Effect of Individual Patient Characteristics and Treatment Choices on Reliever Medication Use in Moderate-Severe Asthma: A Poisson Analysis of Randomised Clinical Trials.

INTRODUCTION: Even though increased use of reliever medication, including short-acting beta agonists (SABA), provides an indirect measure of symptom worsening, there have been limited efforts to assess how different patterns of reliever use correlate with symptom control and future risk of exacerbations. Here, we evaluate the effect of individual baseline characteristics on reliever use in patients with moderate-severe asthma on regular maintenance therapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR). METHODS: A drug-disease model describing the number of 24-h puffs and overnight occasions was developed with data from five clinical studies (N = 6212). The model was implemented using a nonlinear mixed effects approach and a Poisson function, considering clinical and demographic baseline characteristics. Goodness of fit and model predictive performance were assessed. Heatmaps were created to summarise the effect of concurrent baseline factors on reliever utilisation. RESULTS: The final model accurately described individual patterns of reliever use, which is significantly increased with time since diagnosis, smoking, higher Asthma Control Questionnaire (ACQ-5) score and higher body mass index (BMI) at baseline. Whilst the number of puffs decreases slowly after an initial drop relative to the start of treatment, exacerbating patients utilise significantly more reliever than those who do not exacerbate. The mean effect of FP/SAL (median dose: 250/50 µg BID) on reliever use was slightly higher than that of BUD/FOR (median dose: 160/4.5 µg BID), i.e. a 75.3% vs 69.3% reduction in reliever use, respectively. CONCLUSIONS: The availability of individual-level patient data in conjunction with a parametric approach enabled the characterisation of interindividual differences in the patterns of reliever use in patients with moderate-severe asthma. Taken together, individual demographic and clinical characteristics, as well as exacerbation history, can be considered an indicator of the degree of asthma control. High SABA reliever use suggests suboptimal clinical management of patients on maintenance therapy.

In this study, we tried to understand how patients with moderate to severe asthma use their quick-relief inhalers (like albuterol), how it relates to their symptoms and the risk of having asthma attacks. To evaluate whether differences in reliever inhaler use between patients are associated with factors like smoking or their asthma symptoms at the beginning of treatment, we gathered data from five clinical studies (n = 6212 patients). These data allowed us to create a model that predicts how often patients use their reliever inhalers (expressed as number of puffs in 24 h) during maintenance therapy with inhaled corticosteroids alone or in combination with long-acting beta agonists. The final model showed that reliever inhaler use is higher in patients who have been diagnosed with asthma for > 10 years, are smokers, have higher asthma symptom scores, and are obese or extremely obese. Patients who had asthma attacks also used their reliever inhalers more often. In addition, to understand how relief inhalers are used in real-life situations, we also created heatmaps that include a wide range of patient characteristics. By using individual patient data together with this model, we have learned that smoking, asthma control, BMI, long history of asthma and previous asthma attacks significantly influence reliever use. This information can help physicians and healthcare professionals understand know how well someone's asthma is managed. A patient who uses their reliever inhaler often is likely not to have their asthma well controlled by their regular medications.

Insights from Overviewing Selective International Guidelines for Pediatric Asthma.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.

Stepwise management of COPD: What is next after bronchodilation?

Inhaled bronchodilator therapy with long-acting muscarinic antagonists (LAMAs) and long-acting ß2-agonists (LABAs) in combination is currently the mainstay of treatment for chronic obstructive pulmonary disease (COPD). Treatment guidelines recommend the addition of inhaled corticosteroids (ICS) to LABA/LAMA only in patients with a history of frequent/severe exacerbations and high blood eosinophil counts, or in those with concomitant asthma. Despite this, real-world data suggest that clinicians are not adhering to this guidance and that ICS are frequently overused. This is possibly due to the incorrect assumption that when LABA/LAMA therapy is not sufficient, adding an ICS to the treatment regimen is the logical next step. In this narrative review, we describe global and country-specific guideline recommendations from Germany, Spain, and Japan and compare these with real-world data on LABA/LAMA and ICS use in clinical practice. We also provide a clinical guide to the use of add-on therapies with LABA/LAMA for different patient phenotypes, including (1) patients still symptomatic (but not exacerbating) despite LABA/LAMA treatment; (2) patients still exacerbating despite LABA/LAMA treatment who have high blood eosinophil counts; and (3) patients still exacerbating despite LABA/LAMA treatment who do not have high blood eosinophils or concomitant asthma.

