LABA Research Articles

Bronchodilator effect of oral doxofylline and procaterol in asthma: A randomized crossover study

Background Oral bronchodilators may be used as an adjunctive treatment, especially in patients with uncontrolled asthma or poor inhaler technique. This study aimed to determine the differences in asthma symptoms and bronchodilator effect between oral doxofylline and oral procaterol in adults with asthma. Methods A crossover randomized controlled trial was conducted. Asthmatic patients aged 18 years or older with stable inhaled corticosteroids and long-acting beta2-agonists (ICS/LABA) treatment were included. Each patient received 2 weeks of treatment with either doxofylline or procaterol followed by a 1-week washout period and 2 weeks of treatment with the other drug. Asthma symptoms were assessed using the Asthma Control Questionnaire-5 (ACQ-5) scores, pulmonary function was assessed by spirometry with bronchodilator testing, and adverse events were recorded. Results A total of 21 patients were randomly allocated to either the doxofylline or procaterol groups. The mean age of the patients was 53.0±14.8 years. ACQ-5 scores were 1.4±1.1. After two weeks of treatment, the ACQ-5 scores and all pulmonary function parameters were not significantly different between the two groups (P>0.05). However, significant improvements in ACQ-5 scores were found in both groups (mean change: -0.381± 0.740, P=0.029 and -0.476± 0.873, P=0.021 for the doxofylline and procaterol groups, respectively). None of the patients experienced asthma exacerbations. Conclusions Doxofylline and procaterol can improve asthma symptoms, although they cannot enhance lung function. These oral bronchodilators might be used as an add-on therapy in asthmatic patients with persistent symptoms despite treatment with an ICS/LABA combination.

Pharmaceutical treatment status of patients with COPD in the community based on medical Internet of Things: a real-world study

This study aimed to investigate the real-world standardisation and adherence of medical treatment regimens in patients with chronic obstructive pulmonary disease (COPD) in the community for making future management strategy. The follow-up data and treatment information of patients with COPD, which were collected through the Management Information Center of COPD (MICCOPD) in 21 community health service centres in Songjiang District, a countryside region of Shanghai. Concordance between the pharmaceutical treatment plan and recommendation of 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) report during the follow-up management period, as well as the medication adherence by patients,were analysed. Out of the 2044 patients diagnosed with COPD, 814 patients (39.8%) who had an initial record of medication use were found to meet the inclusion criteria. The most common medication regimens were long-acting beta-agonist plus inhaled corticosteroids (35.9%) and oral bronchodilators (41.9%). Among these 814 patients, 45.7%, 38.0%, 31.6% and 14.6% adhered to the treatment after 6, 12, 18 and 24 months of follow-up, respectively. The concordance rate with the regimens recommended by the 2017 GOLD guidelines was 35.5% at baseline, 35.5% at 6 months, 32.7% at 12 months, 35.4% at 18 months and 37% at 24 months. The compliance and guideline consistency rates of patients with COPD in the community under the management of general practitioners need to be improved. Enhancing general practitioner proficiency in the prevention and management of COPD and increasing patient awareness of the condition, are crucial standardising and improving adherence to initial and follow-up COPD treatments.

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.

The Incidence, Mortality and Medical Expenditure in Patients with Asthma in Taiwan: Ten-year Nationwide Study

BackgroundThis study examines incidence, mortality, medical expenditure and prescription patterns for asthma on a national scale, particularly in Asian countries for asthma is limited. Our aim is to investigate incidence, mortality, prescription patterns and provide a comprehensive overview of healthcare utilization trends for asthma from 2009 to 2018.MethodsWe included patients diagnosed with asthma between 2009 and 2018. We excluded patients with missing demographic data. Our analysis covered comorbidities, including diabetes mellitus, hypertension, allergic rhinitis, eczema, atopic dermatitis, coronary artery disease, congestive heart failure, chronic kidney disease, chronic hepatitis, stroke, and cancer. Investigated medications comprised oral and intravenous steroids, short-acting beta-agonists, inhaled corticosteroids (ICS), combinations of ICS and long-acting beta-agonists, long-acting muscarinic antagonists, and leukotriene receptor antagonists montelukast. We also assessed the number of outpatient visits, emergency visits, and hospitalizations per year, as well as the average length of hospitalization and average medical costs.ResultsThe study included a final count of 88,244 subjects from 1,998,311 randomly selected samples between 2000 and 2019. Over the past decade, there was a gradual decline in newly diagnosed asthma patients per year, from 10,140 to 6,487. The mean age annually increased from 47.59 in 2009 to 53.41 in 2018. Over 55% of the patients were female. Eczema was diagnosed in over 55% of the patients. Around 90% of the patients used oral steroids, with a peak of 97.29% in 2018, while the usage of ICS varied between 86.20% and 91.75%. Intravenous steroids use rose from 40.94% in 2009 to 54.14% in 2018. The average annual hospital stay ranged from 9 to 12 days, with a maximum of 12.26 days in 2013. Lastly, the average medical expenses per year ranged from New Taiwan dollars 5558 to 7921.ConclusionsIn summary, both asthma incidence and all-cause mortality rates decreased in Taiwan from 2009 to 2018. Further analysis of medical expenses in patients with asthma who required multiple hospitalizations annually revealed an increase in outpatient and emergency visits and hospitalizations, along with longer hospital stays and higher medical costs.

