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Background: Recent guidelines recommend riociguat, a soluble guanylate cyclase (sGC) stimulator, and the type 5 phosphodiesterase inhibitor (PDE5i) tadalafil or sildenafil as treatments for pulmonary arterial hypertension. We compared the safety profiles of sildenafil, tadalafil, and riociguat in pulmonary hypertension.Methods: We combined two approaches. First, we performed a meta-analysis of safety data extracted from randomized controlled trials. Second, we conducted a disproportionality analysis of data from VigiBase, the World Health Organization's global database of individual case safety reports, to compare the safety profiles with real-life data.Results: In the meta-analysis, a significant difference between the three drugs was only detected for gastrointestinal disorders, in disfavor of riociguat (P < .01 for interaction). In the disproportionality analysis, the use of riociguat was associated with fewer reports of visual disorders but increased reporting of gastrointestinal, hemorrhagic, and musculoskeletal disorders compared with sildenafil and tadalafil. Pharmacovigilance signals of hearing/vestibular disorders were heterogeneous: vestibular disorders (dizziness) were reported more frequently for riociguat, whereas hearing disorders (deafness) were reported less frequently compared with PDE5is.Conclusions: The safety profiles of PDE5is and sGC stimulators significantly differ in pulmonary hypertension. Accordingly, there is a safety rationale in switching between PDE5is and sGC stimulators because of their different side effects.Trial Registry: PROSPERO; No.: CRD42016051986; URL: https://www.crd.york.ac.uk/prospero/. [ABSTRACT FROM AUTHOR]

The author reflects on the potential of the use of fractional exhaled nitric oxide (FENO) for treatment of asthma, with particular focus on initial equipment cost and cost of the tests preventing the incorporation of FENO into clinical management. He discusses a study by Mummadi and Hahn within the issue, highlighting the challenges of achieving reimbursement coverage for the use of FENO and its widespread coverage in the U.S.

The article presents a study on the effect of inhaled ciclesonide in asthma, airway hyperresponsiveness (AHR), exhaled nitric oxide, and eosinophil levels in induced sputum. 21 asthmatics underwent a randomized, double-blind, crossover study in which they inhaled ciclesonide in different concentrations and placebo for 7 days and eNO, AHR, and eosinophil levels were assessed. Results indicate inhalation of ciclesonide significantly reduced eNO, AHR, and Forced Expiratory Volume (FEV) improved.

The article presents a study on the usefulness of exhaled nitric oxide (eNO) and induced-sputum eosinophils (sEos) for the long term control of eosinophilic asthma. 14 asthma patients underwent clinical evaluation and pulmonary function tests (PFTs), methacholine tests, and eNO and sEos counts. Results show a significant decrease in eNo and sEos counts after 6 months and patients treated with antiinflammatory markers showed lesser symptoms and exacerbations.

Study objectives: In patients with pulmonary hypertension (PH) secondary to congestive heart failure, inhaled nitric oxide (NO) increases pulmonary vascular smooth-muscle intracellular cyclic guanosine monophosphate (cGMP) concentration, thereby decreasing pulmonary vascular resistance (PVR) and increasing cardiac index (CI). However, these beneficial effects of inhaled NO are limited in magnitude and duration, at least in part due to cGMP hydrolysis by the type 5 isoform of phosphodiesterase (PDE5). The goal of this study was to determine the acute pulmonary and systemic hemodynamic effects of the selective PDE5 inhibitor, sildenafil, administered alone or in combination with inhaled NO in patients with congestive heart failure and PH. Design: Single center, case series, pharmacohemodynamic study. Setting: Cardiac catheterization laboratory of a tertiary care academic teaching hospital. Patients: We studied 11 patients with left ventricular systolic dysfunction due to coronary artery disease or idiopathic dilated cardiomyopathy who had PH. Interventions: We administered oral sildenafil (50 mg), inhaled NO (80 ppm), and the combination of sildenafil and inhaled NO during right-heart and micromanometer left-heart catheterization. Measurements and results: Sildenafil administered alone decreased mean pulmonary artery pressure by 12 ± 5%, PVR by 12 ± 5%, systemic vascular resistance (SVR) by 13 ± 6%, and pulmonary capillary wedge pressure by 12 ± 7%, and increased CI by 14 ± 5% (all p <0.05) 11± SEMI. The combination of inhaled NO and sildenafil decreased PVR by 50 ± 4%, decreased SVR by 24 ± 3%, and increased CI by 30 ± 4% (all p < 0.01). These effects were greater than those observed with either agent alone (p < 0.05). In addition, sildenafil prolonged the pulmonary vasodilator effect of inhaled NO. Administration of sildenafil alone or in combination with inhaled NO did not change systemic arterial pressure or indexes of myocardial systolic or diastolic function. Conclusions: PDE5 inhibition with sildenafil improves cardiac output by balanced pulmonary and systemic vasodilation, and augments and prolongs the hemodynamic effects of inhaled NO in patients with chronic congestive heart failure and PH. [ABSTRACT FROM AUTHOR]

