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

The long-term use of pediatric medications can lead to discoloration of dental restorations, which affects their durability and longevity. The present in vitro study evaluated the effects of commonly used pediatric medications on the color stability of a conventional and a bulk-fill composite resin. For this study, 80 disc-shaped specimens of each composite were prepared in molds with a diameter of 6 mm and thicknesses of 2 or 4 mm (n = 40 per thickness per material). A spectrophotometer was used toevaluate the baseline color of the specimens in the International Commission on Illumination L*a*b* color space. Each specimen was immersed separately in a container holding 1 of 8 liquid medications (n = 5 per thickness per medication): amoxicillin/clavulanate, clarithromycin, cephalexin, acetaminophen, ibuprofen, levetiracetam, multivitamin, or albuterol. After the container was shaken for 2 minutes, the specimen was removed from the medication and stored in artificial saliva. The cycle was repeated every 8 hours for 1 week. The color measurements were repeated after 1 week of immersion cycles, and the overall color change (82*) was calculated; a value of AE* > 3.3 was considered clinically perceptible. The data were analyzed with 1-way and 2-way analyses of variance as well as the Levene test and Games-Howell post hoc test (P < 0.05). All specimens displayed clinically perceptible color changes after exposure to medications commonly used by children. The mean color change in the 4-mm bulk-fill composite resin group was significantly greater than that in all other groups (P < 0.05). However, there was no significant difference in color change based on the immersion drug for either of the composites (P > 0.05). Thestudy findings show that exposure of composite resin to certain commonly used pediatric drugs causes color changes that are clinically perceptible. [ABSTRACT FROM AUTHOR]

Background: Bronchodilator responsiveness (BDR) in asthma involves both the central and peripheral airways but is primarily relieved with beta-2-agonists and evaluated by spirometry. To date, antimuscarinics can be added as a reliever medication in more severe asthma. We hypothesize that combining both short-acting beta-2 agonist (SABA) and short-acting muscarinic antagonist (SAMA) could also improve the responsiveness in mild-moderate asthma. Therefore, we aimed to compare the direct effects of inhaling SABA alone, SAMA alone or combining both SABA and SAMA on the central and peripheral airways in asthma.Methods: Twenty-three patients with mild-moderate BDR in asthma performed dynamic spirometry and impulse oscillometry before (baseline) and multiple timepoints within an hour after inhalation of SABA (salbutamol), SAMA (ipratropium bromide), or both SABA and SAMA at three different visits.Results: The use of SAMA alone did not show any improvement compared to the use of SABA alone. Inhalation of SABA+SAMA, however, averaged either similar or better BDR than SABA alone in FEV1, MMEF, FVC, R5, R20 and R5-R20. Inhaling SABA+SAMA reached a stable BDR in more patients within 0– 10 minutes and also reached the FEV1 (Δ%)> 12% faster (3.5 minutes) than inhaling SABA alone (5.1 minutes). Inhaling SABA+SAMA was significantly better than SAMA alone in FEV1 (p = 0.015), MMEF (p = 0.0059) and R20 (p = 0.0049). Using these three variables highlighted a subgroup (30%, including more males) of patients that were more responsive to inhaling SABA+SAMA than SABA alone.Conclusion: Overall, combining SAMA with SABA was faster and more consistent at increasing the lung function than SABA alone or SAMA alone, and the additive effect was best captured by incorporating peripheral-related variables. Therefore, SAMA should be considered as an add-on reliever for mild-moderate patients with BDR in asthma. [ABSTRACT FROM AUTHOR]

Inhaled long acting B2-agonist combined with inhaled steroid being longed used in chronic persistent bronchial asthma as a therapy to reduce the needs for admission to hospital and to improve quality of life instead of isolated single uses. Patients and Methods: Two hundred Seven patients with chronic persistent bronchial asthma on variety of inhalers, enrolled randomly in this study, One hundred Twenty (58.0%) were female and Eighty Seven (42.0%) were male, their ages range from sixteen to seventy five with mean ages (45.59±14.67) year's. type of inhalers used, dose, control with a question about admission to hospital, adherence to inhalers, confidents and recording the parameter of pulmonary function test FEV1, FVC and PEFR while patients on own inhalers type used. Results: In this study there are statistically significant different between, single and combined inhalers in chronic persistent asthma (p value0.005)in FEV1LFVC but not between the types of combined inhalers (p.value 0.12), age in both types of comparisons indicate no statistically significant effects(p value 0.85,0.47) respectively. Conclusions: combined inhalers therapy for patients with persistent asthma superior for either alone, preferred and confident by patients; ages of patients neither significantly alter the response nor the patients desire. [ABSTRACT FROM AUTHOR]

