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1.
J Med Internet Res ; 23(10): e25163, 2021 10 08.
Article in English | MEDLINE | ID: covidwho-1496813

ABSTRACT

BACKGROUND: Pulmonary arterial hypertension restricts the ability of patients to perform routine physical activities. As part of pulmonary arterial hypertension treatment, inhaled iloprost can be administered via a nebulizer that tracks inhalation behavior. Pulmonary arterial hypertension treatment is guided by intermittent clinical measurements, such as 6-minute walk distance, assessed during regular physician visits. Continuous digital monitoring of physical activity may facilitate more complete assessment of the impact of pulmonary arterial hypertension on daily life. Physical activity tracking with a wearable has not yet been assessed with simultaneous tracking of pulmonary arterial hypertension medication intake. OBJECTIVE: We aimed to digitally track the physical parameters of patients with pulmonary arterial hypertension who were starting treatment with iloprost using a Breelib nebulizer. The primary objective was to investigate correlations between changes in digital physical activity measures and changes in traditional clinical measures and health-related quality of life over 3 months. Secondary objectives were to evaluate inhalation behavior, adverse events, and changes in heart rate and sleep quality. METHODS: We conducted a prospective, multicenter observational study of adults with pulmonary arterial hypertension in World Health Organization functional class III who were adding inhaled iloprost to existing pulmonary arterial hypertension therapy. Daily distance walked, step count, number of standing-up events, heart rate, and 6-minute walk distance were digitally captured using smartwatch (Apple Watch Series 2) and smartphone (iPhone 6S) apps during a 3-month observation period (which began when iloprost treatment began). Before and at the end of the observation period (within 2 weeks), we also evaluated 6-minute walk distance, Borg dyspnea, functional class, B-type natriuretic peptide (or N-terminal pro-B-type natriuretic peptide) levels, health-related quality of life (EQ-5D questionnaire), and sleep quality (Pittsburgh Sleep Quality Index). RESULTS: Of 31 patients, 18 were included in the full analysis (observation period: median 91.5 days, IQR 88.0 to 92.0). Changes from baseline in traditional and digital 6-minute walk distance were moderately correlated (r=0.57). Physical activity (daily distance walked: median 0.4 km, IQR -0.2 to 1.9; daily step count: median 591, IQR -509 to 2413) and clinical measures (traditional 6-minute walk distance: median 26 m, IQR 0 to 40) changed concordantly from baseline to the end of the observation period. Health-related quality of life showed little change. Total sleep score and resting heart rate slightly decreased. Distance walked and step count showed short-term increases after each iloprost inhalation. No new safety signals were identified (safety analysis set: n=30). CONCLUSIONS: Our results suggest that despite challenges, parallel monitoring of physical activity, heart rate, and iloprost inhalation is feasible in patients with pulmonary arterial hypertension and may complement traditional measures in guiding treatment; however, the sample size of this study limits generalizability. TRIAL REGISTRATION: ClinicalTrials.gov NCT03293407; https://clinicaltrials.gov/ct2/show/NCT03293407. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/12144.


Subject(s)
Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Administration, Inhalation , Adult , Heart Rate , Humans , Hypertension, Pulmonary/drug therapy , Iloprost/therapeutic use , Prospective Studies , Quality of Life , Treatment Outcome , Vasodilator Agents/therapeutic use , Walking
2.
BMJ Case Rep ; 14(9)2021 Sep 07.
Article in English | MEDLINE | ID: covidwho-1398608

ABSTRACT

We report a case of a previously fit woman who presented at 26 weeks into her fourth pregnancy with a dry cough. Following a nasopharyngeal swab, she was diagnosed with a pertussis infection, and treated with antibiotics. A chest X-ray showed right atrial dilatation and an echocardiogram was scheduled outpatient. However, after re-presenting with worsening cough and dyspnoea, an inpatient echocardiogram was performed which suggested elevated pulmonary pressures with significant tricuspid regurgitation, as confirmed by subsequent cardiac catheterisation. She had an elective caesarean section at 34 weeks and underwent repeat right heart catheterisation which revealed persistent, and likely pre-existing, pulmonary arterial hypertension. This case highlights the importance of thorough assessment of non-obstetric symptoms in pregnancy in formulating alternative differentials, even after a diagnosis has been made, to prevent potentially life-threatening conditions from being missed. It also shows that although often associated, respiratory and cardiac causes may coexist separately.


