Albuterol Metered-dose Inhaler Research Articles

Comparison of Systemic Exposure Between Epinephrine Delivered via Metered-Dose Inhalation and Intramuscular Injection.

Background: Primatene® MIST, an epinephrine metered-dose inhaler (MDI), has long been questioned by some medical professionals for asthma treatment despite having been approved by the Food and Drug Administration. One of the primary reasons for their concerns stemmed from potential cardiovascular complications following epinephrine administration. However, the majority of documented cardiovascular complications seemed to occur following the injection route of the epinephrine. The aim of this study was to evaluate the systemic exposure of epinephrine delivered through different administration routes and to understand its relationship with cardiovascular effects. Since albuterol inhalers are commonly recommended for asthma, albuterol was also studied as a comparator drug. Method: A randomized, evaluator-blinded, three-arm crossover study was conducted in 28 healthy adult subjects to compare the profiles of systemic exposure for epinephrine delivered by MDI versus epinephrine intramuscular (IM) injection and albuterol MDI. Serially sampled plasma epinephrine and albuterol levels were measured and compared between treatment groups. Safety was assessed by adverse events, serial vital signs, electrocardiograms (ECGs), and clinical laboratory tests obtained at each crossover dosing visit. Results: Systemic exogenous drug exposure for inhaled epinephrine MDI (39 pg/mL × hour) was ∼9 times lower than that of epinephrine IM (435 pg/mL × hour) and 122 times lower than that of albuterol MDI (3453 pg/mL × hour) after dose normalization. The Cmax in epinephrine MDI (345 pg/mL) was approximately half of that of epinephrine IM (816 pg/mL) and that of albuterol MDI (681 pg/mL). Plasma drug concentrations for epinephrine MDI dropped rapidly to baseline (∼0.6 hour), while epinephrine IM took ∼8 hours, and albuterol MDI required more than 24 hours. Epinephrine MDI and albuterol MDI resulted in minimal, clinically insignificant changes in vital signs and ECGs, whereas epinephrine IM led to mild transient increases in systolic blood pressure, heart rate, and corrected QT interval. Conclusion: Epinephrine MDI (Primatene MIST) had ∼9 times lower systemic drug exposure (SDE) than that of epinephrine IM and ∼122 times lower than that of albuterol MDI. The lower SDE of inhaled epinephrine also correlated with reassuring safety findings, with no significant cardiovascular adverse effects found, compared with transient effects seen after IM epinephrine. Clinical trial registration number: NCT04207840.

Metered-Dose Inhaler Versus Nebulizer Treatment for Acute Asthma Exacerbation: A Process Evaluation.

Background: The prevalence of childhood asthma in the United States is 6.5%. During the COVID-19 pandemic, a Federally Qualified Health Center (FQHC) implemented metered-dose inhalers (MDIs) with spacers instead of nebulized albuterol to reduce aerosolization of pathogens and reduce costs. Objective: The objective of the study is to assess the safety, efficacy, and efficiency of a change to the asthma exacerbation protocol at an urban FQHC. Methods: A retrospective chart review compared nebulized albuterol versus an MDI with a spacer in pediatric patients experiencing asthma exacerbation. The evaluation aimed to measure (a) the 30-day return to care in either the emergency department (ED) or clinic, (b) the total number of treatments administered, and (c) the documented use of an oral steroid with albuterol treatments. Results: Return to clinic was the only statistically significant variable. Zero MDI patients returned, whereas 61% of those nebulized returned within 30 days (p < .00001). Conclusions: Albuterol MDI with a spacer was more effective than a nebulizer in reducing follow-up visits to the clinic and was effective at reducing ED visits within 30 days. Implications for Nursing: Treating asthma exacerbations in the primary care clinic with an MDI is effective and reduces cost and airborne exposure.

Effect of MDI Actuation Timing on Inhalation Dosimetry in a Human Respiratory Tract Model.

