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1.
Int J Mol Sci ; 22(4)2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33673372

RESUMO

One of the most severe effects of coronavirus disease 2019 (COVID-19) is lung disorders such as acute respiratory distress syndrome. In the absence of effective treatments, it is necessary to search for new therapies and therapeutic targets. Platelets play a fundamental role in respiratory disorders resulting from viral infections, being the first line of defense against viruses and essential in maintaining lung function. The direct application of platelet lysate (PL) obtained from the platelet-rich plasma of healthy donors could help in the improvement of the patient due its anti-inflammatory, immunomodulatory, antifibrotic, and repairing effects. This work evaluates PL nebulization by analyzing its levels of growth factors and its biological activity on lung fibroblast cell cultures, besides describing a scientific basis for its use in this kind of pathology. The data of the work suggest that the molecular levels and biological activity of the PL are maintained after nebulization. Airway administration would allow acting directly on the lung tissue modulating inflammation and stimulating reparative processes on key structures such as the alveolocapillary barrier, improving the disease and sequels. The protocol developed in this work is a first step for the study of nebulized PL both in animal experimentation and in clinical trials.


Assuntos
Anti-Inflamatórios/farmacologia , Fatores Imunológicos/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Plasma Rico em Plaquetas , Adulto , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/imunologia , Plaquetas/imunologia , Linhagem Celular , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/imunologia , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Masculino , Nebulizadores e Vaporizadores , Plasma Rico em Plaquetas/imunologia , Resultado do Tratamento
2.
Cochrane Database Syst Rev ; 2: CD011878, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33543473

RESUMO

BACKGROUND: Transient tachypnea of the newborn is characterized by tachypnea and signs of respiratory distress. Transient tachypnea typically appears within the first two hours of life in term and late preterm newborns. Although transient tachypnea of the newborn is usually a self-limited condition, it is associated with wheezing syndromes in late childhood. The rationale for the use of salbutamol (albuterol) for transient tachypnea of the newborn is based on studies showing that ß-agonists can accelerate the rate of alveolar fluid clearance. This review was originally published in 2016 and updated in 2020. OBJECTIVES: To assess whether salbutamol compared to placebo, no treatment or any other drugs administered to treat transient tachypnea of the newborn, is effective and safe for infants born at 34 weeks' gestational age with this diagnosis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2020, Issue 4) in the Cochrane Library; PubMed (1996 to April 2020), Embase (1980 to April 2020); and CINAHL (1982 to April 2020). We applied no language restrictions. We searched the abstracts of the major congresses in the field (Perinatal Society of Australia New Zealand and Pediatric Academic Societies) from 2000 to 2020 and clinical trial registries. SELECTION CRITERIA: Randomized controlled trials, quasi-randomized controlled trials and cluster trials comparing salbutamol versus placebo or no treatment or any other drugs administered to infants born at 34 weeks' gestational age or more and less than three days of age with transient tachypnea of the newborn. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology for data collection and analysis. The primary outcomes considered in this review were duration of oxygen therapy, need for continuous positive airway pressure and need for mechanical ventilation. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: Seven trials, which included 498 infants, met the inclusion criteria. All trials compared a nebulized dose of salbutamol with normal saline. Four studies used one single dose of salbutamol; in two studies, three to four doses were provided; in one study, additional doses were administered if needed. The certainty of the evidence was low for duration of hospital stay and very low for the other outcomes. Among the primary outcomes of this review, four trials (338 infants) reported the duration of oxygen therapy, (mean difference (MD) -19.24 hours, 95% confidence interval (CI) -23.76 to -14.72); one trial (46 infants) reported the need for continuous positive airway pressure (risk ratio (RR) 0.73, 95% CI 0.38 to 1.39; risk difference (RD) -0.15, 95% CI -0.45 to 0.16), and three trials (254 infants) reported the need for mechanical ventilation (RR 0.60, 95% CI 0.13 to 2.86; RD -0.01, 95% CI -0.05 to 0.03). Both duration of hospital stay (4 trials; 338 infants) and duration of respiratory support (2 trials, 228 infants) were shorter in the salbutamol group (MD -1.48, 95% CI -1.8 to -1.16; MD -9.24, 95% CI -14.24 to -4.23, respectively). One trial (80 infants) reported duration of mechanical ventilation and pneumothorax but data could not be extracted due to the reporting of these outcomes (type of units of effect measure and unclear number of events, respectively). Five trials are ongoing. AUTHORS' CONCLUSIONS: There was limited evidence to establish the benefits and harms of salbutamol in the management of transient tachypnea of the newborn. We are uncertain whether salbutamol administration reduces the duration of oxygen therapy, duration of tachypnea, need for continuous positive airway pressure and for mechanical ventilation. Salbutamol may slightly reduce hospital stay. Five trials are ongoing. Given the limited and low certainty of the evidence available, we could not determine whether salbutamol was safe or effective for the treatment of transient tachypnea of the newborn.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Albuterol/uso terapêutico , Taquipneia Transitória do Recém-Nascido/tratamento farmacológico , Pressão Positiva Contínua nas Vias Aéreas/estatística & dados numéricos , Humanos , Recém-Nascido , Ventilação com Pressão Positiva Intermitente/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Nebulizadores e Vaporizadores , Oxigenoterapia/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo
3.
A A Pract ; 15(2): e01376, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33560642

