Treating Inflammation Associated with Pulmonary Hypertension: An Overview of the Literature

Figures & data

Figure 1 Hemodynamic integration and cell injury and repair that illustrate the cardiopulmonary condition of severe pulmonary arterial hypertension (PAH). Data from Voelkel et al.⁷

Figure 2 Schematic illustration of inflammation and infection-mediated vascular remodeling: upon stimulation by infection and/or inflammation, lung vascular cells produce and release inflammatory mediators (chemokines and cytokines), thereby recruiting the inflammatory cells. Under the coordination of inflammatory mediators, inflammatory cells can promote the release of cytokines and chemokines, which leads to chronic vasoconstriction, vascular remodeling by vascular cell proliferation, collagen deposition and plexiform lesions. The progressive process causes pulmonary arterial hypertension.

Abbreviations: IL, interleukin; TNF-α, tumor necrosis factor-α; FGF, fibroblast growth factor; PDGF, platelet-derived growth factor; VEGF, vascular endothelial growth factor.

Table 1 Updated Clinical Classification of Pulmonary Hypertension

Group 1: PAH  1.1 Idiopathic PAH  1.2 Heritable PAH  1.3 Drug and toxin-induced PAH  1.4 PAH associated with:   1.4.1 Connective tissue disease   1.4.2 HIV infection   1.4.3 Portal hypertension   1.4.4 Congenital heart disease   1.4.5 Schistosomiasis  1.5 PAH long-term responders to calcium channel blockers  1.6 PAH with overt features of venous/capillaries (PVOD/PCH) involvement  1.7 Persistent PH of the newborn syndrome Group 2: PH due to left heart disease  2.1 PH due to heart failure with preserved LVEF  2.2 PH due to heart failure with reduced LVEF  2.3 Valvular heart disease  2.4 Congenital/acquired cardiovascular conditions leading to postcapillary PH Group 3: PH due to lung diseases and/or hypoxia  3.1 Obstructive lung disease  3.2 Restrictive lung disease  3.3 Other lung disease with mixed restrictive/obstructive pattern  3.4 Hypoxia without lung disease  3.5 Developmental lung disorders Group 4: PH due to pulmonary artery obstructions  4.1 Chronic thromboembolic PH  4.2 Other pulmonary artery obstructions Group 5: PH with unclear and/or multifactorial mechanisms  5.1 Hematological disorders  5.2 Systemic and metabolic disorders  5.3 Others

Abbreviations: LVEF, left ventricular ejection; PAH, pulmonary arterial hypertension; PCH, pulmonary capillary hemangiomatosis; PH, pulmonary hypertension; PVOD, pulmonary veno-occlusive disease. Data from Simonneau et al.²

Table 2 Classes of Therapeutic Drugs Specific to PAH

	Endothelin Receptor Antagonists	PDE5 Inhibitors	Prostacyclin Analogues	Prostacyclin Receptor Agonists	sGC Stimulators
Generic names	Bosentan, ambrisentan, macitentan	Sildenafil, tadalafil	Epoprostenol, Iloprost, treprostinil, beraprost	Selexipag	Riociguat
Route of administration	Oral	Oral	Intravenous, inhaled, subcutaneous, oral	Oral	Oral
Common side effects	Hepatotoxity, peripheral edema, nasal congestion, nasopharyngitis, headache, anemia	Headache, dyspepsia, diarrhea, myalgia, flushing epistaxis	Central venous access infection, or blockage, cough, headache, flushing, jaw pain	Headache, nasopharyngitis, edema, nausea, anemia, jaw pain,	Headache, dyspepsia, peripheral edema, dizziness, hypotension

Abbreviations: PAH, pulmonary arterial hypertension; PDE5, phosphodiesterase type 5; sGC, soluble guanylate cyclase. Data from Galiè et al.¹

Voelkel NF, Gomez-Arroyo J, Abbate A, Bogaard HJ, Nicolls MR. Pathobiology of pulmonary arterial hypertension and right ventricular failure. Eur Respir J. 2012;40:1555–1565. doi:10.1183/09031936.00046612

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Simonneau G, Montani D, Celermajer DS, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019;53(1):1801913. doi:10.1183/13993003.01913-2018

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Galiè N, Channick RN, Frantz RP, et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J. 2019;53(1):1801889. doi:10.1183/13993003.01889-2018

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