Project description:BACKGROUND Asthma is a common disease in the U.S. POPULATION:Initial therapy in the stepwise approach for asthma management is short-acting ??-agonist (SABA) therapy as needed for symptom control. However, a significant adverse event that can occur with administration is bronchospasm. Here, we report a case of paradoxical bronchospasm with administration of SABAs during multiple pulmonary function tests (PFTs). CASE REPORT A 25-year-old, non-smoking, African American male with a history of moderate asthma and allergic rhinitis treated with fluticasone/salmeterol diskus, albuterol hydrofluoroalkane (HFA) inhaler, and montelukast presented to our clinic complaining of recurrent episodes of acute shortness of breath immediately following each administration of albuterol for 4 weeks. PFTs were performed with levalbuterol (Xopenex) and albuterol (ProAir), yielding significant decrease in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). Nebulized albuterol and ipratropium bromide also improved FEV1 and FVC. He was successfully transitioned to an ipratropium rescue inhaler for asthma exacerbations. CONCLUSIONS Paradoxical bronchoconstriction is the unexpected constriction of smooth muscle walls of the bronchi that occurs in the setting of an expected bronchodilatory response. This phenomenon has been observed with ??-agonist-containing inhaler formulations and is an under-recognized adverse event. Theories suggest that the formulation excipients can trigger airway hyperresponsiveness in patients with allergically inflamed airways. Removal of excipients or use of anticholinergic inhalers improved respiratory function. Clinicians should be aware of paradoxical bronchospasm as an adverse effect with common inhaler formulations containing ??-agonists and counsel patients accordingly in the appropriate clinical setting.
Project description:BackgroundIn adults and adolescents with asthma, use of ≥3 short-acting β2 -agonist (SABA) canisters/year is associated with increased exacerbation risk. Whether this association is present in younger children remains unknown. In this SABA use IN Asthma (SABINA) Junior study, we assessed the association of SABA collection with exacerbation risk in the general Swedish pediatric asthma population.MethodsThis population-based cohort study utilized linked data from the Swedish national healthcare registries involving patients with asthma (<18 years) treated in secondary care between 2006-2015. Exacerbation risk, by baseline SABA collection (0-2 vs. ≥3 canisters, further examined as ordinal/continuous variable) and stratified on comorbid atopic disease (allergic rhinitis, dermatitis and eczema, and food/other allergies), was assessed for 1-year follow-up using negative binomial regression.ResultsOf 219,561 patients assessed, 45.4%, 31.7%, and 26.5% of patients aged 0-5, 6-11, and 12-17 years, respectively, collected ≥3 SABA canisters during the baseline year (high use). Collection of ≥3 SABA canisters (vs. 0-2) was associated with increased exacerbation risk during follow-up (incidence rate ratios [95% confidence interval]: 1.35 [1.29-1.42], 1.22 [1.15-1.29], and 1.26 [1.19-1.34] for 0-5-, 6-11-, and 12-17-year-olds, respectively); the association persisted with SABA as a continuous variable and was stronger among patients without atopic diseases (32%-44% increased risk versus. 14%-21% for those with atopic disease across groups).ConclusionsHigh SABA use was associated with increased asthma exacerbation risk in children, particularly in those without comorbid atopic diseases, emphasizing the need for asthma medication reviews and reformative initiatives by caregivers and healthcare providers on SABA use.
Project description:Short-acting β2-agonist (SABA) prescriptions and associated outcomes were assessed in 1440 patients with asthma from the SABA use IN Asthma (SABINA) III study treated in primary care. Data on asthma medications were collected, and multivariable regression models analysed the association of SABA prescriptions with clinical outcomes. Patients (mean age, 47.9 years) were mostly female (68.6%); 58.3% had uncontrolled/partly controlled asthma and 38.8% experienced ≥1 severe exacerbation (reported in 39% of patients with mild asthma). Overall, 44.9% of patients were prescribed ≥3 SABA canisters (over-prescription) and 21.5% purchased SABA over-the-counter. Higher SABA prescriptions (vs 1-2 canisters) were associated with significantly decreased odds of having at least partly controlled asthma (6-9 and 10-12 canisters) and an increased incidence rate of severe exacerbations (10-12 and ≥13 canisters). Findings revealed a high disease burden, even in patients with 'mild' asthma, emphasising the need for local primary care guidelines based on international recommendations.
