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2.
Cureus ; 16(4): e59039, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38803713

ABSTRACT

Introduction Chronic obstructive pulmonary disease (COPD) affects millions in China and imposes a considerable economic burden on hospitalized patients who experience exacerbations. Nebulized short-acting beta-2 agonists (SABA) are recommended as initial therapy for exacerbation patients, but the optimal SABA remains uncertain. This study aimed to evaluate the impact of different SABAs, such as albuterol and levalbuterol, on the length of stay (LOS) and direct medical costs among hospitalized patients diagnosed with COPD. Methods This retrospective cohort study uses linked hospital administrative data from three hospitals in Chongqing. Patients with COPD, aged 40 years and older, who had been continuously treated with nebulized albuterol or levalbuterol during hospitalization, were eligible for the study. Patients were matched 1:1 by sex, age, and severity according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-4. Patients were grouped according to the different SABA treatments they received. Demographic, economic, and clinical data were retrieved. LOS and direct healthcare costs were assessed. Results A total of 158 COPD patients were included, with 79 in each treatment group. Patients treated with levalbuterol had a significantly shorter median LOS (7.0 days vs. 8.0 days, P=0.003) and fewer direct healthcare median costs (total cost: ¥8,868.3 vs. ¥10,290.7, P=0.014; COPD-related western medicine fees: ¥383.8 vs. ¥505.3). Patients aged 60 or older were more likely to experience longer LOS and higher direct costs. Conclusion This retrospective cohort analysis supports that albuterol was associated with longer LOS and higher costs than levalbuterol.

3.
Toxicol Res (Camb) ; 13(2): tfae048, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38559756

ABSTRACT

Acute anticholinesterase pesticide poisoning is a serious clinical problem, particularly in developing countries. Atropine is the most acceptable treatment for acute anticholinesterase poisoning. However, it only stops fluid production. Albuterol is a beta-2 receptor agonist that can increase fluid removal and speed the return of effective oxygen exchange. This study aims to evaluate the safety and efficacy of nebulized albuterol as an adjuvant therapy in patients with acute anticholinesterase poisoning. This stratified block randomized, single-blinded, placebo-controlled, parallel-group clinical trial was conducted between November 2020 and October 2021. It enrolled 80 patients with acute anticholinesterase pesticide poisoning who were admitted to Tanta University Poison Control Center. Patients were allocated into two groups (40 patients each). The strata were based on the severity of poisoning (moderate and severe). Patients in group I received 10 mg of nebulized albuterol. Group II received an equivalent volume of nebulized normal saline. Additionally, standard treatment was provided to both groups. Outcomes included oxygenation, mortality, need for endotracheal intubation and mechanical ventilation, hospital stay duration, time to atropinization, and total doses of atropine and oxime. We found insignificant differences in sociodemographics, exposure characteristics, clinical manifestations, or routine laboratory tests between the studied groups. The median values of oxygen saturation by pulse oximetry were 99% in the albuterol moderate toxicity group and 98% in the control moderate toxicity group. Albuterol significantly improved oxygen saturation in moderate intoxicated patients (P = 0.039). Therefore, nebulized albuterol is a safe drug. Moreover, it may improve oxygenation in acute anticholinesterase pesticide poisoning.

4.
Article in English | MEDLINE | ID: mdl-38657950

ABSTRACT

BACKGROUND: Patients with status asthmaticus (SA) frequently present with lactic acidosis (LA). Our goal is to identify the nature of this LA using the Stewart physicochemical model and to identify the independent factors associated with LA in children with SA. METHODS: Analytical study of a retrospective cohort using a nested case-control design. Twenty-eight episodes of SA in 24 children were included. Patients admitted to a paediatric intensive care unit (PICU) for SA over a 9-year period were recruited consecutively. Data were analysed using the Stewart model and the Strong Ion Calculator. Data were analysed using descriptive statistics and regression models were fitted within the general linear model. RESULTS: Hyperlacticaemia (Lact[mM/L] = 3.905 [95% CI = 3.018-4.792]) and acidosis (pH = 7.294 [95% CI = 7.241-7.339]) were observed in 18 episodes (15 patients; 62.5%). According to the Stewart model, acidosis was caused by a decrease in strong ion difference. Initially, pCO2 was high (pCO2[mmHg] = 45.806 [95% CI = 37.314-54.298]) but the net unmeasured ion (NUI) component was normal (NUI = -4,461 [95% CI = -3.51 to -5.412]), and neither changed significantly over the clinical course. There was no need to determine pyruvate, as the NUI was normal and the LA was type B (non-hypoxic, lactate/pyruvate < 25). We observed a correlation (P = .023) between LA and intramuscular epinephrine administered on arrival at hospital, but not between LA and the cumulative dose of nebulized salbutamol. CONCLUSIONS: Most patients with SA presented LA. The Stewart model confirmed that LA is not hypoxic, probably due to sympathomimetic-related glycolysis.

