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Background: Patients with congenital long QT syndrome (LQTS) are prone to ventricular dysrhythmia but may be initially asymptomatic with a normal QTc interval on resting electrocardiogram (ECG). Albuterol is listed as a medication that poses a "special risk" to patients with congenital LQTS, but its effects have been rarely described. We present a case of previously unknown, asymptomatic congenital LQTS unmasked by albuterol in an adolescent with asthma., Case Report: A 12-year-old girl with a history of asthma presented to the emergency department (ED) with shortness of breath, wheezing, and tachycardia for 24 h, consistent with acute asthma exacerbation. She received two doses of her home albuterol inhaler 2 h prior to presentation. Initial ECG demonstrated a QTc of 619 ms. Her remaining history, clinical examination, and laboratory workup, including electrolytes, were unremarkable. She was observed with cardiac monitoring before being discharged from the ED in stable condition for next-day outpatient pediatric cardiology follow-up. Resting office ECGs revealed QTcs from 440-470 ms. Exercise stress test revealed QTc prolongation of 520 ms and 500 ms at minute-2 and minute-4 of recovery, respectively. Genetic testing revealed heterozygous pathogenic variants in KCNQ1, consistent with type 1 LQTS. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Albuterol may be a cause of marked QTc prolongation in ED patients with underlying congenital LQTS, which can be a diagnostic clue in previously unidentified patients. Extreme QTc prolongation also serves as an indication in the ED for Cardiology consultation, laboratory evaluation for electrolyte imbalances, and observation with cardiac monitoring., Competing Interests: Declaration of competing interest No conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Global Initiative for Asthma (GINA) recommends that short-acting β 2 -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., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors have disclosed no conflicts of interest.

The aim of asthma treatment is to reduce airway inflammation by avoiding environmental triggers and using daily anti-inflammatory medications. This study aimed to compare the effects of fluticasone propionate (FP) and budesonide (Bud) on the clinical symptoms and control of asthma in children with moderate to severe asthma. In this open-label study, children with moderate to severe asthma were randomly selected to receive either FP 250 mcg or Bud 400 mcg for 3 months. Asthma control test scores were measured in both groups monthly. The clinical symptoms, drug adherence, and rescue medication were also evaluated. A total of 50 patients with ages between 4 and 7 years old were included in the study (25 cases received Bud and 25 cases received FP). Asthma control test scores, daily and nocturnal symptoms, and cough rates were significantly improved in both groups. The average asthma control scores for the fluticasone group were 21.68±3.32 in the second month and 24.84±2.67 in the third month, whereas the budesonide group had scores of 18.52±3.32 and 22.48±4.12 during the same periods. These variances were statistically significant. Additionally, the requirement for salbutamol use was notably reduced in the fluticasone group compared to the budesonide group throughout all three months. The efficacy of fluticasone propionate in decreasing the need for rescue medication and enhancing asthma control test scores was markedly superior to that of budesonide.

Various drugs such as corticosteroids, salbutamol, and β2 agonist are available for the treatment of asthma an inflammatory disease and its symptoms, although the ingredient and the mode of action of these drugs are not clearly elucidated. Hence this research aimed at carrying out improved scientific research with respect to the use of natural product rosmarinic acid which poses minima, side effects. Herein, we first carried out extraction, isolation, and spectroscopic (FT-IR, 1 H-NMR and 13 C-NMR) investigation, followed by molecular modeling analysis on the naturally occurring rosmarinic acid extracted from Rosmarinus officinalis . A detailed comparison of the experimental and theoretical vibrational analysis has been carried out using five DFT functionals: BHANDH, HSEH1PBE, M06-2X, MPW3PBE and THCTHHYB with the basis set 6-311++G (d, p) to investigate into the structural, reactivity, and stability of the isolated compound. Frontier molecular orbital analysis and appropriate quantum descriptors were calculated. Results showed that the compound was more stable at M06-2X and more reactive at HSEH1PBE with an energy gap of 6.43441 eV and 3.8047 eV, respectively, which was later affirmed by the global quantum reactivity parameters. From natural bond orbital analysis, π* → π* is the major contributor to electron transition with the summation perturbation energy of 889.57 kcal/mol, while π → π* had the perturbation energy totaling of 145.3 kcal/mol. Geometry analysis shows BHANDH to have lower bond length values and lesser deviation from 120 ° in carbon-carbon angle. The potency of the title molecule as an asthma drug was tested via a molecular docking approach and the binding score of -8.2 kcal/mol was observed against -7.0 of salbutamol standard drug, suggesting romarinic acid as a potential natural organic treatment for asthma.Communicated by Ramaswamy H. Sarma.

Introduction: The standard therapy for bronchial asthma consists of combinations of acute (short-acting ß 2 -sympathomimetics) and, depending on the severity of disease, additional long-term treatment (including inhaled glucocorticoids, long-acting ß 2 -sympathomimetics, anticholinergics, anti-IL-4R antibodies). The antidepressant amitriptyline has been identified as a relevant down-regulator of immunological T H 2-phenotype in asthma, acting-at least partially-through inhibition of acid sphingomyelinase (ASM), an enzyme involved in sphingolipid metabolism. Here, we investigated the non-immunological role of amitriptyline on acute bronchoconstriction, a main feature of airway hyperresponsiveness in asthmatic disease., Methods: After stimulation of precision cut lung slices (PCLS) from mice (wildtype and ASM-knockout), rats, guinea pigs and human lungs with mediators of bronchoconstriction (endogenous and exogenous acetylcholine, methacholine, serotonin, endothelin, histamine, thromboxane-receptor agonist U46619 and leukotriene LTD4, airway area was monitored in the absence of or with rising concentrations of amitriptyline. Airway dilatation was also investigated in rat PCLS by prior contraction induced by methacholine. As bronchodilators for maximal relaxation, we used IBMX (PDE inhibitor) and salbutamol (ß 2 -adrenergic agonist) and compared these effects with the impact of amitriptyline treatment. Isolated perfused lungs (IPL) of wildtype mice were treated with amitriptyline, administered via the vascular system (perfusate) or intratracheally as an inhalation. To this end, amitriptyline was nebulized via pariboy in-vivo and mice were ventilated with the flexiVent setup immediately after inhalation of amitriptyline with monitoring of lung function., Results: Our results show amitriptyline to be a potential inhibitor of bronchoconstriction, induced by exogenous or endogenous (EFS) acetylcholine, serotonin and histamine, in PCLS from various species. The effects of endothelin, thromboxane and leukotrienes could not be blocked. In acute bronchoconstriction, amitriptyline seems to act ASM-independent, because ASM-deficiency (Smdp1 -/- ) did not change the effect of acetylcholine on airway contraction. Systemic as well as inhaled amitriptyline ameliorated the resistance of IPL after acetylcholine provocation. With the flexiVent setup, we demonstrated that the acetylcholine-induced rise in central and tissue resistance was much more marked in untreated animals than in amitriptyline-treated ones. Additionally, we provide clear evidence that amitriptyline dilatates pre-contracted airways as effectively as a combination of typical bronchodilators such as IBMX and salbutamol., Conclusion: Amitriptyline is a drug of high potential, which inhibits acute bronchoconstriction and induces bronchodilatation in pre-contracted airways. It could be one of the first therapeutic agents in asthmatic disease to have powerful effects on the T H 2-allergic phenotype and on acute airway hyperresponsiveness with bronchoconstriction, especially when inhaled., (© 2023. The Author(s).)

