) of symptoms such as exertional dyspnea, evaluate functional capacity, inform exercise prescription, and determine the effects of pharmacological and non-pharmacological interventions on exercise capacity and exertional symptoms. However, preliminary evidence suggests that CPET in ILD may also provide valuable prognostic information and can be used to ascertain the degree of exercise-induced pulmonary hypertension. Despite these recent advances, additional research is required to confirm the utility of CPET in patients with ILD. This brief review outlines the clinical utility of CPET in patients with ILD. Typical patterns of response are described and practical issues concerning CPET interpretation in ILD are addressed. Additionally, important unanswered questions relating to the clinical utility of CPET in the assessment, prognostication, and management of patients with ILD are identified.

Keywords: dyspnea; exercise capacity; hypoxemia; idiopathic pulmonary fibrosis; ventilatory limitation.

Copyright © 2020 Molgat-Seon, Schaeffer, Ryerson and Guenette.

References

    1. Agusti A. G., Roca J., Gea J., Wagner P. D., Xaubet A., Rodriguez-Roisin R. (1991). Mechanisms of gas-exchange impairment in idiopathic pulmonary fibrosis. Am. Rev. Respir. Dis. 143 219–225. 10.1164/ajrccm/143.2.219
    1. Agusti A. G., Roca J., Rodriguez-Roisin R., Xaubet A., Agusti-Vidal A. (1988). Different patterns of gas exchange response to exercise in asbestosis and idiopathic pulmonary fibrosis. Eur. Respir. J. 1 510–516.
    1. Agusti C., Xaubet A., Agusti A. G., Roca J., Ramirez J., Rodriguez-Roisin R. (1994). Clinical and functional assessment of patients with idiopathic pulmonary fibrosis: results of a 3 year follow-up. Eur. Respir. J. 7 643–650. 10.1183/09031936.94.07040643
    1. American Thoracic S., American College of Chest P. (2003). ATS/ACCP Statement on cardiopulmonary exercise testing. Am. J. Respir. Crit. Care Med. 167 211–277. 10.1164/rccm.167.2.211
    1. Arena R., Sietsema K. E. (2011). Cardiopulmonary exercise testing in the clinical evaluation of patients with heart and lung disease. Circulation 123 668–680. 10.1161/CIRCULATIONAHA.109.914788
    1. Armstrong H. F., Thirapatarapong W., Dussault N. E., Bartels M. N. (2013). Distinguishing pulmonary hypertension in interstitial lung disease by ventilation and perfusion defects measured by cardiopulmonary exercise testing. Respiration 86 407–413. 10.1159/000350445
    1. Assayag D., Camp P. G., Fisher J. H., Johannson K. A., Kolb M., Lohmann T., et al. (2018). Comprehensive management of fibrotic interstitial lung diseases: a Canadian Thoracic Society position statement. Can. J. Respir. Crit. Care Sleep Med. 2 234–243. 10.1080/24745332.2018.1503456
    1. Bagnato G., Harari S. (2015). Cellular interactions in the pathogenesis of interstitial lung diseases. Eur. Respir. Rev. 24 102–114. 10.1183/09059180.00003214
    1. Baughman R. P., Culver D. A., Judson M. A. (2011). A concise review of pulmonary sarcoidosis. Am. J. Respir. Crit. Care Med. 183 573–581. 10.1164/rccm.201006-0865CI
    1. Baughman R. P., Gerson M., Bosken C. H. (1984). Right and left ventricular function at rest and with exercise in patients with sarcoidosis. Chest 85 301–306. 10.1378/chest.85.3.301
    1. Bernard S., Ribeiro F., Maltais F., Saey D. (2014). Prescribing exercise training in pulmonary rehabilitation: a clinical experience. Rev. Port. Pneumol. 20 92–100. 10.1016/j.rppneu.2013.10.005
    1. Blanco I., Ribas J., Xaubet A., Gomez F. P., Roca J., Rodriguez-Roisin R., et al. (2011). Effects of inhaled nitric oxide at rest and during exercise in idiopathic pulmonary fibrosis. J. Appl. Physiol. 110 638–645. 10.1152/japplphysiol.01104.2010
    1. Bonini M., Fiorenzano G. (2017). Exertional dyspnoea in interstitial lung diseases: the clinical utility of cardiopulmonary exercise testing. Eur. Respir. Rev. 26:160099. 10.1183/16000617.0099-2016