5.
Preprint in Portuguese | SciELO Preprints | ID: pps-8393

ABSTRACT

Objective: To calculate the carbon footprint of pressurized gas-type metered-dose inhalers for asthma and chronic obstructive pulmonary disease control (COPD) dispensed by the brazilian national health service (SUS) in Brazil and in Porto Alegre (RS) in 2019. Method: Collection and analysis of data on the dispensation of salbutamol and beclomethasone by the SUS network and Farmácia Popular do Brasil in 2019, obtained by request to the Ministry of Health. Dispensations were multiplied by the proportional carbon footprint of each device using data already published in the literature. Results: In 2019, the prescription of pMDIs (pressurized metered-dose inhalers) within the Brazilian Unified Health System (SUS) resulted in the emission of approximately 24,889,141 to 60,878,728 metric tons of CO2 equivalent into the atmosphere across Brazil, which is equivalent to traveling by a typical gasoline-powered car from the northernmost to the southernmost point of the country between 23 to 57 million times. Furthermore, in the specific context of Porto Alegre, the emissions ranged from approximately 459,830 to 1,151,008 metric tons of CO2 equivalent, corresponding to traveling by a typical gasoline-powered car from the northernmost to the southernmost point of Brazil between 433,000 to 1 million times. Conclusion: The national health service in Brazil is responsible for emitting a massive amount of GHGs each year due to pMDI-type inhalation devices.  Switching to DPIs or SMIs in the indicated cases would avoid a great environmental damage, and at the same time would be of clinical benefit to patients, since they are the first choice currently recommended by the clinical guidelines for the treatment of asthma and COPD, promoting public health and, at the same time, planetary health.


Objetivo: Calcular la huella de carbono de los inhaladores de dosis medida de gas presurizado utilizados para el control del asma y la enfermedad pulmonar obstructiva crónica (EPOC) dispensados por el Sistema Único de Salud (SUS) en Brasil y en Porto Alegre (RS) en el año 2019. Método: Recopilación y análisis de datos de dispensación de salbutamol y beclometasona por la red SUS y Farmácia Popular do Brasil en 2019, obtenidos a través de una solicitud al Ministerio de Salud en virtud de la Ley de Acceso a la Información. Las dispensaciones se multiplicaron por la huella de carbono proporcional de cada dispositivo utilizando datos previamente publicados en la literatura. Resultados: La prescripción de los inhaladores de dosis medida de gas presurizado en el SUS en 2019 resultó en la emisión de entre 24,889,141 y 60,878,728 toneladas de CO2-eq en todo Brasil, equivalente a viajar en un automóvil de gasolina común desde el extremo norte hasta el extremo sur del país entre 23 y 57 millones de veces. En el caso de la ciudad de Porto Alegre, las emisiones oscilaron entre 459,830 y 1,151,008 toneladas de CO2-eq, lo que equivale a recorrer la distancia de norte a sur de Brasil entre 433,000 y 1 millón de veces en un automóvil de gasolina común. Conclusión: En el SUS, se emite una enorme cantidad de gases de efecto invernadero (GEE) cada año debido a los dispositivos inhaladores del tipo pMDI. El cambio a DPIs o SMIs en los casos indicados evitaría un gran daño ambiental y, al mismo tiempo, proporcionaría beneficios clínicos a los pacientes, ya que es la primera opción actualmente recomendada por las directrices clínicas para el tratamiento del asma y la EPOC, promoviendo la salud pública y al mismo tiempo la salud del planeta.


