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Objectives Inherited defects of the neuromuscular junction (NMJ) comprise an increasingly diverse range of diseases. Several recently identified genes highlight the overlap between peripheral neuropathies and congenital myasthenic syndromes (CMS). The beta-2 adrenergic receptor agonist salbutamol has been shown to provide symptomatic benefit in CMS, while improving structural defects at the NMJ. Based on these findings, we identified cases of motor neuropathy with NMJ dysfunction and assessed the effect of salbutamol on motor function. Methods Cases of motor neuropathy with significant NMJ dysfunction, were identified using repetitive nerve stimulation and single fibre electromyography. Oral salbutamol was administered for 12 months. Repeat neurophysiological and clinical assessments were undertaken at baseline, 6 months and 12 months. Results Significant defects of neuromuscular transmission were identified in 15 patients harbouring a range of genetic defects, including mutations in GARS1, DNM2, SYT2 and DYNC1H. No clear benefit on motor function was seen following the administration of 12 months of oral salbutamol; however, there was a significant improvement in patient reported fatigue. In addition, no clear effect on neurophysiological parameters was seen in patients treated with salbutamol. Side-effects due to off-target beta-adrenergic effects were significant in the patient cohort. Conclusion These results highlight the involvement of the NMJ in several subtypes of motor neuropathies, including subtypes of neuropathy due to deficits in mitochondrial fusion-fission, synaptic vesicle transport, calcium channels and tRNA synthetases. Whether the NMJ dysfunction is simply due to muscle reinnervation or a pathology unrelated to denervation is unknown. The involvement of the NMJ may represent a novel therapeutic target in these conditions. However, treatment regimens will need to be more targeted for patients with primary inherited defects of neuromuscular transmission.

Docking protein 7 (DOK7) congenital myasthenic syndrome (CMS) is characterized by limb-girdle weakness and lack of fluctuating fatigability simulating many familial myopathies. Albuterol is the first line of therapy in view of consistent improvement. Two brothers with progressive predominant biceps weakness for 1-3 years responded to prednisone treatment for 40-50 years. Various studies including muscle biopsy and many laboratory studies were unsuccessful for the definite diagnosis. Gene study, 40 years after the initial evaluation, confirmed the diagnosis of DOK7 CMS. These are the first reported cases of DOK7 CMS associated with a sustained benefit from corticosteroids.

Respiratory-related complaints prompt most pediatric visits to Karl Heusner Memorial Hospital Authority's (KHMHA) Emergency Department (ED) in Belize. We developed and taught a novel pediatric respiratory emergencies module for generalist practitioners there. We assessed the curriculum's clinical impact on pediatric asthma emergency management.This study assesses the clinical impact of a pediatric emergency medicine curriculum on management of pediatric asthma emergencies at KHMHA in Belize City, Belize.We conducted a randomized chart review of pediatric (aged 2-16 y) visits for asthma-related diagnosis at the KHMHA ED between 2015 and 2018 to assess the training module's clinical impact. Primary outcomes included time to albuterol and steroids. Secondary outcomes included clinical scoring tool (Pediatric Respiratory Assessment Measure [PRAM]) usage, ED length of stay, usage of chest radiography, return visit within 7 days, and hospital admission rates. Kaplan-Meier survival analysis and Cox proportional hazard regression were used.Two hundred eighty-three pediatric asthma-related diagnoses met our inclusion criteria. The patients treated by trained and untrained physician groups were demographically and clinically similar. The time to albuterol was significantly faster in the trained (intervention) group compared with the untrained (control) physician group when evaluating baseline of the group posttraining (P0.05). However, the time to steroids did not reach statistical significance posttraining (P = 0.93). The PRAM score utilization significantly increased among both control group and intervention group. The untrained physician group was more likely to use chest radiography or admit patients. The trained physician group had higher return visit rates within 7 days and shorter ED length of stay, but this did not reach statistical significance.The curriculum positively impacted clinical outcomes leading to earlier albuterol administration, increased PRAM score use, obtaining less chest radiographs, and decreased admission rates. The timeliness of systemic steroid administration was unaffected.

Background. Asthma airway remodeling is closely related to the abnormal migration of human airway smooth muscle cells (ASMCs), and vascular endothelial growth factor (VEGF) is involved in the pathophysiological process of asthma. This study aimed to investigate the effect of VEGF on ASMC migration through in vitro cell experiments and to intervene in ASMC migration with different asthma drugs and signaling pathway inhibitors to provide a basis for screening effective drugs for airway remodeling. Methods. The effect of VEGF on the proliferation of ASMCs was detected by the CCK-8 method, and the effect of VEGF on the migration of ASMCs was proven by scratch and transwell assays. Different asthma drugs and signaling pathway inhibitors were used to interfere with the migration of ASMCs. The number of migrating cells was compared between the intervention and nonintervention groups. Results. Our results showed that VEGF induction enhanced ASMC migration; pretreatment with the commonly used asthma drugs (salbutamol, budesonide, and ipratropium bromide) significantly attenuated VEGF-induced ASMC migration; and inhibitors SB203580, LY294002, and Y27632 blocked the VEGF-induced activation of p38 MAPK, PI3K, and ROCK signaling pathway targets in ASMCs and inhibited migration. Conclusion. This study shows that the current commonly used asthma drugs salbutamol, budesonide, and ipratropium have potential value in the treatment of airway remodeling, and the p38 MAPK, PI3K, and ROCK signaling pathway targets are involved in the VEGF-induced ASMC migration process. Signaling pathway inhibitor drugs may be a new way to treat asthma-induced airway remodeling in asthma patients in the future. However, the related mechanism and safety profile still need further research.

Pulmonary drug delivery has gained great attention in local or systemic diseases therapy, however it is still difficult to scale-up DPI production due to the complexity of interactions taking place in DPI systems and limited understanding between flowability and inter-particle interactions in DPI formulations. Therefore, finding some quantitative parameters related to DPI delivery performance for predicting the in vitro drug deposition behavior is essential. Therefore, this study introduces a potential model for predicting aerodynamic performance of carrier-based DPIs, as well to find more relevant fine powder size and optimal shape to improve aerodynamic performance. Using salbutamol sulfate as a model drug, Lactohale®206 as coarse carrier, Lactohale®300, Lactohale®230, and Lactohale®210 as third fine components individually, the mixtures were prepared at 1% (w/w) drug content accompanied with carriers and the third component (ranging from 3% to 7%), influence of lactose fines size on DPI formulation's rheological and aerodynamic properties was investigated. The optimum drug particle shape was also confirmed by computer fluid dynamics model. This study proved that pulmonary deposition efficiency could be improved by decreasing lactose fines size. Only fines in the size range of 0-11 μm have a good linear relationship with FPF, attributed to the fluidization energy enhancement and aggregates mechanism. Once exceeding 11 μm, fine lactose would act as a second carrier, with increased drug adhesion. Computational fluid dynamics (CFD) models indicated fibrous drug particles were beneficial to transfer to the deep lung. Furthermore, good correlations between rheological parameters and FPF of ternary mixtures with different lactose fines were established, and it was disclosed that the FPF was more dependent on interaction parameters than that of flowability.

Although studies on epileptic seizures occurring during acute asthma attacks are limited, there is widespread belief among families and physicians that salbutamol causes seizures.To investigate whether salbutamol triggers seizures in patients with epilepsy and asthma.A retrospective cohort study.Epilepsy and asthma in patients aged 2-18 years who were admitted to the pediatric emergency department because of asthma attacks between January 2016 and December 2016 in a university hospital were evaluated retrospectively. The inclusion criteria were age 2–18 years, previous diagnosis of epilepsy and asthma, and admission to the pediatric emergency department due to asthma attacks.276 medical records were evaluated. The seizure group had a longer period of diagnosis for epilepsy than the seizure absent group in the pediatric emergency department (5.4 years and 3.1, respectively). According to the logistic regression analysis, the duration of seizures in the emergency department, duration of asthma diagnosis, duration of epilepsy diagnosis, uncontrolled asthma, and severity of asthma attack in the pediatric emergency department have significantly increased the possibility of having a seizure during an asthma attack in our study population.This study shows that patients using salbutamol have a lower risk of epileptic seizures than those who do not use salbutamol. This result should be verified by studies containing a large number of patients.

