Next Article in Journal
Usefulness of Blood Biomarkers in Screening Patients with Obstructive Sleep Apnea: Could Albumin Indices and Uric Acid-to-HDL Ratio Be New OSAS Severity Indices?
Previous Article in Journal
Real-World Efficacy of Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrronium on Diaphragmatic Workload Assessed by Ultrasound and Lung Function in Patients with Uncontrolled Asthma
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
ARM
Volume 93
Issue 5
10.3390/arm93050041
arm-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Development of a Tool to Assess the Severity of Pulmonary Hypertension in Patients with Interstitial Lung Disease: A Guide to Assist Therapeutic Choices

by
Garrett Fiscus
1,*,
Chebly Dagher
2,
David O’Sullivan
3,
Brett Carollo
1,
Kristen Swanson
1,
Harrison W. Farber
4 and
Raj Parikh
1
1
Division of Pulmonary, Critical Care and Sleep, Hartford Hospital, Hartford, CT 06106, USA
2
Division of Internal Medicine, University of Connecticut, Farmington, CT 06030, USA
3
Department of Research Administration, Hartford HealthCare, Hartford, CT 06106, USA
4
Division of Pulmonary, Sleep and Critical Care Medicine, Tufts Medical Center, Boston, MA 02111, USA
*
Author to whom correspondence should be addressed.
Adv. Respir. Med. 2025, 93(5), 41; https://doi.org/10.3390/arm93050041
Submission received: 22 August 2025 / Revised: 25 September 2025 / Accepted: 30 September 2025 / Published: 6 October 2025
Browse Figure
Versions Notes

Abstract

Highlights

What are the main findings?
  • We created such a scoring tool to guide PH-specific therapy in PH-ILD patients using subjective and objective information (WHO FC, CI, TAPSE, PVR).
  • A score of 3 or greater in the PH-ILD Severity score yielded an AUC of 0.831 for the composite endpoint of clinical worsening.
What is the implication of the main finding?
  • Similarly to the way that risk assessment tools can guide subsequent steps in therapy of PH patients, this PH-ILD Severity score will triage patients who may benefit from inhaled medications, who may require parenteral prostacyclin therapy, and who should be considered for expedited lung transplant evaluation.

Abstract

Background: Pulmonary hypertension (PH) is a frequent complication in patients with interstitial lung disease (ILD); its occurrence results in significant morbidity and mortality. Currently approved treatment options for PH-ILD include inhaled prostacyclin therapy, although this approach may be insufficient in patients who have developed simultaneous right ventricular failure. Moreover, there is no available treatment algorithm regarding the optimal therapy and timing of lung transplant referral for PH-ILD patients based on disease severity. Design/Methods: In this study, we created such a tool to guide PH-specific therapy in PH-ILD patients, especially as further treatment strategies are developed. We developed a 4-point PH-ILD Severity score that integrated both subjective and objective information (WHO FC, CI, TAPSE, PVR) from retrospective analysis of 57 PH-ILD patients. Results: A score of 3 or greater in the PH-ILD Severity score yielded an AUC of 0.831 (p < 0.001) for the composite endpoint of clinical worsening (hospitalization due to a cardiopulmonary indication; decrease in 6 min walk distance by >15% at 2 consecutive visits; all-cause mortality; lung transplantation). Conclusions: Further confirmation and evolution of this PH-ILD Severity score will assist in the development of optimal treatment plans in ILD patients diagnosed with concomitant PH.

1. Introduction

Pulmonary hypertension (PH) is a condition characterized by increased mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) that ultimately leads to right ventricular failure (RVF) and death. PH is classified into five groups based on the causative effect. World Health Organization (WHO) Group 3 PH is a frequent complication in patients with interstitial lung disease (ILD). When diagnosed, PH-ILD is associated with a worse functional status, increased need for supplemental oxygen, and poorer outcomes [1,2,3,4,5,6,7,8].
Until recently, there had been no standard regarding which patients should undergo screening for PH-ILD as there is typically an overlap of symptoms between the two entities. Recently, however, Parikh et al. have developed a PH-ILD Detection tool that strongly suggests concomitant PH in a timely manner, allowing for earlier interventions such as initiation of PH therapy and referral for lung transplant evaluation [5,9]. The clinical benefit of PH-specific therapy in PH-ILD patients was recently demonstrated in the INCREASE trial in which inhaled treprostinil improved 6-min walk distance (6MWD) compared to placebo [10]. Unfortunately, in some patients, PH-ILD can present at an advanced stage with concomitant RV dysfunction, similar to WHO Group 1 pulmonary arterial hypertension (PAH). In such patients, parental prostacyclin therapy may be considered [11,12]. However, while parenteral prostacyclins have well-established benefits in WHO Group 1 PAH, similar outcomes have not been demonstrated in PH-ILD; in addition, these therapies have the potential to worsen hypoxemia by causing ventilation/perfusion (V/Q) mismatch in the setting of parenchymal lung disease [13,14,15].
At present, there is no assessment tool specifically for patients with PH-ILD that can predict disease severity, clinical trajectory, and/or help guide management. To address this gap in PH-ILD management, we have developed a severity score to assist in the treatment approach for PH-ILD patients.