RESUMO

We present a case where nitroglycerin tablets dissolved in saline and intravenous nitroglycerin solution were nebulized as surrogates for inhaled nitric oxide (iNO) after our iNO supply was depleted during the coronavirus disease 2019 (COVID-19) surge in New York. We gave this treatment to a COVID-19 patient with severe acute respiratory distress syndrome (ARDS) and hypercarbia. In response, the patient had immediate and clinically meaningful improvement in multiple organ systems despite no other interventions or ventilator changes.


Assuntos
/tratamento farmacológico , Nebulizadores e Vaporizadores , Nitroglicerina/administração & dosagem , Vasodilatadores/administração & dosagem , /complicações , Humanos , Masculino , Pessoa de Meia-Idade , Nitroglicerina/síntese química , /etiologia
4.
Trials ; 22(1): 60, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33461602

RESUMO

OBJECTIVES: Basic and clinical studies have shown that magnesium sulphate ameliorates lung injury and controls asthma attacks by anti-inflammatory and bronchodilatory effects. Both intravenous and inhaled magnesium sulphate have a clinical impact on acute severe asthma by inhibition of airway smooth muscle contraction. Besides, magnesium sulphate can dilate constricted pulmonary arteries and reduce pulmonary artery resistance. However, it may affect systemic arteries when administered intravenously. A large number of patients with covid-19 admitted to the hospital suffer from pulmonary involvement. COVID-19 can cause hypoxia due to the involvement of the respiratory airways and parenchyma along with circulatory impairment, which induce ventilation-perfusion mismatch. This condition may result in hypoxemia and low arterial blood oxygen pressure and saturation presented with some degree of dyspnoea and shortness of breath. Inhaled magnesium sulphate as a smooth muscle relaxant (natural calcium antagonist) can cause both bronchodilator and consequently vasodilator effects (via a direct effect on alveolar arterioles in well-ventilated areas) in the respiratory tract. We aim to investigate if inhaled magnesium sulphate as adjuvant therapy to standard treatment can reduce ventilation-perfusion mismatch in the respiratory tract and subsequently improve arterial oxygen saturation in hospitalized patients with COVID-19. TRIAL DESIGN: A multi-centre, open-label, randomised controlled trial (RCT) with two parallel arms design (1:1 ratio) PARTICIPANTS: Patients aged 18-80 years hospitalized at Masih Daneshvari Hospital and Shahid Dr. Labbafinejad hospital in Tehran and Shahid Sadoughi Hospital in Yazd will be included if they meet the inclusion criteria of the study. Inclusion criteria are defined as 1. Confirmed diagnosis of SARS-CoV-2 infection based on polymerase chain reaction (PCR) of nasopharyngeal secretions or clinical manifestations along with chest computed tomography (chest CT) scan 2. Presenting with moderate or severe COVID-19 lung involvement confirmed with chest CT scan and arterial oxygen saturation below 93% 3. Length of hospital stay ≤48 hours. Patients with underlying cardiovascular diseases including congestive heart failure, bradyarrhythmia, heart block, the myocardial injury will be excluded from the study. INTERVENTION AND COMPARATOR: Participants will be randomly divided into two arms. Patients in the intervention arm will be given both standard treatment for COVID-19 (according to the national guideline) and magnesium sulphate (5 cc of a 20% injectable vial or 2 cc of a 50% injectable vial will be diluted by 50 cc distilled water and nebulized via a mask) every eight hours for five days. Patients in the control (comparator) arm will only receive standard treatment for COVID-19. MAIN OUTCOMES: Improvement of respiratory function and symptoms including arterial blood oxygen saturation, dyspnoea (according to NYHA functional classification), and cough within the first five days of randomization. RANDOMISATION: Block randomisation will be used to allocate eligible patients to the study arms (in a 1:1 ratio). Computer software will be applied to randomly select the blocks. BLINDING (MASKING): The study is an open-label RCT without blinding. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The trial will be performed on 100 patients who will be randomly divided into two arms of control (50) and intervention (50). TRIAL STATUS: The protocol is Version 5.0, January 05, 2021. Recruitment of the participants started on July 30, 2020, and it is anticipated to be completed by February 28, 2021. TRIAL REGISTRATION: The trial was registered in the Iranian Registry of Clinical Trials (IRCT) on July 28, 2020. It is available on https://en.irct.ir/trial/49879 . The registration number is IRCT20191211045691N1. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Sulfato de Magnésio/uso terapêutico , Administração por Inalação , Gasometria , Broncodilatadores , Tosse/fisiopatologia , Dispneia/fisiopatologia , Humanos , Hipóxia/fisiopatologia , Irã (Geográfico) , Nebulizadores e Vaporizadores , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do Tratamento , Vasodilatadores , Relação Ventilação-Perfusão
5.
J Hosp Infect ; 110: 108-113, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33484782

