National expert consensus on short-acting beta2-agonist overreliance in asthma care in Malaysia.

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.

Pharmacological treatment of asthma in Sweden from 2005 to 2015.

OBJECTIVE: Despite access to effective therapies many asthma patients still do not have well-controlled disease. This is possibly related to underuse of inhaled corticosteroids (ICS) and overuse of short-acting ß2-agonists (SABA). Our aim was to investigate longitudinal trends and associated factors in asthma treatment. METHODS: Two separate cohorts of adults with physician-diagnosed asthma were randomly selected from 14 hospitals and 56 primary health centers in Sweden in 2005 (n = 1182) and 2015 (n = 1225). Information about symptoms, maintenance treatment, and use of rescue medication was collected by questionnaires. Associations between treatment and sex, age, smoking, education, body mass index (BMI), physical activity, allergic asthma, and symptom control were analyzed using Pearson's chi2-test. Odds ratios (ORs) were calculated using logistic regression. RESULTS: Maintenance treatment with ICS together with long-acting ß2-agonists (LABA) and/or montelukast increased from 39.2% to 44.2% (p = 0.012). The use of ICS + LABA as-needed increased (11.1-18.9%, p < 0.001), while SABA use decreased (46.4- 41.8%, p = 0.023). Regular treatment with ICS did not change notably (54.2-57.2%, p = 0.14). Older age, former smoking, and poor symptom control were related to treatment with ICS + LABA/montelukast. In 2015, 22.7% reported daily use of SABA. A higher step of maintenance treatment, older age, obesity, shorter education, current smoking, allergic asthma, low or very high physical activity, and a history of exacerbations were associated with daily SABA use. CONCLUSIONS: The use of ICS + LABA both for maintenance treatment and symptom relief has increased over time. Despite this, the problem of low use of ICS and high use of SABA remains.

Inhaled beta2 -agonist, formoterol, enhances intense exercise performance, and sprint ability in elite cyclists.

PURPOSE: Many athletes use long-acting beta2 -agonist formoterol in treatment of asthma. However, studies in non-athlete cohorts demonstrate that inhaled formoterol can enhance sprint performance calling into question whether its use in competitive sports should be restricted. We investigated whether formoterol at upper recommended inhaled doses (54 µg) would enhance sprint ability and intense exercise performance in elite cyclists. METHODS: Twenty-one male cyclists (V̇O2max : 70.4 ± 4.3 mL × min-1 × kg-1 , mean ± SD) completed two 6-s all-out sprints followed by 4-min all-out cycling after inhaling either 54 µg formoterol or placebo. We also assessed cyclists' leg muscle mass by dual-energy X-ray absorptiometry and muscle fiber type distribution of vastus lateralis biopsies. RESULTS: Peak and mean power output during the 6-s sprint was 32 W (95% CI, 19-44 W, p < 0.001) and 36 W (95% CI, 24-48 W, p < 0.001) higher with formoterol than placebo, corresponding to an enhancing effect of around 3%. Power output during 4-min all-out cycling was 9 W (95% CI, 2-16 W, p = 0.01) greater with formoterol than placebo, corresponding to an enhancing effect of 2.3%. Performance changes in response to formoterol were unrelated to cyclists' VO2max and leg lean mass, whereas muscle fiber Type I distribution correlated with change in sprinting peak power in response to formoterol (r2 = 0.314, p = 0.012). CONCLUSION: Our findings demonstrate that an inhaled one-off dose of 54 µg formoterol has a performance-enhancing potential on sprint ability and short intense performance in elite male cyclists, which is irrespective of training status but partly related to muscle fiber type distribution for sprint ability.

Expert Consensus on SABA Use for Asthma Clinical Decision-Making: A Delphi Approach.

