Exploiting inhalable microparticles incorporating hybrid polymer-lipid nanoparticles loaded with Iloprost manages lung hyper-inflammation.

This study focuses on developing of a novel inhalation therapy for managing lung hyper-inflammation, producing hybrid polymer-lipid nanoparticles loaded with Iloprost (Ilo). These nanoparticles showed a size of approximately 100 nm with a core-shell structure and provided prolonged drug release, reaching 28 wt% after 6 h of incubation. The phospholipid composition and quantity (64 wt% on the total sample weight) result in minimal interaction with mucin and a significant effect on the rheology of a cystic fibrosis mucus model, in terms of reducing complex viscosity. To obtain an inhalable microparticulate matrix suitable for incorporating Ilo@PEG-LPHNPs, the qualitative and quantitative composition of the feed fluid for the spray drying (SD) process was optimized. The selected composition (10 % wt/vol of mannitol and 10 % wt of ammonium bicarbonate relative to the weight of mannitol) was used to produce Nano-into Microparticles (NiM). The characterization of NiM revealed excellent aerodynamic properties, with a Mass Median Aerodynamic Diameter (MMAD) of 4.34 µm and a Fine Particle Fraction (FPF) of approximately 57 %. Biological characterization revealed that the particles are non-toxic to 16-HBE cells and can effectively evade macrophage uptake, likely due to the presence of PEG in their composition. Moreover, the delivered Iloprost significantly downregulates the production of the pro-inflammatory cytokine IL-6, showing the therapeutic potential of this drug delivery system.

Effects of Local Vasodilators and the Autonomic Nervous System on Microcirculation and Mitochondrial Function in Septic Rats.

Systemic vasodilating agents like nitroglycerin (NG) or iloprost (Ilo) show beneficial effects on intestinal microcirculation during sepsis, which could be attenuated by activation of the sympathetic nervous system or systemic side effects of vasodilating agents. This exploratory study aimed to investigate the effects of topically administered vasodilators and the parasympathetic drug carbachol on colonic microcirculatory oxygenation (µHbO2), blood flow (µFlow) and mitochondrial respiration. A total of 120 male Wistar rats were randomly assigned to twelve groups and underwent either colon ascendens stent peritonitis (CASP) or sham surgery. After 24 h, animals received the following therapeutic regimes: (1) balanced full electrolyte solution, (2) carbachol, (3) NG, (4) Ilo, (5) NG + carbachol, and (6) Ilo + carbachol. Mitochondrial respiration was measured in colon homogenates by respirometry. In sham animals, NG (-13.1%*) and Ilo (-10.5%*) led to a decrease in µHbO2. Additional application of carbachol abolished this effect (NG + carbachol: -4.0%, non-significant; Ilo + carbachol: -1.4%, non-significant). In sepsis, carbachol reduced µHbO2 when applied alone (-10.5%*) or in combination with NG (-17.6%*). Thus, the direction and degree of this effect depend on the initial pathophysiologic condition.

A Case of Interstitial Lung Disease-Related Pulmonary Hypertension Successfully Treated with Inhaled Iloprost.

Pulmonary hypertension (PH) associated with interstitial lung disease (ILD) (PH-ILD) significantly worsens clinical symptoms and survival, with no effective treatment available. This case report presents the successful treatment of PH-ILD with inhaled iloprost in a patient with idiopathic pulmonary fibrosis (IPF). The patient, a 68-year-old female, was diagnosed with IPF in 2018 and was maintained on pirfenidone. She experienced stable disease until March 2023, when she developed progressive exertional dyspnea, despite stability indicated by a computed tomography (CT) scan, without progression. Transthoracic echocardiography (TTE) and right heart catheterization (RHC) confirmed PH-ILD with a mean pulmonary artery pressure (mPAP) of 43 mmHg. Due to the ineffectiveness of sildenafil and a CT scan indicating stable IPF, a repeat RHC was performed, which showed a worsening of PH (mPAP 62 mmHg). Consequently, inhaled iloprost, at a dosage of 10 mcg every eight hours, was added to the existing antifibrotic agent. After two months, the patient experienced reduced exertional dyspnea and home oxygen requirements. By the seventh month, pulmonary function tests, the six-minute walk test, and RHC parameters (mPAP 37 mmHg) showed marked improvements. This case suggests that inhaled iloprost may be beneficial for managing PH-ILD. Further research is needed to confirm the efficacy of iloprost in PH-ILD treatment.

