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Published in: BMC Pulmonary Medicine 1/2024

Open Access 01-12-2024 | Six Minute Walk Test | Research

The acute effect of inhaled nitric oxide on the exercise capacity of patients with advanced interstitial lung disease: a randomized controlled trial

Authors: Lev Freidkin, Mordechai R Kramer, Dror Rosengarten, Shimon Izhakian, Shani Taieb, Barak Pertzov

Published in: BMC Pulmonary Medicine | Issue 1/2024

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Abstract

Background

Inhaled nitric oxide (iNO) selectively acts on the pulmonary vasculature of ventilated lung tissue by reducing pulmonary vascular resistance and intrapulmonary shunt. This effect may reduce ventilation/perfusion mismatch and decrease pulmonary hypertension in patients with interstitial lung disease.

Methods

In a prospective, single-blinded, randomized, placebo-controlled trial, participants with advanced interstitial lung disease, underwent two separate six-minute walk tests (6MWT): one with iNO and the other with a placebo. The primary outcome measured the difference in meters between the distances covered in the two tests. Secondary outcomes included oxygen saturation levels, distance-saturation product, and Borg dyspnea score. A predefined subgroup analysis was conducted for patients with pulmonary hypertension.

Results

Overall, 44 patients were included in the final analysis. The 6MWT distance was similar for iNO treatment and placebo, median 362 m (IQR 265-409) vs 371 m (IQR 250-407), respectively (p = 0.29). Subgroup analysis for patients with pulmonary hypertension showed no difference in 6MWT distance with iNO and placebo, median 339 (256-402) vs 332 (238-403) for the iNO and placebo tests respectively (P=0.50). No correlation was observed between mean pulmonary artery pressure values and the change in 6MWT distance with iNO versus placebo (spearman correlation Coefficient 0.24, P=0.33).

Conclusion

In patients with advanced interstitial lung disease, both with and without concurrent pulmonary hypertension, the administration of inhaled nitric oxide failed to elicit beneficial effects on the six-minute walk distance and oxygen saturation. The use of inhaled NO was found to be safe and did not lead to any serious side effects.

