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1.
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
2.
Allergol. immunopatol ; 48(3): 214-222, mayo-jun. 2020. graf, tab
Artigo em Inglês | IBECS | ID: ibc-192022

RESUMO

INTRODUCTION AND OBJECTIVES: Functional and inflammatory measures have been recommended to corroborate asthma diagnosis in schoolchildren, but the evidence in this regard is conflicting. We aimed to determine, in real-life clinical situation, the value of spirometry, spirometric bronchial reversibility to salbutamol (BDR), bronchial responsiveness to methacholine (MCT) and fractional exhaled nitric oxide (FENO), to corroborate the diagnosis of asthma in children on regular inhaled corticosteroids (ICS) referred from primary care. METHODS: One hundred and seventy-seven schoolchildren with mild-moderate persistent asthma, on treatment with regular ICS, participated in the study. Abnormal tests were defined as FENO ≥ 27 ppb, BDR (FEV1 ≥ 12%) and methacholine PC20 ≤ 4 mg/mL. RESULTS: The proportions of positive BDR, FENO and MCT, were 16.4%, 33.3%, and 87.0%, respectively. MCT was associated with FENO (p < 0.03) and BDR (p = 0.001); FENO was associated with BDR (p = 0.045), family history of asthma (p = 0.003) and use of asthma medication in the first two years of life (p = 0.004). BDR was significantly related with passive tobacco exposure (p = 0.003). CONCLUSIONS: Spirometry, BDR and BDR had a poor performance for corroborating diagnosis in our asthmatic children on ICS treatment; on the contrary, MCT was positive in most of them, which agrees with previous reports. Although asthma tests are useful to corroborate asthma when positive, clinical diagnosis remains the best current approach for asthma diagnosis, at least while better objective and feasible measurements at the daily practice are available. At present, these tests may have a better role for assessing the management and progression of the condition


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Assuntos
Humanos , Masculino , Feminino , Criança , Asma/diagnóstico , Asma/tratamento farmacológico , Albuterol/administração & dosagem , Óxido Nítrico/administração & dosagem , Cloreto de Metacolina/administração & dosagem , Espirometria/instrumentação , Corticosteroides/administração & dosagem , Poluição por Fumaça de Tabaco/efeitos adversos , Estudos Transversais , Consentimento Livre e Esclarecido , Análise de Dados
4.
Pediatrics ; 145(4)2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32165556

RESUMO

BACKGROUND AND OBJECTIVES: The albuterol dropper bottle used to prepare solutions for continuous nebulization contains the preservative benzalkonium chloride (BAC). BAC, by itself, has been shown to cause bronchospasm. We hypothesized that BAC would decrease the therapeutic efficacy of albuterol in patients with acute asthma exacerbations. METHODS: We performed a retrospective cohort study comparing the clinical outcomes of patients <18 years of age receiving continuous nebulized albuterol with and without BAC. For the primary end point (duration of continuous albuterol nebulization), we compared the 2 groups with Kaplan-Meier estimate of survival curves, conducted a log-rank test of difference, and adjusted for baseline characteristics using multivariable Cox regression. A P value <.05 was considered significant. RESULTS: A total of 477 patients were included in the analysis (236 exposed to BAC and 241 controls). The duration of continuous nebulization was significantly longer in the BAC group than in the control group (median of 9 vs 6 hours; 15.7% required continuous nebulization compared to 5.8% of controls at 24 hours). The control group was 79% more likely to stop continuous nebulization at any particular point in time (hazard ratio 1.79; 95% confidence interval: 1.45 to 2.22; P < .001) and 43% more likely to stop additional respiratory support (hazard ratio 1.43; 95% confidence interval: 1.16 to 1.75; P < .001). CONCLUSIONS: BAC is a functional albuterol antagonist associated with a longer duration of continuous albuterol nebulization treatment and additional respiratory support, suggesting that preservative-free albuterol formulations are safer for use in continuous nebulization.


