RARE DISEASE
High altitude pulmonary edema
High altitude pulmonary edema
High altitude pulmonary edema
Synonyms: HAPE
Synonyms: HAPE
Synonyms: HAPE
Drug discovery
2
drugs
With orphan designations
Overview
High-altitude pulmonary edema (HAPE) is a life-threatening, non-cardiogenic pulmonary edema caused by rapid ascent to altitudes >2,500 meters. Pathophysiology involves exaggerated hypoxic pulmonary vasoconstriction, leading to elevated pulmonary artery pressure, capillary stress failure, and protein-rich fluid leakage into alveoli. Symptoms include dyspnea at rest, productive cough, cyanosis, and rales. Untreated, mortality exceeds 50% due to hypoxemia and respiratory failure [1][2][16].
Therapies
Immediate descent (500–1,000m) and supplemental oxygen to maintain SpO₂ ≥90% [2][16].
Pharmacotherapy: Nifedipine (30mg SR BID) or PDE5 inhibitors (e.g., sildenafil 50mg TID) for vasodilation; dexamethasone (8mg BID) in severe cases [3][8][9].
Portable hyperbaric chambers (Gamow Bag®) as temporizing measures in remote settings [1][2].
Categories: rare respiratory diseases
Research Papers
528 drug discovery papers about High altitude pulmonary edema, with 2 first-in-class and 8 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
528 drug discovery papers about High altitude pulmonary edema, with 2 first-in-class and 8 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-08 | High-Altitude Oxygenation: A Comprehensive Review of Physiological Mechanisms, Clinical Applications, and Emerging Therapeutic Strategies in Hypobaric Environments
High-altitude oxygenation represents a critical physiological and therapeutic intervention designed to mitigate the profound challenges posed by hypobaric hypoxia in elevated terrestrial environments. This comprehensive review examines the fundamental pathophysiological mechanisms underlying high-altitude illness, explores the diagnostic and therapeutic approaches available for prevention and management, and evaluates emerging strategies for optimizing oxygen delivery in extreme environments. The progressive reduction in barometric pressure with increasing elevation diminishes the partial pressure of inspired oxygen, precipitating a cascade of physiological responses that may culminate in acute mountain sickness, high-altitude pulmonary edema, or high-altitude cerebral edema. The International Society for Mountain Medicine categorizes high-altitude environments into three distinct tiers—high (1,500-3,500 m), very high (3,500-5,500 m), and extreme (≥5,500 m)—each corresponding to progressively diminished oxygen availability and escalating physiological challenge. Recent advances in molecular genetics have elucidated specific mitochondrial DNA haplogroups and nuclear gene variants, including EPAS1, EGLN1, and NOS3, that modulate individual susceptibility to altitude illness, revealing evolutionary adaptations in high-altitude populations. Diagnostic capabilities have been enhanced through point-of-care ultrasound, optic nerve sheath diameter measurement, and wearable oximetry technologies, facilitating early detection in remote settings. Therapeutic approaches encompass pharmacological interventions—predominantly acetazolamide, dexamethasone, and emerging phytochemical agents—alongside nonpharmacological strategies including supplemental oxygen, portable hyperbaric chambers, and auto-positive end-expiratory pressure techniques. Interprofessional collaboration, augmented by telemedicine platforms and continuous physiologic monitoring, remains essential for optimizing outcomes in high-altitude environments. This review synthesizes current evidence to provide a framework for understanding the pathophysiology, diagnosis, prevention, and treatment of high-altitude illness, while identifying promising directions for future research and clinical practice.
2026-06-30 | Cognitive-behavioral therapy in high-altitude respiratory care: Critical considerations for physiological interpretation
High-altitude respiratory diseases, characterized by hypoxia-induced complications such as pulmonary edema and chronic bronchitis, present critical challenges to both physical and mental health in vulnerable populations. The recent study by Meng et al demonstrates that integrating cognitive-behavioral therapy (CBT) with standard care significantly improves anxiety levels and sleep quality in affected patients. These key findings hold direct implications for advancing respiratory management in hypoxic environments. Meng et al ’s observation of reduced serum hypoxia biomarkers (hypoxia-inducible factor-1α and erythropoietin) further suggests potential enhancements in physiological adaptation. However, the interpretation of these biomarker changes as evidence of improved hypoxia tolerance requires cautious examination. The study’s reliance on indirect indicators fails to establish whether CBT’s benefits stem primarily from psychological modulation or genuine cellular adaptation. Furthermore, the 5-day intervention window coincides with the half-life of erythropoietin, raising questions about the durability of these effects in the context of hypoxic acclimatization, which typically requires weeks to months. To resolve these ambiguities, future studies should prioritize longitudinal designs tracking both respiratory function and molecular biomarkers over clinically relevant timeframes. Integrating CBT with objective pulmonary assessments would clarify its role in optimizing oxygen utilization pathways. Such advances could refine targeted interventions for high-altitude respiratory rehabilitation, ultimately strengthening evidence-based care for this unique patient population.
