Albuterol-budesonide fixed-dose combination rescue inhaler for asthma: a plain language summary of the MANDALA study.

What is this summary about?This summary describes the results of a clinical study called MANDALA that was published in the New England Journal of Medicine in 2022. In the MANDALA study, researchers looked at a new asthma rescue inhaler that contains both albuterol and budesonide in a single inhaler (known as albuterol-budesonide, AIRSUPRA™). This summary describes the results for people aged 18 yearsand older who took part in the study.

Reducing short-acting beta-agonist use in asthma: Impact of national incentives on prescribing practices in England and the findings from SENTINEL Plus early adopter sites.

Short-acting beta-agonist (SABA) over-use in asthma is harmful for patients and the environment. The Investment and Impact Fund (IIF) 2022/2023 financially rewarded English primary care networks that achieved specific targets, including reducing SABA over-use (RESP-02) and lowering the mean carbon footprint per salbutamol inhaler prescribed (ES-02). SENTINEL Plus is a co-designed quality improvement package that aims to improve asthma outcomes and reduce asthma's environmental impact by addressing SABA over-use. We investigated the impact of (i) the IIF incentives and (ii) SENTINEL Plus implementation on asthma prescribing. Using Openprescribing.net data, we demonstrate that IIF 2022-2023 had no significant impact on the total number of SABA prescribed in England (25,927,252 during 12-months pre- and 25,885,213 12-months post-IIF; 0.16% decrease; p=NS), but lower carbon footprint SABA inhaler use increased (Salamol™ prescribing increased from 5.1% to 19% of SABA prescriptions, p < 0.01). In contrast, SENTINEL Plus sites significantly reduced SABA prescribing post-implementation (5.43% decrease, p < 0.05).

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

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

The effect of salbutamol sulphate inhalation (an anti-asthmatic medication) on the surfaces of orthodontic Archwires.

OBJECTIVES: This study aimed to compare the surface roughness and friction of different orthodontic archwires after exposure to salbutamol sulphate inhalation, an anti-asthmatic medication. METHODS: Orthodontic archwires (stainless-steel [StSt], nickel-titanium [NiTi], beta-titanium [ß-Ti], and copper-NiTi [Cu-NiTi]) were equally divided into two groups. The exposed groups were subjected to 20 mg salbutamol sulphate for 21 days and kept in artificial saliva. The control groups were only kept in artificial saliva. Surface changes were visualized using scanning electron microscopy (SEM). The average surface roughness (Ra) was evaluated using atomic force microscopy (AFM), and friction resistance forces were assessed using a universal testing machine. Statistical analyses were performed using t-tests and ANOVA followed by post hoc tests. RESULTS: Salbutamol sulphate did not change the surface roughness of StSt and NiTi archwires (p > .05). However, the change in the surfaces of ß-Ti and Cu-NiTi archwires was significant (p < .001). The frictional forces of exposed StSt, NiTi, and Cu-NiTi archwires did not change (p > .05). However, the frictional forces of ß-Ti archwires increased significantly after exposure to salbutamol sulphate (p = .021). Brushing with fluoride after exposure to salbutamol sulphate increased the frictional forces of ß-Ti only (p = .002). CONCLUSIONS: Salbutamol sulphate inhalation significantly affected the surface texture of ß-Ti and Cu-NiTi orthodontic archwires and increased the friction of ß-Ti archwires. These deteriorating effects were not detected on the surface of StSt and NiTi archwires. Therefore, we suggest that ß-Ti and copper titanium archwires should be used cautiously in individuals under salbutamol sulphate inhalation treatment.

Effects of R-salbutamol on the inflammatory response and acute lung injury in endotoxemic mice.