RESUMO

BACKGROUND: Several medical procedures involving the respiratory tract are considered as 'aerosol-generating procedures'. Aerosols from these procedures may be inhaled by bystanders, and there are consequent concerns regarding the transmission of infection or, specific to nebulized therapy, secondary drug exposure. AIM: To assess the efficacy of a proprietary high-efficiency-particulate-air-filtering extractor tent on reducing the aerosol dispersal of nebulized bronchodilator drugs. METHODS: The study was conducted in an unoccupied outpatient room at St. James's Hospital, Dublin, Ireland. A novel real-time, fluorescent particle counter, the Wideband Integrated Bioaerosol Sensor (WIBS), monitored room air continuously for 3 h. Baseline airborne particle count and count during nebulization of bronchodilator drug solutions were recorded. FINDINGS: Nebulization within the tent prevented any increase over background level. Nebulization directly into room air resulted in mean fluorescent particle counts of 4.75 x 105/m3 and 4.21 x 105/m3 for Ventolin and Ipramol, respectively, representing more than 400-fold increases over mean background level. More than 99.3% of drug particles were <2 µm in diameter and therefore small enough to enter the lower respiratory tract. CONCLUSION: The extractor tent was completely effective for the prevention of airborne spread of drug particles of respirable size from nebulized therapy. This suggests that extractor tents of this type would be efficacious for the prevention of airborne infection from aerosol-generating procedures during the COVID-19 pandemic.


Assuntos
Aerossóis/normas , Filtros de Ar/normas , /transmissão , Transmissão de Doença Infecciosa/prevenção & controle , Nebulizadores e Vaporizadores/normas , Pandemias/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Material Particulado , Guias de Prática Clínica como Assunto
6.
Drug Discov Today ; 26(3): 631-636, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33385574

RESUMO

The Coronavirus 2019 (COVID-19) pandemic represents the greatest worldwide public health crisis of recent times. The lack of proven effective therapies means that COVID-19 rages relatively unchecked. Current anti-COVID-19 pharmacotherapies are drugs originally designed for other diseases, and administered orally or intravascularly. Thus, they can have various adverse effects. A specific anti-Coronavirus drug should not only target the virus per se, but also treat the related respiratory and cardiovascular symptoms. Here, we examine the advantages and disadvantages of current anti-COVID-19 pharmacotherapies, and analyze the reasons why in the era of big data we have not yet established specific coronavirus therapies and related technical bottlenecks. Finally, we present our design of a novel nebulized S-nitrosocaptopril that is under development for targeting both coronaviruses and their related symptoms.


