Looking for Airways Periostin in Severe Asthma: Could It Be Useful for Clustering Type 2 Endotype? (Carroll)

Carpagnano GE, et al. Looking for Airways Periostin in Severe Asthma: Could It Be Useful for Clustering Type 2 Endotype? Chest. 2018 Nov;154(5):1083-1090.

BACKGROUND: Severe asthma is heterogeneous clinically and biologically and is often difficult to control. In particular, the type 2 (T2) immunity endotype of severe asthma is gaining increasing interest because it is susceptible to newly developed biologic treatments that can transform the quality of life of these patients. The aim of this study was to analyze periostin concentrations in the airways of patients with severe asthma, evaluating its role in clustering the T2 endotype.

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High-Dose Magnesium Sulfate Infusion for Severe Asthma in the Emergency Department: Efficacy Study. (Patel)

Irazuzta JE, et al. High-Dose Magnesium Sulfate Infusion for Severe Asthma in the Emergency Department: Efficacy Study. Pediatr Crit Care Med. 2016 Feb;17(2):e29-33.

OBJECTIVE: To assess the efficacy of a high-dose prolonged magnesium sulfate infusion in patients with severe, noninfectious-mediated asthma.

DESIGN: Prospective, randomized, open-label study.

SETTING: Twenty-nine-bed pediatric emergency department located in a children’s hospital in Asuncion, Paraguay.

PATIENTS: All patients of 6-16 years old who failed to improve after 2 hours of standard therapy for asthma.

INTERVENTIONS: Subjects were randomized to receive magnesium sulfate, 50 mg/kg over 1 hour (bolus) or high-dose prolonged magnesium sulfate infusion of 50 mg/kg/hr for 4 hours (max, 8.000 mg/4 hr). Patients were monitored for cardiorespiratory complications.

MEASUREMENTS AND MAIN RESULTS: Asthma severity was assessed via asthma scores and peak expiratory flow rates at 0-2-6 hours. The primary outcome was discharge to home at 24 hours. An analysis of the hospital length of stay and costs was a secondary outcome. Thirty-eight patients were enrolled, 19 in each group. The groups were of similar ages, past medical history of asthma, asthma score, and peak expiratory flow rate. There was a significant difference in the patients discharged at 24 hours: 47% in high-dose prolonged magnesium sulfate infusion (9/19) versus 10% (2/21) in the bolus group (p = 0.032) with an absolute risk reduction 37% (95% CI, 10-63) and a number needed to treat of 2.7 (95% CI, 1.6-9.5) to facilitate a discharge at or before 24 hours. The length of stay was shorter in the high-dose prolonged magnesium sulfate infusion group (mean ± SD in hr: high-dose prolonged magnesium sulfate infusion, 34.13 ± 19.54; bolus, 48.05 ± 18.72; p = 0.013; 95% CI, 1.3-26.5). The cost per patient in the high-dose prolonged magnesium sulfate infusion group was one third lower than the bolus group (mean ± SD: high-dose prolonged magnesium sulfate infusion, $603.16 ± 338.47; bolus, $834.37 ± 306.73; p < 0.016). There were no interventions or discontinuations of magnesium sulfate due to adverse events.

CONCLUSIONS: The early utilization of high-dose prolonged magnesium sulfate infusion (50 mg/kg/hr/4 hr), for non-infectious mediated asthma, expedites discharges from the emergency department with significant reduction in healthcare cost.

Albuterol administration is commonly associated with increases in serum lactate in asthmatics treated for acute exacerbation of asthma. (Fortenberry)

Lewis LM, Ferguson I, House SL, Aubuchon K, Schneider J, Johnson K, Matsuda K. Albuterol administration is commonly associated with increases in serum lactate in asthmatics treated for acute exacerbation of asthma. Chest. 2014 Jan; 145(1): 53–59.

BACKGROUND: Controversy exists surrounding the incidence and cause of hyperlactatemia during asthma exacerbations. We evaluate incidence, potential causes, and adverse events of hyperlactatemia in patients with acute asthma exacerbation.