Assuntos
Albuterol/administração & dosagem , Asma/tratamento farmacológico , Compostos de Benzalcônio/administração & dosagem , Broncodilatadores/administração & dosagem , Conservantes Farmacêuticos/administração & dosagem , Administração por Inalação , Adolescente , Albuterol/antagonistas & inibidores , Albuterol/química , Compostos de Benzalcônio/efeitos adversos , Broncodilatadores/antagonistas & inibidores , Broncodilatadores/química , Criança , Pré-Escolar , Progressão da Doença , Interações Medicamentosas , Feminino , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Modelos Lineares , Masculino , Conservantes Farmacêuticos/efeitos adversos , Análise de Regressão , Estudos Retrospectivos
5.
Pediatrics ; 145(3)2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32051218

RESUMO

Since the discovery of propranolol in the treatment of infantile hemangioma (IH), there has been emergent investigation of ß-adrenergic receptor (ß-AR) signaling in IH and the mechanisms of action for which ß-AR blockers regulate hemangioma cell proliferation. However, ß-AR agonists and antagonists are known to act antithetically via the same intracellular ß-AR-driven proangiogenic pathways. We present the case of a patient with involuted IH treated with propranolol that showed a full and rapid regrowth during the intravenous administration of salbutamol, a selective ß2-adrenergic agonist, for an episode of severe obstructive bronchitis. This observation brings forward the clinical implication of ß-signaling effects in IH and raises awareness of the potential proliferative response of IH to ß-AR agonists such as salbutamol.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Albuterol/efeitos adversos , Hemangioma/patologia , Recidiva Local de Neoplasia/induzido quimicamente , Neoplasias Cutâneas/patologia , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Albuterol/administração & dosagem , Bronquite/tratamento farmacológico , Pré-Escolar , Feminino , Hemangioma/tratamento farmacológico , Humanos , Infusões Intravenosas , Propranolol/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Vasodilatadores/uso terapêutico
6.
Int J Pharm ; 575: 119000, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31893544

RESUMO

Based on dry powder inhaler (DPI) inhalation process, powder properties have a key influence on fluidization and deagglomeration behavior during aerosol generation. The aim of this study was to explore the influence of drug content on DPI powder properties and further reveal the correlations between powder properties and pulmonary deposition efficiency. Using salbutamol sulfate as a model drug, Lactohale® 100 as carrier, carrier-based binary mixtures were prepared at drug content from 0.5 to 10% (w/w), characterized with powder rheometer, faraday cage and Next Generation Impactor. It was demonstrated that drug content had a remarkable influence on powder behavior, and good correlations between powder properties and fine particle fraction (FPF) were established in drug content range 0.5-7%. A negative correlation between basic flowability energy and FPF, reflected a good flowability is beneficial for powder fluidization. Further properties characterization, including aeration ratio, permeability, pre-shear stress and aerodynamic specific charge, suggested a strong interaction is beneficial for powder deagglomeration. It's the first time that interaction indicator and flowability indicator were extracted with principal component analysis (PCA). In conclusion, drug content has a significant influence on powder properties. DPI formulations with a stronger interaction and meanwhile a better flowability are desirable for enhanced pulmonary drug delivery.


Assuntos
Albuterol/administração & dosagem , Broncodilatadores/administração & dosagem , Química Farmacêutica/métodos , Lactose/química , Administração por Inalação , Inaladores de Pó Seco , Tamanho da Partícula , Reologia , Propriedades de Superfície
7.
Pediatr Pulmonol ; 55(4): 866-873, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31951679

RESUMO

OBJECTIVES: Although the benefits of albuterol delivered via metered-dose inhalers with a spacer (MDI+S) have been increasingly recognized, the evidence regarding the cost-effectiveness of MDI+S compared to nebulization (NEB) is not sufficient, especially in less-affluent countries, where the clinical and economic burden of the disease is the greatest. The aim of the present study was to evaluate the cost-effectiveness of MDI+S vs NEB for delivering albuterol for the treatment of pediatric asthma exacerbations. METHODS: A decision-analysis model was developed to estimate the cost-effectiveness of MDI+S vs NEB for delivering albuterol for the treatment of pediatric asthma exacerbations. Effectiveness parameters were obtained from a systematic review of the literature. Cost data were obtained from hospital bills and from the national manual of drug prices in Colombia. The study was carried out from the perspective of the national healthcare system in Colombia, a middle-income country (MIC). The main outcome of the model was the avoidance of hospital admission. RESULTS: For the base-case analysis, the model showed that compared to NEB, using MDI+S for the delivery of albuterol was associated with lower total costs (US$96.68 vs US$121.41 average cost per patient) and a higher probability of hospital admission avoided (0.9219 vs 0.8900), thus leading to dominance. CONCLUSIONS: This study shows that in Colombia, an MIC, compared with NEB, the use of MDI+S for delivering albuterol for the treatment of pediatric asthma exacerbations is the preferred strategy because it is associated with a lower probability of hospital admission at lower total treatment costs.


