Clinical Consequences of the Overuse of Short-Acting β2-Adrenergic Agonists (SABA) in the Treatment of Asthma in Spain: The SABINA Study.
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SUBMITTER: Molina J
PROVIDER: S-EPMC10369590 | biostudies-literature | 2023 Apr-Jun
REPOSITORIES: biostudies-literature
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Clinical Consequences of the Overuse of Short-Acting β2-Adrenergic Agonists (SABA) in the Treatment of Asthma in Spain: The SABINA Study.
Molina Jesús J Plaza Vicente V Nuevo Javier J Gutiérrez Martín M Sicras-Mainar Antoni A Valero Antonio A
Open respiratory archives 20230113 2
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Project description:This study aims to investigate the prevalence of short-acting β2-agonist (SABA) overuse in asthma and the associated risk of acute exacerbation and mortality in Taiwan. We used the Taiwanese pay-for-performance asthma program database, which included patients aged between 12 and 100 years who were enrolled in the program between 2001 and 2015. Among a total of 218,039 patients, 34,641 (15.9%) patients are classified as SABA over-users. Compared with patients who did not receive inhaled corticosteroids (ICS) and collected ≤2 canisters, SABA over-users had a higher risk of severe exacerbations. SABA over-users had a higher risk of all-cause mortality compared with patients who did not receive ICS and collected ≤2 canisters. The overall prevalence of SABA overuse in Taiwan is 15.9%, and this is even higher in concomitant ICS users. In addition, the overuse of SABA is associated with an increased risk of severe exacerbation and death.
| S-EPMC8058069 | biostudies-literature
Project description:BackgroundShort-acting β2-agonists (SABA) overuse is associated with asthma morbidity and mortality. The SABA use IN Asthma (SABINA) program aimed to describe the global use of SABA in patients with asthma. SABINA III study was a cross-sectional study covering 24 countries.MethodsWe performed statistical analysis of the Russian population (618 patients recruited in 12 centers) from the SABINA III study. In this study in patients aged ≥12 years, data on disease characteristics and asthma treatments were collected using real-time electronic case report forms. Patients were classified by asthma severity and control according to the 2017 GINA. All variables (asthma severity and control, number of severe exacerbations, SABA and other medications use) were analyzed descriptively only, no hypothesis was tested.ResultsMajority of the study population consisted of patients with moderate/severe asthma (78.5%), while mild asthma was seen in 21.5%. Asthma was uncontrolled in 36.1% of patients and partly controlled in 33.5%. More than 80% of patients were treated with ICS/LABA fixed-dose combination. Almost half of all patients (47.0%) had at least 1 severe exacerbation in the previous 12 months. SABA over-prescription (≥3 canisters per year) was seen in 37% of patients. The frequency of SABA over-prescription was similar in patients with mild (35%) and moderate/severe (38%) asthma. SABA was purchased over-the-counter (OTC) in the past 12 months by 30.1% of all patients, and 14% purchased ≥3 canisters of SABA per year. About 91% of patients who purchased SABA OTC already received prescriptions for SABA, of whom 59% were prescribed ≥3 canisters per year.ConclusionRussia is seeing very high level of SABA over-prescription. This is potentially associated with poor asthma control and frequent severe exacerbations. Over-prescription may serve as the main cause for SABA overuse in Russia. To reduce SABA overuse and improve overall asthma control in Russia, it is necessary to educate not just the patients but also the doctors, while actively implementing up-to-date asthma treatments.
| S-EPMC8965337 | biostudies-literature
Project description:Corticosteroid insensitivity (CI) is a major barrier to treating severe asthma. Despite intensive research, the molecular mechanism of CI remains uncertain. The aim of this study was to determine abnormality in corticosteroid action in severe asthma and to identify the molecular mechanism of the long-acting β(2)-adrenergic agonists (LABAs) formoterol and salmeterol on restoration of corticosteroid sensitivity in severe asthma in vitro. Peripheral blood mononuclear cells (PBMCs) were obtained from 16 subjects with severe corticosteroid-insensitive asthma, 6 subjects with mild corticosteroid-sensitive asthma, and 11 healthy volunteers. Corticosteroid (dexamethasone) sensitivity was determined on tumor necrosis factor-α (TNF-α)-induced interleukin (IL)-8 production. Glucocorticoid receptor (GR) phosphorylation and kinase phosphorylation were evaluated by immunoprecipitation-Western blotting analysis and kinase phosphorylation array in IL-2/IL-4-treated corticosteroid insensitive model in PBMCs. In vitro corticosteroid sensitivity on TNF-α-induced IL-8 production was significantly lower in patients with severe asthma than in healthy volunteers and patients with mild asthma. This CI seen in severe asthma was associated with reduced GR nuclear translocation and with hyperphosphorylation of GR, which were reversed by LABAs. In IL-2/IL-4-treated PBMCs, LABAs inhibited phosphorylation of Jun-NH(2)-terminal kinase and p38 mitogen-activated protein kinase-γ (p38MAPK-γ) as well as GR. In addition, cells with p38MAPK-γ knockdown by RNA interference did not develop CI in the presence of IL-2/IL-4. Furthermore, p38MAPK-γ protein expression was up-regulated in PBMCs from some patients with severe asthma. In conclusion, p38 MAPK-γ activation impairs corticosteroid action and p38 MAPK-γ inhibition by LABAs has potential for the treatment of severe asthma.