Evaluation of changes in cardiac longitudinal strain rate in patients with systemic sclerosis undergoing iloprost treatment: an observational study.

OBJECTIVES: Systemic Sclerosis (SSc) is characterized by widespread microangiopathy and fibrosis of skin and visceral organs. Left ventricle involvement is usually subclinical, characterized by systolic and/or diastolic dysfunction. The global longitudinal strain (GLS), a validated and reliable technique for the measurement of ventricular longitudinal deformation by means of echocardiography, may detect subclinical systolic dysfunction of SSc myocardium. The improvement of myocardial perfusion by means of intravenous Iloprost administration could ameliorate the contractility of SSc heart. Therefore, we aimed to evaluate GLS in a series of SSc patients prior and after Iloprost infusion. METHODS: Fifteen consecutive SSc patients (age: 54 ± 11 years; 12 females) treated with Iloprost because of the presence/history of digital ulcers underwent echocardiography, including GLS technique. This evaluation was conducted immediately before Iloprost administration and at the end of the 6-h infusion session. RESULTS: Significant improvement in the mean GLS was observed after Iloprost administration (from -13.5 ± 2.5 to -15 ± 3.3; p= 0.011). The echocardiographic data obtained from the four-chamber view showed the best quality for GLS analysis and showed a highly significant improvement of the strain after Iloprost administration (from -13.4 ± 2.2 to -15.6 ± 3; p= 0.001). The degree of GLS improvement did not correlate with any SSc parameters. CONCLUSION: Iloprost administration improved GLS, suggesting that the increase of myocardial perfusion allowed, at least in part, a correction of left ventricular systolic dysfunction. Further studies are needed to confirm these findings, further exploring the mid/long-term effects of Iloprost on myocardial contraction.

BK Channels in Tail Artery Vascular Smooth Muscle Cells of Normotensive (WKY) and Hypertensive (SHR) Rats Possess Similar Calcium Sensitivity But Different Responses to the Vasodilator Iloprost.

It has been reported that, in the spontaneously hypertensive rat (SHR) model of hypertension, different components of the G-protein/adenylate cyclase (AC)/Calcium-activated potassium channel of high conductance (BK) channel signaling pathway are altered differently. In the upstream part of the pathway (G-protein/AC), a comparatively low efficacy has been established, whereas downstream BK currents seem to be increased. Thus, the overall performance of this signaling pathway in SHR is elusive. For a better understanding, we focused on one aspect, the direct targeting of the BK channel by the G-protein/AC pathway and tested the hypothesis that the comparatively low AC pathway efficacy in SHR results in a reduced agonist-induced stimulation of BK currents. This hypothesis was investigated using freshly isolated smooth muscle cells from WKY and SHR rat tail artery and the patch-clamp technique. It was observed that: (1) single BK channels have similar current-voltage relationships, voltage-dependence and calcium sensitivity; (2) BK currents in cells with a strong buffering of the BK channel activator calcium have similar current-voltage relationships; (3) the iloprost-induced concentration-dependent increase of the BK current is larger in WKY compared to SHR; (4) the effects of activators of the PKA pathway, the catalytic subunit of PKA and the potent and selective cAMP-analogue Sp-5,6-DCl-cBIMPS on BK currents are similar. Thus, our data suggest that the lower iloprost-induced stimulation of the BK current in freshly isolated rat tail artery smooth muscle cells from SHR compared with WKY is due to the lower efficacy of upstream elements of the G-Protein/AC/BK channel pathway.

Cold Injury.

Cold injury has been documented for centuries and remains a concern for military personnel, winter recreationalists, and urban homeless populations. Treatment advances in the last decades have included thrombolytic and prostaglandin therapies however the mainstay remains early recognition and rapid rewarming. This chapter focuses on frostbite, with a brief overview of other cold related conditions.

Safety and Tolerability of Continuous Inhaled Iloprost Therapy for Severe Pulmonary Hypertension in Neonates and Infants.