Assuntos
Albuterol/administração & dosagem , Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Broncodilatadores/economia , Inaladores Dosimetrados , Nebulizadores e Vaporizadores , Administração por Inalação , Albuterol/economia , Criança , Colômbia , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Hospitalização/estatística & dados numéricos , Humanos , Inaladores Dosimetrados/economia
8.
AAPS PharmSciTech ; 21(2): 53, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907655

RESUMO

To achieve adequate inhalation therapy, a proper inhalation technique is needed in clinical practice. However, there is limited information on proper inhalation flow patterns of commercial inhalers. Here, we quantitatively estimated airway deposition of two commercial pressurized metered dose inhalers (pMDIs) to determine their optimal inhalation patterns. Sultanol® inhaler (drug particles suspended in a propellant, suspension-pMDI) and QVAR™ (drug dissolved in a propellant with ethanol, solution-pMDI) were used as model pMDIs. Aerodynamic properties of the two pMDIs were determined using an Andersen cascade impactor with human inhalation flow simulator developed by our laboratory. As indices of peripheral-airway drug deposition, fine particle fractions (FPFPA) at different inhalation flow rates were calculated. The time-dependent particle diameters of sprayed drug particles were determined by laser diffraction. On aerodynamic testing, FPFPA of suspension-pMDI significantly decreased depending on the increasing inhalation flow rate, while solution-pMDI achieved higher and constant FPFPA in the range of the tested inhalation flow rates. The particle diameter of solution-pMDI markedly decreased from 5 to 3 µm in a time-dependent manner. Conversely, that of suspension-pMDI remained at 4 µm during the spraying time. Although "slow inhalation" is recommended for pMDIs, airway drug deposition via solution-pMDI (extra-fine particles) is independent of patients' inhalation flow pattern. Clinical studies should be performed to validate instruction for use of pMDIs for each inhaler for the optimization of inhalation therapy.


Assuntos
Albuterol/administração & dosagem , Inaladores Dosimetrados , Administração por Inalação , Humanos , Tamanho da Partícula
9.
Pediatr Pulmonol ; 55(2): 322-329, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31782914

RESUMO

OBJECTIVES: Transnasal pulmonary aerosol delivery using high-flow nasal cannula (HFNC) devices has become a popular route of aerosol administration in toddlers. Clinically, albuterol is administered using an infusion pump or unit doses. However, little evidence is available to compare the two administration strategies. METHODS: A toddler manikin (15 kg) with appropriate anatomic airway was connected with collecting filter to a simulator of distressed breathing. HFNC device with mesh nebulizer placed at the inlet of a humidifier at 37°C, with the gas flow set at 25 and 3.75 L/min. Five milligrams of albuterol was delivered in all experiments. With infusion pump administration, albuterol concentrations of 5 and 1 mg/mL were delivered at 4 and 20 mL/hr for 15 minutes. With unit dose administration, 1 mL (5 mg/mL) and 2 mL (2.5 mg/mL) of albuterol were nebulized. Additional tests with mouth open and nebulizers via mask were using 5 mg/1 mL for mesh nebulizer and 5 mg/3 mL for jet nebulizer (n = 3). The drug was eluted from the filter and assayed with UV spectrophotometry (276 nm). RESULTS: The inhaled dose was higher with unit dose than infusion pump administration with gas flows of 25 L/min (2.66 ± 0.38 vs 1.16 ± 0.28%; P = .004) and 3.75 L/min (10.51 ± 1.29 vs 8.58 ± 0.68%; P = .025). During unit dose administration, compared with closed-mouth breathing, open-mouth breathing generated a higher inhaled dose at 3.75 L/min and lower inhaled dose at 25 L/min. Compared to the nebulizers via mask with both open and closed-mouth breathing, nebulization via HFNC at 3.75 L/min generated greater inhaled dose, while HFNC at 25 L/min generated lower inhaled dose. CONCLUSIONS: During transnasal aerosol delivery, the inhaled dose was higher with medication administrated using unit dose than using an infusion pump.