Objetivo: Calcular a pegada de carbono dos inaladores do tipo gás pressurizado dosimetrado para controle da asma e doença pulmonar obstrutiva crônica (DPOC) dispensados pelo Sistema Único de Saúde (SUS) no Brasil e em Porto Alegre (RS) no ano de 2019. Método: Coleta e análise de dados de dispensação de salbutamol e beclometasona pela rede SUS e Farmácia Popular do Brasil em 2019, obtidas por solicitação ao Ministério da Saúde através da Lei de Acesso à Informação. As dispensações foram multiplicadas pela pegada de carbono proporcional de cada dispositivo utilizando dados já publicados na literatura. Resultados: A prescrição de pMDI no SUS, em 2019, resultou entre 24.889.141 e 60.878.728 toneladas de CO2-eq liberados na atmosfera em todo o Brasil (equivalente a percorrer 23 a 57 milhões de vezes a distância de norte a sul do Brasil com um carro comum a gasolina); e entre 459.830 e 1.151.008 toneladas de CO2-eq na cidade de Porto Alegre (correspondente a percorrer 433mil a 1 milhão de vezes a distância de norte a sul do Brasil com um carro comum a gasolina). Conclusão: No SUS, emite-se enorme quantidade de GEEs a cada ano devido aos dispositivos inalatórios do tipo pMDI. A troca por DPIs ou SMIs nos casos indicados evitaria um grande dano ambiental, e ao mesmo tempo benefício clínico aos pacientes, pois trata-se da primeira escolha atual preconizada pelas diretrizes clínicas para o tratamento de asma e DPOC, promovendo a saúde pública e ao mesmo tempo a saúde planetária.

7.
Respir Care ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38538009

ABSTRACT

BACKGROUND: Intrapulmonary percussive ventilation (IPV) is frequently used for airway clearance, together with delivery of aerosolized medications. Drug delivery via IPV alone increases with decreasing percussion frequency and correlates with tidal volume (VT), whereas drug delivery via IPV during invasive ventilation is not well characterized. We hypothesized that drug delivery via IPV-invasive ventilation would differ from IPV alone due to control of ventilation by invasive ventilation. METHODS: An adult ventilator circuit was used for IPV-invasive ventilation. A normal or a diseased lung model was configured to airway resistance of 5 cm H2O/L/s and lung compliance of 100 mL/cm H2O or to airway resistance of 20 cm H2O/L/s and lung compliance of 50 mL/cm H2O, respectively. The ventilator settings were the following: pressure control continuous mandatory ventilation mode, 10 breaths/min; PEEP, 5 cm H2O; FIO2 , 0.21; inspiratory time, 1 s; no bias flow; and inspiratory pressure, 10 or 15 cm H2O for the normal or the diseased lung model, respectively, to reach VT 500 mL with IPV off. Albuterol nebulized from an IPV device was captured in a filter placed before the lung model and quantitated by spectrophotometry. RESULTS: The maximum efficiency of albuterol delivery via IPV-invasive ventilation was not different from that via IPV alone (mean ± SD of loading dose, 3.7 ± 0.2% vs 4.2 ± 0.3%, respectively; P = .12). The mean ± SD albuterol delivery efficiency with IPV-invasive ventilation was lower for the diseased lung model versus the normal model (1.6 ± 0.3% vs 3.2 ± 0.5%; P < .001), which increased with decreasing percussion frequency. In contrast, the mean ± SD VT was lower for the normal lung model versus the diseased model (401 ± 14 mL vs 470 ± 11 mL; P < .001). CONCLUSIONS: Albuterol delivery via IPV-invasive ventilation was modulated by percussion frequency but was not increased with increasing VT. The delivery efficiency was not sufficiently high for clinical use, in part due to nebulizer retention and extrapulmonary deposition.

8.
J Allergy Clin Immunol Pract ; 12(4): 889-893, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38346474

ABSTRACT

Overuse of reliever as short-acting beta-agonist and associated underuse of controller as inhaled corticosteroid (ICS) administered via separate inhalers results in worse asthma outcomes. Such discordance can be obviated by combining both controller and reliever in the same inhaler. So-called anti-inflammatory reliever (AIR) therapy comprises the use of a single inhaler containing an ICS such as budesonide (BUD) in conjunction with a reliever as either albuterol (ALB) or formoterol (FORM), to be used on demand, with variable dosing driven by asthma symptoms in a flexible patient-centered regimen. Global guidelines now support the use of BUD-ALB as AIR therapy to reduce exacerbations, either on its own in mild asthma or in conjunction with fixed-dose maintenance ICS-long-acting beta-agonist in moderate to severe asthma. Using BUD-FORM on its own allows patients to seamlessly move in an intuitive flexible fashion between AIR and maintenance and reliever therapy, by stepping up and down the dosing escalator across a spectrum of asthma severities. Head-to-head clinical studies are indicated to compare BUD-FORM versus BUD-ALB as AIR in mild asthma, and also BUD-FORM as maintenance and reliever therapy versus BUD-ALB as AIR plus maintenance ICS-long-acting beta-agonist in moderate to severe asthma. Patients should be encouraged to make an informed decision in conjunction with their health care professional regarding the best therapeutic option tailored to their individual needs, which in turn is likely to result in long-term compliance and associated optimal asthma control.