Accurate knowledge of the delivery of locally acting drug products, such as metered-dose inhaler (MDI) formulations, to large and small airways is essential to develop reliable in vitro/in vivo correlations (IVIVCs). However, challenges exist in modeling MDI delivery, due to the highly transient multiscale spray formation, the large variability in actuation–inhalation coordination, and the complex lung networks. The objective of this study was to develop/validate a computational MDI-releasing-delivery model and to evaluate the device actuation effects on the dose distribution with the newly developed model. An integrated MDI–mouth–lung (G9) geometry was developed. An albuterol MDI with the chlorofluorocarbon propellant was simulated with polydisperse aerosol size distribution measured by laser light scatter and aerosol discharge velocity derived from measurements taken while using a phase Doppler anemometry. The highly transient, multiscale airflow and droplet dynamics were simulated by using large eddy simulation (LES) and Lagrangian tracking with sufficiently fine computation mesh. A high-speed camera imaging of the MDI plume formation was conducted and compared with LES predictions. The aerosol discharge velocity at the MDI orifice was reversely determined to be 40 m/s based on the phase Doppler anemometry (PDA) measurements at two different locations from the mouthpiece. The LES-predicted instantaneous vortex structures and corresponding spray clouds resembled each other. There are three phases of the MDI plume evolution (discharging, dispersion, and dispensing), each with distinct features regardless of the actuation time. Good agreement was achieved between the predicted and measured doses in both the device, mouth–throat, and lung. Concerning the device–patient coordination, delayed MDI actuation increased drug deposition in the mouth and reduced drug delivery to the lung. Firing MDI before inhalation was found to increase drug loss in the device; however, it also reduced mouth–throat loss and increased lung doses in both the central and peripheral regions.

A Survey of Provider-Reported Use and Perceived Effectiveness of Medications for Symptom Management in Telemedicine and Outpatient Visits for Mild COVID-19.

IntroductionMany patients with mild coronavirus disease 2019 (COVID-19) have symptoms requiring acute and follow-up care. The aims of this study were to assess (1) provider-reported use of medications and their perceived effectiveness and (2) degree of difficulty managing specific symptoms at episodic COVID-19 care sites and in a longitudinal monitoring program.MethodsWe sent an online survey to physicians, advanced practice providers, and registered nurses redeployed to COVID-19 care sites at an academic medical center from March to May 2020. We asked about the use of medications and perceived effectiveness of medications to treat symptoms of COVID-19 and the perceived challenge of symptom management. Comparison was made by provider type (episodic or longitudinal site of care).ResultsResponses from 64 providers were included. The most frequently used medications were acetaminophen (87.1% of respondents), benzonatate (83.9%), and albuterol metered dose inhalers (MDI) (80.6%). Therapies for lower respiratory tract symptoms were reported as more commonly used by longitudinal follow-up providers compared to episodic providers including guaifenesin (90.6% vs 60.0%, p = 0.007), benzonatate (93.8% vs 73.3%, p = 0.04), nebulized albuterol for patients with asthma (75.0% vs 43.3%, p = 0.019), and albuterol MDIs for patients without asthma (90.6% vs 66.7%, p = 0.029). Medications found to have the highest perceived efficacy by respondents using the therapy (> 80% reporting “very efficacious”) included albuterol, acetaminophen for fever, non-sedating antihistamines, nasal steroid spray, and non-steroidal anti-inflammatory drugs (NSAIDs) for myalgia, arthralgia, or headache. Lower respiratory symptoms and anxiety were rated as the most challenging symptoms to manage.ConclusionsProviders reported that clinical care of mild COVID-19 with medications in common use for other respiratory infections is effective, both at episodic care and longitudinal sites of care, but that specific symptoms are still challenging to manage.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00432-8.

Retrospective evaluation of albuterol inhalant exposure in dogs: 36 cases (2007-2017).

To describe the clinical features, clinicopathological features, treatment, and outcome of dogs presented for albuterol exposure. Retrospective case series from January 2007 to December 2017. Tertiary veterinary facility. Thirty-six client-owned dogs presenting for known or suspected albuterol exposure secondary to chewing on albuterol metered-dose inhalers (MDIs). None. All dogs presented with clinical signs attributable to albuterol exposure. The most common physical examination abnormality was sinus tachycardia, noted in 34 of 36 (94%) dogs. Twenty-seven patients (75%) were admitted to the hospital for therapy, with a median length of hospitalization of 20.5hours (16.75-24.5). Thirty-two of 36 dogs had serum electrolytes evaluated at admission, with 22 of 32 (69%) presenting with hypokalemia ([K+]<3.62mmol/L]). Hyperlactatemia ([lactate]>2.80mmol/L) was noted in 23 of 28 (82%) dogs. A negative correlation was found between serum lactate and potassium (r=-0.64, r2 = 0.40, P= 0.0003). Hyperglycemia ([glucose]>6.44mmol/L) was noted in 20 of 30 (67%) dogs. Beta antagonist therapy was utilized in 20 of 36 (56%) of dogs. Although uncommon, albuterol intoxication can lead to significant clinical and electrolyte abnormalities. Albuterol-induced hypokalemia and associated tachyarrhythmias can be successfully managed, and albuterol intoxication has an excellent prognosis for survival to discharge. A minimum database should be evaluated in all dogs presenting for suspected albuterol exposure, with lactate and glucose monitored carefully in dogs with moderate or severe hypokalemia given the correlation found.