Salbutamol, which consists of an R-isomer and S-isomer, is an effective and widely used ß2 adrenoreceptor agonist that may possess anti-inflammatory properties in addition to its bronchodilator activity. Whether the salbutamol R-isomer has advantages over its racemic mixture and effectiveness in treating endotoxemia and endotoxin-induced lung injury has not been well studied. In this study, we investigated the preventive and therapeutic effects of R-salbutamol (R-sal), S-salbutamol (S-sal), and their racemic mixture (Rac-sal) on a mouse model of lipopolysaccharide (LPS)-induced endotoxemia. Dexamethasone (Dex) was used for comparison. The results showed that R-sal markedly improved the 7-day survival rate of endotoxic mice when administered before and after LPS treatment. Dex was toxic and accelerated the death of endotoxic mice when administered before LPS injection. Histological examination of the lungs revealed that the LPS challenge resulted in acute lung damage, including inflammatory cell infiltration, thickened alveolar septa, and congestion. R-sal pre-treatment effectively inhibited these changes, accompanied by markedly reduced lung myeloperoxidase levels, serum cytokine levels, and lactate release, significant restoration of lymphocyte count, and reduction of monocyte count. This may have occurred through inhibition of M1 macrophage inflammatory responses by enhancement of ß-arrestin2 expression and suppression of NF-κB activation. Rac-sal exhibited diminished effects compared to that of R-sal, while S-sal showed enhanced release of some inflammatory cytokines. In addition, R-sal pre-treatment showed a better improvement in prognostic pulmonary function on day 4 compared to that by Rac-sal. Collectively, our results indicate the potential benefits of R-sal in regulating inflammatory responses to endotoxemia and endotoxin-induced lung injury.

Albuterol-Budesonide Fixed-Dose Combination Rescue Inhaler for Asthma.

BACKGROUND: As asthma symptoms worsen, patients typically rely on short-acting ß2-agonist (SABA) rescue therapy, but SABAs do not address worsening inflammation, which leaves patients at risk for severe asthma exacerbations. The use of a fixed-dose combination of albuterol and budesonide, as compared with albuterol alone, as rescue medication might reduce the risk of severe asthma exacerbation. METHODS: We conducted a multinational, phase 3, double-blind, randomized, event-driven trial to evaluate the efficacy and safety of albuterol-budesonide, as compared with albuterol alone, as rescue medication in patients with uncontrolled moderate-to-severe asthma who were receiving inhaled glucocorticoid-containing maintenance therapies, which were continued throughout the trial. Adults and adolescents (≥12 years of age) were randomly assigned in a 1:1:1 ratio to one of three trial groups: a fixed-dose combination of 180 µg of albuterol and 160 µg of budesonide (with each dose consisting of two actuations of 90 µg and 80 µg, respectively [the higher-dose combination group]), a fixed-dose combination of 180 µg of albuterol and 80 µg of budesonide (with each dose consisting of two actuations of 90 µg and 40 µg, respectively [the lower-dose combination group]), or 180 µg of albuterol (with each dose consisting of two actuations of 90 µg [the albuterol-alone group]). Children 4 to 11 years of age were randomly assigned to only the lower-dose combination group or the albuterol-alone group. The primary efficacy end point was the first event of severe asthma exacerbation in a time-to-event analysis, which was performed in the intention-to-treat population. RESULTS: A total of 3132 patients underwent randomization, among whom 97% were 12 years of age or older. The risk of severe asthma exacerbation was significantly lower, by 26%, in the higher-dose combination group than in the albuterol-alone group (hazard ratio, 0.74; 95% confidence interval [CI], 0.62 to 0.89; P = 0.001). The hazard ratio in the lower-dose combination group, as compared with the albuterol-alone group, was 0.84 (95% CI, 0.71 to 1.00; P = 0.052). The incidence of adverse events was similar in the three trial groups. CONCLUSIONS: The risk of severe asthma exacerbation was significantly lower with as-needed use of a fixed-dose combination of 180 µg of albuterol and 160 µg of budesonide than with as-needed use of albuterol alone among patients with uncontrolled moderate-to-severe asthma who were receiving a wide range of inhaled glucocorticoid-containing maintenance therapies. (Funded by Avillion; MANDALA ClinicalTrials.gov number, NCT03769090.).

Salbutamol Increases Leg Glucose Uptake and Metabolic Rate but not Muscle Glycogen Resynthesis in Recovery From Exercise.