Subject(s)
Anti-Asthmatic Agents , Asthma , Humans , Budesonide/therapeutic use , Albuterol/therapeutic use , Bronchodilator Agents/therapeutic use , Anti-Asthmatic Agents/therapeutic use , Ethanolamines/therapeutic use , Drug Combinations , Asthma/drug therapy , Budesonide, Formoterol Fumarate Drug Combination/therapeutic use , Formoterol Fumarate/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Administration, Inhalation
9.
J Allergy Clin Immunol Pract ; 12(4): 870-879, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38237858

ABSTRACT

The Global Initiative for Asthma (GINA) recommends that short-acting ß2-agonist (SABA) monotherapy should no longer be prescribed, and that as-needed combination inhaled corticosteroids (ICS)-formoterol is the preferred reliever therapy in adults and adolescents with mild asthma. These recommendations are based on the risks of SABA monotherapy, the evidence that ICS-formoterol reliever therapy markedly decreases the occurrence of severe asthma exacerbations compared with SABA reliever therapy alone, and because ICS-formoterol reliever therapy has a favorable risk/benefit profile compared with maintenance ICS plus SABA reliever therapy. Data supporting the use of combination ICS-albuterol reliever therapy in mild asthma are more limited, but there are studies that inform its use in this population. In this review, we compare, using a pros and cons format, the (1) long-term safety and efficacy of ICS-formoterol reliever therapy versus SABA reliever therapy alone, (2) long-term safety and efficacy of ICS-albuterol reliever therapy versus SABA reliever therapy alone, (3) immediate bronchodilator effects of ICS-formoterol versus SABA alone, and (4) clinical and regulatory factors that may inform reliever therapy prescription decisions. By presenting the evidence of these reliever inhaler options, we hope to inform the reader while also calling for necessary future effectiveness and implementation research.


Subject(s)
Anti-Asthmatic Agents , Asthma , Adult , Adolescent , Humans , Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Asthma/epidemiology , Bronchodilator Agents/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Formoterol Fumarate/therapeutic use , Albuterol/therapeutic use , Administration, Inhalation , Budesonide/therapeutic use , Ethanolamines/therapeutic use
10.
J Clin Pharmacol ; 64(5): 619-625, 2024 May.
Article in English | MEDLINE | ID: mdl-38100157

ABSTRACT

There is limited literature evaluating the use of nebulized albuterol in the management of hyperkalemia. The objective was to evaluate the efficacy of insulin alone compared with the addition of nebulized albuterol for the treatment of hyperkalemia. This is a retrospective, single-center evaluation of adult patients with hyperkalemia attending the Emergency Department of a large urban academic medical center. Consecutive patients with a potassium level of >5 mmol/L were included. Patients without a repeat potassium level within 4 hours of medication administration, those receiving hemodialysis before a repeat serum potassium, or those that had a hemolyzed blood sample were excluded. The primary outcome was the change in potassium level within 4 hours in patients who received insulin monotherapy versus patients who received insulin and albuterol. The secondary outcomes included hospital length of stay, intensive care unit (ICU) admission, and mortality. Out of the 204 patients, 141 received insulin, whereas 63 received insulin and nebulized albuterol. There was no difference in the change in potassium level between the insulin and the insulin and nebulized albuterol groups (0.85 ± 0.6 vs 0.96 ± 0.78 mmol/L; P = .36). There was no difference in median hospital length of stay (8.6 days, IQR 13.2 days, vs 5.6 days, IQR 8.2 days; P = .09), ICU admission (31.9% vs 38.1%; P = .39), and all-cause mortality (14.9% vs 17.5%; P = .64). In this retrospective analysis, the addition of albuterol to insulin for the treatment of hyperkalemia did not result in a greater change in potassium level within 4 hours of therapy.


Subject(s)
Albuterol , Emergency Service, Hospital , Hyperkalemia , Insulin , Nebulizers and Vaporizers , Humans , Albuterol/administration & dosage , Albuterol/therapeutic use , Hyperkalemia/drug therapy , Hyperkalemia/blood , Retrospective Studies , Male , Female , Insulin/administration & dosage , Insulin/therapeutic use , Middle Aged , Aged , Administration, Inhalation , Length of Stay , Potassium/blood , Administration, Intravenous , Drug Therapy, Combination , Intensive Care Units , Adult
11.
Pediatr Cardiol ; 45(2): 441-445, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38145427