This is a single-center retrospective study to assess the safety and tolerability of continuous inhaled iloprost use as rescue therapy for refractory pulmonary hypertension (PH) in critically ill neonates and infants. A retrospective chart review was performed on 58 infants and data were collected at baseline, 1, 6, 12, 24, 48 and 72 h of iloprost initiation. Primary outcomes were change in heart rate (HR), fraction of inspired oxygen (FiO2), mean airway pressures (MAP), blood pressure (BP) and oxygenation index (OI). Secondary outcomes were need for extracorporeal membrane oxygenation (ECMO) and death. 51 patients treated for >6 h were analyzed in 2 age groups, neonate (≤28 days: n = 32) and infant (29-365 days: n = 19). FiO2 (p < 0.001) and OI (p = 0.01) decreased, while there were no significant changes in MAP, BP and HR. Of the fifteen patients placed on ECMO, seven were bridged off ECMO on iloprost and eight died. Twenty-four out of fifty-one patients (47%) recovered without requiring ECMO, while twelve (23%) died. Iloprost as add-on therapy for refractory PH in critically ill infants in the NICU has an acceptable tolerability and safety profile. Large prospective multicenter studies using iloprost in the neonatal ICU are necessary to validate these results.

Long peripheral catheters for intravenous infusions of iloprost or alprostadil therapy in rheumatologic outpatients.

BACKGROUND: Long peripheral catheters (LPCs) role in Difficult IntraVenous Access (DIVA) patients admitted to the emergency department has already been studied, resulting in a rapid, safe, and cost-effective procedure. Although their use in outpatient settings is established, there is a lack of studies assessing their benefits. In particular, rheumatologic outpatients affected by scleroderma, especially those affected by digital ulcers, are often treated with intravenous infusions of prostaglandin I2 (PGI2) analog (IV-PGI2A). OBJECTIVE AND METHODS: From 1 October 2021 to 31 March 2024, we conducted a prospective study enrolling DIVA outpatients affected by systemic sclerosis or undifferentiated connective tissue disease who needed IV-PGI2A therapy at L. Sacco Hospital in Milan (Italy). Each treatment cycle consisted of four consecutive days of infusion of iloprost or alprostadil. The primary aim was to assess the efficacy and potential complications associated with LPCs for IV-PGI2A. RESULTS: Twenty-six patients were enrolled 23 were females (88.5%), and the median age was 72 years (IQR 56-78.7). In total, 97 LPCs were inserted, with a mean number of insertions per patient/year of 2.3. An increase in LPCs insertion during the 30 months of the enrollment period was observed. Eighteen patients required more than one LPC placement, and in 61% of them, the second venipuncture was executed at a different site. No procedural complications were registered (accidental puncture of the brachial artery, accidental median nerve puncture, bleeding) nor late complications (Catheter-Related Thrombosis, Catheter-Related Bloodstream Infections, Accidental Removal). CONCLUSIONS: Our experience shows that LPCs could be valuable and safe for rheumatologic outpatients. The increased number of insertions and new and total patients enrolled each year defines the satisfaction of patients and health care professionals.

Stable measurement of chemistry, immunochemistry, and hematology analytes in a heparin-based anticoagulant with iloprost additive: A promising candidate for the polyvalent blood collection tube.

INTRODUCTION: A polyvalent blood collection tube could potentially reduce the number and volume of blood samples drawn from patients and reduce the risk of tube mix-ups in a point-of-care setting in the emergency department and the intensive care unit. METHODS: Four different concentrations of our experimental heparin anticoagulant with iloprost additive (HEP-ILOP 50 nM, 150 nM, 1000 nM, and 10 µM, respectively) were tested for significant differences and bias performance specifications against EDTA for 29 hematology analytes, and the highest concentration (HEP-ILOP 10 µM) against lithium heparin for 14 chemistry and immunochemistry analytes. Samples were drawn from 79 consenting subjects from the Oncology Department (n = 38) and the Intensive and Intermediary Care Unit (n = 41). RESULTS: For hematology analytes, the HEP-ILOP formulation generally provided stable measurement within optimal requirements within 5 h after sampling (mean 104 ± 56 min), with very little difference between the four HEP-ILOP concentrations. Because of differences in platelet and red blood cell swelling between EDTA and HEP-ILOP, all size-dependent analytes required proportional factorization to produce similar results. Platelet count by impedance similarly required factorization, whereas the fluorescent method provided results identical with EDTA. Chemistry and immunochemistry analytes were within optimal requirements except for potassium, lactate dehydrogenase, and glucose, indicating a cytoprotective effect of iloprost reducing cell metabolism and rupture, thereby producing results closer to in vivo conditions. CONCLUSIONS: Our novel dry-sprayed anticoagulant formulation, HEP-ILOP, is a promising candidate for a polyvalent blood collection tube, enabling the analysis of hematology, chemistry, and immunochemistry analytes in the same tube.

Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Frostbite: 2024 Update.

The Wilderness Medical Society convened an expert panel to develop a set of evidence-based guidelines for the prevention and treatment of frostbite. We present a review of pertinent pathophysiology. We then discuss primary and secondary prevention measures and therapeutic management. Recommendations are made regarding each treatment and its role in management. These recommendations are graded on the basis of the quality of supporting evidence and balance between the benefits and risks or burdens for each modality according to methodology stipulated by the American College of Chest Physicians. This is an updated version of the guidelines published in 2019.

Positive Vasoreactivity Testing in Pulmonary Arterial Hypertension: Therapeutic Consequences, Treatment Patterns, and Outcomes in the Modern Management Era.

BACKGROUND: Among patients with pulmonary arterial hypertension (PAH), acute vasoreactivity testing during right heart catheterization may identify acute vasoresponders, for whom treatment with high-dose calcium channel blockers (CCBs) is recommended. However, long-term outcomes in the current era remain largely unknown. We sought to evaluate the implications of acute vasoreactivity response for long-term response to CCBs and other outcomes. METHODS: Patients diagnosed with PAH between January 1999 and December 2018 at 15 pulmonary hypertension centers were included and analyzed retrospectively. In accordance with current guidelines, acute vasoreactivity response was defined by a decrease of mean pulmonary artery pressure by ≥10 mm Hg to reach <40 mm Hg, without a decrease in cardiac output. Long-term response to CCBs was defined as alive with unchanged initial CCB therapy with or without other initial PAH therapy and World Health Organization functional class I/II and/or low European Society of Cardiology/European Respiratory Society risk status at 12 months after initiation of CCBs. Patients were followed for up to 5 years; clinical measures, outcome, and subsequent treatment patterns were captured. RESULTS: Of 3702 patients undergoing right heart catheterization for PAH diagnosis, 2051 had idiopathic, heritable, or drug-induced PAH, of whom 1904 (92.8%) underwent acute vasoreactivity testing. A total of 162 patients fulfilled acute vasoreactivity response criteria and received an initial CCB alone (n=123) or in combination with another PAH therapy (n=39). The median follow-up time was 60.0 months (interquartile range, 30.8-60.0), during which overall survival was 86.7%. At 12 months, 53.2% remained on CCB monotherapy, 14.7% on initial CCB plus another initial PAH therapy, and the remaining patients had the CCB withdrawn and/or PAH therapy added. CCB long-term response was found in 54.3% of patients. Five-year survival was 98.5% in long-term responders versus 73.0% in nonresponders. In addition to established vasodilator responder criteria, pulmonary artery compliance at acute vasoreactivity testing, low risk status and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels at early follow-up correlated with long-term response and predicted survival. CONCLUSIONS: Our data display heterogeneity within the group of vasoresponders, with a large subset failing to show a sustained satisfactory clinical response to CCBs. This highlights the necessity for comprehensive reassessment during early follow-up. The use of pulmonary artery compliance in addition to current measures may better identify those likely to have a good long-term response.

Local carbachol application induces oral microvascular recruitment and improves gastric tissue oxygenation during hemorrhagic shock in dogs.

Introduction: Hemorrhagic shock is characterized by derangements of the gastrointestinal microcirculation. Topical therapy with nitroglycerine or iloprost improves gastric tissue oxygenation but not regional perfusion, probably due to precapillary adrenergic innervation. Therefore, this study was designed to investigate the local effect of the parasympathomimetic carbachol alone and in combination with either nitroglycerine or iloprost on gastric and oral microcirculation during hemorrhagic shock. Methods: In a cross-over design five female foxhounds were repeatedly randomized into six experimental groups. Carbachol, or carbachol in combination with either nitroglycerine or iloprost were applied topically to the oral and gastric mucosa. Saline, nitroglycerine, or iloprost application alone served as control groups. Then, a fixed-volume hemorrhage was induced by arterial blood withdrawal followed by blood retransfusion after 1h of shock. Gastric and oral microcirculation was determined using reflectance spectrophotometry and laser Doppler flowmetry. Oral microcirculation was visualized with videomicroscopy. Statistics: 2-way-ANOVA for repeated measurements and Bonferroni post-hoc analysis (mean ± SEM; p < 0.05). Results: The induction of hemorrhage led to a decrease of gastric and oral tissue oxygenation, that was ameliorated by local carbachol and nitroglycerine application at the gastric mucosa. The sole use of local iloprost did not improve gastric tissue oxygenation but could be supplemented by local carbachol treatment. Adding carbachol to nitroglycerine did not further increase gastric tissue oxygenation. Gastric microvascular blood flow remained unchanged in all experimental groups. Oral microvascular blood flow, microvascular flow index and total vessel density decreased during shock. Local carbachol supply improved oral vessel density during shock and oral microvascular flow index in the late course of hemorrhage. Conclusion: The specific effect of shifting the autonomous balance by local carbachol treatment on microcirculatory variables varies between parts of the gastrointestinal tract. Contrary to our expectations, the improvement of gastric tissue oxygenation by local carbachol or nitroglycerine application was not related to increased microvascular perfusion. When carbachol is used in combination with local vasodilators, the additional effect on gastric tissue oxygenation depends on the specific drug combination. Therefore, modulation of tissue oxygen consumption, mitochondrial function or alterations in regional blood flow distribution should be investigated.