Trial registration

(NCT03873298, MOH_2018-04-24_002331).
Appendix
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Literature
1.
go back to reference Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacological Reviews. 1991;43(2):109 LP – 142. Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacological Reviews. 1991;43(2):109 LP – 142.
2.
go back to reference Palmer RMJ, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987;327(6122):524–6.CrossRefPubMed Palmer RMJ, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987;327(6122):524–6.CrossRefPubMed
3.
go back to reference Griffiths MJD, Evans TW. Inhaled Nitric Oxide Therapy in Adults. N Engl J Med. 2005;353(25):2683–95.CrossRefPubMed Griffiths MJD, Evans TW. Inhaled Nitric Oxide Therapy in Adults. N Engl J Med. 2005;353(25):2683–95.CrossRefPubMed
4.
go back to reference Ichinose F, Roberts JD, Zapol WM. Inhaled nitric oxide: a selective pulmonary vasodilator: current uses and therapeutic potential. Circulation. 2004;109(25):3106–11.CrossRefPubMed Ichinose F, Roberts JD, Zapol WM. Inhaled nitric oxide: a selective pulmonary vasodilator: current uses and therapeutic potential. Circulation. 2004;109(25):3106–11.CrossRefPubMed
5.
go back to reference Rossaint R, Falke KJ, Lopez F, Slama K, Pison U, Zapol WM. Inhaled Nitric Oxide for the Adult Respiratory Distress Syndrome. New England Journal of Medicine. 1993;328(6):399–405.CrossRefPubMed Rossaint R, Falke KJ, Lopez F, Slama K, Pison U, Zapol WM. Inhaled Nitric Oxide for the Adult Respiratory Distress Syndrome. New England Journal of Medicine. 1993;328(6):399–405.CrossRefPubMed
6.
go back to reference Abe S, Ishida K, Masuda M, Ueda H, Kohno H, Matsuura K, et al. A prospective, randomized study of inhaled prostacyclin versus nitric oxide in patients with residual pulmonary hypertension after pulmonary endarterectomy. General Thoracic and Cardiovascular Surgery. 2017;65(3):153–9.CrossRefPubMed Abe S, Ishida K, Masuda M, Ueda H, Kohno H, Matsuura K, et al. A prospective, randomized study of inhaled prostacyclin versus nitric oxide in patients with residual pulmonary hypertension after pulmonary endarterectomy. General Thoracic and Cardiovascular Surgery. 2017;65(3):153–9.CrossRefPubMed
7.
go back to reference Fernandes JL, Sampaio RO, Brandão CM, Accorsi TAD, Cardoso LF, Spina GS, et al. Comparison of Inhaled Nitric Oxide Versus Oxygen on Hemodynamics in Patients With Mitral Stenosis and Severe Pulmonary Hypertension After Mitral Valve Surgery. The American Journal of Cardiology. 2011;107(7):1040–5.CrossRefPubMed Fernandes JL, Sampaio RO, Brandão CM, Accorsi TAD, Cardoso LF, Spina GS, et al. Comparison of Inhaled Nitric Oxide Versus Oxygen on Hemodynamics in Patients With Mitral Stenosis and Severe Pulmonary Hypertension After Mitral Valve Surgery. The American Journal of Cardiology. 2011;107(7):1040–5.CrossRefPubMed
8.
go back to reference Parsons S, Celermajer D, Savidis E, Miller O, Young I. The Effect of Inhaled Nitric Oxide on 6-Minute Walk Distance in Patients With Pulmonary Hypertension. Chest. 1998;114(1):70S-72S.CrossRefPubMed Parsons S, Celermajer D, Savidis E, Miller O, Young I. The Effect of Inhaled Nitric Oxide on 6-Minute Walk Distance in Patients With Pulmonary Hypertension. Chest. 1998;114(1):70S-72S.CrossRefPubMed
9.
go back to reference Taylor RW. Low-Dose Inhaled Nitric Oxide in Patients With Acute Lung Injury: a Randomized Controlled Trial. JAMA. 2004;291(13):1603.CrossRefPubMed Taylor RW. Low-Dose Inhaled Nitric Oxide in Patients With Acute Lung Injury: a Randomized Controlled Trial. JAMA. 2004;291(13):1603.CrossRefPubMed
10.
go back to reference Maitre B, Djibre M, Katsahian S, Habibi A, Stankovic Stojanovic K, Khellaf M, et al. Inhaled nitric oxide for acute chest syndrome in adult sickle cell patients: a randomized controlled study. Intensive Care Medicine. 2015;41(12):2121–9.CrossRefPubMed Maitre B, Djibre M, Katsahian S, Habibi A, Stankovic Stojanovic K, Khellaf M, et al. Inhaled nitric oxide for acute chest syndrome in adult sickle cell patients: a randomized controlled study. Intensive Care Medicine. 2015;41(12):2121–9.CrossRefPubMed
11.