ABSTRACT

Clinically significant bradycardia is an uncommon problem in children, but one that can cause significant morbidity and sometimes necessitates implantation of a pacemaker. The most common causes of bradycardia are complete heart block (CHB), which can be congenital or acquired, and sinus node dysfunction, which is rare in children with structurally normal hearts. Pacemaker is indicated as therapy for the majority of children with CHB, and while early mortality is lower in postnatally diagnosed CHB than in fetal CHB, it is still up to 16%. In young children, less invasive transvenous pacemaker systems can be technically challenging to place and carry a high risk of complications, often necessitating surgical epicardial pacemaker placement, which usually entails a median sternotomy. We report three cases of pediatric patients referred for pacemaker implantation for different types of bradycardia, treated at our institution with oral albuterol with therapeutic results that avoided the need for surgical pacemaker implantation at that time.


Subject(s)
Bradycardia , Pacemaker, Artificial , Humans , Child , Child, Preschool , Bradycardia/drug therapy , Bradycardia/etiology , Cardiac Pacing, Artificial/methods , Pacemaker, Artificial/adverse effects , Sick Sinus Syndrome/drug therapy , Sick Sinus Syndrome/complications , Administration, Oral
12.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1535399

ABSTRACT

Introducción: En Colombia son escasos los datos sobre el uso de los inhaladores en pacientes con EPOC. Objetivo: Describir la técnica de uso de inhaladores de dosis medida y polvo seco en pacientes de un hospital colombiano. Materiales y métodos: Estudio descriptivo en pacientes mayores de 40 años con EPOC atendidos en un hospital en La Virginia, Risaralda, Colombia, entre el 1 de septiembre de 2019 al 31 de enero de 2020. La unidad de análisis fueron los pacientes. Se incluyeron variables sociodemográficas, clínicas y lista de chequeo para uso de inhaladores. Se aplicaron frecuencias y proporciones para variables discretas, estadísticas de tendencia central y dispersión para variables continuas. Resultados: Se incluyeron 104 pacientes con edad media de 73,6 ± 10,1 años; 57 eran mujeres (54,8 %). Además, 48 pacientes estaban clasificados como GOLD-D (46,2 %). Igualmente, 89 pacientes manifestaron haber recibido educación sobre el uso de broncodilatadores (85,6 %). Los más frecuentes fueron los inhaladores de dosis medida (DM) en 95 casos (91,3 %), seguido de los de polvo seco unidosis (7,7 %). Así mismo, 37 pacientes que usaron DM sin inhalocámara (35,6 %) no cumplieron los pasos de la lista de chequeo. En el sistema multidosis, el más realizado fue cerrar de manera adecuada el inhalador y el menos ejecutado, expulsar el aire lentamente evitando hacerlo cerca del inhalador (n = 6; 5,7 %). Discusión: Se lograron describir las características de la técnica de uso de los inhaladores en pacientes con EPOC. A pesar de que ningún paciente logró utilizar el inhalador de forma "perfecta", la mayoría han recibido educación por parte de los profesionales de la salud. Conclusión: Un alto porcentaje de pacientes usa inadecuadamente los dispositivos para suministrar los broncodilatadores. Esto puede impactar negativamente en el control de la enfermedad.


Introduction: In Colombia, there is limited data on the use of inhalers in patients with COPD. Objective: The objective was to describe the technique of using metered-dose inhalers and dry powder in patients in a Colombian hospital. Methods: Observational, descriptive study of patients over 40 years of age with COPD, treated in a hospital in La Virginia, Risaralda, Colombia, between September 1st, 2019 and January 31st, 2020. The unit of analysis were patients in consultation. Sociodemographic and clinical variables, and a checklist for use of inhalers were included. Frequencies and proportions were applied for discrete variables, statistics of central tendency and dispersion for continuous variables. Results: A total of 104 patients with an average age of 73.6 ± 10.1 years were included; 57 were women (54.8%). In addition, 48 patients were classified as GOLD-D (46.2%). Similarly, 89 patients reported having received education on the use of bronchodilators (85.6%). The most common were metered-dose (MD) inhalers in 95 cases (91.3%), followed by single-dose dry powder inhalers in eight patients (7.7%). Likewise, 37 patients who used DM without inhalochamber (35.6%) did not comply with the steps of the checklist. In the multidose system, the most performed was to properly close the inhaler and the least performed was to expel the air slowly, avoiding doing so near the inhaler (n=6; 5.7%). Discussion: The characteristics of the technique of using inhalers in patients with COPD were described. Although no patient was able to use the inhaler "perfectly", most have received education from health professionals. Conclusion: A high percentage of patients misuse the devices to deliver bronchodilators. This can negatively impact the control of the disease.