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.

Managing Small Airway Disease in Patients with Severe Asthma: Transitioning from the "Silent Zone" to Achieving "Quiet Asthma".

Background/Objectives: Several studies have demonstrated the positive clinical and functional impact of adding Long-Acting Muscarinic Antagonist (LAMA) to Inhaled Corticosteroids (ICS) and Long-Acting Beta-Agonists (LABA) therapy in the treatment of severe asthma. Aim and objectives: To demonstrate that treating Small Airways Disease (SAD) in severe asthma patients who are candidates for biologics can improve respiratory symptoms, lung function, and airways inflammation, potentially avoiding or delaying the use of biological therapy. Methods: Thirty-two severe asthma patients with SAD were transitioned from separate inhalers for ICS/LABA and LAMA to extrafine single-inhaler beclomethasone, formoterol, and glycopyrronium. None of these patients underwent biological therapy before the study. Follow-up evaluations were conducted at baseline (T0) and three months after initiation (T3). Assessments included clinical evaluations, spirometry, oscillometry, and inflammation markers. Results: Transitioning to single-inhaler triple therapy from T0 to T3 resulted in significant improvements in Asthma Control Test (ACT) and SAD parameters, including increased Forced Expiratory Volume in the mid-range of lung capacity and improved airway resistance and reactance measurements using impulse oscillometry. A significant reduction in airway inflammation was evidenced by lower levels of Fractional Exhaled Nitric Oxide 350 (FeNO 350) (p < 0.001 for all). Conclusions: Adopting a single-inhaler triple therapy notably enhanced clinical control and small airway function in patients with severe asthma and SAD, supporting the positive impact of target-therapy for the achievement of a stable state termed "Quiet Asthma".

New clinical guidelines for COPD - a paradigm shift: A review

Chronic obstructive pulmonary disease is now one of the most common noncommunicable diseases and the main causes of morbidity, disability and mortality in the world. In recent years, new approaches to epidemiology, diagnosis, classification (categorization), evaluation of phenotypes, as well as characterization and assessment of the severity of сhronic obstructive pulmonary disease exacerbations have emerged. Modern approaches to starting and subsequent drug therapy have changed significantly. This is largely due to the results of recently conducted major clinical trials, demonstrated high efficacy of triple fixed combinations, including inhaled glucocorticosteroids, long-acting beta-agonists and long-acting anticholinergic drugs. The use of non-medication methods (smoking cessation, physical activity and respiratory rehabilitation) and modern approaches to the treatment of respiratory failure and antibiotic therapy remain important. In terms of their significance, all these updates have a significant impact on real clinical practice and can be considered as a novel paradigm of the approaches to the diagnosis and management of this disease.

