Background: Pulmonary hypertension (PH) is common in interstitial lung disease (ILD). Since cardiopulmonary exercise testing (CPET) is useful in understanding the pathophysiology of respiratory disorders and can distinguish between ventilation and perfusion (V/Q) defects, it may have a role in the detection of PH in ILD. We evaluated whether CPET can detect PH through analysis of V/Q defects in ILD. Objectives: We aimed to use CPET to determine if there are changes in the ventilation and the activity pattern of mixed-expired carbon dioxide pressure (PECO2) and end-tidal carbon dioxide pressure (PetCO2) in ILD patients with and without PH. Methods: A retrospective chart review was done of all patients who received lung transplants at the Columbia University Medical Center between 2000 and 2011 with the diagnosis of ILD. CPETs were performed during the 2 years prior to transplantation; right heart catheterizations and pulmonary function tests were performed within 4 months of CPET. Results: The ILD patients with PH demonstrated significantly lower PetCO2 and PECO2 during certain levels of exercise with a distinctive activity pattern for PECO2/PetCO2. Conclusions: Evaluation of V/Q defects through the PECO2 and PetCO2 patterns on CPET in ILD patients can distinguish between patients with and without PH.

Strange C, Highland KB: Pulmonary hypertension in interstitial lung disease. Curr Opin Pulm Med 2005;11:452-455.
Polomis D, Runo JR, Meyer KC: Pulmonary hypertension in interstitial lung disease. Curr Opin Pulm Med 2008;14:462-469.
Hansen JE, Ulubay G, Chow BF, Sun XG, Wasserman K: Mixed-expired and end-tidal CO2 distinguish between ventilation and perfusion defects during exercise testing in patients with lung and heart diseases. Chest 2007;132:977-983.
ATS/ACCP statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med 2003;167:211-277.
American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. Am J Respir Crit Care Med 2002;165:277-304.
Group NETT: A randomized trial comparing lung volume reduction surgery with medical therapy for severe emphysema. N Engl J Med 2003;348:2059-2073.
American Thoracic Society, American College of Chest Physicians: ATS/ACCP statement on cardiopulmonary exercise testing. Am J Respir Crit Car Med 2003;167:211-277.
Wasserman K, Hansen J, Sue D, Stringer W, Whipp B: Principles of Exercise Testing and Interpretation, ed 3. Philadelphia, Lippincott Williams & Wilkins, 1999.
Jones N, Makrides L, Hitchcock C, Chypchar T, McCartney N: Normal standards for an incremental progressive cycle ergometer test. Am Rev Respir Dis 1985;131:700-708.
Wanger J, Clausen JL, Coates A, Pedersen OF, Brusasco V, Burgos F, Casaburi R, Crapo R, Enright P, van der Grinten CPM, Gustafsson P, Hankinson J, Jensen R, Johnson D, MacIntyre N, McKay R, Miller MR, Navajas D, Pellegrino R, Viegi G: Standardisation of the measurement of lung volumes. Eur Respir J 2005;26:511-522.
Crapo R, Morris A, Clayton P, Nixon C: Lung volumes in healthy nonsmoking adults. Bull Eur Physiopathol Respir 1982;18:419-425.
Crapo R, Morris A, Gardner R: Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis 1981;123:659-664.
Crapo R, Morris A: Standardized single-breath normal values for carbon monoxide diffusing capacity. Am Rev Respir Dis 1981;123:185-189.
Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery J-L, Barbera JA, Beghetti M, Corris P, Gaine S, Gibbs JS, Gomez-Sanchez MA, Jondeau G, Klepetko W, Opitz C, Peacock A, Rubin L, Zellweger M, Simonneau G, ESC Committee for Practice Guidelines (CPG): Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J 2009;30:2493-2537.
Badesch DB, Champion HC, Gomez Sanchez MA, Hoeper MM, Loyd JE, Manes A, McGoon M, Naeije R, Olschewski H, Oudiz RJ, Torbicki A: Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol 2009;54:S55-S66.
Boutou AK, Pitsiou GG, Trigonis I, Papakosta D, Kontou PK, Chavouzis N, Nakou C, Argyropoulou P, Wasserman K, Stanopoulos I: Exercise capacity in idiopathic pulmonary fibrosis: the effect of pulmonary hypertension. Respirology 2011;16:451-458.
Launay D, Mouthon L, Hachulla E, Pagnoux C, de Groote P, Remy-Jardin M, Matran R, Lambert M, Queyrel V, Morell-Dubois S, Guillevin L, Hatron P-Y: Prevalence and characteristics of moderate to severe pulmonary hypertension in systemic sclerosis with and without interstitial lung disease. J Rheumatol 2007;34:1005-1011.
Pitsiou G, Papakosta D, Bouros D: Pulmonary hypertension in idiopathic pulmonary fibrosis: a review. Respiration 2011;82:294-304.
Andersen CU, Mellemkjær S, Hilberg O, Nielsen-Kudsk JE, Simonsen U, Bendstrup E: Pulmonary hypertension in interstitial lung disease: prevalence, prognosis and 6 min walk test. Respir Med 2012;106:875-882.
Leuchte HH, Neurohr C, Baumgartner R, Holzapfel M, Giehrl W, Vogeser M, Behr J: Brain natriuretic peptide and exercise capacity in lung fibrosis and pulmonary hypertension. Am J Respir Crit Care Med 2004;170:360-365.
Lettieri CJ, Nathan SD, Barnett SD, Ahmad S, Shorr AF: Prevalence and outcomes of pulmonary arterial hypertension in advanced idiopathic pulmonary fibrosis. Chest 2006;129:746-752.
Dumitrescu D, Oudiz RJ, Karpouzas G, Hovanesyan A, Jayasinghe A, Hansen JE, Rosenkranz S, Wasserman K: Developing pulmonary vasculopathy in systemic sclerosis, detected with non-invasive cardiopulmonary exercise testing. PLoS One 2010;5:e14293.
Arena R, Guazzi M, Myers J, Grinnen D, Forman DE, Lavie CJ: Cardiopulmonary exercise testing in the assessment of pulmonary hypertension. Expert Rev Respir Med 2011;5:281-293.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.