go back to reference Kline JA, Hall CL, Jones AE, Puskarich MA, Mastouri RA, Lahm T. Randomized trial of inhaled nitric oxide to treat acute pulmonary embolism: The iNOPE trial. Vol. 186, American Heart Journal. 2017. p. 100–10. Kline JA, Hall CL, Jones AE, Puskarich MA, Mastouri RA, Lahm T. Randomized trial of inhaled nitric oxide to treat acute pulmonary embolism: The iNOPE trial. Vol. 186, American Heart Journal. 2017. p. 100–10.
12.
go back to reference Potapov E, Meyer D, Swaminathan M, Ramsay M, El Banayosy A, Diehl C, et al. Inhaled nitric oxide after left ventricular assist device implantation: A prospective, randomized, double-blind, multicenter, placebo-controlled trial. Journal of Heart and Lung Transplantation. 2011;30(8):870–8. Potapov E, Meyer D, Swaminathan M, Ramsay M, El Banayosy A, Diehl C, et al. Inhaled nitric oxide after left ventricular assist device implantation: A prospective, randomized, double-blind, multicenter, placebo-controlled trial. Journal of Heart and Lung Transplantation. 2011;30(8):870–8.
13.
go back to reference Karampitsakos T, Tzouvelekis A, Chrysikos S, Bouros D, Tsangaris I, Fares WH. Pulmonary hypertension in patients with interstitial lung disease. Pulm Pharmacol Ther. 2018;50:38–46.CrossRefPubMed Karampitsakos T, Tzouvelekis A, Chrysikos S, Bouros D, Tsangaris I, Fares WH. Pulmonary hypertension in patients with interstitial lung disease. Pulm Pharmacol Ther. 2018;50:38–46.CrossRefPubMed
14.
go back to reference Patel NM, Lederer DJ, Borczuk AC, Kawut SM. Pulmonary hypertension in idiopathic pulmonary fibrosis. Chest. 2007;132(3):998–1006.CrossRefPubMed Patel NM, Lederer DJ, Borczuk AC, Kawut SM. Pulmonary hypertension in idiopathic pulmonary fibrosis. Chest. 2007;132(3):998–1006.CrossRefPubMed
15.
go back to reference Blanco I, Ribas J, Xaubet A, Gómez FP, Roca J, Rodriguez-Roisin R, et al. Effects of inhaled nitric oxide at rest and during exercise in idiopathic pulmonary fibrosis. J Appl Physiol. 2011;110(3):638–45.CrossRefPubMed Blanco I, Ribas J, Xaubet A, Gómez FP, Roca J, Rodriguez-Roisin R, et al. Effects of inhaled nitric oxide at rest and during exercise in idiopathic pulmonary fibrosis. J Appl Physiol. 2011;110(3):638–45.CrossRefPubMed
16.
go back to reference Nathan SD, Flaherty KR, Glassberg MK, Raghu G, Swigris J, Alvarez R, et al. A Randomized, Double-Blind, Placebo-Controlled Study of Pulsed, Inhaled Nitric Oxide in Subjects at Risk of Pulmonary Hypertension Associated With Pulmonary Fibrosis. Chest. 2020;158(2):637–45.CrossRefPubMed Nathan SD, Flaherty KR, Glassberg MK, Raghu G, Swigris J, Alvarez R, et al. A Randomized, Double-Blind, Placebo-Controlled Study of Pulsed, Inhaled Nitric Oxide in Subjects at Risk of Pulmonary Hypertension Associated With Pulmonary Fibrosis. Chest. 2020;158(2):637–45.CrossRefPubMed
17.
go back to reference King CS, Flaherty KR, Glassberg MK, Lancaster L, Raghu G, Swigris JJ, et al. A Phase-2 Exploratory Randomized Controlled Trial of INOpulse in Patients with Fibrotic Interstitial Lung Disease Requiring Oxygen. Ann Am Thorac Soc. 2022;19(4):594–602.CrossRefPubMed King CS, Flaherty KR, Glassberg MK, Lancaster L, Raghu G, Swigris JJ, et al. A Phase-2 Exploratory Randomized Controlled Trial of INOpulse in Patients with Fibrotic Interstitial Lung Disease Requiring Oxygen. Ann Am Thorac Soc. 2022;19(4):594–602.CrossRefPubMed
18.
go back to reference Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44–68. Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44–68.
19.
go back to reference Stanojevic S, Kaminsky DA, Miller MR, Thompson B, Aliverti A, Barjaktarevic I, et al. ERS/ATS technical standard on interpretive strategies for routine lung function tests. Eur Respir J. 2022;60(1):2101499.CrossRefPubMed Stanojevic S, Kaminsky DA, Miller MR, Thompson B, Aliverti A, Barjaktarevic I, et al. ERS/ATS technical standard on interpretive strategies for routine lung function tests. Eur Respir J. 2022;60(1):2101499.CrossRefPubMed
20.
go back to reference Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl. 1993;16:5–40. Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl. 1993;16:5–40.
21.
go back to reference Idiopathic Pulmonary Fibrosis Clinical Research Network, Zisman DA, Schwarz M, Anstrom KJ, Collard HR, Flaherty KR, et al. A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis. N Engl J Med. 2010;363(7):620–8. Idiopathic Pulmonary Fibrosis Clinical Research Network, Zisman DA, Schwarz M, Anstrom KJ, Collard HR, Flaherty KR, et al. A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis. N Engl J Med. 2010;363(7):620–8.