2026-06-16 | PARK7 alleviates high-altitude pulmonary edema by suppressing BACH1 to attenuate lipid peroxidation-driven pro-inflammatory skewing of macrophages.
With the steady increase in global travel, mountaineering, and logistics at extreme elevations, high-altitude pulmonary edema (HAPE) remains a life-threatening emergency with mortality rates reaching up to 50% if untreated. Current clinical management relies heavily on rapid descent or supplemental oxygen, which are often logistically unfeasible in remote areas, while existing pharmacological interventions face challenges regarding efficacy and side effects. There is an urgent need to identify the fundamental molecular switches that translate hypobaric hypoxia into the catastrophic "cytokine storm" and barrier failure characteristic of HAPE. This study investigates the role of the antioxidant protein parkinsonism associated deglycase (PARK7) as a potential therapeutic target. A mouse model simulating 6000 m altitude (72 h) and CoCl₂-induced hypoxia in MLE-12 and RAW264.7 cells were used. PARK7 expression in lung tissue and hypoxic cells was analyzed via RNA-seq, qPCR, and western blot analyses. Lung-specific PARK7 and Bach1 overexpression or knockdown was achieved using AAV9-mediated intratracheal instillation. Pulmonary edema, vascular permeability, histopathology, and ultrastructure were assessed. Lipid peroxidation and M1 macrophage polarization (F4/80⁺iNOS⁺) were evaluated using C11-BODIPY staining, 4-HNE immunohistochemistry, and flow cytometry. PARK7 expression was markedly reduced in HAPE lungs and hypoxic cells. Restoration of PARK7 alleviated pulmonary edema, barrier dysfunction, mitochondrial damage, and inflammatory cell infiltration, primarily macrophages. Mechanistically, PARK7 suppressed lipid peroxidation, reducing MDA and 4-HNE accumulation, thereby blocking pro-inflammatory M1 macrophage polarization. Hypoxia stabilized the antioxidant repressor BTB and CNC Homology 1 (BACH1), whereas PARK7 inhibited BACH1 to exert its protective effect. Re-expression of BACH1 negated PARK7's benefits, restoring lipid peroxidation and M1 macrophage infiltration. This study suggests PARK7 as a key protective factor during HAPE progression. PARK7 inhibits lipid peroxidation through downregulation of BACH1, thereby preventing pro-inflammatory M1 polarization of macrophages and ultimately preserving alveolar-capillary barrier integrity. Targeting the PARK7-BACH1 axis may offer a novel therapeutic strategy for the prevention and treatment of HAPE.
2026-07-08 | High-Altitude Oxygenation: A Comprehensive Review of Physiological Mechanisms, Clinical Applications, and Emerging Therapeutic Strategies in Hypobaric Environments
High-altitude oxygenation represents a critical physiological and therapeutic intervention designed to mitigate the profound challenges posed by hypobaric hypoxia in elevated terrestrial environments. This comprehensive review examines the fundamental pathophysiological mechanisms underlying high-altitude illness, explores the diagnostic and therapeutic approaches available for prevention and management, and evaluates emerging strategies for optimizing oxygen delivery in extreme environments. The progressive reduction in barometric pressure with increasing elevation diminishes the partial pressure of inspired oxygen, precipitating a cascade of physiological responses that may culminate in acute mountain sickness, high-altitude pulmonary edema, or high-altitude cerebral edema. The International Society for Mountain Medicine categorizes high-altitude environments into three distinct tiers—high (1,500-3,500 m), very high (3,500-5,500 m), and extreme (≥5,500 m)—each corresponding to progressively diminished oxygen availability and escalating physiological challenge. Recent advances in molecular genetics have elucidated specific mitochondrial DNA haplogroups and nuclear gene variants, including EPAS1, EGLN1, and NOS3, that modulate individual susceptibility to altitude illness, revealing evolutionary adaptations in high-altitude populations. Diagnostic capabilities have been enhanced through point-of-care ultrasound, optic nerve sheath diameter measurement, and wearable oximetry technologies, facilitating early detection in remote settings. Therapeutic approaches encompass pharmacological interventions—predominantly acetazolamide, dexamethasone, and emerging phytochemical agents—alongside nonpharmacological strategies including supplemental oxygen, portable hyperbaric chambers, and auto-positive end-expiratory pressure techniques. Interprofessional collaboration, augmented by telemedicine platforms and continuous physiologic monitoring, remains essential for optimizing outcomes in high-altitude environments. This review synthesizes current evidence to provide a framework for understanding the pathophysiology, diagnosis, prevention, and treatment of high-altitude illness, while identifying promising directions for future research and clinical practice.