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., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Among many sterilization methods, radiosterilization is a preferred method in the pharmaceutical industry because of its advantages. However, the detection of radiosterilization of drugs is a growing concern for many government regulatory agencies around the world because of changes in the drug's structure because of exposure to radiation. Electron Paramagnetic Resonance (EPR) proved to be a very sensitive technique to discriminate between irradiated and nonirradiated drugs and detect radicals for days even to years. In this study, the focus is on the detection of radiosterilization of irradiated three asthma drugs (Airfix, Ventolin and Prednol) by using EPR spectroscopy. Regarding the commercial aspects of drugs, it was found that radicals can be detected at least 2 y after irradiation. Therefore, paramagnetic centers formed by the effect of radiation in the samples were determined and the stability of these centers was examined for 2 y by performing the fading study., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Several states in the United States (U.S.) have laws permitting stock inhalers, including short-acting beta-agonist inhalers, such as albuterol, and spacers to be prescribed to, dispensed to, and stocked in schools for use in students in respiratory distress, based on a protocol. This survey study assessed Arizona pharmacists' (1) levels of comfort for dispensing a short-acting beta-agonist inhaler to an individual child versus a stock inhaler to a school, and (2) awareness of the related Arizona state law. Researchers surveyed pharmacists licensed in Arizona who self-reported practicing in an outpatient pharmacy setting. Among 251 pharmacist participants, 62% practiced in a chain community pharmacy. About 80.8% felt comfortable filling a prescription for an albuterol inhaler in a pediatric patient case, whereas only 26.7% felt comfortable filling a prescription for albuterol inhalers to be used as stock inhalers for a given school. Among those who would not fill the stock inhaler prescription, only 5.5% reported awareness of the state law compared to 42.6% of those who would fill it (p < 0.0001). This survey identified a lack of pharmacist awareness of state laws pertaining to stock inhalers for schools., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Practical Relevance: Feline inflammatory airway diseases, including (but not limited to) asthma, chronic bronchitis and bronchiectasis, are common and incurable disorders. These diseases require lifelong therapy and may result in substantial morbidity and, in some cases, mortality. Goals of therapy include reduction or resolution of clinical signs and the underlying pathologic processes driving those clinical signs. Inhalational therapy has the advantage of topical delivery of drugs to target tissues at higher doses with fewer systemic effects than oral medications. There are multiple options for delivery devices, and proper selection and training on the use of these devices - including acclimation of the cat to the device - can maximize therapeutic efficacy., Aim: As inhalational therapy is uncommonly used by many veterinarians and owners, this review article provides a foundation on the selection and use of devices and inhalant medications for specific feline inflammatory airway diseases. Cats present a unique challenge with respect to the use of inhalers, and easy-to-follow steps on acclimating them to the devices are provided. The review also discusses the mechanics of inhalational therapy and helps clarify why certain medications, such as albuterol (salbutamol), fluticasone or budesonide, are chosen for certain diseases. The ultimate aim is that the practitioner should feel more comfortable managing common airway diseases in cats., Evidence Base: In compiling their review, the authors searched the veterinary literature for articles in English that discuss inhalational therapy in cats, and which focus primarily on inhaled glucocorticoids and bronchodilators. While most literature on inhalational therapy in cats is based on experimental feline asthma models, there are some studies demonstrating successful treatment in cats with naturally occurring inflammatory airway disease.

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., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

BACKGROUND: The aim of these clinical standards is to aid the diagnosis and management of asthma in low-resource settings in low- and middle-income countries (LMICs). METHODS: A panel of 52 experts in the field of asthma in LMICs participated in a two-stage Delphi process to establish and reach a consensus on the clinical standards. RESULTS: Eighteen clinical standards were defined: Standard 1, Every individual with symptoms and signs compatible with asthma should undergo a clinical assessment; Standard 2, In individuals (>6 years) with a clinical assessment supportive of a diagnosis of asthma, a hand-held spirometry measurement should be used to confirm variable expiratory airflow limitation by demonstrating an acute response to a bronchodilator; Standard 3, Pre- and post-bronchodilator spirometry should be performed in individuals (>6 years) to support diagnosis before treatment is commenced if there is diagnostic uncertainty; Standard 4, Individuals with an acute exacerbation of asthma and clinical signs of hypoxaemia or increased work of breathing should be given supplementary oxygen to maintain saturation at 94-98%; Standard 5, Inhaled short-acting beta-2 agonists (SABAs) should be used as an emergency reliever in individuals with asthma via an appropriate spacer device for metered-dose inhalers; Standard 6, Short-course oral corticosteroids should be administered in appropriate doses to individuals having moderate to severe acute asthma exacerbations (minimum 3-5 days); Standard 7, Individuals having a severe asthma exacerbation should receive emergency care, including oxygen therapy, systemic corticosteroids, inhaled bronchodilators (e.g., salbutamol with or without ipratropium bromide) and a single dose of intravenous magnesium sulphate should be considered; Standard 8, All individuals with asthma should receive education about asthma and a personalised action plan; Standard 9, Inhaled medications (excluding dry-powder devices) should be administered via an appropriate spacer device in both adults and children. Children aged 0-3 years will require the spacer to be coupled to a face mask; Standard 10, Children aged <5 years with asthma should receive a SABA as-needed at step 1 and an inhaled corticosteroid (ICS) to cover periods of wheezing due to respiratory viral infections, and SABA as-needed and daily ICS from step 2 upwards; Standard 11, Children aged 6-11 years with asthma should receive an ICS taken whenever an inhaled SABA is used; Standard 12, All adolescents aged 12-18 years and adults with asthma should receive a combination inhaler (ICS and rapid onset of action long-acting beta-agonist [LABA] such as budesonide-formoterol), where available, to be used either as-needed (for mild asthma) or as both maintenance and reliever therapy, for moderate to severe asthma; Standard 13, Inhaled SABA alone for the management of patients aged >12 years is not recommended as it is associated with increased risk of morbidity and mortality. It should only be used where there is no access to ICS.The following standards (14-18) are for settings where there is no access to inhaled medicines. Standard 14, Patients without access to corticosteroids should be provided with a single short course of emergency oral prednisolone; Standard 15, Oral SABA for symptomatic relief should be used only if no inhaled SABA is available. Adjust to the individual's lowest beneficial dose to minimise adverse effects; Standard 16, Oral leukotriene receptor antagonists (LTRA) can be used as a preventive medication and is preferable to the use of long-term oral systemic corticosteroids; Standard 17, In exceptional circumstances, when there is a high risk of mortality from exacerbations, low-dose oral prednisolone daily or on alternate days may be considered on a case-by-case basis; Standard 18. Oral theophylline should be restricted for use in situations where it is the only bronchodilator treatment option available. CONCLUSION: These first consensus-based clinical standards for asthma management in LMICs are intended to help clinicians provide the most effective care for people in resource-limited settings.