Project description:BackgroundOver-reliance on short-acting β2-agonists (SABAs) is associated with poor asthma outcomes. However, the extent of SABA use in Turkey is unclear owing to a lack of comprehensive healthcare databases. Here, we describe the demographics, disease characteristics and treatment patterns from the Turkish cohort of the SABA use IN Asthma (SABINA) III study.MethodsThis observational, cross-sectional study included patients aged ≥ 12 years with asthma from 24 centres across Turkey. Data on sociodemographics, disease characteristics and asthma treatments were collected using electronic case report forms. Patients were classified by investigator-defined asthma severity (guided by the 2017 Global Initiative for Asthma [GINA]) and practice type (primary/specialist care). The primary objective was to describe SABA prescription patterns in the 12 months prior to the study visit.ResultsOverall, 579 patients were included (mean age [standard deviation; SD]: 47.4 [16.1] years; 74.3% female), all of whom were treated by specialists. Most patients had moderate-to-severe asthma (82.7%, GINA steps 3-5), were overweight or obese (70.5%), had high school or university/post-graduate education (51.8%) and reported fully reimbursed healthcare (97.1%). The mean (SD) asthma duration was 12.0 (9.9) years. Asthma was partly controlled/uncontrolled in 56.3% of patients, and 46.5% experienced ≥ 1 severe exacerbation in the preceding 12 months. Overall, 23.9% of patients were prescribed ≥ 3 SABA canisters in the previous 12 months (considered over-prescription); 42.9% received no SABA prescriptions. As few patients had mild asthma, only 5.7% were prescribed SABA monotherapy. Therefore, most patients (61.5%) were prescribed SABA in addition to maintenance therapy, with 42.8% receiving ≥ 3 SABA canisters in the previous 12 months. Inhaled corticosteroids (ICS), ICS + a long-acting β-agonist fixed-dose combination and oral corticosteroids were prescribed to 14.5%, 88.3% and 28.5% of all patients, respectively. Additionally, 10.2% of patients purchased SABA over the counter, of whom 27.1% purchased ≥ 3 canisters in the preceding 12 months.ConclusionsDespite all patients being treated by specialists and most receiving fully reimbursed healthcare, nearly a quarter of patients received prescriptions for ≥ 3 SABA canisters in the previous 12 months. This highlights a public health concern and emphasizes the need to align clinical practices with the latest evidence-based recommendations.
Project description:BackgroundUS national guidelines recommend assessing short-acting beta-agonist (SABA) medication use as a marker of asthma severity and control. However, the relationship between recent SABA use and asthma exacerbations is not currently known.ObjectiveTo evaluate the proximal relationship between the type and frequency of SABA use and asthma-related outcomes.MethodsWe evaluated SABA use among patients with asthma ages 5 to 56 years who were members of a large health maintenance organization in southeast Michigan. Frequency of use was estimated from pharmacy data assessing the timing and amount of SABA fills. Cox proportional hazards models were used to examine the prospective relationship between average daily SABA use for 3 months and outcomes associated with poor asthma control (ie, oral corticosteroids use, asthma-related emergency department visits, and asthma-related hospitalizations). We separately accounted for SABA metered-dose inhaler (MDI) and SABA nebulizer use.ResultsOf the 2,056 patients who met study criteria, 1,569 (76.3%) had used a SABA medication in their baseline year. After adjusting for potential confounders, SABA nebulizer use was associated with asthma-related emergency department visits (adjusted hazard ratio [aHR], 6.32; 95% confidence interval [CI], 2.38 to 16.80) and asthma-related hospitalizations (aHR, 21.62; 95% CI, 3.17 to 147.57). In contrast, frequency of SABA MDI use was not associated with these outcomes.ConclusionsFrequency of SABA use during a 3-month period was associated with poor asthma outcomes. The relationship with poor asthma outcomes was strongest for SABA nebulizer use, suggesting that the type of SABA used is also of prognostic importance.