Summary: Anaesthetists may be required to work in hybrid theatres for procedures using fluoroscopic imaging. Adequate knowledge of fluoroscopic images allows prompt and effective emergency management of complications which arise during procedures. Here, we present a case of severe hypotension and hypoxia occurring shortly after induction of anaesthesia. Atelectasis was mistaken for a pneumothorax due to misinterpretation of fluoroscopic imaging, which demonstrated a dark pleural cavity peripheral to a partially collapsed left lung, leading to an incorrect diagnosis. This case highlights the importance of understanding greyscale inversion in fluoroscopy. [ABSTRACT FROM AUTHOR]

Medication dosing errors are common in prehospital pediatric patients. Prior work has shown the overall medication error rate by emergency medical services (EMS) in Michigan was 34.7%. To reduce these errors, the state of Michigan implemented a pediatric dosing reference in 2014 listing medication doses and volume to be administered. To examine changes in pediatric dosing errors by EMS in Michigan after implementation of the pediatric dosing reference. We conducted a retrospective review of the Michigan Emergency Medical Services Information System of children ≤ 12 years of age from June 2016–May 2017 treated by 16 EMS agencies. Agencies were a mix of public, private, third-service, and fire-based. A dosing error was defined as >20% deviation from the weight-appropriate dose listed on the pediatric dosing reference. Descriptive statistics with confidence intervals and standard deviations are reported. During the study period, there were 9,247 pediatric encounters, of whom 727 (7.9%) received medications and are included in the study. There were 1078 medication administrations, with 380 dosing errors (35.2% [95% CI 25.3–48.4]). The highest error rates were for dextrose 50% (3/4 or 75% [95% CI 32.57–100.0]) and glucagon (3/4 or 75% [95% CI 32.57–100.0]). The next highest proportions of incorrect doses were opioids: intranasal fentanyl (11/16 or 68.8% [95% CI 46.04–91.46]) and intravenous fentanyl (89/130 or 68.5% [95% CI 60.47–76.45]). Morphine had a much lower error rate (24/51 or 47.1% [95% CI 33.36–60.76]). Midazolam had the third highest error rate, for intravenous (27/50 or 54.0% [95% CI (40.19–67.81]) and intramuscular (25/68 or 36.8% [95% CI 40.19–67.81]) routes. Epinephrine 1 mg/10 ml had an incorrect dosage rate of 35/119 (29.4% [95% CI 20.64–36.99]). Asthma medications had the lowest rate of incorrect dosing (albuterol sulfate 9/247 or 3.6% [95% CI 1.31–5.98]). Medications administered to prehospital pediatric patients continue to demonstrate dosing errors despite pediatric dosing reference implementation. Although there have been improvements in error rates in asthma medications, the overall error rate has increased. Continued work to build patient safety strategies to reduce pediatric medication dosing errors by EMS is needed. [ABSTRACT FROM AUTHOR]

Purpose: Salbutamol has been used to alleviate bronchospasm in airway disease for decades, while its potential risks have not been systematically investigated yet. The risk of any potential adverse events (AEs) in patients treated with salbutamol was assessed through systematic review and meta‐analysis. Methods: A systematic search of the literature was conducted, using EMBASE, PubMed and Cochrane library, until 3 April 2023. Once the AE incidence was evaluated, randomized controlled trials (RCTs) were eligible for review. The endpoints included the incidence of total AEs, severe AEs, treatment discontinuation and specific AEs. The pooled AEs incidence was analysed via random‐effects model in a single‐arm meta‐analysis. A subgroup study was carried out to examine whether the pooled incidence of AE differed by indications or formulations. Results: Of the 8912 studies that were identified, 58 RCTs met the inclusion criteria and involved 12 961 participants. The analysis showed the pooled incidences of total AEs, severe AEs and treatment discontinuation in patients treated with salbutamol were 34%, 2% and 3%, respectively. Subgroup analysis indicated that premature labour users and intravenous salbutamol users were more likely associated with total AEs. The most frequently observed specific AEs were palpitations or tachycardia. Conclusion: This meta‐analysis indicated that salbutamol was associated with a very common risk of palpitations or tachycardia. Clinical vigilance and research efforts are needed to optimize the safe use of salbutamol. [ABSTRACT FROM AUTHOR]