PURPOSE OF REVIEW: A modified Delphi process was undertaken to provide a US expert-led consensus to guide clinical action on short-acting beta2-agonist (SABA) use. This comprised an online survey (Phase 1), forum discussion and statement development (Phase 2), and statement adjudication (Phase 3). RECENT FINDINGS: In Phase 1 (n = 100 clinicians), 12% routinely provided patients with ≥4 SABA prescriptions/year, 73% solicited SABA use frequency at every patient visit, and 21% did not consult asthma guidelines/expert reports. Phase 3 experts (n = 8) reached consensus (median Likert score, interquartile range) that use of ≥3 SABA canisters/year is associated with increased risk of exacerbation and asthma-related death (5, 4.75-5); SABA use history should be solicited at every patient visit (5, 4.75-5); usage patterns over time, not absolute thresholds, should guide response to SABA overuse (5, 4.5-5). Future asthma guidelines should include clear recommendations regarding SABA usage, using expert-led thresholds for action.

Short-acting ß2-agonists over-prescription in patients with asthma: an Indian subset analysis of international SABINA III study.

OBJECTIVE: The SABINA (SABA use IN Asthma) program was initiated to describe short-acting ß2-agonists (SABA) prescription patterns and assess the impact of its over-prescription on exacerbation risk and asthma control. We evaluated SABA prescription patterns in patients with asthma in the Indian cohort of SABINA III. METHODS: This multi-centre, observational, cross-sectional study included retrospective and real-time electronic data collection. Data were extracted from medical records of patients with asthma (aged >12 years) having >3 consultations with the same healthcare practitioners between March 2019 and January 2020. The data included prescriptions of SABA and other asthma treatments and over-the-counter (OTC) purchases of SABA. SABA prescriptions were categorized by the number of SABA canisters prescribed in the 12 months preceding the study visit. RESULTS: A total of 510 patients with asthma were included from specialist care (mean age 49.1 years; 57.65 females), with 8.2% classified with mild asthma and 91.8% with moderate-to-severe asthma. SABA as monotherapy and add-on to maintenance therapy was prescribed to 4.5% (n = 23) and 44.9% (n = 229) of patients, respectively. While ICS monotherapy and ICS/LABA were prescribed to 5.1% (n = 26) and 93.3% (n = 476) of patients, respectively. SABA was found to be over-prescribed (≥3 SABA canisters/year) among 23.9% of patients (n = 122). Additionally, 8% of patients (n = 41) purchased SABA OTC without prescription. CONCLUSIONS: Nearly one-fourth of patients with asthma in India were over-prescribed SABA. Educational programmes targeted at national and regional levels should be expanded to raise greater asthma awareness and encourage the adoption of guideline-directed asthma treatment plans among healthcare practitioners.

Assessment of the effectiveness of Saba shielding with the composition of Cu-Bi in neck CT imaging: a phantom and patient study.

The use of computed tomography (CT) is a very well-established medical diagnostic imaging modality, however, the high radiation dose due to this imaging method is a major concern. Therefore, dose reduction methods are necessary, especially for superficial radiosensitive organs like the thyroid. The aim of this study is to construct and assess a CT shield with composition of 90% Cu and 10% Bi (Saba shield) with regard to dose reduction and image quality. The efficiency of the constructed shields for dose reduction was assessed by measuring entrance skin dose (ESD), using thermoluminescence dosimeters placed on an anthropomorphic phantom. Image quality was assessed quantitatively based on image noise and CT number accuracy by drawing regions of interest on CT images of the anthropomorphic phantom. Image quality was further investigated qualitatively in a patient study. Application of the Saba shield and 100% Bi shield with the thickness of one thickness (1T) reduced ESD by 50.2% and 51.7%, respectively, and using a three-fold thickness reduced ESD by 64.6% and 65.1%, respectively. Saba shield with thickness of 1T had no significant change in image noise in the anterior part, and image noise and mean CT number in the posterior part (P> 0.05). The statistical analysis performed did not find any meaningful difference between the study and control groups in image quality assessment of the patient study (P> 0.05). The 1T Saba shield reduced thyroid dose efficiently during neck CT imaging without causing unwanted effects on image quality.

Muscle hypertrophic effect of inhaled beta2 -agonist is associated with augmented insulin-stimulated whole-body glucose disposal in young men.