CONTEXT: Exercise blunts the effect of beta2-agonists on peripheral glucose uptake and energy expenditure. Whether such attenuation extends into recovery is unknown. OBJECTIVE: To examine the effect of a beta2-agonist on leg glucose uptake and metabolic rate in recovery from exercise. METHODS: Using leg arteriovenous balance technique and analyses of thigh muscle biopsies, we investigated the effect of a beta2-agonist (24 mg of oral salbutamol) vs placebo on leg glucose, lactate, and oxygen exchange before and during quadriceps exercise, and 0.5 to 5 hours in recovery from quadriceps exercise, as well as on muscle glycogen resynthesis and activity in recovery. Twelve healthy, lean, young men participated. RESULTS: Before exercise, leg glucose uptake was 0.42 ±â€…0.12 and 0.20 ±â€…0.02 mmol × min-1 (mean ±â€…SD) for salbutamol and placebo (P = .06), respectively, while leg oxygen consumption was around 2-fold higher (P < .01) for salbutamol than for placebo (25 ±â€…3 vs 14 ±â€…1 mL × min-1). No treatment differences were observed in leg glucose uptake, lactate release, and oxygen consumption during exercise. But in recovery, cumulated leg glucose uptake, lactate release, and oxygen consumption was 21 mmol (95% CI 18-24, P = .018), 19 mmol (95% CI 16-23, P < .01), and 1.8 L (95% CI 1.6-2.0, P < .01) higher for salbutamol than for placebo, respectively. Muscle glycogen content was around 30% lower (P < .01) for salbutamol than for placebo in recovery, whereas no treatment differences were observed in muscle glycogen resynthesis or glycogen synthase activity. CONCLUSION: Exercise blunts the effect of beta2-agonist salbutamol on leg glucose uptake, but this attenuation diminishes in recovery. Salbutamol increases leg lactate release in recovery, which may relate to glycolytic trafficking due to excessive myocellular glucose uptake.

Short- and long-term effects of fluticasone furoate/vilanterol in exercising asthmatic adolescents: A randomized and open label trial.

PURPOSE: Relvar® (fluticasone furoate [FF]/vilanterol [VI]) is a once-daily inhaler with bronchodilator effect lasting 24 h. Our aim was to investigate the short- and long-term effects of FF/VI on exercise-induced asthma (EIA) in adolescents. METHODS: Ninety-three adolescent asthmatics aged 12-18 years were referred for evaluation of EIA. Following a positive exercise challenge test (ECT), 22/44 were allocated to a single administration of salbutamol (400 µg) and 22/44 to FF/VI (92/22 µg) in a double-blind method. Thirty-five subjects were reassessed by repeat ECT 30-60 days of FF/VI. RESULTS: Median FEV1 change post-ECT at baseline was -22.8% predicted (interquartile range [IQR] -26.1 and -18.0) for salbutamol and -21.0 (IQR -30.7 and -16.8) for FF/VI. Following bronchodilator, FEV1 improved similarly in both groups. Repeat ECT following 30-60 days of FF/VI resulted in negative ECT in 33/35 subjects; the median decrease in FEV1 of these 35 subjects was 22.6% predicted (IQR 29-18) before, and 4.6% predicted (IQR 8.7-2.5) after 30-60 days of FF/VI treatment (p < 0.0001). CONCLUSIONS: FF/VI is effective in reversing EIA after 15 min in adolescents and in protecting EIA after 30-60 days in adolescents. Larger studies are needed to assess the effect of FF/VI on EIA.

Superhydrophobic Surface for Enhancing the Bioavailability of Salbutamol Sulfate from Cross-Linked Microspheres: Formulation, Characterization, and in vivo Evaluation.

INTRODUCTION: The aim of the work was to formulate salbutamol sulfate (SB) microspheres by using superhydrophobic surface (SHS) under different processing factors for improving its encapsulation efficiency, controling its release rate, and hence enhancing its bioavailability. METHODS: Cross-linked microspheres of chitosan (CN) and carrageenan (KN) were made on a SHS under a glutaraldehyde-saturated atmosphere. The formulations were designed and optimized based on 42 factorial design. Percentage encapsulation efficiency (%EE), particle size, swelling ratio, and in vitro release rate were characterized, and the in vivo performance of optimized formula was investigated in beagle dogs. RESULTS: The results showed that the prepared microspheres have a high %EE (97.11±0.78%) for F13. The swelling ratio was 4.2 at the end of the 8 hours for the optimized formula, and the in vitro release rate was controlled for 12 hours. In vivo study verified that there was a 1.61-fold enhancement in SB bioavailability from optimized formula (F13) compared to market tablet. CONCLUSION: The study suggested that microspheres prepared from CN/KN crosslinking on an SHS using glutaraldehyde atmosphere is a promising technique that can encapsulate and sustain the release of water-soluble drugs such as SB in addition to improving its in vivo pharmacokinetic profile.