The family of calcium-activated chloride channels, TMEM16, plays a significant role in contributing to the pathogenesis of airway inflammatory diseases. Targeting these ion channels and aiming to modulate them may provide an interesting new approach to the therapy of these potentially fatal diseases. We tested this hypothesis in both healthy and ovalbumin (OVA)-sensitized male Dunkin-Hartley guinea pigs. The ion channel activity was modulated by TMEM16A-nonselective (benzbromarone) and TMEM16A-selective blockers (CaCCinh-A01). In vivo airway reactivity, induced by histamine and methacholine, was expressed as specific airway resistance (sRaw) values. The number of citric acid-induced coughs was counted using a double-chambered body plethysmograph, and the frequency of ciliary beating (CBF) was assessed in vitro by brushing method. For comparison, salbutamol and codeine were tested under the same conditions. The results showed significant differences in the responses of unsensitized and sensitized airways to both TMEM16 blockers administered. CaCCinh-A01 and benzbromarone significantly reduced the number of cough efforts in the group of OVA-sensitized guinea pigs. Significant improvement in sRaw values could be observed in OVA-sensitized TMEM16 blocker–treated animals compared to salbutamol when challenged with inhalational histamine, and the outcome was similar to salbutamol when challenged with methacholine. CBF was significantly inhibited in animals sensitized to OVA treated with selective inhibition of TMEM16A. The results demonstrated that treatment with blockers of TMEM16 can reduce both cough effort and sRaw, and the difference between TMEM16A-selective and TMEM16A-nonselective blocking is only negligibly in favor of CaCCinh-A01. It is also worthwhile to note the impairment of CBF in OVA-sensitized animals treated with CaCCinh-A01. [ABSTRACT FROM AUTHOR]

In recent years, some new concepts have been added to asthma treatment such as "anti-inflammatory reliever" (β2-agonist use associated to an inhaled corticosteroid (ICS) as a reliever treatment) that combines the benefits of both therapies and provides short- and long-term benefits for treatment in asthma patients. Robust evidence has been presented in patients over 12 years, and the main changes in the international guidelines for asthma treatment were originally made in this age group. However, a few suggestions have been added to treatments in younger patients, in part because of the scarce evidence that exists in this group. We aim to analyze the information regarding the utilization of ICS + fast-acting beta-agonist (FABA) combination in children between 6 and 11 years. Although up until today only three published trials exist (two studies use beclomethasone + albuterol and one study uses budesonide + formoterol), they provide significant information on the benefits of ICS + FABA use in this population. [ABSTRACT FROM AUTHOR]

Purpose: Globally breast cancer accounts for 24.5% in incidence and 15.5% in cancer deaths in women. The triple-negative subtype lacks any specific therapy and is treated with chemotherapy, resulting in significant side-effects. We aimed to investigate if the dose of chemotherapeutic drugs could be diminished by co-administering it with the β2-agonist salbutamol. Methods: Cell proliferation was measured by thymidine incorporation; gene expression, by real-time PCR and protein phosphorylation by WB. Apoptosis was assessed by acridine orange / ethidium bromide and TUNEL tests. Public patient databases were consulted. Cells were inoculated to nude mice and their growth assessed. Results: The β2-agonist salbutamol synergizes in MDA-MB-231 cells in vitro with paclitaxel and doxorubicin on cell proliferation through ADRB2 receptors, while the β-blocker propranolol does not. The expression of this receptor was assessed in patient databases and other cell lines. Triple negative samples had the lowest expression. Salbutamol and paclitaxel decreased MDA-MB-231 cell proliferation while their combination further inhibited it. The pathways involved were analyzed. When these cells were inoculated to nude mice, paclitaxel and salbutamol inhibited tumor growth. The combined effect was significantly greater. Paclitaxel increased the expression of MDR1 while salbutamol partially reversed this increase. Conclusion: While the effect of salbutamol was mainly on cell proliferation, suboptimal concentrations of paclitaxel provoked a very important enhancement of apoptosis. The latter enhanced transporter proteins as MDR1, whose expression were diminished by salbutamol. The expression of ADRB2 should be assessed in the biopsy or tumor to eventually select patients that could benefit from salbutamol repurposing. [ABSTRACT FROM AUTHOR]