2. Methods

We performed a retrospective analysis of 57 PH-ILD patients from a single tertiary academic center. Patients were identified by the International Classification of Diseases 10th Revision (ICD-10) using the diagnosis of PH-ILD from August 2020 to January 2023, who were then followed for one year to assess for clinical worsening [16]. The diagnosis of ILD was confirmed by diffuse parenchymal lung disease on CT chest. The diagnosis of pre-capillary PH was confirmed by right heart catheterization (RHC) with mPAP ≥ 20 mmHg, pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg, and PVR > 3 Wood units (WU) [17,18]. Other causes of pre-capillary PH, including chronic thromboembolic pulmonary hypertension (CTEPH), along with PH-associated with connective tissue diseases due to the potential for pulmonary arterial hypertension. All 57 patients were initiated PH therapy with either inhaled or parenteral prostacyclin therapy following confirmatory diagnosis via RHC. No other PH therapies were added following the initiation of inhaled/advanced (i.e., subcutaneous, intravenous) therapies. Follow up visits occurred approximately every eight to sixteen weeks following medication initiation. This study was approved by the Hartford HealthCare Institutional Review Board (HHC-2022-0014).

2.1. Development of PH-ILD Severity Score

We developed a PH-ILD Severity score that integrated both subjective and objective information: exercise capacity and symptoms from WHO functional class (FC), RHC hemodynamics including Fick-derived cardiac index (CI) and PVR, and echocardiogram (TTE) measurement of tricuspid annular plane systolic excursion (TAPSE) (Table 1). Data were collected prior to initiation of any pulmonary vasodilators. The justification for the inclusion of each of these specific parameters is detailed in the Discussion.
When evaluating these four metrics for the development of the PH-ILD Severity score, several computations were analyzed. The final severity score, ranging from 0 to 4, with each parameter receiving 1 point, performed the best when evaluating for the composite variable of clinical worsening in comparison to the other two versions of the severity score with an area-under-the-curve (AUC) of 0.835 (Table 2). We then evaluated the most appropriate cut-off within the PH-ILD Severity score; this was found to be ≥ 3 based on an AUC of 0.831 (p < 0.001).

2.2. Clinical Worsening in PH-ILD

The composite endpoint of clinical worsening was utilized as a means for assessing the utility of the PH-ILD Severity score, which was adapted from the INCREASE trial [10]. Clinical worsening was defined as any of the following events: (1) hospitalization due to a cardiopulmonary indication, (2) decrease in 6 min walk distance (6MWD) by >15% at 2 consecutive visits when compared to 6MWD at time of initial PH-ILD diagnosis, (3) all-cause mortality, and (4) lung transplantation [10,17]. Each variable was equally weighted in terms of composite worsening. Although lung transplantation was considered in the clinical worsening composite variable, none of the 57 patients underwent transplantation during the time frame of the study.

2.3. Statistical Analysis

A receiver operating characteristics (ROC) curve was generated, and an AUC was calculated from the values of sensitivity (SN) and specificity (SP). All statistical analyses were performed with SPSS v. 29 (IBM, Armonk, NY, USA, 2022), using an a priori alpha level of 0.05.

3. Results

3.1. Patient Demographics

Patient demographics, baseline clinical data, and subtypes of ILD are shown in Table 3. Within the entire cohort, the mean age was 71 years and there was a male predominance (54%). The most common subtype of ILD was idiopathic pulmonary fibrosis (IPF; 47%), followed by combined pulmonary fibrosis and emphysema (CPFE; 21%). There was a statistically significant difference for DLCO but not for use of supplemental oxygen between the low-risk and high-risk groups as determined by the PH-ILD Severity score. Five patients (17.9%) in the low-risk group were treated with parenteral prostacyclin therapy compared to 15 (51.7%) in the high-risk group (p = 0.012).
Of the 12 CPFE patients included in the cohort, 10 patients met the composite endpoint of clinical worsening. There was a heightened concern for adverse effects in response to parenteral prostacyclin in this subtype of ILD; instead, it was noted that 7 of these 10 patients were receiving inhaled therapy at the time of clinical worsening. There were no significant V/Q mismatching that occurred during the year-long follow up.

3.2. PH-ILD Severity Score and Parameters

In the low-risk group, patients categorized as WHO FC 2–4 each accounted for approximately one-third of the cohort; however, in the high-risk group, almost two-thirds of patients were categorized as FC 4. Table 4 shows that in the high-risk group, there were significant differences in PVR (p < 0.001), CI (p < 0.001) and TAPSE (p < 0.001) compared to the low-risk group.

3.3. PH-ILD Severity Score and Clinical Worsening

A score of ≥3 on the PH-ILD Severity score yielded an AUC of 0.831 (p < 0.001) for the composite endpoint of clinical worsening (Figure 1).