To evaluate the budgetary impact of using budesonide + formoterol (Symbicort Turbuhaler) as maintenance therapy in real clinical practice compared with standard therapy for asthma of varying severity: for mild asthma with on-demand salbutamol; for moderate and severe asthma with the drug salmeterol + fluticasone and salbutamol on demand.A static mathematical model was built to assess the impact on the budget when introducing the drug budesonide + formoterol (Symbicort Turbuhaler) in the treatment of asthma into clinical practice from the point of view of the state. Demographic data was taken from the official data of the Federal State Statistics Service. Direct medical costs included the cost of medicines, the cost of hospitalization of patients associated with the development of asthma exacerbations, and the cost of scheduled outpatient visits. Indirect costs considered the loss of GDP due to hospitalization of patients against the background of asthma exacerbations. A one-way sensitivity analysis was performed to confirm the robustness of the study results.Assessment of direct costs in the treatment of mild, moderate and severe asthma showed that a gradual increase in the proportion of patients receiving the drug budesonide + formoterol (Symbicort Turbuhaler) over the years to 5.5, 7.7 and 9.7% accordingly, led to an increase in the cost of pharmacotherapy over 3 years by 1.7 billion rubles, while direct non-drug costs associated with the treatment of complications that developed during the treatment of asthma decreased by 8.3 billion rubles. Thus, the reduction in total direct costs amounted to RUB 6.7 billion. At the same time, indirect costs decreased by 6.0 billion rubles. The total reduction in all costs (direct and indirect) when switching patients to budesonide + formoterol (Symbicort Turbuhaler) amounted to 12.5 billion rubles. In addition, the use of the drug budesonide + formoterol (Symbicort Turbuhaler) resulted in a decrease in the number of exacerbations: in the first year by 3137, in the second by 4393 and in the third by 5534 cases. A total of 13 064 asthma exacerbations were prevented over 3 years.Increasing the proportion of patients with asthma of varying severity receiving therapy with budesonide + formoterol (Symbicort Turbuhaler) will reduce the financial burden on both the healthcare system and the budgetary system.Цель. Оценить влияние препарата будесонид + формотерол (Симбикорт Турбухалер 160/4,5 мкг/доза) на бюджет при его применении в качестве поддерживающей терапии в реальной клинической практике в сравнении со стандартной терапией при бронхиальной астме (БА) различной степени тяжести: для БА легкого течения с сальбутамолом по требованию, для БА среднетяжелого и тяжелого течения с препаратом салметерол + флутиказон и сальбутамолом по требованию. Материалы и методы. Построена статическая математическая модель для оценки влияния лекарственного препарата будесонид + формотерол (Симбикорт Турбухалер 160/4,5 мкг/доза) в лечении БА на бюджет при внедрении его в клиническую практику с точки зрения государства. Демографические данные взяты из официальных данных Федеральной службы государственной статистики. Прямые медицинские затраты включали расходы на лекарственные средства, затраты на госпитализацию пациентов, сопряженную с развитием обострений БА, и затраты на плановые амбулаторные визиты. Косвенные затраты учитывали потерю ВВП в связи с госпитализацией пациентов на фоне обострений БА. Односторонний анализ чувствительности провели для подтверждения надежности результатов исследования. Результаты. Оценка прямых затрат при лечении БА легкого, среднетяжелого и тяжелого течения показала, что постепенное увеличение доли пациентов, получающих препарат будесонид + формотерол (Симбикорт Турбухалер 160/4,5 мкг/доза), в 1, 2, 3-й год приема до 5,5, 7,7 и 9,7% соответственно, привело к возрастанию затрат на фармакотерапию за это время на 1,7 млрд руб., при том что прямые нелекарственные затраты, связанные с лечением осложнений, развившихся на фоне лечения БА, уменьшились на 8,3 млрд руб. Таким образом, снижение суммарных прямых затрат составило 6,7 млрд руб. Косвенные затраты при этом сократились на 6,0 млрд руб. Общее снижение всех затрат (прямых и косвенных) при переключении пациентов на будесонид + формотерол (Симбикорт Турбухалер 160/4,5 мкг/доза) составило 12,5 млрд руб. Кроме того, препарат будесонид + формотерол (Симбикорт Турбухалер 160/4,5 мкг/доза) помог снизить число обострений: в 1-й год на 3137, во 2-й на 4393 и в 3-й на 5534 случая. Суммарно за 3 года было предотвращено 13 064 обострения БА. Заключение. Увеличение доли пациентов с БА различной степени тяжести, получающих терапию с препаратом будесонид + формотерол (Симбикорт Турбухалер 160/4,5 мкг/доза), позволит снизить финансовую нагрузку как на систему здравоохранения, так и на бюджетную систему государства в целом.

Purpose In patients with chronic obstructive pulmonary disease (COPD), bronchial responsiveness after acute administration of short acting bronchodilators is conventionally assessed by measuring the improvement of forced expiratory volume in the first second (FEV1) during a maximal forced expiratory maneuver. This study aimed to measure the variation of intrathoracic airway wall compliance (AWC) after acute administration of short acting beta-2 agonist in COPD patients since this might influence the final modification of airway caliber during maximal expiratory effort and the resulting bronchodilation as inferred by FEV1 changes. Methods In a group of 10 patients suffering from COPD, intrathoracic AWC was measured at middle (50% of Forced Vital Capacity (FVC) and low (75% of FVC) lung volumes using the interrupter method during forced expiratory maneuver in basal conditions and after acute inhalation of albuterol (salbutamol) (400 mcg by MDI). Ten healthy subjects were examined similarly as a control group. Results Lower values of baseline intrathoracic AWC at both lung volumes were found in COPD patients (1.72 ± 0.20 ml/cmH2O and 1.08 ± 0.20 ml/cmH2O, respectively) as compared to controls (2.28 ± 0.27 ml/cmH2O and 1.44 ± 0.22 ml/cmH2O, respectively) (p 2O and 1.31 ± 0.39 ml/cmH2O, respectively (p Conclusion In COPD patients, AWC is reduced compared to controls, but after bronchodilator, the intrathoracic airways become more compliant. The consequent increased collapsibility under high positive pleural pressure could limit the airway caliber improvement seen after bronchodilator, as assessed by the FEV1 changes during the forced expiratory maneuver, underestimating the effective bronchodilation achieved in these patients.

Identifying positive bronchodilator reversibility (BDR) helps the diagnosis of asthma. However, not all patients can adequately perform the forced expiration during the spirometry test. An alternative test is required. Impulse oscillometry (IOS) is an effort-independent technique that enables the measurement of lung mechanics during quiet tidal breathing. We investigated the potentiality of IOS to evaluate BDR in untreated adult patients with newly diagnosed asthma (UAPNDS).All UAPNDS (aged 20-80 years) who never smoke and underwent IOS and spirometry before and after salbutamol inhalation at their initial visit to the hospital from March 22, 2017, to December 31, 2019, were identified. A total of 323 patients were enrolled. Data from the medical record, including demographic characteristics, laboratory examination, spirometric data, and IOS parameters, were retrospectively reviewed. The associations of parameters with the positive BDR and the performance of parameters in predicting the positive BDR were evaluated by statistical methods.Patients (n = 323) had a median age of 64 years and were mostly female (67.5%). Several variables, including serum total immunoglobulin level, blood eosinophil counts, blood eosinophil percentage (%), and two IOS parameters, were found to be different between the positive (n = 93) and negative BDR (n = 230) groups. Multivariate logistic regression analyses after adjustment by cofactors revealed that the percentage change of the area under the reactance curve between 5 Hz and resonant frequency [ΔAx (%)] after salbutamol inhalation was the only independent factor for the positive BDR. The area under the receiver operating characteristic curve of ΔAx (%) in predicting the positive BDR was 0.614 ( p = 0.0013), and its optimal cutoff value was -53.8% (sensitivity, 39.78% and specificity, 80.43%).In addition to spirometry, ΔAx (%), an IOS parameter, may serve as a novel indicator to evaluate BDR in UAPNDS.