Assuntos
Albuterol/administração & dosagem , Broncodilatadores/administração & dosagem , Cânula , Administração por Inalação , Aerossóis/administração & dosagem , Albuterol/uso terapêutico , Broncodilatadores/uso terapêutico , Pré-Escolar , Desenho de Equipamento , Humanos , Umidificadores , Bombas de Infusão , Pulmão , Manequins , Nebulizadores e Vaporizadores , Respiração
10.
Pediatr Pulmonol ; 55(1): 83-89, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31626398

RESUMO

BACKGROUND: Asthma is a common pediatric diagnosis for emergency medical services (EMS) transports, however there is a paucity of data on prehospital asthma management. The purpose of this study was to describe prehospital management of pediatric patients with suspected asthma exacerbation. METHODS: We conducted a retrospective review of electronic medical records from 24 ground EMS agencies in Southwestern Pennsylvania between 1 January 2014 to 31 December 2017. We identified patients 2 to 17 years with documented wheezing, excluding those with suspected anaphylaxis. Patients with documented respiratory distress were classified as severe asthma. We report descriptive statistics of demographics, vital signs, and management including administration of medications and performance of procedures. RESULTS: Of 19 246 pediatric transports, 1078 (5.6%) patients had wheezing. Of these, 532 (49%) met criteria for severe asthma. Patients with severe asthma were more likely to be adolescents compared to those with nonsevere asthma (49.6% vs 6%; P < .001). While rates of intravenous methylprednisolone administration were higher in patients with severe asthma (68/532, 12.8%) compared to those with nonsevere asthma (13/546, 2.4%; P < .001), overall use of steroids was low (7.5%). Other therapies provided included albuterol (n = 699, 64.8%), ipratropium bromide (n = 271, 25.1%), and oxygen (n = 280, 26.0%). One hundred eighty patients (16.7%) received a peripheral IV line. Two patients (0.4%) were given continuous positive airway pressure. CONCLUSION: Approximately 6% of pediatric EMS transports are for asthma. Steroid usage was low in even those with severe asthma, representing an area of process improvement. These data provide a baseline to future research to identify interventions that may improve outcomes.


Assuntos
Asma/terapia , Adolescente , Albuterol/administração & dosagem , Anafilaxia , Criança , Serviços Médicos de Emergência , Feminino , Humanos , Infusões Intravenosas , Ipratrópio , Masculino , Metilprednisolona , Monitorização Fisiológica , Oxigênio , Sons Respiratórios , Estudos Retrospectivos
11.
Mol Genet Metab ; 129(2): 67-72, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31839530

RESUMO

This 24-week, Phase I/II, double-blind, randomized, placebo-controlled study investigated the safety and efficacy of extended-release albuterol in late-onset Pompe disease stably treated with enzyme replacement therapy at the standard dose for 4.9 (1.0-9.4) years and with no contraindications to intake of albuterol. Twelve of 13 participants completed the study. No serious adverse events were related to albuterol, and transient minor drug-related adverse events included muscle spasms and tremors. For the albuterol group, forced vital capacity in the supine position increased by 10% (p < .005), and forced expiratory volume in one second increased by 8% (p < .05); the six-minute walk test increased 25 m (p < .05; excluding one participant unable to complete muscle function testing); the Gross Motor Function Measure increased by 8% (p < .005) with the greatest increases in the Standing (18%; p < .05) and Walking, Running, and Jumping (11%; p < .005) subtests. No significant improvements would be expected in patients with late-onset Pompe disease who were stably treated with enzyme replacement therapy. The placebo group demonstrated no significant increases in performance on any measure. These data support a potential benefit of extended-release albuterol as adjunctive therapy in carefully selected patients with late-onset Pompe disease based on ability to take albuterol on enzyme replacement therapy (NCT01885936).