Assuntos
Antivirais , Captopril/análogos & derivados , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Antivirais/classificação , Antivirais/farmacologia , /epidemiologia , /virologia , Captopril/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/metabolismo , Desenvolvimento de Medicamentos/métodos , Reposicionamento de Medicamentos/métodos , Humanos , Nebulizadores e Vaporizadores , Preparações Farmacêuticas , Sistema Respiratório/diagnóstico por imagem , Sistema Respiratório/metabolismo , /fisiologia , Resultado do Tratamento
7.
J Chromatogr A ; 1638: 461839, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33434814

RESUMO

The application of supercritical fluid chromatography (SFC) coupled to an evaporative light scattering detector (ELSD) and mass spectrometer (MS) was evaluated for the characterisation of three analogues of functionalised polyethylene glycol (PEG) 2000 (m-PEG-OH, m-PEG-cm and cm-PEG-cm (where m = OCH3 and cm = OCH2COOH)). These polymers are common excipients in drug product formulations for pharmaceuticals as they help provide the desired pharmacokinetic profile for successful drug delivery. A SFC-ELSD-MS method was developed which was selective to all three polymers, and allowed visualisation of these low UV chromophore materials. The method provided baseline resolution of the individual oligomers which allowed facile calculation of the polymer dispersity. A number of molecular weight characteristics were calculated, which showed the SFC-ELSD-MS methodology to be comparable with the current standard of analysis using size exclusion chromatography (SEC) with a triple detector array (TDA). The increased resolving power of SFC compared to SEC revealed a bimodal distribution of oligomers in the cm-PEG-cm 2000 polymer, which was not observed using SEC-TDA and exemplified SFC-ELSD as an orthogonal approach for polymer characterisation with the potential for much simpler, reduced sample and instrument preparation, calibration-less dispersity determination. When combined with SEC-TDA data, this combination allows a more complete characterisation of complex formulations excipients.


Assuntos
Cromatografia em Gel/métodos , Cromatografia com Fluido Supercrítico/métodos , Excipientes/química , Luz , Polietilenoglicóis/química , Espalhamento de Radiação , Calibragem , Hidrodinâmica , Espectrometria de Massas , Peso Molecular , Nebulizadores e Vaporizadores , Temperatura , Viscosidade
8.
Biomed Pharmacother ; 133: 111072, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378971

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a progressive pulmonary interstitial inflammatory disease of unknown etiology, and is also a sequela in severe patients with the Coronavirus Disease 2019 (COVID-19). Nintedanib and pirfenidone are the only two known drugs which are conditionally recommended for the treatment of IPF by the FDA. However, these drugs pose some adverse side effects such as nausea and diarrhoea during clinical applications. Therefore, it is of great value and significance to identify effective and safe therapeutic drugs to solve the clinical problems associated with intake of western medicine. As a unique medical treatment, Traditional Chinese Medicine (TCM) has gradually exerted its advantages in the treatment of IPF worldwide through a multi-level and multi-target approach. Further, to overcome the current clinical problems of oral and injectable intakes of TCM, pulmonary drug delivery system (PDDS) could be designed to reduce the systemic metabolism and adverse reactions of the drug and to improve the bioavailability of drugs. Through PubMed, Google Scholar, Web of Science, and CNKI, we retrieved articles published in related fields in recent years, and this paper has summarized twenty-seven Chinese compound prescriptions, ten single TCM, and ten active ingredients for effective prevention and treatment of IPF. We also introduce three kinds of inhaling PDDS, which supports further research of TCM combined with PDDS to treat IPF.