Women with threatened preterm labor in remote Australia often require tocolysis in the prevention of in-flight birth during air medical retrieval. However, debate exists over the tocolytic choice.A retrospective analysis was undertaken on data containing women who required air medical retrieval for threatened preterm labor within Western Australia between the years 2013 and 2018.A total number of 236 air medical retrievals were deemed suitable for inclusion; 141 received nifedipine, and 95 women received salbutamol + nifedipine. Tocolytic efficaciousness was reported in 151 cases, proportionally more (P.05) from the women who received salbutamol + nifedipine (n = 68, 71.6%) compared with the women who received nifedipine only (n = 83, 58.9%). Those receiving salbutamol + nifedipine were more likely to suffer maternal tachycardia (n = 87 [91.6%] vs. n = 62 [44.0%]), fetal tachycardia (n = 26 [27.4%] vs. n = 13 [9.2%]), nausea (n = 17 [17.9] vs. n = 5 [3.55%]), and vomiting (n = 12 [12.6%] vs. n = 2 [1.4%]). Three women who received salbutamol + nifedipine had serious side effects including echocardiographic changes, chest pain, and metabolic and lactic acidosis.Salbutamol + nifedipine tocolysis was proven to be more effective than nifedipine only. Although salbutamol + nifedipine had increased temporary side effects, most were nonsevere and managed in-flight.

Salbutamol was included in the prohibited list of the World Anti-Doping Agency (WADA) in 2004. Although systemic intake is banned, inhalation for asthma is permitted but with dosage restrictions. The WADA established a urinary concentration threshold to distinguish accordingly prohibited systemic self-administration from therapeutic prescription by inhalation. This study aimed at evaluating the ability of the WADA threshold to differentiate salbutamol therapeutic use from violation of antidoping rules. Concentration-time profile of salbutamol in plasma and its excretion in urine was characterized through a model-based meta-analysis of individual and aggregate data collected after administration of a large range of doses following different modes of administration and under a variety of conditions. The developed model adequately fitted salbutamol plasma and urine concentration-time profiles of the 13 selected studies. Model-based simulations confirmed that a wide range of salbutamol urine concentrations might be measured after drug intake. Although violation of the WADA Code can be strongly suspected in individuals showing very high salbutamol urine concentrations, uncertainty remains for values close to the WADA threshold as they can be compatible with both permitted therapeutic use and violation. Although not entirely discriminant, the current WADA rule is globally supported by our appraisal. It could be further improved by a slight and reasonable adjustment of inhaled daily dosages allowed for therapeutic use. Our model might help antidoping experts in the evaluation of suspected doping cases through confronting the athlete's urine measurements with their allegations about salbutamol treatment.

This study aimed to compare statewide emergency medical services protocols for the management of pediatric respiratory distress.We performed a descriptive study of emergency medical services protocols for the management of pediatric respiratory distress in the United States, excluding those without model or mandatory protocols. We compared medication recommendations for specific disease processes, including asthma, croup, epiglottitis, anaphylaxis, generalized respiratory distress, intubation, and drug assisted intubation.Thirty-four state protocols were included. All had protocols to address the management of pediatric respiratory distress. There was high agreement in albuterol use for bronchospasm and epinephrine use in anaphylaxis. Epinephrine was recommended in all anaphylaxis protocols, 27 croup protocols (79%), and 3 epiglottitis protocols (9%). Six states (18%) called for albuterol in patients with generalized respiratory distress. Steroid recommendations and indications had variance among states; 26 states (76%) allowed steroid use in patients with asthma, 19 states (56%) recommended steroid use in anaphylaxis, and 11 (32%) recommended steroid use in croup protocols. The route for steroid administration also varied among protocols. Five states (15%) allowed continuous positive airway pressure application in pediatric patients, whereas endotracheal intubation and rapid sequence intubations had varying requirements as well as recommendations for use. Twelve (35%) listed impending or current respiratory failure as an indication, whereas other states had specific markers, such as Glasgow Coma Scale or oxygen saturation, as indications.All included states had specific recommendations for the management of pediatric respiratory distress. There was consistency in recommendations for albuterol use for wheezing and epinephrine use for anaphylaxis. However, there was wide variability in other uses for epinephrine, steroid administration, continuous positive airway pressure use, and specific treatments for croup and epiglottitis. The findings of this study provide a base for important future evidence-based protocol developments and changes in prehospital pediatric respiratory distress treatment.

Racemic salbutamol ((RS)-sal), which consist of the same amount of (R)-sal and (S)-sal, has been used for asthma and COPD due to its bronchodilation effect. However, the effect of (R)-sal on repeated dextran sulfate sodium (DSS)-induced chronic colitis has not yet been investigated. In this study evaluated the potential effect of (R)-, (S)-, and (RS)-sal in mice with repeated DSS-induced chronic colitis and investigated the underlying mechanisms. Here, we verified that chronic colitis was significantly attenuated by (R)-sal, which was evidenced by notably mitigated body weight loss, disease activity index (DAI), splenomegaly, colonic lengths shortening, and histopathological scores. (R)-sal treatment noticeably diminished the levels of inflammatory cytokines (such as TNF-α, IL-6, IL-1β, and IFN-γ). Notably, the efficacy of (R)-sal was better than that of (RS)-sal. Further research revealed that (R)-sal mitigated colonic CD4 leukocyte infiltration, decreased NF-κB signaling pathway activation, improved the Nrf-2/HO-1 signaling pathway, and increased the expression of ZO-1 and occludin. In addition, (R)-sal suppressed the levels of TGF-β1, α-SMA, and collagen in mice with chronic colitis. Furthermore, the 16S rDNA sequences analyzed of the intestinal microbiome revealed that (R)-sal could mitigate the intestinal microbiome structure and made it more similar to the control group, which mainly by relieving the relative abundance of pathogens (such as Bacteroides) and increasing the relative abundance of probiotics (such as Akkermansia). Therefore, (R)-sal ameliorates repeated DSS-induced chronic colitis in mice by improving inflammation, suppressing oxidative stress, mitigating intestinal barrier function, relieving intestinal fibrosis, and regulating the intestinal microbiome community. These results indicate that (R)-sal maybe a novel treatment alternative for chronic colitis.

The impact of the crystallinity of organic solid materials on their tribocharging propensity is well reported. However, no unequivocal explanation about the potential underlying mechanism(s) could be found so far in the literature. This study reports the effect that different degrees of crystalline disorder has on the tribocharging propensity of a small molecular organic material, salbutamol sulfate (SS). Ball-milling was used to induce structural transformations in the crystalline structure of SS. Particles with different nanostructures were produced and analyzed for their solid-state, particle properties, and tribocharging. It was found that differences in the amorphous content among the processed particles and related moisture levels had an impact on powder tribocharging. A correlation between the latter and the nanostructural properties of the particles was also established. The presence of interfaces between nanodomains of different densities and shorter average lengths within the phases seems to lead to a mitigation of charge. This suggests that undetected, subtle nanostructural differences of materials can affect powder handling and processability by altering their tribocharging. The present findings demonstrate the nanostructural implications of powder triboelectrification, which can help toward the rational design of a wide variety of organic solids.