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 FEV 1 area under the curve from 0 to 6 h (FEV 1 AUC 0-6h ) over 12 weeks (assessing albuterol effect) and trough FEV 1 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 FEV 1 AUC 0-6h 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 FEV 1 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., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Importance: High-deductible health plans with health savings accounts (HDHP-HSAs) incentivize patients to use less health care, including necessary care. Preventive drug lists (PDLs) exempt high-value medications from the deductible, reducing out-of-pocket cost sharing; the associations of PDLs with health outcomes among patients with asthma is unknown., Objective: To evaluate the associations of a PDL for asthma medications on utilization, adverse outcomes, and patient spending for HDHP-HSA enrollees with asthma., Design, Setting, and Participants: This case-control study used matched groups of patients with asthma before and after an insurance design change using a national commercial health insurance claims data set from 2004-2017. Participants included patients aged 4 to 64 years enrolled for 1 year in an HDHP-HSA without a PDL in which asthma medications were subject to the deductible who then transitioned to an HDHP-HSA with a PDL that included asthma medications; these patients were compared with a matched weighted sample of patients with 2 years of continuous enrollment in an HDHP-HSA without a PDL. Models controlled for patient demographics and asthma severity and were stratified by neighborhood income. Analyses were conducted from October 2020 to June 2023., Exposures: Employer-mandated addition of a PDL that included asthma medications to an existing HDHP-HSA., Main Outcomes and Measures: Outcomes of interest were utilization of asthma medications on the PDL (controllers and albuterol), asthma exacerbations (oral steroid bursts and asthma-related emergency department use), and out-of-pocket spending (all and asthma-specific)., Results: A total of 12 174 participants (mean [SD] age, 36.9 [16.9] years; 6848 [56.25%] female) were included in analyses. Compared with no PDL, PDLs were associated with increased rates of 30-day fills per enrollee for any controller medication (change, 0.10 [95% CI, 0.03 to 0.17] fills per enrollee; 12.9% increase) and for combination inhaled corticosteroid long-acting β2-agonist (ICS-LABA) medications (change, 0.06 [95% CI, 0.01 to 0.10] fills per enrollee; 25.4% increase), and increased proportion of days covered with ICS-LABA (6.0% [0.7% to 11.3%] of days; 15.6% increase). Gaining a PDL was associated with decreased out-of-pocket spending on asthma care (change, -$34 [95% CI, -$47 to -$21] per enrollee; 28.4% difference), but there was no significant change in asthma exacerbations and no difference in results by income., Conclusions and Relevance: In this case-control study, reducing cost-sharing for asthma medications through a PDL was associated with increased adherence to controller medications, notably ICS-LABA medications used by patients with more severe asthma, but was not associated with improved clinical outcomes. These findings suggest that PDLs are a potential strategy to improve access and affordability of asthma care for patients in HDHP-HSAs.

Objective: The objective of this research was to examine how different measurements of poverty (household-level and neighborhood-level) were associated with asthma care utilisation outcomes in a community health centre setting among Latino, non-Latino black and non-Latino white children., Design, Setting and Participants: We used 2012-2017 electronic health record data of an open cohort of children aged <18 years with asthma from the OCHIN, Inc. network. Independent variables included household-level and neighborhood-level poverty using income as a percent of federal poverty level (FPL). Covariate-adjusted generalised estimating equations logistic and negative binomial regression were used to model three outcomes: (1) ≥2 asthma visits/year, (2) albuterol prescription orders and (3) prescription of inhaled corticosteroids over the total study period., Results: The full sample (n=30 196) was 46% Latino, 26% non-Latino black, 31% aged 6-10 years at first clinic visit. Most patients had household FPL <100% (78%), yet more than half lived in a neighbourhood with >200% FPL (55%). Overall, neighbourhood poverty (<100% FPL) was associated with more asthma visits (covariate-adjusted OR 1.26, 95% CI 1.12 to 1.41), and living in a low-income neighbourhood (≥100% to <200% FPL) was associated with more albuterol prescriptions (covariate-adjusted rate ratio 1.07, 95% CI 1.02 to 1.13). When stratified by race/ethnicity, we saw differences in both directions in associations of household/neighbourhood income and care outcomes between groups., Conclusions: This study enhances understanding of measurements of race/ethnicity differences in asthma care utilisation by income, revealing different associations of living in low-income neighbourhoods and households for Latino, non-Latino white and non-Latino black children with asthma. This implies that markers of family and community poverty may both need to be considered when evaluating the association between economic status and healthcare utilisation. Tools to measure both kinds of poverty (family and community) may already exist within clinics, and can both be used to better tailor asthma care and reduce disparities in primary care safety net settings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Evidence for the use of dexamethasone for pediatric critical asthma is limited. We sought to compare the clinical efficacy and safety of dexamethasone versus methylprednisolone among children hospitalized in the pediatric intensive care unit (PICU) for critical asthma., Methods: A prospective, single center, open-label, two-arm, parallel-group, nonrandomized trial among children ages 5-17 years hospitalized within the PICU from April 2019 to December 2021 for critical asthma consented to receive methylprednisolone (standard care) or dexamethasone (intervention) at a 2:1 allocation ratio, respectively. The intervention arm received intravenous dexamethasone 0.25 mg/kg/dose (max: 15 mg/dose) every 6 h for 48 h and the standard care arm intravenous methylprednisolone 1 mg/kg/dose every 6 h (max dose: 60 mg/dose) for 5 days. Study endpoints were clinical efficacy (i.e., length of stay [LOS], continuous albuterol duration, and a composite of adjunctive asthma interventions) and safety (i.e., corticosteroid-related adverse events)., Results: Ninety-two participants were analyzed of whom 31 were allocated to the intervention arm and 61 the standard care arm. No differences in demographics, clinical characteristics, or acute/chronic asthma severity indices were observed. Regarding efficacy and safety endpoints, no differences in hospital LOS, continuous albuterol duration, adjunctive asthma intervention rates, or corticosteroid-related adverse events were noted. Compared to the intervention arm, participants in the standard care arm more frequently were prescribed corticosteroids at discharge (72% vs. 13%, p < 0.001)., Conclusions: Among children hospitalized for critical asthma, dexamethasone appears safe and warrants further investigation to fully assess clinical efficacy and potential advantages over commonly applied agents such as methylprednisolone., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: Albuterol is the drug most widely used as asthma treatment among African Americans despite having a lower bronchodilator drug response (BDR) than other populations. Although BDR is affected by gene and environmental factors, the influence of DNA methylation is unknown., Objective: This study aimed to identify epigenetic markers in whole blood associated with BDR, study their functional consequences by multi-omic integration, and assess their clinical applicability in admixed populations with a high asthma burden., Methods: We studied 414 children and young adults (8-21 years old) with asthma in a discovery and replication design. We performed an epigenome-wide association study on 221 African Americans and replicated the results on 193 Latinos. Functional consequences were assessed by integrating epigenomics with genomics, transcriptomics, and environmental exposure data. Machine learning was used to develop a panel of epigenetic markers to classify treatment response., Results: We identified 5 differentially methylated regions and 2 CpGs genome-wide significantly associated with BDR in African Americans located in FGL2 (cg08241295, P = 6.8 × 10 -9 ) and DNASE2 (cg15341340, P = 7.8 × 10 -8 ), which were regulated by genetic variation and/or associated with gene expression of nearby genes (false discovery rate < 0.05). The CpG cg15341340 was replicated in Latinos (P = 3.5 × 10 -3 ). Moreover, a panel of 70 CpGs showed good classification for those with response and nonresponse to albuterol therapy in African American and Latino children (area under the receiver operating characteristic curve for training, 0.99; for validation, 0.70-0.71). The DNA methylation model showed similar discrimination as clinical predictors (P > .05)., Conclusions: We report novel associations of epigenetic markers with BDR in pediatric asthma and demonstrate for the first time the applicability of pharmacoepigenetics in precision medicine of respiratory diseases., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The effectiveness of a fix-dose salmeterol/fluticasone combination therapy in asthma was previously shown for the original product. The study aim was to evaluate the clinical effectiveness and safety of a second entry DPI - dry powder inhaler (Salflumix Easyhaler) in patients with asthma in everyday clinical practice., Patients and Methods: This multicenter Investigator-Initiated Study that enrolled 2,037 adult outpatients with asthma treated with Salflumix Easyhaler, was conducted by 220 pulmonologists across Poland. Asthma control was assessed during 3 visits with 6 ± 2 weeks intervals based on the Asthma Control Test (ACT). In addition, patient Satisfaction with Asthma Treatment Questionnaire (SATQ) and adherence and adverse events (AEs) were monitored., Results: During the observation (86 ± 30 days) the percentage of patients with controlled asthma (ACT 20-25 pts) increased from 35.5% at the first visit to 86.5% at the third visit ( p  < 0.001). In the subgroup analysis, there were more patients not obtaining asthma control among patients that switched from the treatment with other devices than in naive ones. Global SATQ scores increased from 5.8 ± 0.7 to 6.2 ± 0.6 during the observation. Patients' satisfaction with the use of the Salflumix Easyhaler was high. Adherence exceeded 95%. Eight AEs were reported., Conclusions: Salflumix Easyhaler is highly effective and well-tolerated by naïve patients with asthma and those switching from another device. In general, patients show good compliance with medical product and are satisfied with the use of this new device, and not reporting difficulties and errors related to its' use. Their physicians' overall perception of Salflumix Easyhaler use is very positive.

