Change in Oxygen Consumption Following Inhalation of Albuterol in Comparison with Levalbuterol in Healthy Adult Volunteers.

BACKGROUND: Albuterol is the most commonly used ß agonist to treat reversible lower airway obstruction. Albuterol contains a racemic mixture of two enantiomers. Levalbuterol contains the single R form enantiomer. Levalbuterol is frequently prescribed to limit cardiovascular toxicity. OBJECTIVE: We examined changes in oxygen consumption (V'O2) and heart rate (HR) following administration of albuterol and levalbuterol. METHODS: This is a prospective, randomized, single-blinded, controlled study of healthy adult volunteers. Subjects separately received albuterol (5 mg) and levalbuterol (2.5 mg) aerosolized over 15 min. V'O2 and vital signs were measured before the medications and 5, 10, 20, 40, and 60 min after. RESULTS: We enrolled 24 volunteers with a median age of 32 years. Compared to baseline, there was a significant maximum increase in V'O2 following administration of both albuterol (median 17% (1, 3 IQR 9, 43%) p < 0.001) and levalbuterol (median 23% (1, 3 IQR 10, 32%) p < 0.001). There was no significant difference between the maximum increase in V'O2 following administration of albuterol compared to levalbuterol (p = 0.57). Compared to baseline, there was a significant maximal increase in HR with both albuterol (median 30% (1, 3 IQR 19, 43%) p < 0.001) and levalbuterol (median 23% (1, 3 IQR 19, 31%) p < 0.001). There was a statistically significant greater increase in maximal HR following administration of albuterol as compared to levalbuterol (p = 0.009). CONCLUSION: Albuterol and levalbuterol both cause a significant increase in V'O2 and HR. There was no significant difference between albuterol and levalbuterol regarding the maximum increase in V'O2. There was a statistically significant but likely clinically insignificant difference in maximum increase in HR in patients with adequate oxygen delivery when comparing albuterol to levalbuterol.

Clinical outcomes of levalbuterol versus racemic albuterol in pediatric patients with asthma: Propensity score matching approach in a medicaid population.

OBJECTIVE: Racemic albuterol and levalbuterol are used to treat acute episodes of asthma. The main objective of this study was to compare levalbuterol therapy to albuterol therapy on incidence rates of subsequent emergency department (ED) visits and hospitalizations. METHOD: We conducted a retrospective cohort study of asthmatic children who had pharmacy refills for levalbuterol/albuterol in the South Carolina Medicaid database in 2002-2011. Children receiving levalbuterol were matched to those receiving albuterol using propensity score matching technique. For ED visits and separately for hospitalizations, multivariable negative binomial regression was used to estimate the two group-specific incidence rates and the incidence rate ratio (IRR). RESULTS: A total of 8,172 asthmatic patients aged 2-18 years were identified in the South Carolina Medicaid database. During the 12-month follow-up period, the levalbuterol group had fewer asthma-related ED visits and hospitalizations: 939 (11.49%) children had asthma-related ED visits (levalbuterol: 8.76%; albuterol: 14.21%), and 89 (1.09%) children had asthma-related hospitalizations (levalbuterol: 1.07%; albuterol: 1.12%). Comparing the levalbuterol group to the albuterol group, the adjusted IRR estimate was 0.57 (95% confidence interval [CI], 0.49-0.65) for of asthma-related ED visits, and 0.93 (95%CI, 0.99-1.63) for hospitalizations. Children filling levalbuterol also had a lower IRR of all-cause ED visit (0.88; 95%CI, 0.82-0.95), but similar IRR of all-cause hospitalizations (1.08; 95%CI, 0.82-1.42). CONCLUSION: This observational study of children aged 2-18 demonstrated levalbuterol prescription fills were associated with reduced ED visits, but not hospitalizations. Additional research may be necessary to assess this association. Pediatr Pulmonol. 2017;52:516-523. © 2016 Wiley Periodicals, Inc.

Efficacy of Inhaled Levalbuterol Compared to Albuterol in Horses with Recurrent Airway Obstruction.

BACKGROUND: The (R)-enantiomer of racemic albuterol (levalbuterol) has bronchodilatory properties whereas the (S)-enantiomer causes adverse effects in human airways, animal models, and isolated equine bronchi. Levalbuterol is commercially available and improves pulmonary function of asthmatic patients with a longer duration of effect than albuterol. OBJECTIVE: To determine the dose at which inhaled levalbuterol produces maximal bronchodilatory effect (EDmax) and determine its duration of action in recurrent airway obstruction (RAO)-affected horses in comparison to racemic albuterol. ANIMALS: Nine horses with inducible and reversible RAO. METHODS: Randomized, crossover trial. Horses were challenged with moldy hay to induce airway obstruction. Horses were treated with nebulized albuterol or levalbuterol chosen randomly. Pulmonary function testing (PFT) was measured before and for up to 3 hours after bronchodilatation challenge. Maximum change in transpulmonary pressure (DPmax ) was measured to assess the dose effect and duration of action of each drug. After a 24 hours washout period, the bronchodilatation challenge was repeated with the second bronchodilator. RESULTS: The duration of effect was 60 minutes for albuterol and 120 minutes for levalbuterol. The dose of bronchodilator EDmax was not significantly different between albuterol and levalbuterol (EDmax = 125.0 [125-125 µg] and EDmax = 188 [125-188 µg] respectively; P = .068). The magnitude of bronchodilatation was not significantly different between the 2 treatments (61.1 and 59.9% decrease in DPmax for albuterol and levalbuterol respectively; P = .86). CONCLUSIONS AND CLINICAL IMPORTANCE: Levalbuterol is as effective a bronchodilator as albuterol; although levalbuterol lasts twice as long as albuterol, its duration of action is still too short to make it practical for RAO treatment.

