Albuterol as an adjuvant in acute anticholinesterase pesticide poisoning: a randomized, placebo-controlled clinical trial.

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.

Hyperlacticaemia in children with status asthmaticus. The Stewart approach.

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 - -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 = 0.023) 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.

Albuterol delivery via in-line intrapulmonary percussive ventilation superimposed on conventional mechanical ventilation in an adult lung model.

Background: Intrapulmonary percussive ventilation (IPV) is frequently used for airway clearance, together with delivery of aerosols containing medications. Drug delivery via IPV alone increases with decreasing percussion frequency and correlates with tidal volume (VT) while drug delivery via IPV during conventional mechanical ventilation (IPV/CMV) is not well characterized. We hypothesized that drug delivery via IPV/CMV would take place differently from that via IPV alone due to control of ventilation by CMV. Methods: An adult ventilator circuit was used for IPV/CMV. A normal or diseased lung model was configured to airway resistance (Raw) 5 cm H2O/L/s and lung compliance (CL) 100 mL/cm H2O or Raw 20 cm H2O/L/s and CL 50 mL/cm H2O, respectively. The ventilator settings were: 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 diseased lung model, respectively, to reach VT 500 mL with IPV off. Albuterol nebulized from Phasitron 5 was captured in a filter placed before the lung model and quantitated by spectrophotometry. Results: The maximal efficiency of albuterol delivery via IPV/CMV was not different from that via IPV alone (3.7 ± 0.2% vs 4.2 ± 0.3%, mean ± SD of loading dose, P= .12). Albuterol delivery efficiency with IPV/CMV was lower for the diseased lung model than for the normal model (1.6 ± 0.3% vs 3.2 ± 0.5%, mean ± SD, P < .001), which increased with decreasing percussion frequency. In contrast, VT was lower for the normal lung model than for the diseased model (401 ± 14 mL vs 470 ± 11 mL, mean ± SD, P < .001). Conclusions: Albuterol delivery via IPV/CMV was modulated by percussion frequency but not increased with increasing VT The delivery efficiency was not sufficiently high for clinical use, in part due to nebulizer retention and extrapulmonary deposition.

Budesonide/Formoterol or Budesonide/Albuterol as Anti-Inflammatory Reliever Therapy for Asthma.

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.

The Role of ICS-Containing Rescue Therapy Versus SABA Alone in Asthma Management Today.

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.

A Retrospective Analysis of Intravenous Insulin versus Insulin and Nebulized Albuterol for the Treatment of Hyperkalemia in the Emergency Department.

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.

Oral Albuterol Treatment in Three Pediatric Patients with Bradycardia: A Novel Therapy.

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.

Uso de inhaladores para la enfermedad pulmonar obstructiva crónica en un grupo de pacientes colombianos

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.

Improving rates of successful extubation: Medications.

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.

Albuterol Delivery During Invasive Mechanical Ventilation via In-Line Intrapulmonary Percussive Ventilation in a Pediatric Lung Model.

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.

Epigenomic response to albuterol treatment in asthma-relevant airway epithelial cells.

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.

Peripheral airway dysfunction in prematurity-associated obstructive lung disease identified by oscillometry.

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.

The Effect of Albuterol Spray on Hypoxia and Bronchospasm in Patients with Chronic Obstructive Pulmonary Disease (COPD) under General Anesthesia: A bouble-Blind Randomized Clinical Trial.

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.

Evaluation of intratracheal salbutamol effects in addition to surfactant in the clinical course of premature neonates with respiratory distress syndrome.

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.

Treatment of Facioscapulohumeral Muscular Dystrophy (FSHD): A Systematic Review.

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.

A Discrete Choice Experiment to Assess Patient Preferences for Asthma Rescue Therapy and Disease Management.

BACKGROUND: With the expanding treatment landscape for asthma, the process of identifying best-fit, individualized management options is becoming increasingly complicated. Understanding patients' preferences can inform shared decision-making between clinicians and patients. OBJECTIVES: To examine preferences of adults with asthma for therapeutic and management attributes and determine how these preferences vary among patients. METHODS: We conducted an online discrete choice experiment survey in US adults with asthma. Patient preferences were analyzed using logit models. Factors affecting patients' preferences were identified by least absolute shrinkage and selection operator analysis. RESULTS: A total of 1,184 patients completed the survey (60% female; mean [SD] age, 49.2 [15.0] years). Patients most valued fewer asthma attacks requiring urgent health care professional visits, fewer exacerbations requiring oral corticosteroids, and a reduced risk for oral thrush. Higher value was placed on reducing the risk of short-term (oral thrush) versus long-term side effects (diabetes). Patients were willing to increase rescue medication use in exchange for decreasing exacerbations requiring oral corticosteroids and attacks requiring urgent health care professional visits. Patients preferred a single inhaler for rescue and maintenance and least valued asthma action plans. Demographic, socioeconomic, and clinical factors affected patient preferences. CONCLUSIONS: Patients sought convenient management options that focused mainly on decreasing the short-term morbidity associated with asthma exacerbations and therapies. Preferences varied by demographics, clinical factors, and socioeconomics. It is important for shared decision-making discussions to include conversations about morbidity and how available therapeutic options align with individual patient preferences.

