Long-acting Beta Research Articles

An Overview of Pathological Pathway of Asthma and Molecular Mechanisms of Anti-Asthmatic Phytoconstituents

: Asthma presents with chronic inflammation and airway constriction triggered by allergens or pollution. Inflammatory mediators such as histamine and leukotrienes, released in response to inflammation, prompt bronchoconstriction, contracting the smooth muscles around the airways. This constriction obstructs airflow and worsens symptoms such as coughing, wheezing, and breathlessness. Additionally, airways become hyperresponsive, reacting excessively even to harmless stimuli. Persistent inflammation leads to the production of thick mucus, further blocking airflow and worsening symptoms. Mast cell-released histamine triggers bronchoconstriction, leukotrienes, and prostaglandins (eg, Interleukin-4, Interleukin-13) and promotes airway inflammation while cytokines drive Th2-mediated immune responses. Current therapies in asthma include long-acting beta agonists, leukotriene modifiers, inhaled corticosteroids, and immunomodulators. Natural products, due to their anti-inflammatory, antioxidant and immunomodulatory properties, have emerged as promising anti-asthmatic candidates. Polyphenols (quercetin, resveratrol, curcumin, etc.) and Omega-3 fatty acids offer anti-inflammatory benefits by suppressing cytokines and oxidative stress. Natural products intervene at various levels of these pathways. Quercetin inhibits the release of mast cell histamines, alleviating bronchoconstriction. Curcumin suppresses Th2 cytokines, mitigating the allergic response. Omega-3 fatty acids modulate leukotriene and prostaglandin production, reducing airway inflammation. This review concludes that natural phytobioactives have potential in asthma management due to their complex mechanisms that target various immuno-inflammatory mediators.

In Vitro Analysis of Aerodynamic Properties and Co-Deposition of a Fixed-Dose Combination of Fluticasone Furoate, Umeclidinium Bromide, and Vilanterol Trifenatate.

Effective airway delivery of a fixed-dose combination of triple-aerosolized inhaled corticosteroid (ICS)/long-acting beta agonist (LABA)/long-acting muscarinic antagonist (LAMA) is likely to positively affect therapeutic responses predicted in patients with asthma and chronic obstructive pulmonary disease. This study aimed to conduct in vitro fluticasone furoate, vilanterol trifenatate, and umeclidinium bromide depositions in a Next Generation Impactor. The aerodynamic properties of these inhaled medications influence the spatial distribution and drug abundance, particularly in the smaller airways, to reverse or alleviate disease pathology. The Next Generation Impactor was used to demonstrate the aerodynamic particle size distributions of fluticasone furoate, vilanterol trifenatate, and umeclidinium bromide delivered from a dry powder inhaler at different flow rates across all stages of the impactors. This in vitro study analyzed the distribution pattern of individual drug components to simulate mono-component deposition and co-deposition in the official model in the United States Pharmacopeia. An Andersen cascade impactor together with scanning electron microscope-energy-dispersive X-ray was employed to observe the drug deposition on each stage of the impactor. We found that the distribution pattern of each component at the same cascade level was comparable, and the aerosol particles of the three drugs reached the in vitro representation of the lower airway compartment. The specified flow rates generated the desired fine particle fraction, fine particle dose, and mass median aerodynamic diameter. Our results also demonstrated visualized deposition patterns of the delivered drugs from different stages of the cascade impactor that may predict deposition as it occurs in vivo. Spatial distribution and abundance of ICS/LABA/LAMA in the same cascade levels were closely comparable, and the aerosol particles were able to reach the small aerosol-sized cascades at the lower levels to some extent.

Bronchial asthma with normal forced expiratory volume in 1 second (FEV1) compared with low FEV1.