OBJECTIVE Status asthmaticus is commonly treated in pediatric patients by using continuous albuterol, which can cause hypokalemia. The primary aim of this study was to determine if serial potassium monitoring is necessary by examining treatment frequency of hypokalemia. METHODS This retrospective analysis was performed in 185 pediatric patients admitted with status asthmaticus requiring continuous albuterol between 2017 and 2019. All patients were placed on intravenous fluids containing potassium. The primary outcome measure was the treatment of hypokalemia in relation to the number of laboratory draws for potassium levels. The secondary outcome measure was hypokalemia frequency and relation to the duration and initial dose of continuous albuterol. RESULTS Included were 156 patients with 420 laboratory draws (average, 2.7 per patient) for potassium levels. The median lowest potassium level was 3.40 mmol/L (interquartile range, 3.2–3.7). No correlation was found between initial albuterol dose and lowest potassium level (P = .52). Patients with hypokalemia had a mean albuterol time of 12.32 (SD, 15.76) hours, whereas patients without hypokalemia had a mean albuterol time of 11.50 (SD, 12.53) hours (P = .29). Potassium levels were treated 13 separate times. CONCLUSIONS The number of laboratory draws for potassium levels was high in our cohort, with few patients receiving treatment for hypokalemia beyond the potassium routinely added to maintenance fluids. Length of time on albuterol and dose of albuterol were not shown to increase the risk of hypokalemia. Serial laboratory measurements may be decreased to potentially reduce health care costs, pain, and anxiety surrounding needlesticks.

To determine the common clinical signs, with onset and duration, treatments given, and outcome in dogs with acute, accidental exposure to salbutamol.Retrospective study.Five hundred and one canine cases reported to the UK's Veterinary Poisons Information Service (VPIS).A review of all records in the VPIS database for dogs exposed to salbutamol was carried out. After applying inclusion and exclusion criteria, the records of 501 dogs were further analyzed. The most common clinical signs were tachycardia (80.6%), tachypnea (32.9%), depression (21.0%), and vomiting (19.2%). The dose was unknown in most cases as the dogs typically pierced a salbutamol inhaler. The blood potassium concentration was measured in at least 142 dogs and hypokalemia was reported in 21.2% (106/501), 18 (17%) of which had associated weakness, twitching, or collapse. Three dogs had paralysis probably as a result of hypokalemia, although no potassium concentration was reported in these cases. Arrhythmias occurred in 17 dogs (3.4%), and 7 required pharmacological intervention. There were no reports of persistent cardiac injury or thermal injury from the compressed gas present in some salbutamol products. Signs were rapid in onset, generally within 1-3 h, and, where time to outcome was recorded (n = 172), 78% of dogs recovered within 24 h. Of the 501 dogs, no treatment was required in 27.9%. Beta-blockers were used in 39.5%, intravenous fluids in 28.7%, and potassium supplementation in 15.8%. Overall, 30 dogs remained asymptomatic (6.0%), 469 recovered (93.6%), and 2 dogs (0.4%) died.Most dogs exposed to salbutamol rapidly develop clinical signs; these were commonly increased heart and respiration rates. Hypokalemia and arrhythmias (particularly ventricular arrhythmias) are potential complications. Any dog that chews a salbutamol inhaler should be assessed promptly for signs of toxicosis. Prognosis in dogs with acute salbutamol exposure is good, but more guarded in those with severe tachycardia and at risk of cardiac injury.

Background: Bacillus Calmette-Guerin (BCG) is a vaccine used to protect against tuberculosis primarily in infants to stop early infection in areas of the world where the disease is endemic. Normally administered as a percutaneous injection, BCG is a live significantly attenuated bacteria that is now being investigated for its potential within an inhalable vaccine formulation. This study investigates the feasibility and performance of two jet and two vibrating mesh nebulizers aerosolizing BCG and the resulting particle characteristics and residual viability of the bacteria postaerosolization. Methods: A jet nebulizer (Collison), outfitted either with a 3- or 6-jet head, was compared with two clinical nebulizers, the vibrating mesh Omron MicroAir and Aerogen Solo devices. Particle characteristics, including aerodynamic particle sizing, was performed on all devices within a common aerosol chamber configuration and comparable BCG innocula concentrations. Integrated aerosol samples were collected for each generator and assayed for bacterial viability using conventional microbiological technique. Results: A batch lot of BCG (Danish) was grown to titer and used in all generator assessments. Aerosol particles within the respirable range were generated from all nebulizers at four different concentrations of BCG. The jet nebulizers produced a uniformly smaller particle size than the vibrating mesh devices, although particle concentrations by mass were similar across all devices tested with the exception of the Aerogen Solo, which resulted in a low concentration of BCG aerosols. Conclusions: The resulting measured viable BCG aerosol concentration fraction produced by each device approximated one another; however, a measurable decrease of efficiency and overall viability reduction in the jet nebulizer was observed in higher BCG inoculum starting concentrations, whereas the vibrating mesh nebulizer returned a remarkably stable viable aerosol fraction irrespective of inoculum concentration.

Bronchospasm is a common respiratory adverse event in pediatric anesthesia. First line treatment commonly includes inhaled salbutamol. This review focusses on the current best practice to deliver aerosolized medications to awake as well as anesthetized pediatric patients and discusses the advantages and disadvantages of various administration techniques. Additionally, we detail the differences between various airway devices used in anesthesia. We highlight the unmet need for innovation of orally inhaled drug-products to deliver aerosolized medications during pediatric respiratory critical events such as bronchospasm. It is therefore important that clinicians remain up to date with the best clinical practice for aerosolized drug delivery in order to prevent and efficiently treat pediatric patients experiencing life-threatening respiratory emergencies.

Inhalation therapy with corticosteroids and long-acting βThis study aimed to evaluate asthma control and device usability with salmeterol/fluticasone fixed-dose combination (FDC) administered through SynchrobreatheThe present study was a prospective, open-label, non-comparative, multi-center, observational study.The study enrolled 490 patients with documented diagnoses of asthma who were treatment-naive or uncontrolled due to poor inhaler technique associated with a previous device. The primary endpoint was a change from baseline in the Asthma Control Questionnaire-6 (ACQ-6) score at week 12.Mean ACQ-6 score reduced from 2.2 ± 1.07 (baseline) to 0.4 ± 0.49 (mean change: -1.9 ± 1.12,Treatment with salmeterol/fluticasone FDC administered through SynchrobreatheThe study was registered with the Clinical Trial Registry of India (CTRI/2018/12/016629).

BACKGROUND Acute cervical spinal cord injury (ACSCI) is commonly complicated by spinal shock, resulting in hemodynamic instability characterized by bradycardia and hypotension that can have fatal consequences. Current guidelines recommend the use of intravenous beta and dopamine agonists, such as norepinephrine and dopamine, respectively. We sought to determine whether enteral albuterol would be a safe and feasible treatment for bradycardia without an increase in the occurrence of known side effects of albuterol in patients with ACSCI. METHODS A retrospective review of patients with ACSCI admitted to an intensive care unit at a level I trauma center and treated with enteral albuterol was conducted. Patients were excluded for the following reasons: pure beta blocker use prior to injury, concurrent use of pacemaker, age of less than 18 years, or age more than 75 years. As part of the standard of care, all patients underwent mean arterial pressure (MAP) augmentation to reach a goal of greater than 85 mm Hg during the first 7 days post injury. All eligible patient charts were reviewed for demographic characteristics, daily minimum and maximum heart rate and MAP, and concomitant vasoactive medication use. Bradycardia and tachycardia were defined as heart rate less than 60 beats per minute (bpm) and greater than 100 bpm, respectively. Factors found to be associated with bradycardia on univariate analysis were entered into a multivariable generalized estimating equation analysis to determine factors independently associated with bradycardia during the study period. RESULTS There were 58 patients with cervical ASCI (age 45 ± 18 years, 76% men) admitted between January 1, 2016, and December 31, 2017, that met the study criteria. The mean time to initiation of albuterol was 1.5 ± 1.7 days post injury, with a duration of 9.3 ± 4.5 days and a mean daily dosage of 7.8 ± 4.5 mg. Bradycardia was observed in 136 of 766 patient days (17%). There were a few episodes of hyperglycemia (1%) and tachycardia (3%), but no episodes of hypokalemia. In a multivariable analysis, female sex (P = 0.006) and American Spinal Cord Injury Association grade A, B, or C (P

One of the most common causes of respiratory distress in newborns is transient tachypnea of the newborn (TTN). Salbutamol is often suggested to increase the rate of pulmonary fluid absorption in newborns with TTN. This study aimed to evaluate the efficacy of inhaled salbutamol in TTN management.This double-blind clinical trial was conducted on 52 newborns admitted to the neonatal ICU of Fatemieh Hospital of Hamadan, Iran. The newborns were randomly assigned to 2 groups of equal members: one group received 2 mL of nebulized sodium chloride concentration (control group), and the other group was treated with 0.1 mg/kg of salbutamol (treatment group). The clinical outcomes were then compared before and 0.5, 1, and 4 h after the intervention. The data were recorded in a checklist and then were statistically analyzed in SPSS 16: the significant level was decided to beThe comparison of TTN scores revealed a significant difference between the 2 groups 1 h (The study results indicated that inhaled salbutamol significantly decreased the TTN clinical score, oxygen demands, and duration of respiratory support, whereas there was no significant difference between the groups in terms of LOS.