What are the options for patients with COPD when LABA/LAMA is not enough?Treatment guidelines for chronic obstructive pulmonary disease (COPD) recommend dual bronchodilator therapy for the majority of patients, consisting of an inhaled combination of long-acting ß₂-agonist (LABA) and long-acting muscarinic antagonist (LAMA). Patients whose COPD is not well controlled on LABA/LAMA require further clinical intervention, which may or may not involve treatment with additional drugs.Data from observational studies reflecting routine clinical practice suggest that inhaled corticosteroids (ICS) are often added to LABA/LAMA, even though treatment guidelines recommend only adding ICS in a specific group of patients with a history of exacerbations and high levels of eosinophils (a type of inflammatory cell) in the blood, or in those with current asthma. As long-term ICS use may be associated with an increased risk of side effects such as pneumonia, it is important to avoid overuse of ICS. When a patient's COPD is not well controlled on LABA/LAMA, other treatable conditions should first be ruled out, and factors such as medication adherence, inhaler technique, and co-existing health conditions should also be considered.This review gives advice on what follow-up options physicians should consider when LABA/LAMA is not providing adequate control of a patient's COPD. Specifically, recommendations are given for three different patient profiles:1. Patients who still have symptoms of COPD (but no acute/sudden worsenings of symptoms, known as exacerbations).2. Patients who have exacerbations, as well as high levels of eosinophils in the blood.3. Patients who have exacerbations, but without high levels of eosinophils in the blood or current asthma.

Dietary Exposure and Risk Assessment of Beta-Agonist Residues in Commercial Beef and Pork in Taiwan.

Beta-agonists (ß-agonists) in meat products in one's diet raise concerns about the possibility of foodborne illness. It may also lead to discomfort, such as headaches and occasional irregular heartbeats, which might be linked to a heightened concern for cardiovascular issues. Taiwan's high demand for meat and reliance on imported meat products from certain countries where ß-agonists are permitted has raised concerns. Recent import border checks and monitoring of meat products in the market have revealed the concentration of non-compliance with ß-agonist residue regulations, which is ten ppb. This study aims to analyze the concentration of ß-agonist residues in meat products sold in Taiwan and assess the current levels of exposure and dietary risk for consumers. The study analyzed 1415 samples of domestically produced and imported livestock products from supermarkets, traditional markets, and bulk stores in New Taipei City between 2019 and 2023. The samples were analyzed using the method for detecting 21 ß-agonists based on the Taiwan Food and Drug Administration's specifications. Estimated daily intake (EDI) of ß-agonists for different age groups and the target hazard quotient (THQ) were used to assess dietary exposure and risk. The results showed that all 1415 samples were compliant with regulations. Among them, 43 beef samples showed residues of ractopamine originating from the United States, with residue concentrations ranging from 1 to 10 µg/kg and an average residue concentration of 3.3 ± 1.9 µg/kg. Under average consumption, the highest EDI for the exposed population was observed in the 6-12 age group, with values of 0.1469 µg/kg/day, 0.0734 µg/kg/day, and 0.0242 µg/kg/day for the three residue concentrations (maximum detected residue, maximum allowable residue, and average detected residue, respectively). The THQs for ractopamine in imported beef samples were all less than 1, indicating no health hazards at the current intake levels of each age group and the residue concentrations in commercially available beef. Despite the findings, traders need to acknowledge regulatory variations between Taiwan and exporting countries when importing meat products. Traders should provide inspection reports to monitor ß-agonist residue levels in imports or explore sourcing beef from countries with ß-agonist bans.