Albuterol-Budesonide Pressurized Metered Dose Inhaler in Patients With Mild-to-Moderate Asthma: Results of the DENALI Double-Blind Randomized Controlled Trial.

BACKGROUND: In the phase 3 MANDALA trial, as-needed albuterol-budesonide pressurized metered-dose inhaler significantly reduced severe exacerbation risk vs as-needed albuterol in patients with moderate-to-severe asthma receiving inhaled corticosteroid-containing maintenance therapy. This study (DENALI) was conducted to address the US Food and Drug Administration combination rule, which requires a combination product to demonstrate that each component contributes to its efficacy. RESEARCH QUESTION: Do both albuterol and budesonide contribute to the efficacy of the albuterol-budesonide combination pressurized metered-dose inhaler in patients with asthma? STUDY DESIGN AND METHODS: This phase 3 double-blind trial randomized patients aged ≥ 12 years with mild-to-moderate asthma 1:1:1:1:1 to four-times-daily albuterol-budesonide 180/160 µg or 180/80 µg, albuterol 180 µg, budesonide 160 µg, or placebo for 12 weeks. Dual-primary efficacy end points included change from baseline in FEV1 area under the curve from 0 to 6 h (FEV1 AUC0-6h) over 12 weeks (assessing albuterol effect) and trough FEV1 at week 12 (assessing budesonide effect). RESULTS: Of 1,001 patients randomized, 989 were ≥ 12 years old and evaluable for efficacy. Change from baseline in FEV1 AUC0-6h over 12 weeks was greater with albuterol-budesonide 180/160 µg vs budesonide 160 µg (least-squares mean [LSM] difference, 80.7 [95% CI, 28.4-132.9] mL; P = .003). Change in trough FEV1 at week 12 was greater with albuterol-budesonide 180/160 and 180/80 µg vs albuterol 180 µg (LSM difference, 132.8 [95% CI, 63.6-201.9] mL and 120.8 [95% CI, 51.5-190.1] mL, respectively; both P < .001). Day 1 time to onset and duration of bronchodilation with albuterol-budesonide were similar to those with albuterol. The albuterol-budesonide adverse event profile was similar to that of the monocomponents. INTERPRETATION: Both monocomponents contributed to albuterol-budesonide lung function efficacy. Albuterol-budesonide was well tolerated, even at regular, relatively high daily doses for 12 weeks, with no new safety findings, supporting its use as a novel rescue therapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03847896; URL: www. CLINICALTRIALS: gov.

New Air-Jet Dry Powder Insufflator for High-Efficiency Aerosol Delivery to Rats.

Pulmonary deposition of lung-targeted therapeutic aerosols can achieve direct drug delivery to the site of action, thereby enhancing the efficacy and reducing systemic exposure. In this study, we investigated the in vitro and in vivo aerosol performance of the novel small animal air-jet dry powder insufflator (Rat AJ DPI) using spray-dried albuterol excipient-enhanced-growth (EEG) powder as a model formulation. The in vitro aerosolization performance of the optimized albuterol EEG powder was first assessed using the Rat AJ DPI. The performance of Rat AJ DPI to deliver albuterol EEG aerosol to rat lungs was then compared to that of the Penn-Century Insufflator. Albuterol EEG powders dispersed using the Rat AJ DPI demonstrated narrow unimodal aerosol size distribution profiles, which were independent of the loaded powder dose (1, 2, and 5 mg). In addition, the span value for Rat AJ DPI (5 mg powder mass) was 1.32, which was 4.2-fold lower than that for Penn-Century insufflator (5 mg powder mass). At a higher loaded mass of 5 mg, the Rat AJ DPI delivered significantly larger doses to rat lungs compared with the Penn-Century DPI. The Rat AJ DPI with hand actuation delivered approximately 85% of the total emitted dose (2 and 5 mg loadings), which was comparatively higher than that for Penn-Century DPI (approximately 75%). In addition, percentage deposition in each of the lung lobes for the Rat AJ DPI was observed to be independent of the administration dose (2 and 5 mg loadings) with coefficients of variation below 12%, except in the right middle lobe. Automatic actuation of a 5 mg powder mass using the Rat AJ DPI demonstrated a similar delivered dose compared to manual actuation of the same dose, with 82% of the total emitted dose reaching the lung lobes. High-efficiency delivery of the aerosol to the lobar lung region and low sensitivity of the interlobar delivery efficiency to the loaded dose highlight the suitability of the new air-jet DPI for administering therapeutic pharmaceutical aerosols to small test animals.