Subcutaneous terbutaline as an alternative to metered-dose inhalers for asthma during the COVID-19 pandemic.

In a well-written and informative article, Whittle et al1 “Respiratory Support for Adult Patients with COVID-19,” correctly recommend against using nebulizer therapy for asthmatics and suggests metered-dose inhalers. During the COVID-19 epidemic, asthmatics will continue to have exacerbations, frequently requiring emergency room care in a physician's office, urgent care center, or emergency department of a hospital. It is recommended that asthmatic patients continue to be managed according to asthma guideline recommendations.2 Nebulizer use is discouraged unless essential during a pandemic because nebulized therapy is more likely to aerosolize SARS-CoV-2 and increase risk of contagion. As such, asthma therapy delivered by a metered-dose inhaler would be more appropriate in the healthcare setting.3 Nevertheless, some patients are so tight that using a metered-dose inhaler, even with a spacer, might be problematic, particularly if they have uncontrolled coughing, have severe life-threatening asthma, or those who are uncooperative or unable to follow directions required for the metered-dose inhaler, even with a spacer. A recent article4 demonstrated that, in a prospective study, 85 asthmatic patients treated with subcutaneous terbutaline significantly improved after already receiving multiple albuterol treatments with either nebulized aerosols or albuterol metered-dose inhalers. Advantages of terbutaline over epinephrine include: (1) a more pronounced effect with a longer duration of action on forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC),5 and (2) preferred over epinephrine in pregnancy.6 Terbutaline is inexpensive and readily accessible, even though a previous survey of physicians in the Cleveland area reveal that 98% of physicians rarely or never use subcutaneous terbutaline for an exacerbation of asthma.7 From a colleague in New York City reading about my work with terbutaline, “This is great! Not only that, but the feasibility of subcutaneous terbutaline as an administration route during a high-volume/war-like situation is underappreciated.” Additionally, the American College of Allergy, Asthma, and Immunology (ACAAI) has reported that some areas around the country are experiencing shortages in albuterol inhalers as a result of an increased demand, because hospitals are using inhalers rather than nebulizers to treat COVID-19 patients.8 Finally, although metered-dose inhalers frequently work, the use of subcutaneous terbutaline would obviate the need for these inhalers or aerosols.

Adherence and usage patterns of inhaled corticosteroids-long-acting beta-agonists by using inhaler-monitoring technology.

Background: Results of previous research indicate that adherence to prescribed inhaled corticosteroid-long-acting beta2-agonist (ICS-LABA) asthma controller medications is suboptimal, yet actual daily-use patterns are unclear and may be influenced by regimen complexity or dosing frequency. Objective: To investigate real-world use of asthma medications by using inhaler sensors for the ICS-LABA controllers: twice-daily fluticasone propionate (FP) plus salmeterol (SAL) and once-daily fluticasone furoate (FF) plus vilanterol (VI); and albuterol rescue medication. Methods: This longitudinal, two-phase, observational study included adults with asthma-prescribed FP-SAL (phase I) or FF-VI (phase II), and albuterol metered-dose inhalers. The participants completed baseline and follow-up surveys, and used clip-on inhaler sensors to monitor real-time inhaler use over the 6-month study period. Pharmacy claims data for the 6-month follow-up period were used to assess refills of ICS-LABA and albuterol inhalers. Results: Patients who used twice-daily FP-SAL received a sufficient dose (≥2 actuations/day) approximately one third of the time, those on once-daily FF-VI received a sufficient dose (≥1 actuation/day) ∼60% of the time. Patients who used once-daily FF-VI were more likely to take their medication as prescribed versus those who used twice-daily FP-SAL. There were no significant differences in the percentage of albuterol-free days (FP-SAL, 68.06% [n = 241]; FF-VI, 72.67% [n = 127]; p = 0.230). Exploratory outcomes are reported in this article's Online Supplemental Material. Claims-based measures of adherence were higher than sensor-based measures, hence claims data may have overestimated adherence, whereas sensors may have more accurately measured patients' medication use. Conclusion: These data supported the use of inhaler sensors as tools to directly and accurately measure ICS-LABA adherence and rescue medication use, and the adherence benefits of once-daily versus twice-daily ICS-LABA regimens.