Subject(s)
Hypertension, Pulmonary , Tricuspid Valve Insufficiency , Whooping Cough , Cesarean Section , Echocardiography , Female , Humans , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/etiology , Pregnancy , Whooping Cough/complications , Whooping Cough/diagnosis , Whooping Cough/drug therapy
3.
Int J Mol Sci ; 22(17)2021 Aug 24.
Article in English | MEDLINE | ID: covidwho-1374422

ABSTRACT

The lungs play a very important role in the human respiratory system. However, many factors can destroy the structure of the lung, causing several lung diseases and, often, serious damage to people's health. Nerve growth factor (NGF) is a polypeptide which is widely expressed in lung tissues. Under different microenvironments, NGF participates in the occurrence and development of lung diseases by changing protein expression levels and mediating cell function. In this review, we summarize the functions of NGF as well as some potential underlying mechanisms in pulmonary fibrosis (PF), coronavirus disease 2019 (COVID-19), pulmonary hypertension (PH), asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. Furthermore, we highlight that anti-NGF may be used in future therapeutic strategies.


Subject(s)
Airway Remodeling/drug effects , Lung/pathology , Nerve Growth Factor/antagonists & inhibitors , Signal Transduction/drug effects , Asthma/drug therapy , Asthma/pathology , COVID-19/drug therapy , COVID-19/pathology , Humans , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/pathology , Lung/drug effects , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Molecular Targeted Therapy/methods , Nerve Growth Factor/metabolism , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/pathology , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/pathology
4.
J Enzyme Inhib Med Chem ; 36(1): 1230-1235, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1254219

ABSTRACT

The ongoing Covid-19 is a contagious disease, and it is characterised by different symptoms such as fever, cough, and shortness of breath. Rising concerns about Covid-19 have severely affected the healthcare system in all countries as the Covid-19 outbreak has developed at a rapid rate all around the globe. Intriguing, a clinically used drug, acetazolamide (a specific inhibitor of carbonic anhydrase, CA, EC 4.2.1.1), is used to treat high-altitude pulmonary oedema (HAPE), showing a high degree of clinical similarities with the pulmonary disease caused by Covid-19. In this context, this preliminary study aims to provide insights into some factors affecting the Covid-19 patients, such as hypoxaemia, hypoxia as well as the blood CA activity. We hypothesise that patients with Covid-19 problems could show a dysregulated acid-base status influenced by CA activity. These preliminary results suggest that the use of CA inhibitors as a pharmacological treatment for Covid-19 may be beneficial.


Subject(s)
Acetazolamide/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Carbonic Anhydrase Inhibitors/therapeutic use , Carbonic Anhydrases/blood , Acid-Base Equilibrium/drug effects , Altitude Sickness/blood , Altitude Sickness/drug therapy , Anticonvulsants/therapeutic use , Bicarbonates/blood , COVID-19/blood , COVID-19/diagnostic imaging , COVID-19/virology , Carbon Dioxide/blood , Cough/blood , Cough/drug therapy , Cough/pathology , Cough/virology , Drug Repositioning , Dyspnea/blood , Dyspnea/drug therapy , Dyspnea/pathology , Dyspnea/virology , Fever/blood , Fever/drug therapy , Fever/pathology , Fever/virology , Humans , Hydrogen-Ion Concentration , Hypertension, Pulmonary/blood , Hypertension, Pulmonary/drug therapy , Hypoxia/blood , Hypoxia/drug therapy , Hypoxia/pathology , Hypoxia/virology , Oximetry , Research Design , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Severity of Illness Index , Tomography, X-Ray Computed
6.
Molecules ; 26(7)2021 Mar 29.
Article in English | MEDLINE | ID: covidwho-1159212

ABSTRACT

The COVID-19 pandemic has reached over 100 million worldwide. Due to the multi-targeted nature of the virus, it is clear that drugs providing anti-COVID-19 effects need to be developed at an accelerated rate, and a combinatorial approach may stand to be more successful than a single drug therapy. Among several targets and pathways that are under investigation, the renin-angiotensin system (RAS) and specifically angiotensin-converting enzyme (ACE), and Ca2+-mediated SARS-CoV-2 cellular entry and replication are noteworthy. A combination of ACE inhibitors and calcium channel blockers (CCBs), a critical line of therapy for pulmonary hypertension, has shown therapeutic relevance in COVID-19 when investigated independently. To that end, we conducted in silico modeling using BIOiSIM, an AI-integrated mechanistic modeling platform by utilizing known preclinical in vitro and in vivo datasets to accurately simulate systemic therapy disposition and site-of-action penetration of the CCBs and ACEi compounds to tissues implicated in COVID-19 pathogenesis.