Evidence of off-label inhalation therapy on pediatric asthma practice in Japan.

BACKGROUND: In Japan, many asthma inhalers do not have formal approval for use in the pediatric population because of the lack of domestic data. In real-world settings, however, numerous off-label medications are prescribed. Currently, the nature of off-label prescriptions of asthma inhalers on pediatric patients in Japan remains unclear. METHODS: Using public open-source national medical claims data, we investigated the real-world descriptive epidemiology of off-label prescriptions for asthma inhalers for pediatric patients. We obtained the number of off-label prescriptions of formulations for patients aged 0-14 years from anonymously summarized prescription data for a 7-year period starting from April 2014. The actual prescription numbers and their chronology over time were then analyzed. RESULTS: In 2019, 143,439 asthma inhalers were used off label in children and adolescents. Overall, 96.1% were inhaled corticosteroids (ICSs) or long-acting beta stimulants (LABAs), and 3.9% were high-dose ICS. Of ICSs and LABAs, 18.8% were off-label prescriptions. The total number of off-label ICS/LABA prescriptions and their percentage relative to the overall formulations gradually decreased but a notable disparity was observed among inhaler types. CONCLUSIONS: There was a surprisingly large number of off-label prescriptions of asthma inhalers in the pediatric population in Japan. The proper use of ICSs/LABAs and expansion of insurance coverage should be advocated to reduce off-label use.

Application of wastewater-based epidemiology to estimate the usage of beta-agonists in 31 cities in China.

The illegal use of beta-agonists could cause severe problems to human health. In this study, the usage of beta-agonists in 31 cities across China was estimated using wastewater-based epidemiology (WBE). The proposed method is based on solid-phase extraction (SPE) and LC-MS/MS and was developed and validated to determine the concentration of seven beta-agonists in wastewater. A population model based on cotinine (COT), NH4-N and the flow volume was constructed to estimate the population equivalents for different wastewater treatment plants (WWTPs). Clenbuterol and ractopamine are banned in China for both animal husbandry and medical use, but were nevertheless detected in some wastewater samples at rates of 6.2 % and 4.7 %, respectively (n = 339). The WBE-based consumption of clenbuterol and ractopamine were compared with the acceptable daily intake (ADI) and the health risks were assessed by their hazard quotients (0.26-6.62 for clenbuterol and 9.27 × 10-4-0.05 for ractopamine). Salbutamol, clorprenaline and terbutaline were observed in practically all wastewater samples at concentrations of up to several ng/L, whereas the formoterol and bambuterol concentrations were below the detection limit in all samples. Salbutamol consumption (7.35 ± 4.14 mg/1000 inh/day) was highest among the examined beta-agonists and varied regionally. Beta-agonist consumption based on WBE was higher in some cities than that based on medical survey data, indicating potential illegal use. These results show that WBE can be a straightforward and supplementary method for monitoring beta-agonist usage at the population level and spatially.

Novel vinylene-based covalent organic framework as a promising adsorbent for the rapid extraction of beta-agonists in meat samples.

Beta-agonists are potent bronchodilators approved for the treatment of asthma and tocolysis. However, they have been extensively misused as feed additives in the veterinary field to improve feed efficiency. The concern over their potential hazard to health has come to the fore again. In this study, a novel vinylene-based covalent organic framework (V-COF-1) with a two-dimensional structure was developed. The structure shows good tolerance in a variety of mediums, which can be attributed to the low polarity linkage. The high specific surface area and variable interaction with analytes accelerate the extraction time. Furthermore, the swelling resulting from the formation of hydrogen bonds by the protic solvent intercalation with the triazine group also improves the adsorption efficiency. Finally, due to its great reusability, it is economical material in sample preparation application. The V-COF-1 based µ-dSPE approach was coupled with UHPLC-MS/MS to develop a highly sensitive and selective method. The linearity of the method ranged from 0.05 to 20 ng g-1 with a correlation coefficient (R2) higher than 0.9958, and the limits of detection and quantification fell in the ranges of 0.01-0.10 ng g-1 and 0.04-0.32 ng g-1. The proposed method has been successfully applied to determine beta-agonists in meat samples, and the results indicated good recovery of 82.2-116%. The intra-day and inter-day precision were less than 6.61%, indicating the potential for sustainable application in food analysis.