Practice pattern for the use of intravenous iloprost for the treatment of peripheral vasculopathy in systemic sclerosis: A case-control study from the Italian national multicenter "SPRING" (Systemic Sclerosis Progression InvestiGation) Registry.

Background: Intravenous iloprost has been widely used for the treatment of systemic sclerosis peripheral vasculopathy. No agreement has been found on the regimen and the dosage of intravenous iloprost in different scleroderma subset conditions. This study aimed to evaluate the modalities of intravenous iloprost administration within a large cohort of systemic sclerosis patients from the SPRING Registry and to identify any associated clinical-demographic, instrumental or therapeutic data. Patients and Methods: Data of systemic sclerosis patients treated with intravenous iloprost for at least 1 year (case group) were retrospectively analyzed, including different timing and duration of intravenous iloprost session, and compared with those of untreated patients (control group). Results: Out of 1895 analyzed patients, 937 (49%) received intravenous iloprost treatment, while 958 (51%) were assigned to the control group. Among cases, about 70% were treated every 4 weeks, 24% with an interval of more than 4 weeks, and only 6% of less than 4 weeks. Most patients receiving the treatment every 4 weeks, or less, underwent infusion cycle for 1 day only, while if it was scheduled with an interval of more than 4 weeks, a total number of 5 consecutive days of infusions was the preferred regimen. The comparison between the two groups revealed that patients treated with intravenous iloprost had a higher frequency of DUs (p < 0.001), pitting scars (p < 0.001), diffuse cutaneous involvement (p < 0.001), interstitial lung disease (p < 0.002), as well as higher rates of anti-topoisomerase I, "late" scleroderma pattern at nailfold videocapillaroscopy. These findings were confirmed by multivariate analysis. Conclusion: Our data provide a picture on the Italian use of intravenous iloprost among systemic sclerosis patients and showed that it was usually employed in patients with a more aggressive spectrum of the disease. The disparity of intravenous iloprost treatment strategies in the different centers suggests the need of a rational therapeutical approach based on the clinical characteristics of different patients' subsets.

Prolonged critical avalanche burial for nearly 23 h with severe hypothermia and severe frostbite with good recovery: a case report.

BACKGROUND: Accidental hypothermia with severe frostbite is a rare combination of injuries with a high risk for long-term sequelae. There are widely accepted recommendations for the management of avalanche victims and for frostbite treatment, but no recommendation exists for the treatment of frostbite in severe hypothermic patients, specifically for the management of hypothermic avalanche victims presenting with frostbite. CASE PRESENTATION: We present a case of a previously healthy, 53-year-old male skier who was critically buried by an avalanche at 2300 m of altitude at an ambient temperature of - 8 °C for nearly 23 h. The victim was found with the right hand out of the snow and an air connection to outside. He was somnolent with Glasgow Coma Scale 11 (Eye 4, Verbal 2, Motor 5) and spontaneously breathing, in a severely hypothermic state with an initial core temperature of 23.1 °C and signs of cold injuries in all four extremities. After rescue and active external forced air rewarming in the intensive care unit, the clinical signs of first-degree frostbite on both feet and the left hand vanished, while third- to fourth-degree frostbite injuries became apparent on all fingers of the right hand. After reaching a core body temperature of approximately 36 °C, aggressive frostbite treatment was started with peripheral arterial catheter-directed thrombolysis with alteplase, intravenous iloprost, ibuprofen, dexamethasone and regional sympathicolysis with a right-sided continuous axillary block. After ten months, the patient had no tissue loss but needed neuropathic pain treatment with pregabalin. CONCLUSION: The combination of severe accidental hypothermia and severe frostbite is rare and challenging, as drug metabolism is unpredictable in a hypothermic patient and no recommendations for combined treatment exist. There is general agreement to give hypothermia treatment the priority and to begin frostbite treatment as early as possible after full rewarming of the patient. More evidence is needed to identify the optimal dosage and time point to initiate treatment of frostbite in severely hypothermic patients. This should be taken into consideration by future treatment recommendations.