4. Discussion

PH is an entity that carries significant morbidity and mortality eventually progressing to RVF and death if left untreated [18,19,20,21]. In PAH, utilizing routine risk assessment tools in management has become standard of care, as it not only allows clinicians a consistent method to follow patients longitudinally, but also informs on therapeutic decision-making, including medication titration and referral for lung transplant evaluation. Early recognition of concomitant PH remains a challenge in PH-ILD patients, and the diagnosis may not be established until the disease has progressed to RV dysfunction [5,22,23]. Despite the findings from the INCREASE trial, PH-ILD management is much more complex than a single medication treatment algorithm, especially in the patient who has already progressed to significant RV dysfunction [11,12,17]. Understanding the nuance of the disease and its overall severity and progression, including an evaluation of concomitant RV dysfunction, is paramount to the PH-ILD management approach including evaluation for lung transplant. More importantly, such a tool will certainly become more useful and necessary as additional therapies for ILD are developed and PH-ILD treatment options expand.

4.1. Justification of the PH-ILD Severity Score Variables

Developing a severity assessment tool that incorporates both subjective and objective variables while also focusing on parameters that assess RV decompensation was the priority in creating the PH-ILD Severity score. To accomplish this, we extrapolated information from well-established risk assessment tools such as REVEAL and European Society of Cardiology (ESC)/European Respiratory Society (ERS) in order to develop the metrics that were included in this initial PH-ILD Severity score. This iteration of the PH-ILD Severity score included four variables, each allotted 1 point. If the composite score was ≥ 3, the patient was categorized as high-risk PH-ILD since this score was an accurate predictor of the composite endpoint of clinical worsening.

4.1.1. WHO FC

WHO FC is a validated assessment of dyspnea in PH patients [21]. It is widely utilized in disease monitoring and has frequently been employed in PAH clinical trials to assess response to therapy [18,24]. Prior studies have shown a robust association between WHO FC and hemodynamic parameters; since its development, this measurement has been one of the strongest indicators for survival in PAH patients [24,25,26,27,28]. In fact, a worsening WHO FC is considered the most alarming indicator of disease progression [24]. As a result, we incorporated WHO FC ≥ 3 into the PH-ILD Severity score as a validated assessment of a patient’s subjective dyspnea.

4.1.2. PVR

The REVEAL Registry is the largest and most comprehensive registry providing insight into factors that influence survival and prognosis in PAH [29,30]. Similarly to the WHO FC, PVR is included in REVEAL 2.0; a PVR > 5 WU is considered a greater risk for morbidity and mortality [29]. In the INCREASE trial, the average PVR for both treatment and placebo groups was 6.2 WU [17]. Therefore, we established a cut-off of > 5 WU to identify high-risk PH-ILD patients.

4.1.3. Cardiac Index

RVF is a consequence of poorly controlled PH; as such, the ability to improve RV function with PH-specific therapy is an important aspect of disease management [28]. The interventricular septum and ventricular interdependence play an important role in the development of RVF from PH [21,31]. In decompensated PH, RV pressure exceeds left ventricular (LV) pressure causing the interventricular septum to shift leftward leading to the dysfunction of an under-filled LV cavity and subsequent low cardiac output [21]. Thus, CI is an important predictor of survival in PH and as a result, has been included as a staple in several risk assessment scores for PAH [20,21,32]. In PH-ILD, RV dysfunction, reflected by a depressed CI, is believed to play a similar role; therefore, we included CI < 2.0 as a variable in the PH-ILD Severity score to identify patients who should be considered for parenteral prostacyclin therapy in the hope of reversing RV dysfunction [33,34].

4.1.4. TAPSE

Similarly to RHC-derived CI, TTE-derived TAPSE is another method to assess RV function [35,36]. We incorporated a TAPSE < 1.6 cm in the severity assessment of PH-ILD patients since multiple studies have established TAPSE as a reliable prognosticator of poorer outcome in PAH and a marker of significant RV remodeling and dysfunction [18,24,35,36,37,38,39,40,41,42,43,44,45].

4.2. Strengths and Limitations

The present study has several limitations including: (1) the data were collected from a single institution, which may introduce data bias; (2) the sample size was relatively small; (3) the parameters were adopted from well-established risk assessment scores that have been evaluated in PAH, but not in PH-ILD; and (4) the severity score relies on TTE-derived TAPSE even though TTE is known to have its limitations in the ILD population [24,45,46,47]. Nonetheless, the development of this severity score and the robust findings from this study introduce a novel concept of PH-ILD risk assessment. Moreover, the tool can and will evolve and will become even more robust as other predictive metrics more specific to PH-ILD are identified and more specific cut points are defined.

5. Conclusions

PH-ILD patients have an unacceptably high morbidity and mortality [1,2,3,4,5,6,7]. As such, it is crucial to understand the factors that contribute to this outcome so that current and future therapies, including medical and surgical options, can be considered in a timely manner. While inhaled prostacyclin therapy is now approved for use in PH-ILD, a subset of these patients have severe disease with associated RV dysfunction; in such patients, parenteral prostacyclin therapy may be considered [12]. Similarly to the way that risk assessment tools can guide subsequent steps in therapy of PAH patients, this PH-ILD Severity score will triage patients who may benefit from inhaled medications, patients who may require parenteral prostacyclin therapy and patients who should be considered for expedited lung transplant evaluation. With further validation and evolution as more specific PH-ILD risk metrics and cut-points are identified, such as has occurred with the PAH risk assessment tools, the PH-ILD Severity score will assist in developing optimal treatment plans for ILD patients diagnosed with concomitant PH.