A Report of an Asthma Pathway Leading to Improved Resource Use.

Asthma pathways have been shown to improve resource use and decrease length of stay (LOS). A tertiary care hospital implemented an asthma pathway in May 2015 to standardize inpatient care. We predicted that the pathway would increase the use of albuterol metered-dose inhalers (MDIs) and steroids; decrease use of albuterol nebulizer, antibiotics, chest radiograph (CXR), and respiratory viral panel (RVP); and decrease LOS. This retrospective cohort study selected patients between the ages of 2 and 18 years who were admitted for asthma as a primary diagnosis between May 2014 and May 2016 (1 year preimplementation to 1 year postimplementation). Patients' complex chronic conditions were excluded. We analyzed use of albuterol nebulizer, MDI, and continuous nebulization, ipratropium bromide, oral steroids, antibiotics, inhaled steroids, CXR, and RVP. We also evaluated LOS and readmission rate. There were 1131 and 925 patients identified before and after asthma pathway implementation, respectively. The percent that received albuterol nebulizer decreased from 14.1% to 6.1% (p < 0.001). The percent that received albuterol MDI increased from 97.0% to 99.4% (p < 0.001). The average number of MDI administrations decreased from 11.6 to 10.4 (p = 0.004). Continuous albuterol use increased from 52.3% to 59.1% (p = 0.002). There was no change in ipratropium bromide, oral steroid, inhaled steroid, or CXR use. Antibiotic (p = 0.049) and RVP (p = 0.03) use decreased. The average LOS decreased from 1.84 days to 1.71 days (p = 0.02). Readmission rates did not change significantly. The asthma pathway improved inpatient albuterol MDI use. The LOS decreased while maintaining readmission rates.

The Effect of a Holding Chamber on Albuterol Metered-Dose Inhaler Product Differences

JL Johnson, D Guthrie, J Hyde, T Hanson, K Karlage, PB Myrdal. Ann Allergy Asthma Immunol. 2016;117(3):246–250 To investigate the differences in 3 albuterol sulfate metered-dose inhaler (MDI) products and their particle size. The study also evaluated if use of a valved holding chamber (VHC) would impact drug delivery and/or diminish systemic adverse effects. The study did not use human subjects, but rather examined Ventolin hydrofluoroalkane (HFA), Proventil HFA, and ProAir HFA, the 3 racemic albuterol sulfate pressurized MDI products available in the United States. The experimental design involved a nonviable 8-stage Anderson Cascade Impactor (ACI) with a US Pharmacopeia (USP) throat model with a mean (SD) airflow rate of 28.3 (0.5) mL/min. Each of the 3 albuterol MDI products …

Can a Short Video Improve Inhaler Use in Urban Youth?

The primary aim was to determine whether watching a short video in the inpatient setting could produce an immediate improvement in pediatric patients' asthma knowledge and inhaler technique. This prospective, quasi-experimental, pre-post study was conducted in a single center, in Detroit, Michigan, which primarily serves an urban, African-American population. Patients were eligible if they were between 8- and 16-years-old, had asthma, and would be discharged with an albuterol metered-dose inhaler. The primary outcome was improvement in the composite score of a knowledge and technique assessment before and after watching a 5-minute video. The lead author developed the video with content validation by pharmacists, pediatricians, elementary school teachers, and a pediatric health education specialist. Secondary outcomes at 30 days included change in asthma control and whether the video was revisited after discharge. Thirty patients were enrolled. Their average age was 11 ± 2.1 years; they were primarily African American (83%), female (53%), and insured by Medicaid (87%). The composite score of technique assessment and written quiz increased by 3.53 (95% confidence interval [CI] 2.81 to 4.85) of a possible 16 points after watching the video. There was no significant change in asthma control at 30 days as measured by the asthma control test (2, 95% CI -0.53 to 4.53). Eight of 22 patients revisited the video after discharge. A brief educational video delivered during a pediatric inpatient visit in an urban medical center resulted in an immediate improvement in patients' disease knowledge and inhaler technique.

