Case Report: Rethinking pulmonary arterial hypertension: immune and metabolic adaptations in a 34-year case of insidious progression

Our plain-English summary of Case Report: Rethinking pulmonary arterial hypertension: immune and metabolic adaptations in a 34-year case of insidious progression, by B. Erickson-Keith (Frontiers in Cardiovascular Medicine, 2026).

The study

• Author: B. Erickson-Keith
• Journal: Frontiers in Cardiovascular Medicine
• Published: 2026;13:1727803
• Type of article: Case report
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Pulmonary arterial hypertension (PAH) is traditionally characterized as a rapidly progressive, fatal disease. Yet increasing evidence suggests that immune dysregulation, endothelial injury, and metabolic adaptation can sustain subclinical disease for decades before recognition.

Case Presentation: We report a 73-year-old U.S. Army veteran with terminal PAH whose symptoms began in 1972-nearly fifty years before diagnosis. Despite a childhood splenectomy and extensive exposure to pulmonary toxins during a 21-year career in military aviation (JP-4/JP-8 fuels, asbestos, burn pits, and talc pleurodesis), no follow-up imaging was performed after retirement in 1992. After a 24-year gap, a 2016 chest x-ray revealed pulmonary artery enlargement consistent with pulmonary hypertension, but the finding was not pursued until 2021, when right-heart catheterization confirmed severe PAH with pulmonary artery pressures of 82/29 mm Hg (mean ≈47 mm Hg). A transthoracic echocardiogram in October 2025 demonstrated an estimated right-ventricular systolic pressure (RVSP) of 66 mm Hg with right-atrial pressure 8 mm Hg, preserved biventricular function, normal ejection fraction (LVEF 68%), mild concentric left-ventricular hypertrophy, and only trace tricuspid and mitral regurgitation. Brain natriuretic peptide (BNP) levels remained normal, suggesting right-ventricular metabolic adaptation rather than decompensation.

Discussion: This case supports a model of slowly progressive PAH driven by chronic immune imbalance from asplenia, toxin-induced oxidative stress, and nitric-oxide scavenging by free hemoglobin. Over decades, these mechanisms produced endothelial remodeling while right-ventricular metabolism shifted toward glycolysis ("fetal-like" adaptation), delaying failure. The patient's trajectory parallels post-COVID data linking endothelial inflammation and microvascular injury to delayed pulmonary hypertension.

Conclusion: PAH can evolve silently across decades in individuals with immune or hematologic dysregulation. Recognition of immune-metabolic phenotypes and early screening of asplenic or toxin-exposed populations may enable earlier intervention and alter the disease's natural history.

© 2026 Erickson-Keith.

In plain English

This was a case report describing one 73-year-old U.S. Army veteran with severe pulmonary arterial hypertension (high blood pressure in the lung arteries). The patient had the spleen removed after trauma at age 16 and served 21 years in military aviation (1971 to 1992), with exposure to JP-4/JP-8 jet fuels, methyl-ethyl-ketone, asbestos and burn pits. The patient also underwent talc pleurodesis in 1991. The article gave no fiber type, duration or amount for the asbestos exposure. Final military imaging in 1992 showed pleural thickening, which was interpreted as post-surgical change. A 2016 chest x-ray suggested pulmonary hypertension, but CT did not confirm it. Right-heart catheterization in 2021 found pulmonary artery pressures of 82/29 mm Hg (mean approximately 47). The right ventricle was only mildly enlarged with preserved function, and BNP, a blood marker of heart strain, was normal at 75 pg/mL. An October 2025 echocardiogram estimated right-ventricular systolic pressure at 66 mm Hg with preserved heart function. The author proposed that absent spleen function, toxin exposures and heart adaptation produced slow disease over decades. The author stated that a single case cannot establish causality.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Case report (single patient, retrospective)
• Who was studied: One 73-year-old U.S. Army veteran in the United States with a trauma-related splenectomy at age 16 and 21 years of active-duty aviation service (1971 to 1992)
• Exposure: Military service exposures to JP-4/JP-8 jet fuels, methyl-ethyl-ketone (MEK), asbestos and burn pits, plus talc pleurodesis in 1991 for recurrent spontaneous pneumothoraces. No asbestos fiber type, duration or dose was given.
• Main results:
  • Final military imaging in 1992 showed pleural thickening and blunted costophrenic angles. The article's table interpreted these as post-surgical change.
  • In 2016, a chest x-ray in this patient showed prominent pulmonary arteries and right-heart border enlargement, interpreted as suggestive of pulmonary hypertension. Subsequent CT imaging did not confirm this.
  • Right-heart catheterization in 2021 confirmed severe pulmonary arterial hypertension in this patient, with pulmonary artery pressures of 82/29 mm Hg (mean approximately 47 mm Hg).
  • Despite the elevated pressures, the patient's right-ventricular enlargement was mild, systolic function was preserved, and BNP was within normal limits (75 pg/mL).
  • The October 2025 echocardiogram showed an estimated right-ventricular systolic pressure of 66 mm Hg (right atrial pressure 8 mm Hg), preserved biventricular function, LVEF of 68%, and TAPSE of 1.8 cm.
  • Laboratory trends over time showed chronically low lymphocyte counts, low-normal red blood cell indices, and intermittent low sodium and chloride.
  • Supplemental oxygen was started in 2023. It improved exertional tolerance but did not fully relieve symptoms.
• The authors' conclusion: The author concluded that the case supports a model of slow, immune-mediated vascular remodeling leading to advanced PAH after decades of compensation. The author linked this to the patient's asplenia, chronic inflammation, environmental toxin exposure and delayed diagnosis.
• Limitations the authors state:
  • A single retrospective case cannot establish causality.
  • Historical data were reconstructed from records spanning five decades, and some laboratory or imaging details were unavailable.
  • No hemodynamic measurements were obtained before 2021, limiting precision about when the disease began and how it progressed.
  • Genetic testing for heritable PAH markers such as BMPR2 was not performed.
  • The interpretation needs prospective validation.

Topics

Medical terms in this study, explained in our Lexicon: Talc Pleurodesis, Chest X-Ray, Pulmonary Hypertension, Echocardiogram, Oxidative Stress, Inflammation.

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