Usefulness Of Glucocorticoids In The Management Of Foreign Body Aspiration.

Foreign body aspiration can be a life-threatening emergency. An aspirated solid or semi-solid object may lodge in the larynx, trachea or other breathing airways. If the object is large enough to cause nearly complete obstruction of the airway, asphyxia may rapidly cause death. We report a 19-year old man admitted with right lower lobe pneumonia who spontaneously expelled a foreign body, one day after admission and glucocorticoids administration. Glucocorticoids should be considered in foreign body aspiration management because improvement of the inflammatory reaction may facilitate expontaneous expulsion or foreign body extraction

Repeated ß2-adrenergic receptor agonist therapy attenuates the response to rescue bronchodilation in a hyperoxic newborn mouse model.

BACKGROUND: Preterm infants with neonatal lung injury are prone to wheezing and are often treated with ß2-adrenergic receptor (ß-AR) agonists although the benefits of ß-AR agonists may be lost with chronic use. OBJECTIVE: To investigate if repeated ß-AR agonist exposure downregulates ß-ARs in the immature lung resulting in a decreased response to bronchodilator rescue and whether hyperoxic exposure aggravates this response. METHODS: Newborn mice were raised for 21 days in 60 or 21% oxygen and received daily aerosols of formoterol or saline. Respiratory system resistance (Rrs) and compliance (Crs) were measured in response to methacholine challenge and rescue bronchodilation with levalbuterol. Western blot analysis quantified the relative amount of lung ß-ARs. RESULTS: Hyperoxia increased the airway reactivity to methacholine. Animals raised in hyperoxia that received daily formoterol were most sensitive to methacholine and exhibited a blunted response to levalbuterol bronchodilation. Hyperoxia-exposed animals receiving daily formoterol versus saline showed a significant decrease in the relative amount of lung ß-ARs. CONCLUSIONS: In this hyperoxia-exposed neonatal mouse model, repeated ß-AR agonist treatments increased the airway reactivity and attenuated the response to a rescue bronchodilator. The blunted bronchodilator response could be explained by a reduced quantity of lung ß-ARs. Our findings may account for the time-dependent decrease in the therapeutic benefit of ß-AR agonists in preterm infants with neonatal lung injury, which may have clinical consequences for patients already prone to airway hyperreactivity.

Hospital readmissions following initiation of nebulized arformoterol tartrate or nebulized short-acting beta-agonists among inpatients treated for COPD.

BACKGROUND: Inpatient admissions for chronic obstructive pulmonary disease (COPD) represent a significant economic burden, accounting for over half of direct medical costs. Reducing 30-day readmissions could save health care resources while improving patient care. Recently, the Patient Protection and Affordable Care Act authorized reduced Medicare payments to hospitals with excess readmissions for acute myocardial infarction, heart failure, and pneumonia. Starting in October 2014, hospitals will also be penalized for excess COPD readmissions. This retrospective database study investigated whether use of arformoterol, a nebulized long-acting beta agonist, during an inpatient admission, had different 30-day all-cause readmission rates compared with treatment using nebulized short-acting beta agonists (SABAs, albuterol, or levalbuterol). METHODS: A US nationally representative hospital database was used to study adults aged ≥40 years, discharged between January, 2006 and March, 2010, and with a diagnosis of COPD. Patients receiving arformoterol on ≥80% of days following treatment initiation were compared with patients receiving a nebulized SABA during hospitalization. Arformoterol and nebulized SABA patients were matched (1:2) for age, sex, severity of inpatient admission, and primary/secondary COPD diagnosis. Logistic regression compared the odds of readmission while adjusting for age, sex, race, admission type, severity, primary/secondary diagnosis, other respiratory medication use, respiratory therapy use, oxygen use, hospital size, and teaching status. RESULTS: This retrospective study compared 812 arformoterol patients and 1,651 nebulized SABA patients who were discharged from their initial COPD hospital admission. An intensive care unit stay was more common among arformoterol patients (32.1% versus 18.4%, P<0.001), suggesting more severe symptoms during the initial admission. The observed readmission rate was significantly lower for arformoterol patients than for nebulized SABA patients (8.7% versus 11.9%, P=0.017), as were the adjusted odds of readmission (odds ratio 0.69, 95% confidence interval 0.51-0.92). CONCLUSION: All-cause 30-day readmission rates were significantly lower for arformoterol patients than nebulized SABA patients, both before and after adjusting for patient and hospital characteristics.