Objective: To compare hospital costs and resource utilization for pediatric asthma admissions based on the hospitals' availability of continuous albuterol aerosolization administration (CAA) in non-intensive care unit (ICU) settings., Methods: We conducted a retrospective cohort study of children ages 2-17 years admitted in 2019 with a principal diagnosis of asthma using the Pediatric Health Information System. Hospitals and hospitalizations were categorized based on location of CAA administration, ICU-only versus general inpatient floors. Hospitals preforming CAA in an intermediate care unit were excluded. We calculated total cost, standardized unit costs and rates of interventions. Groups were compared using Chi-Square, t-test and Wilcoxon rank-sum test as indicated. A log linear mixed model was created to evaluate potential confounders., Results: Twenty-one hospitals (7084 hospitalizations) allowed CAA on the floor.Twenty-four hospitals (6100 hospitalizations) allowed CAA in the ICU-only. Median total cost was $4639 (Interquartile Range (IQR) $3060-$7512) for the floor group and $5478 (IQR $3444-$8539) for the ICU-only group ( p  < 0.001) (mean cost difference of $775 per patient). Hospitalization costs were $4,726,829 (95% CI $3,459,920-$5,993,860) greater for the children treated at hospitals restricting CAA to the ICU. We observed higher standardized laboratory, imaging, clinical and other unit costs, along with higher use of interventions in the ICU-only group. After adjustment, we found that ICU stay and hospital LOS were the main drivers of cost difference between the groups., Conclusions: There was cost savings and decreased resource utilization for hospitals that performed CAA on the floor. Further studies exploring variations in asthma management are warranted.

Objective: Medication maintenance is critical in the management of asthma. We investigated the differences in electronic health record (EHR) documentation of medication refills for Spanish- and English-speaking Latino children and non-Hispanic white children by examining rates of albuterol rescue inhaler refills from 2005 to 2017, and and inhaled corticosteroid refills from 2015 to 2017 in a multi-state network of community health centers (CHCs)., Methods: We used data from the ADVANCE network of CHCs. Our sample consisted of children aged 3-17, with a diagnosis of asthma and either albuterol or inhaled corticosteroid prescriptions ( n  = 39,162; n  = 4,738 children, respectively). Negative binomial regression was used to calculate rates of refills per prescription adjusted for relevant patient-level covariates. Analyses stratified by asthma severity were also conducted., Results: English-speaking Latino children had lower rates of albuterol refills compared with non-Hispanic white children (rate ratio [RR] = 0.88, 95% confidence interval [CI]: 0.80-0.98), a trend that persisted among children with moderate/severe persistent asthma severity (RR = 0.85, 95% CI: 0.76-0.95). Spanish-speaking Latino and non-Hispanic white children had similar albuterol refills. Inhaled corticosteroid refill rates were comparable between all groups., Conclusions: In a multi-state network, these findings suggest that CHCs deliver equitable asthma care related to prescription refills between their Latino and white patients, but there is still opportunity for providers to ensure that their English-speaking Latino patients have access to necessary emergency asthma medication.

Background: Standardized acute asthma management with score-based, respiratory therapist (RT)-driven pathways and protocols improves outcomes including decreased length of stay (LOS) and time on continuous albuterol therapy. Limited data are available for the safety of continuous albuterol used outside of pediatric ICU (PICU). We use a modified pediatric asthma score (PAS) for the asthma pathway at our institution. The safety and effectiveness of using PAS to initiate/stop continuous albuterol as part of a score-based, RT-driven asthma pathway were evaluated., Methods: A retrospective review of children ≥ 2 y admitted for asthma exacerbation to the PICU and step-down unit who received continuous albuterol as part of the asthma pathway during 2017-2019 was completed. Demographic and clinical data were extracted including PAS, dose and duration of continuous albuterol, LOS, and complications. Outcomes of subjects admitted to the PICU and step-down unit were compared., Results: Results are expressed as median (interquartile range). The study included 412 children (61% male, 59.9% Black, 92.7% non-Hispanic, 44.9% moderate persistent asthma) with age and weight of 6.4 (4.0-10.0) y and 24.8 (17.3-39.5) kg, respectively. Most children were admitted to step-down unit (71.1%). Initial albuterol dose, duration, and LOS were 15 (10-20) mg/h, 9.1 (5.7-16.0) h, and 1.4 (0.9-2.3) d, respectively. Respiratory support was required by 29% of subjects. Need to restart therapy (2.9%), transfer to PICU (1.7%), and intubation (0.5%) were infrequent. No pneumothoraces or deaths were reported. Emergency department visits (3.9%) or readmissions (0.7%) within 30 d of discharge were low. Subjects admitted to the PICU were sicker and required more therapies and respiratory support than those admitted to the step-down unit., Conclusions: Use of an RT-driven, score-based pathway for initiation and discontinuation of continuous albuterol for treatment of pediatric asthma exacerbation was safe and effective in the PICU and step-down unit., Competing Interests: Dr Berlinski discloses relationships with Cystic Fibrosis Foundation, Mylan, National Institutes of Health, Therapeutic Development Network, Trudell Medical International, Vertex, and the International Pharmaceutical Aerosol Consortium on Regulation and Science. Ms Willis is a section editor for Respiratory Care. The remaining authors have disclosed no conflicts of interest., (Copyright © 2022 by Daedalus Enterprises.)