| S-EPMC3228526 | biostudies-literature
Project description:Background/aimsDespite short-acting β2-agonist (SABA) overuse being associated with poor asthma outcomes, data on SABA use in South Korea is scarce. Herein, we describe prescription patterns of SABA and other asthma medications in patients from the South Korean cohort of the SABA use IN Asthma (SABINA) III study.MethodsThis study included patients with asthma aged ≥ 12 years, who had ≥ 3 consultations with the same healthcare provider, and medical records containing data for ≥ 12 months prior to the study visit. Patients were classified by investigator-defined asthma severity (per 2017 Global Initiative for Asthma recommendations) and practice type (primary or specialist care). Data on disease characteristics, asthma treatments, and clinical outcomes in the 12 months before the study visit were collected using electronic case report forms.ResultsData from 476 patients (mean age, 55.4 years; female, 63.0%) were analyzed. Most patients were treated by specialists (83.7%) and had moderate-to-severe asthma (91.0%). Overall, 7.6% of patients were prescribed ≥ 3 SABA canisters (defined as over-prescription). In patients prescribed SABA in addition to maintenance therapy, 47.4% were over-prescribed SABA. Most patients (95.4%) were prescribed a fixed-dose combination of an inhaled corticosteroid and a long-acting β2-agonist as maintenance therapy. Although asthma was well-controlled/partly-controlled in 91.6% of patients, 29.6% experienced ≥ 1 severe asthma exacerbation.ConclusionSABA over-prescription was reported in nearly 50% of patients prescribed SABA in addition to maintenance therapy, underscoring the need to align clinical practices with the latest evidence-based recommendations and educate physicians and patients on appropriate SABA use.
| S-EPMC10790050 | biostudies-literature
Project description:Asthma is an inflammatory disease of the airway that poses a major threat to human health. With increase industrialization in the developed and developing countries, the incidence of asthma is on the rise. The β2-adrenergic receptor is an important target in designing anti-asthmatic drugs. The synthetic agonists of the β2-adrenergic receptor used over the years proved effective, but with indispensable side effects, thereby limiting their therapeutic use on a long-term scale. Inverse agonists of this receptor, although initially contraindicated, had been reported to have long-term beneficial effects. Phytochemicals from Agemone mexicana were screened against the human β2-adrenergic receptor in the agonist, inverse agonist, covalent agonist, and the antagonist conformations. Molecular docking of the phyto-constituents showed that the plant constituents bind better to the inverse agonist bound conformation of the protein, and revealed two flavanones; eriodictyol and hesperitin, with lower free energy (ΔG) values and higher affinities to the inverse agonist bound receptor than the co-crystallized ligand. Eriodictyol and hesperitin bind with the glide score of -10.684 and - 9.958 kcal/mol respectively, while the standard compound ICI-118551, binds with glide score of -9.503 kcal/mol. Further interaction profiling at the protein orthosteric site and ADME/Tox screening confirmed the drug-like properties of these compounds.
| S-EPMC5879945 | biostudies-literature
Project description:BackgroundThe extent of short-acting Beta-2-agonist (β2-agonist) (SABA) use across Asian countries is not well documented. As part of the SABA use IN Asthma (SABINA) III study, we assessed SABA prescriptions and clinical outcomes in patients with asthma from Asia.MethodsThis cross-sectional study recruited patients (aged ≥12 years) with asthma from 8 Asian countries. Data on disease characteristics and asthma treatments were collected using electronic case report forms. Patients were classified by practice type (primary or specialist care) and investigator-defined asthma severity (per Global Initiative for Asthma [GINA] 2017 recommendations). The association of SABA prescriptions with clinical outcomes was analyzed using multivariable regression models.ResultsOverall, 3066 patients were analyzed, with a mean (standard deviation) age of 51.8 (16.7) years; of these patients, 2116 (69%) were female, 2517 (82.1%) had moderate-to-severe asthma and 2498 (81.5%) and 559 (18.2%) were treated in specialist and primary care, respectively. In total, 1423 (46.4%) patients had partly controlled/uncontrolled asthma, with 1149 (37.5%) patients experiencing ≥1 severe asthma exacerbation in the previous year. Overall, 800 (26.7%) patients were prescribed ≥3 SABA canisters in the previous year, which is regarded as overprescription and was associated with a significantly decreased odds of at least partly controlled asthma and increased incidence rates of severe exacerbations (P < 0.01 for both associations).ConclusionThe findings from this cohort of predominantly specialist-treated patients with asthma indicate SABA overprescription in at least 1 in every 4 patients, and this overprescription is associated with poor clinical outcomes. These data highlight the need for adherence to recently updated asthma treatment recommendations in Asia.