Assuntos
Albuterol/administração & dosagem , Doença de Depósito de Glicogênio Tipo II/tratamento farmacológico , Transtornos de Início Tardio/tratamento farmacológico , Músculo Esquelético/efeitos dos fármacos , Adulto , Método Duplo-Cego , Terapia de Reposição de Enzimas , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiologia , Resultado do Tratamento , Capacidade Vital , Teste de Caminhada
12.
Eur J Pediatr ; 179(3): 455-461, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31797080

RESUMO

Most pediatric asthma guidelines offer evidence-based or best practice approaches to the management of asthma exacerbations but struggle with evidence-based approaches for severe acute asthma (SAA). We aimed to investigate current practices in children with SAA admitted to European pediatric intensive care units (PICUs), in particular, adjunct therapies, use of an asthma severity score, and availability of a SAA guideline. We designed a cross-sectional electronic survey across European PICUs. Thirty-seven PICUs from 11 European countries responded. In 8 PICUs (22%), a guideline for SAA management was unavailable. Inhaled beta-agonists and anticholinergics, combined with systemic steroids and IV MgSO4 was central in SAA treatment. Seven PICUs (30%) used a loading dose of a short-acting beta-agonist. Eighteen PICUs (49%) used an asthma severity score, with 8 different scores applied. Seventeen PICUs (46%) observed an increasing trend in SAA admissions.Conclusion: Variations in the treatment of children with SAA mainly existed in the use of adjunct therapies and asthma severity scores. Importantly, in 22% of the PICUs, a SAA guideline was unavailable. Standardizing SAA guidelines across PICUs in Europe may improve quality of care. However, the limited number of PICUs represented and the data compilation method are constraining our findings.What is Known:• Recent reports demonstrate increasing numbers of children with SAA requiring PICU admission in several countries across the world.• Most pediatric guidelines offer evidence-based approaches to the management of asthma exacerbations, but struggle with evidence-based approaches for SAA beyond these initial steps.What is New:• A large arsenal of adjunct therapies and 8 different asthma scores were used.• In a large number of PICUs, a written guideline for SAA management is lacking.


Assuntos
Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Estado Asmático/terapia , Albuterol/administração & dosagem , Broncodilatadores/administração & dosagem , Criança , Estudos Transversais , Europa (Continente)/epidemiologia , Humanos , Guias de Prática Clínica como Assunto , Índice de Gravidade de Doença , Estado Asmático/mortalidade , Inquéritos e Questionários
13.
J Sports Sci Med ; 18(4): 716-721, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31827356

RESUMO

The purpose of the study was to investigate the effect of inhaling 1600 µg of salbutamol (SAL) on 30 m sprint before and after the Yo-Yo Intermittent Recovery test. In a randomised cross over single blind study 13 male non-asthmatic, football players volunteered (mean ± SD; age 18.1 ± 0.9 years; weight 69.5 ± 8.3 kg; height 1.78 ± 0.07 m). Participants completed two visits and were randomly assigned to either (SAL) or (PLA) treatment and performed a set of three sprints of 30 m before and after the Yo-Yo Intermittent Recovery Test (Yo-Yo IRT). Best sprint and mean sprint were analysed in addition to the distance covered during the Yo-Yo IRT; rating of perceived exertion and heart rate were collected at the end of each level completed. Repeated measures ANOVA were performed to investigate changes in performance between groups. Following the inhalation of supra-therapeutic salbutamol dose (1600 µg) neither 30 m sprint time (PLA 4.43 ± 0.14 s; SAL 4.44 ± 0.15 s, p = 0.76) nor distance covered in the Yo-Yo IRT test reported significant variation between PLA conditions (1660 ± 217 m) and SAL (1610 ± 229 m, p = 0.16). Moreover, lactate values, heart rate and RPE did not differ significantly between groups. The inhalation of 1600 µg salbutamol does not enhance 30 m sprint performance in non-fatigued and fatigue conditions. Our findings suggest when football players acutely inhale double the permitted dose of salbutamol, as indicated in the World Anti-Doping Agency List of Prohibited Substances and Methods, they will not experience improvements in sprint or endurance performance.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Albuterol/farmacologia , Teste de Esforço/métodos , Substâncias para Melhoria do Desempenho , Corrida/fisiologia , Futebol/fisiologia , Adolescente , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Afeto , Albuterol/administração & dosagem , Estudos Cross-Over , Frequência Cardíaca/efeitos dos fármacos , Humanos , Ácido Láctico/sangue , Masculino , Motivação , Percepção/efeitos dos fármacos , Esforço Físico/efeitos dos fármacos , Corrida/psicologia , Método Simples-Cego , Futebol/psicologia
14.
Rev Fac Cien Med Univ Nac Cordoba ; 76(4): 222-226, 2019 11 27.
Artigo em Espanhol | MEDLINE | ID: mdl-31833745