METHODS: Sub-analysis of placebo subjects from a prospective, randomized trial evaluating an intravenous beta-adrenergic agonist in acute asthma exacerbation (clinicaltrials.gov identifier NCT00683449).Subjects had plasma albuterol, serum lactate and bicarbonate concentrations measured at baseline and 1.25 hours as well as dyspnea score and spirometry measured at baseline and hourly for 3 hours. All subjects had a therapeutic trial consisting of 5-15 mg of nebulized albuterol, 0.5-1 mg of nebulized ipratropium, and at least 50 mg of oral prednisone, or its equivalent prior to initiation of the study. Following randomization, subjects were treated with continued albuterol and intravenous magnesium at the discretion of their treating physician. Subjects were followed to admission or discharge with follow up at 24 hours and 1 week.

Results: 175 subjects were enrolled in the parent trial, 84 in the placebo group. 65 had complete data. Mean albuterol administration prior to baseline was 12.3mg (SD±5.3).Mean baseline lactate was 18.5mg/dL (SD±8.4) vs. 26.5mg/dL (SD±11.8) at 1.25 hours; p>0.001. 45 subjects (69.2%) had hyperlactatemia. Mean baseline bicarbonate was 22.6mEq/L (SD±2.9) vs. 21.9mEq/L (SD±4.0) at 1.25 hours; p=0.11.Plasma albuterol concentration correlated to lactate concentration (β coefficient=0.45; p<0.001), and maintained significant association after adjusting for asthma severity (β=0.41; p=0.001). Hyperlactatemia did not increase the risk of hospitalization/relapse (p=0.26), nor was it associated with lower %FEV1 at 3 hours (p=0.54).

CONCLUSION: Plasma albuterol was significantly correlated with serum lactate concentration, after adjusting for asthma severity. Hyperlactatemia was not associated with poorer pulmonary function as measured by 3-hour %FEV1, or increased hospitalization/relapse at one week.

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Corticosteroid therapy in critically ill pediatric asthmatic patients. (Carmean)

Pediatr Crit Care Med. 14(5), June 2013, p 467–470 PMID: 23628833

OBJECTIVES: IV corticosteroids are routinely prescribed to treat critically ill children with asthma. However, no specific dosing recommendations have been made for children admitted to the PICU. We aim to determine current asthma corticosteroid dosing preferences in PICUs within North America.

DESIGN: Cross-sectional, self-administered survey.

SETTING: North American PICUs.

SUBJECTS: Pediatric intensivists working in the United States and Canada.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: A total of 104 intensivists completed the survey. Of these, 70% worked in the United States, 67% attended in PICUs with at most 20 beds, and 79% had more than 10 years of PICU experience. The majority of asthmatics were admitted to PICUs based on clinical asthma examination/score or because the patient was receiving continuous albuterol. IV methylprednisolone is prescribed by the large majority of intensivists (96%). Of those who prescribe methylprednisolone, 66% use a starting dose of 4mg/kg/d, whereas 31% use a starting dose of 2mg/kg/d, and only 3% use 1mg/kg/d. The large majority of respondents (85%) use “clinical experience” as their rationale for their preferred dosage. In multivariate logistic regression analysis, only knowledge of the National Heart, Lung, and Blood Institute guidelines was an independent predictor of prescribing an initial corticosteroid dose of 4mg/kg/d (odds ratio, 3.69 [95% CI, 1.26-10.80]; p = 0.017). Country of practice, years of experience, and PICU size were not associated with corticosteroid dosing preference.

CONCLUSIONS: Most intensivists administer methylprednisolone to critically ill asthmatics at doses 2-4 times higher than recommended by the National Heart, Lung, and Blood Institute guidelines for hospitalized asthmatic children. The rationale for these decisions is likely multifactorial, but in the absence of evidence-based data, most of them cite clinical experience as their deciding factor. Future research is needed to determine the most appropriate corticosteroid dosage in this critically ill patient population.

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