Association Between Intravenous Magnesium Therapy in the Emergency Department and Subsequent Hospitalization Among Pediatric Patients With Refractory Acute Asthma: Secondary Analysis of a Randomized Clinical Trial.

Importance: Despite guidelines recommending administration of intravenous (IV) magnesium sulfate for refractory pediatric asthma, the number of asthma-related hospitalizations has remained stable, and IV magnesium therapy is independently associated with hospitalization. Objective: To examine the association between IV magnesium therapy administered in the emergency department (ED) and subsequent hospitalization among pediatric patients with refractory acute asthma after adjustment for patient-level variables. Design, Setting, and Participants: This post hoc secondary analysis of a double-blind randomized clinical trial of children with acute asthma treated from September 26, 2011, to November 19, 2019, at 7 Canadian tertiary care pediatric EDs was conducted between September and November 2020. In the randomized clinical trial, 816 otherwise healthy children aged 2 to 17 years with Pediatric Respiratory Assessment Measure (PRAM) scores of 5 points or higher after initial therapy with systemic corticosteroids and inhaled albuterol with ipratropium bromide were randomly assigned to 3 nebulized treatments of albuterol plus either magnesium sulfate or 5.5% saline placebo. Exposures: Intravenous magnesium sulfate therapy (40-75 mg/kg). Main Outcomes and Measures: The association between IV magnesium therapy in the ED and subsequent hospitalization for asthma was assessed using multivariable logistic regression analysis. Analyses were adjusted for year epoch at enrollment, receipt of IV magnesium, PRAM score after initial therapy and at ED disposition, age, sex, duration of respiratory distress, previous intensive care unit admission for asthma, hospitalizations for asthma within the past year, atopy, and receipt of oral corticosteroids within 48 hours before arrival in the ED, nebulized magnesium, and additional albuterol after inhaled magnesium or placebo, with site as a random effect. Results: Among the 816 participants, the median age was 5 years (interquartile range, 3-7 years), 517 (63.4%) were boys, and 364 (44.6%) were hospitalized. A total of 215 children (26.3%) received IV magnesium, and 190 (88.4%) of these children were hospitalized compared with 174 of 601 children (29.0%) who did not receive IV magnesium. Multivariable factors associated with hospitalization were IV magnesium receipt from 2011 to 2016 (odds ratio [OR], 22.67; 95% CI, 6.26-82.06; P < .001) and from 2017 to 2019 (OR, 4.19; 95% CI, 1.99-8.86; P < .001), use of additional albuterol (OR, 5.94; 95% CI, 3.52-10.01; P < .001), and increase in PRAM score at disposition (per 1-U increase: OR, 2.24; 95% CI, 1.89-2.65; P < .001). In children with a disposition PRAM score of 3 or lower, receipt of IV magnesium therapy was associated with hospitalization (OR, 8.52; 95% CI, 2.96-24.41; P < .001). Conclusions and Relevance: After adjustment for patient-level characteristics, receipt of IV magnesium therapy after initial asthma treatment in the ED was associated with subsequent hospitalization. This association also existed among children with mild asthma at ED disposition. Evidence of a benefit of IV magnesium regarding hospitalization may clarify its use in the treatment of refractory pediatric asthma. Trial registration: ClinicalTrials.gov: NCT01429415.

Dose-Ranging and Cumulative Dose Studies of Albuterol Sulfate MDI in Co-Suspension Delivery™ Technology (AS MDI; PT007) in Patients with Asthma: the ASPEN and ANTORA Trials.