Occurrence, consumption level, fate and ecotoxicology risk of beta-agonist pharmaceuticals in a wastewater treatment plant in Eastern China.

Beta-agonist pharmaceuticals are widely used in humans and livestock for disease treatment, legal or illegal growth promotion in food animals, bodybuilding, weight loss, and sports doping. The occurrence of beta-agonists in wastewater treatment plants and their subsequent environmental impacts require greater attention. This study determined the levels of 12 beta-agonists in a wastewater treatment plant and evaluated their ecotoxicological risks as well as consumption levels and risks to human health. Among the 12 selected beta-agonists, all were detected in wastewater and 11 in sludge. In most cases, the concentrations of beta-agonists were higher in spring than in summer. Their total average daily mass loads per capita in the influent and effluent were 1.35 µg/d/p and 2.11 µg/d/p, respectively. The overall removal efficiencies of individual beta-agonists ranged from -295.3 to 71.2%. Ecotoxicological risk assessment revealed a low risk to daphnid and green algae from the levels of fenoterol and the mixture of 12 selected beta-agonists in the effluent. The daily consumption levels of individual beta-agonists per capita were 0.028-1.200 µg/d/p. Regular monitoring of beta-agonists in municipal sewage systems and their risk assessment based on toxicological data are urgently required in the future.

Thyroid Hormone Receptor-ß Agonists in NAFLD Therapy: Possibilities and Challenges.

Nonalcoholic fatty liver disease (NAFLD) is a progressive metabolic liver disease with an unknown pathogenesis and no FDA-approved drug treatment to date. Hypothyroidism has been identified as a risk factor for NAFLD as thyroxine is required for regulating metabolism in adults. Thyroxine has been shown to reduce fat in the livers of murine models with experimentally induced NAFLD. The use of synthetic thyroxine has been shown to increase lipid metabolism leading to weight loss; however, thyroxine has also been shown to cause many side effects, especially in the heart. Overcoming these cardiac side effects involves designing agonists specific to one of the 2 gene subtypes for the thyroid hormone (TH) receptor (TR), TRß. While the other TH receptor subtype, TRα, is mainly expressed in the heart and is responsible for thyroxine's cardiac function, TRß is mainly expressed in the liver and is involved in liver function. Using TRß-specific agonists to treat NAFLD can prevent cardiac and other adverse side effects. Several TRß-specific agonists have shown positive therapeutic effects in NAFLD animal models and have entered clinical trials. We seek to provide a comprehensive updated reference of TRß-specific agonists in this review and explore the future therapeutic potential of TRß-specific activation in the treatment of NAFLD.

Respiratory Syncytial Virus is the Most Common Causative Agent of Viral Bronchiolitis in Young Children: An Updated Review.

