iloprost and Pulmonary-Disease--Chronic-Obstructive

The ventilation/perfusion mismatch in chronic obstructive pulmonary disease (COPD) patients can exacerbate cardiac function as well as pulmonary oxygenation. We hypothesized that inhaled iloprost can ameliorate pulmonary oxygenation with lung mechanics and myocardial function during one-lung ventilation (OLV) in COPD patients combined with poor lung oxygenation.. A total of 40 patients with moderate to severe COPD, who exhibited the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FIO2) <150 mm Hg 30 minutes after initiating OLV, were enrolled in this study. Patients were randomly allocated into either ILO group (n = 20) or Control group (n = 20), in which iloprost (20 μg) and saline were inhaled, respectively. The PaO2/FIO2 ratio, dead space, dynamic compliance, and tissue Doppler imaging with myocardial performance index (MPI) were assessed 30 minutes after initiating OLV (pre-Tx) and 30 minutes after completion of drug inhalation (post-Tx). Repeated variables were analyzed using a linear mixed-model between the groups.. At pre-Tx, no differences were observed in measured parameters between the groups. At post-Tx, PaO2/FIO2 ratio (P < .001) and dynamic compliance (P = .023) were significantly higher and dead space ventilation was significantly lower (P = .001) in iloprost group (ILO group) compared to Control group. Left (P = .003) and right ventricular MPIs (P < .001) significantly decreased in ILO group compared to Control group.. Inhaled iloprost improved pulmonary oxygenation, lung mechanics, and cardiac function simultaneously during OLV in COPD patients with poor lung oxygenation.

Topics: Administration, Inhalation; Adult; Aged; Aged, 80 and over; Female; Humans; Iloprost; Lung; Male; Middle Aged; One-Lung Ventilation; Positive-Pressure Respiration; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Pulmonary Ventilation; Respiratory Mechanics; Treatment Outcome; Vasodilator Agents

There is a high incidence of pulmonary hypertension during the lung transplant peri-operative period, and could lead to a haemodynamic deterioration that may require the need of extracorporeal circulation. Our aim was to study the haemodynamic effects on the pulmonary and systemic circulation of the combination of inhaled nitric oxide and iloprost and oral sildenafil in patients with severe pulmonary hypertension during lung transplant surgery.. Seventeen patients received 10μg of nebulised iloprost during the peri-operative period of the lung transplant when their mean pulmonary pressure exceeded 50mmHg. AU the patients received 50mg of oral sildenafil 30min before anaesthetic induction, 20ppm of inhaled nitric oxide after tracheal intubation. The haemodynamic and respiratory variables were recorded at baseline (after anaesthetic induction), prior to the administering of iloprost, and at 5 and 30min after it was given.. The administering of iloprost significantly reduced the pulmonary arterial pressure and significantly increases the cardiac Índex and the right ventrícular ejection fractíon. There were no signíficant changes occurred in the systemic arterial pressure.. The triple combination significantly reduces the pulmonary pressures in the lung transplant peri-operative and should be considered when there is severe pulmonary hypertension during the surgery or during the immediate post-operative period of lung transplantation.

Topics: Administration, Inhalation; Administration, Oral; Adult; Aged; Cystic Fibrosis; Dobutamine; Drug Therapy, Combination; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Intraoperative Complications; Lung Transplantation; Male; Middle Aged; Nebulizers and Vaporizers; Nitric Oxide; Norepinephrine; Piperazines; Preoperative Care; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Vasodilator Agents