Identification and treatment of persistent small airway dysfunction in paediatric patients with asthma: a retrospective cohort study

BackgroundAsthma is a common respiratory disease. In asthma, the small airways have more intensive inflammation and prominent airway remodelling, compared to the central airways. We aimed to investigate the predictive value of risk factors and the fractional concentration of exhaled nitric oxide (FeNO) for persistent small airway dysfunction (p-SAD), and compare the effects of different treatment modalities.MethodsThis retrospective cohort study included 248 children with asthma (aged 4–11 years). Binary logistic regression was used to analyse the risk factors for p-SAD. Correlations among FEV1/FVC, small airway function parameters, and FeNO levels in patients with asthma were analysed using Spearman’s rank correlation. The receiver operating characteristic curve and the Delong test were used to analyse the predictive value of FeNO for p-SAD. Differences in the treatment effects of inhaled corticosteroids (ICS) and ICS with a long-acting beta-agonist (ICS/LABA) on p-SAD were analysed using Fisher’s exact test.ResultsAsthmatic children with older age of receiving the regular treatment (OR 1.782, 95% CI 1.082–2.935), with younger age at the time of onset of suspected asthma symptoms (OR 0.602, 95% CI 0.365–0.993), with longer duration of using ICS or ICS/LABA (OR 1.642, 95% CI 1.170–2.305) and with worse asthma control (OR 3.893, 95% CI 1.699–8.922) had increased risk for p-SAD. Significant negative correlations of small airway function parameters with FeNO at a 200 mL/s flow rate (FeNO200), and the concentration of nitric oxide in the alveolar or acinar region (CaNO) were observed. The areas under the curve of FeNO200 (cut-off:10.5ppb), CaNO (cut-off:5.1ppb), and FeNO200 combined with CaNO were 0.743, 0.697, and 0.750, respectively, for asthma with p-SAD. After using ICS or ICS/LABA, switching to ICS/LABA was easier than continuing with ICS to improve small airway dysfunction (SAD) in the 8th month.ConclusionsPaediatric asthma with p-SAD is associated with older age at receiving regular treatment, younger age at the time of onset of suspected asthma symptoms, longer duration of using ICS or ICS/LABA, worse asthma control, and higher FeNO200 and CaNO levels, all of which can be combined with small airway function indicators to distinguish p-SAD from asthma. ICS/LABA improves SAD better than ICS alone.

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.

A comparison of GOLD 2019 and 2023 recommendations to contemporaneous real-world inhaler treatment patterns for chronic obstructive pulmonary disease management in Singapore.

In 2019 and 2023, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) provided updated strategies for modifying the therapy of patients with chronic obstructive pulmonary disease (COPD) and high exacerbation risk. A key update since the 2019 guidelines recommends considering blood eosinophil count to guide decisions on inhaled corticosteroid (ICS) treatment. To evaluate the potential impact of these updated recommendations, this study aimed to assess how extensively future practice would diverge from contemporaneous prescribing practices at a single center in Singapore, assuming adherence to the 2019 and 2023 GOLD guidelines. Retrospective cohort analysis of the Changi General Hospital COPD data warehouse involving patients aged ≥40 years hospitalized for a COPD exacerbation (October 2018-April 2020) receiving long-acting muscarinic antagonist (LAMA), LAMA plus a long-acting beta2-agonist (LABA), or an ICS plus LABA at admission. The proportion of patients eligible for treatment escalations per GOLD 2019 and 2023 recommendations was calculated. In total, 268 patients were included (mean age 73 years; 91% male). At admission, 19%, 59%, and 22% of patients were receiving LAMA, LAMA + LABA, and ICS + LABA, respectively. Overall, 226 patients would have been eligible for treatment escalation per GOLD 2019 or 2023 recommendations; 31 (13.7%) had treatment escalations consistent with GOLD 2019 guidelines and 34 (15%) received treatment escalations consistent with GOLD 2023 guidelines. A total of 205 patients (76.5%) remained on the same treatment regimen at hospital discharge as they were receiving at admission. Lower measured post-bronchodilator forced expiratory volume in 1 second was associated with treatment escalations that would have been GOLD-concordant (P=0.028), as was increased number of emergency department/hospital visits in the last year (P=0.048). Compared with real-world clinical practice, a significantly higher proportion of patients may be eligible for treatment escalation under the GOLD 2019 and 2023 eosinophil-directed algorithms.

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.

Insights from Overviewing Selective International Guidelines for Pediatric Asthma.