BACKGROUND: Aerosol delivery via high-flow nasal cannula (HFNC) has gained popularity due to the increased use of the modality for treating hypoxemic and hypercapnic respiratory failure. Various HFNC devices are available in the United States; however, the effectiveness of aerosol delivery via HFNC devices remains unclear. Thus, this study aimed to investigate the impact of various commercially available devices on transnasal aerosol delivery. METHODS: This was a bench study that used a 2-chamber lung model, in which one chamber was connected to an adult manikin with anatomically correct upper-airway proportions. The other chamber was connected to a critical care ventilator used to simulate spontaneous breathing. A size large nasal cannula was placed at the nasal opening of the manikin. Five different HFNC devices (Hamilton-C1, OptiFlow, Airvo2, V60 Plus, and Vapotherm) were compared. Four flow settings were used on each device, with a vibrating mesh nebulizer placed at the humidifier. Salbutamol (2.5 mg/3 mL) was used during the experiments to quantify inhaled drug doses. A collection filter was placed between the manikin's trachea and the lung model. The drug was eluted from the filter and assayed with ultraviolet spectrophotometry (276 nm). RESULTS: Among the 5 HFNC devices, OptiFlow had the highest inhaled dose at 10 L/min (mean ± SD 18.2% ± 1.2%). At 20 L/min, the Hamilton-C1 (mean ± SD 13.5% ± 0.4%) performed marginally better than the OptiFlow (mean ± SD 12.6% ± 1.9%) and Airvo2 (mean ± SD 12.8% ± 1%). At high flow settings (40--60 L/min), the inhaled dose of Hamilton-C1 was 2--3 times that of the Airvo2 and V60 Plus. When compared with the other devices, the mean inhaled dose with the Vapotherm was lower (0.9-2.5%). In all devices, the inhaled dose decreased as the flow increased. CONCLUSIONS: Transnasal aerosol delivery was significantly impacted by the types of HFNC devices and flow settings. Nominal doses might need to be adjusted if changing HFNC devices or flow is not an option. [ABSTRACT FROM AUTHOR]

Background: Post-acute COVID-19 is known to affect multiple organs. It is essential to determine factors that affect post-acute COVID-19 syndrome and medications needed by patients for optimized care. Methods: A prospective cohort study was conducted among patients recruited by stratified sampling from two COVID-19 hospitals in Malaysia. Patients were followed up for 6 months using a standard questionnaire to identify demographics, symptoms, medications taken, and factors associated with post-acute COVID-19 syndrome. Results: A total of 388 were successfully followed up. The most frequently reported symptom was respiratory symptoms (N = 168, 43.30%), of which cough (N = 134, 34.54%) was the most common. After 12 weeks of follow-up, respiratory syndrome (N = 56,14.43%) was frequently reported, of which cough (N = 41, 10.57%) was the most common. For respiratory syndrome, patients were commonly managed with diphenhydramine cough suppressants (N = 6, 1.55%, month 4) and metered dose inhaler (MDI) salbutamol (N = 7, 1.8%, month 4). The risk factors for post-acute COVID-19 syndrome were increased by 1.02 times (95% CI: 1.01, 1.04) with each advanced year of age and 2.87 times (95%CI: 1.51-5.48) in the presence of co-morbidities. Conclusions: Post-acute COVID-19 causes multiorgan involvement, and symptoms may remain for months, with patients taking various medications. Patients with risk factors should be monitored closely for post-acute COVID-19 symptoms. [ABSTRACT FROM AUTHOR]

Abstract Background Albuterol is the first-line asthma medication used in diverse populations. Although DNA methylation (DNAm) is an epigenetic mechanism involved in asthma and bronchodilator drug response (BDR), no study has assessed whether albuterol could induce changes in the airway epithelial methylome. We aimed to characterize albuterol-induced DNAm changes in airway epithelial cells, and assess potential functional consequences and the influence of genetic variation and asthma-related clinical variables. Results We followed a discovery and validation study design to characterize albuterol-induced DNAm changes in paired airway epithelial cultures stimulated in vitro with albuterol. In the discovery phase, an epigenome-wide association study using paired nasal epithelial cultures from Puerto Rican children (n = 97) identified 22 CpGs genome-wide associated with repeated-use albuterol treatment (p

The article offers information on the use of noninvasive respiratory support (NRS) in pediatric critical asthma, including high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), and noninvasive ventilation (NIV). Topics include the challenges of determining the optimal role of each NRS modality due to limited high-quality data, the variation in NRS use among institutions, and the association between NRS use and outcomes such as PICU length of stay and intubation rates.

The article discusses a case of acute levalbuterol toxicity in an 8-year-old child due to excessive use of a metered dose inhaler (MDI), highlighting the importance of recognizing and managing β2 agonist overdose. Topics include distinguishing features of levalbuterol toxicity, its rarity compared to racemic albuterol toxicity, and the need for patient education on appropriate inhaler use to prevent overdose.

