Dexamethasone improves pulmonary hemodynamics in COPD-patients going to altitude: A randomized trial

Lichtblau, Mona; Furian, Michael; Aeschbacher, Sayaka S.; Bisang, Maya; Ulrich, Silvia; Saxer, Stéphanie; Sheraliev, Ulan; Marazhapov, Nuriddin H.; Osmonov, Batyr; Estebesova, Bermet; Sooronbaev, Talant; Bloch, Konrad E.; Ulrich, Silvia

doi:10.1016/j.ijcard.2018.12.052

Cited by 17 publications

(24 citation statements)

References 24 publications

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“…Inhaled NO Soluble guanylate cyclase stimulator decreases sPAP and improves oxygenation in HAPE-prone subjects at HA [112] reduces mPAP and PVR in HAPE patients at HA [113] decreases PAP and PVR in hypoxia-breathing healthy subjects [112] Sildenafil Phosphodiesterase 5 inhibitor prevents an increase in PAP and PVR in hypoxia-breathing healthy subjects [20,151] decreases sPAP and improves exercise capacity under hypoxic breathing and at HA in healthy subjects [114] decreases sPAP and improves blood oxygenation upon acute HA exposure in healthy subjects [117] attenuates sPAP increase and RV dysfunction upon acute HA exposure in healthy subjects [22] Tadalafil Phosphodiesterase 5 inhibitor attenuates an increase in PAP and prevents HAPE development [64] Bosentan Endothelin receptor receptor A/B antagonist prevents an increase in sPAP and PVR in hypoxia breathing healthy subjects [125][126][127] prevents an increase in sPAP and improves arterial oxygen saturation in healthy subjects exposed to HA [122] Sitaxentan Endothelin receptor antagonist prevents an increase of PAP and PVR and exercise capacity decline in hypoxia-breathing healthy subjects [129] reduces PVR and improves lung diffusion capacity and exercise capacity in healthy subjects exposed to HA [152] reduces PAP and PVR and improves exercise capacity in healthy subjects exposed to HA [129] Nifedipine Calcium channel blocker reduces PAP and improves HAPE symptoms [66] attenuates an increase in PAP and prevents HAPE development [63] Dexamethasone Anti-inflammatory and immunosuppressive agent attenuates an increase in PAP and prevents HAPE development [64] attenuates an increase in TRG and PVR and improves oxygenation in COPD patients at HA [153] attenuates an increase in TRG and improves exercise capacity [154] Acetazolamide Carbonic anhydrase inhibitor prevents an increase in TRG in hypoxia-breathing healthy subjects [136] HA, high altitude; PAP, pulmonary artery pressure; sPAP, systolic pulmonary artery pressure; RVSP, right ventricular systolic pressure; TRG, tricuspid regurgitation gradient; PVR, pulmonary vascular resistance; HAPE, high altitude pulmonary edema; COPD, chronic obstructive pulmonary disease; NOS, nitric oxide synthase; PAEC, pulmonary artery endothelial cell; PASMC, pulmonary artery smooth muscle cell.…”

Section: Mechanism Of Action Effects Referencesmentioning

confidence: 99%

Pulmonary Hypertension in Acute and Chronic High Altitude Maladaptation Disorders