Inhaled iloprost potentially improves hemodynamics and gas exchange in patients with chronic obstructive pulmonary disease (COPD) and secondary pulmonary hypertension (PH).. To evaluate acute effects of aerosolized iloprost in patients with COPD-associated PH.. A randomized, double blind, crossover study was conducted in 16 COPD patients with invasively confirmed PH in a single tertiary care center. Each patient received a single dose of 10 µg iloprost (low dose), 20 µg iloprost (high dose) and placebo during distinct study-visits. The primary end-point of the study was exercise capacity as assessed by the six minute walking distance.. Both iloprost doses failed to improve six-minute walking distance (p = 0.36). Low dose iloprost (estimated difference of the means -1.0%, p = 0.035) as well as high dose iloprost (-2.2%, p<0.001) significantly impaired oxygenation at rest. Peak oxygen consumption and carbon dioxide production differed significantly over the three study days (p = 0.002 and p = 0.003, accordingly). As compared to placebo, low dose iloprost was associated with reduced peak oxygen consumption (-76 ml/min, p = 0.002), elevated partial pressure of carbon dioxide (0.27 kPa, p = 0.040) and impaired ventilation during exercise (-3.0l/min, p<0.001).. Improvement of the exercise capacity after iloprost inhalation in patients with COPD-associated mild to moderate PH is very unlikely.. Controlled-Trials.com ISRCTN61661881.

Topics: Administration, Inhalation; Adult; Aerosols; Aged; Cross-Over Studies; Female; Humans; Hypertension, Pulmonary; Iloprost; Male; Oxygen; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange

Nonselective systemic vasodilators worsen ventilation perfusion (V/Q) matching and gas exchange in patients with chronic obstructive pulmonary disease (COPD). Inhaled iloprost has the potential to act preferentially in ventilated regions of the lung, thereby reducing pulmonary hypertension (PH) while alveolar ventilation is still maintained.. To investigate the acute effects of inhaled iloprost on V/Q matching in patients with COPD and PH.. Ten males with COPD and PH on echocardiography were evaluated before and after inhaling 2 doses of iloprost (2.5 microg). Measurements included lung function, arterial blood gas, 6-min walk test (6MWT) as well as ventilatory equivalents for oxygen (V(E)/VO(2)) and carbon dioxide (V(E)/VCO(2)) taken at baseline, 30 min following each dose of iloprost, and 2 h after the second dose.. Mean differences in V(E)/VCO(2) and V(E)/VO(2) were -13.3 (95% CI -36.5 to -2.7; p = 0.002) and -15.0 (95% CI -36.7 to -0.4; p = 0.02), respectively, and the mean change in (A-a) gradient was -3.7 mm Hg (95% CI -6.1 to -1.0; p = 0.01) after a single dose of iloprost, whereas mean improvement in 6MWT was 49.8 m (95% CI 14.8 to 84.7; p = 0.02). Arterial blood gas, venous admixture, dead space fraction and lung functions were maintained after iloprost. The effects of iloprost were reproducible after the second dose. All measurements returned to baseline 2 h after the last dose. No adverse effects on systemic blood pressure or oxygen saturation were seen.. Iloprost inhalation was safe in patients with COPD and PH, and was associated with improved V/Q matching and exercise tolerance.

Topics: Administration, Inhalation; Aged; Blood Gas Analysis; Exercise Tolerance; Humans; Hypertension, Pulmonary; Iloprost; Male; Nebulizers and Vaporizers; Oxygen Consumption; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Vasodilator Agents

Topics: Humans; Iloprost; Lung; One-Lung Ventilation; Pulmonary Disease, Chronic Obstructive; Pulmonary Ventilation

Topics: Humans; Iloprost; One-Lung Ventilation; Pulmonary Disease, Chronic Obstructive; Pulmonary Ventilation

Involvement of pulmonary vascular remodelling is a characteristic sign in COPD. Vascular mediators such as vascular endothelial growth factor (VEGF) and prostacyclin may regulate fibroblast activity. The objective was to study the synthesis of VEGF and interactions with prostacyclin and transforming growth factor (TGF)-β. Iloprost and TGF-β. VEGF is synthesized in high amounts by distal lung fibroblasts and may have a crucial role in ongoing vascular remodelling processes in the distal lung compartments.