The choice of bronchodilators for responsiveness testing (BRT) is a clinical decision according to ATS/ERS. Since January 2019 we use budesonide/formoterol for BRT in asthma at our center in Argentina. The aim was to compare budesonide/formoterol with salbutamol for BRT in stable asthmatic patients that were followed up in a short-acting beta2 agonist (SABA)-free asthma center. From the Hospital database, we found for the same patient at least one BRT using salbutamol 200 µg and another with budesonide/formoterol 320/9 µg. We found similar BRT between salbutamol and budesonide/formoterol in 101 asthmatic individuals (26 males) aged 38.14 ± 16.1 yrs (mean ± Standard deviation). The absolute response was 0.18 ± 0.21 L in FEV1 after salbutamol and 0.20 ± 0.22 L in FEV1 after budesonide/formoterol. Afterwards, we showed 202 patients tested with budesonide/formoterol; the mean absolute response was 0.21 ± 0.22 L in FEV1. There were no unexpected safety findings. In asthmatic patients, we demonstrated similar efficacy between Budesonide/formoterol and salbutamol for BRT. [ABSTRACT FROM AUTHOR]

Objective: To assess and compare the effects of two pediatric anti-asthmatic medication doses on the microhardness of enamel and microhardness, surface roughness and color of restorative materials. Methods: Human enamel samples and packable and flowable composite restorations were used. The samples were exposed to Salbutamol (0.6 mL/6 mL saline) and Budesonide (2 mL/2 mL saline) via a custom-made chamber connected to a nebulizer. Medication administration was conducted for 10 days. The samples were brushed with an electronic brush in a continuous and circular mode for 10 s after 10 min of medication administration. Assessments of microhardness, surface roughness and color were carried out at three different time intervals: baseline (T0), 5 days (T1) and 10 days (T2). One-way analysis of variance (ANOVA), a two-sample t-test and a Bonferroni multiple comparison test were used to analyze the data and compare between the groups. Results: Both medications significantly (p < 0.05) decreased the microhardness of the enamel and composite samples after 10 days. Both medications lowered the surface roughness of both types of composite with a greater effect observed after 10 days of Budesonide administration (p < 0.05). Both medications had comparable detectable color change on both types of composite with a greater effect observed after 10 days of Budesonide administration (p < 0.05). Conclusion: Salbutamol and Budesonide significantly decreased microhardness in the enamel samples. Both medications affected the properties of packable and flowable composites. The packable composite showed more resistance to microhardness changes. Both medications showed a clinically detectable change in the color of packable and flowable composites. [ABSTRACT FROM AUTHOR]

Objective: To describe the presentation of rebound hyperkalemia as a delayed side effect of albuterol toxicity in a dog. Case Summary: A 3‐year‐old female neutered mixed‐breed dog was presented for albuterol toxicosis that led to a severe hypokalemia, hyperlactatemia, and hyperglycemia. The dog also experienced sinus tachycardia and generalized weakness. Treatment was instituted with intravenous fluid therapy and potassium supplementation, and the dog was monitored with a continuous electrocardiogram. Resolution of hypokalemia was documented 12 hours after initial presentation, at which time fluid therapy and potassium supplementation were discontinued. There were no further periods of sinus tachycardia, but instead the dog developed ventricular ectopy with rapid couplets (instantaneous rates of 300/min). An echocardiogram revealed normal cardiac size and function. Twenty‐four hours after presentation, the patient developed severe hyperkalemia, despite discontinuation of fluids and potassium supplementation for 12 hours. Serial venous and urinary electrolytes were performed for determination of the fractional excretion of electrolytes. These data confirmed rebound hyperkalemia (7.0 mmol/L), consistent with a markedly increased fractional excretion of potassium, and secondary to the release of potassium from inside the cells. Fluid therapy with dextrose supplementation was provided until 36 hours postpresentation. The hyperkalemia resolved, and the dog was discharged after 44 hours of hospitalization. New or Unique Information Provided: This case documents rebound hyperkalemia following treatment of albuterol toxicosis in a dog. This case highlights the importance of understanding the distribution of total body potassium when treating serum hypokalemia. Transcellular shifts of potassium, as in the case of albuterol toxicosis, can lead to rebound hyperkalemia even after discontinuation of potassium supplementation. This case further explores the utility of fractional excretion of electrolytes in elucidating the etiology and management of electrolyte disturbances. [ABSTRACT FROM AUTHOR]