BACKGROUND: Viral bronchiolitis is a common condition and a leading cause of hospitalization in young children. OBJECTIVE: This article provides readers with an update on the evaluation, diagnosis, and treatment of viral bronchiolitis, primarily due to RSV. METHODS: A PubMed search was conducted in December 2021 in Clinical Queries using the key terms "acute bronchiolitis" OR "respiratory syncytial virus infection". The search included clinical trials, randomized controlled trials, case control studies, cohort studies, meta-analyses, observational studies, clinical guidelines, case reports, case series, and reviews. The search was restricted to children and English literature. The information retrieved from the above search was used in the compilation of this article. RESULTS: Respiratory syncytial virus (RSV) is the most common viral bronchiolitis in young children. Other viruses such as human rhinovirus and coronavirus could be etiological agents. Diagnosis is based on clinical manifestation. Viral testing is useful only for cohort and quarantine purposes. Cochrane evidence-based reviews have been performed on most treatment modalities for RSV and viral bronchiolitis. Treatment for viral bronchiolitis is mainly symptomatic support. Beta-agonists are frequently used despite the lack of evidence that they reduce hospital admissions or length of stay. Nebulized racemic epinephrine, hypertonic saline and corticosteroids are generally not effective. Passive immunoprophylaxis with a monoclonal antibody against RSV, when given intramuscularly and monthly during winter, is effective in preventing severe RSV bronchiolitis in high-risk children who are born prematurely and in children under 2 years with chronic lung disease or hemodynamically significant congenital heart disease. Vaccines for RSV bronchiolitis are being developed. Children with viral bronchiolitis in early life are at increased risk of developing asthma later in childhood. CONCLUSION: Viral bronchiolitis is common. No current pharmacologic treatment or novel therapy has been proven to improve outcomes compared to supportive treatment. Viral bronchiolitis in early life predisposes asthma development later in childhood.

Successful and safe treatment of severe steroid depended eosinophilic asthma with mepolizumab in a woman during pregnancy.

A 26-year-old female with steroid dependent eosinophilic asthma and nasal polyps who had successfully been treated with mepolizumab for 17 consecutive months with complete steroid withdrawal and symptoms control, stopped biologic treatment due to pregnancy efforts. Mepolizumab discontinuation resulted in frequent exacerbations and daily symptoms despite high dose ICS/LABA and re-initiation of oral steroids. Mepolizumab was initiated again, followed by improvement of asthma control and gradual withdrawal of steroids within 2 months. The patient became pregnant during the fourth month of mepolizumab re-initiation. The patient presented two asthma exacerbations during pregnancy treated with short course (3 days) oral steroids and delivery was uneventful (female, Apgar 9, weight 2750 g, length 59 cm) in week 40 by caesarean section.

Recent advances in the treatment of childhood asthma: a clinical pharmacology perspective.

INTRODUCTION: Childhood asthma is a complex heterogenous inflammatory disease that can pose a large burden on patients and their caregivers. There is a strong need to adapt asthma treatment to the individual patient taking into account underlying inflammatory profiles, moving from a 'one size fits all' approach toward a much-needed personalized approach. AREAS COVERED: This review article aims to provide an overview of recent advances in the management and treatment of pediatric asthma, including novel insights on the molecular heterogeneity of childhood asthma, the emergence of biologicals to treat severe asthma, and innovative e-health and home monitoring techniques to make asthma management more convenient and accessible. EXPERT OPINION: Molecular technologies have provided new treatment leads. E-health and home monitoring technologies have helped to gain more insights into disease dynamics and improve adherence to treatment while bringing health care to the patient. However, uncontrolled childhood asthma is still a major unmet clinical need and precision-medicine approaches are still scarce in clinical practice. Advanced omics methods may help researchers or clinicians to more accurately phenotype and treat subtypes of childhood asthma and gain more insight into the complexity of the disease.

Utilization Patterns and Trends in the Use of Medications for Asthma in a Cohort of Colombian Patients.

Purpose: Asthma affects approximately 358 million people worldwide. This study aimed to determine the trend for the use of medications intended to treat asthma in a group of patients affiliated with the Colombian health system. Patients and Methods: This was a retrospective study on prescription patterns of medications used to treat asthma in patients over 5 years of age between 2017 and 2019. Sociodemographic variables, medications used and combinations, the persistence of use, and prescribing physicians were considered. Data were obtained from a drug-dispensing database from Colombia. Results: A total of 10,706 people diagnosed with asthma were identified, including predominantly females (56.8%), with a mean age of 32.2 ± 26.1 years. At the beginning of the follow-up, 53.2% of patients aged 5-11 years were receiving monotherapy, with a mean of 1.5 ± 0.6 drugs/patient, especially inhaled corticosteroids (ICSs; 55.9%) and short-acting ß-agonists (SABAs; 55.6%). Moreover, in patients older than 12 years, 53.5% were treated with monotherapy, with a mean of 1.6 ± 0.7 drugs/patient, 45.9% of whom were on SABAs, while 37.1% were on ICSs. Between 63.0% and 83.6% of patients were treated by a general practitioner. 12.5% of patients (n = 495) received triple therapy (ICS/LABA + LAMA [long-acting antimuscarinic]), particularly fluticasone/salmeterol + tiotropium. Conclusion: The identification of treatment patterns will allow physicians and decision makers to implement strategies in order to promote adherence to treatment and improve asthma medication use.