Rodent studies highlight enhancement of glucose tolerance and insulin sensitivity as potential clinically relevant effects of chronic beta2 -agonist treatment. However, the doses administered to rodents are not comparable with the therapeutic doses used for humans. Thus, we investigated the physiological effects of prolonged beta2 -agonist treatment at inhaled doses resembling those used in respiratory diseases on insulin-stimulated whole-body glucose disposal and putative mechanisms in skeletal muscle and adipose tissue of healthy men. Utilizing a randomized placebo-controlled parallel-group design, we assigned 21 healthy men to 4 weeks daily inhalation of terbutaline (TER; 4 mg × day-1 , n = 13) or placebo (PLA, n = 8). Before and after treatments, we assessed subjects' whole-body insulin-stimulated glucose disposal and body composition, and collected vastus lateralis muscle and abdominal adipose tissue biopsies. Glucose infusion rate increased by 27% (95% CI: 80 to 238 mg × min-1 , P = 0.001) in TER, whereas no significant changes occurred in PLA (95% CI: -37 to 195 mg × min-1 , P = 0.154). GLUT4 content in muscle or adipose tissue did not change, nor did hexokinase II content or markers of mitochondrial volume in muscle. Change in lean mass was associated with change in glucose infusion rate in TER (r = 0.59, P = 0.03). Beta2 -agonist treatment in close-to-therapeutic doses may augment whole-body insulin-stimulated glucose disposal in healthy young men and part of the change is likely to be explained by muscle hypertrophy. These findings highlight the therapeutic potential of beta2 -agonists for improving insulin sensitivity. KEY POINTS: While studies in rodents have highlighted beta2 -agonists as a means to augment insulin sensitivity, these studies utilized beta2 -agonists at doses inapplicable to humans. Herein we show that a 4-week treatment period with daily therapeutic inhalation of beta2 -agonist increases insulin-stimulated whole-body glucose disposal in young healthy lean men. This effect was associated with an increase of lean mass but not with changes in GLUT4 and hexokinase II or basal glycogen content in skeletal muscle nor GLUT4 content in abdominal adipose tissue. These findings suggest that the enhanced insulin-stimulated whole-body glucose disposal induced by a period of beta2 -agonist treatment in humans, at least in part, is attributed to muscle hypertrophy. Our observations extend findings in rodents and highlight the therapeutic potential of beta2 -agonists to enhance the capacity for glucose disposal and whole-body insulin sensitivity, providing important knowledge with potential application in insulin resistance.

Expert Opinion on Practice Patterns in Mild Asthma After the GINA 2019 Updates: A Major Shift in Treatment Paradigms from a Long-Standing SABA-Only Approach to a Risk Reduction-Based Strategy with the Use of Symptom-Driven (As-Needed) Low-Dose ICS/LABA.

PURPOSE OF REVIEW: This expert opinion, prepared by a panel of chest disease specialists, aims to review the current knowledge on practice patterns in real-life management of mild asthma and to address the relevant updates in asthma treatment by The Global Initiative for Asthma (GINA) to guide clinicians for the best clinical practice in applying these new treatment paradigms. RECENT FINDINGS: On the basis of the emerging body of evidence suggesting the non-safety of short-acting ß2-agonists (SABA)-only therapy and comparable efficacy of the as-needed inhaled corticosteroids (ICS)-formoterol combinations with maintenance ICS regimens, GINA recently released their updated Global Strategy for Asthma Management and Prevention Guide (2019). The new GINA 2019 recommendations no longer support the SABA-only therapy in mild asthma but instead includes new off-label recommendations such as symptom-driven (as-needed) low-dose ICS-formoterol and "low dose ICS taken whenever SABA is taken." The GINA 2019 asthma treatment recommendations include a major shift from long-standing approach of clinical practice regarding the use of symptom-driven SABA treatment alone in the management of mild asthma. This expert opinion supports the transition from a long-standing SABA-only approach to a risk reduction-based strategy, with the use of symptom-driven (as-needed) low-dose ICS/LABA in mild asthma patients, particularly in those with poor adherence to controller medications. The thoughtful and comprehensive approach of clinicians to these strategies is important, given that the exact far-reaching impact of this major change in management of mild asthma in the real-world settings will only be clarified over time.

Beta2 -agonist increases skeletal muscle interleukin 6 production and release in response to resistance exercise in men.