Author Contributions

Conceptualization, G.F., D.O., H.W.F. and R.P.; methodology, G.F., D.O., H.W.F. and R.P.; software, D.O.; validation, G.F., D.O., H.W.F. and R.P.; formal analysis, D.O.; investigation, G.F., D.O., H.W.F. and R.P.; data curation, G.F., C.D., B.C., K.S. and R.P.; writing—original draft preparation, G.F., C.D., D.O., B.C., K.S., H.W.F. and R.P.; writing—review and editing, G.F., D.O., H.W.F. and R.P.; visualization, G.F., D.O. and R.P.; funding acquisition, none. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki and approved by the Hartford HealthCare Institutional Review Board (protocol code HHC-2022-0014, date 2 January 2022).

Informed Consent Statement

Informed consent was waived due to all data was retrospectively analyzed.

Data Availability Statement

The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author.

Conflicts of Interest

The authors declare no conflict of interest.

Abbreviations

6MWD6 min walk distance
AUCarea under the curve
CIFick-derived cardiac index
COcardiac output
COMPERAComparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension
COPcryptogenic organizing pneumonia
CPFEcombined pulmonary fibrosis and emphysema
CTEPHchronic thromboembolic pulmonary hypertension
DLCOdiffusional capacity of carbon monoxide
FCfunctional class
FPHRFrench Pulmonary Hypertension Registry
ICD-10International Classification of Diseases 10th Revision
ILDinterstitial lung disease
IPFidiopathic pulmonary fibrosis
IVintravenous
mPAPmean pulmonary arterial pressure
NSIPnon-specific interstitial pneumonia
NYHANew York Heart Association
PCWPpulmonary capillary wedge pressure
PHpulmonary hypertension
PAHpulmonary arterial hypertension
PHISSPH-ILD severity score
PVRpulmonary vascular resistance
RB-ILDrespiratory bronchiolitis-associated interstitial lung disease
RHCright heart catheterization
ROCreceiver operating characteristics
RVright ventricle
RVFright ventricular failure
SNsensitivity
SPspecificity
TAPSEtricuspid annular plane systolic excursion
VQventilation/perfusion
WHOWorld Health Organization
WUWood unit