Is This Medication Safe for My Child? How to Discuss Safety of Commonly Used Medications With Parents.

All drugs have potential side effects, but thoughtful use can maximize benefits while minimizing risks. Children should not be considered just small adults regarding drug safety because their growth and development are discordant with their ability to sense and self-report drug side effects. Detecting side effects requires vigilance and education from prescribers to parents, who are tasked with monitoring their child over time. A drug's safety profile is published in the package label after pivotal trials are conducted in relatively small and sometimes narrow segments of the population during the U.S. Food and Drug Administration approval process. Drug safety profiles can change as data from postmarketing reports and long-term monitoring during phase IV trials emerge. As such, prescribers are obligated to maintain current understanding of any changes to drug labels. Discussing potential side effects, monitoring, and when to report concerns can be a time-consuming process during patient encounters. This review offers current information regarding potential side effects of some of the most commonly used medications for allergic conditions, asthma, and atopic dermatitis. This information and discussion will hopefully assist clinicians in their conversations with parents, including advice surrounding prescribing medication to minimize adverse effects, parental monitoring, and documentation.

Reducing Tolerance for SABA and OCS towards the Extreme Ends of Asthma Severity.

Asthma is a heterogeneous chronic inflammatory airway disease that imposes a great burden on public health worldwide. In the past two years, fundamental changes have been addressed in the Global Initiative for Asthma (GINA) recommendations focusing mainly on the management of mild and severe asthma. The use of as-needed treatment containing inhaled corticosteroids plus fast-acting bronchodilators (either short or long-acting formoterol) in mild asthma has dominated the field, and both randomized and real-world studies favor such an approach and associate it with fewer exacerbations and good asthma control. At the same time, the effort to diminish the use of oral steroids (OCS) as maintenance treatment in severe asthma was substantially accomplished with the initiation of treatment with biologics. Still, these options are available at the moment only for severe asthmatics with a T2-high endotype, and relevant studies on biologics have yielded, as a primary outcome, the reduction or even cessation of OCS. Accordingly, OCS should be considered as a temporary option, mainly for the treatment of asthma exacerbations, and as a maintenance treatment only for a minority of patients with severe asthma, after ensuring good inhaler technique, modification of all possible contributory factors and comorbidities, and optimized pharmacotherapy using all other add-on treatments including biologics in the armamentarium of anti-asthma medication.

Treatment Transitions in Chronic Obstructive Pulmonary Disease: Retrospective Analyses of US and UK Healthcare Databases.