Cough variant asthma (CVA) is characterized by cough as a sole symptom and normal pulmonary function. However, it is unclear whether CVA really common among asthmatic patients with normal forced expiratory volume in 1 second (FEV1). The aim of this study was to evaluate the incidence of cough alone symptom among the subjects with normal FEV1 and to evaluate their differences from ordinary asthmatic subjects. We defined normal FEV1 as ≥90% predicted based on the article of Kotti GH. Of the patients with normal FEV1, we chose subjects without wheeze, and the duration of cough was not to ask, since the symptoms often occurred with acute exacerbation and timing of visiting a doctor depended on each patient's perception. Test for airway hyperresponsiveness was not performed in this study. Visual analogue scale (VAS) scores for cough and dyspnea, FEV1, and fractional exhaled nitric oxide (FeNO) responsiveness to inhaled corticosteroid (ICS)/long-acting beta2 agonist (LABA) treatment were compared in patients with normal FEV1 and with low FEV1 <90%. Correlations of changes in symptoms with changes of FEV1, FeNO, peripheral eosinophil count, and serum immunoglobulin E (IgE) at single time point were also examined in each group and in overall patients. The participants were 329 physician-diagnosed treatment-naive patients with asthma who were divided into 187 in normal FEV1 and 142 in low FEV1 groups. Cough without dyspnea was present in 16 patients (8.6%) in the normal FEV1 group, suggesting candidates for CVA in this analysis were quite few. Improvement in symptoms after treatment was similar between both groups. But VAS scores of dyspnea were still higher in the low FEV1 group. The degree of improvement in FEV1 after ICS/LABA treatment was less in the normal FEV1 group than in the low FEV1 group, but was still evident. Peripheral eosinophil count, serum IgE, and FeNO values before treatment were lower in the normal FEV1 group. In overall patients, improvements of symptoms after treatment were significantly correlated with FEV1 changes. Improvement of dyspnea was also significantly related to peripheral eosinophil count and change of FeNO, whereas improvement of cough was not related to these T helper 2 (Th2) response markers. Candidates for CVA among the patients with asthma with predicted FEV1 ≥90% were few. Participants with normal FEV1 respond well to ICS/LABA treatment for improvement of symptom. The change of FEV1 after treatment, and the pre-treatment blood eosinophil count, serum IgE, and FeNO were lower in normal FEV1 cases than in low FEV1 cases. These observations suggest asthmatic patients with normal FEV1, including candidates for CVA having just common mild asthma. In overall participants, symptoms of cough and dyspnea were similar, but were not identical in relation to the Th2 background.

Breathing for Two: Asthma Management, Treatment, and Safety of Pharmacological Therapy during Pregnancy.

The primary objectives of asthma management during pregnancy are to achieve adequate symptom control, reduce the risk of acute exacerbations, and maintain normal pulmonary function, all of which contribute to ensuring the health and well-being of both the mother and the baby. The Global Initiative for Asthma (GINA) recommends that pregnant women with asthma continue using asthma medications throughout pregnancy, as the benefits of well-controlled asthma for both the mother and fetus outweigh the potential risks of medication side effects, poorly controlled asthma, and exacerbations. The classification of asthma medications by the US Food and Drug Administration (FDA) into categories A, B, C, D, and X is no longer applied. Instead, the potential benefits and risks of each medication during pregnancy and lactation are considered individually. The use of medications to achieve good asthma control and prevent exacerbations during pregnancy is justified, encompassing inhaled corticosteroids (ICS), some leukotriene receptor antagonists (LTRA), short-acting beta-2 agonists (SABA), long-acting beta-2 agonists (LABA), short-acting muscarinic antagonists (SAMA), long-acting muscarinic antagonists (LAMA), and, recently, biological therapies, even in the absence of definitive safety data during pregnancy.

For people with uncontrolled asthma, how does adding long-acting beta2 agonists (LABA) or long-acting muscarinic antagonists (LAMA) to different doses of inhaled corticosteroids (ICS) or doubling the dose of ICS compare with medium-dose ICS?