Project description:IntroductionPreliminary results from the SABINA (SABA use IN Asthma) program showed lower overuse of short-acting β2-agonist (SABA) in Italy compared to other European countries. The aim of the present study was to ascertain whether SABINA's results might have been affected by the Italian National Health System and pharmaceutical market dynamics, by examining patients' characteristics in relation to SABA prescription/purchase habits.MethodsMultiple approaches were used: (1) a retrospective study using the General Practitioners' (GPs) Italian IQVIA Longitudinal Patient Database (LPD) to assess SABA overuse (more than two canisters/year) and its association with exacerbation risk; (2) a survey conducted across 200 Italian pharmacies to calculate the proportions of SABA purchases without a prescription; (3) a cross-sectional study on the specialists' IQVIA Patient Analyzer database to understand the SABA prescription habits of specialists.ResultsAmong SABA users identified through IQVIA LPD, the proportion of patients having more than two SABA canisters/year was 32%. Overall, patients prescribed more than two SABA canisters/year by GPs had 30% higher risk of exacerbations than patients with a maximum of two SABA canisters/year. The joint evaluation of IQVIA LPD and survey's findings revealed that IQVIA LPD tracks three out of four SABA canisters dispensed. The survey showed that, on average, SABA users purchased four canisters/year. Patients prescribed SABA by specialists were more frequently men, younger, thinner, and had higher spirometry values.ConclusionSABA overuse is common in Italy, with a share of consumption not regulated by medical prescriptions. Because SABA overuse increases exacerbation risk, changes to national guidelines should be encouraged to ensure implementation of global recommendations.
Project description:BackgroundTo gain a global perspective on short-acting β2-agonist (SABA) prescriptions and associated asthma-related clinical outcomes in patients with asthma, we assessed primary health data across 24 countries in five continents.MethodsSABINA III was a cross-sectional study that employed electronic case report forms at a study visit (in primary or specialist care) to record prescribed medication(s), over-the-counter (OTC) SABA purchases and clinical outcomes in asthma patients (≥12 years old) during the past 12 months. In patients with ≥1 SABA prescriptions, associations of SABA with asthma symptom control and severe exacerbations were analysed using multivariable regression models.ResultsOf 8351 patients recruited (n=6872, specialists; n=1440, primary care), 76.5% had moderate-to-severe asthma and 45.4% experienced ≥1 severe exacerbations in the past 12 months. 38% of patients were prescribed ≥3 SABA canisters; 18.0% purchased OTC SABA, of whom 76.8% also received SABA prescriptions. Prescriptions of 3-5, 6-9, 10-12 and ≥13 SABA canisters (versus 1-2) were associated with increasingly lower odds of controlled or partly controlled asthma (adjusted OR 0.64 (95% CI 0.53-0.78), 0.49 (95% CI 0.39-0.61), 0.42 (95% CI 0.34-0.51) and 0.33 (95% CI 0.25-0.45), respectively; n=4597) and higher severe exacerbation rates (adjusted incidence rate ratio 1.40 (95% CI 1.24-1.58), 1.52 (95% CI 1.33-1.74), 1.78 (95% CI 1.57-2.02) and 1.92 (95% CI 1.61-2.29), respectively; n=4612).ConclusionsThis study indicates an association between high SABA prescriptions and poor clinical outcomes across a broad range of countries, healthcare settings and asthma severities, providing support for initiatives to improve asthma morbidity by reducing SABA overreliance.
