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1.
Turk J Pediatr ; 64(2): 400-407, 2022.
Article in English | MEDLINE | ID: covidwho-1876416

ABSTRACT

BACKGROUND: High Altitude Pulmonary Edema (HAPE) is a fatal form of severe high-altitude illness. It is a form of noncardiogenic, noninfectious pulmonary edema secondary to alveolar hypoxia. The exact incidence of HAPE in children is unknown; however, most literature reports an incidence between 0.5-15%. There are three proposed HAPE types including classic HAPE, reentry HAPE, and high-altitude resident pulmonary edema (HARPE). CASE: We present three pediatric patients who were diagnosed with re-entry high altitude pulmonary edema and did not have any underlying cardiac abnormalities. All patients reside in areas of high altitude with a history of travelling to places of lower altitude. They had respiratory infections prior to the manifestation of HAPE. CONCLUSIONS: These are the first reported cases of children with reentry HAPE in Saudi Arabia. Reentry HAPE can occur in otherwise healthy children. Rapid ascent to high altitude and recent respiratory infections are the most commonly reported triggers. Prognosis is very favorable with a very rapid response to oxygen therapy. Education about HAPE is mandatory for families and health care workers working in high altitude areas.


Subject(s)
Altitude Sickness , Pulmonary Edema , Respiratory Tract Infections , Altitude , Altitude Sickness/complications , Altitude Sickness/diagnosis , Child , Humans , Hypertension, Pulmonary , Hypoxia/complications , Pulmonary Edema/etiology , Respiratory Tract Infections/complications
2.
BMC Med Res Methodol ; 22(1): 148, 2022 May 21.
Article in English | MEDLINE | ID: covidwho-1854773

ABSTRACT

BACKGROUND: Missing data prove troublesome in data analysis; at best they reduce a study's statistical power and at worst they induce bias in parameter estimates. Multiple imputation via chained equations is a popular technique for dealing with missing data. However, techniques for combining and pooling results from fitted generalized additive models (GAMs) after multiple imputation have not been well explored. METHODS: We simulated missing data under MCAR, MAR, and MNAR frameworks and utilized random forest and predictive mean matching imputation to investigate a variety of rules for combining GAMs after multiple imputation with binary and normally distributed outcomes. We compared multiple pooling procedures including the "D2" method, the Cauchy combination test, and the median p-value (MPV) rule. The MPV rule involves simply computing and reporting the median p-value across all imputations. Other ad hoc methods such as a mean p-value rule and a single imputation method are investigated. The viability of these methods in pooling results from B-splines is also examined for normal outcomes. An application of these various pooling techniques is then performed on two case studies, one which examines the effect of elevation on a six-minute walk distance (a normal outcome) for patients with pulmonary arterial hypertension, and the other which examines risk factors for intubation in hospitalized COVID-19 patients (a dichotomous outcome). RESULTS: In comparison to the results from generalized additive models fit on full datasets, the median p-value rule performs as well as if not better than the other methods examined. In situations where the alternative hypothesis is true, the Cauchy combination test appears overpowered and alternative methods appear underpowered, while the median p-value rule yields results similar to those from analyses of complete data. CONCLUSIONS: For pooling results after fitting GAMs to multiply imputed datasets, the median p-value is a simple yet useful approach which balances both power to detect important associations and control of Type I errors.


Subject(s)
COVID-19 , Hypertension, Pulmonary , COVID-19/epidemiology , Colorado , Hospitalization , Humans , Hypertension, Pulmonary/diagnosis , Models, Statistical , Registries
3.
Intensive Care Med ; 48(6): 667-678, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1800369

ABSTRACT

PURPOSE: Severely ill patients affected by coronavirus disease 2019 (COVID-19) develop circulatory failure. We aimed to report patterns of left and right ventricular dysfunction in the first echocardiography following admission to intensive care unit (ICU). METHODS: Retrospective, descriptive study that collected echocardiographic and clinical information from severely ill COVID-19 patients admitted to 14 ICUs in 8 countries. Patients admitted to ICU who received at least one echocardiography between 1st February 2020 and 30th June 2021 were included. Clinical and echocardiographic data were uploaded using a secured web-based electronic database (REDCap). RESULTS: Six hundred and seventy-seven patients were included and the first echo was performed 2 [1, 4] days after ICU admission. The median age was 65 [56, 73] years, and 71% were male. Left ventricle (LV) and/or right ventricle (RV) systolic dysfunction were found in 234 (34.5%) patients. 149 (22%) patients had LV systolic dysfunction (with or without RV dysfunction) without LV dilatation and no elevation in filling pressure. 152 (22.5%) had RV systolic dysfunction. In 517 patients with information on both paradoxical septal motion and quantitative RV size, 90 (17.4%) had acute cor pulmonale (ACP). ACP was associated with mechanical ventilation (OR > 4), pulmonary embolism (OR > 5) and increased PaCO2. Exploratory analyses showed that patients with ACP and older age were more likely to die in hospital (including ICU). CONCLUSION: Almost one-third of this cohort of critically ill COVID-19 patients exhibited abnormal LV and/or RV systolic function in their first echocardiography assessment. While LV systolic dysfunction appears similar to septic cardiomyopathy, RV systolic dysfunction was related to pressure overload due to positive pressure ventilation, hypercapnia and pulmonary embolism. ACP and age seemed to be associated with mortality in this cohort.