14.
Semin Fetal Neonatal Med ; 28(5): 101490, 2023 10.
Article in English | MEDLINE | ID: mdl-38030435

ABSTRACT

This chapter focuses on the pharmacological management of newborn infants in the peri-extubation period to reduce the risk of re-intubation and prolonged mechanical ventilation. Drugs used to promote respiratory drive, reduce the risk of apnoea, reduce lung inflammation and avoid bronchospasm are critically assessed. When available, Cochrane reviews and randomised trials are used as the primary sources of evidence. Methylxanthines, particularly caffeine, are well studied and there is accumulating evidence to guide clinicians on the timing and dosage that may be used. Efficacy and safety for doxapram, steroids, adrenaline and salbutamol are summarised. Management of term infants, extubation following surgery, accidental and complicated extubation and the use of cuffed endotracheal tubes are presented. Overall, caffeine is the only drug with a substantial evidence base, proven to increase the likelihood of successful extubation in preterm infants; no drugs are needed to facilitate extubation in most term infants. Future studies might further define the role of caffeine in late preterm infants and evaluate medications for post-extubation stridor, bronchospasm or apnoea not responsive to methylxanthines.


Subject(s)
Bronchial Spasm , Infant, Premature , Infant, Newborn , Humans , Caffeine/therapeutic use , Apnea/drug therapy , Ventilator Weaning , Bronchial Spasm/drug therapy , Intermittent Positive-Pressure Ventilation , Airway Extubation
15.
Clin Epigenetics ; 15(1): 156, 2023 10 03.
Article in English | MEDLINE | ID: mdl-37784136

ABSTRACT

BACKGROUND: Albuterol is the first-line asthma medication used in diverse populations. Although DNA methylation (DNAm) is an epigenetic mechanism involved in asthma and bronchodilator drug response (BDR), no study has assessed whether albuterol could induce changes in the airway epithelial methylome. We aimed to characterize albuterol-induced DNAm changes in airway epithelial cells, and assess potential functional consequences and the influence of genetic variation and asthma-related clinical variables. RESULTS: We followed a discovery and validation study design to characterize albuterol-induced DNAm changes in paired airway epithelial cultures stimulated in vitro with albuterol. In the discovery phase, an epigenome-wide association study using paired nasal epithelial cultures from Puerto Rican children (n = 97) identified 22 CpGs genome-wide associated with repeated-use albuterol treatment (p < 9 × 10-8). Albuterol predominantly induced a hypomethylation effect on CpGs captured by the EPIC array across the genome (probability of hypomethylation: 76%, p value = 3.3 × 10-5). DNAm changes on the CpGs cg23032799 (CREB3L1), cg00483640 (MYLK4-LINC01600), and cg05673431 (KSR1) were validated in nasal epithelia from 10 independent donors (false discovery rate [FDR] < 0.05). The effect on the CpG cg23032799 (CREB3L1) was cross-tissue validated in bronchial epithelial cells at nominal level (p = 0.030). DNAm changes in these three CpGs were shown to be influenced by three independent genetic variants (FDR < 0.05). In silico analyses showed these polymorphisms regulated gene expression of nearby genes in lungs and/or fibroblasts including KSR1 and LINC01600 (6.30 × 10-14 ≤ p ≤ 6.60 × 10-5). Additionally, hypomethylation at the CpGs cg10290200 (FLNC) and cg05673431 (KSR1) was associated with increased gene expression of the genes where they are located (FDR < 0.05). Furthermore, while the epigenetic effect of albuterol was independent of the asthma status, severity, and use of medication, BDR was nominally associated with the effect on the CpG cg23032799 (CREB3L1) (p = 0.004). Gene-set enrichment analyses revealed that epigenomic modifications of albuterol could participate in asthma-relevant processes (e.g., IL-2, TNF-α, and NF-κB signaling pathways). Finally, nine differentially methylated regions were associated with albuterol treatment, including CREB3L1, MYLK4, and KSR1 (adjusted p value < 0.05). CONCLUSIONS: This study revealed evidence of epigenetic modifications induced by albuterol in the mucociliary airway epithelium. The epigenomic response induced by albuterol might have potential clinical implications by affecting biological pathways relevant to asthma.


