Parth Rali, MD, MBBS, FCCP, pulmonologist at Temple Health, discusses interim findings from the PHINDER study evaluating pulmonary hypertension (PH) screening strategies in patients with interstitial lung disease (ILD).
Understanding Pulmonary Hypertension in Patients with ILD
PH associated with ILD is classified as Group 3 pulmonary hypertension, and Dr. Rali shared that patients with ILD-related PH typically have worse outcomes than those without PH. The challenge is identifying these patients, because historically, there haven’t been established screening tools, and treatment options are limited.
After the INCREASE study (NCT02630316), inhaled treprostinil was approved for ILD-related PH, but with that designation came the need to identify affected patients earlier.
Dr. Rali shared that earlier identification would make it easier for clinicians to begin treatment and even stabilize ILD. He added that this could be particularly beneficial for patients undergoing lung transplant evaluation because identifying and controlling PH is essential in this population.
The PHINDER study was designed to establish repeatable screening strategies for PH in patients with ILD.
PHINDER Analysis Reveals Higher Predicted Mortality Risk Among IPF Patients
PHINDER (NCT05776225) was a multicenter, prospective, open-label, non-randomized study evaluating PH screening strategies in patients with ILD. Researchers combined several clinical and imaging criteria to identify patients who should undergo right heart catheterization, which is considered the gold standard for PH diagnosis. These criteria included:
- Patient symptoms and clinical presentation
- Echocardiographic findings
- CT-based measurements
Dr. Rali said that more than 50% of patients enrolled in the study had ILD-related PH, while approximately 15% of those patients had severe PH.
For the interim analysis presented at CHEST 2026 Annual Meeting, investigators applied the PVD-B65 model to 119 patients with PH to evaluate their predicted one-year mortality risk. The PVD-B65 model uses clinical characteristics associated with mortality in ILD-related PH patients and has been externally validated using the Pulmonary Vascular Disease Phenomics (PVDOMICS) registry.
PVD-B65 assigns points based on five parameters:
- Fibrotic ILD
- B-type natriuretic peptide (BNP) greater than 200 pg/mL
- Age greater than 65 years
- Pulmonary vascular resistance (PVR) greater than 5 Wood units
- 6-minute walk distance (6MWD) less than 150 meters
Some of the most notable findings from the interim analysis included:
- Higher scores among patients with higher pulmonary artery pressures
Patients with mean pulmonary artery pressure (mPAP) of at least 25 mmHg had a numerically higher mean PVD-B65 score than those with mPAP of 21 to 24 mmHg.1
- Fewer patients classified as low risk
Only 38% of patients with mPAP of at least 25 mmHg were classified as low risk, compared to 60% of those with mPAP of 21 to 24 mmHg.1
- IPF patients had the highest predicted mortality risk
Patients with IPF had a mean PVD-B65 score of 7.9 ± 1.9, higher than the other ILD subgroups.1
- No IPF patients were classified as low risk
In comparison, 64% of patients with hypersensitivity pneumonitis, 78% with connective tissue disease, and 80% with nonspecific interstitial pneumonia (NSIP) were classified as low risk.1
Dr. Rali emphasized that these findings don’t represent actual mortality outcomes. Instead, the analysis applied an established mortality prediction model to the PHINDER population, evaluating participants’ potential risk of adverse outcomes.
He noted that IPF patients appeared to be sicker than other ILD subgroups due to their higher pulmonary artery pressures and predicted mortality risk scores.
Earlier Screening Could Make It Easier to Identify High-Risk Patients
Dr. Rali explained that PH may go undetected in patients with ILD if clinicians rely solely on clinical judgment or standard echocardiographic findings. He said certain CT-based measurements, such as the right ventricular-to-left ventricular (RV/LV) ratio and the pulmonary artery-to-aorta ratio, could make it easier to identify patients with PH, particularly when combined with an individual’s symptoms and clinical presentation. These findings suggest clinicians may need to consider PH earlier when evaluating patients with advanced ILD instead of waiting for more obvious symptoms to appear.
Once PH is diagnosed, Dr. Rali believes the PVD-B65 model could make it easier for clinicians to assess disease severity and predicted mortality risk with routinely available clinical information. He also said that he hopes electronic medical record systems (EMRs) will eventually incorporate the score.
Expanding Research into Earlier PH Detection
The complete PHINDER cohort is expected to provide additional information to help investigators develop an evidence-based screening tool for patients with ILD-related PH. Furthermore, Dr. Rali underscored the importance of collaboration between ILD specialists and PH experts, including pulmonologists and cardiologists. He explained that ILD and PH shouldn’t be treated as two separate disease states, as they can occur simultaneously and require coordinated care.
In closing, Dr. Rali shared that researchers at Temple Lung Center are prospectively evaluating the PVD-B65 model in ILD patients and plan to monitor their scores over time. He said his team hopes to present these additional findings at a future American Thoracic Society (ATS) or American College of Chest Physicians (CHEST) meeting.
In Their Own Words
“I think we need to kind of lower our thought process of thinking about pulmonary hypertension. If 55% of your patients have pulmonary hypertension, I think you should have a very low threshold to screen. You should have a reason why not to screen rather than why to screen in patients with interstitial lung disease.” – Parth Rali, MD, MBBS, FCCP, pulmonologist at Temple Health
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