Subject(s)
Antiviral Agents/pharmacokinetics , COVID-19/drug therapy , Drug Repositioning/methods , Hypertension, Pulmonary/drug therapy , Angiotensin-Converting Enzyme Inhibitors/pharmacokinetics , Antiviral Agents/blood , Biosimilar Pharmaceuticals , COVID-19/complications , Calcium Channel Blockers/pharmacokinetics , Computer Simulation , Databases, Pharmaceutical , Drug Development/methods , Humans , Hypertension, Pulmonary/virology , Tissue Distribution
7.
Hepatology ; 74(3): 1674-1686, 2021 09.
Article in English | MEDLINE | ID: covidwho-1103301

ABSTRACT

Pulmonary disease in liver cirrhosis and portal hypertension (PH) constitutes a challenging clinical scenario and may have important implications with regard to prognosis, liver transplantation (LT) candidacy, and post-LT outcome. Pre-LT evaluation should include adequate screening for pulmonary diseases that may occur concomitantly with liver disease as well as for those that may arise as a complication of end-stage liver disease and PH, given that either may jeopardize safe LT and successful outcome. It is key to discriminate those patients who would benefit from LT, especially pulmonary disorders that have been reported to resolve post-LT and are considered "pulmonary indications" for transplant, from those who are at increased mortality risk and in whom LT is contraindicated. In conclusion, in this article, we review the impact of several pulmonary disorders, including cystic fibrosis, alpha 1-antitrypsin deficiency, hereditary hemorrhagic telangiectasia, sarcoidosis, coronavirus disease 2019, asthma, chronic obstructive pulmonary disease, pulmonary nodules, interstitial lung disease, hepatic hydrothorax, hepatopulmonary syndrome, and portopulmonary hypertension, on post-LT survival, as well as the reciprocal impact of LT on the evolution of lung function.


Subject(s)
Hypertension, Portal/complications , Liver Cirrhosis/complications , Liver Transplantation/mortality , Lung Diseases/complications , Adult , Asthma/diagnosis , Asthma/epidemiology , Asthma/mortality , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/mortality , COVID-19/virology , Child , Cystic Fibrosis , End Stage Liver Disease/complications , Hepatopulmonary Syndrome/diagnosis , Hepatopulmonary Syndrome/epidemiology , Hepatopulmonary Syndrome/mortality , Humans , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/etiology , Liver Transplantation/methods , Lung Diseases/epidemiology , Lung Diseases/pathology , Lung Diseases/physiopathology , Mass Screening , Patient Selection/ethics , Prognosis , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/mortality , Respiratory Function Tests/methods , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Sarcoidosis/diagnosis , Sarcoidosis/epidemiology , Sarcoidosis/mortality , Survival Rate/trends , Telangiectasia, Hereditary Hemorrhagic/diagnosis , Telangiectasia, Hereditary Hemorrhagic/epidemiology , Telangiectasia, Hereditary Hemorrhagic/mortality , alpha 1-Antitrypsin Deficiency/diagnosis , alpha 1-Antitrypsin Deficiency/epidemiology , alpha 1-Antitrypsin Deficiency/mortality
8.
Med Hypotheses ; 149: 110539, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1091701

ABSTRACT

Using folic acid (FA) as placebo complicates the interpretation of the findings of few RCTs evaluating safety and efficacy of hydroxychloroquine prophylaxis in COVID-19. FA is found to bind to furin-protease and spike: ACE2 interface of SARS-CoV-2. In clinical studies, FA level was lowest among severe patients compared to mild and moderate disease. A single controlled study reported the benefit of combination of folic acid with Pyridoxine & cyanocobalamin in terms of clinical and laboratory cure parameters. One hypothesis associates the differences in geographical variation of disease severity with prevalence of methyl tertahydrofolic acid reductase (MTHFR) C677T polymorphism. Other possible domains, where FA is hypothesized to be beneficial are COVID-19 associated pulmonary hypertension and hyper-homocystinemia. So, scientific justification of using folic acid as placebo in COVID-19 trials seems scientifically not credible and this may be one of the major factors for failure of many agents. We need to be more careful in choosing our placebo especially when conducting a placebo controlled trial.


Subject(s)
COVID-19/prevention & control , Folic Acid/therapeutic use , Hydroxychloroquine/therapeutic use , Placebos , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/complications , COVID-19/drug therapy , Humans , Hyperhomocysteinemia/complications , Hyperhomocysteinemia/drug therapy , Hypertension, Pulmonary/complications , Hypertension, Pulmonary/drug therapy , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Models, Theoretical , Nitric Oxide Synthase Type III/metabolism , Protein Binding , Randomized Controlled Trials as Topic , Research Design
9.
ESC Heart Fail ; 8(1): 714-718, 2021 02.
Article in English | MEDLINE | ID: covidwho-932426