Topics: Aged; Biglycan; Cell Movement; Cell Proliferation; Cells, Cultured; Cyclooxygenase Inhibitors; Fibroblasts; Heparan Sulfate Proteoglycans; Humans; Iloprost; Indomethacin; Lung; Middle Aged; Pulmonary Disease, Chronic Obstructive; Receptors, Vascular Endothelial Growth Factor; Transforming Growth Factor beta1; Vascular Endothelial Growth Factor A; Vascular Remodeling

Patients with severe pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD) present a poor outcome. Specific PH treatment could improve the clinical and hemodynamic status of these patients but may worsen arterial blood gases.. Our study retrospectively included 28 patients with severe precapillary PH (mean pulmonary arterial pressure >35 mm Hg) associated with mild-to-moderate COPD [forced expiratory volume in 1 s (FEV1) >50% predicted]. All patients underwent specific pulmonary arterial hypertension (PAH) treatment as mono-, bi- or triple therapy.. Our single-center study was conducted based on retrospective data of 537 right heart catheterizations (RHCs) performed on patients with COPD from January 2004 to June 2014. An echocardiography, comprehensive blood tests, pulmonary function tests, and a high-resolution computed tomography were performed before the RHCs. All patients underwent RHC with a Swan-Ganz catheter.. Compared to baseline, patients treated with specific PAH drugs showed a significant increase in cardiac index at long term (2.5 ± 0.7 liters/min/m2 at baseline vs. 3.2 ± 0.6 liters/min/m2 at 6/12 months; p = 0.003) as well as a decrease in pulmonary vascular resistance in the long term (8.4 ± 4.2 Wood units at baseline vs. 5 ± 1.7 Wood units at 6/12 months; p = 0.008). There was a slight decrease in arterial oxygen tension (PaO2) after 3 months of treatment (-2.4 ± 7.21 mm Hg; p = 0.066). During a median follow-up of 3 years, 12 patients (42.8%) died (including all causes of death).. This preliminary report suggests that the use of specific PH therapy in severe PH associated with mild-to-moderate COPD can improve pulmonary hemodynamic parameters, with worsening of PaO2, which had no clinical significance and did not lead to specific PAH therapy withdrawal in any patient.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Blood Gas Analysis; Calcium Channel Blockers; Carbon Dioxide; Endothelin Receptor Antagonists; Epoprostenol; Female; Forced Expiratory Volume; Humans; Hypertension, Pulmonary; Iloprost; Kaplan-Meier Estimate; Male; Middle Aged; Partial Pressure; Phosphodiesterase 5 Inhibitors; Proportional Hazards Models; Pulmonary Diffusing Capacity; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Severity of Illness Index; Treatment Outcome; Vasodilator Agents; Vital Capacity

Pulmonary endothelial prostacyclin appears to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The effect of treatment with a prostacyclin analog in animal models of previously established COPD is unknown. We evaluated the short- and long-term effect of iloprost on inflammation and airway hyperresponsiveness (AHR) in a murine model of COPD. Nineteen mice were exposed to LPS/elastase, followed by either three doses of intranasal iloprost or saline. In the long-term treatment experiment, 18 mice were exposed to LPS/elastase and then received 6 wk of iloprost or were left untreated as controls. In the short-term experiment, iloprost did not change AHR but significantly reduced serum IL-5 and IFN-γ. Long-term treatment with iloprost for both 2 and 6 wk significantly improved AHR. After 6 wk of iloprost, there was a reduction in bronchoalveolar lavage (BALF) neutrophils, serum IL-1β (30.0 ± 9.2 vs. 64.8 ± 7.4 pg/ml, P = 0.045), IL-2 (36.5 ± 10.6 vs. 83.8 ± 0.4 pg/ml, P = 0.01), IL-10 (75.7 ± 9.3 vs. 96.5 ± 3.5 pg/ml, P = 0.02), and nitrite (15.1 ± 5.4 vs. 30.5 ± 10.7 μmol, P = 0.01). Smooth muscle actin (SMA) in the lung homogenate was also significantly reduced after iloprost treatment (P = 0.02), and SMA thickness was reduced in the small and medium blood vessels after iloprost (P < 0.001). In summary, short- and long-term treatment with intranasal iloprost significantly reduced systemic inflammation in an LPS/elastase COPD model. Long-term iloprost treatment also reduced AHR, serum nitrite, SMA, and BALF neutrophilia. These data encourage future investigations of prostanoid therapy as a novel treatment for COPD patients.

