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

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.

Graphical abstract

Figure 1

Flow Chart of Patient Classification Of the 270 patients, 248 were treatment naive, and were further categorized by the presence or absence of initial treatment. In the initial treatment group, response rate was compared according to the severity of PH and VI. PH = pulmonary hypertension; VI = ventilatory impairment.

Figure 2

Survival Curves Based on IP and CPFE No difference was seen between the survival curves of the 2 diseases. The solid line represents the Kaplan-Meier survival plot. CPFE = combined pulmonary fibrosis and emphysema; IP = interstitial pneumonia; RHC = right heart catheterization.

Figure 3

Comparison of Survival Curves in Treatment-Naive Patients (A) Women vs men: Men had a worse prognosis compared with women. (B) Stratified by WHO-FC: The prognosis differed according to the severity of WHO-FC. (C) Mild and severe VI groups: Patients with mild VI had a significantly better prognosis than those with severe VI. (D) Severe and mild PH groups: Patients with PVR >5 WU had a worse prognosis than those with PVR ≤5 WU. PVR = pulmonary vascular resistance; WHO-FC = World Health Organization Functional Class; other abbreviations as in Figure 1.

Figure 4

Survival Comparisons Between the Severe and Mild PH Groups (A) Initial treatment group: There was no difference in prognosis between severe and mild PH when limited to the initial treatment group. (B) Noninitial treatment group: There was a significant difference in prognosis between severe and mild PH in the noninitial treatment group. Abbreviation as in Figure 1.

Figure 5

Survival Comparisons Between the Initial and Noninitial Treatment Groups (A) Severe PH (PVR >5 WU): There was no difference in prognosis between the initial and noninitial treatment groups in cases with PVR >5 WU. (B) Mild PH (PVR ≤5 WU): Similarly, there was no difference in prognosis between the initial and noninitial treatment groups in cases with PVR ≤5 WU. Abbreviations as in Figures 1 and 3.

Figure 6

Survival Comparisons Between the Initial and Noninitial Treatment Groups (A) Severe PH (PVR >5 WU) with mild VI: The initial treatment group showed significantly better survival compared with the noninitial treatment group. (B) Mild PH (PVR ≤5 WU) with mild VI: In contrast, there was no difference between the 2 groups. Abbreviations as in Figures 1 and 3.

Central Illustration

Different Response According to the Severity of Pulmonary Hypertension and Ventilatory Impairment The prevalence of severe PH with severe VI, mild PH with severe VI, severe PH with mild VI, and mild PH with mild VI was 20.0%, 28.2%, 26.7%, and 25.1%, respectively. The response rate in the severe PH with mild VI group was significantly higher than that in the other groups (48.1% vs 21.8%, ratio 2.21 [95% CI: 1.17-4.16]). Prevalence percentages were calculated by using the total number of treatment-naive patients as the denominator. The response rate was based on the number of patients who responded in each group. FEV1, %pred. = percent predicted forced expiratory volume in 1 second; FVC, %pred. = percent predicted forced vital capacity; PH = pulmonary hypertension; PVR = pulmonary vascular resistance; VI = ventilatory impairment; WHO-FC = World Health Organization's functional class.

Figure 7

Survival Comparisons From the Assessment Date Between Responders and Nonresponders (A) Severe PH (PVR >5 WU): Responders had a better prognosis than nonresponders from the response assessment date. (B) Mild PH (PVR ≤5 WU): The number of cases was too small to be evaluated. No better trend for prognosis was observed in responders compared with nonresponders. Abbreviations as in Figures 1 and 3.