BACKGROUND: The recommended treatment of COPD exacerbations includes administration of short-acting bronchodilators that act to reverse bronchoconstriction, restore lung volumes, and relieve breathlessness. In vitro studies demonstrate vibrating mesh nebulizers (VMNs) provide greater drug delivery to the airway compared to standard small-volume nebulizers (SVNs). We examined whether the physiological and symptom response to nebulized bronchodilators during a COPD exacerbation differed between these 2 modes of bronchodilator delivery. METHODS: Subjects hospitalized with a COPD exacerbation participated in a comparative clinical effectiveness study of 2 methods of nebulization. Using block randomization, 32 participants in this open-label trial were administered salbutamol 2.5 mg/ipratropium bromide 0.5 mg via vibrating mesh (VMN group, n 5 16) or small-volume jet nebulizer (SVN group, n 5 16) on one occasion. Spirometry, body plethysmography, and impulse oscillometry were performed and Borg breathlessness scores recorded pre bronchodilator and at 1 h post bronchodilator. RESULTS: Baseline demographics were comparable between groups. Mean FEV1 was 48% predicted. Significant changes in lung volumes and airway impedance were seen in both groups. Inspiratory capacity (IC) increased by 0.27 6 0.20 L and 0.21 6 0.20 L in the VMN and SVN group, respectively, between group difference P 5 .40. FVC increased in the VMN group by 0.41 6 0.40 L compared to 0.19 6 0.20 L with SVN, between group difference P 5 .053; and residual volume (RV) decreased by 0.36 6 0.80 L and 0.16 6 0.50 L in the VMN and SVN group, respectively, between group difference P 5 .41. The VMN group had a significant reduction in Borg breathlessness score, P 5 .034. CONCLUSIONS: Greater improvement in symptoms, and larger absolute change in FVC, was observed in response to equivalent doses of standard bronchodilators administered by VMN, compared to SVN, but no substantial difference in change in IC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Secondhand exposure to fugitive aerosols may cause airway diseases in health providers. We hypothesized that redesigning aerosol masks to be closed-featured would reduce the fugitive aerosol concentrations during nebulization. This study aimed to evaluate the influence of a mask designed for a jet nebulizer on the concentration of fugitive aerosols and delivered doses. METHODS: An adult intubation manikin was attached to a lung simulator to mimic normal and distressed adult breathing patterns. The jet nebulizer delivered salbutamol as an aerosol tracer. The nebulizer was attached to 3 aerosol face masks: an aerosol mask, a modified non-- rebreathing mask (NRM, with no vent holes), and an AerosoLess mask. An aerosol particle sizer measured aerosol concentrations at parallel distances of 0.8 m and 2.2 m and a frontal distance of 1.8 m from the manikin. The drug dose delivered distal to the manikin's airway was collected, eluted, and analyzed using a spectrophotometer at a 276 nm wavelength. RESULTS: With a normal breathing pattern, the trends of aerosol concentrations were higher with an NRM followed by an aerosol mask and AerosoLess mask (P < .001) at 0.8 m; however, the concentrations were higher with an aerosol mask followed by NRM and AerosoLess mask at 1.8 m (P < .001) and 2.2 m (P < .001). With a distressed breathing pattern, the aerosol concentrations were higher with an aerosol mask followed by an NRM and AerosoLess mask at 0.8 m, 1.8 m (P < .001), and 2.2 m (P 5 .005). The delivered drug dose was significantly higher with AerosoLess mask with a normal breathing pattern and with an aerosol mask with a distressed breathing pattern. CONCLUSIONS: Mask design influences fugitive aerosol concentrations in the environment, and a filtered mask reduces the concentration of aerosols at 3 different distances and with 2 breathing patterns. [ABSTRACT FROM AUTHOR]

Spray freeze-drying has emerged as a valid alternative to traditional spray drying to produce therapeutic dry microparticles. In particular, the spherical shape and high porosity of spray freeze-dried microparticles make them suitable for pulmonary drug delivery through dry powder inhalers. However, an appropriate particle size and fine particle fraction are required to guarantee lung deposition. This study used ultrasonic spray freeze-drying to generate dry microparticles composed of mannitol either alone or added with the bronchodilator salbutamol sulphate. The influence of the solid concentration and the feed flow rate on the particle size, morphology, surface area, porosity, and crystallinity was investigated. Growing particle size was observed, increasing the concentration and feed flow rate. Similarly, the addition of the drug led to a larger particle size and surface area. The in vitro simulation of drug deposition highlighted the dependence of the aerodynamic properties on the solid concentration and feed flow rate. Due to the lower density and particle geometric size, the highest fine particle fraction (26%) and smallest mass median aerodynamic diameter (4.4 μm) were reached at the lowest solid concentration and feed flow rate. [ABSTRACT FROM AUTHOR]