| S-EPMC10587767 | biostudies-literature
Project description:Introduction: Asthma is one of the major public health problems that imposes a great burden on societal, financial, and healthcare around the world. Asthma poorly affects the health-related quality of life and daily activities of patients. Treatment of asthma, including inhaled corticosteroids (ICS) and long-acting beta-agonists (LABAs), mainly aims to improve the lung function and reduce symptoms and exacerbations. Current treatment regimens are symptom-based strategies, and the status of airway inflammation after treatment is yet unknown. We conducted this study to understand the comprehensive inflammation or airway remodeling status of patients after ICS-LABA treatment through RNA transcriptome analysis. Materials and methods: Eight newly diagnosed asthmatic patients and two healthy subjects were recruited in this study. Asthmatic patients underwent blood tests, lung function test, and RNA transcriptome analysis before and after ICS-LABA treatment. Results: In comparison with healthy subjects, pretreatment asthmatic patients had higher expression of protein tyrosine kinase and related signaling pathways. After ICS-LABA treatment, the expression of nuclear receptor transcription coactivator, N-acetyltransferase, protein tyrosine kinase, nuclear receptor, and RNA polymerase II-activating transcription factor were downregulated. However, the post-treatment asthmatic patients still had higher expression of cysteine-type endopeptidase, endodeoxyribonuclease, apolipoprotein, and unfolded protein was still upregulated than healthy subjects. Conclusions: The combination of ICS/LABAs decreased airway inflammatory and remodeling pathways. However, allergen stimulation-related pathways were still upregulated in patients after ICS/LABA treatment. The combination of medication and allergen removal is a complete strategy for asthma.
| S-EPMC9608042 | biostudies-literature
Project description: Not available
| S-EPMC4498225 | biostudies-literature
Project description:BackgroundShort-acting β2-agonists (SABA), the most potent and rapid-acting relievers are commonly used to provide quick relief of asthma symptoms. However, there is an increasing concern regarding the misuse of SABA medicines.ObjectiveThis qualitative systematic review aims to determine, evaluate, and summarize the perceptions, attitudes, and behaviors towards the use of SABA from the patients' perspectives.MethodsThe databases searched included PubMed, Scopus, PsycINFO, CINAHL, and Cochrane database. Original research articles reporting the perceptions, attitudes, or behaviors of asthma patients towards the use of SABA, which was available as full text, published in the English language between the year 2000 and February 2023 were included in the review. Commentaries, letters to editor, review articles, and conference proceedings were excluded.ResultsA total of five articles were included. Six overarching themes were obtained: (1) perceptions on health status; (2) perceptions and attitudes towards the impact of asthma; (3) perceptions towards asthma control; (4) perceptions towards asthma knowledge; (5) risk perceptions; (6) perceptions, attitudes, and behaviors towards the use of SABA.ConclusionDespite the fact that SABA could rapidly alleviate asthma symptoms, SABA over-users were less likely to describe their health status and asthma control as 'excellent'. Most SABA over-users did not know that frequent SABA usage would worsen their asthma control, and they exhibited psychological linkage towards the use of SABA. Collaborative efforts between policymakers, healthcare professionals and patients are warranted to reconstruct SABA prescribing practice and usage.
| S-EPMC10118161 | biostudies-literature
Project description:BackgroundEvidence suggests that variation in the length of the poly-C repeat in the 3' untranslated region (3'UTR) of the β2-adrenergic receptor gene (ADRB2) may contribute to interindividual variation in β-agonist response. However, methodology in previous studies limited the assessment of the effect of sequence variation in the context of poly-C repeat length. The objectives of this study were to design a novel genotyping method to fully characterize sequence variation in the ADRB2 3'UTR poly-C repeat in asthma patients treated with inhaled corticosteroid and long-acting β2-adrenergic agonist (ICS/LABA) combination therapy, and to analyze the effect of the poly-C repeat polymorphism on clinical response.MethodsIn 2,250 asthma patients randomized to treatment with budesonide/formoterol or fluticasone/salmeterol in a six-month study (AstraZeneca study code: SD-039-0735), sequence diversity in the ADRB2 poly-C repeat region was determined using a novel sequencing-based genotyping method. The relationship between the poly-C repeat polymorphism and the incidence of severe asthma exacerbations, and changes in pulmonary function and asthma symptoms from baseline to the average during the treatment period, were analyzed.ResultsPoly-C repeat genotypes were assigned in 97% (2,192/2,250) of patients. Of the 13 different poly-C repeat alleles identified, six alleles occurred at a frequency of >5% in one or more population in this study. The repeat length of these six common alleles ranged from 10 to 14 nucleotides. Twelve poly-C repeat genotypes were observed at a frequency of >1%. No evidence of an association between poly-C repeat genotype and the incidence of severe asthma exacerbations was observed. Patients' pulmonary function measurements improved and asthma symptoms declined when treated with ICS/LABA combination therapy regardless of poly-C repeat genotype.ConclusionsThe extensive sequence diversity present in the poly-C repeat region of the ADRB2 3'UTR did not predict therapeutic response to ICS/LABA therapy.
| S-EPMC3441247 | biostudies-literature