BACKGROUND AND OBJECTIVES: Co-suspension Delivery™ Technology has been developed for the administration of albuterol sulfate pressurised inhalation suspension via metered-dose inhaler (AS MDI, PT007). We assessed the efficacy and safety of AS MDI versus Proventil® in order to determine the optimal dose of AS MDI to take to Phase III clinical trials. METHODS: ASPEN (NCT03371459) and ANTORA (NCT03364608) were Phase II, randomised, crossover, multicentre studies of AS MDI versus Proventil® in patients with persistent asthma. In ASPEN, 46 patients received cumulative-dose treatments (90 µg/inhalation using 1 + 1 + 2 + 4 + 8 inhalations at 30-minute intervals) in 1 of 2 possible sequences: AS MDI/Proventil or Proventil/AS MDI. In ANTORA, 86 patients were randomised to one of 10 treatment sequences of AS MDI (90 µg or 180 µg), placebo MDI, or Proventil (90 µg or 180 µg). The primary endpoints were baseline-adjusted forced expiratory volume in 1 second (FEV1) 30 minutes after each cumulative dose (ASPEN) and change from baseline in FEV1 area under the curve from 0 to 6 h (ANTORA). Safety was assessed in both studies. RESULTS: In ASPEN, AS MDI was equivalent to Proventil (within pre-specified bounds of ± 200 mL) following cumulative doses of albuterol up to 1440 µg for the primary endpoint. In ANTORA, 90 µg and 180 µg doses of AS MDI and Proventil were significantly superior to placebo MDI (p < 0.0001), and AS MDI was non-inferior to Proventil at both doses, based on a margin of 100 mL. No new safety concerns were identified. CONCLUSION: The effects of albuterol delivered via AS MDI and Proventil on bronchodilation were equivalent, supporting the selection of AS MDI 180 µg to be taken into Phase III clinical trials, either alone or in combination with an inhaled corticosteroid. TRIAL REGISTRATION NUMBER: ASPEN (NCT03371459); Date of registration: 29/12/2017. ANTORA (NCT03364608); Date of registration: 15/12/2017.

Hypoxia-mediated alterations in pulmonary surfactant protein expressions: Beneficial effects of quercetin prophylaxis.

We have compared the prophylactic efficacies of quercetin and salbutamol in preventing pulmonary surfactants oxidation under hypoxia. Male SD rats supplemented orally with quercetin (50 mg/Kg BW) and salbutamol (2 mg/Kg BW) were exposed to hypobaric hypoxia (7,620 m for 6 h). Hypoxia-mediated elevation in oxidative stress, inflammation, and extravasations of LDH & albumin content in BALF of rats were assessed. Western blotting and mRNA studies determined the differential expressions of Nrf-2, HO-1, and associated surfactant proteins (SP-A, SP-B, SP-C, & SP-D) in rat lungs. Later, the lung configuration under hypoxia was assessed histopathologically. Quercetin and salbutamol pretreatment considerably restored the expressions of Nrf-2, HO-1, and surfactant proteins to normal by attenuating the increase in oxidative stress, inflammation, and extravasations of plasma proteins in the animals under hypoxia. The histopathology has also evidenced the protective effect of quercetin in retaining normal lung architecture under hypoxia over salbutamol. The present study indicates the effectiveness of quercetin prophylaxis in preventing pulmonary surfactants oxidation under hypoxia over salbutamol.

Effects of salbutamol on the kinetics of sevoflurane and the occurrence of early postoperative pulmonary complications in patients with mild-to-moderate chronic obstructive pulmonary disease: A randomized controlled study.

Bronchodilators dilate the bronchi and increase lung volumes, thereby improving respiratory physiology in patients with chronic obstructive pulmonary disease (COPD). However, their effects on sevoflurane kinetics remain unknown. We aimed to determine whether inhaled salbutamol affected the wash-in and wash-out kinetics of sevoflurane and the occurrence of early postoperative pulmonary complications (PPCs) in patients with COPD undergoing elective surgery. This randomized, placebo-controlled study included 63 consecutive patients with COPD allocated to the salbutamol (n = 30) and control groups (n = 33). The salbutamol group received salbutamol aerosol (2 puffs of ~200 µg) 30 min before anesthesia induction and 30 min before surgery completion. The control group received a placebo. Sevoflurane kinetics were determined by collecting end-tidal samples from the first breaths at 1, 2, 3, 4, 5, 7, 10, and 15 min before the surgery (wash-in) and after closing the vaporizer (wash-out). PPCs were recorded for 7 days. The salbutamol group had higher end-tidal to inhaled sevoflurane ratios (p<0.05, p<0.01) than the control group, from 3 to 10 min during the wash-in period, but no significant differences were observed during the wash-out period. The arterial partial pressure of oxygen to the fraction of inhaled oxygen was significantly higher in the salbutamol group at 30 (320.3±17.6 vs. 291.5±29.6 mmHg; p = 0.033) and 60 min (327.8±32.3 vs. 309.2±30.5 mmHg; p = 0.003). The dead space to tidal volume ratios at 30 (20.5±6.4% vs. 26.3±6.0%, p = 0.042) and 60 min (19.6±5.1% vs. 24.8±5.5%, p = 0.007) and the incidence of bronchospasm (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.23-0.67, p = 0.023) and respiratory infiltration (OR 0.52, 95% CI, 0.40-0.65, p = 0.017) were lower in the salbutamol group. In patients with COPD, salbutamol accelerates the wash-in rate of sevoflurane and decreases the occurrence of postoperative bronchospasm and pulmonary infiltration within the first 7 days.