OBJECTIVE: Several tissues produce and release interleukin-6 (IL-6) in response to beta2 -adrenergic stimulation with selective agonists (beta2 -agonists). Moreover, exercise stimulates muscle IL-6 production, but whether beta2 -agonists regulate skeletal muscle production and release of IL-6 in humans in association with exercise remains to be clarified. Thus, we investigated leg IL-6 release in response to beta2 -agonist salbutamol in lean young men at rest and in recovery from resistance exercise. DESIGN: The study employed a randomized controlled crossover design, where 12 men ingested either salbutamol (16 mg) or placebo for 4 days, followed by the last dose (24 mg) administered 1½ h before exercise. Arterial and femoral venous plasma IL-6 as well as femoral artery blood flow was measured before and ½-5 h in recovery from quadriceps muscle resistance exercise. Furthermore, vastus lateralis muscle biopsies were collected ½ and 5 h after exercise for determination of mRNA levels of IL-6 and Tumor Necrosis Factor (TNF)-α. RESULTS: Average leg IL-6 release was 1.7-fold higher (p = 0.01) for salbutamol than placebo, being 138 ± 76 and 79 ± 66 pg min-1 (mean ± SD) for salbutamol and placebo, respectively, but IL-6 release was not significantly different between treatments within specific sampling points at rest and after exercise. Muscle IL-6 mRNA was 1.5- and 1.7-fold higher (p = 0.001) for salbutamol than placebo ½ and 5 h after exercise, respectively, whereas no significant treatment differences were observed for TNF-α mRNA. CONCLUSIONS: Beta2 -adrenergic stimulation with high doses of the selective beta2 -agonist salbutamol, preceeded by 4 consecutive daily doses, induces transcription of IL-6 in skeletal muscle in response to resistance exercise, and increases muscle IL-6 release in lean individuals.

An assessment of asthma exacerbations in pediatric patients using a long-acting B2-agonist plus inhaled corticosteroid versus an inhaled corticosteroid alone.

Background: An asthma exacerbation is an anticipated sudden worsening of the disease severity, which usually does not respond to conservative therapy. The management of asthma depends on the severity of the disease symptoms, which includes an inhaled corticosteroid (ICS) and a bronchodilator. This study aimed to assess the efficacy of combining a long-acting B2-agonist (LABA) with ICS, compared to ICS alone, to reduce the incidence of asthma exacerbations in pediatric patients, diagnosed with severe persistent asthma. Methods: A retrospective analysis of the medical records was conducted for 586 children, admitted to the Emergency Department (ED) at King Abdullah Specialized Children Hospital in Riyadh, Saudi Arabia, for the management of severe persistent asthma symptoms, from January 2016 to September 2019. Results: The majority (n = 480, 81.9%) of the patients received fluticasone (Flovent)® as the standard of care ICS treatment for controlling asthma, and a small proportion (n = 106, 18.1%) were treated with a combination of LABA and ICS. A significant increase in the frequency of recurrent asthma exacerbation episodes occurred in the group receiving ICS alone (98.5%), compared to 67.0% in the combination group (p < 0.0001). Moderate to severe exacerbations were significantly higher in the ICS group compared to the combination group (95.6% versus 84.5%, respectively, p = 0.0005). Conclusions: The current results confirm the substantial efficacy of the LABA/ICS combination therapy in reducing the incidence and severity of asthma exacerbations in pediatric patients, compared to ICS alone.

Identifying the drivers of patients' reliance on short-acting ß2-agonists in asthma.

BACKGROUND: One of the most commonly observed asthma treatment patterns is the underuse of inhaled corticosteroid (ICS) maintenance therapy when patients are not experiencing symptoms, and the predominant use of short-acting ß2-agonists (SABAs) when patients are experiencing symptoms. This multinational study investigated the current beliefs and behaviors related to reliance on reliever inhalers among asthma patients, and the reasons why patients may not adhere to their recommended maintenance controller treatment. METHODS: This was a qualitative research study, in which 80 patients with asthma who were receiving reliever therapy (i.e. SABAs) were interviewed, in-depth, for 60 min. The interview questions focused on the patients' experience of living with asthma and their inhaled treatment regimens. RESULTS: The key insights identified in the interviews were (a) patients had a strong emotional attachment to SABA relievers driven by their efficacy and success in quickly alleviating asthma symptoms, with the reliever also becoming an emotional support; (b) patients typically did not understand that the frequent use of SABAs indicates poor asthma control; (c) patients had a misperception of ICS, which could lead to a delay in escalation and poor adherence; and (d) severe exacerbations improve adherence to ICS, but only temporarily in many cases. CONCLUSION: This study confirmed the poor level of control patients have over their asthma, and how this affects their lifestyle and daily activities. Our results also confirmed that the patients' perception of both the disease and treatment plays a key role in SABA reliance and ICS underuse.