For people with uncontrolled asthma, how does adding long-acting beta2 agonists (LABA) or long-acting muscarinic antagonists (LAMA) to different doses of inhaled corticosteroids (ICS) or doubling the dose of ICS compare with medium-dose ICS?

A Simulation Study of the Effect of Clinical Characteristics and Treatment Choice on Reliever Medication Use, Symptom Control and Exacerbation Risk in Moderate-Severe Asthma.

The relationship between immediate symptom control, reliever medication use and exacerbation risk on treatment response and factors that modify it have not been assessed in an integrated manner. Here we apply simulation scenarios to evaluate the effect of individual baseline characteristics on treatment response in patients with moderate-severe asthma on regular maintenance dosing monotherapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR). Reduction in reliever medication use (puffs/24h), change in symptom control scores (ACQ-5), and annualised exacerbation rate over 12months were simulated in a cohort of patients with different baseline characteristics (e.g. time since diagnosis, asthma control questionnaire (ACQ-5) symptom score, smoking status, body mass index (BMI) and sex) using drug-disease models derived from large phaseIII/IV clinical studies. Simulation scenarios show that being a smoker, having higher baseline ACQ-5 and BMI, and long asthma history is associated with increased reliever medication use (p < 0.01). This increase correlates with a higher exacerbation risk and higher ACQ-5 scores over the course of treatment, irrespective of the underlying maintenance therapy. Switching non-responders to ICS monotherapy to combination therapy after 3months resulted in immediate reduction in reliever medication use (i.e. 1.3 vs. 1.0 puffs/24h for FP/SAL and BUD/FOR, respectively). In addition, switching patients with ACQ-5 > 1.5 at baseline to FP/SAL resulted in 34% less exacerbations than those receiving regular dosing BUD/FOR (p < 0.01). We have identified baseline characteristics of patients with moderate to severe asthma that are associated with greater reliever medication use, poor symptom control and higher exacerbation risk. Moreover, the effects of different inhaled corticosteroid (ICS)/long-acting beta agonist (LABA) combinations vary significantly when considering long-term treatment performance. These factors should be considered in clinical practice as a basis for personalised management of patients with moderate-severe asthma symptoms.

Factors influencing survival and mortality among adult Aboriginal Australians with bronchiectasis-A 10-year retrospective study.

The prevalence of bronchiectasis among adult Aboriginal Australians is higher than that of non-Aboriginal Australians. However, despite evidence to suggest higher prevalence of bronchiectasis among Aboriginal people in Australia, there is sparce evidence in the literature assessing clinical parameters that may predict survival or mortality in this population. Aboriginal Australians residing in the Top End Health Service region of the Northern Territory of Australia aged >18 years with chest computed tomography (CT) confirmed bronchiectasis between 2011 and 2020 were included. Demographics, body mass index (BMI), medical co-morbidities, lung function data, sputum microbiology, chest CT scan results, hospital admissions restricted to respiratory conditions and all-cause mortality were assessed. A total of 459 patients were included, of whom 146 were recorded deceased (median age at death 59 years). Among the deceased cohort, patients were older (median age 52 vs. 45 years, p = 0.023), had a higher prevalence of chronic obstructive pulmonary disease (91 vs. 79%, p = 0.126), lower lung function parameters (median percentage predicted forced expiratory volume in 1 s 29 vs. 40%, p = 0.149), a significantly greater proportion cultured non-Aspergillus fungi (65 vs. 46%, p = 0.007) and pseudomonas (46 vs. 28%, p = 0.007) on sputum microbiology and demonstrated bilateral involvement on radiology. In multivariate models advancing age, prior pseudomonas culture and Intensive care unit (ICU) visits were associated with increased odds of mortality. Higher BMI, better lung function on spirometry, prior positive sputum microbiology for Haemophilus and use of inhaled long-acting beta antagonist/muscarinic agents may have a favourable effect. The results of this study may be of use to stratify high risk adult Aboriginal patients with bronchiectasis and to develop strategies to prevent future mortality.