Patient-Reported Outcomes and Quality of Life Improved with Fluticasone Propionate and Fluticasone Propionate/Salmeterol Multidose Dry Powder Inhalers Versus Placebo in Patients with Persistent Asthma

Patient-reported outcomes, including quality of life, were evaluated in patients receiving fluticasone propionate (Fp) and fluticasone propionate/salmeterol (FS) via a novel multidose dry powder inhaler (MDPI). This phase 3, double-blind, parallel-group study (FSS-AS-301; NCT02139644) evaluated asthmatic patients (ages ≥12 years) using inhaled corticosteroids (ICS) or ICS/long-acting beta2-agonists. After a 14- to 21-day run-in during which patients received albuterol metered-dose inhaler for rescue, beclomethasone dipropionate metered-dose inhaler, 40 mcg twice daily (BID), and placebo MDPI BID, patients randomly received Fp MDPI 50 mcg, Fp MDPI 100 mcg, FS MDPI 50/12.5 mcg, FS MDPI 100/12.5 mcg, or placebo BID for 12 weeks. Efficacy and safety outcomes were previously reported. Patient-reported outcomes including asthma symptoms, rescue medication use, Asthma Quality of Life Questionnaire (AQLQ) scores (patients ≥18 years), and adverse events are reported. The full analysis and safety populations included 640 and 641 patients, respectively. All active treatments significantly improved asthma symptom scores (p<0.05) and significantly decreased rescue medication use (p<0.05) versus placebo over 12 weeks. Improvements in AQLQ from baseline to endpoint for active treatment groups were significantly greater versus placebo (p<0.05). AQLQ improvements from baseline achieved the minimal important difference (≥0.5) for all active treatment groups. Comparisons between Fp MDPI and FS MDPI were not significant for any assessed outcome except AQLQ for Fp MDPI 100 mcg versus FS MDPI 100/12.5 mcg (p<0.05). Adverse events were similar across groups. Low- and mid-dose Fp MDPI and FS MDPI significantly improved patient-reported outcomes and quality of life versus placebo.

The effect of a holding chamber on albuterol metered-dose inhaler product differences

BackgroundThree albuterol sulfate metered-dose inhaled (MDI) products (Ventolin HFA, Proventil HFA, and ProAir HFA) are marketed in the United States to provide the same total dose of albuterol sulfate. However, it is widely known that the fine particle dose (<5 μm) is the portion of the particle distribution that actually reaches the lungs and provides therapeutic benefit. ObjectiveTo examine the differences in particle size between products and how a valved holding chamber (VHC) can mitigate possible adverse effects. MethodsParticle size distributions in each product were measured, with and without a VHC, and were analyzed by high-performance liquid chromatography. ResultsThe only significant mean (SD) difference in total dose was between Proventil (75 [21] μg) and ProAir (107 [12] μg) (P < .01). The fine particle doses of all 3 products were significantly different: 21 (5) μg of albuterol sulfate for Ventolin, 40 (4) μg of albuterol sulfate for Proventil, and 64 (7) μg of albuterol sulfate for ProAir (P < .001 for all 3 cases). The VHC successfully removed the larger particle dose delivered by all 3 products (P ≤ .01) without reducing the fine particle dose (P > .05). ConclusionVentolin, Proventil, and ProAir should not be considered interchangeable products. In this study, the dose of albuterol sulfate likely to reach the lungs with Proventil or ProAir is 2 to 3 times that of Ventolin. As such, patients with asthma may require 3 additional puffs of Ventolin to achieve a clinical benefit similar to Proventil or ProAir. Because all 3 products contain 200 actuations, it also follows that Proventil or ProAir products may last a user 2 to 3 times longer than Ventolin.

Historical cohort study examining comparative effectiveness of albuterol inhalers with and without integrated dose counter for patients with asthma or chronic obstructive pulmonary disease.