Background: 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., Objective: This study assesses the clinical impact of a pediatric emergency medicine curriculum on management of pediatric asthma emergencies at KHMHA in Belize City, Belize., Methods: 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., Results: 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 (P < 0.05). 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., Conclusions: 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., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

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., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Chengtian Lv et al.)

The optimal dose regimen for intravenous (IV) treatment in children with severe acute asthma (SAA) is still a matter of debate. We assessed the efficacy of adding a salbutamol loading dose to continuous infusion with salbutamol in children admitted to a pediatric intensive care unit (PICU) with SAA. This multicentre, placebo-controlled randomized trial in the PICUs of four tertiary care children's hospitals included children (2-18 years) with SAA admitted between 2017 and 2019. Children were randomized to receive either a loading dose IV salbutamol (15 mcg/kg, max. 750 mcg) or normal saline while on continuous salbutamol infusion. The primary outcome was the asthma score (Qureshi) 1 h after the intervention. Analysis of covariance models was used to evaluate sensitivity to change in asthma scores. Serum concentrations of salbutamol were obtained. Fifty-eight children were included (29 in the intervention group). Median baseline asthma score was 12 (IQR 10-13) in the intervention group and 11 (9-12) in the control group (p = 0.032). The asthma score 1 h after the intervention did not differ significantly between the groups (p = 0.508, β-coefficient = 0.283). The median increase in salbutamol plasma levels 10 min after the intervention was 13 μg/L (IQR 5-24) in the intervention group and 4 μg/L (IQR 0-7) in the control group (p = 0.001). Side effects were comparable between both groups., Conclusion: We found no clinical benefit of adding a loading dose IV salbutamol to continuous infusion of salbutamol, in children admitted to the PICU with SAA. Clinically significant side effects from the loading dose were not encountered., What Is Known: • Pediatric asthma guidelines struggle with an evidence-based approach for the treatment of SAA beyond the initial steps of oxygen suppletion, repetitive administration of inhaled β2-agonists, and systemic steroids. • During an SAA episode, effective delivery of inhaled drugs is unpredictable due to severe airway obstruction., What Is New: • This study found no beneficial effect of an additional loading dose IV salbutamol in children admitted to the PICU. • This study found no clinically significant side effects from the loading dose., (© 2022. The Author(s).)

Background: 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)., Methods: 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., Results: 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%)., Conclusion: In addition to spirometry, ΔAx (%), an IOS parameter, may serve as a novel indicator to evaluate BDR in UAPNDS., Competing Interests: Conflicts of interest: Dr. Diahn-Warng Perng, an editorial board member at Journal of the Chinese Medical Association, had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

The propellants in metered-dose inhalers (MDIs) are powerful greenhouse gases, which account for approximately 13% of the NHS's carbon footprint related to the delivery of care. Most MDI use is in salbutamol relievers in patients with poorly controlled disease. The UK lags behind Europe in this regard, with greater reliance on salbutamol MDI and correspondingly greater greenhouse gas emissions, roughly treble that of our European neighbours. There has been a broad switch towards MDIs in asthma treatment in the UK over the last 20 years to reduce financial costs, such that the treatment for two-thirds of asthma patients in the UK is dominated by salbutamol MDI. Strategies that replace overuse of reliever MDIs with regimes emphasising inhaled corticosteroids have the potential to improve asthma control alongside significant reductions in greenhouse gas emissions. Real-world evidence shows that once-daily long-acting combination dry-powder inhalers (DPIs) can improve compliance and asthma control, and reduce the carbon footprint of care. Similarly, maintenance and reliever therapy (MART), which uses combination reliever and inhaled steroids in one device (usually a DPI), can simplify therapy, improve asthma control and reduce greenhouse gas emissions. Both treatment strategies are popular with patients, most of whom would be willing to change treatment to reduce their carbon footprint. By focussing on patients who are currently using high amounts of salbutamol MDI and prioritising inhaled steroids via DPIs, there are golden opportunities to make asthma care in the UK more effective, safer and greener., (© 2021 British Pharmacological Society.)

Introduction: Noninvasive ventilation (NIV) is sometimes used in refractory pediatric status asthmaticus for its potential benefits of stenting airways and dispersing albuterol. However, its effectiveness in pediatric asthma remains unproven. The usage pattern, outcomes, and safety of NIV in pediatric status asthmaticus are described., Methods: Patients 1 to 21 years of age admitted to a tertiary hospital's pediatric intensive care unit (PICU) with status asthmaticus between January 2016 and December 2018 were eligible. Children with tracheostomies and baseline NIV were excluded. Medical history, vital signs, imaging, therapy, type of NIV administered and adverse events were extracted from the electronic medical record., Results: 101 unique admissions were identified. The mean age was 7 years, 63% had previously diagnosed asthma and 27% had prior PICU admissions. 54% received NIV in the form of bilevel positive airway pressure (BPAP) or continuous positive airway pressure (CPAP) with 20 (37%) commencing in the emergency department (ED). Oxygen saturation at presentation was significantly lower in the NIV vs the non NIV group (P < 0.05). Rhinovirus/enterovirus was identified in 82% of the cohort. No pneumothoraces, pneumomediastinum, or aspiration pneumonias were documented on available chest radiographs ( n  = 83)., Discussion: NIV was common in pediatric status asthmaticus and often started in the ED. No major adverse events were observed. Prospective, randomized control trials are needed to determine if NIV affects duration of continuous albuterol or PICU length of stay.

Aim: In the current study, efforts are being made to formulate transdermal salbutamol-cubosomal gel to manage paediatric asthma., Methods: Salbutamol-loaded cubosomal gels were prepared by melt emulsification and sonication. The cubosomal gels were characterised by morphology, particle size, zeta potential, entrapment efficacy, assay, viscosity, and texture profiles. Ex vivo permeation and pharmacokinetic studies were performed using rats., Results: The mean cubosomal particle size (208-361 ± 12.5-32.5 nm), PDI (0.06-0.11 ± 0.01-0.02), viscosity (8527-9019 cp), and entrapment efficacy (76.3-91.0% w/w) increase with the level of monoolein. The ex vivo permeation study showed a biphasic release pattern, with salbutamol cleared from control gel within 8 h, while cubosomal gels showed sustained release up to 72 h. The pharmacokinetic profiles in the rat model showed 8.62-fold higher bioavailability with cubosomal gel., Conclusion: The study demonstrated the potential of cubosomal nanoparticle-laden gel to sustain the release of salbutamol to treat paediatric asthma.

Background: Children with asthma should have immediate access to rescue medication. Yet, <15% of children have access to this life-saving drug while at school., Methods: A search was conducted in the all states database of Westlaw to identify which the US states, territories, and the District of Columbia have a law for K-12 schools. Terms searched included (inhaler or asthma/s medic!) and school and (prescription or order) from conception to December 2020. Demographic data from states with and without a policy were compared. All policies were examined for the following components: (1) type of law (statute or regulation); (2) type of school (charter, private/parochial or public); (3) training requirements; (4) devices; (5) prescriptive authority/safe harbor; (6) medication requirements; and (7) mandated documentation, reporting and funding., Results: Our systematic search revealed 15 locations with existing laws. States with a law had a higher percentage of children under 17-years than states without a law (p = .02). Common components described were the applicability to various types of schools, training requirements for those empowered to administer, and civil liability protections for trained school personnel., Conclusions: Existing stock inhaler laws differ vastly across the United States that may impact access to stock albuterol for children at their schools., (© 2022 American School Health Association.)

