Case Report: Rethinking pulmonary arterial hypertension: immune and metabolic adaptations in a 34-year case of insidious progression
Year: 2026
Type: article
Study design: Case Report
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: 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.
Author: Bronwen Erickson-Keith
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7130510740