The diagnostic impact of fractional exhaled nitric oxide for asthmatic cough in nontuberculous mycobacterial pulmonary disease.

Measurement of exhaled nitric oxide (FeNO) is a potentially useful diagnostic test for asthma. However, no study has explored the relationship between FeNO and respiratory symptoms of nontuberculous mycobacterial pulmonary disease (NTM-PD) complicated with asthma. The objective of this study was to assess the utility of measuring FeNO levels in patients with NTM-PD complicated by asthma. In this single-center retrospective cohort study, 140 NTM-PD patients with FeNO measured were enrolled. We selected NTM-PD patients who complicated with asthma as the NTM+BA group, defined using the following criteria: NTM patients with symptoms consistent with asthma, and NTM patients with symptomatic improvement after diagnostic therapy with ICS ± a long-acting beta 2-agonist (LABA). We then calculated a diagnostic cutoff point to distinguish between the NTM+BA groups and the NTM groups (all others). High-resolution computed tomography (HRCT) images were evaluated using the CT scoring system and their association with FeNO was examined. A total of 89 patients were included in the study. (31 in the NTM+BA group and 58 in the NTM group). Compared with the NTM group, the NTM+BA group had higher rates of allergic disease (51.6% vs. 22.4%; p=0.0085) and higher FeNO values (median, 23 [interquartile range {IQR}, 15.0-43.0] ppb vs. median, 17 [IQR, 11.8-23.0] ppb; p=0.015). With diagnostic asthma care using mainly ICS/LABA with reference to the FeNO, most patients (91.0%, 20/22) in the NTM-preceding subgroup in the NTM+BA group demonstrated a prompt improvement of their symptoms and AFB culture findings did not worsen (Culture positive rate (%): Pre-treatment: 59.1% vs. Post-treatment: 40.9%, p=0.3660) at 6 months after starting diagnostic therapy. The optimal diagnostic cutoff point of FeNO to distinguish between the two groups was calculated as 21.5 ppb by the ROC curve (sensitivity 75%, specificity 71.93%, p<0.0001; area under the curve: 0.7989). No significant correlation was observed between FeNO and the severity of CT images in the patients. A certain number of patients with NTM-PD showed exacerbated respiratory symptoms due to asthmatic complications. Elevated FeNO levels suggest asthma complications, even in patients with NTM.

Effect of fluticasone propionate/formoterol and fluticasone furoate/vilanterol on adolescents with chronic bronchial obstruction

BackgroundThe combination of inhaled corticosteroid and long-acting beta-agonist (ICS/LABA) has shown superiority in improving lung function (FEV1) compared with ICS. The clinical effect of ICS/LABA depends on the fine-particle fraction (FPF) and the pulmonary deposition. ObjectiveWe sought to compare the efficacy of two combinations of an inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA), fluticasone propionate/formoterol and fluticasone furoate/vilanterol, in asthmatic adolescents with chronic bronchial obstruction. MethodsFluticasone propionate/formoterol (FP/FORM) (125/5 μg 2 doses twice daily via the k-haler®) and fluticasone furoate/vilanterol (FF/VI) (92/22 μg once daily via the Ellipta®) were administered to adolescents aged 12 to 17 years who required regular anti-asthmatic medication and had a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio below -1.65 SD in a 2-sequence, 16-week crossover trial. The primary efficacy end point was change in FEV1 compared to baseline. Secondary end points were FEV1/FVC, maximal expiratory flow at 50% of the forced vital capacity (MEF50), impulse oscillometry indices respiratory resistance at 5 Hz (R5), difference of R5 and R20 (R5−20), area of reactance (AX), and Asthma Control Test. ResultsBoth ICS/LABA combinations resulted in a significant improvement in FEV1 and MEF50 Z-scores without any significant difference between FP/FORM and FF/VI. Forty percent of patients achieved a normal prebronchodilator FEV1/FVC Z-score with either treatment. AX or R5−20 did not improve significantly with either treatment. ConclusionBoth ICS/LABA combinations demonstrated significant improvements in FEV1 Z-score. Over one-third of the asthmatic adolescents with prolonged bronchial obstruction achieved a normal prebronchodilator FEV1/FVC level.