Objective: Little is known about the implementation challenges health providers might face with the use of digital health in outpatient asthma care. To qualitatively explore the experience of health providers with electronic medication monitoring (EMM) using an implementation science framework., Methods: Using the Consolidated Framework of Implementation Research (CFIR), we conducted interviews ( n  = 10) exploring health providers' experience with EMM with asthma patients from 5 primary care or specialty clinics. The EMM tracked albuterol and inhaled corticosteroid (ICS) use, and health providers called parents whenever ICS adherence waned, or albuterol use increased. Interviews were audio-recorded, transcribed, and deductively analyzed using directed content analysis., Results: Health providers reported the intervention's primary advantage, compared with current asthma care, was the ability to monitor medication use at-home. Most felt the intervention improved care delivery. Nurses and medical assistants described a process of phone calls and checking alerts, that had varying levels of administrative burden and complexity. Health providers felt that sustained implementation of the intervention model would require additional employees to handle the administrative and clinical workload. Half of the interviewed providers were unsure if patient needs were met by the intervention, while some cited technology syncing issues, others liked the enhanced interactions for asthma education., Conclusion: Health providers reported positive experiences supporting parents and children with asthma using EMM but also highlighted intervention components that needed improvement or refinement to yield successful implementation in outpatient pediatric clinics. Recommendations for enhancing the intervention for a scaled-up implementation were discussed.

Background: PT027 is a fixed-dose combination of albuterol (salbutamol) and budesonide in a single pressurized metered-dose inhaler., Objective: To evaluate the efficacy and safety of albuterol/budesonide compared with placebo in patients with asthma and exercise-induced bronchoconstriction (EIB)., Methods: In this randomized, double-blind, 2-period, single-dose crossover study, adolescents and adults with asthma and EIB (defined by ≥20% decrease from pre-exercise challenge forced expiratory volume in 1 second [FEV 1 ]) were randomized to albuterol/budesonide (180/160 µg) followed by placebo (n = 29) or the reverse sequence (n = 31). Subjects were stratified by background therapy (as-needed short-acting β 2 -agonist alone or low-to-medium dose inhaled corticosteroid plus as-needed short-acting β 2 -agonist). FEV 1 was measured 5 minutes pre-dose, 30 minutes postdose (5 minutes pre-exercise challenge [baseline]), and 5, 10, 15, 30, and 60 minutes postexercise. The primary end point was maximum percentage fall from baseline in FEV 1 up to 60 minutes postexercise challenge., Results: Least squares mean maximum percentage fall in FEV 1 up to 60 minutes postexercise challenge was 5.45% with albuterol/budesonide vs 18.97% with placebo (difference, -13.51% [95% confidence interval, -16.94% to -10.09%]; P < .001). More subjects were fully protected (maximum percentage fall in FEV 1 post-exercise challenge < 10%) with albuterol/budesonide than with placebo (78.3% vs 28.3%; P < .001). The treatment effect was consistent irrespective of background inhaled corticosteroid therapy, and albuterol/budesonide was well tolerated., Conclusion: In adolescents and adults with asthma and EIB, a single dose of albuterol/budesonide 180/160 µg taken approximately 30 minutes before exercise was significantly more effective than placebo in preventing EIB., Trial Registration: ClinicalTrials.gov Identifier: NCT04234464., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: For hospitalized patients with chronic obstructive pulmonary disease (COPD), albuterol and levalbuterol can both be used as relievers to alleviate bronchoconstriction. This study aimed to evaluate levalbuterol and albuterol's cost-utility and budget impact in hospitalized patients with COPD., Interventions: A cost-utility analysis was used to evaluate the impact on the costs of nebulized levalbuterol verse albuterol in hospitalized patients with COPD. The decision tree model was employed to estimate the incremental cost per quality-adjusted life year in the admission setting. A budget impact model was used to examine the impact of budget on levalbuterol's entry into the Chinese market from the healthcare system's perspective. One-way sensitivity and probabilistic sensitivity analyses were performed to test the uncertainty of the parameters., Results: The cost-utility results showed that levalbuterol saved ¥495.7 ($105.1) per hospitalization, while the budget impact analysis revealed a potential saving of ¥22.3 ($6.8) million in 3 years. The sensitivity analysis indicated that the results were robust to the changes in input parameter values., Conclusion: Levalbuterol is a cost-saving option for treating hospitalized patients with COPD in China.

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.

Introduction: Asthma is distinguished by bronchial obstruction reversible by bronchodilators. The first-line treatment for asthmatic exacerbations is the use of inhaled beta-agonists, by pressurized metered-dose inhalers or nebulized with normal saline solution (NSS). There are no reports of nebulized beta agonists' efficacy in asthmatic children when administered with hypertonic saline solution (HSS)., Objective: To evaluate bronchodilator responses (BDR) to albuterol nebulized with 3%-HSS in asthmatic children, compared to albuterol nebulized with NSS., Population and Methods: In a prospective, experimental, double-blind, randomized clinical study, children with a confirmed diagnosis of asthma with mild or moderate bronchial obstruction (FEV 1 40%-79% of predicted) were randomized to receive a nebulization with 2.5 mg of albuterol diluted in 3 cc of 3%-HSS or NSS (0.9%), by means of a jet nebulizer. After 30 min, the BDR was assessed., Results: Fifty patients (mean age 12.0 ± 3 years, 29 males) were enrolled; 25 were randomized to the 3%-HSS group (FEV 1 65.2% ± 10) and 25 to the NSS group (FEV 1 69.1% ± 7.1). The BDR of FEV 1 was 41.2% (SD: ±20.1; 95% confidence interval [CI]: 35.1-50.4) and 17.3% (SD: ±19.4; 95% CI: 9.7-24.9) (p < .0001) and of maximum mid-expiratory flow was 130% (SD: ±90.8; 95% CI: 94.6-166) and 69.8% (SD: ±72.5; 95% CI: 41.4-98.2) (p < .01), for the 3%-HSS and NSS groups, respectively., Conclusion: Albuterol produces a greater BDR when nebulized with 3%-HSS compared to NSS in asthmatic children with mild or moderate bronchial obstruction., (© 2021 Wiley Periodicals LLC.)