References

  1. Nathan, S.D.; Hassoun, P.M. Pulmonary hypertension due to lung disease and/or hypoxia. Clin. Chest Med. 2013, 34, 695–705. [Google Scholar] [CrossRef]
  2. Lettieri, C.J.; Nathan, S.D.; Browning, R.F.; Barnett, S.D.; Ahmad, S.; Shorr, A.F. The distance-saturation product predicts mortality in idiopathic pulmonary fibrosis. Respir. Med. 2006, 100, 1734–1741. [Google Scholar] [CrossRef] [PubMed]
  3. Caminati, A.; Cassando, R.; Harari, S. Pulmonary hypertension in chronic interstitial lung diseases. Eur. Respir. Rev. 2013, 22, 292–301. [Google Scholar] [CrossRef] [PubMed]
  4. Oliveira, R.K.; Pereira, C.A.; Ramos, R.P.; Ferreira, E.V.; Messina, C.M.; Kuranishi, L.T.; Gimenez, A.; Campos, O.; Silva, C.M.; Ota-Arakaki, J.S. A hemodynamic study of pulmonary hypertension in chronic hypersensitivity pneumonitis. Eur. Respir. J. 2014, 44, 415–424. [Google Scholar] [CrossRef]
  5. Parikh, R.; Konstantinidis, I.; O’Sullivan, D.M.; Farber, H.W. Pulmonary hypertension in patients with interstitial lung disease: A tool for early detection. Pulm. Circ. 2022, 12, e12141. [Google Scholar] [CrossRef]
  6. Chebib, N.; Mornex, J.-F.; Traclet, J.; Philit, F.; Khouatra, C.; Zeghmar, S.; Turquier, S.; Cottin, V. Pulmonary hypertension in chronic lung diseases: Comparison to other pulmonary hypertension groups. Pulm. Circ. 2018, 8, 1–10. [Google Scholar] [CrossRef]
  7. Nathan, S.D.; Barbera, J.A.; Gaine, S.P.; Harari, S.; Martinez, F.J.; Olschewski, H.; Olsson, K.M.; Peacock, A.J.; Pepke-Zaba, J.; Provencher, S.; et al. Pulmonary hypertension in chronic lung disease and hypoxia. Eur. Respir. J. 2019, 53, 1801914. [Google Scholar] [CrossRef]
  8. Hoeper, M.M.; Behr, J.; Held, M.; Grunig, E.; Vizza, C.D.; Vonk-Noordegraaf, A.; Lange, T.J.; Claussen, M.; Grohé, C.; Klose, H.; et al. Pulmonary Hypertension in Patients with Chronic Fibrosing Idiopathic Interstitial Pneumonias. PLoS ONE 2015, 10, e0134172. [Google Scholar] [CrossRef]
  9. Parikh, R.; O’SUllivan, D.M.; Farber, H.W. The PH-ILD Detection tool: External validation and use in patients with ILD. Pulm. Circ. 2023, 13, e12273. [Google Scholar] [CrossRef]
  10. Nathan, S.D.; Deng, C.; King, C.S.; DuBrock, H.M.; Elwing, J.; Rajagopal, S.; Rischard, F.; Sahay, S.; Broderick, M.; Shen, E.; et al. Inhaled Treprostinil Dosage in Pulmonary Hypertension Associated With Interstitial Lung Disease and Its Effects on Clinical Outcomes. Chest 2023, 163, 398–406. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  11. Piccari, L.; Allwood, B.; Antoniou, K.; Chung, J.H.; Hassoun, P.M.; Nikkho, S.M.; Saggar, R.; Shlobin, O.A.; Vitulo, P.; Nathan, S.D.; et al. Pathogenesis, clinical features, and phenotypes of pulmonary hypertension associated with interstitial lung disease: A consensus statement from the Pulmonary Vascular Research Institute’s Innovative Drug Development Initiative—Group 3 Pulmonary Hypertension. Pulm. Circ. 2023, 13, e12213. [Google Scholar] [CrossRef] [PubMed]
  12. Nathan, S.D. Progress in the Treatment of Pulmonary Hypertension Associated with Interstitial Lung Disease. Am. J. Respir. Crit. Care Med. 2023, 208, 238–246. [Google Scholar] [CrossRef] [PubMed]
  13. Hinkamp, C.A.; Shah, T.; Bartolome, S.; Torres, F.; Chin, K.M. Parenteral prostanoids for severe Group 3 pulmonary hypertension with right ventricular dysfunction. J. Thorac. Dis. 2021, 13, 1466–1475. [Google Scholar] [CrossRef] [PubMed]
  14. Seraj, D.; Shlobin, O.A.; Khangoora, V.; Aryal, S.; Singhal, A.L.; Thomas, C.A.; Nyquist, A.S.; Nathan, S.D.; King, C.S. Use of Prostanoids For Severe Group 3 Pulmonary Hypertension: Real-World Experience From A Tertiary Care Center. Chest 2022, 162, A2399–A2401. [Google Scholar] [CrossRef]
  15. Sitbon, O.; Humbert, M.; Nunes, H.; Parent, F.; Garcia, G.; Hervé, P.; Rainisio, M.; Simonneau, G.É. Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: Prognostic factors and survival. J. Am. Coll. Cardiol. 2002, 40, 780–788. [Google Scholar] [CrossRef]
  16. International Classification of Diseases, Tenth Revision (ICD-10), World Health Organization (WHO) 2020/2023. Licensed under Creative Commons Attribution-NoDerivatives 3.0 IGO Licence (CC BY-ND 3.0 IGO). Available online: https://www.who.int/standards/classifications/classification-of-diseases (accessed on 20 September 2025).
  17. Waxman, A.; Restrepo-Jaramillo, R.; Thenappan, T.; Ravichandran, A.; Engel, P.; Bajwa, A.; Allen, R.; Feldman, J.; Argula, R.; Smith, P.; et al. Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease. N. Engl. J. Med. 2021, 384, 325–334. [Google Scholar] [CrossRef] [PubMed]
  18. Galiè, N.; Humbert, M.; Vachiery, J.-L.; Gibbs, S.; Lang, I.; Torbicki, A.; Simonneau, G.; Peacock, A.; Noordegraaf, A.V.; Beghetti, M.; et al. 2015 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. 2016, 37, 67–119. [Google Scholar] [CrossRef]
  19. Simonneau, G.; Gatzoulis, M.A.; Adatia, I.; Celermajer, D.; Denton, C.; Ghofrani, A.; Sanchez, M.A.G.; Kumar, R.K.; Landzberg, M.; Machado, R.F.; et al. Updated clinical classification of pulmonary hypertension. J. Am. Coll. Cardiol. 2013, 62, D34–D41. [Google Scholar] [CrossRef]
  20. Benza, R.L.; Miller, D.P.; Gomberg-Maitland, M.; Frantz, R.P.; Foreman, A.J.; Coffey, C.S.; Frost, A.; Barst, R.J.; Badesch, D.B.; Elliott, C.G.; et al. Predicting survival in pulmonary arterial hypertension: Insights from the registry to evaluate early and long-term pulmonary arterial hypertension disease management (REVEAL). Circulation 2010, 122, 164–172. [Google Scholar] [CrossRef]
