Effects of inhaled nitric oxide in chronic obstructive pulmonary disease patients with hypercapnic respiratory failure and pulmonary hypertension
https://doi.org/10.18093/0869-0189-2022-32-2-216-225
Abstract
Therapy with inhaled nitric oxide (iNO) in patients with hypercapnic respiratory failure (RF) and pulmonary arterial hypertension (PAH) is currently of scientific interest.
The aim of this study was to evaluate the effects of iNO therapy on COPD patients with hypercapnic RF and PAH during exacerbation of the disease.
Methods. A randomized, prospective, controlled trial included 30 patients with COPD (age 65 (62; 75) years) with hypercapnic RF and pulmonary arterial hypertension (PAH) treated at the State Budgetary City Teaching Hospital “City Clinical Hospital named after D.D.Pletnev of Healthcare Moscow City Department” (2021). The inclusion criteria were: PaCO2 ≥ 45 mm Hg and pulmonary artery systolic pressure PASP > 40 mm Hg as accessed by Doppler echocardiography. The patients were divided into two groups. Patients of the main group were administered iNO in the form of daily 90-minute sessons for two weeks using Tianoks device (Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics, State Corporation “Rosatom”, Russia). Patients of the control group received treatment that corresponded to the severity of their COPD exacerbation according to the guidelines by Global Initiative for Chronic Obstructive Lung Disease (GOLD), 2020 – 2021. Hemodynamics and gas exchange, exercise tolerance, vascular stiffness, and obstructive disorders were assessed at baseline, on Days 7 and 14.
Results. The main group demonstrated a decrease in PASP (38 (32; 43) mm Hg vs 47 (44; 54) mm Hg; p = 0.001), a decrease in stiffness index (SI) (7.03 m / s (5.3; 19.2) vs 12.2 m / s (5.7; 15.1); p = 0.01), decrease the pulmonary shunt fraction (Qs / Qt) (4.33% (3.7; 6.1) vs 9.12% (7.12; 11.3); p = 0.01), an increase in arterial vascular tone measured by reflective index (RI) (62.4% (51.2; 64.3) vs 58.5% (51.7; 63.8); p = 0.01), and increased exercise tolerance measured by 6-minute walking test (6MWT) (358.1 m (320.5; 368.2) vs 321.5 m (280.4; 329.1); p = 0.001) as compared to the control group.
Conclusion. Our study indicates that iNO-therapy effectively reduces hypoxemia, endothelial dysfunction, improves hemodynamics, walking distance, and exercise tolerance during the exacerbation of COPD in patients with hypercapnic RF and PAH.
About the Authors
Tuyet Thi StruongRussian Federation
Truong Thi Tuyet, Postgraduate student, Department of Hospital Therapy, Pediatric Faculty
ul. Ostrovityanova 1, Moscow, 117997, Russia
L. V. Shogenova
Russian Federation
Lyudmila V. Shogenova, Сandidate of Medicine, Associate Professor, Department of Hospital Therapy, Pediatric Faculty
SPIN: 6210-7482
ul. Ostrovityanova 1, Moscow, 117997, Russia
V. D. Selemir
Russian Federation
Viktor D. Selemir, Doctor of Medicine, Professor, Academician of Russian Academy of Sciences, Director, Research and Production Center for Physics, Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics, Professor, Sarov Physics and Technology Institute of the National Research Nuclear University MEPhI
SPIN: 8060-4296
prosp. Mira 37, Nizhegorodskaya obl., Sarov, 607190, Russia;
ul. Dukhova 6, Nizhegorodskaya obl., Sarov, 607186, Russia
A. G. Chuchalin
Russian Federation
Alexander G. Chuchalin, Doctor of Medicine, Professor, Academician of Russian Academy of Sciences, Head of Department of Hospital Internal Medicine, Pediatric Faculty
ul. Ostrovityanova 1, Moscow, 117997, Russia
References
1. Steudel W., Hurford W.E., Zapol W.M. Inhaled nitric oxide: basic biology and clinical applications. Anesthesiology. 1999; 91 (4): 1090–1121. DOI: 10.1097/00000542-199910000-00030.
2. Levine A.B., Punihaole D., Levine T.B. Characterization of the role of nitric oxide and its clinical applications. Cardiology. 2012; 122 (1): 55–68. DOI: 10.1159/000338150.