Objectives: Little is known about emergency medical services' (EMS') management of pediatric asthma. This study's objective was to describe the demographic, clinical, and geographic characteristics of current EMS' management of pediatric asthma in the state with the fourth-largest pediatric population., Methods: This was a retrospective observational study of EMS patients ages 2 to 18 years with an asthma exacerbation from 2011 to 2016. Patients from Florida's EMS Tracking and Reporting System were included if their EMS chief complaint indicated respiratory distress, if they received at least 1 albuterol treatment, and if they were transported to a hospital., Results: A total of 11,226 patients met the inclusion criteria. The median age was 9 years, and 49% were African-American. Geospatial analysis revealed 4 rural counties with disproportionate numbers of African-American patients. In addition to albuterol, 37% of patients received ipratropium bromide and 9% received systemic corticosteroids. Adjusted logistic regression revealed that the strongest predictors of receiving systemic corticosteroids from EMS were intravenous access (odds ratio, 33.4; 95% confidence interval, 24.4-45.6) and intravenous magnesium sulfate administration (odds ratio, 5.0; 95% confidence interval, 3.4-7.3), indicating a more severe presentation., Conclusions: This statewide study demonstrated low rates of EMS administration of ipratropium bromide and systemic corticosteroids, both evidence-based treatments for asthma exacerbations. Targeted EMS education should attempt to increase utilization of both those medications. In addition, the feasibility and efficacy of EMS administration of oral systemic corticosteroids for children should be explored., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

In 1995, the first Guideline on Diagnosis and Treatment for Childhood Asthma was published in Archivos Argentinos de Pediatría. Updates were made in 2007 and 2016. After 5 years, the new contents are presented. The most relevant modifications, although not the only ones, are observed in therapeutic strategies. In this version, treatment is stratified into "levels" (1 to 5). The current paradigm of change in chronic asthma treatment consists in eradicating the prescription of bronchodilators (salbutamol) on demand. Besides that, the option of intermittent treatment with inhaled corticosteroids plus long-acting bronchodilators (LABA) appears for milder forms (levels 1 and 2) in children > 12 years old. There is still not enough evidence to support these options in<12 years old maintaining the previous recommendations in this group. For more details we suggest reading the full document., Competing Interests: None, (Sociedad Argentina de Pediatría.)

Background: A total of 15 states allow schools to manage respiratory emergencies among multiple students by using a single albuterol inhaler (stock inhaler) paired with a disposable holding chamber., Objective: Our aim was to evaluate implementation barriers and facilitators, as well as satisfaction with a stock inhaler program across K through12 schools in Pima County, Arizona., Methods: All public, charter, private, and parochial schools were offered supplies, web-based training, and technical assistance at no cost. The RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) framework was used to evaluate program implementation. School documentation logs were reviewed, school health personnel were surveyed, and a convenience sample of health personnel were interviewed. Chi-square tests evaluated categoric outcomes and Poisson hurdle regression examined stock inhaler use by school organization type, grade levels served, and type of school health personnel employed., Results: In all, 229 schools (68%) participated, reaching 82% of students in the county. A total of 152 schools (66%) used a stock inhaler, accounting for 1038 events. The mean number of puffs administered was 2.7 (SD = 1.2) per event, and most events (79%) involved students with asthma. Although most events (83.9%) resulted in the student returning to class, 15.6% resulted in students being sent home. Only 6 events resulted in 911 calls, and 5 of these led to an ambulance transport. School health personnel reported high levels of satisfaction, and all schools renewed participation for a second year. Program costs were $156 per school., Conclusion: With technical assistance, stock inhaler programs can be feasibly implemented by schools in a wide range of settings, thereby increasing their capacity to safely manage respiratory emergencies., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: High-flow nasal cannula (HFNC) has been used in the treatment of pediatric asthma, although high-quality data comparing HFNC to aerosol mask nebulizer are lacking. We hypothesized that HFNC would perform similarly to the aerosol mask for meaningful clinical outcomes in children with critical asthma., Methods: We retrospectively reviewed the medical records of children with critical asthma (age 2-17 y) with a modified pulmonary index score (MPIS) ≥ 8 admitted to our pediatric ICU as part of a quality improvement project. Patients were managed with our MPIS-based, respiratory therapist-driven protocol. Subjects were divided into 2 cohorts by initial respiratory support: HFNC or aerosol mask. Data included demographics, initial respiratory support, and MPIS over time. Primary outcome was hospital length of stay (LOS). Secondary outcome was difference in MPIS over time., Results: We included 171 subjects, with 104 in the HFNC group and 67 in the aerosol mask group. Median (interquartile range [IQR]) age was lower in the HFNC group (5 [IQR 4-9] vs 7 [IQR 5-10] y, P = .006)], while other demographic characteristics were similar. Initial MPIS was similar between HFNC and aerosol mask groups (11 [IQR 9-12] vs 10 [IQR 9-12], P = .15). There were no significant differences for hospital LOS (2.9 [IQR 2.1-3.9] vs 3.0 [IQR 2.3-4.4] d, P = .47), pediatric ICU LOS (1.9 [IQR 1.4-2.8] vs 1.8 [IQR 1.5-3.0] d, P = .92), or time to MPIS < 6 (1.0 [IQR 0.6-1.6] vs 1.3 [IQR 0.8-1.9) d, P = .09) between the HFNC and aerosol mask groups, respectively. Median time on continuous albuterol was shorter in the HFNC group compared to the aerosol mask group (1.0 [IQR 0.7-1.8] vs 1.5 [IQR 0.9-2.3] d, P = .048). Of note, 16 (24%) subjects in the aerosol mask group were eventually treated with HFNC. Use of a helium-oxygen mixture and noninvasive ventilation was similar between groups., Conclusions: HFNC performed similarly to aerosol mask in pediatric patients with critical asthma., Competing Interests: Dr Rotta has disclosed relationships with Vapotherm, Breas US, and Elsevier. Mr Miller discloses a relationship with Ventec Life Systems and serves as Section Editor for Respiratory Care. The other authors have disclosed no conflicts of interest., (Copyright © 2021 by Daedalus Enterprises.)

Objective: Social deprivation is associated with worse asthma outcomes. The Social Deprivation Index is a composite measure of social determinants of health used to identify neighbourhood-level disadvantage in healthcare. Our objective was to determine if higher neighbourhood-level social deprivation is associated with documented asthma care quality measures among children treated at community health centres (CHCs)., Methods Setting, Participants, Outcome Measures: We used data from CHCs in 15 states in the Accelerating Data Value Across a National Community Health Center Network (ADVANCE). The sample included 34 266 children with asthma from 2008 to 2017, aged 3-17 living in neighbourhoods with differing levels of social deprivation measured using quartiles of the Social Deprivation Index score. We conducted logistic regression to examine the odds of problem list documentation of asthma and asthma severity, and negative binomial regression for rates of albuterol, inhaled steroid and oral steroid prescription adjusted for patient-level covariates., Results: Children from the most deprived neighbourhoods had increased rates of albuterol (rate ratio (RR)=1.22, 95% CI 1.13 to 1.32) compared with those in the least deprived neighbourhoods, while the point estimate for inhaled steroids was higher, but fell just short of significance at the alpha=0.05 level (RR=1.16, 95% CI 0.99 to 1.34). We did not observe community-level differences in problem list documentation of asthma or asthma severity., Conclusions: Higher neighbourhood-level social deprivation was associated with more albuterol and inhaled steroid prescriptions among children with asthma, while problem list documentation of asthma and asthma severity varied little across neighbourhoods with differing deprivation scores. While the homogeneity of the CHC safety net setting studied may mitigate variation in diagnosis and documentation of asthma, enhanced clinician awareness of differences in community risk could help target paediatric patients at risk of lower quality asthma care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: The associations of 2 nonsynonymous single nucleotide polymorphisms (Arg16Gly and Gln27Glu) in the adrenoceptor β2 (ADRB2) gene with response after albuterol use are conflicting. We conducted a meta-analysis to examine the cumulative evidence of the effects of these 2 variants on percent forced expiratory volume in 1 second (FEV1.0%) after albuterol use in asthma patients., Methods: We conducted a comprehensive literature search using MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify studies examining the association between ADRB2 Arg16Gly and Gln27Glu and FEV1.0% shortly after albuterol administration. The individual study results were combined with weights based on the inverse variance method. This systematic review was registered in the PROSPERO (registration number: CRD42019074554)., Results: Among 273 initial studies identified, 7 studies met the inclusion criteria for quantitative evaluation. Results of the overall meta-analysis indicated no statistically significant mean difference of FEV1.0% between genotypes of Arg16Gly and Gln27Glu. In subgroup analyses, significant associations were found for Arg16Gly GG (vs AA) among studies where no methacholine bronchoconstriction was conducted (mean difference, -3.92; 95% confidence interval, -7.29 to -0.54; I 2 = 0%), and for Arg16Gly GG (vs GA) among studies that included patients with no comorbidities (mean difference, -1.93; 95% confidence interval, -3.77 to -0.10; I 2 = 0%)., Conclusion: Synthesis of the studies to date shows weak evidence for an association between ADRB2 Arg16Gly and Gln27Glu and FEV1.0% after albuterol use, results of which underscore significant heterogeneity across studies and the need for careful design and sample size considerations., (© 2020 British Pharmacological Society.)

