Nighttime short-acting beta-agonist (SABA) in asthma and COPD

Objective Current standard of care, patient self-report and clinician estimation, overestimates true inhaled corticosteroids (ICS) adherence. We compare self-reported inhaled ICS and short-acting beta 2-agonists (SABA) use with objective data from electronic medication monitors (EMMs). Methods Adults with uncontrolled asthma and prescribed ICS and SABA were enrolled. At visit one, participants’ ICS and SABA inhalers were fitted with EMMs to track real-time medication usage over 14 days. Participants were asked to complete paper diaries to self-report medication usage over the same period. Participant self-report of ICS adherence and SABA use versus objective ICS adherence and SABA use was compared using Wilcoxon signed-rank tests. Results One hundred participants (80% female, mean age 48.5 years, 60% completed college, 80% privately insured) had complete data. Participant self-report (median (IQR): 0.8 (0.0, 2.0)) was greater than objectively measured (median (IQR): 0.43 (0.1, 2.1)) SABA use, but the difference was not statistically significant (P = 0.64). Participant self-report (median (IQR): 97 (67, 100)) was significantly greater than objectively measured (median (IQR): 75 (54, 93)) ICS adherence (P = 0.002). Conclusions Significant discrepancies between self-report and objective ICS usage were observed. EMM can provide clinicians with accurate data on ICS medication taking behavior, thus reducing medication regimen complexity, side effects, and costs.

<h3>Introduction</h3> Although generalised anxiety (GA) has a substantial influence on asthma outcomes, the underlying mechanisms remain unclear. This study examined individuals’ ‘Self-efficacy’ (SE) or their own belief in their ability to manage their asthma and ‘Experiential Avoidance’ (EA), the tendency to avoid unpleasant internal states as potential mechanisms that mediate the relationship between GA and asthma outcomes. <h3>Methods</h3> Four NHS Scotland Outpatient Respiratory clinics included adults with asthma aged 16 to 75 years. 65 participants completed cross-sectional questionnaires: The Generalised Anxiety Disorder Questionnaire, Brief Experiential Avoidance Questionnaire, Perceived Control of Asthma Questionnaire, Mini Asthma Quality of Life Questionnaire and Asthma Control Test. Correlations and path analyses were used to explore relationships between variables and mediating effects. Key asthma outcomes included: Asthma Quality of Life (QoL), Asthma Control and Short-Acting Beta Agonist (SABA) use. <h3>Results</h3> Higher levels of GA were significantly correlated with poorer asthma control (r=-0.428**), poorer asthma related QoL (r=-0.540**) and higher SABA use (r=0.412*). Higher GA was also significantly correlated with lower SE to manage asthma (r=-0.525**) and higher EA (r=0.565**). Significant indirect effects were found from increased GA to both decreased asthma control and QoL through decreased SE (b=-0.117, SE=0.061, 95%CI=[-0.262,-0.025]) and (b=-0.709, SE=0.239, 95% CI=[-1.21,-0.025]) respectively. The indirect effects from increased GA to both decreased asthma control and QoL through increased EA were also significant (b=-0.110, SE=0.049, 95%CI=[-0.214,-0.021]) and (b=-0.582, SE=0.259, 95%CI=[-1.16,-0.137]) respectively. Indirect effects from GA to SABA through SE and EA were not significant. These findings could not be explained by other covariates such as steroid medication use, SABA use or years living with asthma. P values (*p&lt;0.005,**p&lt;0.001). <h3>Conclusions</h3> These findings highlight the significance of Self-efficacy and Experiential Avoidance as potential mechanisms through which co-morbid Generalised Anxiety impacts on poorer asthma control and Quality of Life. It provides preliminary support for the use of psychological interventions which focus on these factors such as the Cognitive Behavioural Therapy and Acceptance and Commitment Therapy but will require replication in a longitudinal study.