Biologic therapies for severe asthma with persistent type 2 inflammation.

Asthma is a chronic inflammatory airways disease with reversible airflow obstruction, characterised in the majority by type 2 airway inflammation. Type 2 inflammation results in secretion of interleukin-4, -5 and -13 in the airways, recruitment of inflammatory cells (especially eosinophils and mast cells), and airway changes such as mucus hypersecretion and increased airway reactivity. Approximately 5 to 10% of people with asthma, despite optimal therapy and adherence to treatment with inhaled corticosteroids and long-acting beta2 agonists, are unable to obtain good symptom control and continue to experience exacerbations requiring oral corticosteroids; this is known as 'severe asthma'. In many cases, this is associated with persistent type 2 inflammation, indicated by the persistent elevation of blood eosinophils or fractional exhaled nitric oxide. In people with severe asthma and persistent type 2 inflammation, biologic (monoclonal antibody) therapy is indicated. Biologic therapies currently available in Australia for asthma are benralizumab, dupilumab, mepolizumab and omalizumab. They are administered subcutaneously and are generally well tolerated. Biologic asthma therapies are very effective in improving symptoms, and reducing the rate of exacerbations and use of oral corticosteroids, in people with severe asthma and persistent type 2 inflammation. Inhaled corticosteroid treatment should be continued in people using a biologic therapy.

Economic burden assessment for the management of asthma patients at Mexico's National Institute for Respiratory Diseases

Determinar la carga económica anual del asma, desde una perspectiva institucional y con base en la clasificación recomendada por GINA, en una cohorte retrospectiva de adultos atendidos en el Instituto Nacional de Enfermedades Respiratorias (INER) de México. Estudio observacional, longitudinal y retrospectivo, llevado a cabo a partir de la información recabada de 247 pacientes femeninas con asma. Se estimaron los costos directos anuales: visitas, pruebas de laboratorio, tratamiento farmacológico y de las crisis o exacerbaciones, para determinar la carga anual de la enfermedad desde una perspectiva institucional, y según la clasificación de la Iniciativa Global para el Asma. El costo promedio anual fue de $43,813,92, que aumentó en relación con la necesidad de aumento de dosis de corticoides inhalados y beta-agonistas de acción prolongada. El costo promedio de la consulta médica fue de $2004.57, $982.82 por gestión de crisis y $2645.95 por pruebas de laboratorio. El tratamiento farmacológico representó la principal carga económica, con un costo promedio anual de $38,180.58. Los resultados resaltan una carga económica del asma estimada en un costo anual por paciente de $43,813.92 MXN (DE=93,348.85), en el contexto del tercer nivel de atención en el sistema de salud público mexicano. La gravedad del asma, los tratamientos y los biológicos fueron los principales factores que aumentaron los costos directos de la atención.

Long-acting B-2 agonists (LABA) or long-acting muscarinic antagonists (LAMA): which one may be the first option in group A COPD patients?