Lactic acidosis is a common complication of status asthmaticus in adults. However, data is sparse in children. The aim of this study was to describe the prevalence and risk factors for lactic acidosis in children hospitalised for acute moderate or severe asthma. A total of 154 children 2-17 years of age were enrolled in a prospective observational study conducted in a tertiary hospital. All had capillary blood gas assessment 4 h after the first dose of salbutamol in hospital. The primary endpoint was the prevalence of lactic acidosis. Potential contributing factors such as age, sex, BMI, initial degree of asthma severity, type of salbutamol administration (nebuliser or inhaler), steroids, ipratropium bromide, and glucose-containing maintenance fluid represented secondary endpoints. All in all, 87% of patients had hyperlactatemia (lactate concentration > 2.2 mmol/l). Lactic acidosis (lactate concentration > 5 mmol/l and anion gap ≥ 16 mmol/l) was observed in 26%. In multivariate analysis, age more than 6 years (OR = 2.8, 95% CI 1.2-6.6), glycemia above 11 mmol/l (OR = 3.2 95% CI 1.4-7.4), and salbutamol administered by nebuliser (OR = 10, 95% CI 2.7-47) were identified as risk factors for lactic acidosis in children with moderate or severe asthma.Conclusion: Lactic acidosis is a frequent and early complication of acute moderate or severe asthma in children. What is Known: • Lactic acidosis during acute asthma is associated with b2-mimetics administration. • Salbutamol-related lactic acidosis is self-limited but important to recognise, as compensatory hyperventilation of lactic acidosis can be mistaken for respiratory worsening and lead to inappropriate supplemental bronchodilator administration. What is New: • Lactic acidosis is a frequent complication of acute asthma in the paediatric population. • Age older than 6 years, hyperglycaemia, and nebulised salbutamol are risk factors for lactic acidosis during asthma.

Background: Protocol-driven therapy has been successful in managing patients with asthma on pediatric wards, but there is wide variability in ICU-level management that is often provider-dependent. This study aimed to determine if a standardized protocol for critical asthma treatment could improve clinical outcomes., Methods: A pre-intervention cohort consisting of subjects age 2-18 y, excluding patients with airway obstruction that was not felt to be due to asthma, who were admitted to the ICU for critical asthma. Demographics and data along with medication administration information were gathered using the hospital electronic medical record. A post-intervention cohort was obtained over 13 months in an identical manner. The primary end point was time on continuous albuterol. Subjects adhering to the protocol were examined as a subset., Results: 71 post-intervention subjects were compared with a historical cohort of 52 pre-intervention subjects over a similar time frame. There were no significant differences in demographic characteristics. Median time on continuous albuterol (14.4 h vs 8.1 h, P = .14) and secondary end points of median ICU length of stay (LOS), hospital LOS, and time from discontinuing continuous albuterol to transfer out of ICU were not significantly reduced in the post-intervention cohort. Overall adherence to the clinical protocol through completion was 42%. When comparing the pre-intervention cohort with the protocol-adherent subjects, significant reductions were seen in time on continuous albuterol (14.4 h vs 3.0 h, P < .001), ICU LOS (38.7 h vs 21.0 h, P < .001), and hospital LOS (2.8 d vs 1.7 d, P = .005)., Conclusions: Implementation of an asthma protocol in the pediatric ICU did not result in significant improvements in time on continuous albuterol or hospital and pediatric ICU LOS, likely due to low adherence to the protocol. However, in subjects who did adhere to the protocol there were significant reductions in the outcome measures., Competing Interests: The authors have disclosed no conflicts of interest. This work was supported by National Institutes of Health’s National Center for Advancing Translational Sciences Grant UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health’s National Center for Advancing Translational Sciences., (Copyright © 2021 by Daedalus Enterprises.)

Inability to access an albuterol inhaler at school increases risk to students of severe asthma attack. Students typically must bring their own albuterol for use at school. In this program, albuterol is sent from a pharmacy to the school at no cost to families following a child's hospitalization or health care encounter.

Background: Pediatric Asthma Assessment tools used to guide the weaning of inhaled therapies during inpatient hospitalization require further evaluation and validation. This study aimed to compare 2 asthma assessment tools: an asthma scale versus an asthma score., Methods: A prospective, physician-blinded, comparison study was conducted in 2 separate 6-week phases of patients > 2 y old admitted to a tertiary care children's hospital with status asthmaticus between July and November 2014. The asthma scale categorized 5 components (oxygen, auscultation, dyspnea, breathing frequency, and pulse oximetry) into 1 of 3 respiratory assessments: mild, moderate, or severe. The asthma score used a sum of the components, resulting in a score of 1-15. Study tool predictability was measured using a metric based on hours on continuous albuterol, with area under the curve ≥ 0.8 indicating good predictability. Agreement between clinicians was measured using the Cohen kappa statistic. Study tool clinical correlation was measured using Spearman coefficient. Usability was evaluated using web-based surveys., Results: Phase 1 included 1,971 assessments (97 unique subjects), whereas phase 2 included 607 assessments (69 unique subjects). Using the continuous albuterol metric, predictability of the asthma scale had an area under the curve of 0.62 versus the asthma score area under the curve of 0.80. Agreement early in hospitalization for the asthma scale was kappa = 0.34 (95% CI 0.18-0.5; n = 84) versus kappa = 0.55 (95% CI 0.35-0.76; n = 44) for the asthma score. Agreement late in hospitalization for the asthma scale was kappa = 0.38 (95% CI 0.17-0.59; n = 66) versus kappa = 0.41 (95% CI 0.13-0.69; n = 33) for the asthma score. Clinical correlation for the asthma scale (no. = 1,908) was r = 0.57 ( P < .001) versus r = 0.80 ( P < .001) for the asthma score (no. = 558). Mean asthma scale usability was 3.38 versus 3.68 for the asthma score., Conclusions: The asthma score showed better clinical predictability and clinical correlation compared to the asthma scale. Numerical scores provided more objective assessments compared to categorical scores. Validated scoring tools such as the asthma score are crucial to the success of management of inpatient asthma care., (Copyright © 2021 by Daedalus Enterprises.)