BackgroundThe widespread use of short-acting beta-2 agonists (SABA) as an as-needed treatment for asthma is well-established. However, excessive use of SABA has been linked to undesirable outcomes such as increased risk of asthma attacks, exacerbations, and even death. The availability of SABA as an over-the-counter (OTC) medication has contributed to their overuse, leading to undertreated asthma and reduced access to asthma education.ObjectiveThis systematic review aimed to summarize the prevalence, characteristic features of, and factors contributing to over-the-counter SABA purchase or overuse.MethodsThe databases searched included PubMed, Scopus, Springer Link, Google Scholar, CINAHL, and APA PsycArticles. Original research articles reporting the prevalence, characteristics features, and factors regarding over-the-counter SABA use, available as full text, published in English language between the year 2000 and April 2023 were included in this review. Commentaries, letters to editor, review articles, qualitative studies, clinical trials, and conference proceedings were excluded. Data extraction was followed by a review of the quality of studies included and data were then synthesized for meaningful findings. This systematic review had been registered in the PROSPERO with registration number CRD42023421007.ResultsA total of 18 articles were included. The prevalence range of OTC SABA users in populations were 1.4% to 39.6% and SABA over-users among OTC users were 14% to 66.4%. Factors mostly associated with this behavior were moderate–severe asthma, and less use of preventers. On top of that, not understanding the risk of SABA overuse was clear in many studies that explored this factor.ConclusionOver-the-counter purchase and overuse of SABA medication is a common problem, leading to adverse consequences such as uncontrolled asthma and increased healthcare utilization. Addressing these issues requires improved patient education about their conditions and adequate information regarding the potential long-term effects of SABA use by the healthcare providers. Management and education of asthma patients, including regular monitoring and follow-up, can help reduce overuse of SABA medication and prevent negative consequences.

Combination of assist use of short-acting beta-2 agonists inhalation and guidance based on patient-specific restrictions in daily behavior: Impact on physical activity of Japanese patients with chronic obstructive pulmonary disease.

<b>Background:</b> Exercise induced bronchoconstriction (EIB) occurs frequently among athletes. Standard prevention plus pharmacological treatment cannot relieve EIB induced symptom in a part of patients. The usefulness of tiotropium on uncontrolled EIB has so far remained unclear. In this study, we report 8 cases of the difficult-to-control EIB treated with tiotropium. <b>Objective:</b> To examine the impact of tiotropium on the difficult-to-control EIB. <b>Methods:</b> In total, 8 cases of EIB were enrolled in this study. All the patients cannot achieve symptom-control with standard prevention and pharmacological treatment with rescue use of inhaled short-acting beta 2-agonist (SABA) and maintenance with inhaled corticosteroid plus long-acting beta 2-agonist. The delivered dose of tiotropium 5 microgram via respimat inhaler was added on maintenance medication. Symptom and the frequency of additional SABA use were compared before and 2 to 4 weeks after the initiation of tiotropium. Symptom was evaluated with visual analog scale (VAS) scale. More than 50% reduction of VAS scale plus rescue SABA use were defined "effective". <b>Results:</b> Demographics of 8 cases were follows: mean age was 43 (15 - 56), 4 males, smoking status: one current, 2 former, and 5 never smokers, %FEV1 was 92.0 (78.2 - 106.4)%, Fe-NO 22 (14 - 30) ppb. Tiotropium was effective on 6 among 8 cases of difficult-to-control EIB. <b>Conclusions:</b> Tiotropium could be a useful choice to manage difficult-to-control EIB.

Objective Inappropriate use of short-acting beta2-agonists (SABA) in asthma has been associated with undesired outcomes. This national expert consensus was developed to increase awareness of SABA overuse and provide recommendations on the ways to eliminate SABA overprescription and overreliance in Malaysia. Data sources This expert consensus was developed by searching the PubMed database, using index terms to identify SABA overuse-related burden and recommendations made in asthma guidelines. Consensus recommendations were made via the Delphi method, involving a Malaysian expert committee comprising 13 healthcare professionals (five pulmonologists, four family medicine specialists, two emergency medicine physicians and two pharmacists). Study selections The articles reviewed include randomized controlled trials, systematic reviews, meta-analyses, observational studies, guidelines, and surveys, with abstracts in English and published up until June 2023. Relevant recommendations were also sourced from verified websites of medical organizations and societies. Results Eleven consensus statements were developed, each statement achieving a priori agreement level of at least 70%. The statements reflect SABA overreliance in asthma care, as well as recommendations to eliminate SABA overprescription and overreliance in Malaysia. Supporting evidence in the literature as well as expert committee discussions leading to the development of the finalized statements were elaborated. Conclusion This national expert consensus discussed the burden of SABA overreliance and made specific recommendations to eliminate SABA overprescription and overreliance in the Malaysian context. This consensus document is anticipated to impart better awareness among Malaysian healthcare providers and contribute to the continuous improvement of asthma care in the country.

Short acting beta2-agonists (SABAs) such as salbutamol and terbutaline are commonly used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). According to the guideline produced by the British Thoracic Society (BTS) and the Scottish Intercollegiate Guidelines Network (SIGN), SABAs are considered to be the first line of treatment in asthma management. The National Institute for Health and Clinical Excellence (NICE) guidelines also recommend the use of SABA as the first line of treatment for managing patients with COPD. The recommendations in NICE guidelines state that in COPD patients, breathlessness and exercise limitation should be first medicated with short-acting bronchodilators (including beta2-agonists or anticholinergics) when it is required. Both salbutamol and terbutaline have been widely used for asthma and COPD, and they have been found to be extremely beneficial in the two pathologic conditions.