  21. von Siebenthal, C.; Aubert, J.-D.; Mitsakis, P.; Yerly, P.; Prior, J.O.; Nicod, L.P. Pulmonary Hypertension and Indicators of Right Ventricular Function. Front. Med. 2016, 3, 23. [Google Scholar] [CrossRef]
  22. Rahaghi, F.F.; Kolaitis, N.A.; Adegunsoye, A.; de Andrade, J.A.; Flaherty, K.R.; Lancaster, L.H.; Lee, J.S.; Levine, D.J.; Preston, I.R.; Safdar, Z.; et al. Screening strategies for pulmonary hypertension in patients with interstitial lung disease: A multidisciplinary Delphi study. Chest 2022, 162, 145–155. [Google Scholar] [CrossRef]
  23. Bax, S.; Jacob, J.; Ahmed, R.; Bredy, C.; Dimopoulos, K.; Kempny, A.; Kokosi, M.; Kier, G.; Renzoni, E.; Molyneaux, P.L.; et al. Right ventricular to left ventricular ratio at CT pulmonary angiogram predicts mortality in interstitial lung disease. Chest 2020, 157, 89–98. [Google Scholar] [CrossRef] [PubMed]
  24. Humbert, M.; Kovacs, G.; Hoeper, M.M.; Badagliacca, R.; Berger, R.M.F.; Brida, M.; Carlsen, J.; Coats, A.J.S.; Escribano-Subias, P.; Ferrari, P.; et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: Developed by the 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 the International Society for Heart and Lung Transplantation (ISHLT) and the European Reference Network on rare respiratory diseases (ERN-LUNG). Eur. Heart J. 2002, 43, 3618–3731. [Google Scholar] [CrossRef]
  25. Highland, K.B.; Crawford, R.; Classi, P.; Morrison, R.; Doward, L.; Nelsen, A.C.; Castillo, H.; Mathai, S.C.; DuBrock, H.M. Development of the Pulmonary Hypertension Functional Classification Self-Report: A patient version adapted from the World Health Organization Functional Classification measure. Health Qual. Life Outcomes 2021, 19, 202. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  26. Wronski, S.L.; Mordin, M.; Kelley, K.; Anguiano, R.H.; Classi, P.; Shen, E.; Manaker, S. The role of noninvasive endpoints in predicting long-term outcomes in pulmonary arterial hypertension. Lung 2020, 198, 65–86. [Google Scholar] [CrossRef]
  27. Tang, Y.; Luo, Q.; Liu, Z.; Ma, X.; Zhao, Z.; Huang, Z.; Gao, L.; Jin, Q.; Xiong, C.; Ni, X. Oxygen uptake efficiency slope predicts poor outcome in patients with idiopathic pulmonary arterial hypertension. J. Am. Heart Assoc. 2017, 6, e005037. [Google Scholar] [CrossRef]
  28. Helgeson, S.A.; Imam, J.S.; Moss, J.E.; Hodge, D.O.; Burger, C.D. Comparison of brain natriuretic peptide levels to simultaneously obtained right heart hemodynamics in stable outpatients with pulmonary arterial hypertension. Diseases 2018, 6, 33. [Google Scholar] [CrossRef]
  29. Benza, R.L.; Gomberg-Maitland, M.; Miller, D.P.; Frost, A.; Frantz, R.P.; Foreman, A.J.; Badesch, D.B.; McGoon, M.D. The REVEAL Registry risk score calculator in patients newly diagnosed with pulmonary arterial hypertension. Chest 2012, 141, 354–362. [Google Scholar] [CrossRef] [PubMed]
  30. Benza, R.L.; Gomberg-Maitland, M.; Elliott, C.G.; Farber, H.W.; Foreman, A.J.; Frost, A.E.; McGoon, M.D.; Pasta, D.J.; Selej, M.; Burger, C.D.; et al. Predicting Survival in Patients With Pulmonary Arterial Hypertension: The REVEAL Risk Score Calculator 2.0 and Comparison With ESC/ERS-Based Risk Assessment Strategies. Chest 2019, 156, 323–337. [Google Scholar] [CrossRef] [PubMed]
  31. Bernheim, H. Venous asystole in hypertrophy of the left heart with associated stenosis of the right ventricle. Rev. Med. 1910, 30, 785–801. [Google Scholar]
  32. Hassoun, P.M.; Nikkho, S.; Rosenzweig, E.B.; Moreschi, G.; Lawrence, J.; Teeter, J.; Meier, C.; Ghofrani, A.H.; Minai, O.; Rinaldi, P.; et al. Updating clinical endpoint definitions. Pulm. Circ. 2013, 3, 206–216. [Google Scholar] [CrossRef] [PubMed]
  33. Montalescot, G.; Drobinski, G.; Meurin, P.; Maclouf, J.; Sotirov, I.; Philippe, F.; Choussat, R.; Morin, E.; Thomas, D. Effects of prostacyclin on the pulmonary vascular tone and cardiac contractility of patients with pulmonary hypertension secondary to end-stage heart failure. Am. J. Cardiol. 1998, 82, 749–755. [Google Scholar] [CrossRef] [PubMed]
  34. Barst, R.J.; Rubin, L.J.; Long, W.A.; McGoon, M.D.; Rich, S.; Badesch, D.B.; Groves, B.M.; Tapson, V.F.; Bourge, R.C.; Primary Pulmonary Hypertension Study Group; et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N. Engl. J. Med. 1996, 334, 296–301. [Google Scholar] [CrossRef] [PubMed]
  35. Santiago-Vacas, E.; Lupón, J.; Gavidia-Bovadilla, G.; Gual-Capllonch, F.; de Antonio, M.; Domingo, M.; Núñez, J.; Zamora, E.; Teis, A.; Moliner, P.; et al. Pulmonary hypertension and right ventricular dysfunction in heart failure: Prognosis and 15-year prospective longitudinal trajectories in survivors. Eur. J. Hear. Fail. 2020, 22, 1214–1225. [Google Scholar] [CrossRef] [PubMed]
  36. Ghio, S.; Pazzano, A.S.; Klersy, C.; Scelsi, L.; Raineri, C.; Camporotondo, R.; D’Armini, A.; Visconti, L.O. Clinical and prognostic relevance of echocardiographic evaluation of right ventricular geometry in patients with idiopathic pulmonary arterial hypertension. Am. J. Cardiol. 2011, 107, 628–632. [Google Scholar] [CrossRef] [PubMed]
  37. Forfia, P.R.; Fisher, M.R.; Mathai, S.C.; Housten-Harris, T.; Hemnes, A.R.; Borlaug, B.A.; Chamera, E.; Corretti, M.C.; Champion, H.C.; Abraham, T.P.; et al. Tricuspid annular displacement predicts survival in pulmonary hypertension. Am. J. Respir. Crit. Care Med. 2006, 174, 1034–1041. [Google Scholar] [CrossRef] [PubMed]
  38. Albakri, A. Low-output heart failure: A review of clinical status and meta-analysis of diagnosis and clinical management methods. Clin. Med Investig. 2019, 4. [Google Scholar] [CrossRef]