3. Bloch K.D., Ichinose F., Roberts J.D. Jr, Zapol W.M. Inhaled NO as a therapeutic agent. Cardiovasc. Res. 2007; 75 (2): 339–348. DOI: 10.1016/j.cardiores.2007.04.014.
4. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2021 Report. Available at: https://goldcopd.org/wp-content/uploads/2020/11/GOLD-REPORT-2021-v1.0-11Nov20_WMV.pdf
5. Gaynitdinova V.V., Avdeev S.N. Chronic obstructive pulmonary disease and pulmonary hypertension: clinical course, survival and mortality predictors. Pul’monologiya. 2017; 27 (3): 357–365. DOI: 10.18093/0869-0189-2017-27-3-357-365 (in Russian).
6. Barberà J.A., Peinado V.I., Santos S. Pulmonary hypertension in chronic obstructive pulmonary disease. Eur. Respir. J. 2003; 21 (5): 892–905. DOI: 10.1183/09031936.03.00115402.
7. Weitzenblum E., Hirth C., Ducolone A. et al. Prognostic value of pulmonary artery pressure in chronic obstructive pulmonary disease. Thorax. 1981; 36 (10): 752–758. DOI: 10.1136/thx.36.10.752.
8. George I., Xydas S., Topkara V.K. et al. Clinical indication for use and outcomes after inhaled nitric oxide therapy. Ann. Thorac. Surg. 2006; 82 (6): 2161–2169. DOI: 10.1016/j.athoracsur.2006.06.081.
9. Klinger J.R., Mandel J., Finlay G. Inhaled nitric oxide in adults: Biology and indications for use. UpToDate. Available at: https://www.uptodate.com/contents/inhaled-nitric-oxide-in-adults-biology-and-in-dications-for-use
10. Öztürk E., Haydin S., Tanıdır İ.C. et al. Use of inhaled nitric oxide in pediatric cardiac intensive care unit. Turk Kardiyol. Dern. Ars. 2016; 44 (3): 196–202. DOI: 10.5543/tkda.2015.23255.
11. Cockrill B.A., Kacmarek R.M., Fifer M.A. et al. Comparison of the effects of nitric oxide, nitroprusside, and nifedipine on hemodynamics and right ventricular contractility in patients with chronic pulmonary hypertension. Chest. 2001; 119 (1): 128–136. DOI: 10.1378/chest.119.1.128.
12. Lama V.N., Flaherty K.R., Toews G.B. et al. Prognostic value of desaturation during a 6-minute walk test in idiopathic interstitial pneumonia. Am. J. Respir. Crit. Care Med. 2003; 168 (9): 1084–1090. DOI: 10.1164/rccm.200302-219OC.
13. Frostell C., Fratacci M.D., Wain J.C. et al. Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction. Circulation. 1991; 83 (6): 2038–2047. DOI: 10.1161/01.cir.83.6.2038.
14. Pepke-Zaba J., Higenbottam T.W., Dinh-Xuan A.T. et al. Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension. Lancet. 1991; 338 (8776): 1173–1174. DOI: 10.1016/0140-6736(91)92033-x.
15. Tworetzky W., Bristow J., Moore P. et al. Inhaled nitric oxide in neonates with persistent pulmonary hypertension. Lancet. 2001; 357 (9250): 118–120. DOI: 10.1016/S0140-6736(00)03548-0.
16. Thabut G., Brugière O., Lesèche G. et al. Preventive effect of inhaled nitric oxide and pentoxifylline on ischemia/reperfusion injury after lung transplantation. Transplantation. 2001; 71 (9): 1295–1300. DOI: 10.1097/00007890-200105150-00019.
17. Sitbon O., Brenot F., Denjean A. et al. Inhaled nitric oxide as a screening vasodilator agent in primary pulmonary hypertension. A dose-response study and comparison with prostacyclin. Am. J. Respir. Crit. Care Med. 1995; 151 (2, Pt 1): 384–389. DOI: 10.1164/ajrccm.151.2.7842196
Review
For citations:
Struong T.T., Shogenova L.V., Selemir V.D., Chuchalin A.G. Effects of inhaled nitric oxide in chronic obstructive pulmonary disease patients with hypercapnic respiratory failure and pulmonary hypertension. PULMONOLOGIYA. 2022;32(2):216-225. (In Russ.) https://doi.org/10.18093/0869-0189-2022-32-2-216-225