Vaso reactivity test using inhaled nitric oxide for pulmonary arterial hypertension accompanied by severe interstitial lung disease attributed to systemic sclerosis: A case report


      A 70-year-old man with severe interstitial pneumonia attributed to limited cutaneous systemic sclerosis was referred to our institution because of worsening dyspnea. High-resolution computed tomography did not show considerable progression compared with previous images, whereas transthoracic echocardiography showed severe right ventricular dysfunction. Oxygen saturation was decreased to 84% at room air. A blood test showed an increase in the plasma brain natriuretic peptide level (289.4 pg/mL). Right heart catheterization (RHC) showed a remarkably high mean pulmonary arterial pressure (mPAP) of 48 mmHg at room air. A vaso reactivity test using inhaled nitric oxide showed improvement of mPAP, pulmonary vascular resistance (PVR), and partial pressure of arterial oxygen. These findings suggested that the patient responded to pulmonary hypertension (PH)-targeted drugs. We then prescribed tadalafil 10 mg and inhaled iloprost 5 µg six times daily. Three weeks after initiating PH-targeted drugs, RHC indicated hemodynamic improvement similar to hemodynamic changes in the vaso reactivity test (mPAP: 28 mmHg; PVR: 4.2 W.U.). He was discharged with improved symptoms. Inhaled nitric oxide during RHC might be helpful to consider the treatment strategy when patients have PH comorbid systemic sclerosis and severe interstitial lung disease.


      To read this article in full you will need to make a payment


        • Galiè N
        • Humbert M
        • Vachiery JL
        • Gibbs S
        • Lang I
        • Torbicki A
        • Simonneau G
        • Peacock A
        • A Vonk Noordegraaf
        • Beghetti M
        • Ghofrani A
        • MA Gomez Sanchez
        • Hansmann G
        • Klepetko W
        • Lancellotti P
        • et al.
        ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint 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: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).
        Eur Heart J. 2015; 37 (2016): 67-119
        • Overbeek MJ
        • Vonk MC
        • Boonstra A
        • Voskuyl AE
        • Vonk-Noordegraaf A
        • Smit EF
        • Dijkmans BA
        • Postmus PE
        • Mooi WJ
        • Heijdra Y
        • Grünberg K.
        Pulmonary arterial hypertension in limited cutaneous systemic sclerosis: a distinctive vasculopathy.
        Eur Respir J. 2009; 34: 371-379
        • Ogawa A
        • Miyaji K
        • Yamadori I
        • Shinno Y
        • Miura A
        • Kusano KF
        • Ito H
        • Date H
        • Matsubara H.
        Safety and efficacy of epoprostenol therapy in pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis.
        Circ J. 2012; 76: 1729-1736
        • Plazak W
        • Gryga K
        • Sznajd J
        • Wilisowska J
        • Czarnobilska E
        • Goncerz G
        • Podolec P
        • Musial J.
        Reactivity of pulmonary circulation and right ventricle function to inhaled nitric oxide in systemic sclerosis patients.
        Clin Rheumatol. 2012; 31: 99-104
        • Preston IR
        • Klinger JR
        • Houtchens J
        • Nelson D
        • Mehta S
        • Hill NS.
        Pulmonary edema caused by inhaled nitric oxide therapy in two patients with pulmonary hypertension associated with the CREST syndrome.
        Chest. 2002; 121: 656-659
        • Humbert M
        • Coghlan JG
        • Ghofrani HA
        • Grimminger F
        • He JG
        • Riemekasten G
        • Vizza CD
        • Boeckenhoff A
        • Meier C
        • de Oliveira Pena J
        • Denton CP.
        Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2.
        Ann Rheum Dis. 2017; 76: 422-426
        • Nathan SD
        • Behr J
        • Collard HR
        • Cottin V
        • Hoeper MM
        • Martinez FJ
        • Corte TJ
        • Keogh AM
        • Leuchte H
        • Mogulkoc N
        • Ulrich S
        • Wuyts WA
        • Yao Z
        • Boateng F
        • Wells AU.
        Riociguat for idiopathic interstitial pneumonia-associated pulmonary hypertension (RISE-IIP): a randomized, placebo-controlled phase 2b study.
        Lancet Respir Med. 2019; 7: 780-790
        • Zisman DA
        • Schwarz M
        • Anstrom KJ
        • Collard HR
        • Flaherty KR
        • Hunninghake GW.
        A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis.
        N Engl J Med. 2010; 363: 620-628
        • Olschewski H
        • Simonneau G
        • Galiè N
        • Higenbottam T
        • Naeije R
        • Rubin LJ
        • Nikkho S
        • Speich R
        • Hoeper MM
        • Behr J
        • Winkler J
        • Sitbon O
        • Popov W
        • Ghofrani HA
        • Manes A
        • et al.
        Inhaled iloprost for severe pulmonary hypertension.
        N Engl J Med. 2002; 347: 322-329
        • Waxman A
        • Restrepo-Jaramillo R
        • Thenappan T
        • Ravichandran A
        • Engel P
        • Bajwa A
        • Allen R
        • Feldman J
        • Argula R
        • Smith P
        • Rollins K
        • Deng C
        • Peterson L
        • Bell H
        • Tapson V
        • et al.
        Inhaled treprostinil in pulmonary hypertension due to interstitial lung disease.
        N Engl J Med. 2021; 384: 325-334