Subject(s)
Asthma , DNA Methylation , Child , Humans , Epigenomics , Asthma/drug therapy , Asthma/genetics , Albuterol/pharmacology , Albuterol/therapeutic use , Epigenesis, Genetic , Bronchodilator Agents/pharmacology , Bronchodilator Agents/therapeutic use , Epithelial Cells , Genome-Wide Association Study
16.
Respir Care ; 2023 Oct 03.
Article in English | MEDLINE | ID: mdl-37788859

ABSTRACT

BACKGROUND: Patients receiving mechanical ventilation often require airway clearance and inhaled therapies. Intrapulmonary percussive ventilation (IPV) combines a high-frequency percussive ventilator with a jet nebulizer. Data on aerosol delivery efficiency of the device are scarce. We evaluated albuterol delivery efficiency while using an IPV in-line adapter under different conditions. METHODS: A pediatric lung model of invasive mechanical ventilation was used. The following independent variables were evaluated: lung condition (normal vs ARDS), ventilator mode (adaptive pressure ventilation vs pressure control), percent opening of adapter (0% vs 25% vs 50%), IPV driving pressure (25 psi vs 40 psi), IPV percussion setting (easy vs hard), and endotracheal tube (ETT) size (3.5 mm vs 5.5 mm). Albuterol delivery efficiency (mass captured in the filter expressed as percentage of loading dose) was selected as the dependent variable. Albuterol was captured on a filter at the tip of the ETT and quantified via spectrophotometry (276 nm). RESULTS: Albuterol delivery efficiency ranged from 0-2.89%. Median (interquartile range) and 95% CI around the median were 0.54% (0.37-1.00) and 0.50-0.63%, respectively. The coefficient of determination (R2) for the model including all variables was 0.363. The 2 main contributors were percent of adapter opening (R2 0.30) and IPV setting (R2 0.039). CONCLUSIONS: Albuterol delivery during invasive mechanical ventilation via in-line IPV in a pediatric lung model was inefficient. Alternative methods of delivering bronchodilators and other inhaled medications should be considered when IPV is used.

17.
Pediatr Pulmonol ; 58(11): 3279-3292, 2023 11.
Article in English | MEDLINE | ID: mdl-37701982

ABSTRACT

INTRODUCTION: Mechanisms underlying lung dysfunction after preterm birth are poorly understood. Studying phenotypes of prematurity-associated lung disease may aid understanding of underlying mechanisms. Preterm-born children with and without lung dysfunction and term controls were assessed using oscillometry before and after exercise, and after postexercise bronchodilation. METHODS: Preterm-born children, born at gestation of 34 weeks or less, were classified into those with prematurity-associated obstructive lung disease (POLD; FEV1 < LLN, FEV1 /FVC < LLN), prematurity-associated preserved ratio of impaired spirometry (pPRISm; FEV1 < LLN, FEV1 /FVC ≥ LLN) and compared to preterm (FEV1 ≥ LLN) and term controls (%predicted FEV1 > 90%). All children underwent cardiopulmonary exercise, and oscillometry assessment at baseline, postexercise, and after postexercise bronchodilator administration. RESULTS: From 241 participants aged 7-12 years, complete data were available from 179: 15 children with POLD and 11 with pPRISm were compared with 93 preterm and 60 term controls. POLD group, when compared to both control groups, had impaired impedance, greater resistance, more negative (greater magnitude) reactance at low frequencies, and also had decreased compliance. pPRISm group demonstrated impaired reactance and compliance compared to term controls. No differences were noted between the preterm and term controls. Exercise had little impact on oscillometry values, but children with POLD had greatest improvements after postexercise bronchodilator administration, with decreased resistance and decreased magnitude of reactance, particularly at low frequencies. CONCLUSION: Preterm-born children with obstructive airway disease had the greatest oscillometry impairments and the largest improvements after postexercise bronchodilator compared to control groups. Oscillometry can potentially be used to identify preterm-born children with lung disease to institute treatment.


Subject(s)
Infant, Newborn, Diseases , Lung Diseases, Obstructive , Lung Diseases , Premature Birth , Child , Female , Humans , Infant, Newborn , Bronchodilator Agents/therapeutic use , Bronchodilator Agents/pharmacology , Oscillometry , Forced Expiratory Volume , Lung , Spirometry
18.
Ethiop J Health Sci ; 33(3): 491-498, 2023 May.
Article in English | MEDLINE | ID: mdl-37576161