INTRODUCTION: Previous studies have reported that more patients receive inhaled corticosteroid (ICS)-containing therapies than would be expected based on exacerbation history, suggesting overprescribing. We aimed to describe patterns of treatment switching from first (1MT) to second maintenance therapy (2MT) among COPD patients in the US and UK. METHODS: We used healthcare data from the US IBM® MarketScan® and UK Clinical Practice Research Datalink databases (2015 - 2018) to assess transitions between 1MT and 2MT among COPD patients. Patients with a recorded asthma diagnosis prior to 1MT were excluded. We assessed whether prescribed treatments (long-acting muscarinic antagonists [LAMA], long-acting ß2-agonists [LABA], inhaled corticosteroids [ICS], as monotherapy or in combination) were consistent with global and national recommendations for COPD, identified patient characteristics associated with treatment transitions, and evaluated treatment duration. RESULTS: Overall, 7028 patients in the US and 2461 in the UK initiated 2MT within a median (IQR) 160.0 (76.0; 335.0) and 218.0 (86.0; 428.0) days after 1MT, respectively. In the US, 33.6% of patients initiating 2MT had no recorded exacerbations in the previous year, whereas 23.1% had one and 43.3% had ≥ 2. In the UK, 54.9% of patients had no recorded exacerbations in the previous year, whereas 20.9% had one and 24.2% had ≥ 2. At 2MT, most patients switched to LAMA/LABA/ICS (26.1%) or LABA/ICS (25.8%) in the US, and LAMA/LABA (39.4%) or LAMA/LABA/ICS (27.8%) in the UK; 62.2% (US) and 47.5% of patients (UK) were prescribed ICS-containing regimens. The most common treatment transition from 1MT to 2MT was LABA/ICS to LAMA/LABA/ICS (13.0%) in the US; and LAMA to LAMA/LABA (32.5%) and LAMA to LAMA/LABA/ICS (14.3%) in the UK. CONCLUSIONS: At 2MT, the proportion of patients on LAMA/LABA/ICS was similar between the US and UK, but treatment pathways were different.

People with chronic obstructive pulmonary disease (COPD) take inhaled medication to control symptoms such as breathlessness and cough. There are two types of inhaler: 'reliever' inhalers for immediate symptom relief, and 'maintenance' inhalers for long-term disease control. Maintenance inhalers can be used on their own or together, and treatment is often escalated based on the persistence of symptoms or exacerbations (flare-ups), for which inhaled corticosteroids (ICS) are often prescribed. We wanted to see whether doctors' prescribing habits are in line with clinical guidelines, so we looked at data from COPD patients who switched from their first maintenance therapy (1MT) to a second, different maintenance therapy (2MT) between 2015 and 2018. Our data sources were a US health claims database (~ 7000 patients) and a UK general practice database (~ 2500 patients). We excluded people with a diagnosis of both COPD and asthma, as similar inhalers are used to treat these two conditions, although the clinical decisions for when to prescribe them differ. On average, the time between 1MT and 2MT was 160 days (US) and 218 days (UK). Overall, 50% (UK) and 60% of patients (US) were prescribed ICS as part of their treatment regimen at 2MT, and ICS use in both countries was higher than expected based on the guidelines, which recommend ICS only for patients with severe COPD who meet certain criteria. This means that some patients are being given medication without a known clinical benefit, which puts them at risk of side effects, possibly increasing unnecessary healthcare costs.

First Maintenance Therapy for Chronic Obstructive Pulmonary Disease: Retrospective Analyses of US and UK Healthcare Databases.

INTRODUCTION: Inhaled corticosteroids (ICS) are often prescribed inappropriately alongside long-acting bronchodilators for chronic obstructive pulmonary disease (COPD). We aimed to investigate if prescribing habits in the US and UK differ from recommendations for initiation of COPD maintenance therapy. METHODS: We used healthcare data from the US IBM® MarketScan® and UK Clinical Practice Research Datalink databases to assess exacerbations and comorbidities in patients with COPD initiating first maintenance therapy (1MT) between 2015 and 2018. Patients with a recorded asthma diagnosis prior to initiation of 1MT were excluded. We evaluated time from recorded diagnosis of COPD until initiation of 1MT, and treatment regimen at 1MT (long-acting muscarinic antagonist [LAMA], long-acting ß2-agonist [LABA], ICS, as monotherapy or in combination). RESULTS: In the US and UK, median (IQR) time between recorded COPD diagnosis and 1MT was 158 (12; 839) and 29 (1; 521) days, respectively. Among the 53,473 US patients and 8786 UK patients who initiated 1MT, 50.9% and 32.4% had ≥ 1 exacerbation in the previous year. In the US, 20% of patients initiated LAMA, 1% LABA, 13% LAMA/LABA, and 66% an ICS-containing regimen (49% LABA/ICS, 13% ICS, and 4% LAMA/LABA/ICS). In the UK, 53% of patients initiated LAMA, 4% LABA, 16% LAMA/LABA, and 27% an ICS-containing regimen (14% LABA/ICS, 9% ICS, and 4% LAMA/LABA/ICS). CONCLUSIONS: At 1MT, two-thirds of patients in the US received ICS-containing therapies, with almost half on LABA/ICS. In contrast, less than one-third received ICS-containing therapy in the UK and more than half of patients received LAMA. In both countries, more patients received ICS-containing therapies at initiation of 1MT than would be expected based on their exacerbation history, suggesting overprescribing.