Assuntos
/complicações , Medicamentos de Ervas Chinesas/uso terapêutico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Fitoterapia , Composição de Medicamentos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , História do Século XV , História do Século XVI , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , História Antiga , História Medieval , Humanos , Fibrose Pulmonar Idiopática/etiologia , Fibrose Pulmonar Idiopática/prevenção & controle , Medicina Tradicional Chinesa/história , Nebulizadores e Vaporizadores , Terapia Respiratória
9.
Med Gas Res ; 10(4): 193-200, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33380588

RESUMO

Recent development regarding mixture of H2 (concentration of ~66%) with O2 (concentration of ~34%) for medical purpose, such as treatment of coronavirus disease-19 (COVID-19) patients, is introduced. Furthermore, the design principles of a hydrogen inhaler which generates mixture of hydrogen (~66%) with oxygen (~34%) for medical purpose are proposed. With the installation of the liquid blocking module and flame arresters, the air pathway of the hydrogen inhaler is divided by multiple isolation zones to prevent any unexpected explosion propagating from one zone to the other. An integrated filtering/cycling module is utilized to purify the impurity, and cool down the temperature of the electrolytic module to reduce the risk of the explosion. Moreover, a nebulizer is provided to selectively atomize the water into vapor which is then mixed with the filtered hydrogen-oxygen mix gas, such that the static electricity of a substance hardly occurs to reduce the risk of the explosion. Furthermore, hydrogen concentration detector is installed to reduce the risk of hydrogen leakage. Result shows that the hydrogen inhaler implementing the aforesaid design rules could effectively inhibit the explosion, even ignition at the outset of the hydrogen inhaler which outputs hydrogen-oxygen gas (approximately 66% hydrogen: 34% oxygen).


Assuntos
/terapia , Hidrogênio/administração & dosagem , Nebulizadores e Vaporizadores , Oxigenoterapia/métodos , Oxigênio/administração & dosagem , Explosões/prevenção & controle , Humanos , Nebulizadores e Vaporizadores/normas , Oxigenoterapia/normas , Eletricidade Estática/efeitos adversos , Volatilização
11.
BMJ Case Rep ; 13(12)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33370982

RESUMO

There are several causes for sudden onset unilateral mydriasis, however impending transtentorial uncal herniation needs to be ruled out. This unique case highlights an uncommon adverse response to a common mode of treatment that leads to a diagnostic dilemma. A 3-year-old boy with a ventriculoperitoneal (VP) shunt for an obstructive hydrocephalus presented with an acute respiratory distress. He developed unilateral mydriasis with absent light reflex during treatment with nebulisers. An urgent CT scan of the brain did not show any new intracranial abnormality. A case of pharmacological anisocoria was diagnosed that resolved completely within 24 hours of discontinuation of ipratropium bromide. Although ipratropium-induced anisocoria has been reported in children, but to our knowledge none in a child with VP shunt for hydrocephalus. This emphasises the urgency in evaluating unilateral mydriasis to rule out life-threatening conditions. Clinicians should remember that ipratropium administered through ill-fitting face masks could cause this completely reversible adverse effect.


Assuntos
Anisocoria/induzido quimicamente , Hidrocefalia/cirurgia , Ipratrópio/efeitos adversos , Midríase/induzido quimicamente , Derivação Ventriculoperitoneal , Administração por Inalação , Anisocoria/diagnóstico , Encéfalo/diagnóstico por imagem , Pré-Escolar , Humanos , Hidrocefalia/complicações , Ipratrópio/administração & dosagem , Masculino , Midríase/diagnóstico , Nebulizadores e Vaporizadores , Tomografia Computadorizada por Raios X
12.
Nicotine Tob Res ; 22(Suppl 1): S14-S24, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33320250