Introduction: Fugitive aerosol concentrations generated by different nebulizers and interfaces in vivo, and mitigation of aerosol dispersion into the environment with various commercially available devices are not known. Methods: Nine healthy volunteers were given 3 mL saline with a small volume nebulizer (SVN) or vibrating mesh nebulizer (VMN) with a mouthpiece, a mouthpiece with an exhalation filter, an aerosol mask with open ports for SVN and a valved facemask for VMN, and a facemask with a scavenger (Exhalo) in random order. Five of the participants received treatments using a face tent scavenger (Vapotherm) and a mask with exhalation filter with SVN and VMN in a random order. Treatments were performed in an ICU room, with 2 particle counters positioned 1 and 3 feet from participants measuring aerosol concentrations at sizes of 0.3-10 µm at baseline, before, during and after each treatment. The Ethics Committee at Rush University approved this study. Results: Fugitive aerosol concentrations were higher with SVN than VMN and higher with a facemask than a mouthpiece. Adding an exhalation filter to a mouthpiece reduced aerosol concentrations of 0.3-1.0 µm in size for VMN and 0.3-3.0 µm for SVN (all p

Context Exercise blunts the effect of beta2-agonists on peripheral glucose uptake and energy expenditure. Whether such attenuation extends into recovery is unknown. Objective To examine the effect of a beta2-agonist on leg glucose uptake and metabolic rate in recovery from exercise. Methods Using leg arteriovenous balance technique and analyses of thigh muscle biopsies, we investigated the effect of a beta2-agonist (24 mg of oral salbutamol) vs placebo on leg glucose, lactate, and oxygen exchange before and during quadriceps exercise, and 0.5 to 5 hours in recovery from quadriceps exercise, as well as on muscle glycogen resynthesis and activity in recovery. Twelve healthy, lean, young men participated. Results Before exercise, leg glucose uptake was 0.42 ± 0.12 and 0.20 ± 0.02 mmol × min–1 (mean ± SD) for salbutamol and placebo (P = .06), respectively, while leg oxygen consumption was around 2-fold higher (P Conclusion Exercise blunts the effect of beta2-agonist salbutamol on leg glucose uptake, but this attenuation diminishes in recovery. Salbutamol increases leg lactate release in recovery, which may relate to glycolytic trafficking due to excessive myocellular glucose uptake.

Introduction Asthma is a leading cause of pediatric emergency department (ED) visits. A metered-dose inhaler and spacer (MDI-S) device is equivalent to and more cost effective than delivery by nebulization in the ED management of mild asthma exacerbations. We aimed to increase the use of albuterol MDI-S among patients with mild asthma exacerbations using a quality improvement framework. Methods We evaluated albuterol use for mild asthma exacerbations between January 2019 and March 2020 in our pediatric EDs. Results Our primary outcome was the proportion of albuterol delivered through an MDI-S. Our process measure was the use of a new electronic order set. Balancing measures included ED length of stay, admission rates, and the use of intravenous magnesium. Interventions included forging multidisciplinary partnerships, revising clinical practice guidelines, establishing an electronic order set, and leading educational initiatives for clinicians. We demonstrated a center line shift of MDI-S use from 34.4% to 47.7%. The average length of stay, hospital admissions, and magnesium use were not affected by our interventions. Conclusion Forging multidisciplinary partnerships, creating an electronic order set prioritizing albuterol MDI-S use, and educational initiatives led to a sustained increase in albuterol MDI-S use for mild asthma in our pediatric EDs.

SUMMARY OBJECTIVE: The aim of this study was to investigate the efficacy and safety of combined doxofylline and salbutamol in the treatment of acute exacerbation of chronic obstructive pulmonary disease. METHODS: A total of 68 acute exacerbation of chronic obstructive pulmonary disease patients were randomly divided into control group (34 cases) and experimental group (34 cases), who received the doxofylline treatment and combined doxofylline and salbutamol treatment for 1 week, respectively. During the treatment, the remission time of typical respiratory manifestations was recorded, and the adverse reactions were observed. At the end of treatment, the treatment efficacy was evaluated. Before and after treatment, the pulmonary function indexes and serological indicators were detected. RESULTS: After treatment, compared with control group, in experimental group, the effective rate of treatment was significantly increased (p0.05). CONCLUSIONS: In the treatment of acute exacerbation of chronic obstructive pulmonary disease, the combined use of doxofylline and salbutamol can quickly relieve the respiratory symptoms, mitigate the pulmonary dysfunction, and reduce the inflammatory response, thus promoting the outcome of patients.

Rationale: For children with asthma, access to quick-relief medications is critical to minimizing morbidity and mortality. An innovative and practical approach to ensure access at school is to maintain a supply of stock albuterol that can be used by any student who experiences respiratory distress. To make this possible, state laws allowing for stock albuterol are needed to improve medication access. Objectives: To provide policy recommendations and outline steps for passing and implementing stock albuterol laws. Methods: We assembled a diverse stakeholder group and reviewed guidelines, literature, statutes, regulations, and implementation documents related to school-based medication access. Stakeholders were divided into two groups—legislation and implementation—on the basis of expertise. Each group met virtually to review documents and draft recommendations. Recommendations were compiled and revised in iterative remote meetings with all stakeholders. Main Results: We offer several recommendations for crafting state legislation and facilitating program implementation. 1) Create a coalition of stakeholders to champion legislation and implement stock albuterol programs. The coalition should include school administrators, school nurses and health personnel, parents, or caregivers of children with asthma, pediatric primary care and subspecialty providers (e.g., pulmonologists/allergists), pharmacists, health department staff, and local/regional/national advocacy organizations. 2) Legislative components critical for effective implementation of stock albuterol programs include specifying that medication can be administered in good faith to any child in respiratory distress, establishing training requirements for school staff, providing immunity from civil liability for staff and prescribers, ensuring pharmacy laws allow prescriptions to be dispensed to schools, and suggesting inhalers with valved holding chambers/spacers for administration. 3) Select an experienced and committed legislator to sponsor legislation and guide revisions as needed during passage and implementation. This person should be from the majority party and serve on the legislature’s health or education committee. 4) Develop plans to disseminate legislation and regulations/policies to affected groups, including school administrators, school nurses, pharmacists, emergency responders, and primary/subspecialty clinicians. Periodically evaluate implementation effectiveness and need for adjustments. Conclusions: Stock albuterol in schools is a safe, practical, and potentially life-saving option for children with asthma, whether asthma is diagnosed or undiagnosed, who lack access to their personal quick-relief medication. Legislation is imperative for aiding in the adoption and implementation of school stock albuterol policies, and key policy inclusions can lay the groundwork for success. Future work should focus on passing legislation in all states, implementing policy in schools, and evaluating the impact of such programs on academic and health outcomes.