Subject(s)
COVID-19 , Heart Failure , Hypertension, Pulmonary , Pulmonary Embolism , Ventricular Dysfunction, Left , Ventricular Dysfunction, Right , Aged , Echocardiography , Female , Humans , Intensive Care Units , Male , Retrospective Studies , Ventricular Dysfunction, Right/diagnostic imaging
5.
J Zhejiang Univ Sci B ; 23(2): 102-122, 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1706587

ABSTRACT

Molecular hydrogen exerts biological effects on nearly all organs. It has anti-oxidative, anti-inflammatory, and anti-aging effects and contributes to the regulation of autophagy and cell death. As the primary organ for gas exchange, the lungs are constantly exposed to various harmful environmental irritants. Short- or long-term exposure to these harmful substances often results in lung injury, causing respiratory and lung diseases. Acute and chronic respiratory diseases have high rates of morbidity and mortality and have become a major public health concern worldwide. For example, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. An increasing number of studies have revealed that hydrogen may protect the lungs from diverse diseases, including acute lung injury, chronic obstructive pulmonary disease, asthma, lung cancer, pulmonary arterial hypertension, and pulmonary fibrosis. In this review, we highlight the multiple functions of hydrogen and the mechanisms underlying its protective effects in various lung diseases, with a focus on its roles in disease pathogenesis and clinical significance.


Subject(s)
COVID-19/immunology , COVID-19/therapy , Hydrogen/therapeutic use , Lung Diseases/therapy , Acute Lung Injury , Aging , Animals , Anti-Inflammatory Agents , Antioxidants/chemistry , Asthma/therapy , Autophagy , COVID-19/drug therapy , Humans , Hypertension, Pulmonary/therapy , Inflammation , Lung Neoplasms/therapy , Mice , Oxidative Stress , Pulmonary Disease, Chronic Obstructive/therapy , Pulmonary Fibrosis/therapy , Pyroptosis , Reactive Oxygen Species
6.
Cardiol Young ; 32(2): 315-319, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1692709

ABSTRACT

Chronic thromboembolic pulmonary hypertension is an uncommon condition in the children. It almost always accompanies a hypercoagulable state. We described a rare case of Behçet's disease presenting with chronic thromboembolic pulmonary hypertension and initially misdiagnosed as coronavirus disease 2019 pneumonia.


Subject(s)
Behcet Syndrome , COVID-19 , Hypertension, Pulmonary , Behcet Syndrome/complications , Behcet Syndrome/diagnosis , Child , Humans , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/etiology , SARS-CoV-2
7.
Nitric Oxide ; 121: 20-33, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1665319

ABSTRACT

Inhaled nitric oxide (iNO) acts as a selective pulmonary vasodilator and it is currently approved by the FDA for the treatment of persistent pulmonary hypertension of the newborn. iNO has been demonstrated to effectively decrease pulmonary artery pressure and improve oxygenation, while decreasing extracorporeal life support use in hypoxic newborns affected by persistent pulmonary hypertension. Also, iNO seems a safe treatment with limited side effects. Despite the promising beneficial effects of NO in the preclinical literature, there is still a lack of high quality evidence for the use of iNO in clinical settings. A variety of clinical applications have been suggested in and out of the critical care environment, aiming to use iNO in respiratory failure and pulmonary hypertension of adults or as a preventative measure of hemolysis-induced vasoconstriction, ischemia/reperfusion injury and as a potential treatment of renal failure associated with cardiopulmonary bypass. In this narrative review we aim to present a comprehensive summary of the potential use of iNO in several clinical conditions with its suggested benefits, including its recent application in the scenario of the COVID-19 pandemic. Randomized controlled trials, meta-analyses, guidelines, observational studies and case-series were reported and the main findings summarized. Furthermore, we will describe the toxicity profile of NO and discuss an innovative proposed strategy to produce iNO. Overall, iNO exhibits a wide range of potential clinical benefits, that certainly warrants further efforts with randomized clinical trials to determine specific therapeutic roles of iNO.