Long-acting muscarinic antagonists (LAMA) or beta-2 agonists (LABA) have been recommended for symptom control in group A COPD patients as a first-line bronchodilator treatment in GOLD guidelines. However, there is no mention of priority/superiority between the two treatment options. We aimed to compare the effectiveness of these treatments in this group. The study cohort was formed of all subjects from six pulmonology clinics with an initial diagnosis of COPD who were new users of a LAMA or LABA from January 2020 to December 2021. Seventy-six group A COPD patients, in whom LABA or LAMA therapy had been started in the last 1month as a first-line treatment, were included in our study. Participants were evaluated with spirometry, COPD Assessment Test (CAT), mMRC scale, and St. George Respiratory Questionnaire (SGRQ) for three times (baseline, 6-12th months). There were 76 group A COPD patients with LAMA (67.1%) and LABA (32.9%). The number of patients who improved in CAT score at the end of the first year was significantly higher in patients using LAMA than those using LABA (p = 0.022); the improvement at minimum clinically important difference (MCID) in CAT score of LAMA group at 1st year was also significant (p = 0.044). SGRQ total and impact scores were found to be statistically lower at 1st year compared to baseline in patients using LAMA (p = 0.010 and 0.006, respectively). Significant improvement was detected in CAT and SGRQ scores at the 6th month visit in the LAMA group having emphysema (p = 0.032 and 0.002, respectively). According to significant improvements in CAT and SGRQ score, LAMA may be preferred over LABA as a bronchodilator agent in group A COPD patients, especially in emphysema-dominant phenotype.

The Impact of Australian Bushfires on Asthma Medicine Prescription Dispensing.

Air pollution can cause numerous health problems and increase the need for medicines to treat and prevent asthma in affected areas. There is limited evidence about the association between airborne particles with a diameter of 2.5 micrometres or smaller (PM2.5) and asthma medicine usage. This study examined the potential association between the levels of PM2.5 and the supply of prescription asthma medicines in the Australian Capital Territory (ACT), Australia, during the severe bushfire season between November 2019-January 2020. Daily data was obtained from an ACT air quality monitoring station from November 2019 to January 2020 (study period) and November 2018 to January 2019 (control period, no bushfire). The number and types of government-funded asthma medicine prescriptions were obtained from the Services Australia (government) website by searching under 'Pharmaceutical Benefits Scheme Item Reports' and using relevant item codes during the study and control periods. The medians for PM2.5 levels for the study period were significantly higher than those for the control period (p < 0.001). There were increases in the number of dispensed prescriptions of short-acting beta-2 agonists (SABA), inhaled corticosteroids, and long-acting beta-2 agonists combined with inhaled corticosteroids. The greatest difference was seen with the inhaled corticosteroids: a 138% increase. The increase in the number of dispensed asthma prescriptions during the bushfire season should be used to inform the stock holdings of these medicines in preparation for future events to ensure access to lifesaving asthma medicines.

Determining Adherence to Inhaled Corticosteroids From the Epic Electronic Medical Record

OBJECTIVE Often we call the patient’s pharmacy to obtain a refill history to assess inhaled corticosteroid (ICS) adherence. The purpose of this project was to determine the accuracy of refill histories for ICS (with or without long-acting beta agonist) listed in Epic’s Medication Dispense History. METHODS We evaluated 61 patients and used data from 38 who met the following criteria: 1) under the care of the UF Pediatric Severe Asthma Clinic; 2) taking the same dose of the same ICS product for 6 months before the patient’s last clinic visit; and 3) having data available from the pharmacy where the last ICS prescription was electronically sent. We called the pharmacies to obtain a verbal report of their refill record. Then, we compared the number of refills reported to the number listed in Epic’s records using a Wilcoxon matched-pairs signed-ranks test. RESULTS Of the 293 refill dates listed in Epic, 157 were duplicates, giving a 54% error. After deleting duplicates, the mean (SD) number of refills listed in Epic was 3.6 (2.0) compared with 3.3 (2.0) in pharmacies over a period of 6 months (p &amp;lt; 0.0001). After removing duplicates Epic correctly reported the total number of refills for 30 of the 38 patients (78.9%). Seven of the remaining patients had more refills listed in Epic while 1 patient had more refills dispensed. CONCLUSION This study indicates that our version of Epic over-reports refills thus limiting assessment of adherence. In contrast, absence of refills in Epic is a clear indication of poor adherence.

Higher risk of osteoporosis in adult-onset asthma than childhood-onset asthma: from genetic and prospective evidence.