OBJECTIVES A bronchiolitis integrated care pathway (BICP) proved useful in reducing the use of unnecessary medications at a local level. The aim of this study was to reduce overtreatment by scaling up the BICP across our regional health service in the 2019 and 2020 bronchiolitis season. METHODS We conducted a quality improvement (QI) initiative in 115 primary care (PC) centers and 7 hospitals in the Basque Country, Spain, from October 2019 to March 2020. The primary outcome measure was the percentage of children prescribed salbutamol comparing the rate to that in the previous bronchiolitis season (October 2018–March 2019). Secondary outcomes were the use of other medications. Balancing measures were hospitalization and unscheduled return rates. RESULTS We included 8153 PC visits, 3424 emergency department (ED) attendances, and 663 inpatient care episodes, of which 3817 (46.8%), 1614 (47.1%), and 328 (49.4%) occurred in the postintervention period, respectively. Salbutamol use decreased from 27.1% to 4.7%, 29.5% to 3.0%, and 44.4% to 3.9% (P < .001) in PC centers, Eds, and hospital wards, respectively. In PC, corticosteroid and antibiotic prescribing rates fell from 10.1% to 1.7% and 13.7% to 5.1%, respectively (P < .001). In EDs and hospital wards, epinephrine use rates fell from 14.2% to 4.2% (P < .001) and 30.4% to 19.8% (P = .001), respectively. No variations were noted in balancing measures. CONCLUSIONS The scaling up of the BICP was associated with significant decreases in the use of medications in managing bronchiolitis across a regional health service without unintended consequences.

Exploiting adsorbents with highly efficient extraction performance is of great promise for extracting small organic molecules from biological samples. In this work, a novel Zn

Albuterol by inhalation (IH) is a common treatment for hyperkalemia in humans but its effect on blood potassium concentrations in dogs is unknown.Determine whether albuterol (IH) decreases blood potassium concentrations in healthy normokalemic dogs and if effects are dose-dependent.Ten healthy dogs.Prospective, crossover experimental study. Albuterol sulfate was administered at a low-dose (90 μg) in phase I and, 7 days later, high-dose (450 μg) in phase II. Blood potassium and glucose concentrations (measured via blood gas analyzer) and heart rates were obtained at baseline and then 3, 5, 10, 15, 30, 60, 90, 120, 180, and 360 minutes after inhaler actuation.Blood potassium concentrations decreased rapidly after albuterol delivery with a significant reduction compared to baseline within 30 minutes in both phases (P = .05). The potassium nadir concentration of phase I occurred at 60 minutes (mean, SD; 4.07 mmol/L, 0.4) and was significantly decreased from baseline, (4.30 mmol/L, 0.3; t(9) = 2.40, P = .04). The potassium nadir concentration of phase II occurred at 30 minutes (mean, SD; 3.96 mmol/L, 0.39) and was also significantly decreased from baseline, (4.33 mmol/L, 0.4; t(9) = 2.22, P = .05). The potassium nadir concentration decreased by 0.1 mmol/L for each 10 μg/kg increase in dose of albuterol (P = .01). Five dogs had ≥1 hyperglycemic measurement (ie,112 mg/dL). No median heart rate was tachycardic nor was any mean blood glucose concentration hyperglycemic at any time point.Albuterol IH decreases blood potassium concentrations in a dose-dependent manner without clinically meaningful alterations to heart rate or blood glucose concentrations in healthy dogs. The mean decrease in potassium concentration at the high-dose of albuterol was modest (0.38 mmol/L).

Albuterol has been a cornerstone of asthma treatment for several decades, but evidence suggests that it may be overused at the expense of more efficacious treatment. Albuterol may not even be appropriate for sole first-line rescue medication in some patients. Inflammatory mechanisms have been shown to play a role early in the course of developing bronchospasm, suggesting that inhaled corticosteroids should be included as part of initial rescue treatment. Newer biologics target inflammatory cytokine pathways, which may be needed in patients with moderate to severe disease. Evidence-based recommendations for the management of asthma and bronchospasm are continuing to evolve.

Previous numerical studies of pulmonary drug delivery using metered-dose inhalers (MDIs) often neglected the momentum transfer from droplets to fluid. However, Kolmogorov length scales in MDI flows can be comparable to the droplet sizes in the orifice vicinity, and their interactions can modify the spray behaviors. This study aimed to evaluate the two-way coupling effects on spray plume evolutions compared to one-way coupling. The influences from the mass loading, droplet size, and inhaler type were also examined. Large-eddy simulation and Lagrangian approach were used to simulate the flow and droplet motions. Two-way coupled predictions appeared to provide significantly improved predictions of the aerosol behaviors close to the Ventolin orifice than one-way coupling. Increasing the applied MDI dose mass altered both the fluid and aerosol dynamics, notably bending the spray plume downward when applying a dose ten times larger. The droplet size played a key role in spray dynamics, with the plume being suppressed for 2-µm aerosols and enhanced for 20-µm aerosols. The Kolmogorov length scale ratio dp/η correlated well with the observed difference in spray plumes, with suppressed plumes when dp/η < 0.1 and enhanced plumes when dp/η > 0.1. For the three inhalers considered (Ventolin, ProAir, and Qvar), significant differences were predicted using two-way and one-way coupling despite the level and manifestation of these differences varied. Two-way coupling effects were significant for MDI sprays and should be considered in future numerical studies.

PURPOSE Relvar® (fluticasone furoate [FF]/vilanterol [VI]) is a once-daily inhaler with bronchodilator effect lasting 24 h. Our aim was to investigate the short- and long-term effects of FF/VI on exercise-induced asthma (EIA) in adolescents. METHODS Ninety-three adolescent asthmatics aged 12-18 years were referred for evaluation of EIA. Following a positive exercise challenge test (ECT), 22/44 were allocated to a single administration of salbutamol (400 μg) and 22/44 to FF/VI (92/22 μg) in a double-blind method. Thirty-five subjects were reassessed by repeat ECT 30-60 days of FF/VI. RESULTS Median FEV1 change post-ECT at baseline was -22.8% predicted (interquartile range [IQR] -26.1 and -18.0) for salbutamol and -21.0 (IQR -30.7 and -16.8) for FF/VI. Following bronchodilator, FEV1 improved similarly in both groups. Repeat ECT following 30-60 days of FF/VI resulted in negative ECT in 33/35 subjects; the median decrease in FEV1 of these 35 subjects was 22.6% predicted (IQR 29-18) before, and 4.6% predicted (IQR 8.7-2.5) after 30-60 days of FF/VI treatment (p

Asthma is the most common noncommunicable chronic childhood disease, affecting more than 5 million children in the United States. Asthma is the leading cause of school absenteeism. Treatments for asthma are divided into fast-acting medications that are used to relieve symptoms and slower acting (controller) medications that prevent symptoms. Albuterol is the most common fast acting medication for asthma, and it exists in multiple forms, including metered-dose inhaler and nebulized therapy. The use of spacers and holding chambers can further improve medication deposition in the airway. The cornerstone controller therapy for asthma is inhaled corticosteroid. Other medications for asthma include long-acting beta agonists, long-acting antimuscarinics, and antileukotrienes. The newest agents for controller asthma therapies are biologics.

The thiazide-sensitive sodium-chloride-cotransporter (NCC) in the kidney distal convoluted tubule (DCT) plays an essential role in sodium and potassium homeostasis. Here, we demonstrate that NCC activity is increased by the β2-adrenoceptor agonist salbutamol, a drug prevalently used to treat asthma. Relative to β1-adrenergic receptors, the β2-adrenergic receptors were greatly enriched in mouse DCT cells. In mice, administration of salbutamol increased NCC phosphorylation (indicating increased activity) within 30 minutes but also caused hypokalemia, which also increases NCC phosphorylation. In ex vivo kidney slices and isolated tubules, salbutamol increased NCC phosphorylation in the pharmacologically relevant range of 0.01-10 μM, an effect observed after 15 minutes and maintained at 60 minutes. Inhibition of the inwardly rectifying potassium channel (Kir) 4.1 or the downstream with-no-lysine kinases (WNKs) and STE20/SPS1-related proline alanine-rich kinase (SPAK) pathway greatly attenuated, but did not prevent, salbutamol-induced NCC phosphorylation. Salbutamol increased cAMP in tubules, kidney slices and mpkDCT cells (model of DCT). Phosphoproteomics indicated that protein phosphatase 1 (PP1) was a key upstream regulator of salbutamol effects. A role for PP1 and the PP1 inhibitor 1 (I1) was confirmed in tubules using inhibitors of PP1 or kidney slices from I1 knockout mice. On normal and high salt diets, salbutamol infusion increased systolic blood pressure, but this increase was normalized by thiazide suggesting a role for NCC. Thus, β2-adrenergic receptor signaling modulates NCC activity via I1/PP1 and WNK-dependent pathways, and chronic salbutamol administration may be a risk factor for hypertension.