Sydykov

Mamazhakypov

Maripov

et al. 2021

IJERPH

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Alveolar hypoxia is the most prominent feature of high altitude environment with well-known consequences for the cardio-pulmonary system, including development of pulmonary hypertension. Pulmonary hypertension due to an exaggerated hypoxic pulmonary vasoconstriction contributes to high altitude pulmonary edema (HAPE), a life-threatening disorder, occurring at high altitudes in non-acclimatized healthy individuals. Despite a strong physiologic rationale for using vasodilators for prevention and treatment of HAPE, no systematic studies of their efficacy have been conducted to date. Calcium-channel blockers are currently recommended for drug prophylaxis in high-risk individuals with a clear history of recurrent HAPE based on the extensive clinical experience with nifedipine in HAPE prevention in susceptible individuals. Chronic exposure to hypoxia induces pulmonary vascular remodeling and development of pulmonary hypertension, which places an increased pressure load on the right ventricle leading to right heart failure. Further, pulmonary hypertension along with excessive erythrocytosis may complicate chronic mountain sickness, another high altitude maladaptation disorder. Importantly, other causes than hypoxia may potentially underlie and/or contribute to pulmonary hypertension at high altitude, such as chronic heart and lung diseases, thrombotic or embolic diseases. Extensive clinical experience with drugs in patients with pulmonary arterial hypertension suggests their potential for treatment of high altitude pulmonary hypertension. Small studies have demonstrated their efficacy in reducing pulmonary artery pressure in high altitude residents. However, no drugs have been approved to date for the therapy of chronic high altitude pulmonary hypertension. This work provides a literature review on the role of pulmonary hypertension in the pathogenesis of acute and chronic high altitude maladaptation disorders and summarizes current knowledge regarding potential treatment options.

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Section: Mechanism Of Action Effects Referencesmentioning

confidence: 99%

Pulmonary Hypertension in Acute and Chronic High Altitude Maladaptation Disorders

Sydykov

Mamazhakypov

Maripov

et al. 2021

IJERPH

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“…The primary outcome of the main trial, the effect of dexamethasone on the incidence of AMS/ARAHE (9), nocturnal arterial oxygen saturation (8), breathing pattern and basic echocardiographic findings have been published (16). The particular focus of the present study was the prevalence and type of RLS evaluated by contrast echocardiography at 760 m and 3,100 m with placebo and dexamethasone.…”

Section: Methodsmentioning

confidence: 99%

“…Echocardiographic recordings were obtained with a real-time phased-array sector scanner (CX 50; Philips Respironics, Zofingen, Switzerland) with an integrated color Doppler system and a transducer containing crystal sets for imaging (1-5 MHz) and for continuous-wave Doppler recording. Echocardiography was performed according to the guidelines of the European Association of Echocardiography (14) and a previous report of the study (16). The transtricuspid pressure gradient [right ventricular(RV)/ right atrial (RA) pressure gradient) was calculated from peak systolic velocity (V max) of the tricuspid regurgitation with the simplified Bernoulli equation: ⌬P ϭ 4 ϫ V max 2 .…”

Section: Methodsmentioning

confidence: 99%

“…It has been shown that patients with mild to moderate COPD tolerate exposure to altitude generally well without severe adverse events. However, impairments of exercise capacity, postural control, more severe exertional oxygen desaturation, increased central sleep apnea, and, of interest, increased PAP were demonstrated in COPD during a short stay at altitude (8,9,16,17,26). Glucocorticosteroids such as dexamethasone not only are used to treat airway inflammation and airflow obstruction in exacerbated COPD (27) but are commonly used to treat acute high-altitude illnesses.…”

Section: Introductionmentioning

confidence: 99%

“…Glucocorticosteroids such as dexamethasone not only are used to treat airway inflammation and airflow obstruction in exacerbated COPD (27) but are commonly used to treat acute high-altitude illnesses. We recently showed that dexamethasone mitigated the PAP increase when patients with mild to moderate COPD were exposed to 3,100 m (16).…”

Section: Introductionmentioning

confidence: 99%

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Right-to-left shunts in lowlanders with COPD traveling to altitude: a randomized controlled trial with dexamethasone