Salbutamol use in relation to maintenance bronchodilator efficacy in COPD: a prospective subgroup analysis of the EMAX trial.

BACKGROUND: Short-acting ß2-agonist (SABA) bronchodilators help alleviate symptoms in chronic obstructive pulmonary disease (COPD) and may be a useful marker of symptom severity. This analysis investigated whether SABA use impacts treatment differences between maintenance dual- and mono-bronchodilators in patients with COPD. METHODS: The Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised symptomatic patients with low exacerbation risk not receiving inhaled corticosteroids 1:1:1 to once-daily umeclidinium/vilanterol 62.5/25 µg, once-daily umeclidinium 62.5 µg or twice-daily salmeterol 50 µg for 24 weeks. Pre-specified subgroup analyses stratified patients by median baseline SABA use (low, < 1.5 puffs/day; high, ≥1.5 puffs/day) to examine change from baseline in trough forced expiratory volume in 1 s (FEV1), change in symptoms (Transition Dyspnoea Index [TDI], Evaluating Respiratory Symptoms-COPD [E-RS]), daily SABA use and exacerbation risk. A post hoc analysis used fractional polynomial modelling with continuous transformations of baseline SABA use covariates. RESULTS: At baseline, patients in the high SABA use subgroup (mean: 3.91 puffs/day, n = 1212) had more severe airflow limitation, were more symptomatic and had worse health status versus patients in the low SABA use subgroup (0.39 puffs/day, n = 1206). Patients treated with umeclidinium/vilanterol versus umeclidinium demonstrated statistically significant improvements in trough FEV1 at Week 24 in both SABA subgroups (59-74 mL; p < 0.001); however, only low SABA users demonstrated significant improvements in TDI (high: 0.27 [p = 0.241]; low: 0.49 [p = 0.025]) and E-RS (high: 0.48 [p = 0.138]; low: 0.60 [p = 0.034]) scores. By contrast, significant reductions in mean SABA puffs/day with umeclidinium/vilanterol versus umeclidinium were observed only in high SABA users (high: - 0.56 [p < 0.001]; low: - 0.10 [p = 0.132]). Similar findings were observed when comparing umeclidinium/vilanterol and salmeterol. Fractional polynomial modelling showed baseline SABA use ≥4 puffs/day resulted in smaller incremental symptom improvements with umeclidinium/vilanterol versus umeclidinium compared with baseline SABA use < 4 puffs/day. CONCLUSIONS: In high SABA users, there may be a smaller difference in treatment response between dual- and mono-bronchodilator therapy; the reasons for this require further investigation. SABA use may be a confounding factor in bronchodilator trials and in high SABA users; changes in SABA use may be considered a robust symptom outcome. FUNDING: GlaxoSmithKline (study number 201749 [NCT03034915]).

Precision Medicine in Childhood Asthma: Omic Studies of Treatment Response.

Asthma is a heterogeneous and multifactorial respiratory disease with an important impact on childhood. Difficult-to-treat asthma is not uncommon among children, and it causes a high burden to the patient, caregivers, and society. This review aims to summarize the recent findings on pediatric asthma treatment response revealed by different omic approaches conducted in 2018-2019. A total of 13 studies were performed during this period to assess the role of genomics, epigenomics, transcriptomics, metabolomics, and the microbiome in the response to short-acting beta agonists, inhaled corticosteroids, and leukotriene receptor antagonists. These studies have identified novel associations of genetic markers, epigenetic modifications, metabolites, bacteria, and molecular mechanisms involved in asthma treatment response. This knowledge will allow us establishing molecular biomarkers that could be integrated with clinical information to improve the management of children with asthma.