RESUMO

Introduction: Asthma is related to caries but the risk factors are not completely determined. Therefore, the objective of the study was to determine the risk of dental caries in pediatric asthmatic patients in inhalation treatment with salbutamol and budesonide who went to the National Hospital Arzobispo Loayza. Methods: Case-control study that consisted of 184 pediatric patients, between 5 and 12 years old, who attended the pneumology and pediatric dentistry service of the National Hospital Arzobispo Loayza during the years 2016-2017. The group of cases (n = 92) was composed of patients with moderate asthma medicated with inhaled salbutamol and budesonide, while the control group (n = 92) was composed of healthy patients. The risk of dental caries was evaluated with the dietary record, oral hygiene index and number of carious lesions. Results: The risk according to the type of cariogenic diet was moderate in both groups (p = 0.768). The oral hygiene index in the control group was regular in 63% (n = 58) and in the case group, bad in 60.9% (n = 56); p=0.001. The number of carious lesions in the control group was moderate in 50% (n = 46) and in the case group, high in 47.8% (n = 44); p = 0.001. Therefore, the risk of dental caries in the case group was high in 50% (n = 46) and in the control group it was moderate in 72.8% (n = 67); p = 0.001. Conclusion: The risk of dental caries in asthmatic patients on inhaled therapy with salbutamol and budesonide is significantly higher than that of healthy patients.


Assuntos
Albuterol/efeitos adversos , Antiasmáticos/efeitos adversos , Asma/tratamento farmacológico , Budesonida/efeitos adversos , Cárie Dentária/induzido quimicamente , Administração por Inalação , Albuterol/administração & dosagem , Antiasmáticos/administração & dosagem , Budesonida/administração & dosagem , Estudos de Casos e Controles , Criança , Pré-Escolar , Cárie Dentária/epidemiologia , Feminino , Humanos , Incidência , Masculino , Higiene Bucal , Peru/epidemiologia , Projetos Piloto , Fatores de Risco
15.
Pulm Pharmacol Ther ; 59: 101857, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31678460

RESUMO

AIMS: Our aim was to evaluate whether the number of puffs or antistatic treatment have significant effect on drug delivery of six different valved holding chambers (VHCs). METHODS: We used simulated paediatric breathing pattern with 25/min frequency and 200 ml tidal volume. When comparing the effect of antistatic treatment, we used 100 µg of salbutamol (one puff Ventolin Evohaler 100 µg/dos) actuated into each VHC before and after detergent wash. When comparing the effect of one or two puffs (100 vs. 200 µg), all VHCs were washed prior to the measurements. RESULTS: All VHC were significantly affected by antistatic treatment. Washing improved drug delivery of four VHCs (1.3-2.2 fold increase in median filter dose) but had an opposite effect in two devices (54-61% decrease). The effect of dose doubling resulted in a 2.03-2.93 fold increase on filter dose in two VHCs. Four out of the six VHC showed significantly poorer performance with two puffs as opposed to one puff (ratio of two puffs to one puff varied between 1.19 and 1.77). CONCLUSION: VHCs marketed as antistatic are significantly affected by antistatic treatment. To ensure optimal drug delivery, salbutamol should be actuated to VHCs one puff at a time. Each VHC brand has its unique characteristic that affects drug delivery in a way that cannot be generalised to another VHC. There is a need for universal standardisation of VHCs. KEY NOTES: Valved holding chambers (VHCs) that are marketed as antistatic are significantly affected by antistatic treatment. Multiple actuations before inhalation tend to decrease the drug delivery efficacy of VHCs. Each VHC brand has its unique characteristic that affects drug delivery in a way that cannot be generalised to another VHC. There is a need for comprehensive and financially independent testing and standardisation of VHCs.


