LABA Research Articles

Challenges in treating patients with comorbid asthma and bronchiectasis.

The management of patients with overlapping asthma and bronchiectasis requires a tailored approach, starting with a comprehensive assessment of the patient's clinical profile, including the severity of asthma and the extent of bronchiectasis. Inhaled corticosteroids (ICS) are often recommended, but their use should be carefully monitored because of the risk of increased infection. If the asthma is well controlled and the bronchiectasis remains stable, a gradual reduction in the dose of ICS may be considered. Adjunctive therapies such as macrolides, which have anti-inflammatory and antimicrobial effects, or leukotriene receptor antagonists may be beneficial. However, leukotriene receptor antagonists should be used with caution in patients with bronchiectasis. Long-acting muscarinic antagonists (LAMA), especially in combination with ICS and long-acting beta-agonists (LABA), can improve bronchodilation and reduce inflammation. Although triple therapy (ICS/LABA/LAMA) is promising, its efficacy in bronchiectasis has not yet been confirmed by randomised controlled trials (RCTs). Ongoing monitoring is essential to adjust treatment as the patient's condition evolves. Preventive measures, including vaccination and regular sputum cultures, are important to minimize the risk of infection. Further research and RCTs are needed to better understand the role of dual bronchodilators and triple therapy in the management of overlapping asthma-bronchiectasis.

A Pharmacovigilance Study on Anti-Asthmatic Agent

Pharmacovigilance plays a critical role in ensuring the safety and efficacy of anti-asthmatic agents, including inhaled corticosteroids (ICS), long-acting beta-agonists (LABAs), and leukotriene receptor antagonists (LTRAs). This study evaluates adverse drug reactions (ADRs) associated with these medications, emphasizing their clinical impact, risk factors, and patient outcomes. A systematic approach, including spontaneous ADR reporting, database reviews, and post-marketing surveillance, was utilized to identify patterns of drug-related complications, such as dysphonia, oral candidiasis, and cardiovascular risks. Findings highlight the importance of monitoring combination therapies, optimizing medication use, and enhancing patient education to improve asthma management while minimizing risks. Future directions include integrating pharmacogenomic data into safety assessments to personalize asthma treatment

Genotype-Guided Asthma Treatment Reduces Exacerbations in Children: Meta-Analysis of Two RCTs.

Long-acting beta2-agonists (LABA) in combination with inhaled corticosteroids (ICS) are commonly used to treat asthma, however, some children lack response to the addition of LABA. This might be partially due to the presence of the Arg16Gly polymorphism, encoded by rs1042713 G>A in the ADRB2 gene. Carrying the A allele (Arg16) at this variant has been associated with an increased risk of exacerbations despite LABA treatment. We investigated whether genotype-guided treatment improved asthma-related outcomes. We conducted an individual participant data meta-analysis of two randomised controlled trials: PUFFIN (Dutch and Swiss 6-18 year-olds) and PACT (English and Scottish 12-18 year-olds). Children with uncontrolled asthma despite ICS who required a step-up in treatment were included. Participants were randomised to genotype-guided treatment or the control group with a follow-up of at least 6 months. Genotype-guided treatment consisted of adding LABA for children with ADRB2 Gly16/Gly16, whilst children with ADRB2 Arg16/Arg16 or Arg16/Gly16 were treated with double dose ICS (PUFFIN) or add-on montelukast (PACT). The primary outcome was a change in asthma control; secondary outcomes included exacerbation rate and time to exacerbation. Repeated measures mixed models and Cox regression were used. Fifty-nine out of 102 (PUFFIN) and 59 out of 91 (PACT) children had at least one Arg (A allele). Amongst all 193 children, no difference was observed in asthma control between the study groups. However, genotype-guided treatment resulted in lower asthma exacerbation rates (-0.08 (95%CI -0.16 to -0.00, p = 0.04)) compared to the control group. Genotype-guided step-up treatment for children with uncontrolled asthma on ICS may lower asthma exacerbation rates and may be useful for personalising asthma care.

Minimising inhaled corticosteroids for COPD.