Topics: Administration, Intranasal; Animals; Anti-Inflammatory Agents; Cytokines; Disease Models, Animal; Drug Evaluation, Preclinical; Iloprost; Lipopolysaccharides; Male; Mice, Inbred C57BL; Neutrophil Infiltration; Pulmonary Disease, Chronic Obstructive; Respiratory Hypersensitivity

The aim of the current study is to evaluate acute vasoreactivity test (AVT) results in severe pulmonary hypertension patients with chronic obstructive pulmonary disease and to compare the demographical, clinical, and laboratory variables in positive and negative cases.. This retrospective, clinical study was performed on 29 cases in the departments of cardiology and chest diseases of our tertiary care center. AVT was positive in 12 (41.4%) cases and negative in 17 (58.6%) cases. Demographical variables, cardiopulmonary indicators, and laboratory findings were compared in these two subgroups.. The mean age was 62.3±7.8 years for AVT negative group, while it was 64.8±7.3 years in AVT positive group (P=0.38). Except for the changes in systolic, diastolic, and mean pulmonary arterial pressures before and after iloprost administration, there were no statistically significant differences regarding any of the parameters under investigation in both groups.. Despite the high rate of positivity for AVT in severe pulmonary hypertension patients with chronic obstructive pulmonary disease, none of the variables under investigation displayed a noteworthy difference between AVT negative and positive groups. Identification of factors likely to influence AVT results is important for establishment of appropriate treatment protocols especially for AVT negative cases.

Topics: Administration, Inhalation; Aged; Arterial Pressure; Cardiac Output; Diagnostic Techniques, Cardiovascular; Female; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Predictive Value of Tests; Prognosis; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Severity of Illness Index; Tertiary Care Centers; Turkey; Vasodilator Agents

Prostacyclin analogs are potent vasodilators and possess anti-inflammatory properties. However, the effect of prostacyclin on extracellular matrix (ECM) in COPD is not well known. Collagen fibrils and proteoglycans are essential ECM components in the lung and fibroblasts are key players in regulating the homeostasis of ECM proteins. The aim was to study the synthesis of prostacyclin and its effect on fibroblast activity and ECM production, and in particular collagen I and the collagen-associated proteoglycans biglycan and decorin.. Parenchymal lung fibroblasts were isolated from lungs from COPD patients (GOLD stage IV) and from lungs and transbronchial biopsies from control subjects. The prostacyclin analog iloprost was used to study the effect of prostacyclin on ECM protein synthesis, migration, proliferation and contractile capacity of fibroblasts.. TGF-β1 stimulation significantly increased prostacyclin synthesis in fibroblasts from COPD patients (p < 0.01), but showed no effect on fibroblasts from control subjects. Collagen I synthesis was decreased by iloprost in both control and COPD fibroblasts (p < 0.05). Conversely, iloprost significantly altered biglycan and decorin synthesis in control fibroblasts, but iloprost displayed no effect on these proteoglycans in COPD fibroblasts. Proliferation rate was reduced (p < 0.05) and contractile capacity was increased in COPD fibroblasts (p < 0.05) compared to control fibroblasts. Iloprost decreased proliferative rate in control fibroblasts (p < 0.05), whereas iloprost attenuated contraction capacity in both COPD (p < 0.01) and control fibroblasts (p < 0.05).. Iloprost reduced collagen I synthesis and fibroblast contractility but did not affect the collagen-associated proteoglycans or proliferation rate in fibroblasts from COPD patients. Enhanced prostacyclin production could lead to improper collagen network fibrillogenesis and a more emphysematous lung structure in severe COPD patients.

Topics: Adult; Biglycan; Biopsy; Case-Control Studies; Cell Movement; Cell Proliferation; Cells, Cultured; Collagen Type I; Decorin; Epoprostenol; Female; Fibroblasts; Humans; Iloprost; Lung; Male; Phenotype; Pulmonary Disease, Chronic Obstructive; Transforming Growth Factor beta1; Young Adult

Pulmonary hypertension secondary to respiratory disease most often occurs as a complication of chronic obstructive pulmonary disease, which currently constitutes one of the leading causes of death. Some patients with hypoxaemia reveal "out of proportion" pulmonary hypertension with inappropriate increase of pulmonary artery pressure. Iloprost, analogue of prostacyclin, dilates systemic vessels and pulmonary vessels in particular if administered by inhalation. It appears to be important, life-saving, complementary therapy. However, there is no evidence for its routine use in out of proportion arterial pulmonary hypertension. This case study presents a 44-year old man with chronic obstructive pulmonary disease and "out of proportion" pulmonary hypertension. We present the results of his treatment with iloprost.. In a patient with "out of proportion" pulmonary hypertension due to chronic obstructive pulmonary disease, inhaled iloprost led to improvement in clinical status and echocardiographic parameters, including a reduction of right ventricular systolic pressure.