BACKGROUND: The purpose of this study was to evaluate how factors (ambient temperature, shaking the inhaler before use, suspension of the inhaler in water, and the variation over the lifetime of the inhaler) affect the particle-size distributions from albuterol HFA inhalers. METHODS: We used a laser particle-size analyzer to measure the percentage of particles in the 1- to 5-μm range (fine-particle fraction) serially 2,500 times per second to obtain a window of useful measurements with each inhaler actuation. We compared the inhaler performance results as follows: cold versus hot, full versus partial versus empty inhaler actuations, shaken versus unshaken, and inhaler characteristics after water submersion. RESULTS: The effect of temperature was as follows: fine-particle fraction was 14.4% at 5°C, 37.9% at 24 - 25°C, and 38.1% at 45°C. The fine-particle fraction at the start, middle, end, and past the end of the inhaler’s rated lifetime were 37.9, 26.3, 27.9, and 22.0%, respectively. Shaking the inhaler did not improve the inhaler’s fine-particle fraction. Submerging the inhaler reduced the fine-particle fraction to 14.3% without purging and to 20.5% with purging compared with the 42.1% for the control inhaler, which was not submerged. CONCLUSIONS: Temperature made a difference, with cold inhalers producing a lower fine-particle fraction. The early portion of the inhaler had a better fine-particle fraction than the middle and end of the inhaler’s lifespan. We could not demonstrate that shaking the inhaler had a significant effect on the fine-particle fraction. Submerging the inhaler in water significantly reduced the fine-particle fraction.

Standard spirograms are widely used in the respiratory disease management community to help diagnosis asthma and provide longitudinal information. Surprisingly, basic information obtained on the spirogram, beyond the FEVLimited data has been published on FEVNew data on FEV

Objective This study aimed to compare the efficacy of using dexmedetomidine with salbutamol and salbutamol nebulization alone in patients with acute exacerbation of asthma presenting to the emergency department. Methods This clinical trial included 60 patients, in the age range of 18 to 55 years, with signs of bronchospasm presenting to the emergency department. In the intervention group, dexmedetomidine 0.5 µg/kg was injected intravenously and three doses of salbutamol nebulization were administered over 60 minutes. In the control group, salbutamol nebulization was administered for 60 minutes three times. The patient's clinical status, based on clinical symptoms, consciousness, speech, breathing rate, heart rate, and blood pressure were recorded before the intervention, and peak expiratory flow rate and forced expiratory volume in 1 second were measured at 20, 40, and 60 minutes after intervention. Patients who did not respond to the intervention were excluded from the study within 60 minutes. Results The increased mean forced expiratory volume in 1 second and mean peak expiratory flow rate were found to be similar in both groups during the treatment (P=0.304). The mean systolic and diastolic blood pressure recorded at 40 and 60 minutes were significantly lower in the intervention group. During this study, no patient was excluded before 60 minutes. Conclusion Administration of dexmedetomidine in addition to standard salbutamol treatment has no beneficial effect in patients with acute asthma attacks and merely causes hypotension in patients.

Background: Acute rhinovirus-induced wheezing is common in young children and may respond to systemic corticosteroid. There are no trials on the efficacy of inhaled beta₂-agonist in this clinical scenario. Objective: To study post hoc the short-term (up to 2 months) efficacy of inhaled beta2-agonist with and without oral corticosteroid in the first acute rhinovirus-induced severe wheezing episode in young hospitalized children. Methods: The study population came from two randomized controlled trials comparing oral prednisolone (2 mg/kg/d for 3 days) to placebo: Vinku (n = 35, NCT00494624) used high-dose regular nebulized salbutamol (0.15 mg/kg 2–4 h intervals) and Vinku2 (n = 60, NCT00731575, EudraCT 2006-007100-42) used inhaled salbutamol on-demand. Both studies used identical detailed follow-up assessments. The primary outcome of the former was the duration of hospitalization and of the latter the occurrence of and the time to a new physician-confirmed wheezing episode within 2 months after discharge. Treatment groups included salbutamol high-dose vs. salbutamol on-demand while adjusting for prednisolone status and acknowledging for interactions with exception of the duration of hospitalization in which prednisolone groups could not be fully used due to protocol differences. Results: Median age of subjects was 13 months, 32% were sensitized and 22% had doctor-diagnosed eczema. In the duration of hospitalization, salbutamol high-dose/placebo versus salbutamol on-demand/placebo groups did not differ (p = .12). In the occurrence of and time to relapse within 2 months, a significant group × treatment interaction was observed (both p = .02), such that high-dose group had less and longer time to relapses than on-demand group in prednisolone arm (both p < .05), but no difference was detected in placebo arm (both p > .26). Conclusions: In young, hospitalized children with first episode of rhinovirus-induced wheezing, high-dose inhaled salbutamol may interact with oral prednisolone. However, further trials are warranted.

Salbutamol (SAL), a β-2 adrenoreceptor agonist, is an unpopular addition to livestock and poultry, causing several side effects to human health. Thus, it is very important to develop a simple and rapid analytical method to screen SAL in the field of food safety. Here, we present an immunochromatographic assay (ICA) method for sensitively detecting SAL with polydopamine-decorated iridium oxide nanoparticles (IrO2@PDA NPs) as a signal tag. The IrO2@PDA with excellent hydrophilicity, biocompatibility, and stability was synthesized by oxidating self-polymerization of dopamine hydrochloride (DAH) on the surface of IrO2 NPs and used to label monoclonal antibodies (mAbs) through simple physical adsorption. Compared with IrO2 NPs, the IrO2@PDA also possessed superior optical properties and higher affinity with mAbs. With the proposed method, the limit of detection for SAL was 0.002 ng/mL, which was improved at least 24-fold and 180-fold compared with the IrO2 NPs-based ICA and conventional gold nanoparticles-based ICA, respectively. Furthermore, the SAL residuals in pork, pork liver, and beef were successfully detected by the developed biosensor and the recoveries ranged from 85.56% to 115.56%. Briefly, this work indicated that the powerful IrO2@PDA-based ICA can significantly improve detection sensitivity and has huge potential for accurate and sensitive detection of harmful small molecules analytes in food safety fields.

BACKGROUND: Suspensions delivered via a pressurized metered-dose inhaler (pMDI) require shaking the canister before actuation to prevent drug sedimentation. We hypothesized that a shake-actuation delay of an albuterol hydrofluoroalkane (HFA) pMDI will increase and decrease delivered dose (DOSE) at the beginning and end of the canister’s life, respectively, and that aerosol characteristics will remain unchanged with the delay. METHODS: Albuterol HFA pMDIs (90 µg/actuation, 200 doses) operated with and without a 30-s shake-actuation delay, and with and without a valved holding chamber (VHC), were studied. Ten puffs, with a 30-s interval between puffs and 5s of shaking, were actuated into a drug-recovery apparatus. Inhalers were studied throughout their entire life (from 200 doses to 0 remaining doses). Particle size analysis was performed with cascade impaction at the beginning, middle, and end of the canister’s life. Albuterol mass was determined via spectrophotometry (276 nm). RESULTS: Mean (99% CI) delivered dose without shake-actuation delay was 100.4% (98.1–102.9%) of the nominal dose. Mean (99% CI) delivered dose with a VHC without a shake-actuation delay was 48.6% (46.2–50.9%) of the nominal dose. The shake-actuation delay increased and decreased delivered dose at the beginning and end of the canister’s life, respectively, irrespective of VHC use. Decline in delivered dose began when 110–120 doses remained in the canister. Aerosol characteristics remained constant throughout the canister’s life except for the amount of drug captured by the impactor for the pMDI with delay and the pMDI/VHC with delay. Adding a VHC to a pMDI operated with a delay increased fine-particle fraction and decreased the amount of drug captured by the impactor at the middle and at the end of the canister’s life. CONCLUSIONS: A 30-s shake-actuation delay of an albuterol HFA pMDI increased and decreased delivered dose at the beginning and end of canister’s life, respectively. Particle size characteristics at the end of the canister’s life changed when the pMDI and pMDI/VHC were operated with a shake-actuation delay. Patients should re-shake the pMDI if it is not actuated immediately after shaking the canister.