22.
go back to reference Nathan SD, Behr J, Collard HR, Cottin V, Hoeper MM, Martinez FJ, et al. Riociguat for idiopathic interstitial pneumonia-associated pulmonary hypertension (RISE-IIP): a randomised, placebo-controlled phase 2b study. Lancet Respir Med. 2019;7(9):780–90.CrossRefPubMed Nathan SD, Behr J, Collard HR, Cottin V, Hoeper MM, Martinez FJ, et al. Riociguat for idiopathic interstitial pneumonia-associated pulmonary hypertension (RISE-IIP): a randomised, placebo-controlled phase 2b study. Lancet Respir Med. 2019;7(9):780–90.CrossRefPubMed
23.
go back to reference Waxman A, Restrepo-Jaramillo R, Thenappan T, Ravichandran A, Engel P, Bajwa A, et al. Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease. N Engl J Med. 2021;384(4):325–34.CrossRefPubMed Waxman A, Restrepo-Jaramillo R, Thenappan T, Ravichandran A, Engel P, Bajwa A, et al. Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease. N Engl J Med. 2021;384(4):325–34.CrossRefPubMed
24.
go back to reference Lettieri CJ, Nathan SD, Browning RF, Barnett SD, Ahmad S, Shorr AF. The distance-saturation product predicts mortality in idiopathic pulmonary fibrosis. Respiratory Medicine. 2006;100(10):1734–41.CrossRefPubMed Lettieri CJ, Nathan SD, Browning RF, Barnett SD, Ahmad S, Shorr AF. The distance-saturation product predicts mortality in idiopathic pulmonary fibrosis. Respiratory Medicine. 2006;100(10):1734–41.CrossRefPubMed
25.
go back to reference Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. European Respiratory Journal. 2023;61(1):2200879.CrossRefPubMed Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. European Respiratory Journal. 2023;61(1):2200879.CrossRefPubMed
27.
go back to reference Holland AE, Spruit MA, Troosters T, Puhan MA, Pepin V, Saey D, et al. An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease. European Respiratory Journal. 2014;44(6):1428–46.CrossRefPubMed Holland AE, Spruit MA, Troosters T, Puhan MA, Pepin V, Saey D, et al. An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease. European Respiratory Journal. 2014;44(6):1428–46.CrossRefPubMed
29.
go back to reference Kline JA, Hall CL, Jones AE, Puskarich MA, Mastouri RA, Lahm T. Randomized trial of inhaled nitric oxide to treat acute pulmonary embolism: The iNOPE trial. Am Heart J. 2017;186:100–10.CrossRefPubMedPubMedCentral Kline JA, Hall CL, Jones AE, Puskarich MA, Mastouri RA, Lahm T. Randomized trial of inhaled nitric oxide to treat acute pulmonary embolism: The iNOPE trial. Am Heart J. 2017;186:100–10.CrossRefPubMedPubMedCentral
30.
go back to reference Hajian B, Shivalkar B, Ferreira F, Holsbeke CV, Voss W, Backer JD, et al. Pulsed inhaled nitric oxide (iNO) improves exercise tolerance and shortness of breath (SOB) in severe COPD subjects with pulmonary hypertension (PH). European Respiratory Journal [Internet]. 2018 [cited 2024 Apr 13];52(suppl 62). Available from: https://erj.ersjournals.com/content/52/suppl_62/OA5341 Hajian B, Shivalkar B, Ferreira F, Holsbeke CV, Voss W, Backer JD, et al. Pulsed inhaled nitric oxide (iNO) improves exercise tolerance and shortness of breath (SOB) in severe COPD subjects with pulmonary hypertension (PH). European Respiratory Journal [Internet]. 2018 [cited 2024 Apr 13];52(suppl 62). Available from: https://​erj.​ersjournals.​com/​content/​52/​suppl_​62/​OA5341
31.
go back to reference Vonbank K, Ziesche R, Higenbottam TW, Stiebellehner L, Petkov V, Schenk P, et al. Controlled prospective randomised trial on the effects on pulmonary haemodynamics of the ambulatory long term use of nitric oxide and oxygen in patients with severe COPD. Thorax. 2003;58(4):289–93.CrossRefPubMedPubMedCentral Vonbank K, Ziesche R, Higenbottam TW, Stiebellehner L, Petkov V, Schenk P, et al. Controlled prospective randomised trial on the effects on pulmonary haemodynamics of the ambulatory long term use of nitric oxide and oxygen in patients with severe COPD. Thorax. 2003;58(4):289–93.CrossRefPubMedPubMedCentral
32.