ABSTRACT

AIMS: This study aims to analyse whether inhaled nitric oxide (iNO) was beneficial in the treatment of coronavirus disease 2019 (COVID-19) patients with pulmonary hypertension. METHODS AND RESULTS: Five critically ill COVID-19 patients with pulmonary hypertension designated Cases 1-5 were retrospectively included. Clinical data before and after iNO treatment were serially collected and compared between patients with or without iNO treatment. The five cases experienced pulmonary artery systolic pressure (PASP) elevation (≥50 mmHg) at 30, 24, 33, 23, and 24 days after illness onset (d.a.o), respectively. Cases 1-3 received iNO treatment on the 24th, 13th, and 1st day after the first elevation of PASP, with concentrations varied from 10 to 20 ppm based on the changes of PASP and blood pressure for 10, 9, and 5 days, respectively. Upon iNO treatment, PASP of Cases 1 and 2 returned to normal on the 10th day and 1st day, and maintained between 50 and 58 mmHg in Case 3. Pa02 /Fi02 increased from 88 to 124, 51 to 118, and 146 to 244, respectively. SPO2 increased from 91% to 97% for Case 1 and maintained a high level above 97% for Case 2. Cardiac function remained normal in the three patients after treatment. Moreover, Cases 1 and 3 survived from severe acute respiratory syndrome coronavirus 2 infection, while Case 2 finally died on the 36th day after the first elevation of PASP due to severe complications. Both cases who did not receive iNO treatment experienced a sudden decrease of PASP and Pa02 /Fi02 due to right heart failure and then died. CONCLUSIONS: Inhaled nitric oxide treatment was beneficial in reducing and stabilizing the PASP and might also reduce the risk of right heart failure in COVID-19 with pulmonary hypertension.


Subject(s)
COVID-19/drug therapy , Hypertension, Pulmonary/drug therapy , Nitric Oxide/therapeutic use , Administration, Inhalation , COVID-19/complications , Humans , Hypertension, Pulmonary/etiology , Middle Aged , Nitric Oxide/administration & dosage , Retrospective Studies
11.
J Intensive Care Med ; 36(1): 3-8, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-760426

ABSTRACT

Coronavirus Disease 2019 (COVID-19) has had a devastating impact on the ability of highly trained healthcare providers to render sufficient care, due to both the significant demand on resources and the unique nature of this disease that make it resistant to traditional therapies. This review sought to determine the potential role of phosphodiesterase-5 inhibitors (PDE-5) in the management of COVID-19 by extrapolating relevant data and clinical studies from other related disease states, including acute respiratory distress syndrome, acute lung injury, and high altitude pulmonary edema. Following a literature search, 4 reports were analyzed and included in this review. While the heterogenicity of data and the small number of trials included limit the interpretation and applicability, it was consistently demonstrated that PDE-5 inhibitors lowered pulmonary arterial pressures. The overall benefit of these agents is seemingly dependent upon the etiology of the respiratory failure, which warrants expanded clinical investigation for COVID-19.


Subject(s)
Altitude Sickness/drug therapy , COVID-19 , Hypertension, Pulmonary/drug therapy , Phosphodiesterase 5 Inhibitors/pharmacology , Respiratory Distress Syndrome/drug therapy , COVID-19/drug therapy , COVID-19/metabolism , Humans , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , Pulmonary Artery/drug effects , Pulmonary Artery/metabolism
12.
Med Hypotheses ; 143: 110142, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-671909

ABSTRACT

BACKGROUND: Pulmonary hypertension is a significant complication for some patients with COVID-19 pneumonia, especially those requiring intensive care. Tachyphylaxis to the current therapy, inhaled nitric oxide (iNO), is also common. In vitro, folic acid directly increases nitric oxide (NO) production and extends its duration of action; effects which could be of benefit in reversing pulmonary hypertension and severe hypoxaemia. Our work has shown that, in the systemic circulation, folic acid in high dose rapidly improves nitric oxide mediated vasodilation, by activating endothelial nitric oxide synthase (eNOS). HYPOTHESIS: A similar effect of high dose folic acid on pulmonary endothelial function would be expected from the same mechanism and would lead to improvement in pulmonary perfusion. We therefore hypothesise that folic acid, 5 mg or greater, is a useful therapeutic option for pulmonary hypertension and/or refractory severe hypoxaemia, in patients with severe COVID-19 associated pneumonia in whom NO therapy is considered, with a very low risk of adverse effects.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Folic Acid/therapeutic use , Hypertension, Pulmonary/drug therapy , Nitric Oxide/metabolism , Pandemics , Pneumonia, Viral/complications , Administration, Inhalation , Animals , COVID-19 , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiology , Enzyme Activation/drug effects , Folic Acid/administration & dosage , Folic Acid/pharmacology , Humans , Hypertension, Pulmonary/complications , Hypoxia/drug therapy , Hypoxia/etiology , Mice , Nitric Oxide/administration & dosage , Nitric Oxide/therapeutic use , Nitric Oxide Synthase Type III/drug effects , SARS-CoV-2 , Tachyphylaxis
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