Asthma is a chronic atopic and inflammatory bronchial disease characterized by recurring symptoms and, episodic reversible bronchial obstruction and easily triggered bronchospasms. Asthma often begins in childhood. International guidelines are widely accepted and implemented; however, there are similarities and differences in the management approaches. There is no national guideline in many cities in Asia. This review aims to provide a practical perspective on current recommendations in the management of childhood asthma, specifically in the following aspects: diagnosis, classification of severity, treatment options, and asthma control, and to provide physicians with up-to-date information for the management of asthma. We used the PubMed function of Clinical Queries and searched keywords of "Asthma", "Pediatric," AND "Guidelines" as the search engine. "Clinical Prediction Guides", "Etiology", "Diagnosis", "Therapy," "Prognosis," and "Narrow" scope were used as filters. The search was conducted in November 2022. The information retrieved from this search was used in compiling the present article. Diagnosis is clinically based on symptom pattern, response to therapy with bronchodilators and inhaled corticosteroids, and spirometric pulmonary function testing (PFT). Asthma is classified in accordance with symptom frequency, peak expiratory flow rate (PEFR), forced expiratory volume in one second (FEV1), atopic versus nonatopic etiology, where atopy means a predisposition toward a type 1 hypersensitivity reaction. Asthma is also classified as intermittent or persistent (mild to severe). Unfortunately, there is no disease cure for asthma. However, symptoms can be prevented by trigger avoidance and suppressed with inhaled corticosteroids. Antileukotriene agents or long-acting beta-agonists (LABA) may be used together with inhaled corticosteroids if symptoms of asthma are not controlled. Rapidly worsening symptoms are usually treated with an inhaled short-acting beta-2 agonist (SABA, e.g., salbutamol) and oral corticosteroids. Intravenous corticosteroids and hospitalization are required in severe cases of asthma attacks. Some guidelines also provide recommendations on the use of biologics and immunotherapy. Asthma is diagnosed clinically, with supporting laboratory testing. Treatment is based on severity classification, from intermittent to persistent. Inhaled bronchodilator and steroid anti-inflammatory form the main stay of management.

Cost-utility of tiotropium in patients with severe asthma

SummaryAdd-on therapy with tiotropium was cost-effective when added to usual care in patients who remain uncontrolled despite treatment with medium or high-dose ICS/LABA in a middle-income country.BackgroundA significant proportion of asthma patients remain uncontrolled despite inhaled corticosteroids and long-acting beta-agonists. Some add-on therapies, such as tiotropium bromide, have been recommended for this subgroup of patients. This study aimed to assess the cost-effectiveness of tiotropium as an add-on therapy to inhaled corticosteroids and long-acting b2 agonists for patients with severe asthma.MethodsA probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with severe asthma in Colombia. Total costs and QALYs of two interventions include standard therapy with inhaled corticosteroids and long-acting bronchodilators versus add-on therapy with tiotropium. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $5180.ResultsThe expected incremental cost per QALY (ICER) is estimated at US$–2637.59. There is a probability of 0.77 that tiotropium + ICS + LABA is more cost-effective than ICS + LABA at a threshold of US$5180 per QALY. The strategy with the highest expected net benefit is Tiotropium, with an expected net benefit of US$800. Our base-case results were robust to parameter variations in the deterministic sensitivity analyses.ConclusionAdd-on therapy with tiotropium was cost-effective when added to usual care in patients who remain uncontrolled despite treatment with medium or high-dose inhaled corticosteroids and long-acting bronchodilators. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other middle-income countries.

Clinical characteristics and healthcare resource utilization in patients with chronic obstructive pulmonary disease in Hong Kong

ObjectivesChronic obstructive pulmonary disease (COPD) is a significant cause of mortality, with its prevalence projected to rise in Asia. The primary objective of this study was to describe clinical characteristics, maintenance treatment, and healthcare resource utilization (HCRU) among patients with COPD in Hong Kong. Secondary objectives were to assess patient demographics and clinical characteristics by eosinophil (EOS) levels, and compare the demographics, clinical characteristics, and treatment patterns of patients on multiple-inhaler triple therapy (MITT). MethodsThis study analyzed a cohort of patients with COPD who had entered a previously initiated prospective cohort study involving patients with COPD and/or asthma at the Prince of Wales Hospital between 2017 and 2019. ResultsPatients with COPD were enrolled (N = 220, mean age 74.3 years, 97 % male). Twelve months prior to baseline assessment, 66 % of patients were on MITT, 17 % on long-acting muscarinic antagonists (LAMAs)/long-acting beta-agonists (LABAs), and 7 % on inhaled corticosteroids (ICS)/LABA. Compared with ICS/LABA or LAMA/LABA, more patients on MITT experienced ≥1 exacerbation (26.7 %, 10.5 %, 39.7 %, respectively). Patients on MITT also had a higher mean (SD) COPD Assessment Test score (9.4 [5.9]) and modified Medical Research Council Dyspnea Scale score (1.7 [0.7]) and incurred the most COPD-related and total HCRU costs. Compared with patients with EOS ≤300 cells/μL, those with EOS >300 cells/μL had a higher number of exacerbations. ConclusionsPatients with COPD in Hong Kong treated with MITT presented more severe disease profiles and incurred higher costs. These data can be used for decision making in patients with moderate-to-severe COPD in Hong Kong.