biBackground:/i/bSuboptimal use of pressurized metered dose inhaler (pMDI) remains a major barrier to inhaled therapy success. Verbal inhaler technique training (VT) fails to maintain patients' good pMDI use, thus training tools might help. Trainhalersup®/sup(THR device) and Flo-Tonesup®/supCR (FTCR device), two novel pMDI technique training tools, were evaluated and compared in terms of relative lung and systemic bioavailability and oropharyngeal deposition of salbutamol inhaled from Ventolinsup®/supEvohalersup®/sup(GlaxoSmithKline) either alone following THR or connected to FTCR.biMethods:/i/bSixteen healthy adults inhaled 2 × 100 μg salbutamol puffs (1 minute apart) from Ventolin using the THR device or FTCR device in a two-period, randomized crossover study. A 7-day washout separated THR and FTCR approaches. Immediately after each puff inhalation, each subject gargled with 20 mL water for oropharyngeal deposition determination. Urine samples were collected 0.5 hour (pre-inhalation) and 0.5, 1.0, and 2.0 hours post-inhalation. Urine was then pooled till 24-hour post-inhalation. The relative lung bioavailability (0- to 0.5-hour urinary salbutamol excretion-USAL0.5) and relative systemic bioavailability (0- to 24-hour urinary excretion of salbutamol and its metabolite-USALMET24) were determined.biResults:/i/bThe mean (standard deviation [SD]) USAL0.5 of the THR and FTCR groups was 5.70 (6.43) and 11.39 (9.67) μg, respectively. The mean (SD) oropharyngeal deposition was 11.11 (4.37) and 6.09 (1.89) μg, respectively. The THR and FTCR devices were statistically significantly different in USAL0.5 and oropharyngeal deposition (ip/i lt; 0.001), whereas there was no statistically significant difference in USALMET24.biConclusion:/i/bThe THR device and the FTCR device showed positive impact on inhaled pMDI delivery. Indeed, the FTCR device doubled the relative lung bioavailability and minimized the unwanted oropharyngeal deposition of inhaled salbutamol. In practice, these pMDI trainers would complement and maintain VT.bStudy Registration:/bThe study was registered on the ISRCTN registry (Reference: ISRCTN88332465-06/12/2017 [Prospectively Registered]).

Clinical drug analyses and identification of pharmaceuticals in biological samples are highly crucial for therapeutic drug monitoring, pharmacokinetic studies, and screening of illicit drugs. Various analytical tools, such as potentiometric electrodes, are used to conduct these investigations. These potentiometric electrodes are superior to other techniques in terms of greenness and cost efficacy, and thus present a good alternative for researchers. In this study, we develop an advanced electrode for the in-situ monitoring of salbutamol in plasma, this electrode was synthesized using multiwalled carbon nanotubes (MWCNT) as hydrophobic conductive substance and copper oxide nanoparticle (CuO NP) as a surface modifier, the developed electrode was compared to traditional liquid contact electrode as well as solid contact electrode and proved its superiority. The use of MWCNT improved the stability of the electrode via preventing the formation of this water layer and the CuO NP improved the sensitivity due to its high surface area and rich electronic properties. CuO NP modified electrode was used for the determination of salbutamol with a Nernstian slope of 57.4 over a linearity range of range 1.0 × 10

BACKGROUND AND OBJECTIVES Options to treat and prevent episodic wheezing in children are scarce. Our objective was to assess the efficacy of intermittent tiotropium bromide treatment in early childhood episodic wheezing. METHODS This 48-week, randomized, open-label, controlled, parallel-group trial was conducted at 4 hospitals in Finland. Children aged 6 to 35 months with 2 to 4 physician-confirmed episodes of wheeze and/or shortness of breath were considered eligible. Study participants were randomly allocated to receive 1 of 3 treatments: once-daily tiotropium bromide 5 µg for 7 to 14 days during respiratory tract infections and as-needed albuterol sulfate 0.2 mg (n = 27), twice-daily fluticasone propionate 125 µg for 7 to 14 days during respiratory tract infections and as-needed albuterol sulfate 0.2 mg (n = 25), or as-needed albuterol sulfate 0.2 mg alone (n = 28). The primary outcome was efficacy, assessed as intention-to-treat by comparing the proportion of episode-free days (the days lacking symptoms or treatments) between the treatment groups. RESULTS The proportion of episode-free days was higher in those receiving intermittent tiotropium bromide (median 97% [interquartile range, 93% to 99%]) than in those receiving intermittent fluticasone propionate (87% [78% to 93%], P = .002), or with as-needed albuterol sulfate alone (88% [79% to 95%], P = .003). Adjustment with allergic sensitization, the baseline number of physician-confirmed episodes of wheeze and/or shortness of breath, or short-course glucocorticoid treatment in the 2 weeks before the enrollment, did not affect the result. Intervention-related adverse events were not seen. CONCLUSIONS Intermittent tiotropium bromide treatment may be an effective alternative to current therapies for episodic wheezing. Before implementation of use, further research on safety and efficacy is indicated.

Background There is inconclusive evidence on the role of nebulized magnesium sulphate (MgSO4) in the management of acute asthma in paediatric population. Objectives Whether the use of nebulized salbutamol with or without MgSO4 in the management of acute asthma results in clinically significant improvement in lung function in Indian children? The primary outcome measure was to assess improvements in peak expiratory flow rate (PEFR), heart rate, respiratory rate and SpO2. Methods This was a single centre; prospective double-blind randomized control trial conducted in paediatric intensive care unit of a tertiary care centre. Ninety children of 6–14 years with acute exacerbations of bronchial asthma were enrolled to receive either inhaled magnesium sulphate (95 mg) with salbutamol (5 mg) or inhaled salbutamol (5 mg) alone. All patients got three nebulizations done during the first hour at 20 min intervals, two nebulizations during the second hour at 30 min intervals, hourly for the next 2 h and then at 24 and 48 h. Results Eighty-five patients were finally analysed as per protocol analysis. The trial showed that PEFR increased gradually in both groups over the study duration, but it was statistically not significant. Heart rate decreased significantly in both groups over the study duration. Respiratory rate decreased significantly between the groups at 24 and 48 h only. SpO2 improved too in both groups but was not significant statistically. Conclusion The addition of nebulized MgSO4 to salbutamol does not seem to result in improvement in lung function in the management of acute asthma in Indian children.

Treatment with beta-agonist tocolytics preceding external cephalic version (ECV) attempt increases success rates. Most studies have focused on intravenously and orally administered beta-agonists, while other administration routes including intramuscularly (IM) and subcutaneously (SC) are understudied. The aim of this study was to compare the efficacy of IM ritodrine to SC salbutamol given prior to ECV.A retrospective study of patients who underwent ECV between 1/2012 and 12/2019 at two medical centers. We compared patients undergoing ECV following IM ritodrine versus SC salbutamol. We matched the two groups by parity and placental location. Maternal, pregnancy, ECV procedure and neonatal characteristics were compared.Overall, 601 women were included in each group. Median maternal age and amniotic fluid index (AFI) were lower in the Ritodrine group (27 vs. 32 years, P0.001, 11 vs. 15 AFI cm, P0.001, respectively). The median gestational age at ECV was higher in the Ritodrine group (38Intramuscular ritodrine significantly improved the success rate of ECV compared to SC salbutamol, and both drugs were safe and acceptable before ECV.

Budesonide and salbutamol-loaded liposomes were prepared using an innovative one step supercritical CO