Overuse of short-acting beta-agonist bronchodilators in COPD during periods of clinical stability

Although there is a generally accepted consensus on the therapeutic objectives for bronchial asthma (BA) management and the availability of numerous effective treatment modalities, disease control remains suboptimal in a substantial proportion of patients globally. This review evaluates data from clinical studies assessing the therapeutic efficacy, safety, and rationale for the clinical use of the combination drug budesonide/salbutamol in routine practice. Publications indexed in the Google Scholar and Web of Science databases from 2000 to 2023 were analyzed as part of this study. Multiple investigations have highlighted the notably frequent and, in some cases, uncontrolled use of short-acting beta-agonists (SABAs) among BA patients. A novel technology has been introduced for the delivery of a budesonide/salbutamol suspension via a single metered-dose inhaler (MDI), offering a potential alternative for emergency therapy. Furthermore, this combined formulation can be utilized alongside any volume of baseline asthma therapy to promptly alleviate acute symptoms and prevent severe exacerbations. Several studies have also demonstrated the safety and efficacy of the budesonide/salbutamol combination in preventing bronchial obstruction in asthma patients. The use of a fixed combination of budesonide/salbutamol as a rescue therapy in BA patients may mitigate the risks associated with SABA monotherapy and decrease the frequency of asthma exacerbations. Consequently, this approach could lead to a reduction in the use of systemic corticosteroids in BA treatment. KEYWORDS: bronchial asthma, short-acting β2-agonists, salbutamol, budesonide, fixed combination. FOR CITATION: Simonova O.V., Sobko E.A., Demko I.V. Possibilities and rationale for the use of a fixed combination of inhaled glucocorticoid or short-acting β2-agonist in bronchial asthma. Russian Medical Inquiry. 2025;9(2):133–137 (in Russ.). DOI: 10.32364/2587-6821-2025-9-2-6

29 Impact of acute exacerbations

BackgroundGSK2190915 is a high affinity 5-lipoxygenase-activating protein inhibitor being developed for the treatment of asthma. The objective of this study was to evaluate GSK2190915 efficacy, dose–response and safety in subjects with persistent asthma treated with short-acting beta2-agonists (SABAs) only.MethodsEight-week multicentre, randomised, double-blind, double-dummy, stratified (by age and smoking status), parallel-group, placebo-controlled study in subjects aged ≥12 years with a forced expiratory volume in 1 second (FEV1) of 50–85% predicted. Subjects (n = 700) were randomised to receive once-daily (QD) oral GSK2190915 (10–300 mg), twice-daily inhaled fluticasone propionate 100 μg, oral montelukast 10 mg QD or placebo. The primary endpoint was mean change from baseline (randomisation) in trough (morning pre-dose and pre-rescue bronchodilator) FEV1 at the end of the 8-week treatment period. Secondary endpoints included morning and evening peak expiratory flow, symptom-free days and nights, rescue-free days and nights, day and night-time symptom scores, day and night-time rescue medication use, withdrawals due to lack of efficacy, Asthma Control Questionnaire and Asthma Quality of Life Questionnaire scores.ResultsFor the primary endpoint, there was no statistically significant difference between any dose of GSK2190915 QD and placebo. However, repeated measures sensitivity analysis demonstrated nominal statistical significance for GSK2190915 30 mg QD compared with placebo (mean difference: 0.115 L [95% confidence interval: 0.00, 0.23], p = 0.044); no nominally statistically significant differences were observed with any of the other doses. For the secondary endpoints, decreases were observed in day-time symptom scores and day-time SABA use for GSK2190915 30 mg QD versus placebo (p ≤ 0.05). No dose–response relationship was observed for the primary and secondary endpoints across the GSK2190915 dose range studied; the 10 mg dose appeared to be sub-optimal. GSK2190915 was associated with a dose-dependent reduction in urinary leukotriene E4. The profile and incidence of adverse events were similar between treatment groups.ConclusionEfficacy was demonstrated for GSK2190915 30 mg compared with placebo in day-time symptom scores and day-time SABA use. No additional improvement on efficacy endpoints was gained by administration of GSK2190915 doses greater than 30 mg. GSK2190915 was well-tolerated. These results may support further studies with GSK2190915 30 mg.Trial registrationClinicaltrials.gov:NCT01147744.