Subject(s)
Critical Illness , Hypertension, Pulmonary/drug therapy , Infant, Newborn, Diseases/drug therapy , Nitric Oxide/therapeutic use , Vasodilator Agents/therapeutic use , Adult , COVID-19/complications , COVID-19/drug therapy , COVID-19/virology , Humans , Hypertension, Pulmonary/etiology , Infant, Newborn , Infant, Newborn, Diseases/etiology , Nitric Oxide/pharmacology , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , Vasodilator Agents/pharmacology
8.
Int J Surg Pathol ; 30(4): 443-447, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1571682

ABSTRACT

COVID-19, the syndrome caused by the novel coronavirus SARS-CoV-2, has spread throughout the world, causing the death of at least three million people. For the over 81 million who have recovered, however, the long-term effects are only beginning to manifest. We performed a bilateral lung transplant on a 31-year-old male patient for chronic hypoxic respiratory failure, severe pulmonary hypertension and radiographically identified pulmonary fibrosis five months after an acute COVID-19 infection. The explant demonstrated moderate pulmonary vascular remodeling with intimal thickening and medial hypertrophy throughout, consistent with pulmonary hypertension. The parenchyma demonstrated an organizing lung injury in the proliferative phase, with severe fibrosis, histiocytic proliferation, type II pneumocyte hyperplasia, and alveolar loss consistent with known COVID-19 pneumonia complications.This report highlights a novel histologic finding in severe, chronic COVID-19. Although the findings in acute COVID-19 pneumonia have been well-examined at autopsy, the chronic course of this complex disease is not yet understood. The case presented herein suggests that COVID-induced pulmonary hypertension may become more common as more patients survive severe SARS-CoV-2-related pneumonia. Pulmonologists and pulmonary pathologists should be aware of this possible association and look for the clinical, radiographic, and histologic criteria in the appropriate clinical setting.


Subject(s)
COVID-19 , Hypertension, Pulmonary , Hypertension , Adult , Autopsy , COVID-19/complications , Humans , Hypertension, Pulmonary/etiology , Lung/diagnostic imaging , Lung/pathology , Male , SARS-CoV-2
9.
Nat Rev Cardiol ; 19(5): 314-331, 2022 May.
Article in English | MEDLINE | ID: covidwho-1555484

ABSTRACT

The lungs are the primary target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with severe hypoxia being the cause of death in the most critical cases. Coronavirus disease 2019 (COVID-19) is extremely heterogeneous in terms of severity, clinical phenotype and, importantly, global distribution. Although the majority of affected patients recover from the acute infection, many continue to suffer from late sequelae affecting various organs, including the lungs. The role of the pulmonary vascular system during the acute and chronic stages of COVID-19 has not been adequately studied. A thorough understanding of the origins and dynamic behaviour of the SARS-CoV-2 virus and the potential causes of heterogeneity in COVID-19 is essential for anticipating and treating the disease, in both the acute and the chronic stages, including the development of chronic pulmonary hypertension. Both COVID-19 and chronic pulmonary hypertension have assumed global dimensions, with potential complex interactions. In this Review, we present an update on the origins and behaviour of the SARS-CoV-2 virus and discuss the potential causes of the heterogeneity of COVID-19. In addition, we summarize the pathobiology of COVID-19, with an emphasis on the role of the pulmonary vasculature, both in the acute stage and in terms of the potential for developing chronic pulmonary hypertension. We hope that the information presented in this Review will help in the development of strategies for the prevention and treatment of the continuing COVID-19 pandemic.


Subject(s)
COVID-19 , Hypertension, Pulmonary , Humans , Lung , Pandemics , SARS-CoV-2
10.
Ann Intern Med ; 174(1): 139-140, 2021 01.
Article in English | MEDLINE | ID: covidwho-1554303
12.
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
13.
Chest ; 161(4): 1060-1072, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1464625

ABSTRACT

Pulmonary arterial hypertension (PAH) is a rare disease associated with abnormally elevated pulmonary pressures and right heart failure resulting in high morbidity and mortality. Although the prognosis for patients with PAH has improved with the introduction of pulmonary vasodilators, disease progression remains a major problem. Given that available therapies are inadequate for preventing small-vessel loss and obstruction, there is active interest in identifying drugs capable of targeting angiogenesis and mechanisms involved in the regulation of cell growth and fibrosis. Among the mechanisms linked to PAH pathogenesis, preclinical studies have identified promising compounds that are currently being tested in clinical trials. These drugs target seven of the major mechanisms associated with PAH pathogenesis: bone morphogenetic protein signaling, tyrosine kinase receptors, estrogen metabolism, extracellular matrix, angiogenesis, epigenetics, and serotonin metabolism. In this review, we discuss the preclinical studies that led to prioritization of these mechanisms, and discuss completed and ongoing phase 2/3 trials using novel interventions such as sotatercept, anastrozole, rodatristat ethyl, tyrosine kinase inhibitors, and endothelial progenitor cells, among others. We anticipate that the next generation of compounds will build on the success of the current standard of care and improve clinical outcomes and quality of life for patients with PAH.