Performance of Low Air Volume Dry Powder Inhalers (LV-DPI) when Aerosolizing Excipient Enhanced Growth (EEG) Surfactant Powder Formulations.

Efficient delivery of dry powder aerosols dispersed with low volumes of air is challenging. This study aims to develop an efficient dry powder inhaler (DPI) capable of delivering spray-dried Survanta-EEG powders (3-10 mg) with a low volume (3 mL) of dispersion air. A series of iterative design modifications were made to a base low air volume actuated DPI. The modifications included the replacement of the original capsule chamber with an integral dose containment chamber, alteration of the entrainment air flow path through the device (from single-sided (SS) to straight through (ST)), change in the number of air inlet holes (from one to three), varying the outlet delivery tube length (45, 55, and 90 mm) and internal diameter (0.60, 0.89, and 1.17 mm). The modified devices were evaluated by determining the influence of the modifications and powder fill mass on aerosol performance of spray-dried Survanta-EEG powders. The optimal DPI was also evaluated for its ability to aerosolize a micronized powder. The optimized dose containment unit DPI had a 0.21 mL powder chamber, ST airflow path, three-0.60 mm air inlet holes, and 90 mm outlet delivery tube with 0.89 mm internal diameter. The powder dispersion characteristics of the optimal device were independent of fill mass with good powder emptying in one 3 mL actuation. At 10 mg fill mass, this device had an emitted mass of 5.3 mg with an aerosol Dv50 of 2.7 µm. After three 3 mL actuations, >85% of the spray-dried powder was emitted from the device. The emitted mass of the optimal device with micronized albuterol sulfate was >72% of the nominal fill mass of 10 mg in one 3 mL actuation. Design optimization produced a DPI capable of efficient performance with a dispersion air volume of 3 mL to aerosolize Survanta-EEG powders.

Elucidating the Effect of Fine Lactose Ratio on the Rheological Properties and Aerodynamic Behavior of Dry Powder for Inhalation.

Dry powder inhaler (DPI) is recognized as the first choice for lung diseases' treatment. However, it lacks a universal way for DPI formulation development. Fine lactose is commonly added in DPIs to improve delivery performance; however, the fine ratio-dependent mechanism is unclear. Therefore, the objective of this study is to explore the influence of fine lactose ratio on DPI powder properties and aerodynamic behavior, and the fine lactose ratio-dependent mechanism involved during powder fluidization and lung deposition. Here salbutamol sulfate was used as a model drug, Lactohale® 206 as coarse carrier, and Lactohale® 300 as fine component; the mixtures were prepared at 1% drug content, with fine content up to 20%. It was shown that with the fine addition, flowability of the mixtures was improved, interaction among particles was increased, and the presence of fines could help to improve DPI's aerosolization performance. When the fines added were less than 3%, the "active site" hypothesis played a leading role. When the added fines were over 3% but less than 10%, fluidization enhancement mechanism was more important. After the added fines reaching 10%, aggregate mechanism started to dominate. However, FPF cannot be further increased once the fines reached 20%. Moreover, the correlations between FPF and dynamic powder parameters were verified in ternary mixtures, and cohesion had a greater impact on FPF than that of flowability. In conclusion, adding lactose fines is an effective way to improve lung deposition of DPI, with the concrete mechanism lactose fine ratio dependent.

Managing respiratory emergencies at school: A county-wide stock inhaler program.

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.

Inhaled Albuterol Use and Impaired Lactate Clearance in Patients With Sepsis: A Retrospective Cohort Study.