&lt;p&gt;Background Inhaled corticosteroids taken regularly reduce exacerbation risk in patients with mild asthma. In clinical practice however, adherence to inhaled corticosteroids is poor and the burden of disease from exacerbations is substantive. In this thesis I explore an alternative approach, that of an inhaled corticosteroid/formoterol combination used as sole reliever therapy, that potentially overcomes the problem of poor adherence. I report the results of my research, known as the PeRsonalised Asthma Combination Therapy: with Inhaled Corticosteroid And fast-onset Long acting beta agonist (PRACTICAL) study. Research aims To investigate the efficacy and safety of as-needed budesonide/formoterol, an inhaled corticosteroid (ICS)/fast-onset long-acting beta agonist (LABA) combination, as compared with maintenance budesonide (ICS) plus as-needed terbutaline, a short-acting beta-agonist (SABA), in adult patients with mild-moderate asthma. Methods This research was performed as a 52-week, open-label, parallel-group, multicentre, phase III randomised controlled trial of adults aged 18-75 with mild to moderate asthma using SABA for symptom relief, with or without low to moderate doses of maintenance ICS in the previous 12 weeks. Participants were randomly assigned (1:1) to either: (i) budesonide/formoterol Turbuhaler, an ICS/fast-onset LABA, 200/6 micrograms (μg), one inhalation as needed for relief of symptoms, or (ii) budesonide Turbuhaler, an ICS, 200µg, one inhalation twice daily, plus terbutaline Turbuhaler, a SABA, 250µg, two inhalations as needed. Participants and investigators were not masked to group assignment. Participants were seen for six study visits: randomisation, and at weeks 4, 16, 28, 40 and 52. The primary outcome was rate of severe exacerbations per patient per year, with severe exacerbations defined as the use of systemic glucocorticoids for at least three days because of asthma, or a hospitalisation or emergency department visit because of asthma requiring systemic glucocorticoids. Findings Between May 4, 2016 and Dec 22, 2017, 890 participants were assigned to treatment. The analysis included 885 of 890 randomised participants; 437 assigned to budesonide/formoterol as needed and 448 to budesonide maintenance plus terbutaline as needed. 70% of participants were using ICS at entry. The annualised severe exacerbation rate was lower with as-needed budesonide/formoterol than with maintenance budesonide (absolute rate 0.119 vs 0.172; relative rate, 0.69 [95% confidence interval [CI], 0.48 to 1.00]; p=0.049). The Asthma Control Questionnaire-5 score with budesonide/formoterol was not significantly different from budesonide maintenance (mean difference, 0.06; 95% CI -0.005 to 0.12). Conclusion This research has demonstrated that in adults with mild to moderate asthma in the real-world setting, budesonide/formoterol reliever therapy was more effective at preventing severe exacerbations than maintenance low-dose budesonide plus as-needed terbutaline without a clinically important worsening in asthma control. The evidence presented in this thesis supports the 2019 Global Initiative for Asthma recommendation that inhaled corticosteroid/formoterol reliever therapy is an alternative regimen to maintenance low-dose inhaled corticosteroid and SABA reliever for the prevention of severe exacerbations for patients with mild to moderate asthma.&lt;/p&gt;