ABSTRACT

Background: Patients with chronic obstructive pulmonary disease (COPD) experience an increased risk of perioperative pulmonary complications. The aim of this study was to evaluate the effect of albuterol spray on hypoxia and bronchospasm in patients with COPD under general anesthesia. Methods: This single-center, double-blind, parallel-group, randomized clinical trial was performed on 120 smoking patients with COPD who were referred to 5 Azar Educational Hospital in Gorgan, Northern Iran, in 2021. Twenty minutes before general anesthesia and also after completion of surgery and before extubation, 60 patients in the intervention group were inhaled with 2 puffs of albuterol spray. In the control group, patients were inhaled with 2 puffs of placebo spray. In perioperative period, the occurrence of wheezing, bronchospasm, coughing, hemodynamic changes, postoperative shivering, dyspnea, and nausea and vomiting were evaluated in all patients. The Consolidated Standards of Reporting Trials (CONSORT) checklist was used to report important aspects of this study. Results: The mean age of the patients was 52.34 ±8.95 years, and 115 (95.8%) of them were males while the rest were females. The difference between systolic blood pressure before induction of anesthesia (after administration of albuterol spray) between the group receiving albuterol spray and the group not receiving it was statistically significant (p=0.04). Also, the difference between the mean arterial oxygen saturation before tracheal extubation (after re-administration of albuterol spray) between the albuterol spray group and the non-albuterol group was statistically significant (p = 0.03). Wheezing and recurrent cough after induction of anesthesia and after extubation (after albuterol spray administration) was lower in the albuterol group than in the control group (p<0.05). No significant side effects were detected in the albuterol-treated group. Conclusion: According to the results of this study, it seems that the prophylactic use of albuterol spray is useful in reducing the incidence of wheezing and recurrent cough before induction of anesthesia in COPD patients with smoking.


Subject(s)
Bronchial Spasm , Pulmonary Disease, Chronic Obstructive , Male , Female , Humans , Adult , Middle Aged , Albuterol/therapeutic use , Bronchial Spasm/etiology , Bronchial Spasm/drug therapy , Bronchodilator Agents/therapeutic use , Cough/drug therapy , Cough/etiology , Respiratory Sounds , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/drug therapy , Anesthesia, General/adverse effects , Hypoxia/etiology , Double-Blind Method
19.
J Res Med Sci ; 28: 53, 2023.
Article in English | MEDLINE | ID: mdl-37496643

ABSTRACT

Background: In addition to surfactant deficiency, secretion of fluid from blood to the lungs and increase in the fluid content of the lung play significant roles in the pathogenesis of respiratory distress syndrome (RDS). Thus, we aimed to evaluate the effect of salbutamol (a beta-agonist) on fluid clearance from the lungs in neonates with RDS. Materials and Methods: This randomized controlled clinical trial included 82 neonates with RDS admitted to the neonatal intensive care units of Alzahra and Shahid Beheshti Hospitals of Isfahan University of Medical Science from 2017 to 2018. Patients were recruited through convenience sampling. They were randomized into two groups, using simple randomization: 42 were only treated with intra-tracheal surfactant (control group) and 40 with intra-tracheal surfactant plus salbutamol (intervention group). The two groups were compared regarding intubation surfactant administration and extubation (INSURE) failure, duration of nasal continuous positive airway pressure, intubation, oxygen therapy, morbidity, and mortality. Results: INSURE failure leading to mechanical ventilation occurred in 3 neonates in the control group and 2 in the intervention group (P = 0.680). Mean hospital length of stay did not differ significantly between groups (P = 0.230). Comparison of controls with the intervention group regarding complications and the incidence of morbidities revealed no statistically significant difference (P > 0.05). Conclusion: Findings of this study were not in favor of the routine use of salbutamol in neonates with RDS as it did not improve the course of the disease among newborns.

20.
Cureus ; 15(6): e39903, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37404420

ABSTRACT

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common type of muscular dystrophy. This disease presents as a slowly progressive asymmetric muscle weakness that involves the facial, scapular, and upper arm muscles mainly. Currently, there is no established consensus on this disease treatment in terms of medications. We assessed the response to the treatment of the drugs utilized in clinical trials by performing a systematic literature review in English using the preferred reporting items for systematic reviews (PRISMA) and meta-analyses. We only used human clinical trials in patients diagnosed with FSHD that received consistent pharmacological treatment. We included 11 clinical trials that fulfilled our criteria. We concluded that albuterol had statistically significant results in three out of four clinical trials, with improved elbow flexors muscle strength. Vitamin C, vitamin E, zinc gluconate, and selenomethionine showed significant improvement in the maximal voluntary contraction and endurance limit time of quadriceps muscle. At the same time, diltiazem and MYO-029 demonstrate no improvement in function, strength, or muscle mass. Losmapimod, currently in phase I of the ReDUX4 trial, showed promising results. Peradventure, more clinical trials are still needed to address this subject. Nevertheless, this review provides a clear and concise update on the treatment for this disease.

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