Effective control of refractory pulmonary hypertension with iloprost inhalation in an infant with congenital absence of the right pulmonary artery: a case report.

Unilateral absence of the pulmonary artery is a rare congenital cardiovascular anomaly that can lead to pulmonary hypertension and poor outcomes. We report the case of a 1-month-old infant with isolated unilateral absence of the pulmonary artery and severe pulmonary hypertension on the right and left sides, respectively. The patient was unresponsive to multiple medications for pulmonary hypertension, and surgical revascularisation was unfeasible. However, iloprost inhalation was effective.

Nebulisation of Paclitaxel, Sotatercept and Iloprost for pulmonary hypertension for lung cancer. From In vitro to In vivo.

Background: Pulmonary hypertension is common symptom among several diseases. The consequences are severe for several organs. Pulmonary hypertension is usually under-diagnosed and the main symptom observed is dyspnea with or without exercise. Currently we have several treatment modalities administered orally, via inhalation, intravenously and subcutaneously. In advanced disease then heart or lung transplantation is considered. The objective of the study was to investigate the optimum method of aerosol production for the drugs: iloprost, paclitaxel and the novel sotatercept. Materials and Methods: In our experiment we used the drugs iloprost, paclitaxel and the novel sotatercept, in an experimental concept of nebulization. We performed nebulization experiments with 3 jet nebulizers and 3 ultrasound nebulizers with different combinations of residual cup designs, and residual cup loadings in order to identify which combination produces droplets of less than 5µm in mass median aerodynamic diameter. Results: We concluded that paclitaxel cannot produce small droplets and is also still very greasy and possible dangerous for alveoli. However; iloprost vs sotatercept had smaller droplet size formation at both inhaled technologies (1.37<2.23 and 1.92<3.11, jet and ultrasound respectively). Moreover; residual cup designs C and G create the smallest droplet size in both iloprost and sotatercept. There was no difference for the droplet formation between the facemask and cone mouthpieces. Discussion: Iloprost and sotatercept can be administered as aerosol in any type of nebulisation system and they are both efficient with the residual cups loaded with small doses of the drug (2.08 and 2.12 accordingly).

Efficacy and safety of iloprost in the treatment of pulmonary arterial hypertension: A systematic review and meta-analysis.

BACKGROUND: The efficacy of iloprost in treating pulmonary arterial hypertension (PAH) is controversial. Adverse reactions such as hypotension may occur during treatment. OBJECTIVES: Aim to evaluate the efficacy and safety of iloprost for PAH. METHODS: Studies were obtained from an electronic search of the CNKI, Wanfang, VIP, SinoMed, PubMed, Medline, Embase, and Cochrane Library databases up to May 18, 2023. A meta-analysis of each study was performed using RevMan 5.4 with a 95 % confidence interval (CI). A randomized or fixed-effects model was applied according to a heterogeneity test. RESULTS: Twelve trials involving 718 participants were selected, including 433 in five randomized controlled trials (RCTs) and 285 in seven prospective clinical trials. All the patients received iloprost inhalation. The short- and prolonged treatment groups significantly improved the 6-minute walking distance (6 MWD). The mortality and clinical deterioration incidences in the iloprost group were not significantly different from those in the control group. The mean pulmonary arterial pressure (mPAP) was reduced after 3 months of iloprost RCTs and 12 months of prospective treatment. Iloprost decreased pulmonary vascular resistance (PVR) by approximately 231.29 units, significantly increased cardiac output (CO), and improved the quality of life (QoL). The main adverse reactions to iloprost treatment were cough (17 %), headache (16.4 %), and flushing (12.4 %). CONCLUSION: Iloprost, either used alone or as adjuvant therapy, can enhance exercise capacity, lower hemodynamic parameters, and improve long-term outcomes. However, the risk of mortality and clinical deterioration remains unknown.