Project description:IntroductionIn Australia, short-acting β2-agonists (SABA) are available both over the counter (OTC) and on prescription. This ease of access may impact SABA use in the Australian population. Our aim was to assess patterns and outcome associations of prescribed, acquired OTC and reported use of SABA by Australians with asthma.MethodsThis was a cross-sectional study, using data derived from primary care electronic medical records (EMRs) and patient completed questionnaires within Optimum Patient Care Research Database Australia (OPCRDA). A total of 720 individuals aged ≥ 12 years with an asthma diagnosis in their EMRs and receiving asthma therapy were included. The annual number of SABA inhalers authorised on prescription, acquired OTC and reported, and the association with self-reported exacerbations and asthma control were investigated.Results92.9% (n = 380/409) of individuals issued with SABA prescription were authorised ≥ 3 inhalers annually, although this differed from self-reported usage. Of individuals reporting SABA use (n = 546) in the last 12 months, 37.0% reported using ≥ 3 inhalers. These patients who reported SABA overuse experienced 2.52 (95% confidence interval [CI] 1.73-3.70) times more severe exacerbations and were 4.51 times (95% CI 3.13-6.55) more likely to have poor asthma control than those who reported using 1-2 SABA inhalers. Patients who did not receive SABA on prescription (43.2%; n = 311/720) also experienced 2.71 (95% CI 1.07-7.26) times more severe exacerbations than those prescribed 1-2 inhalers. Of these patients, 38.9% reported using OTC SABA and other prescription medications, 26.4% reported using SABA OTC as their only asthma medication, 13.2% were prescribed other therapies but not SABA OTC and 14.5% were not using any medication.ConclusionBoth self-reported SABA overuse and zero SABA prescriptions were associated with poor asthma outcomes. The disconnect between prescribing authorisation, OTC availability and actual use, make it difficult for clinicians to quantify SABA use.
Project description:ObjectiveChanges in short-acting beta-agonist (SABA) use are an important signal of asthma control and risk of asthma exacerbations. Inhaler sensors passively capture SABA use and may provide longitudinal data to identify at-riskpatients. We evaluate the performance of several ML models in predicting daily SABA use for participants with asthma and determine relevant features for predictive accuracy.MethodsParticipants with self-reported asthma enrolled in a digital health platform (Propeller Health, WI), which included a smartphone application and inhaler sensors that collected the date and time of SABA use. Linear regression, random forests, and temporal convolutional networks (TCN) were applied to predict expected SABA puffs/person/day from SABA usage and environmental triggers. The models were compared with a simple baseline model using explained variance (R2), as well as using average precision (AP) and area under the receiving operator characteristic curve (ROC AUC) for predicting days with ≥1-10 puffs.ResultsData included 1.2 million days of data from 13 202 participants. A TCN outperformed other models in predicting puff count (R2 = 0.562) and day-over-day change in puff count (R2 = 0.344). The TCN predicted days with ≥10 puffs with an ROC AUC score of 0.952 and an AP of 0.762 for predicting a day with ≥1 puffs. SABA use over the preceding 7 days had the highest feature importance, with a smaller but meaningful contribution from air pollutant features.ConclusionPredicted SABA use may serve as a valuable forward-looking signal to inform early clinical intervention and self-management. Further validation with known exacerbation events is needed.
Project description:This post-hoc analysis of the SABINA III study evaluated the association of short-acting β2-agonist (SABA) prescriptions and self-reported over-the-counter (OTC) SABA purchase in the previous 12 months with asthma-related outcomes using multivariable regression models in 4556 patients (mean age, 48.9 years). Of the 2810 patients prescribed ≥3 SABA canisters, 776 (27.6%) also purchased ≥1 SABA OTC. This subset of 776 patients reported the highest disease burden; 73.2% had ≥1 severe exacerbation and 55.7% had uncontrolled asthma. Asthma-related outcomes worsened with any SABA OTC purchase, regardless of SABA prescriptions; disease burden was the highest in patients with ≥3 SABA prescriptions and ≥1 SABA OTC purchase vs 1-2 SABA prescriptions only (86% lower odds of having at least partly controlled asthma and 124% increased incidence of severe asthma (both P < 0.001). These findings emphasize the need to implement policy changes to restrict SABA purchase without prescriptions and ensure access to affordable asthma care.