This Therapeutic Letter considers the evidence for inhaled corticosteroids (ICS) as a treatment for Chronic Obstructive Pulmonary Disease (COPD). Drug therapy aims to alleviate symptoms, enhance functional capacity and prevent exacerbations, but has not consistently shown to reduce mortality or improve quality of life based on randomised trials.Inhaled corticosteroids have shown limited benefits for COPD symptoms and exacerbations but increased risks of serious harms. Guidelines recommend limiting ICS to severe COPD and only for repeated exacerbations. Studies show withdrawing ICS can be done safely for stable COPD patients with infrequent exacerbations, especially those with lower eosinophil counts. Provincial, national and international guidelines now recommend limiting ICS prescriptions to severe COPD stages. Long-term ICS use may lead to serious side effects, including pneumonia and fractures. Initial COPD therapy should focus on short-acting bronchodilators, not ICS. Adding long-acting bronchodilators is recommended before considering ICS because of limited benefits and risks of serious harms. For persistent symptoms, long-acting muscarinic antagonists (LAMA) or long-acting beta2 agonists (LABA) are recommended, with the addition of ICS reserved for those with repeated exacerbations and severe COPD. Deprescribing ICS can be considered in clinically stable patients, particularly for those with infrequent exacerbations and mild COPD. When applicable, tapering ICS over several months is advised for patients with elevated eosinophil counts. Overall, the risks of serious harms from ICS typically outweigh their limited benefits for mild COPD patients in primary care.

The Effect of Inhaled Beta-2 Agonists on Heart Rate in Patients With Asthma: Sensor-Based Observational Study.

Beta-2 agonists play an important role in the management of asthma. Inhaled long-acting beta-2 agonists (LABAs) and short-acting beta-2 agonists (SABAs) cause bronchodilation by stimulating adrenoceptors. These receptors are also present in cardiac cells and, as a side effect, could also be stimulated by inhaled beta-2 agonists. This study aims to assess the effect of beta-2 agonists on heart rate (HR). The data were retrieved from an observational study, the myAirCoach Quantification Campaign. Beta-2 agonist use was registered by self-reported monthly questionnaires and by smart inhalers. HR was monitored continuously with the Fitbit Charge HR tracker (Fitbit Inc). Patients (aged 18 years and older) were recruited if they had uncontrolled asthma and used inhalation medication. Our primary outcome was the difference in HR between LABA and non-LABA users. Secondary outcomes were the difference in HR on days SABAs were used compared to days SABAs were not used and an assessment of the timing of inhaler use during the day. Patients using LABA did not have a clinically relevant higher HR (average 0.8 beats per minute difference) during the day. Around the moment of SABA inhalation itself, the HR does increase steeply, and it takes 138 minutes before it returns to the normal range. This study indicates that LABAs do not have a clinically relevant effect on HR. SABAs are instead associated with a short-term HR increase. ClinicalTrials.gov NCT02774772; https://clinicaltrials.gov/study/NCT02774772.

Implementation of quality by design and green chemistry principles to validate the stability indicating method on UHPLC for the simultaneous quantification of Glycopyrronium, Fluticasone, Vilanterol in inhaled formulation

The combination of Glycopyrronium, Fluticasone, and Vilanterol is utilized to manage chronic obstructive pulmonary disease (COPD) and mitigate asthma symptoms. Glycopyrronium functions as an anticholinergic compound, Fluticasone serves as a corticosteroid that mitigates inflammation, and Vilanterol operates as a long-acting beta-agonist that facilitates the relaxation of the bronchial passages. The simultaneous quantification of Glycopyrronium, Vilanterol, and Fluticasone was accomplished through the utilization of Ultra-High-Performance Liquid Chromatography (UHPLC) employing a Symmetry Shield C18 column (4.6 mm x 100 mm ID, 2.6µm particle size), with a flow rate of 0.6 mL/min, and a gradient elution employing pH 3.0 Ammonium Formate as mobile phase A and ethanol as mobile phase B. By the guidelines delineated by the International Conference on Harmonization (ICH) Q2, method validation encompassed specificity (with the purity angle for the three chromatographic peaks exceeding the purity threshold under all degradation conditions), linearity (exhibiting an R² value greater than 0.999 from the lower limit of quantification to 200%), accuracy (with recovery rates ranging from 95% to 105%), robustness (the influence of variations in mobile phase buffer pH, column temperature, and flow rate was scrutinized utilizing Analytical Quality by Design principles), and assessments of method precision. The Green Analytical Procedure Index (GAPI), Analytical Greenness (AGREE), and analytical eco-scale evaluations substantiated the method's advantageous characteristics regarding environmental sustainability.