A Retrospective Claims Database Study to Clarify Treatment Reality of Asthma Patients Before and After Referral to a Specialist.

Japanese guidelines recommend that patients with uncontrolled asthma be referred by non-specialists to specialists (allergists and/or pulmonologists). This study investigated the reality of clinical practice in asthma patients referred to specialists in Japan. This was a retrospective, observational cohort study of asthma patients in a health insurance claim database (Cross Fact) referred from facilities with non-specialists to those with specialists from January 2016 to December 2018. The referred asthma patients were defined as patients with ≥4 inhaled corticosteroid (ICS)-containing prescriptions during a 1-year baseline period, with an asthma diagnosis, and who had visited a facility with specialists. Asthma exacerbation, maintenance treatment, laboratory tests, and medical procedures before and after referral were analyzed. Data for 2135 patients were extracted, of which 420 with referral codes were analyzed. The proportion of patients with asthma exacerbations was 50.2% (95% confidence interval [CI]: 45.4-55.1%) before referral and 37.4% (95% CI: 32.7-42.2%) after, a significant decrease (P<0.001; McNemar test). The proportions of patients prescribed ICS alone, long-acting beta-agonists (LABA), and ICS/LABA were lower after referral than before, but the proportions of patients prescribed long-acting muscarinic antagonists (LAMA), ICS/LABA/LAMA, and biologics increased after referral. More asthma-related laboratory tests were performed after referral, and spirometry incidence increased from 16.4% before referral to 51.4% after referral. This study shows a decrease in asthma exacerbations, change in asthma treatments, and increase in laboratory tests after referral to a specialist, suggesting that referrals to specialists lead to better management of asthma.

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.

The clinical characteristics and outcomes of different inhaled therapies in chronic obstructive pulmonary disease patients with frequent cough

Background Cough is a common symptom in patients with chronic obstructive pulmonary disease (COPD). Patients with cough may exhibit various clinical characteristics and experience varying outcomes based on inhaled therapies they receive. Objectives This study aimed to explore the clinical characteristics and outcomes of various inhaled therapies in COPD patients with frequent cough. Methods This was a multicenter, prospective cohort study. Of these patients, the median cough score in COPD assessment test (CAT) was two. Patients were classified into frequent cough group if they scored two or over in the first item of CAT and infrequent cough group otherwise. Patients with frequent cough were then divided into long-acting antimuscarinic (LAMA), long-acting beta2-agonist (LABA)/LAMA, inhaled corticosteroids (ICS)/LABA and ICS/LABA/LAMA groups. Minimum clinically important difference (MCID) (CAT scores decreased ≥2 from baseline) and the improvement of cough (cough score decreased ≥1 from baseline) were collected in the six-month follow-up. Frequent exacerbations (experiencing at least two exacerbations) were collected in the one-year follow-up. Results Of 906 patients, 581 (64.1%) patients reported frequent cough at the initial visit. Frequent cough was associated with the current smokers and CAT scores (p < 0.05). The MCID showed no significant difference between frequent cough and infrequent cough groups in the follow-up. More patients with frequent cough experienced future frequent exacerbations compared to those with infrequent cough. After receiving inhaled therapies, 62% of patients with frequent cough got the cough improved. More patients with frequent cough treated with LABA/LAMA or ICS/LABA/LAMA attained MCID and fewer experienced exacerbations than those treated with LAMA or ICS/LABA (p < 0.05). The change in cough score showed no difference among various inhaled therapies in patients with frequent cough. Conclusion COPD patients with frequent cough were related to current smokers and higher CAT scores. These patients had a higher incidence of frequent exacerbations than those with infrequent cough. Patients with frequent cough who were treated with LABA/LAMA or ICS/LABA/LAMA were more likely to attain MCID and at a lower risk of exacerbation than those treated with LAMA or ICS/LABA.