Lichtblau

Furian

Aeschbacher

et al. 2020

Journal of Applied Physiology

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Right-to-left shunts (RLS) are prevalent in patients with chronic obstructive pulmonary disease (COPD) and might exaggerate oxygen desaturation, especially at altitude. The aim of this study was to describe the prevalence of RLS in patients with COPD traveling to altitude and the effect of preventive dexamethasone. Lowlanders with COPD [Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1–2, oxygen saturation assessed by pulse oximetry ([Formula: see text]) >92%] were randomized to dexamethasone (4 mg bid) or placebo starting 24 h before ascent from 760 m and while staying at 3,100 m for 48 h. Saline-contrast echocardiography was performed at 760 m and after the first night at altitude. Of 87 patients (81 men, 6 women; mean ± SD age 57 ± 9 yr, forced expiratory volume in 1 s 89 ± 22% pred, [Formula: see text] 95 ± 2%), 39 were assigned to placebo and 48 to dexamethasone. In the placebo group, 19 patients (49%) had RLS, of which 13 were intracardiac. In the dexamethasone group 23 patients (48%) had RLS, of which 11 were intracardiac ( P = 1.0 vs. dexamethasone). Eleven patients receiving placebo and 13 receiving dexamethasone developed new RLS at altitude ( P = 0.011 for both changes, P = 0.411 between groups). RLS prevalence at 3,100 m was 30 (77%) in the placebo and 36 (75%) in the dexamethasone group ( P = not significant). Development of RLS at altitude could be predicted at lowland by a higher resting pulmonary artery pressure, a lower arterial partial pressure of oxygen, and a greater oxygen desaturation during exercise but not by treatment allocation. Almost half of lowlanders with COPD revealed RLS near sea level, and this proportion significantly increased to about three-fourths when traveling to 3,100 m irrespective of dexamethasone prophylaxis. NEW & NOTEWORTHY The prevalence of intracardiac and intrapulmonary right-to-left shunts (RLS) at altitude in patients with chronic obstructive pulmonary disease (COPD) has not been studied so far. In a large cohort of patients with moderate COPD, our randomized trial showed that the prevalence of RLS increased from 48% at 760 m to 75% at 3,100 m in patients taking placebo. Preventive treatment with dexamethasone did not significantly reduce the altitude-induced recruitment of RLS. Development of RLS at 3,100 m could be predicted at 760 m by a higher resting pulmonary artery pressure and arterial partial pressure of oxygen and a more pronounced oxygen desaturation during exercise. Dexamethasone did not modify the RLS prevalence at 3,100 m.

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Luteolin suppresses inflammation and oxidative stress in chronic obstructive pulmonary disease through inhibition of the NOX4‐mediated NF‐κB signaling pathway

Wang

et al. 2023

Immunity Inflam & Disease

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Introduction Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation that predominantly affects the lung and peripheral airways. Previous investigation has underlined the efficacy of luteolin in the treatment of inflammation‐related symptoms. Accordingly, our study concentrates on unveiling the effect of luteolin on COPD. Methods Mice or A549 cells were treated with cigarette smoke (CS) to establish COPD models in vivo and in vitro. Then, the serum and bronchoalveolar lavage fluid of mice were harvested. The lung tissues of mice were subjected to hematoxylin‐eosin staining to observe the degree of damage. The inflammation and oxidative stress factors level were calculated via enzyme‐linked immunosorbent assay and quantitative real‐time polymerase chain reaction. The expressions of nuclear factor‐kappa B (NF‐κB) pathway‐related factors were detected by Western blot. Results In in vivo experiments, CS treatment reduced the weight of mice and promoted lung tissue damage, while luteolin attenuated the effect of CS on the mice. Moreover, luteolin inhibited the inflammation factors level, oxidative stress, and NADPH oxidase 4 (NOX4)‐mediated NF‐κB signaling pathway in CS‐induced COPD mice. Similar results were obtained in in vitro experiments that luteolin alleviated CS‐induced inflammation, oxidative stress, and NOX4‐mediated NF‐κB signaling pathway activation in CS‐treated A549 cells. Besides, NOX4 overexpression offset the impacts of luteolin on the CS‐induced A549 cells. Conclusion Luteolin alleviates inflammation and oxidative stress in COPD via NOX4‐mediated NF‐κB signaling pathway, which provides a theoretical basis for the treatment of COPD with luteolin.

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Dexamethasone improves pulmonary hemodynamics in COPD-patients going to altitude: A randomized trial

Cited by 17 publications

References 24 publications

Pulmonary Hypertension in Acute and Chronic High Altitude Maladaptation Disorders

Pulmonary Hypertension in Acute and Chronic High Altitude Maladaptation Disorders

Right-to-left shunts in lowlanders with COPD traveling to altitude: a randomized controlled trial with dexamethasone

Luteolin suppresses inflammation and oxidative stress in chronic obstructive pulmonary disease through inhibition of the NOX4‐mediated NF‐κB signaling pathway

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