Triple inhaled therapy in asthma: Beliefs, behaviours and doubts

Long-acting muscarinic antagonists (LAMA) in association with inhaled corticosteroids (ICS) plus long-acting beta-2 agonists (LABA) are recommended by the GINA report as further option in step 4 and first choice in step 5 treatment. Despite consistent evidence of its efficacy and safety, inhaled triple therapy (ITT) is still not largely used in patients with asthma.With the aim to explore belief and behaviours of asthma specialists, an ad hoc survey has been developed by a panel of Interasma Scientific Network (INESnet) experts and subsequently defined by two Delphi rounds among an international group of physicians. The questionnaire has been distributed through Interasma social media between June and September 2023.Besides a descriptive analysis, to assess the responses gathered from the questionnaire, Spearman's non-parametric statistical method was employed.Totally, three hundred fourteen questionnaires were completed. Clinicians' attitudes and behaviours toward timing and methodologies adopted in prescribing ITT, were analysed. 35.7 % specialists consider ITT as a relevant therapeutic option, 61.8 % that is second option after reaching high dose of ICS-LABA and 89.2 % agreed that optimization of inhaled therapy should be attempted before the use of biological drugs. Persistent flow limitation and high reversibility are considered predictive factors of response.Specialists consider ITT a resource in asthma management. Although its efficacy in decreasing exacerbation rate and improving lung function were well known, the survey revealed persistent uncertainties among clinicians in positioning it highlighting the need for further measures to effectively integrate research findings into day-to-day clinical practice.

Association of moderate-to-vigorous physical activity with reduction of acute exacerbation in COPD patients using a dual ultra-long-acting bronchodilators

Inhaler therapy and physical activity (PA) are important methods of chronic obstructive pulmonary disease (COPD) management. This study aimed to investigate the additional benefit of moderate-to-vigorous PA (MVPA) in patients with COPD using a long-acting beta-agonists (LABA)/long-acting muscarinic antagonist (LAMA) combination. We emulated a target trial to estimate the benefit of MVPA in patients with COPD using a dual ultra-long-acting bronchodilators. We enrolled patients aged ≥ 40 who were diagnosed with COPD between 2014 and 2018, initiated a LABA/LAMA combination, and had not undergone regular MVPA. The main exposure was the initiation of MVPA, defined as vigorous aerobic exercise > 20 min per day on ≥ 3 days/week or moderate aerobic exercise > 30 min per day on ≥ 5 days/week. The main outcomes were the future usage of inhaled corticosteroids (ICS) and severe exacerbation. We identified 1,526 patients who initiated MVPA and 4,516 who did not. The median follow-up period was 3.0 years. The hazard ratio (HR) for future ICS usage in the MVPA initiation group was 0.83 (95% confidence intervals (CI): 0.72, 0.97) compared to the control group. The HR for severe exacerbation in the MVPA initiation group was 0.81 (95% CI: 0.68, 0.96) compared to the control group. Subgroup analyses by age, sex, body mass index, residence area, smoking and drinking status showed consistent benefits in these outcomes. Initiation of MVPA may offer an additional benefit for even COPD patients who use a dual ultra-long-acting bronchodilators.

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.