RESUMO

INTRODUCTION: Chemical elements and their toxicity were evaluated in electronic cigarette (EC) solvents, fluids, and aerosols. AIMS AND METHODS: Element identification and quantification in propylene glycol (PG), glycerin (G), refill fluids before and after use, and aerosols was done using inductively coupled plasma optical emission spectrometry. Cytotoxicity and oxidative stress were evaluated using in vitro assays. RESULTS: Seven elements were present in PG, G, and popular refill fluids, and they transferred to aerosols made with ECs. Selenium was in all products (0.125-0.292 mg/L), while arsenic, aluminum, and tin were frequently in solvent and refill fluid samples at lower concentrations. Iron, chromium, copper, nickel, zinc, and lead were only detected in fluid after EC use, indicating they came from heated atomizers. Elements transferred most efficiently to aerosols made with second-/third-generation ECs. Of the elements in fluid, selenium and arsenic were the most cytotoxic to human bronchial epithelial cells (BEAS-2B) and pulmonary fibroblasts in the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay. Selenium increased superoxide production in mitochondria and nucleoli and elevated selenoprotein H in nucleoli of BEAS-2B cells at concentrations found in EC aerosols (10 nM or 0.002 mg/L). CONCLUSIONS: Elements in EC aerosols came from both e-fluids and atomizing units. Within second-/third-generation products, transfer became more efficient as power increased. In vitro responses occurred at concentrations of selenium found in some EC aerosols. Human exposure to chemical elements in ECs could be reduced by regulating (decreasing) allowable EC power and by improving the purity of PG and G. IMPLICATIONS: PG, G, refill fluids, and e-fluids contained potentially toxic chemical elements that transferred to aerosols. Transfer was more efficient in second- and third-generation EC products and increased as power increased. Selenium and arsenic were the most cytotoxic of the elements tested in the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay. Selenium tetrachloride-induced oxidative stress in BEAS-2B cells, but not in human pulmonary fibroblasts. All fluids contained selenium above the concentration that induced oxidative stress in human bronchial epithelial cells. Selenium increased superoxide in mitochondria and nucleoli and increased selenoprotein H, a redox responsive DNA-binding protein that is upregulated by superoxide and an indicator of nucleolar stress. EC users are exposed to elements in aerosols, which may with chronic exposure contribute to diseases associated with oxidative stress.


Assuntos
Aerossóis/farmacologia , Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Células Epiteliais/patologia , Pulmão/patologia , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/antagonistas & inibidores , Solventes/farmacologia , Células Cultivadas , Células Epiteliais/efeitos dos fármacos , Humanos , Pulmão/efeitos dos fármacos , Nebulizadores e Vaporizadores/estatística & dados numéricos
13.
Thromb Haemost ; 120(12): 1700-1715, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33368089

RESUMO

The dependence of development and homeostasis in animals on the interaction of hundreds of extracellular regulatory proteins with the peri- and extracellular glycosaminoglycan heparan sulfate (HS) is exploited by many microbial pathogens as a means of adherence and invasion. Heparin, a widely used anticoagulant drug, is structurally similar to HS and is a common experimental proxy. Exogenous heparin prevents infection by a range of viruses, including S-associated coronavirus isolate HSR1. Here, we show that heparin inhibits severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) invasion of Vero cells by up to 80% at doses achievable through prophylaxis and, particularly relevant, within the range deliverable by nebulisation. Surface plasmon resonance and circular dichroism spectroscopy demonstrate that heparin and enoxaparin, a low-molecular-weight heparin which is a clinical anticoagulant, bind and induce a conformational change in the spike (S1) protein receptor-binding domain (S1 RBD) of SARS-CoV-2. A library of heparin derivatives and size-defined fragments were used to probe the structural basis of this interaction. Binding to the RBD is more strongly dependent on the presence of 2-O or 6-O sulfate groups than on N-sulfation and a hexasaccharide is the minimum size required for secondary structural changes to be induced in the RBD. It is likely that inhibition of viral infection arises from an overlap between the binding sites of heparin/HS on S1 RBD and that of the angiotensin-converting enzyme 2. The results suggest a route for the rapid development of a first-line therapeutic by repurposing heparin and its derivatives as antiviral agents against SARS-CoV-2 and other members of the Coronaviridae.


Assuntos
Anticoagulantes/farmacologia , Antivirais/farmacologia , Enoxaparina/farmacologia , Heparina/farmacologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Animais , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , Chlorocebus aethiops , Enoxaparina/uso terapêutico , Heparina/uso terapêutico , Humanos , Simulação de Dinâmica Molecular , Nebulizadores e Vaporizadores , Ligação Proteica , Conformação Proteica , Domínios Proteicos/genética , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Relação Estrutura-Atividade , Células Vero , Internalização do Vírus
14.
Ther Adv Respir Dis ; 14: 1753466620954366, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33167796