Topics: Adult; Blood Pressure; Humans; Hypertension, Pulmonary; Iloprost; Male; Pulmonary Disease, Chronic Obstructive; Treatment Outcome; Vasodilator Agents

The etiology of chronic obstructive pulmonary disease (COPD) is complex and involves an aberrant inflammatory response. Prostaglandin (PG)E2 is elevated in COPD, is a key modulator of lung fibroblast functions, and may influence COPD progression. Most studies evaluating the effects of PGE2 on lung fibroblasts have used acute exposures. The current study evaluated whether longer-term exposure would induce attenuation of PGE2 signaling as part of an autoregulatory pathway. Human fetal lung fibroblasts were pretreated with PGE2 for 24 hours, and migration and cAMP accumulation in response to acute stimulation with PGE2 were assessed. Fibroblasts from adults with and without COPD were pretreated, and migration was assessed. PGE2 pretreatment attenuated subsequent PGE2-mediated inhibition of chemotaxis and cAMP stimulation. This attenuation was predominantly due to an increase in phosphodiesterase (PDE)4-mediated degradation of cAMP rather than to decreased activation of PGE2 receptors (receptor desensitization). Albuterol- and iloprost-mediated signaling were also attenuated after PGE2 pretreatment, suggesting that activation of PDE4 was able to broadly modulate multiple cAMP-coupled pathways. Lung fibroblasts from adult control subjects pretreated with PGE2 also developed attenuation of PGE2-mediated inhibition of chemotaxis. In contrast, fibroblasts obtained from patients with COPD maintained inhibitory PGE2 signaling after PGE2 pretreatment. These data identify a PDE4-mediated attenuation of PGE2 inhibitory signaling in normal fibroblasts that appears to be altered in COPD fibroblasts. These alterations may contribute to COPD pathogenesis and could provide novel therapeutic targets.

Topics: Adrenergic beta-2 Receptor Agonists; Albuterol; Aminopyridines; Benzamides; Cells, Cultured; Chemotaxis; Colforsin; Cyclic AMP; Cyclic Nucleotide Phosphodiesterases, Type 4; Cyclopropanes; Dinoprostone; Fibroblasts; Fibronectins; Gene Expression; Humans; Iloprost; Isoenzymes; Lung; Phosphodiesterase 4 Inhibitors; Pulmonary Disease, Chronic Obstructive; Receptors, Epoprostenol; Receptors, Prostaglandin; Receptors, Prostaglandin E, EP2 Subtype; Rolipram; Second Messenger Systems

Pulmonary hypertension is an important complication of COPD. A small subset of patients with COPD have severe pulmonary hypertension (PH) that is out of proportion to the mild increase in pulmonary arterial pressure observed commonly. Severe PH associated with COPD is associated with increased morbidity and mortality. Treatment options in this group of patients are limited with no conclusive evidence of benefit when drugs approved for treatment of pulmonary arterial hypertension are used. We describe a patient with severe PH associated with COPD who improved clinically and hemodynamically when treated with inhaled iloprost. The improvement was sustained for 2 years. Severe PH in patients with COPD needs to be recognized and novel treatment approaches considered.

Topics: Administration, Inhalation; Aged; Blood Gas Analysis; Dose-Response Relationship, Drug; Drug Administration Schedule; Echocardiography, Transesophageal; Follow-Up Studies; Humans; Hypertension, Pulmonary; Iloprost; Male; Maximum Tolerated Dose; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Risk Assessment; Severity of Illness Index; Treatment Outcome; Vasodilator Agents