Greenness assessment of a molecularly imprinted polymeric sensor based on a bio-inspired polymer

Methyldopa, a synthesized dopamine substitute with phenolic, amine, and carboxylic groups, was used to create a selective molecular imprinted polymer (MIP) for detecting formoterol fumarate dihydrate (FFD), a long-acting beta2-agonist for asthma and COPD. The bio-inspired polymer (MD) was electro-grafted onto a pencil graphite electrode (PGE) using cyclic voltammetry in a phosphate buffer (pH 6.5). An indirect method involving a redox probe (ferrocyanide/ferricyanide) and differential pulse voltammetry measured FFD binding to the MIP’s 3D cavities. The sensor showed a linear response range from 1 × 10⁻⁹ M to 2 × 10⁻¹⁰ M, with a detection limit of 1.7 × 10⁻¹¹ M. The polymethyldopa (PMD) and FFD interaction was assessed by UV spectroscopy, and the method was validated per ICH guidelines. Green analytical approaches, including RGB and GAPI, were also implemented. The goal was to use advances in molecularly imprinted polymers to develop a more precise and selective electrochemical sensor for FFD quantification.

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.

Triple Therapy De-Escalation and Withdrawal of Inhaled Corticosteroids to Dual Bronchodilator Therapy in Patients with Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis.

Background/Objectives: The interpretation of evidence on the de-escalation of triple therapy with the withdrawal of inhaled corticosteroids (ICSs) to dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and a long-acting beta-agonist (LABA) in patients with chronic obstructive pulmonary disease (COPD) is conflicting. We evaluated the efficacy and safety of ICS discontinuation from LABA-LAMA-ICS triple therapy compared to its continuation. Methods: We searched PubMed, Embase, Scopus, Web Of Science, clinicaltrial.gov, and CENTRAL for RCTs and observational studies from inception to 22 March 2024, investigating the effect of triple therapy de-escalation with the withdrawal of ICSs to dual therapy on the risk of COPD exacerbation, pneumonia, and lung function. This study was registered with PROSPERO, CRD42024527942. Results: A total of 3335 studies was screened; 3 RCTs and 3 real-world non-interventional studies were identified as eligible. The analysis of the time to the first moderate or severe exacerbation showed a pooled HR of 0.96 (95% CI, 0.80-1.15; I2 = 77%) for ICS withdrawal compared to triple therapy continuation. The analysis according eosinophil levels showed that COPD subjects with ≥300 eosinophils/µL had a significant increase in the incidence of moderate or severe exacerbations when de-escalated to LABA/LAMA (pooled HR: 1.35, 95% CI: 1.00-1.82; I2: 56%). ICS withdrawal did not significantly affect the risk of mortality and pneumonia. Conclusions: The de-escalation of triple therapy with ICS withdrawal does not affect the main outcomes evaluated (moderate or severe exacerbations, change in trough FEV1). COPD patients with high blood eosinophils (≥2% or ≥300 cells/µL) are most likely to benefit from continuing triple therapy.

Benefit of dual bronchodilator therapy on exacerbations in former and current smokers with chronic obstructive pulmonary disease in real-world clinical practice: a multicenter validation study (TOReTO)

BackgroundDual bronchodilator therapy, consisting of a long-acting beta-agonist (LABA) and a long-acting muscarinic antagonist (LAMA), has proven effective for patients with chronic obstructive pulmonary disease (COPD). However, it remains uncertain whether there are efficacy differences between current and former smokers with COPD. This study aims to explore the effectiveness of LABA/LAMA therapies in both these groups.MethodsThe TOReTO trial assessed lung function, symptoms, health status, the occurrence of exacerbations, clinically significant exacerbations, and the use of LABA/LAMA therapies. These therapies include Tio/Olo, umeclidinium/vilanterol (Umec/Vi), and umeclidinium/vilanterol (Umec/Vi) are used in patients with COPD. The study examined the differences in outcomes between current and former smokers. To balance the baseline characteristics, propensity score matching (PSM) was employed.ResultsData from 967 patients were collected. After PSM, the time to the first acute exacerbation in current smokers was analyzed separately for the three treatment groups and was significantly different between them (p = 0.0457). Among, there are differences in the occurrence of acute exacerbation between treatment and smoking status in Umec/Vi (p = 0.0114). There is no significant difference in the treatment of former smokers among the three different groups of LABA/LAMA fixed-dose combinations (p = 0.3079). COPD-related symptoms remained stable throughout the treatment period. There were no significant differences in symptom scores, including CAT and mMRC, among the three groups at the end of the study.ConclusionsThe three fixed-dose combinations of LABA/LAMA showed no difference in reducing exacerbations in former smokers but did show differences in current smokers. This trend has clinical significance, and future research will be conducted to control influencing variables to validate this point. However, due to the non-randomized study design, these findings should be interpreted with caution.