Study of prebiotic properties of selected banana species in Thailand.

Prebiotics are functional foods with health-promoting properties that are used in many developed countries. Thailand is one of the countries that produces many plants that should have prebiotic properties. In this study, we investigated the potential prebiotic effects of powders obtained from Saba, Pisang Awak Banana and Silver bluggoe in vitro in accordance with their physical, chemical and microbiological properties. These selected plants were found to demonstrate good water-/oil-binding properties. They contained chlorophyll, beta carotene and lycopene and showed good resistance to stomach and small-intestine enzymes. The selected plants were further used to evaluate prebiotic properties by supplementing as a carbon source in culturing broth for growing probiotic bacteria and pathogenetic bacteria. The increase in the number of probiotic bacteria during fermentation of these selected plants correlated with decreased pH. The growth of four strains of probiotic bacteria seemed to be promoted in MRS broth containing these selected plants, but no significant differences in the number of probiotic bacterial groups were detected in response to difference concentrations of all these selected plants. In addition, we noted that a decrease in the number of all four strains of pathogenic bacteria during fermentation of these selected plants correlated with a decreased pH. Moreover, the antimicrobial activity of selected plant prebiotics supported probiotic substance production to inhibit growth of pathogenic bacteria. In conclusion, we have shown that the addition of selected prebiotic plants, indicating that they should be used as a prebiotic food ingredient, represents a potential alternative to available commercial prebiotics.

It is time to change the way we manage mild asthma: an update in GINA 2019.

Asthma is a heterogeneous lung disease, usually characterised by chronic airway inflammation. Although evidence-based treatments are available in most countries, asthma control remains suboptimal, and asthma-related deaths continue to be an ongoing concern. Generally, it is believed that between 50 to 75% of patients with asthma can be considered as having mild asthma.Previous versions of Global Initiative for Asthma (GINA) suggested that mild asthma in adults can be well managed with either reliever medications, for example, short-acting beta2 agonists (SABA) alone or with the additional use of controllers such as regular low-dose inhaled corticosteroids (ICS). Given the low frequency or non-bothersome nature of symptoms in mild asthma, patients' adherence towards their controller medications, especially to ICS is usually not satisfactory. Such patients often rely on SABA alone to relieve symptoms, which may contribute to SABA over-reliance. Overuse of relievers such as SABAs has been associated with poor asthma outcomes, such as exacerbations and even deaths. The new GINA 2019 asthma treatment recommendations represent significant shifts in asthma management at Steps 1 and 2 of the 5 treatment steps. The report acknowledges an emerging body of evidence suggesting the non-safety of SABAs overuse in the absence of concomitant controller medications, therefore does not support SABA-only therapy in mild asthma and has included new off-label recommendations such as symptom-driven (as-needed) low dose ICS-formoterol and "low dose ICS taken whenever SABA is taken".The GINA 2019 report highlights significant updates in mild asthma management and these recommendations represent a clear deviation from decades of clinical practice mandating the use of symptom-driven SABA treatment alone in those with mild asthma. While the new inclusions of strategies such as symptom-driven (as-needed) ICS-formoterol and "ICS taken whenever SABA is taken" are based on several key trials, data in this context are still only emergent data, with clear superiority of as needed ICS-formoterol combinations over maintenance ICS regimens yet to be established for valid endpoints. Nevertheless, current and emerging data position the clinical asthma realm at a watershed moment with imminent changes for the way we manage mild asthma likely in going forward.

Perception of asthma control among asthmatics seen inChest Clinic at Tertiary Hospital, Addis Ababa, Ethiopia.

