Pulmonary Hypertension With Interstitial Pneumonia: Initial Treatment Effectiveness and Severity in a Japan Registry

Nobuhiro Tanabe; Hiraku Kumamaru; Yuichi Tamura; Yasuhiro Kondoh; Kazuhiko Nakayama; Naoko Kinukawa; Tomoki Kimura; Osamu Nishiyama; Ichizo Tsujino; Ayako Shigeta; Yoshiteru Morio; Yoshikazu Inoue; Hiroshi Kuraishi; Ken-Ichi Hirata; Kensuke Tanaka; Masataka Kuwana; Tetsutaro Nagaoka; Tomohiro Handa; Koichiro Sugimura; Fumio Sakamaki; Akira Naito; Yu Taniguchi; Hiromi Matsubara; Masayuki Hanaoka; Takumi Inami; Naoki Hayama; Yoshihiro Nishimura; Hiroshi Kimura; Hiroaki Miyata; Koichiro Tatsumi; JRPHS Group

doi:10.1016/j.jacasi.2024.01.009

Pulmonary Hypertension With Interstitial Pneumonia: Initial Treatment Effectiveness and Severity in a Japan Registry

JACC Asia. 2024 Mar 26;4(5):403-417. doi: 10.1016/j.jacasi.2024.01.009. eCollection 2024 May.

Authors

Nobuhiro Tanabe^{1

2}, Hiraku Kumamaru³, Yuichi Tamura⁴, Yasuhiro Kondoh⁵, Kazuhiko Nakayama⁶, Naoko Kinukawa³, Tomoki Kimura⁵, Osamu Nishiyama⁷, Ichizo Tsujino⁸, Ayako Shigeta², Yoshiteru Morio⁹, Yoshikazu Inoue¹⁰, Hiroshi Kuraishi¹¹, Ken-Ichi Hirata¹², Kensuke Tanaka¹³, Masataka Kuwana¹⁴, Tetsutaro Nagaoka¹⁵, Tomohiro Handa¹⁶, Koichiro Sugimura¹⁷, Fumio Sakamaki¹⁸, Akira Naito², Yu Taniguchi¹², Hiromi Matsubara¹⁹, Masayuki Hanaoka²⁰, Takumi Inami²¹, Naoki Hayama²², Yoshihiro Nishimura²³, Hiroshi Kimura²⁴, Hiroaki Miyata²⁵, Koichiro Tatsumi²; JRPHS Group

Affiliations

¹ Pulmonary Hypertension Center, Saiseikai Narashino Hospital, Narashino, Chiba, Japan.
² Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
³ Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁴ Pulmonary Hypertension Center, International University of Health and Welfare Mita Hospital, Tokyo, Japan.
⁵ Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Aichi, Japan.
⁶ Department of Cardiovascular Medicine, Shinko Hospital, Kobe, Japan.
⁷ Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine, Osakasayama, Osaka, Japan.
⁸ Division of Respiratory and Cardiovascular Innovative Research, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
⁹ Center for Pulmonary Diseases and Respiratory Disease Division, National Hospital Organization Tokyo National Hospital, Kiyose, Tokyo, Japan.
¹⁰ Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan.
¹¹ Department of Respiratory Medicine, Nagano Red Cross Hospital, Nagano, Nagano, Japan.
¹² Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
¹³ Department of Chest Medicine, Japan Railway Tokyo General Hospital, Tokyo, Japan.
¹⁴ Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan.
¹⁵ Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
¹⁶ Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
¹⁷ Department of Cardiology, International University of Health and Welfare Narita Hospital, Narita, Japan.
¹⁸ Division of Respiratory Disease, Department of Medicine, Tokai University Hachioji Hospital, Hchioji, Japan.
¹⁹ Department of Cardiology, Okayama Medical Center, Okayama, Japan.
²⁰ First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
²¹ Division of Cardiology Department of Medicine, Kyorin University Hospital, Mitaka, Tokyo, Japan.
²² Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
²³ Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
²⁴ Department of Respiratory Medicine, Fukujuji Hospital, Japan Anti-Tuberculosis Association (JATA), Kiyose, Tokyo, Japan.
²⁵ Department of Health Policy and Management, Keio University School of Medicine, Tokyo, Japan.

Abstract

Background: Recent guidelines discourage the use of pulmonary arterial hypertension (PAH)-targeted therapies in patients with pulmonary hypertension (PH) associated with respiratory diseases. Therefore, stratifications of the effectiveness of PAH-targeted therapies are important for this group.

Objectives: The authors aimed to identify phenotypes that might benefit from initial PAH-targeted therapies in patients with PH associated with interstitial pneumonia and combined pulmonary fibrosis and emphysema.

Methods: We categorized 270 patients with precapillary PH (192 interstitial pneumonia, 78 combined pulmonary fibrosis and emphysema) into severe and mild PH using a pulmonary vascular resistance of 5 WU. We investigated the prognostic factors and compared the prognoses of initial (within 2 months after diagnosis) and noninitial treatment groups, as well as responders (improvements in World Health Organization functional class, pulmonary vascular resistance, and 6-minute walk distance) and nonresponders.

Results: Among 239 treatment-naive patients, 46.0% had severe PH, 51.8% had mild ventilatory impairment (VI), and 40.6% received initial treatment. In the severe PH with mild VI subgroup, the initial treatment group had a favorable prognosis compared with the noninitial treatment group. The response rate in this group was significantly higher than the others (48.2% vs 21.8%, ratio 2.21 [95% CI: 1.17-4.16]). In multivariate analysis, initial treatment was a better prognostic factor for severe PH but not for mild PH. Within the severe PH subgroup, responders had a favorable prognosis.

Conclusions: This study demonstrated an increased number of responders to initial PAH-targeted therapy, with a favorable prognosis in severe PH cases with mild VI. A survival benefit was not observed in mild PH cases. (Multi-institutional Prospective Registry in Pulmonary Hypertension associated with Respiratory Disease; UMIN000011541).

Keywords: interstitial pneumonia; multicenter registry; pulmonary hypertension; respiratory disease; ventilatory impairment.