Study of blood eosinophils and plasma periostin as biomarkers for response of COPD patients to ICS/LABA treatment

BackgroundEosinophilic airway inflammation has been detected in up to 40% of chronic obstructive pulmonary disease (COPD) patients during stable periods of the disease, and increased sputum eosinophil count was associated with better lung function, more future exacerbations, and symptoms that responded better to treatment with inhaled and oral corticosteroids.The aim of this work was to investigate the relationship of blood eosinophils and plasma periostin with lung function changes related to ICS and long-acting beta2-agonist combination treatment in stable COPD patients for 3 months.MethodsThis prospective experimental study was carried out on 50 COPD patients with post-bronchodilator FEV1/FVC ratio < 70%. Patients collected from outpatient clinics of Chest Department Tanta University Hospitals, Tanta Chest Hospital, and Mansoura Chest Hospital from February 2020 to February 2022. Patients were subjected to complete history taking, and clinical examinations including general and local examinations and laboratory investigations (complete blood count to assess eosinophilic count, arterial blood gases, and plasma periostin) and spirometry were done for all patients pre- and post-treatment. All patients received 3 months of treatment with a fixed dose of combined inhalers of ICS and LABA, and then they were classified into FEV1 responder and FEV1 non-responder according to improvement in FEV1 at least 12% and 200 mL from baseline of 3 months of combined treatment with ICS/LABA.ResultsBlood eosinophil count had a significant positive correlation with smoking index (pack/year), negative correlations with FEV1% of predicted, FEV1 actual value (L), and FEV1/FVC ratio. Plasma periostin concentration had significant positive correlation with blood eosinophil count, COPD grade, and FVC actual value (L) and significant negative correlations with FEV1% of predicted, FEV1 actual value (L), and FEV1/FVC. Cutoff values of blood eosinophil count > 265 cell/µL, plasma periostin concentration > 15.747 ng/mL, and FEV1% < 40.5% were associated with posttreatment FEV1 response.ConclusionsCOPD patients with poor lung functions regarding FEV1/FVC ratio, FEV1 actual value (L), and FEV1% of predicted as well as high blood eosinophil count and high plasma periostin concentration are predicted to have FEV1 response with fixed-dose ICS/LABA combination treatment.

Single-Inhaler Triple vs LABA-ICS Therapy for COPD: Comparative Safety in Real-World Clinical Practice

Recent treatment guidelines for COPD have replaced the long-acting beta2-agonist (LABA) and inhaled corticosteroid (ICS) combination with single-inhaler triple therapy that adds a long-acting muscarinic antagonist (LAMA) (LAMA-LABA-ICS). However, the corresponding trials reported numerically higher incidences of cardiovascular adverse events with triple therapy compared with LABA-ICS. Does single-inhaler triple therapy increase the incidence of major adverse cardiovascular events, compared with LABA-ICS, in a real-world clinical practice setting? We identified a cohort of patients with COPD,≥ 40 years of age, treated during 2017-2021, from the UK's Clinical Practice Research Datalink. Among LAMA-naïve patients, initiators of single-inhaler triple therapy were matched 1:1 to LABA-ICS users on time-conditional propensity scores. They were compared on the incidence of major adverse cardiovascular events (MACEs), defined as hospitalization for myocardial infarction or stroke, or all-cause-mortality, over 1 year. The cohort included 10,255 initiators of triple therapy and 10,255 matched users of LABA-ICS. The incidence rate of MACEs was 11.3 per 100 per year with triple therapy compared with 8.7 per 100 per year for LABA-ICS. The corresponding adjusted hazard ratio (HR) of MACEs with triple therapy was 1.28 (95%CI, 1.05-1.55), relative to LABA-ICS; however, the increase was mainly in the first 4months (HR, 1.41; 95%CI, 1.14-1.74). The HR of all-cause death was 1.31 (95%CI, 1.06-1.62), whereas for acute myocardial infarction and stroke hospitalization it was 1.00 (95%CI, 0.56-1.79) and 1.06 (95%CI, 0.48-2.36), respectively, with triple therapy, relative to LABA-ICS. In a real-world setting of COPD treatment, patients who initiated single-inhaler triple therapy had an increased incidence of MACEs compared with similar patients treated with an LABA-ICS inhaler. This small increase was due to the all-cause mortality component, occurring mainly in the first 4months after treatment initiation.