go back to reference Hajian B, De Backer J, Vos W, Van Holsbeke C, Ferreira F, Quinn DA, et al. Pulmonary vascular effects of pulsed inhaled nitric oxide in COPD patients with pulmonary hypertension. Int J Chron Obstruct Pulmon Dis. 2016;11:1533–41.CrossRefPubMedPubMedCentral Hajian B, De Backer J, Vos W, Van Holsbeke C, Ferreira F, Quinn DA, et al. Pulmonary vascular effects of pulsed inhaled nitric oxide in COPD patients with pulmonary hypertension. Int J Chron Obstruct Pulmon Dis. 2016;11:1533–41.CrossRefPubMedPubMedCentral
33.
go back to reference Bentur L, Gur M, Ashkenazi M, Livnat-Levanon G, Mizrahi M, Tal A, et al. Pilot study to test inhaled nitric oxide in cystic fibrosis patients with refractory Mycobacterium abscessus lung infection. J Cyst Fibros. 2020;19(2):225–31.CrossRefPubMed Bentur L, Gur M, Ashkenazi M, Livnat-Levanon G, Mizrahi M, Tal A, et al. Pilot study to test inhaled nitric oxide in cystic fibrosis patients with refractory Mycobacterium abscessus lung infection. J Cyst Fibros. 2020;19(2):225–31.CrossRefPubMed
34.
go back to reference Corte TJ, Keir GJ, Dimopoulos K, Howard L, Corris PA, Parfitt L, et al. Bosentan in Pulmonary Hypertension Associated with Fibrotic Idiopathic Interstitial Pneumonia. American Journal of Respiratory and Critical Care Medicine. 2014;190(2):208–17.CrossRefPubMedPubMedCentral Corte TJ, Keir GJ, Dimopoulos K, Howard L, Corris PA, Parfitt L, et al. Bosentan in Pulmonary Hypertension Associated with Fibrotic Idiopathic Interstitial Pneumonia. American Journal of Respiratory and Critical Care Medicine. 2014;190(2):208–17.CrossRefPubMedPubMedCentral
35.
go back to reference Raghu G. Treatment of Idiopathic Pulmonary Fibrosis With Ambrisentan: A parallel, randomized trial. Annals of Internal Medicine. 2013;158(9):641.CrossRefPubMed Raghu G. Treatment of Idiopathic Pulmonary Fibrosis With Ambrisentan: A parallel, randomized trial. Annals of Internal Medicine. 2013;158(9):641.CrossRefPubMed
36.
go back to reference Behr J, Kolb M, Song JW, Luppi F, Schinzel B, Stowasser S, et al. Nintedanib and Sildenafil in Patients with Idiopathic Pulmonary Fibrosis and Right Heart Dysfunction. A Prespecified Subgroup Analysis of a Double-Blind Randomized Clinical Trial (INSTAGE). American Journal of Respiratory and Critical Care Medicine. 2019;200(12):1505–12. Behr J, Kolb M, Song JW, Luppi F, Schinzel B, Stowasser S, et al. Nintedanib and Sildenafil in Patients with Idiopathic Pulmonary Fibrosis and Right Heart Dysfunction. A Prespecified Subgroup Analysis of a Double-Blind Randomized Clinical Trial (INSTAGE). American Journal of Respiratory and Critical Care Medicine. 2019;200(12):1505–12.
37.
go back to reference Network TIPFCR. A Controlled Trial of Sildenafil in Advanced Idiopathic Pulmonary Fibrosis. New England Journal of Medicine. 2010;363(7):620–8. Network TIPFCR. A Controlled Trial of Sildenafil in Advanced Idiopathic Pulmonary Fibrosis. New England Journal of Medicine. 2010;363(7):620–8.
38.
go back to reference Nathan SD, Behr J, Cottin V, Lancaster L, Smith P, Deng C, et al. Study design and rationale for the TETON phase 3, randomised, controlled clinical trials of inhaled treprostinil in the treatment of idiopathic pulmonary fibrosis. BMJ Open Respiratory Research. 2022;9(1): e001310.CrossRefPubMedPubMedCentral Nathan SD, Behr J, Cottin V, Lancaster L, Smith P, Deng C, et al. Study design and rationale for the TETON phase 3, randomised, controlled clinical trials of inhaled treprostinil in the treatment of idiopathic pulmonary fibrosis. BMJ Open Respiratory Research. 2022;9(1): e001310.CrossRefPubMedPubMedCentral
39.
go back to reference Harari S, Wells AU, Wuyts WA, Nathan SD, Kirchgaessler KU, Bengus M, et al. The 6-min walk test as a primary end-point in interstitial lung disease. Eur Respir Rev. 2022;31(165): 220087.CrossRefPubMedPubMedCentral Harari S, Wells AU, Wuyts WA, Nathan SD, Kirchgaessler KU, Bengus M, et al. The 6-min walk test as a primary end-point in interstitial lung disease. Eur Respir Rev. 2022;31(165): 220087.CrossRefPubMedPubMedCentral
Metadata
Title
The acute effect of inhaled nitric oxide on the exercise capacity of patients with advanced interstitial lung disease: a randomized controlled trial
Authors
Lev Freidkin
Mordechai R Kramer
Dror Rosengarten
Shimon Izhakian
Shani Taieb
Barak Pertzov
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2024
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-024-03051-4

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