BackgroundUsing a metered-dose inhaler (MDI) beyond the labeled number of actuations may result in inadequate dosing of medication, which can lead to poor clinical outcomes. This study compared respiratory-related emergency department (ED) visit rates in patients with asthma, chronic obstructive pulmonary disease, or both when they used albuterol MDIs with versus without dose counters.MethodsThis retrospective study used US claims data to identify patients (ages 4–64 years) with asthma, chronic obstructive pulmonary disease, or both, using albuterol MDIs with or without an integrated dose counter. The study comprised a 1-year baseline period for patient characterization and confounder definition and a 1-year outcome period following the first albuterol prescription. The primary end point was the incidence rate of respiratory-related ED visits, compared using a reduced zero-inflated Poisson regression model. We also compared severe exacerbation rates and rescue medication use.ResultsA total of 93,980 patients were studied, including 67,251 (72%) in the dose counter cohort and 26,729 (28%) in the non-dose-counter cohort. The cohorts were broadly similar at baseline (55,069 [59%] female patients; median age, 37 years). The incidence rate of respiratory-related ED visits during the outcome year was 45% lower in the dose counter cohort than in the non-dose-counter cohort (adjusted rate ratio: 0.55; 95% confidence interval: 0.47–0.64). Exacerbation rates and short-acting β-agonist use were similar between cohorts.ConclusionThese findings suggest that dose counter integration into albuterol MDIs is associated with decreased ED visit rates. The presence of integrated dose counters on rescue inhalers can help patients avoid using an empty or near-empty inhaler during exacerbations, thereby ensuring available medication for relief of their symptoms. Integrated dose counters on rescue MDIs could represent a simple and effective tool to improve clinical outcomes during exacerbations, with a potential for cost savings to health care systems.

A Comparison of Pharmaceutical Product Performance of Albuterol Inhalers Available in the United States and Those Obtained in a Mexican Border Town.

Background: American residents travel to Mexico to purchase medications for a fraction of US cost and frequently without prescription requirements. A previous bioequivalence study found differences in lung function measures between 2 brands of Mexican-manufactured albuterol inhalers (both 100 µg/puff). An investigation of the pharmaceutical performance of different inhalers available may illuminate why different clinical results may be observed and offer insight to consumer and provider expectations of such products. Objective: The purpose of this study is to provide some reasonable expectations for a medical tourist who shops in Mexico for albuterol metered dose inhalers (MDIs) or for their health care providers by comparing pharmaceutical product performance of the consumer-available brands. Methods: Five different albuterol MDI products were purchased in Nogales, Mexico. The albuterol content was quantified through high-performance liquid chromatography. The inhalers were analyzed to determine the amount of the albuterol dose that can be considered respirable and compared with the findings from 2 US innovator products. Results: The mean respirable mass for each brand of albuterol MDI was compared with that of the other 4 brands and the 2 US innovator products using Student's t test. All evaluations showed significant differences (P < .05) except for 3 comparisons (Sacrusyt vs Assal, P = .89; Xeneric-S vs non-US Ventolin, P = .98; Victory vs US Proventil HFA, P = .06). Conclusion: Since pharmaceutical variability was found among the albuterol MDIs evaluated in this study, consumers and clinicians should appreciate possible differences in product performance of albuterol MDIs obtained in Mexico.

A 46-Year-Old Woman With Persistent Asthma and Lung Masses

46-year-old woman presented with diffi culty breathing with exertion for the last few months. She had recently been diagnosed with asthma and was prescribed inhaled bronchodilators without significant improvement. She was using rescue bronchodilators three times a day. She denied fevers, chronic cough, hemoptysis, chest pain, nasal congestion, or postnasal drip. There was no history of nocturnal symptoms, heartburn, weight loss, or loss of appetite. She had previously never had a chest radiograph. Her past medical history was otherwise negative. She was using an albuterol metered-dose inhaler as needed. She did not smoke or use any illicit substances. She was unemployed and had no pets. Family history was unremarkable.