Subject(s)
Heart Failure , Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Familial Primary Pulmonary Hypertension/complications , Heart Failure/complications , Humans , Quality of Life
14.
Pulm Pharmacol Ther ; 71: 102082, 2021 12.
Article in English | MEDLINE | ID: covidwho-1492538

ABSTRACT

COVID-19 pandemic has changed the world dramatically since was first reported in Wuhan city, China [1]. Not only as a respiratory illness that could lead to fatal respiratory failure, but also some evidences suggest that it can propagate as a chronic disease associated with a variety of persistent post COVID-19 pathologies that affect patients' life [2,3]. Pulmonary hypertension (PH) is one of the challenging diseases that may develop as a consequence of SARS-COV-2 infection in some COVID-19 survivors [4,5]. The vasopressor, proliferative, proinflammatory, and prothrombotic actions of endothelin [6] may be encountered in the COVID-19-induced PH pathology. And so, endothelin blockers may have an important role to restrict the development of serious PH outcomes with special precautions considering patients with significant hypoxemia.


Subject(s)
COVID-19 , Endothelins , Hypertension, Pulmonary , COVID-19/complications , Humans , Hypertension, Pulmonary/virology , Pandemics
17.
Medicina (Kaunas) ; 57(9)2021 Sep 20.
Article in English | MEDLINE | ID: covidwho-1430921

ABSTRACT

In this article, we present the case of a 38-year-old female who suffered from serious respiratory distress. After an extensive pulmonary artery imaging diagnostic work-up (CTPA, MRA and PET), we were unable to differentiate between chronic thromboembolic pulmonary hypertension (CTEPH) vs. pulmonary artery sarcoma (PAS) due to extensive filling defects and extraluminal findings. Although surgery was postponed for nine months due to the COVID-19 pandemic, CTEPH diagnosis, due to a high-thrombus burden, was finally confirmed after pulmonary endarterectomy (PEA). Conclusively, imaging findings of rare cases of CTEPH might mimic PAS and the surgical removal of the lesion are both needed for a final diagnosis. What is Already Known about This Topic? Pulmonary artery sarcoma (PAS) is a rare but aggressive malignancy, which originates from the intimal layer of the pulmonary artery (PA); Chronic thromboembolic pulmonary hypertension (CTEPH) is based on chronic, organized flow-limiting thrombi inside PA circulation and subsequent pulmonary hypertension. What Does This Study Contribute? Since radiological findings of CTEPH cases might rarely mimic PAS, pulmonary artery endarterectomy and subsequent histopathologic study are needed for a final diagnosis.


Subject(s)
COVID-19 , Hypertension, Pulmonary , Pulmonary Embolism , Sarcoma , Thrombosis , Adult , Chronic Disease , Female , Humans , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/etiology , Pandemics , Pulmonary Artery/diagnostic imaging , Pulmonary Artery/surgery , Pulmonary Embolism/diagnosis , Pulmonary Embolism/diagnostic imaging , SARS-CoV-2 , Sarcoma/diagnosis , Sarcoma/diagnostic imaging
18.
BMJ Case Rep ; 14(9)2021 Sep 17.
Article in English | MEDLINE | ID: covidwho-1416641

ABSTRACT

A 47-year-old woman presented with a headache to the acute medical unit, 10 days after receiving AstraZeneca vaccination for COVID-19. Brain imaging was normal, but her blood tests showed a remarkably low platelet count, mildly deranged liver function tests and a high D-dimer. Further within her hospital admission, she developed right-sided abdominal pain and chest pain, and subsequent cross-sectional imaging confirmed a small segmental pulmonary embolism, and an acute portal vein thrombosis extending to the splenic and superior mesenteric veins. On the basis of her investigations, she was diagnosed as a case of vaccine-induced thrombotic thrombocytopenia and was treated with intravenous immunoglobulins. In a time where there is a strategic goal to vaccinate the global population from COVID-19 to inhibit the spread of infection and reduce hospitalisation, this particular clinical scenario emphasises the need of all clinicians to remain vigilant for rare complications of the COVID-19 vaccination.


Subject(s)
COVID-19 , Hypertension, Pulmonary , Thrombocytopenia , Thrombosis , Vaccines , COVID-19 Vaccines , Female , Hospitals, General , Humans , Middle Aged , Pulmonary Artery , SARS-CoV-2 , United Kingdom
19.
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
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