RESUMO

Coronavirus disease 2019 (COVID-19), caused by the highly contagious novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a worldwide pandemic and currently represents a major public health issue. COVID-19 has highlighted the need for clear and accurate guidance on the use of aerosol-generating procedures, such as nebulization, for the treatment of patients with respiratory diseases with or without COVID-19. Despite the lack of evidence, there is heightened concern about the potential risk of transmission of SARS-CoV-2 in the form of aerosolized respiratory droplets during the nebulized treatment of patients with COVID-19. Consequently, the use of metered-dose inhalers (MDIs) has risen considerably as an alternative to nebulized therapy, which has led to inadequate supplies of MDIs in some parts of the United States. In this article, we review and discuss the role of nebulization in patients with SARS-CoV-2 and the treatment of noninfected patients with chronic respiratory diseases. The following two important questions are addressed: (1) should nebulized therapy be used in hospital or home settings by patients infected with SARS-CoV-2; and (2) should nebulized therapy be continued in patients already using it for chronic respiratory disease management in hospital or home settings?The reviews of this paper are available via the supplemental material section.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/transmissão , Nebulizadores e Vaporizadores , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/transmissão , Administração por Inalação , Aerossóis , Infecções por Coronavirus/complicações , Humanos , Pandemias , Pneumonia Viral/complicações
15.
Pediatrics ; 146(5)2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33060258

RESUMO

BACKGROUND: Exogenous surfactants to treat respiratory distress syndrome (RDS) are approved for tracheal instillation only; this requires intubation, often followed by positive pressure ventilation to promote distribution. Aerosol delivery offers a safer alternative, but clinical studies have had mixed results. We hypothesized that efficient aerosolization of a surfactant with low viscosity, early in the course of RDS, could reduce the need for intubation and instillation of liquid surfactant. METHODS: A prospective, multicenter, randomized, unblinded comparison trial of aerosolized calfactant (Infasurf) in newborns with signs of RDS that required noninvasive respiratory support. Calfactant was aerosolized by using a Solarys nebulizer modified with a pacifier adapter; 6 mL/kg (210 mg phospholipid/kg body weight) were delivered directly into the mouth. Infants in the aerosol group received up to 3 treatments, at least 4 hours apart. Infants in the control group received usual care, determined by providers. Infants were intubated and given instilled surfactant for persistent or worsening respiratory distress, at their providers' discretion. RESULTS: Among 22 NICUs, 457 infants were enrolled; gestation 23 to 41 (median 33) weeks and birth weight 595 to 4802 (median 1960) grams. In total, 230 infants were randomly assigned to aerosol; 225 received 334 treatments, starting at a median of 5 hours. The rates of intubation for surfactant instillation were 26% in the aerosol group and 50% in the usual care group (P < .0001). Respiratory outcomes up to 28 days of age were no different. CONCLUSIONS: In newborns with early, mild to moderate respiratory distress, aerosolized calfactant at a dose of 210 mg phospholipid/kg body weight reduced intubation and surfactant instillation by nearly one-half.


Assuntos
Produtos Biológicos/administração & dosagem , Surfactantes Pulmonares/administração & dosagem , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Administração Oral , Aerossóis , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Intubação Intratraqueal/estatística & dados numéricos , Masculino , Nebulizadores e Vaporizadores , Estudos Prospectivos
16.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5531-5536, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019232

RESUMO

The estimation of inhalation flow rate (IFR) using acoustic devices has recently received attention. While existing work often assumes that the microphone is placed at a fixed distance from the acoustic device, this assumption does not hold in real settings. This leads to poor estimation of the IFR since the received acoustic energy varies significantly with the distance. Despite the fact that the acoustic source is passive and only one microphone is used, we show in this paper that the distance can be estimated by exploiting the inhaler actuation sound, generated when releasing the medication. Indeed, this sound is used as a reference acoustic signal which is leveraged to estimate the distance in real settings. The resulting IFR estimation is shown to be highly accurate (R2 = 80.3%).


Assuntos
Acústica , Asma , Asma/tratamento farmacológico , Humanos , Nebulizadores e Vaporizadores , Taxa Respiratória , Som
17.
J Anesth Hist ; 6(3): 168-169, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32921491

RESUMO

An Ohio dentist, Corydon Munson, patented a gasometer with an attachment for vaporizing trace amounts of volatile general anesthetics or their mixtures into unoxygenated nitrous oxide. After vaporizing a variant of George Harley's ACE mixture into nitrous oxide, Munson branded his own novel anesthetic combination as ACENO.