Salbutamol (SAL) is a β2-agonist and belongs to a category of drugs used to maintain bronchodilation. Unfortunately, some athletes have misused these medications as performance-enhancing drugs to improve their performance. Thus, to ensure fair competition, the World Anti-Doping Agency (WADA) prohibits its usage among athletes. Herein, we have designed, a novel, non-enzymatic electrochemical sensor by wrapping benzimidazolium-1-acetate liquid (IL) around Co3O4 (derived from the pyrolysis of ZIF-67) embedded in N-doped porous C (IL@NC–Co), for the detection of SAL in urine for dope tests. The fabricated material was characterized through SEM, XRD, and FTIR techniques, which confirmed the successful synthesis of the material. The designed novel IL@NC–Co electrochemical sensor showed excellent electrocatalytic activity because of its highly porous structure and fast electron transfer due to the presence of carboxyl functional groups and aromatic rings in IL, thus resulting in an enhanced current response. The developed sensor exhibited excellent selectivity even in the presence of co-existing interferences and good sensitivity (0.0039 μA nM−1 cm−2) with a linear response to SAL concentrations ranging from 2 to 2500 μM with a low detection limit of 0.0014 nM. The designed electrode showed an excellent stability of 96.58% with RSD 2.45% even after 24 h. The fabricated electrode was successfully utilized for selective monitoring of SAL in urine samples, thus suggesting the reliability of the designed system to be applicable for dope tests. [ABSTRACT FROM AUTHOR]

A positive response in reversibility testing is widely used to diagnose patients with airway limitations. However, despite its simple procedure, it doesn't accurately reflect the exact airway irreversibility. This study aimed to investigate the efficacy of a bronchodilation reversibility test using salbutamol and fluticasone/salmeterol combination in obese non-smoker subjects. The study included patients without a history of obstructive lung disease or bronchodilators. A sub-classification of patients based on body mass index (BMI) was carried out into normal (< 24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (BMI ≥ 30). Spirometry measurements were performed before and after salbutamol or fluticasone/salmeterol administration. The study included 415 (49.9% male) patients with a mean age of 40.92 ± 10.86 years. Obese subjects showed a high prevalence of restrictive patterns (23.4%), with non-significantly lower spirometric values compared to normal and overweight subjects (p > 0.05). The magnitude of bronchodilation, as identified by spirometry, following fluticasone/salmeterol was higher in all participants, with a significant increase in obese subjects with a p-value of 0.013, 0.002, and 0.035 for FEV1, FEV1% predicted, and FEV1/FVC, respectively. Fluticasone/salmeterol combination increases FEV1, FEV1% of predicted, and FEV1/FVC ratio than the conventional test using salbutamol inhaler, and it can be a potential candidate for assessment of airway obstruction using reversibility test, especially among the obese population. [ABSTRACT FROM AUTHOR]

Airsupra inhalation aerosol is a recently approved FDA medication that combines albuterol and budesonide for treating or preventing bronchoconstriction and lowering the risk of relapses in asthma patients who are 18 years of age and older. To selectively determine albuterol and budesonide in both pure and pharmaceutical dosage forms, two analytical methods were developed: the zero-order absorption method and the dual-wavelength method. Even though the two drugs absorption spectra overlapped, the distinctive peak of budesonide at the zero absorbance point of albuterol, 245 nm, allowed for direct detection of budesonide in the combination using the zero-order absorption method. The mathematical dual-wavelength method, on the other hand, allowed for the measurement of both albuterol and budesonide by choosing two wavelengths for each drug in such a way that the absorbance difference for the second drug was zero. Budesonide exhibited comparable absorbance values at wavelengths 227 and 261.40 nm; hence, these two wavelengths were utilized to identify albuterol; similarly, 221.40 and 231.20 nm were chosen to determine budesonide in their binary mixes. The methods were validated according to the ICH guideline for validation of analytical procedures Q2(R1) and demonstrated excellent linearity, sensitivity, accuracy, precision, and selectivity for determining both drugs in synthetic mixed solutions and pharmaceutical formulations. The availability of these analytical methods would be valuable for the pharmaceutical industry and regulatory authorities for quality control and assessment of pharmaceutical formulations containing albuterol and budesonide. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We present the case of a 42-year-old female patient, known with the diagnosis of severe persistent l asthma stage 3 Gina since 2012, for which she is on treatment with Formoterol/Budesonid (Symbicort) 160mcg/4.5 mcg 1 puff/12 h, inhaler, daily and Salbutamol (Ventolin) 100 mcg, 2 puffs as needed, maximum 6 puffs/24 h, inhaler, who is being treated for exacerbation of respiratory symptoms. It is important to mention the onset of asthma - at the age of 1 year, with rapidly progressive evolution towards the severe stage and association of multiple pulmonary complications. In order to determine the evolutionary stage of the disease and the therapeutic management, spirometry, DLCO examination and native thoraco-pulmonary CT was performed, the patient presenting an important atopic field: multiallergy-environmental factors and iodine. After the establishment of the therapeutic step and the degree of severity, a complex, multimodal treatment was initiated, with a relatively good evolution and prognosis, provided the patient's compliance. [ABSTRACT FROM AUTHOR]