Childhood-onset asthma (COA) differs with adult-onset asthma (AOA) on genetic susceptibility, severity, and co-morbidities. Whether COA or AOA is independently associated with osteoporosis is unexplored. We aimed to determine the effects of COA and AOA on osteoporosis at genetic and individual level. We used two-sample Mendelian randomization analysis to explore the causal effects of COA and AOA on osteoporosis. In the UK Biobank cohort, we included 478,289 osteoporosis-free participants at baseline (2006-2010). Participants were classified as non-asthma, COA, and AOA at recruitment. Multivariate Cox regression analysis was used to evaluate the effects of COA, AOA, and multiple asthma medications on incident osteoporosis risk. COA and AOA were causally related to osteoporosis, with odds ratio of 1.007 (95% confidence interval (CI), 1.0003-1.0132) and 1.012 (95% CI, 1.002-1.023), respectively. Multivariate Cox regression analysis suggested that COA (hazard ratio (HR), 1.46; 95% CI, 1.32-1.61) and AOA (HR, 1.70; 95% CI, 1.61-1.80) were independently associated with incident osteoporosis, and the risk was greatly higher in AOA (HR, 1.51; 95% CI, 1.34-1.70). In addition to corticosteroids, monotherapy with leukotriene modifiers (HR, 1.70; 95% CI, 1.20-2.42), long-acting beta agonists (HR, 1.49; 95% CI, 1.18-1.87), and short-acting beta agonists (HR, 1.72; 95% CI1.01-2.93) were independently associated with a higher risk of osteoporosis. Both COA and AOA have a genetically causal effect on osteoporosis, and the risk of osteoporosis is greatly higher in AOA. Besides corticosteroids, the increased risk of osteoporosis among asthma patients should be attributed to genetic susceptibility and other asthma medications.

Frequency and characteristics of asthma in smokers attending smoking cessation units in Spain

Introduction The interaction between smoking and asthma impairs lung function and increases airflow obstruction severity. The identification of smoking patterns in smokers with and without asthma is crucial to provide the best care strategies. The aims of this study are to estimate asthma frequency, describe asthma features, and characterize smoking in smokers attending smoking cessation units. Material and methods We carried out a cross-sectional study in five smoking cessation units with different geographical distribution to estimate asthma frequency in smokers, characterize asthma features in smokers, as well as smoking in asthmatic smokers. Results Asthma frequency among smokers was 18.6%. Asthmatic smokers presented high passive exposure, low smoking self-efficacy and will to quit smoking, as well as a high exacerbation frequency, severe symptoms, and frequent use of long-acting beta agonists, inhaled steroids, and short-acting beta agonists. Discussion Smokers with asthma constitute a high-risk group with worsened evolution of pulmonary involvement. All smokers should be regularly screened for asthma. Effective smoking cessation strategies should be proposed to smokers with asthma in order to reverse the harmful effects of smoking on the airway, together with a comprehensive and integral approach.

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

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. 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. 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). 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.

Characteristics and outcomes of adult patients with asthma presenting with COVID-19: A comparative cohort study.

Bronchial asthma affects about 20% of Qatar's population. The impact of asthma on COVID-19 outcomes is controversial. The aim of this study was to explore the impact of asthma on COVID-19 outcomes and the predictors of COVID-19-related morbidity and mortality in a cohort of asthma patients infected by COVID-19. This is a retrospective cohort study of adult patients with asthma infected with COVID-19, who were recruited from Hamad Medical Corporation (HMC), the main healthcare system in Qatar. Patients were matched to a control group of non-asthmatic COVID-19 patients (1:2) based on sex, age, and other comorbidities. Between March and August 2020, 616 patients with asthma met the inclusion criteria. The need for hospitalization among patients with asthma was independently associated with older age (adjusted odds ratio [aOR] for 10 years, 1.32; 95% confidence interval [CI], 1.13-1.54; p = 0.001) and hypertension (aOR, 2.4; 95% CI, 1.43-3.93; p = 0.001) but not with the use of inhaled corticosteroids (ICS), long-acting beta2 agonists, montelukast, or tiotropium. Patients with asthma required less hospitalization for COVID-19 than non-asthmatic patients (28.2% vs. 37.3%, respectively; aOR, 0.59; 95% CI, 0.77-0.90; p < 0.001). However, admission to the intensive care unit (ICU) was comparable between both groups (3.3% vs. 2.2%; aOR, 1.64; 95% CI, 0.78-3.43; p = 0.193). No difference in mortality rate was observed between the two groups. In Qatar, adult patients with asthma do not appear to be at higher risk of COVID-19-related hospitalization or ICU admission compared to the general adult COVID-19-infected population. Older age and hypertension were the only significant predictors of COVID-19-related hospitalization among patients with asthma. Further larger studies are required to confirm such an association.