2026-06-30 | Cognitive-behavioral therapy in high-altitude respiratory care: Critical considerations for physiological interpretation
High-altitude respiratory diseases, characterized by hypoxia-induced complications such as pulmonary edema and chronic bronchitis, present critical challenges to both physical and mental health in vulnerable populations. The recent study by Meng et al demonstrates that integrating cognitive-behavioral therapy (CBT) with standard care significantly improves anxiety levels and sleep quality in affected patients. These key findings hold direct implications for advancing respiratory management in hypoxic environments. Meng et al ’s observation of reduced serum hypoxia biomarkers (hypoxia-inducible factor-1α and erythropoietin) further suggests potential enhancements in physiological adaptation. However, the interpretation of these biomarker changes as evidence of improved hypoxia tolerance requires cautious examination. The study’s reliance on indirect indicators fails to establish whether CBT’s benefits stem primarily from psychological modulation or genuine cellular adaptation. Furthermore, the 5-day intervention window coincides with the half-life of erythropoietin, raising questions about the durability of these effects in the context of hypoxic acclimatization, which typically requires weeks to months. To resolve these ambiguities, future studies should prioritize longitudinal designs tracking both respiratory function and molecular biomarkers over clinically relevant timeframes. Integrating CBT with objective pulmonary assessments would clarify its role in optimizing oxygen utilization pathways. Such advances could refine targeted interventions for high-altitude respiratory rehabilitation, ultimately strengthening evidence-based care for this unique patient population.
2026-06-16 | PARK7 alleviates high-altitude pulmonary edema by suppressing BACH1 to attenuate lipid peroxidation-driven pro-inflammatory skewing of macrophages.
With the steady increase in global travel, mountaineering, and logistics at extreme elevations, high-altitude pulmonary edema (HAPE) remains a life-threatening emergency with mortality rates reaching up to 50% if untreated. Current clinical management relies heavily on rapid descent or supplemental oxygen, which are often logistically unfeasible in remote areas, while existing pharmacological interventions face challenges regarding efficacy and side effects. There is an urgent need to identify the fundamental molecular switches that translate hypobaric hypoxia into the catastrophic "cytokine storm" and barrier failure characteristic of HAPE. This study investigates the role of the antioxidant protein parkinsonism associated deglycase (PARK7) as a potential therapeutic target. A mouse model simulating 6000 m altitude (72 h) and CoCl₂-induced hypoxia in MLE-12 and RAW264.7 cells were used. PARK7 expression in lung tissue and hypoxic cells was analyzed via RNA-seq, qPCR, and western blot analyses. Lung-specific PARK7 and Bach1 overexpression or knockdown was achieved using AAV9-mediated intratracheal instillation. Pulmonary edema, vascular permeability, histopathology, and ultrastructure were assessed. Lipid peroxidation and M1 macrophage polarization (F4/80⁺iNOS⁺) were evaluated using C11-BODIPY staining, 4-HNE immunohistochemistry, and flow cytometry. PARK7 expression was markedly reduced in HAPE lungs and hypoxic cells. Restoration of PARK7 alleviated pulmonary edema, barrier dysfunction, mitochondrial damage, and inflammatory cell infiltration, primarily macrophages. Mechanistically, PARK7 suppressed lipid peroxidation, reducing MDA and 4-HNE accumulation, thereby blocking pro-inflammatory M1 macrophage polarization. Hypoxia stabilized the antioxidant repressor BTB and CNC Homology 1 (BACH1), whereas PARK7 inhibited BACH1 to exert its protective effect. Re-expression of BACH1 negated PARK7's benefits, restoring lipid peroxidation and M1 macrophage infiltration. This study suggests PARK7 as a key protective factor during HAPE progression. PARK7 inhibits lipid peroxidation through downregulation of BACH1, thereby preventing pro-inflammatory M1 polarization of macrophages and ultimately preserving alveolar-capillary barrier integrity. Targeting the PARK7-BACH1 axis may offer a novel therapeutic strategy for the prevention and treatment of HAPE.
Access all drug discovery articles and probability of success in trials forecasts:
Access all drug discovery articles and probability of success in trials forecasts:
Drug Discovery Landscape
2 orphan drug designations for High altitude pulmonary edema.
2 orphan drug designations for High altitude pulmonary edema.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Cyclo-Cys-Gly-Gln-Arg-Glu-Thr-Pro-Glu-Gly-Ala-Glu-Ala-Lys-Pro-Trp-Tyr-Cys | small molecules | EMA | 2013-02-08 | — | Apeptico Forschung und Entwicklung GmbH |
synthetic peptide; cyclo-Cys-Gly-Gln-Arg-Glu-Thr-Pro-Glu-Gly-Ala-Glu-ALA-Lys-Pro-Trp-Tyr-Cys | peptides | FDA | 2013-01-16 | — | Apeptico Forschung und Entwicklung GmbH |
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