  39. D’Alonzo, G.E.; Barst, R.J.; Ayres, S.M.; Bergofsky, E.H.; Brundage, B.H.; Deere, K.M.; Fishman, A.P.; Goldring, R.M.; Groves, B.M.; Kernis, J.T.; et al. Survival in patients with primary pulmonary hypertension: Results from a national prospective registry. Ann. Intern. Med. 1991, 115, 343–349. [Google Scholar] [CrossRef]
  40. Vonk Noordegraaf, A.; Galiè, N. The role of the right ventricle in pulmonary arterial hypertension. Eur. Respir. Rev. 2011, 20, 243–253. [Google Scholar] [CrossRef]
  41. Howard, L.S. Prognostic factors in pulmonary arterial hypertension: Assessing the course of the disease. Eur. Respir. Rev. 2011, 20, 236–242. [Google Scholar] [CrossRef]
  42. Nickel, N.; Golpon, H.; Greer, M.; Knudsen, L.; Olsson, K.; Westerkamp, V.; Welte, T.; Hoeper, M.M. The prognostic impact of follow-up assessments in patients with idiopathic pulmonary arterial hypertension. Eur. Respir. J. 2012, 39, 589–596. [Google Scholar] [CrossRef] [PubMed]
  43. Mazurek, J.A.; Vaidya, A.; Mathai, S.C.; Roberts, J.D.; Forfia, P.R. Follow-up tricuspid annular plane systolic excursion predicts survival in pulmonary arterial hypertension. Pulm. Circ. 2017, 7, 361–371. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  44. Ghio, S.; Mercurio, V.; Fortuni, F.; Forfia, P.R.; Gall, H.; Ghofrani, A.; Mathai, S.C.; Mazurek, J.A.; Mukherjee, M.; TAPSE in PAH investigators; et al. A comprehensive echocardiographic method for risk stratification in pulmonary arterial hypertension. Eur. Respir. J. 2020, 56, 2000513. [Google Scholar] [CrossRef] [PubMed]
  45. Nathan, S.D.; Shlobin, O.A.; Barnett, S.D.; Saggar, R.; Belperio, J.A.; Ross, D.J.; Ahmad, S.; Saggar, R.; Libra, E.; Lynch, J.P.; et al. Right ventricular systolic pressure by echocardiography as a predictor of pulmonary hypertension in idiopathic pulmonary fibrosis. Respir. Med. 2008, 102, 1305–1310. [Google Scholar] [CrossRef]
  46. King, C.S.; Shlobin, O.A. The trouble with group 3 pulmonary hypertension in interstitial lung disease: Dilemmas in diagnosis and the conundrum of treatment. Chest 2020, 158, 1651–1664. [Google Scholar] [CrossRef]
  47. Keir, G.J.; Wort, S.J.; Kokosi, M.; George, P.M.; Walsh, S.L.; Jacob, J.; Price, L.; Bax, S.; Renzoni, E.A.; Maher, T.M.; et al. Pulmonary hypertension in interstitial lung disease: Limitations of echocardiography compared to cardiac catheterization. Respirology 2018, 23, 687–694. [Google Scholar] [CrossRef]
Arm 93 00041 g001
Figure 1. PH-ILD Severity Score and AUC for Clinical Worsening.
Figure 1. PH-ILD Severity Score and AUC for Clinical Worsening.
Arm 93 00041 g001
Table 1. PH-ILD Severity Score and risk stratification.
Table 1. PH-ILD Severity Score and risk stratification.
ParameterScore
WHO FC ≥ 31
PVR > 5 WU1
CI < 2.0 L/min1
TAPSE < 1.6 cm1
Range 0–4
Low risk: total score < 3
High risk: total score ≥ 3
Table 2. Comparing 3 versions of PH-ILD Severity Score.
Table 2. Comparing 3 versions of PH-ILD Severity Score.
VersionWHO FC—ptsPVR > 5CI < 2TAPSE < 1.6RangeAUCp Value
13—1
4—2		1110–50.811<0.001
2≥3—11110–40.835<0.001
34—11110–40.823<0.001
Table 3. Baseline characteristics of PH-ILD patients.
Table 3. Baseline characteristics of PH-ILD patients.
CharacteristicTotalLow Risk
(≤2)		High Risk
(≥3)		p Value
Sample size (n, % of sample)5728 (49.1)29 (50.9)---
Age, years (mean ± SD)70.9 ± 8.670.8 ± 9.770.9 ± 7.70.974 A
Gender (n, % of category) 0.599 B
  Male31 (54.4)14 (50.0)17 (58.6)
  Female26 (45.6)14 (50.0)12 (41.4)
ILD type (n, %) 0.328 C
  IPF27 (47.4)13 (46.4)14 (48.3)
  CPFE12 (21.1)4 (14.3)8 (27.6)
  NSIP11 (19.3)7 (25.0)4 (13.8)
  Sarcoidosis2 (3.5)2 (7.1)0 (0)
  Chronic HP1 (1.8)1 (3.6)0 (0)
  COP1 (1.8)0 (0)1 (3.4)
  Drug-induced1 (1.8)0 (0)1 (3.4)
  HP1 (1.8)0 (0)1 (3.4)
  RB-ILD1 (1.8)1 (3.6)0 (0)
Antifibrotic therapy (n, %)20 (35.1)11 (39.3)9 (31.0)0.585 B
PH-specific therapy (n, %) 0.012 B
    Inhaled prostacyclin37 (64.9)23 (82.1)14 (48.3)
    Advanced prostacyclin (i.e., IV/ subcutaneous)20 (35.1)5 (17.9)15 (51.7)
mPA pressure (average ± SD)39.2 ± 37.24 ± 44.75 ±
DLCO (mean ± SD)32.5 ± 10.836.2 ± 9.929.0 ± 10.50.010 A
Use of supplemental oxygen (n, %) 48 (84.2)21 (75.0)27 (93.1)0.079 B
Clinical worsening (CW; n, %)39 (68.4)11 (39.3)28 (96.6)<0.001 B
Components of CW (n, %)
  1-year Mortality12 (21.1)3 (10.7)9 (31.0)0.103 B
  Hospitalization30 (52.6)4 (14.3)26 (89.7)<0.001 B
  Decrease in 6MWD of >15%26 (45.6)8 (28.6)18 (62.1)0.017 B
  Lung transplantation0 (0)0 (0)0 (0)---
Values in bold represent statistically significant (p < 0.05) differences. A—Student’s t; B—Fisher’s exact; C—chi square.
Table 4. PH-ILD Severity Score parameters.
Table 4. PH-ILD Severity Score parameters.
ParameterTotal
(n = 57)		Low Risk
(≤2, n = 28)		High Risk
(≥3, n = 29)
WHO FC (n, %)
  12 (3.5)2 (7.1)0 (0)
  29 (15.8)9 (32.1)0 (0)
  320 (35.1)9 (32.1)11 (37.9)
  426 (45.6)8 (28.6)18 (62.1)
PVR (mean ± SD)8.2 ± 3.66.0 ± 2.810.4 ± 2.8
CI (mean ± SD)2.2 ± 0.62.4 ± 0.62.0 ± 0.4
TAPSE (mean ± SD)1.7 ± 0.42.0 ± 0.21.4 ± 0.2
Values in bold represent statistically significant (p < 0.05) differences.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Fiscus, G.; Dagher, C.; O’Sullivan, D.; Carollo, B.; Swanson, K.; Farber, H.W.; Parikh, R. Development of a Tool to Assess the Severity of Pulmonary Hypertension in Patients with Interstitial Lung Disease: A Guide to Assist Therapeutic Choices. Adv. Respir. Med. 2025, 93, 41. https://doi.org/10.3390/arm93050041