Association between use of transdermal tulobuterol and short-term outcomes in patients with stroke and underlying chronic obstructive pulmonary disease: A retrospective cohort study.

Transdermal tulobuterol, a long-acting beta agonist in a transdermal form, is available in some countries, including Japan, Korea, and China. It may provide an alternative treatment option for the management of chronic obstructive pulmonary disease (COPD) in patients who are unable to effectively use inhalers, such as those with acute stroke. This study examined the short-term outcomes of transdermal tulobuterol in patients hospitalized with acute stroke and underlying COPD. Using the Diagnosis Procedure Combination database, a national inpatient database in Japan, we identified patients with stroke and underlying COPD who were hospitalized between July 2010 and March 2021. We performed propensity-score overlap weighting to compare in-hospital death, COPD exacerbation, pneumonia, and cardiac complications between patients who initiated transdermal tulobuterol within 2 days of admission and those who did not use it during hospitalization. Of the 1878 eligible patients, 189 received transdermal tulobuterol within 2 days of admission. After adjusting for baseline variables, transdermal tulobuterol was not associated with a reduction in in-hospital death (18.3% vs 16.1%; odds ratio, 1.17; 95% confidence interval, 0.72-1.90). Additionally, we observed no significant difference in COPD exacerbation, pneumonia, and cardiac complications between both groups. Transdermal tulobuterol was not associated with improving short-term outcomes in patients with acute stroke and underlying COPD. Our study does not support the routine use of transdermal tulobuterol in this patient group. However, further research investigating the long-term efficacy of transdermal tulobuterol in patients with stroke and underlying COPD could help establish its role for the management of these patients.

Study protocol: A comparison of mobile and clinic-based spirometry for capturing the treatment effect in moderate asthma.

Several inefficiencies in drug development trial implementation may be improved by moving data collection from the clinic to mobile, allowing for more frequent measurements and therefore increased statistical power while aligning to a patient-centric approach to trial design. Sensor-based digital health technologies such as mobile spirometry (mSpirometry) are comparable to clinic spirometry for capturing outcomes, such as forced expiratory volume in 1 s (FEV1); however, the impact of remote spirometry measurements on the detection of treatment effect has not been investigated. A protocol for a multicenter, single-arm, open-label interventional trial of long-acting beta agonist (LABA) therapy among 60 participants with uncontrolled moderate asthma is described. Participants will complete twice-daily mSpirometry at home and clinic spirometry during weekly visits, alongside continuous use of a wrist-worn wearable and regular completion of several diaries capturing asthma symptoms as well as participant- and site-reported satisfaction and ease of use of mSpirometry. The co-primary objectives of this study are (A) to quantify the treatment effect of LABA therapy among participants with moderate asthma, using both clinical spirometry (FEV1c ) and mSpirometry (FEV1m ); and (B) to investigate whether FEV1m is as accurate as FEV1c in detecting the treatment effect using a mixed-effect model for repeated measures. Study results will help inform whether the deployment of mSpirometry and a wrist-worn wearable for remote data collection are feasible in a multicenter setting among participants with moderate asthma, which may then be generalizable to other populations with respiratory disease.