A Case of Ropinirole-Induced Compulsive Behavior

To the Editor: Parkinson’s disease is a neuropsychiatric condition. Dopamine agonists are used extensively in the treatment of Parkinson’s. A retrospective review in 2009 of patients with Parkinson’s disease reported a frequency of 13.2% for compulsive behavior including new-onset pathological gambling and hypersexuality after being started on therapeutic doses of pramipexole or ropinirole.1 Several reports and reviews have been published on this topic. Here we present a case of new-onset compulsive behavior with the dopamine agonist ropinirole in a patient who presented in a mental health clinic setting. Case report. Mr A, a 41-year-old white, married male veteran with a history of Parkinson’s disease with cognitive impairment as well as DSM-IV-TR posttraumatic stress disorder and major depressive disorder, single episode, moderate, was referred to the mental health clinic by his primary care physician for management of his psychiatric symptoms. The patient reported that his depressive symptoms had been stable since he started treatment with venlafaxine 2 months earlier, but for the past few months he was having compulsive behavior, including intense sexual desires toward other women, and had started to gamble on scratchcards, on which he had lost $1,000 to $1,500 in a month. This was unusual for him, as he had a supportive and loving wife and had never gambled before. He had noted an increase in appetite (weight gain of 20 lb [9.1 kg]), endorsed that he had compulsive eating behaviors, and drank about a 20-pack of beer per day. He also described having nightmares and vivid dreams and endorsed having visual hallucinations in the form of shadows in the room on multiple occasions. This behavior had been causing stress in his marriage. He had no previous history of strokes, seizures, bipolar disorder, psychosis, impulse-control disorder, or drug dependence. His psychiatric medications included venlafaxine 150 mg twice daily, zolpidem 10 mg at bedtime, and clonazepam 1 mg twice daily, and his Parkinson’s disease medications included tablet carbidopa/levodopa 25 mg/250 mg every 3 hours, ropinirole 3 mg 3 times daily, entacapone 200 mg every 5 hours, and donepezil 10 mg at bedtime. Other medications were tramadol, losartan, flunisolide nasal inhaler, albuterol metered-dose inhaler, cetirizine, formoterol inhaler, and mometasone metered-dose inhaler. Mr A informed us that, at his last visit, his neurologist had increased his ropinirole dosage from 1 mg orally twice daily to 3 mg orally twice daily, as he was experiencing dyskinesia, swallowing difficulty, gradual decline in memory, and worsening of his Parkinson’s symptoms. Review of medical records confirmed that he indeed started having this weight gain and impulsive behavior within the first few weeks after the ropinirole dose was increased. After conducting a literature search on ropinirole, we decided to discontinue the medication. Following discontinuation, the symptoms resolved completely, and Mr A started to have weight loss and did not have the urge to gamble; however, his Parkinson’s motor symptoms reemerged. Thus, he was restarted on ropinirole at 0.5 mg orally twice daily for 1 wk and then increased to 1 mg orally twice daily, which he tolerated well without reemergence of his symptoms. The appearance of symptoms on increasing the dose and then improvement with reducing the dose suggests a strong correlation between ropinirole and impulsive behavior. This case highlights the importance of awareness regarding drug-related psychiatric symptoms that may originate in the course of management of Parkinson’s disease. Physicians who care for patients taking dopamine agonists should watch for and differentiate between conditions including drug-induced adverse effects from primary psychiatric disorders and work in collaboration with neurologists to manage these treatment-emergent adverse effects.

Comparison of the bronchodilating effects of albuterol delivered by valved vs. non‐valved spacers in pediatric asthma

Inhaled therapy using a metered-dose inhaler (MDI) with attached valved holding chamber has been increasingly recognized as the optimal method for delivering bronchodilators for asthma treatment. However, mainly due to the high cost of these valved holding chambers in many developing countries, the use of non-valved spacers is frequent, despite the scarce evidence that supports their efficacy. The aim of this study was to compare the bronchodilator response to albuterol administered by MDI with and without a valved spacer. In a randomized, two-period, two-sequence crossover clinical trial, we analyzed 31 stable asthmatic children (6-18 yrs of age) on two consecutive days, who were randomly assigned to receive 100 μg of albuterol MDI through either a locally produced valved spacer or a non-valved spacer. The next day, a crossover treatment was employed through the use of the other spacer. Spirometry was recorded before and after each albuterol administration. As we were not able to identify any sequence or carryover effect, we tested for treatment effects in both periods. No significant differences in the absolute change in FEV(1) (0.20 ± 0.17 vs. 0.18 ± 0.16, p = 0.63), FVC (0.07 ± 0.13 vs. 0.07 ± 0.16, p = 0.88), or MMEF (0.49 ± 0.31 vs. 0.43 ± 0.39, p = 0.53) after bronchodilator administration were found between the use of valved and non-valved spacers. In stable asthmatic children, albuterol administered through MDI using a non-valved spacer produces a bronchodilator response similar to that of a spacer with a valve that requires an inhalatory opening pressure (with flows between 2 and 32 l/min) that even toddlers with bronchial obstruction can easily generate.