Assuntos
Albuterol/administração & dosagem , Broncodilatadores/administração & dosagem , Sistemas de Liberação de Medicamentos , Eletricidade Estática , Administração por Inalação , Criança , Relação Dose-Resposta a Droga , Desenho de Equipamento , Humanos , Espaçadores de Inalação , Inaladores Dosimetrados , Volume de Ventilação Pulmonar
17.
Pharmacol Rep ; 71(6): 1095-1103, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31629939

RESUMO

BACKGROUND: The regulation of the immune system by the sympathetic nervous system is allowing the design of novel treatments for inflammatory disorders such as arthritis. In this study, we have analyzed the effects of α- and ß-adrenoceptor agonists injected subcutaneously, intrathecally, or intra-articularly in zymosan-induced arthritis. METHODS: Murine arthritis was induced by intra-articular (knee joint) injection of zymosan. α1 (phenylephrine), α2 (clonidine), ß1 (dobutamine), or ß2 (salbutamol)-adrenoceptor agonists were injected subcutaneously (sc), intrathecally (it), or intra-articularly (ia) to activate peripheral, spinal, or intra-articular adrenoceptors and to study their effects on articular edema formation and neutrophil migration into the synovial cavity. RESULTS: Treatments with phenylephrine did not affect the edema formation, but it increased neutrophil migration when injected subcutaneously (155.3%) or intra-articularly (187.7%). Treatments with clonidine inhibited neutrophil migration (59.9% sc, 68.7% it, 42.8% ia) regardless of the route of administration, but it inhibited edema formation only when injected intrathecally (66.7%) or intra-articularly (36%) but not subcutaneously. Treatments with dobutamine inhibited both edema (42.0% sc, 69.5% it, 61.6% ia) and neutrophil migration (28.4% sc, 70.3% it, 82.4% ia) in a concentration dependent manner. Likewise, all the treatments with salbutamol also inhibited edema formation (89.9% sc, 62.4% it, 69.8% ia) and neutrophil migration (76.6% sc, 39.1% it, 71.7% ia). CONCLUSION: Whereas the ß-adrenoceptor agonists induced anti-inflammatory effects regardless of their route of administration, α1- and α2-adrenoceptor agonists induced either pro- and anti-inflammatory effects, respectively.


Assuntos
Agonistas alfa-Adrenérgicos/administração & dosagem , Agonistas alfa-Adrenérgicos/farmacologia , Agonistas Adrenérgicos beta/administração & dosagem , Agonistas Adrenérgicos beta/farmacologia , Artrite Experimental/tratamento farmacológico , Albuterol/administração & dosagem , Albuterol/farmacologia , Animais , Movimento Celular/efeitos dos fármacos , Clonidina/administração & dosagem , Clonidina/farmacologia , Dobutamina/administração & dosagem , Dobutamina/farmacologia , Edema/tratamento farmacológico , Injeções Intra-Articulares , Injeções Intraperitoneais , Injeções Espinhais , Articulação do Joelho , Masculino , Camundongos , Neutrófilos/efeitos dos fármacos , Fenilefrina/administração & dosagem , Fenilefrina/farmacologia , Zimosan
18.
PLoS One ; 14(10): e0223654, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31626649

RESUMO

We examined the effect of liquorice ingestion on haemodynamic responses to exogenous nitric oxide donor (nitroglycerin) and ß2-adrenoceptor agonist (salbutamol), and 11ß-hydroxysteroid dehydrogenase activity, in 21 volunteers and 21 reference subjects. Haemodynamic data was captured before and after sublingual nitroglycerin (0.25 mg) and inhaled salbutamol (400 µg) during orthostatic challenge utilising radial pulse wave analysis and whole-body impedance cardiography. The recordings were performed at baseline and following two weeks of liquorice intake (290-370 mg/d glycyrrhizin). Urinary cortisone and cortisol metabolites were examined. Liquorice intake elevated aortic systolic and diastolic blood pressure and systemic vascular resistance when compared with the reference group. Following research drug administration the liquorice-induced increase in systemic vascular resistance was observed in the presence of nitroglycerin (p<0.05) but no longer in the presence of salbutamol. Liquorice ingestion decreased cardiac chronotropic response to upright posture (p = 0.032) in unadjusted analysis, but when adjusted for age and sex the difference in the upright change in heart rate was no longer significant. The urinary cortisone to cortisol metabolite ratio decreased from 0.70 to 0.31 (p<0.001) after liquorice intake indicating significant inhibition of the 11ß-hydroxysteroid dehydrogenase type 2. In the reference group the haemodynamic variables remained virtually unchanged. These results suggest that liquorice exposure impaired vasodilatation in vivo that was induced by exogenous nitric oxide donor but not that induced by ß2-adrenoceptor stimulation. Trial registration: EU Clinical Trials Register 2006-002065-39 ClinicalTrials.gov NCT01742702.