BACKGROUND: Patient awareness of asthma severity is important for optimal asthma management. However, there is often a discrepancy between physician assessment of asthma control based on guidelines and patient discernment of control. We compared physician and patient perception of asthma control in a clinic population seen at a tertiary hospital in Addis Ababa, Ethiopia. METHODS: In this cross-sectional study, 182 consecutive patients with a physician diagnosis of asthma seen in Chest Clinic at Tikur Anbessa Specialized Hospital (TASH) between July and December 2015 were studied. Demographics, asthma symptoms, medication use in the past month, and self-perception of asthma control in the past 7 days were obtained from the clinic records. Physician assessed asthma control was based on the GINA asthma symptom control assessment tool. Lung function was measured using a Diagnostic EasyOne Plus model 2001 SN spirometer. The institutional review board approved the study protocol. RESULTS: Of the 182 subjects, 68.1% were female. The mean age was 52 ± 12 years, and the mean (SD) duration of asthma was 19.4 ± 12.7 years. Forty-four (24.2%) patients had physician determined well-controlled asthma and 138 (75.8%) patients had physician determined partly controlled/uncontrolled asthma. One hundred and fifty-one (83%) patients thought their asthma control was good. However, the degree of concordance between physician evaluation and patient perception of asthma control was low (kappa index = 0.09). On multivariate analysis, self-perceived poor asthma control was associated with any activity limitation due to asthma and inconsistent inhaled corticosteroid use. CONCLUSION: In our study, the first of its kind in Ethiopia, a high percent of patients with physician determined well-controlled asthma has appropriate perception of their disease state. However, those patients with partly controlled/uncontrolled asthma had poor self-perception of their disease, emphasizing the need for further patient education. These conclusions may be especially useful in the care of asthmatics from other low-income countries.

Administrative databases and clinical governance: The case of COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. However, COPD is still underdiagnosed, undertreated, and not sufficiently prevented. Health administrative databases provide a powerful way of studying COPD in the population. METHODS: This retrospective study used administrative data, collected during 2011 and 2012, retrieved from 3 Italian local health authorities (LHAs). RESULTS: The analysis through administrative databases allowed firstly to identify patients with COPD receiving services by the 3 LHAs: The estimated average is ~3% of the population aged ≥40 years. Furthermore, it was also possible to stratify patients by investigating the health consumption in hospitalization for COPD and use of respiratory drugs. In all 3 LHA patients with moderate COPD were the majority of the population with COPD. Finally, it was possible to distinguish patients who made an appropriate use of SABA (76% of the total), patients who had a potentially inappropriate use (20%), and those with an overuse of SABA (4%). CONCLUSION: The use of SABA consumption patterns can be a reliable proxy variable to detect subgroups who may necessitate therapy revision. Health administrative databases seem beneficial for planning health care interventions, including the COPD field. They are robust information systems subjected to regular data quality controls remaining the prevalent data source, reliable because of the amount of data and the population coverage, especially in countries with a National Health Service System.

Beta2 -adrenoceptor agonist salbutamol increases protein turnover rates and alters signalling in skeletal muscle after resistance exercise in young men.

KEY POINTS: Animal models have shown that beta2 -adrenoceptor stimulation increases protein synthesis and attenuates breakdown processes in skeletal muscle. Thus, the beta2 -adrenoceptor is a potential target in the treatment of disuse-, disease- and age-related muscle atrophy. In the present study, we show that a few days of oral treatment with the commonly prescribed beta2 -adrenoceptor agonist, salbutamol, increased skeletal muscle protein synthesis and breakdown during the first 5 h after resistance exercise in young men. Salbutamol also counteracted a negative net protein balance in skeletal muscle after resistance exercise. Changes in protein turnover rates induced by salbutamol were associated with protein kinase A-signalling, activation of Akt2 and modulation of mRNA levels of growth-regulating proteins in skeletal muscle. These findings indicate that protein turnover rates can be augmented by beta2 -adrenoceptor agonist treatment during recovery from resistance exercise in humans. ABSTRACT: The effect of beta2 -adrenoceptor stimulation on skeletal muscle protein turnover and intracellular signalling is insufficiently explored in humans, particularly in association with exercise. In a randomized, placebo-controlled, cross-over study investigating 12 trained men, the effects of beta2 -agonist (6 × 4 mg oral salbutamol) on protein turnover rates, intracellular signalling and mRNA response in skeletal muscle were investigated 0.5-5 h after quadriceps resistance exercise. Each trial was preceded by a 4-day lead-in treatment period. Leg protein turnover rates were assessed by infusion of [13 C6 ]-phenylalanine and sampling of arterial and venous blood, as well as vastus lateralis muscle biopsies 0.5 and 5 h after exercise. Furthermore, myofibrillar fractional synthesis rate, intracellular signalling and mRNA response were measured in muscle biopsies. The mean (95% confidence interval) myofibrillar fractional synthesis rate was higher for salbutamol than placebo [0.079 (95% CI, 0.064 to 0.093) vs. 0.066 (95% CI, 0.056 to 0.075%) × h-1 ] (P < 0.05). Mean net leg phenylalanine balance 0.5-5 h after exercise was higher for salbutamol than placebo [3.6 (95% CI, 1.0 to 6.2 nmol) × min-1  × 100 gLeg Lean Mass-1 ] (P < 0.01). Phosphorylation of Akt2, cAMP response element binding protein and PKA substrate 0.5 and 5 h after exercise, as well as phosphorylation of eEF2 5 h after exercise, was higher (P < 0.05) for salbutamol than placebo. Calpain-1, Forkhead box protein O1, myostatin and Smad3 mRNA content was higher (P < 0.01) for salbutamol than placebo 0.5 h after exercise, as well as Forkhead box protein O1 and myostatin mRNA content 5 h after exercise, whereas ActivinRIIB mRNA content was lower (P < 0.01) for salbutamol 5 h after exercise. These observations suggest that beta2 -agonist increases protein turnover rates in skeletal muscle after resistance exercise in humans, with concomitant cAMP/PKA and Akt2 signalling, as well as modulation of mRNA response of growth-regulating proteins.