    1. Bradley B., Branley H. M., Egan J. J., Greaves M. S., Hansell D. M., Harrison N. K., et al. (2008). Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society. Thorax 63(Suppl. 5), v1–v58. 10.1136/thx.2008.101691
    1. Burdon J. G., Killian K. J., Jones N. L. (1983). Pattern of breathing during exercise in patients with interstitial lung disease. Thorax 38 778–784. 10.1136/thx.38.10.778
    1. Bush A., Busst C. M. (1988). Cardiovascular function at rest and on exercise in patients with cryptogenic fibrosing alveolitis. Thorax 43 276–283. 10.1136/thx.43.4.276
    1. Chang J. A., Curtis J. R., Patrick D. L., Raghu G. (1999). Assessment of health-related quality of life in patients with interstitial lung disease. Chest 116 1175–1182. 10.1378/chest.116.5.1175
    1. Chetta A., Marangio E., Olivieri D. (2004). Pulmonary function testing in interstitial lung diseases. Respiration 71 209–213. 10.1159/000077416
    1. Collard H. R., Pantilat S. Z. (2008). Dyspnea in interstitial lung disease. Curr. Opin. Support Palliat. Care 2 100–104. 10.1097/SPC.0b013e3282ff6336
    1. D’Alto M., Ghio S., D’Andrea A., Pazzano A. S., Argiento P., Camporotondo R., et al. (2011). Inappropriate exercise-induced increase in pulmonary artery pressure in patients with systemic sclerosis. Heart 97 112–117. 10.1136/hrt.2010.203471
    1. Degani-Costa L. H., Levarge B., Digumarthy S. R., Eisman A. S., Harris R. S., Lewis G. D. (2015). Pulmonary vascular response patterns during exercise in interstitial lung disease. Eur. Respir. J. 46 738–749. 10.1183/09031936.00191014
    1. Dominelli P. B., Archiza B., Ramsook A. H., Mitchell R. A., Peters C. M., Molgat-Seon Y., et al. (2017). Effects of respiratory muscle work on respiratory and locomotor blood flow during exercise. Exp. Physiol. 102 1535–1547. 10.1113/EP086566
    1. du Bois R. M., Weycker D., Albera C., Bradford W. Z., Costabel U., Kartashov A., et al. (2011). Six-minute-walk test in idiopathic pulmonary fibrosis: test validation and minimal clinically important difference. Am. J. Respir. Crit. Care Med. 183 1231–1237. 10.1164/rccm.201007-1179OC
    1. Du Plessis J. P., Fernandes S., Jamal R., Camp P., Johannson K., Schaeffer M., et al. (2017). Exertional hypoxemia is more severe in fibrotic interstitial lung disease than in COPD. Respirology 23 392–398. 10.1111/resp.13226
    1. Faisal A., Alghamdi B. J., Ciavaglia C. E., Elbehairy A. F., Webb K. A., Ora J., et al. (2016). Common mechanisms of dyspnea in chronic interstitial and obstructive lung disorders. Am. J. Respir. Crit. Care Med. 193 299–309. 10.1164/rccm.201504-0841OC
    1. Fulmer J. D., Roberts W. C., von Gal E. R., Crystal R. G. (1979). Morphologic-physiologic correlates of the severity of fibrosis and degree of cellularity in idiopathic pulmonary fibrosis. J. Clin. Invest. 63 665–676. 10.1172/JCI109349
    1. Guenette J. A., Chin R. C., Cory J. M., Webb K. A., O’Donnell D. E. (2013). Inspiratory capacity during exercise: measurement, analysis, and interpretation. Pulm. Med. 2013:956081. 10.1155/2013/956081
    1. Hansen J. E., Wasserman K. (1996). Pathophysiology of activity limitation in patients with interstitial lung disease. Chest 109 1566–1576. 10.1378/chest.109.6.1566
    1. Himelman R. B., Stulbarg M., Kircher B., Lee E., Kee L., Dean N. C., et al. (1989). Noninvasive evaluation of pulmonary artery pressure during exercise by saline-enhanced Doppler echocardiography in chronic pulmonary disease. Circulation 79 863–871. 10.1161/01.cir.79.4.863
    1. Holland A. E. (2010). Exercise limitation in interstitial lung disease - mechanisms, significance and therapeutic options. Chron. Respir. Dis. 7 101–111. 10.1177/1479972309354689
    1. Jackson R. M., Glassberg M. K., Ramos C. F., Bejarano P. A., Butrous G., Gomez-Marin O. (2010). Sildenafil therapy and exercise tolerance in idiopathic pulmonary fibrosis. Lung 188 115–123. 10.1007/s00408-009-9209-8
    1. Jernudd-Wilhelmsson Y., Hornblad Y., Hedenstierna G. (1986). Ventilation-perfusion relationships in interstitial lung disease. Eur. J. Respir. Dis. 68 39–49.