Investigates 10 consecutive patients with primary pulmonary hypertension (PPH) using iNO, iloprost aerosol, and oral sildenafil to test acute hemodynamic response during right-heart catheterization. Indication that all three substances improved pulmonary hemodynamics in patients with PPH; Observation that the most prominent hemodynamic effects and improvement with oxygenation were due to iloprost aerosol.

Study objectives: The effects of inhaled nitric oxide (NO) on hemodynamics and right ventricular (RV) contractility were compared with those of nitroprusside and nifedipine in 14 patients with severe chronic pulmonary hypertension. Study design: Micromanometer and balloon-tipped right heart catheterization were performed. Inhaled NO, IV nitroprusside, and sublingual nifedipine were administered sequentially while patients breathed > 90% oxygen. Setting: Cardiac catheterization laboratory in a tertiary care teaching hospital. Patients: Fourteen patients with severe pulmonary hypertension unrelated to left ventricular dysfunction. Measurements and results: During NO inhalation, mean systemic arterial pressure (MAP) was unchanged, but pulmonary artery (PA) pressure ([mean ± SEM] 49 ± 2 mm Hg vs 44 ± 2 mm Hg; p < 0.01), pulmonary vascular resistance (PVR; 829 ± 68 vs 669 ± 64 dyne · s · cm[sup -5]; p < 0.01) and RV end-diastolic pressure (RVEDP; 12 ± 1 vs 10 ± 1 mm Hg; p < 0.01) decreased. Stroke volume index (SVI; 31 ± 2 vs 35 ± 3 mL/m²; p < 0.05) increased, and the first derivative of RV pressure at 15 mm Hg developed pressure (RV +dP/dt at DP15) was unchanged. During nitroprusside administration, MAP decreased (105 ± 5 vs 76 ± 5 mm Hg; p < 0.01), PA was unchanged (48 ± 2 vs 45 ± 3 mm Hg; p = not significant), and PVR decreased (791 ± 53 vs 665 ± 53 dyne · s · cm[sup -5]; p < 0.01). RV +dP/dt at DP15 increased (425 ± 22 vs 465 ± 29 mm Hg/s; p < 0.05), but SVI was unchanged. Nifedipine decreased MAP (103 ± 5 vs 94 ± 5 mm Hg; p < 0.01), PA and PVR were unchanged, RVEDP increased (12 ± 1 vs 14 ± 2 mm Hg; p < 0.01), and RV +dP/dt at DP15 decreased (432 ± 90 vs 389 ± 21 mm Hg/s; p < 0.05). Conclusions: Inhaled NO is a selective pulmonary vasodilator in patients with chronic... [ABSTRACT FROM AUTHOR]

The author reflects on the use of mechanical ventilation for the treatment of acute respiratory syndrome (ARDS) and lung injury among patients with A(H1N1) pandemic. He argues that nitric oxide supplement for ventilator-dependent patients with severe ARDS must not be considered as care standard for patients with severe hypoxic respiratory failure. The author concludes that extracorporeal membrane oxygenation (ECMO) is still best to offer for patients with life-threatening respiratory failure.

The article presents abstracts of the poster presentations at the Chest 2006 conference about chronic obstructive pulmonary disease (COPD) pharmacology. They include "Acute Effects of Inhaled Nitric Oxide and Sildenafil on Pulmonary Vascular Hemodynamics in COPD," "The Effect of Iloprost Inhalation on Gas Exchange in Patients With COPD," and "Statins Protect Smokers From Lung Disease."

The article presents the case study of a 33-year-old woman with idiopathic pulmonary arterial hypertension and developed a profound hemodynamic response to inhaled nitric oxide and riociguat.