Determination of asthma control using administrative data regarding short-acting beta-agonist inhaler purchase.

BACKGROUND: Symptom control is a primary goal in asthma. We hypothesized that administrative data regarding rescue inhaler purchases may correlate with asthma symptom control. METHODS: We identified all patients who purchased short-acting beta-agonist (SABA) inhalers during the course of one year in the database of a Health Maintenance Organization (HMO). Primary physicians identified asthma patients and classified their asthma symptom control into three groups according to the Global Initiative for Asthma (GINA) guidelines. Asthma patients were asked to answer symptom questionnaires and grade their asthma control. SABA inhaler purchases were compared between asthma control groups as classified by the guidelines, the physicians and the patients. We also compared the agreement on asthma control between the three methods of classification. RESULTS: Of 241 asthma patients, 83 completed the questionnaires. Using the GINA guidelines criteria, 26 were symptom controlled, 46 were partially controlled and 11 were uncontrolled. SABA inhaler purchases were not significantly lower in the controlled group. Using patients' overall impression of their asthma control, the mean numbers of SABA inhalers purchased were 1.5, 4.4 and 6.4 per year in the controlled, partially controlled and uncontrolled groups, respectively (p = 0.03). Patients' classification of asthma control had better agreement (kappa = 0.34) with GINA guidelines than physician's' agreement (kappa = 0.05). CONCLUSION: When using administrative data for asthma patients, 2 or more SABA inhaler purchases in one year should alert the physician for the need for asthma control evaluation. Purchase of at least 4 SABA inhalers a year may be regarded as a marker for asthma that is not controlled.

A Novel Assay for Easy and Rapid Quantification of Helicobacter pylori Adhesion.

BACKGROUND: Reducing adhesion of Helicobacter pylori to gastric epithelial cells could be a new way to counteract infections with this organism. We here present a novel method for quantification of Helicobacter pylori adhesion to cells. METHODS: Helicobacter pylori is allowed to adhere to AGS or MKN45g cells in a 96-well microtiter plate. Then wells are added saponin, which lyses the cells without affecting the bacteria. After addition of alamarBlue(®) (resazurin) and 1- to 2-hour incubation, fluorescence measurements can be used to quantify the number of adherent bacteria. RESULTS: By use of the method, we demonstrate that adhesion of both a sabA and babA deletion mutant of H. pylori is significantly reduced compared to the wild type. CONCLUSION: The method offers a number of applications and may be used to compare the adherence potential of different strains of H. pylori to either cells or different materials or to screen for potential anti-adhesive compounds. The results presented here suggest that this easy and reproducible assay is well suited for quantitative investigation of H. pylori adhesion.