    1. Keogh B. A., Crystal R. G. (1980). Clinical significance of pulmonary function tests. Pulmonary function testing in interstitial pulmonary disease. What does it tell us? Chest 78 856–865. 10.1378/chest.78.6.856
    1. King T. E. (2005). Clinical advances in the diagnosis and therapy of the interstitial lung diseases. Am. J. Respir. Crit. Care Med. 172 268–279. 10.1164/rccm.200503-483OE
    1. King T. E., Tooze J. A., Schwarz M. I., Brown K. R., Cherniack R. M. (2001). Predicting survival in idiopathic pulmonary fibrosis: scoring system and survival model. Am. J. Respir. Crit. Care Med. 164 1171–1181. 10.1164/ajrccm.164.7.2003140
    1. Lama V. N., Flaherty K. R., Toews G. B., Colby T. V., Travis W. D., Long Q., et al. (2003). Prognostic value of desaturation during a 6-minute walk test in idiopathic interstitial pneumonia. Am. J. Respir. Crit. Care Med. 168 1084–1090. 10.1164/rccm.200302-219OC
    1. Lama V. N., Martinez F. J. (2004). Resting and exercise physiology in interstitial lung diseases. Clin. Chest Med. 25 435–453. 10.1016/j.ccm.2004.05.005
    1. Layton A. M., Armstrong H. F., Kim H. P., Meza K. S., D’Ovidio F., Arcasoy S. M. (2017). Cardiopulmonary exercise factors predict survival in patients with advanced interstitial lung disease referred for lung transplantation. Respir. Med. 126 59–67. 10.1016/j.rmed.2017.03.022
    1. Marciniuk D. D., Gallagher C. G. (1994). Clinical exercise testing in interstitial lung disease. Clin. Chest Med. 15 287–303.
    1. Marciniuk D. D., Sridhar G., Clemens R. E., Zintel T. A., Gallagher C. G. (1994a). Lung volumes and expiratory flow limitation during exercise in interstitial lung disease. J. Appl. Physiol. 77 963–973. 10.1152/jappl.1994.77.2.963
    1. Marciniuk D. D., Watts R. E., Gallagher C. G. (1994b). Dead space loading and exercise limitation in patients with interstitial lung disease. Chest 105 183–189. 10.1378/chest.105.1.183
    1. Maron B. A., Cockrill B. A., Waxman A. B., Systrom D. M. (2013). The invasive cardiopulmonary exercise test. Circulation 127 1157–1164. 10.1161/CIRCULATIONAHA.112.104463
    1. McCurry K. R., Shearon T. H., Edwards L. B., Chan K. M., Sweet S. C., Valapour M., et al. (2009). Lung transplantation in the United States, 1998-2007. Am. J. Transplant. 9(4 Pt 2), 942–958. 10.1111/j.1600-6143.2009.02569.x
    1. Mezzani A. (2017). Cardiopulmonary exercise testing: basics of methodology and measurements. Ann. Am. Thorac. Soc. 14 S3–S11. 10.1513/AnnalsATS.201612-997FR
    1. Miller A., Brown L. K., Sloane M. F., Bhuptani A., Teirstein A. S. (1995). Cardiorespiratory responses to incremental exercise in sarcoidosis patients with normal spirometry. Chest 107 323–329. 10.1378/chest.107.2.323
    1. Molgat-Seon Y., Schaeffer M. R., Ryerson C. J., Guenette J. A. (2019). Exercise pathophysiology in interstitial lung disease. Clin. Chest Med. 40 405–420. 10.1016/j.ccm.2019.02.011
    1. Nathan S. D., Noble P. W., Tuder R. M. (2007). Idiopathic pulmonary fibrosis and pulmonary hypertension: connecting the dots. Am. J. Respir. Crit. Care Med. 175 875–880. 10.1164/rccm.200608-1153CC
    1. Nishiyama O., Taniguchi H., Kondoh Y., Kimura T., Ogawa T., Watanabe F., et al. (2005). Quadriceps weakness is related to exercise capacity in idiopathic pulmonary fibrosis. Chest 127 2028–2033. 10.1378/chest.127.6.2028
    1. O’Donnell D. E., Chau L. K., Webb K. A. (1998). Qualitative aspects of exertional dyspnea in patients with interstitial lung disease. J. Appl. Physiol. 84 2000–2009. 10.1152/jappl.1998.84.6.2000
    1. Palange P., Ward S. A., Carlsen K. H., Casaburi R., Gallagher C. G., Gosselink R., et al. (2007). Recommendations on the use of exercise testing in clinical practice. Eur. Respir. J. 29 185–209. 10.1183/09031936.00046906
    1. Panagiotou M., Church A. C., Johnson M. K., Peacock A. J. (2017). Pulmonary vascular and cardiac impairment in interstitial lung disease. Eur. Respir. Rev. 26:160053. 10.1183/16000617.0053-2016
    1. Panagiotou M., Polychronopoulos V., Strange C. (2016). Respiratory and lower limb muscle function in interstitial lung disease. Chron. Respir. Dis. 13 162–172. 10.1177/1479972315626014
    1. Parker C. M., Fitzpatrick M. F., O’Donnell D. E. (2011). “Physiology of interstitial lung disease,” in Interstitial Lung Disease, 5 Edn, eds Schwarz M. I., King T. E. (Beijing: People’s Medical Publishing House; ), 61–84.