Background: The hospitals of the Saint Alphonsus Health System (SAHS) have implemented a metered dose inhaler (MDI) to nebulization therapeutic interchange program in which all orders for albuterol/ipratropium and inhaled corticosteroid/long-acting beta agonists (ICS/LABA) MDIs are therapeutically interchanged to nebulizers by pharmacy. Objectives: The primary outcome measure is to assess the percent of albuterol/ipratropium and ICS/LABA inhalers therapeutically interchanged to nebulized solutions. Secondary outcomes include assessment of readmission rates, the percentage of patients discharged with the appropriate MDI, and a financial analysis of the implementation of the therapeutic interchange program. Methods: This retrospective observational cohort study was approved by the system's institutional review board and conducted between October 15, 2019, and February 15, 2020. Adult patients with history of asthma or COPD admitted to one of the SAHS hosptials with an order placed for ipratropium/albuterol, fluticasone/salmeterol, mometasone/formoterol, or budesonide/formoterol MDIs were eligible for inclusion. Patients were excluded if they were presumed to have or tested positive for COVID-19. Results: Therapeutic interchanges were successfully completed in 94.3% of the orders included in this evaluation. Discharge discrepancies occurred in 14.3% of orders assessed. No correlation was found between discharge discrepancies and 30-day readmissions. The MDI to nebulized solution interchanges saved $13,908.16 in medication cost in the sample population. Conclusion: The first phase of implementing the SAHS inhaler to nebulizer therapeutic interchange program was operationally and clinically successful. The program is projected to continue to reduce medication waste and provide cost savings for the health system. [ABSTRACT FROM AUTHOR]

Acute bronchiolitis is a leading cause of hospitalization in infants. In this retrospective study, 645 patients with acute bronchiolitis diagnosed as respiratory syncytial virus (RSV; n = 538) or human metapneumovirus (HMPV; n = 107) were compared in terms of demographic, clinical, and laboratory findings. The HMPV patients presented later in the winter, were older (20 vs 7.55 months; P <.001)), had higher levels of C-reactive protein (4.55 vs 3.03 mg/dL; P =.007), and a higher prevalence of complications (43.9% vs 32.7%; P =.03). This study highlights the similarities and differences between these 2 common respiratory viral pathogens and shows that HMPV has a slightly more severe disease course than RSV. These findings can help guide approaches to these 2 common viruses that cause bronchiolitis. [ABSTRACT FROM AUTHOR]

Purpose: Patients with mastocytosis have an increased risk of anaphylaxis during surgical procedures with general anesthesia. Therefore, we reviewed the anesthesia course of a large cohort of patients with mastocytosis. Methods: We retrospectively reviewed adult and pediatric patients with mastocytosis who underwent surgical procedures with general anesthesia at Mayo Clinic from January 1, 2000, through June 30, 2021. We also included any procedures with general anesthesia that occurred during the 3-year period preceding mastocytosis diagnosis and designated the patients who underwent these procedures as having an unknown diagnosis at the time of their surgical procedure. We analyzed whether patients received chronic antimediator treatment for mastocytosis and/or prophylactic medications before the procedures. We also determined whether medications indicative of mastocytosis-related adverse events were intraoperatively administered. Results: We identified 113 patients who underwent 219 procedures during the study period; 25 procedures were performed before mastocytosis diagnosis. Of 194 procedures in patients with known mastocytosis, patients received chronic antimediator therapy and/or perioperative prophylactic medications for 178 (91.8%) procedures. Among these procedures, 10 were potentially complicated by mast cell activation, which was inferred from administration of inhaled albuterol (n = 3) or intravenous diphenhydramine (n = 8). In addition, there was only one case of intraoperative anaphylaxis which occurred in a patient who underwent anesthesia before mastocytosis diagnosis and therefore did not receive prophylaxis. Conclusion: Intraoperative anaphylaxis can be the first presenting sign of mastocytosis. Patients with mastocytosis who received chronic antimediator therapy and/or preoperative prophylactic medications had an uneventful surgical course. [ABSTRACT FROM AUTHOR]

Hyperkalemia is a common electrolyte abnormality frequently complicated with chronic kidney disease. By injecting potassium chloride (KCl) solutions intravenously into bullfrogs, we reproduced typical electrocardiogram (ECG) abnormalities of hyperkalemia in the frog hearts, such as the peaked T waves and the widening of QRS complexes. Simultaneous recordings of cardiac action potentials showed morphological changes that synchronized with those of ECG. After 100 mM KCl injection, the widened QRS complexes continued for a while and gradually restored to their baseline widths. However, pre-treatment with sodium bicarbonate or salbutamol, which directly or indirectly stimulates Na+/K+-ATPase activity, significantly facilitated the recovery from the widened QRS duration, indicating the transcellular movement of potassium ions from the extracellular fluid into the intracellular stores. [ABSTRACT FROM AUTHOR]