Nurse‐Initiated Albuterol Metered‐Dose Inhaler for Acute Exacerbations of Chronic Obstructive Pulmonary Disease in an Emergency Department: A Randomised Controlled Trial

ObjectiveA randomised controlled trial (RCT) to assess the effectiveness of nurse‐initiated use of albuterol metered‐dose inhaler (MDI) to patients for relieving the signs and symptoms of acute exacerbations of chronic obstructive pulmonary disease (COPD) prior to consultation in an emergency department (ED).DesignA single‐centre unblinded RCT.MethodsKnown COPD Chinese patients who aged at least 18 years old, previous use of albuterol MDI, competent to blow the peak flow meter and complained of dyspnoea. The anticipated time between nurse‐initiated use of albuterol MDI and consultation was over five minutes. The subjects were recruited from the ED of a hospital in Hong Kong and were allocated to the albuterol or control group by block randomisation. Six albuterol puffs were administered via a MDI to the albuterol group but not the control group. Peak flow rate, blood oxygen saturation, respiratory rate, adverse effects, ED length of stay and admission rate were assessed before nursed‐initiated use of albuterol MDI and prior to consultation.Results110 subjects were recruited and randomly allocated into the albuterol (n=55) or control (n=55) group. The PFR increased 2.4 L/minute (p&lt;0.001) in the albuterol group but not in the control group. The oxygen saturation and symptom of dyspnoea also improved in the albuterol group but not in the control group.ConclusionsNurse‐initiated use of albuterol MDI can improve PFR prior to consultation so that it should be recommended as a standard practice in EDs to reduce the suffering of patients with acute exacerbations of COPD.

A 67-Year-Old Woman With Cough and Shortness of Breath

67-year-old woman was admitted to the hospital with complaints of cough and shortness of breath. She had immigrated to the United States from Pakistan 4 months earlier and subsequently developed the cough, which had worsened over the past months. Two weeks prior to admission she developed worsening dyspnea on exertion. The patient did not speak English, and her daughter did the translation. Her cough was mostly dry with occasional production of minimal whitish-brown sputum. She had received amoxicillinclavulanate and ciprofl oxacin for her symptoms by her primary care physician without any benefi t. She denied any complaints of persistent fever, night sweats, chest pain, skin rash, joint pains, hemoptysis, or weight loss. Her remaining medical history was signifi cant for hypertension, diabetes mellitus, and asthma. Her medications included amlodipine, metformin, glyburide, and albuterol metered-dose inhaler. She denied any history of tobacco or alcohol abuse; however, she had been exposed to biomass fuels as a child. There was no history of prior pulmonary infection or positive purifi ed protein derivative skin test.

Levalbuterol versus albuterol

Albuterol has been used for more than 40 years to treat acute asthma exacerbations as a racemic mixture of isomers: the active form, (R)-albuterol, or levalbuterol, and (S)-albuterol, classically considered inert. The single-isomer formulation, levalbuterol, has been synthesized recently and used therapeutically when the racemate is deemed less desirable. Basic investigations indicate that racemic albuterol and levalbuterol can produce effects that favor asthma remediation, including corticosteroid amplification and reduction of inflammatory mediators; in contrast, (S)-albuterol produces opposite effects. With inhalation of racemic albuterol, circulating (S)-albuterol persists 12 times longer than levalbuterol, suggesting potential for paradoxical effects observed clinically. Although mainly consistent with basic findings, clinical studies suggest no overwhelming superiority of levalbuterol over racemic albuterol; however, levalbuterol's effects may be greatest in moderate to severe asthma patients, especially with racemic albuterol overuse. Recent adoption of the hydrofluoroalkane formulation has narrowed the cost gap between levalbuterol and racemic albuterol metered-dose inhalers, but it remains for the nebulized formulations. Thus, physician selection of these drugs has remained dependent on experience, pharmaceutical knowledge, and established prescribing habits combined with cost factors, formulary structures, and availability, such that racemic albuterol is still used significantly compared with levalbuterol to treat acute asthma exacerbations.