Assuntos
Anestesia Dentária/história , Anestésicos Inalatórios/história , Equipamentos Odontológicos/história , Nebulizadores e Vaporizadores/história , Óxido Nitroso/história , Álcoois/história , Anestesia Dentária/instrumentação , Anestésicos Inalatórios/química , Clorofórmio/história , Éter/história , História do Século XIX , Reino Unido , Estados Unidos
18.
Mol Med ; 26(1): 91, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993479

RESUMO

BACKGROUND: Mechanically ventilated patients with COVID-19 have a mortality of 24-53%, in part due to distal mucopurulent secretions interfering with ventilation. DNA from neutrophil extracellular traps (NETs) contribute to the viscosity of mucopurulent secretions and NETs are found in the serum of COVID-19 patients. Dornase alfa is recombinant human DNase 1 and is used to digest DNA in mucoid sputum. Here, we report a single-center case series where dornase alfa was co-administered with albuterol through an in-line nebulizer system. METHODS: Demographic and clinical data were collected from the electronic medical records of five mechanically ventilated patients with COVID-19-including three requiring veno-venous extracorporeal membrane oxygenation-treated with nebulized in-line endotracheal dornase alfa and albuterol, between March 31 and April 24, 2020. Data on tolerability and response were analyzed. RESULTS: The fraction of inspired oxygen requirements was reduced for all five patients after initiating dornase alfa administration. All patients were successfully extubated, discharged from hospital and remain alive. No drug-associated toxicities were identified. CONCLUSIONS: Results suggest that dornase alfa will be well-tolerated by patients with severe COVID-19. Clinical trials are required to formally test the dosing, safety, and efficacy of dornase alfa in COVID-19, and several have been recently registered.


Assuntos
Albuterol/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Desoxirribonuclease I/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Respiração Artificial , Adulto , Idoso , Albuterol/uso terapêutico , Broncodilatadores/administração & dosagem , Broncodilatadores/uso terapêutico , Infecções por Coronavirus/terapia , Desoxirribonuclease I/uso terapêutico , Feminino , Humanos , Intubação Intratraqueal , Masculino , Nebulizadores e Vaporizadores , Pandemias , Pneumonia Viral/terapia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico
19.
Int J Mol Sci ; 21(17)2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32899381

RESUMO

Respiratory and pulmonary diseases are among the leading causes of death globally. Despite tremendous advancements, there are no effective pharmacological therapies capable of curing diseases such as COPD (chronic obstructive pulmonary disease), ARDS (acute respiratory distress syndrome), and COVID-19. Novel and innovative therapies such as advanced therapy medicinal products (ATMPs) are still in early development. However, they have exhibited significant potential preclinically and clinically. There are several longitudinal studies published, primarily focusing on the use of cell therapies for respiratory diseases due to their anti-inflammatory and reparative properties, thereby hinting that they have the capability of reducing mortality and improving the quality of life for patients. The primary objective of this paper is to set out a state of the art review on the use of aerosolized MSCs and their potential to treat these incurable diseases. This review will examine selected respiratory and pulmonary diseases, present an overview of the therapeutic potential of cell therapy and finally provide insight into potential routes of administration, with a focus on aerosol-mediated ATMP delivery.


Assuntos
Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Pneumonia Viral/terapia , Doença Pulmonar Obstrutiva Crônica/terapia , /terapia , Animais , Humanos , Transplante de Células-Tronco Mesenquimais/instrumentação , Nebulizadores e Vaporizadores , Pandemias
20.
Praxis (Bern 1994) ; 109(12): 985-990, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32933396

RESUMO

Physical and Clinical Aspects of Inhalation Therapy for Asthma and COPD Abstract. Inhalations form the basis of the medicinal treatment of respiratory diseases. In recent years, therapy has become more complex for patients, but also for medical professionals, as new systems have come onto the market. The knowledge required for this shall be conveyed in this article.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Terapia Respiratória , Administração por Inalação , Asma/terapia , Humanos , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica/terapia
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