BACKGROUND: Lactate clearance has become important in the management of sepsis. However, factors unrelated to sepsis-induced hyperlactatemia, including ß-2 adrenergic agonists, can interfere with lactate clearance. OBJECTIVES: To investigate the association of inhaled albuterol with lactate clearance in patients with sepsis. METHODS: This was a single-center retrospective cohort study. Adult patients with sepsis diagnosed in the emergency department from May 2015 to May 2016 with initial lactate levels >2 mmol/L and serial lactate measurements 2 to 6 hours apart were included. Patients were divided into 2 groups based on whether they received inhaled albuterol between lactate measurements. The primary end point was lactate clearance of 10%. Secondary end points included intensive care unit (ICU) consultation and in-hospital mortality. A multivariate logistic regression analysis was performed to assess the effect of inhaled albuterol on lactate clearance. RESULTS: Of 269 patients included, 58 (22%) received inhaled albuterol between lactate measurements. This group had a significantly higher prevalence of pulmonary disease and a lower initial lactate compared to those who did not receive inhaled albuterol. They had a significantly lower rate of lactate clearance (45% vs 77%, P < .001); however, ICU consultation (71% vs 57%, P = .066) and in-hospital mortality (19% vs 22%, P = .64) were not significantly different. A multivariate logistic regression analysis adjusting for age, sex, chronic kidney disease, cirrhosis, cancer, septic shock or severe sepsis, and the amount of intravenous fluids received showed that inhaled albuterol was independently associated with impaired lactate clearance (adjusted odds ratio: 0.26, 95% confidence interval: 0.14-0.50, P < .001). CONCLUSIONS: Inhaled albuterol in patients with sepsis was associated with impaired lactate clearance without an increase in ICU consultation or in-hospital mortality. Impaired lactate clearance in patients with sepsis who receive inhaled albuterol should be interpreted with caution.

Association of various weight-based doses of continuous albuterol on hospital length of stay.

Introduction: Continuous albuterol is a mainstay in management of pediatric status asthmaticus. While the National Heart Lung and Blood Institute Asthma Guidelines suggest 0.5 mg/kg/h as the recommended dosage, there is a paucity of evidence comparing different weight-based rates on hospital outcomes.Methods: Patients requiring continuous albuterol for asthma exacerbation from January 2015 to December 2016 were identified using ICD codes. The concentration of albuterol (5 mg/h-20 mg/h) and the duration of treatment were used to determine total albuterol administration. After dividing by patient weight, average weight-based doses were divided into equal quintiles. Unadjusted and length of stay adjusted for age, initial asthma severity score, and administration of magnesium were compared among the quintiles. The same multivariate analysis was used for duration of continuous albuterol.Results: Five hundred thirty-three hospitalizations for asthma were identified of which 289 received continuous albuterol. Weight-based dosage quintiles ranged from lowest (0.07-0.29 mg/kg/h) to the highest (>0.76-3.2 mg/kg/h). Baseline characteristics were similar aside from age, race, and magnesium administration. There was no difference in adjusted length of stay or adjusted duration of continuous albuterol therapy among the five quintiles.Conclusion: No optimal weight-based dose of continuous albuterol was found. Further investigation is needed to see if lower amounts of continuous albuterol may be as efficacious as higher doses. This could improve cost of status asthmaticus management and limit the number of adverse events associated with high exposure to continuous albuterol.

High frequency percussive ventilation as a rescue mode for refractory status asthmaticus - a case study.

INTRODUCTION: A severe asthma exacerbation is called status asthmaticus when symptoms worsen despite conventional medical treatment in the hospital. If arterial blood gas (ABG) values deteriorate and this is accompanied by respiratory muscle fatigue, the patient will require mechanical ventilation. However, mechanical ventilation of the severe asthmatic presents difficult challenges. CASE STUDY: We report on High Frequency Percussive Ventilation (HFPV) used along with continuous inhaled albuterol and neuromuscular blockade, as rescue therapy for a case of acute, severe asthma that was refractory to conventional treatment and conventional mechanical ventilation. RESULTS: This patient's arterial pH was 6.97 when we initiated HFPV, but ten hours post-intubation her ABG values normalized. She was successfully extubated six days later and discharged from ICU the following day. CONCLUSION: This case describes the successful use of HFPV for a status asthmaticus patient failing conventional mechanical ventilation. We have anecdotal evidence of other medical centers using HFPV for these patients but larger studies are needed to verify its efficacy.