AMA Style

Fiscus G, Dagher C, O’Sullivan D, Carollo B, Swanson K, Farber HW, Parikh R. Development of a Tool to Assess the Severity of Pulmonary Hypertension in Patients with Interstitial Lung Disease: A Guide to Assist Therapeutic Choices. Advances in Respiratory Medicine. 2025; 93(5):41. https://doi.org/10.3390/arm93050041

Chicago/Turabian Style

Fiscus, Garrett, Chebly Dagher, David O’Sullivan, Brett Carollo, Kristen Swanson, Harrison W. Farber, and Raj Parikh. 2025. "Development of a Tool to Assess the Severity of Pulmonary Hypertension in Patients with Interstitial Lung Disease: A Guide to Assist Therapeutic Choices" Advances in Respiratory Medicine 93, no. 5: 41. https://doi.org/10.3390/arm93050041

APA Style

Fiscus, G., Dagher, C., O’Sullivan, D., Carollo, B., Swanson, K., Farber, H. W., & Parikh, R. (2025). Development of a Tool to Assess the Severity of Pulmonary Hypertension in Patients with Interstitial Lung Disease: A Guide to Assist Therapeutic Choices. Advances in Respiratory Medicine, 93(5), 41. https://doi.org/10.3390/arm93050041

Article Metrics

Back to TopTop