    1. Puente-Maestu L., Palange P., Casaburi R., Laveneziana P., Maltais F., Neder J. A., et al. (2016). Use of exercise testing in the evaluation of interventional efficacy: an official ERS statement. Eur. Respir. J. 47 429–460. 10.1183/13993003.00745-2015
    1. Raghu G., Collard H. R., Egan J. J., Martinez F. J., Behr J., Brown K. K., et al. (2011). An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am. J. Respir. Crit. Care Med. 183 788–824. 10.1164/rccm.2009-040GL
    1. Reichenberger F., Voswinckel R., Schulz R., Mensch O., Ghofrani H. A., Olschewski H., et al. (2009). Noninvasive detection of early pulmonary vascular dysfunction in scleroderma. Respir. Med. 103 1713–1718. 10.1016/j.rmed.2009.05.004
    1. Richeldi L., Launders N., Martinez F., Walsh S. L. F., Myers J., Wang B., et al. (2019). The characterisation of interstitial lung disease multidisciplinary team meetings: a global study. ERJ Open Res. 5:00209-2018. 10.1183/23120541.00209-2018
    1. Schaeffer M. R., Molgat-Seon Y., Ryerson C. J., Guenette J. A. (2017a). Supplemental oxygen and dypsnoea in interstitial lung disease: absence of evidence is not evidence of absence. Eur. Respir. Rev. 26:170072. 10.1183/16000617.0033-2017
    1. Schaeffer M. R., Ryerson C. J., Ramsook A. H., Molgat-Seon Y., Wilkie S. S., Dhillon S. S., et al. (2017b). Effects of hyperoxia on dyspnoea and exercise endurance in fibrotic interstitial lung disease. Eur. Respir. J. 49:1602494. 10.1183/13993003.02494-2016
    1. Schaeffer M. R., Ryerson C. J., Ramsook A. H., Molgat-Seon Y., Wilkie S. S., Dhillon S. S., et al. (2018). Neurophysiological mechanisms of exertional dyspnoea in fibrotic interstitial lung disease. Eur. Respir. J. 51 1701726. 10.1183/13993003.01726-2017
    1. Schwaiblmair M., Behr J., Fruhmann G. (1996). Cardiorespiratory responses to incremental exercise in patients with systemic sclerosis. Chest 110 1520–1525. 10.1378/chest.110.6.1520
    1. Seeger W., Adir Y., Barbera J. A., Champion H., Coghlan J. G., Cottin V., et al. (2013). Pulmonary hypertension in chronic lung diseases. J. Am. Coll. Cardiol. 62 D109–D116. 10.1016/j.jacc.2013.10.036
    1. Tonelli R., Cocconcelli E., Lanini B., Romagnoli I., Florini F., Castaniere I., et al. (2017). Effectiveness of pulmonary rehabilitation in patients with interstitial lung disease of different etiology: a multicenter prospective study. BMC Pulm. Med. 17:130. 10.1186/s12890-017-0476-5
    1. Vainshelboim B., Kramer M. R., Izhakian S., Lima R. M., Oliveira J. (2016). Physical activity and exertional desaturation are associated with mortality in idiopathic pulmonary fibrosis. J. Clin. Med. 5:73. 10.3390/jcm5080073
    1. Van Meerhaeghe A., Scano G., Sergysels R., Bran M., De Coster A. (1981). Respiratory drive and ventilatory pattern during exercise in interstitial lung disease. Bull. Eur. Physiopathol. Respir. 17 15–26.
    1. Watanabe F., Taniguchi H., Sakamoto K., Kondoh Y., Kimura T., Kataoka K., et al. (2013). Quadriceps weakness contributes to exercise capacity in nonspecific interstitial pneumonia. Respir. Med. 107 622–628. 10.1016/j.rmed.2012.12.013
    1. Wehr K. L., Johnson R. L. (1976). Maximal oxygen consumption in patients with lung disease. J. Clin. Invest. 58 880–890. 10.1172/JCI108541
    1. Younes M. (1984). Interpretation of clinical exercise testing in respiratory disease. Clin. Chest Med. 5 189–206.
    1. Young I. H., Bye P. T. (2011). Gas exchange in disease: asthma, chronic obstructive pulmonary disease, cystic fibrosis, and interstitial lung disease. Compr. Physiol. 1 663–697. 10.1002/cphy.c090012

Source: PubMed

3
Subscribe