Assuntos
Ingestão de Alimentos , Glycyrrhiza/metabolismo , Doadores de Óxido Nítrico/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Vasodilatação , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Adulto , Albuterol/administração & dosagem , Biomarcadores , Pressão Sanguínea/efeitos dos fármacos , Cardiografia de Impedância , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Vasodilatação/efeitos dos fármacos
19.
Respiration ; 98(5): 401-409, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31473748

RESUMO

BACKGROUND: There has been increasing interest in transnasal pulmonary aerosol administration, but the dose-response relationship has not been reported. OBJECTIVES: To determine the accumulative bronchodilator dose at which patients with stable mild-to-moderate asthma and chronic obstructive pulmonary disease (COPD) achieve similar spirometry responses before and after bronchodilator tests using albuterol via a metered dose inhaler with a valved holding chamber (MDI + VHC). METHOD: Adult patients who met ATS/ERS criteria for bronchodilator responses in pulmonary function laboratory were recruited and consented to participate. After a washout period, patients received escalating doubling dosages (0.5, 1, 2, and 4 mg) of albuterol in a total volume of 2 mL delivered by vibrating mesh nebulizer via a nasal cannula at 37°C with a flow rate of 15-20 L/min using a Venturi air entrainment device. Spirometry was measured at baseline and after each dose. Titration was stopped when an additional forced expiratory volume in 1 second (FEV1) improvement was <5%. RESULTS: 42 patients (16 males) with stable mild-to-moderate asthma (n = 29) and COPD (n = 13) were enrolled. FEV1 increment after a cumulative dose of 1.5 mg of albuterol via nasal cannula at 15-20 L/min was similar to 4 actuations of MDI + VHC (0.34 ± 0.18 vs. 0.34 ± 0.12 L, p = 0.878). Using ATS/ERS criteria of the bronchodilator test, 33.3% (14/42) and 69% (29/42) of patients responded to 0.5 and 1.5 mg of albuterol, respectively. CONCLUSIONS: With a nasal cannula at 15-20 L/min, transnasal pulmonary delivery of 1.5 mg albuterol resulted in similar bronchodilator response as 4 actuations of MDI + VHC.


Assuntos
Albuterol/administração & dosagem , Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Inaladores Dosimetrados , Pessoa de Meia-Idade , Espirometria
20.
Eur J Pharm Sci ; 139: 105065, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31493448

RESUMO

The generation of inhalable sized particles (1-5 µm) usually involves a particle-processing step; most commonly milling but spray drying has shown to be a suitable alternative. Besides particle size, processing may affect other particle properties, like shape and solid-state. For example, spray drying of salbutamol sulphate leads to spherical shaped predominantly amorphous particles whereas jet milling frequently maintains the irregular shape and the crystallinity of the raw material. The aim of the present study was to investigate whether particle properties, especially shape, change the biological action of the inhaled particles as well. Therefore, highly water soluble salbutamol sulphate and poorly water soluble budesonide were compared regarding dissolution, permeation and preferential uptake by epithelial cells compared to macrophages after jet milling and spray drying. For both drugs the spray dried, predominantly amorphous, particles resulted in lower respirable fractions, but higher permeability and cell uptake rates compared to the needle shaped, predominantly crystalline particles. The distinct particle properties did not affect the dissolution behaviour of salbutamol sulphate. In turn for drugs with lower solubility (budesonide), spray dried particles dissolved slower compared to jet milled particles. Preferential uptake by macrophages was higher for spray dried particles, suggesting that processing may improve targeted delivery. The comparison between murine cell lines and human monocyte derived macrophages primary cells showed similar trends in rate and preference of particle uptake.


Assuntos
Albuterol/administração & dosagem , Albuterol/química , Broncodilatadores/administração & dosagem , Broncodilatadores/química , Budesonida/administração & dosagem , Budesonida/química , Pulmão/metabolismo , Administração por Inalação , Animais , Linhagem Celular , Liberação Controlada de Fármacos , Humanos , Macrófagos/metabolismo , Camundongos , Permeabilidade/efeitos dos fármacos , Solubilidade , Propriedades de Superfície
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