&lt;sec&gt;&lt;st&gt;Background&lt;/st&gt; Guidelines advocate the use of spirometry to assess pulmonary function in asthmatic patients. Commonly used measures include forced expiratory volume in 1 second (FEV&lt;inf&gt;1&lt;/inf&gt;), forced expiratory ratio (FEV&lt;inf&gt;1&lt;/inf&gt;/FVC) and forced mid-expiratory flow between 25% and 75% of forced vital capacity (FEF&lt;inf&gt;25–75&lt;/inf&gt;). Impulse oscillometry (IOS) is an effort independent test performed during tidal breathing. IOS may be used to assess the total and central airway resistance at 5 Hz (R5) and 20 Hz (R20) respectively and hence derive the peripheral airway resistance from the difference (R5-R20). &lt;/sec&gt; &lt;sec&gt;&lt;st&gt;Objective&lt;/st&gt; To compare spirometry and IOS as tests of global airway function (i.e. FEV&lt;inf&gt;1&lt;/inf&gt;, FEV&lt;inf&gt;1&lt;/inf&gt;/FVC, R5) and putative measures of small airways function (i.e. FEF&lt;inf&gt;25–75&lt;/inf&gt;, R5-R20) and their relationship to long-term asthma control. &lt;/sec&gt; &lt;sec&gt;&lt;st&gt;Methods&lt;/st&gt; Spirometry and IOS measurements from asthmatics were linked to a health informatics database for oral steroid and short-acting beta agonist (SABA) use 1 year prior to the measurements. &lt;/sec&gt; &lt;sec&gt;&lt;st&gt;Results&lt;/st&gt; 442 patients had both spirometry and IOS, mean FEV&lt;inf&gt;1&lt;/inf&gt;= 86% predicted, 94% on ICS, median dose 800 µg/day. IOS and spirometry measures were equally predictive of impaired asthma control for both oral steroid and SABA use. For oral steroid use, the adjusted odds ratio, OR (95% CI): FEV&lt;inf&gt;1&lt;/inf&gt; &lt;80%: 1.56(0.99–2.47) p = 0.056, FEV&lt;inf&gt;1&lt;/inf&gt;/FVC25–75 &lt;60%: 1.84(1.18–2.86) p = 0.007, R5 &gt;150%: 1.91(1.25–2.95) p = 0.003 and R5-R20 &gt;0.1 kPa·L-1·s 1.73(1.12–2.66) p = 0.013. For SABA use, the adjusted OR (95% CI): FEV&lt;inf&gt;1&lt;/inf&gt; &lt;80%: 2.22(1.43–3.44) p &lt; 0.001, FEV&lt;inf&gt;1&lt;/inf&gt;/FVC 25–75 &lt;60%: 2.51(1.65–3.82) p &lt; 0.001, R5 &gt;150%: 1.76(1.18–2.63) p = 0.006 and R5-R20 &gt;0.1 kPa·L-1·s: 2.94(1.94–4.46) p. &lt;/sec&gt; &lt;sec&gt;&lt;st&gt;Conclusion&lt;/st&gt; Spirometry or IOS measurements are equally useful as potential markers of asthma control in persistent asthmatic patients. &lt;fig loc="float" id="F1"&gt;&lt;no&gt;Abstract P44 Figure 1&lt;/no&gt;&lt;caption&gt; Adjusted odds ratios (95% CI) for oral steroid (A) and short-acting beta-agonist use (B) in the year preceding measurements of FEVi (&lt;80% predicted, n = 140 vs &gt;80% predicted, n = 302), FEV1/FVC (&lt;0.70, n = 131 vs &gt;0.70, n = 311), FEF&lt;inf&gt;25–75&lt;/inf&gt; (&lt;60% predicted, n = 238 vs &gt;60% predicted, n = 204), R5 (&gt;150% predicted, n = 183 vs &lt;150% predicted, n = 259) and R5-R20 (&gt;0.10 kPa-L–1-s, n = 185 vs &lt;0.10 kPa-L–1-s, n = 257). The 95% CIs which exclude unity are defined as being of statistical significance. &lt;/caption&gt; &lt;link locator="Abs_p44_F001"&gt;&lt;/fig&gt; &lt;/sec&gt;

<b>Introduction:</b> Overuse of SABA, which do not treat the underlying inflammation of asthma, is linked to poor clinical outcomes such as increased exacerbation risk. <b>Aims:</b> To estimate the prevalence of SABA overuse and potential risk factors among patients with asthma in Germany as part of the SABINA framework (Cabrera C, et al. <i>ERJ</i>. 2019). <b>Methods:</b> This retrospective study used anonymized electronic healthcare data from the IQVIA Disease Analyzer database. Patients (n=15,640) aged ≥12 years with asthma who received ≥1 SABA prescription between July 2017 and June 2018 in 924 general (GP) and 22 pneumologist (PN) practices were included. SABA overuse was defined as ≥3 prescribed inhalers (~200 puffs each) in the study period. The association between SABA overuse and physician specialty, GINA steps (based on asthma medications), age, sex, and ICS(/LABA) use was estimated using multivariate regression for patients with moderate (GINA step 2) and severe (GINA steps 3–5) asthma. <b>Results:</b> Mean annual number of prescribed SABA inhalers was 3.5 per patient, increasing from 2.9 to 4.9 inhalers in patients at GINA 2 and 5, respectively. Annually, 36% of all patients (GINA 1–5) in GP and 38% in PN practices received ≥3 SABA inhalers. SABA overuse risk was 16% higher in patients treated by a GP vs. PN, 33% and 83% higher in GINA 4 and 5, respectively, vs. GINA 3, and 39% higher in male vs. female patients. SABA overuse risk was higher in patients using ICS(/LABA) at GINA 3–5 vs. at GINA 2. <b>Conclusions:</b> In Germany, SABA overuse is prevalent among patients with asthma across all GINA steps which may indicate suboptimal asthma control. Further studies are needed to investigate the reasons behind the SABA overuse.

Relationship between short-acting beta-agonist use and self-assessment responses in patients with asthma