Chronic obstructive pulmonary disease (COPD), a smoking-related lung disease, restricts airflow in the lungs, causing symptoms such as breathlessness and coughing. To control symptoms, patients use one or more types of inhaled 'maintenance' medication, which can be prescribed alone or together. When patients have a short-term worsening of symptoms, doctors often prescribe inhaled corticosteroids (ICS). We wanted to see whether doctors' prescribing habits for maintenance inhalers are in line with clinical guidelines, so we analyzed data from a US health insurance database (~ 50,000 patients) and UK primary care medical records (~ 8000 patients). We focused on patients with a diagnosis of COPD who were prescribed their first maintenance therapy (1MT) between 2015 and 2018. We excluded people with a diagnosis of both COPD and asthma, as similar inhalers are used to treat these conditions, although the clinical decisions for when to prescribe them differ. The average time between COPD diagnosis and 1MT was longer in the US (158 days) than in the UK (29 days). A higher percentage of patients in the US (~ 65%) versus UK (~ 25%) were prescribed ICS as part of their treatment, and ICS use in both countries was higher than expected based on the guidelines, which recommend ICS only for patients with severe COPD who meet certain criteria. Our findings suggest overprescribing of ICS in both countries (particularly the US), meaning that some patients are being given medication without a known clinical benefit, which puts them at risk of side effects, possibly increasing unnecessary healthcare costs.

Asthma severity and impact on perinatal outcomes: an updated systematic review and meta-analysis.

BACKGROUND: Large-scale studies exploring the associations of asthma severity, exacerbations and medication use with adverse perinatal outcomes have been published in recent years. OBJECTIVES: To update evidence on the associations of asthma severity, exacerbations and medication use with the adverse perinatal outcomes of preterm delivery (PD), low birthweight (LBW) and small-for-gestational-age (SGA). SEARCH STRATEGY: PubMed, Embase, Wanfang, and China National Knowledge Infrastructure (CNKI) from inception to 1 January 2021. SELECTION CRITERIA: Cohort studies comparing the likelihood of adverse perinatal outcomes in groups of asthmatic women stratified by asthma severity, asthma exacerbations or medication use, or comparing the likelihood of adverse perinatal outcomes between non-asthmatic women and asthmatics of various levels of severity and exacerbation. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed risk of bias. Random-effects models were used to meta-analyse the results. MAIN RESULTS: Twenty studies met the inclusion criteria. The odds of delivering SGA babies increased with maternal asthma severity. Pregnant women with an asthma exacerbation had higher odds of delivering LBW babies and SGA babies, compared with pregnant women with asthma but without an exacerbation (pooled adjusted odds ratio [OR] 1.15, 95% CI 1.02-1.29 for LBW; number of studies with adjusted OR 3; I2 = 0%) (pooled adjusted OR 1.13, 95% CI 1.04-1.23 for SGA; number of studies with adjusted OR 4; I2 = 0%) and compared to pregnant women without asthma. Oral corticosteroids use during pregnancy was associated with increased odds of LBW, but not PD. CONCLUSIONS: The available data suggest that maternal asthma severity and exacerbations are associated with increased odds of LBW and SGA babies. TWEETABLE ABSTRACT: A systematic review and meta-analysis found that maternal asthma severity and exacerbations are associated with increased odds of delivering low birthweight and small-for-gestational-age babies.