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.

Elevated Fracture Risks in Patients Using Inhaled Corticosteroids: A Korean Nationwide Study.

In this comprehensive retrospective nationwide cohort study, we examined the relationships between various asthma medications and bone health, utilizing data from the National Health Insurance Service database of South Korea. From 2015 to 2019, the relevant dataset included 168,611 individuals aged 66 years, among whom 8,747 were diagnosed with asthma. We focused on a subset of 6,173 patients, all 66-year-old women. Participants were categorized into four groups: nonusers of asthma medication (n=2,868), leukotriene antagonist users (n=2,281), inhaled corticosteroid (ICS) users (n=517), and those using a combination of ICS and long-acting beta-agonist (ICS+LABA) medication (n=507). The primary outcomes measured were the incidences of major osteoporotic fractures and hip fractures during the follow-up period. Over 2.7 years of follow-up, 615 cases of major osteoporotic fractures and 96 cases of hip fractures were recorded. ICS users exhibited a heightened risk of both injuries, with hazard ratios of 1.38 (95% confidence interval [CI], 1.18 to 1.63; P<0.001) for major osteoporotic fractures and 1.56 (95% CI, 1.33 to 1.83; P<0.001) for hip fractures. Similarly elevated risks were observed in the ICS+LABA group. Notably, the risk associated with ICS was particularly pronounced among patients with osteopenia for both fracture types. Overall, the use of ICS, alone or in combination with LABA, in patients with asthma is associated with significantly increased risks of osteoporotic fractures, especially among those with osteopenia. These findings underscore the importance of considering bone health when managing asthma, especially in older patients and those with existing bone density issues.

DElaying disease Progression In COPD with early escalation to Triple therapy – A Modelling Study (DEPICT-2)

IntroductionIn patients with chronic obstructive pulmonary disease (COPD), dual bronchodilator (long-acting muscarinic antagonist (LAMA)/long-acting beta2-agonist (LABA)) and triple therapy (inhaled corticosteroid (ICS)/LAMA/LABA) reduce risk of exacerbations and lung function decline in short-mid-term, but their long-term impact is unknown. This modelling study explores long-term impact of these therapies on lung function decline, quality of life (QoL) and all-cause mortality.MethodsThis modelling approach used a longitudinal non-parametric superposition model using published data regarding exacerbations, QoL (assessed by St. George's Respiratory Questionnaire (SGRQ)), and mortality. The model simulated disease progression from 40 to 75 years of age and assessed the impact of initiating dual bronchodilator at age 45 years (“LAMA/LABA only” group) and escalation to triple therapy at age 50 years (“Escalation to triple” group) on forced expiratory volume in 1 s (FEV1) decline, QoL, and mortality.ResultsModel simulation predicted that by 75 years of age: “LAMA/LABA only” preserves 159.1 mL of FEV1versusno treatment, “Escalation to triple” preserves an additional 376.5 mL and 217.3 mL of FEV1versusno pharmacotherapy and “LAMA/LABA only”, respectively. In “LAMA/LABA only”, SGRQ score reduces (−3.2)versusno treatment, which further reduces to −7.5 therapy in “Escalation to triple”. In “LAMA/LABA only”, mortality reduces by 5.4% by 75 yearsversusno treatment, while the “Escalation to triple” shows further decrease in mortality by 12.0%.ConclusionEarly pharmacotherapy initiation and escalation from dual bronchodilator to triple therapy could slow disease progression by preserving lung function and improving QoL and survival in patients with COPD.

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?