Inhaled Corticosteroids Research Articles

Outpatient inhaled corticosteroid use in bronchopulmonary dysplasia.

In the outpatient setting, inhaled corticosteroids (ICS) are frequently given to children with bronchopulmonary dysplasia (BPD) for treatment of respiratory and asthma-associated symptoms. In this study we sought to determine if correlations existed between ICS use and ICS initiation and patient characteristics and outpatient respiratory outcomes. This study included children with the diagnosis of BPD (n = 661) who were seen in outpatient pulmonary clinics at the Children's Hospital of Philadelphia between 2016 and 2021. Chart review was used to determine patient demographics, use and timing of ICS initiation, asthma diagnosis, and acute care usage following initial hospital discharge. At the first pulmonary visit, 9.2% of children had been prescribed an ICS at NICU discharge, 13.9% had been prescribed an ICS after NICU discharge but before their first pulmonary appointment, and 6.9% were prescribed an ICS at the completion of initial pulmonary visit. Children started on an ICS as outpatientshad a higher likelihood of ER visits (adjusted odds ratio: 2.68 ± 0.7), hospitalizations (4.81 ± 1.16), and a diagnosis of asthma (3.58 ± 0.84), compared to children never on an ICS. Of those diagnosed with asthma, children prescribed an ICS in the outpatient setting received the diagnosis at an earlier age. No associations between NICU BPD severity scores and ICS use were found. This study identifies an outpatient BPD phenotype associated with ICS use and ICS initiation independent of NICU severity score. Additionally, outpatient ICS initiation correlates with a subsequent diagnosis of asthma and acute care usage in children with BPD.

Inhaled Reliever Therapies for Asthma: A Systematic Review and Meta-Analysis.

The optimal inhaled reliever therapy for asthma remains unclear. To compare short-acting β agonists (SABA) alone with SABA combined with inhaled corticosteroids (ICS) and with the fast-onset, long-acting β agonist formoterol combined with ICS for asthma. The MEDLINE, Embase, and CENTRAL databases were searched from January 1, 2020, to September 27, 2024, without language restrictions. Pairs of reviewers independently selected randomized clinical trials evaluating (1) SABA alone, (2) ICS with formoterol, and (3) ICS with SABA (combined or separate inhalers). Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses synthesized outcomes. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to evaluate the certainty of evidence. Asthma symptom control (5-item Asthma Control Questionnaire; range, 0-6, lower scores indicate better asthma control; minimum important difference [MID], 0.5 points), asthma-related quality of life (Asthma Quality of Life Questionnaire; range, 1-7, higher scores indicate better quality of life; MID, 0.5 points), risk of severe exacerbations, and risk of serious adverse events. A total of 27 randomized clinical trials (N = 50 496 adult and pediatric patients; mean age, 41.0 years; 20 288 male [40%]) were included. Compared with SABA alone, both ICS-containing relievers were associated with fewer severe exacerbations (ICS-formoterol risk ratio [RR], 0.65 [95% CI, 0.60-0.72]; risk difference [RD], -10.3% [95% CI, -11.8% to -8.3%]; ICS-SABA RR, 0.84 [95% CI, 0.73-0.95]; RD, -4.7% [95% CI, -8.0% to -1.5%]) with high certainty. Compared with SABA alone, both ICS-containing relievers were associated with improved asthma control (ICS-formoterol RR improvement [MID] in total score, 1.07 [95% CI, 1.04-1.10]; RD, 4.1% [95% CI, 2.3%-5.9%]; ICS-SABA RR, 1.09 [95% CI, 1.03-1.15]; RD, 5.4% [95% CI, 1.8%-8.5%]) with high certainty. In an indirect comparison with ICS-SABA, ICS-formoterol was associated with fewer severe exacerbations (RR, 0.78 [95% CI, 0.66-0.92]; RD, -5.5% [95% CI, -8.4% to -2.0%]) with moderate certainty. Compared with SABA alone, ICS-formoterol (RD, -0.6% [95% CI, -1.3% to 0%]) was not associated with increased risk of serious adverse events (high certainty) and ICS-SABA (RD, 0% [95% CI, -1.1% to 1.2%]) was not associated with increased risk of serious adverse events (moderate certainty). In this network meta-analysis of patients with asthma, ICS combined with formoterol and ICS combined with SABA were each associated with reduced asthma exacerbations and improved asthma control compared with SABA alone.

Detection of chronic obstructive pulmonary disease and frequency of cardiopulmonary events in patients with a significant smoking history hospitalised for acute myocardial infarction

Abstract Background Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and also myocardial infarction (MI). Patients with COPD are more likely to have MI than those without and adequately treating COPD might improve cardiovascular outcomes. Reliable diagnosis is important for appropriate treatment. Prevalence of COPD in those hospitalised for MI has not been accurately established. Blood eosinophil count is an important guide to the benefit of inhaled corticosteroid (ICS) treatment in COPD. We aimed to accurately characterise lung function, symptom burden, eosinophil count and cardiopulmonary events in those with a significant smoking history hospitalised for acute MI. Methods Participants (n=216) with a smoking history of ≥10 pack-years currently hospitalised for acute MI were recruited at a single UK centre. Microspirometry and completion of the COPD Assessment Test (CAT) questionnaire were performed at enrolment. Presence and severity of COPD was graded using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. A high burden of COPD symptoms was defined as a CAT score of >10. Repeat CAT and assessment for relevant cardiopulmonary events was undertaken at 3 months and 1 year after enrolment. Results In the enrolled cohort, median age was 60 years (IQR 53-67), 26% were female, 57% were current smokers and median pack-year history was 32 (23-45). 41 of 216 (19 %, [95% CI 14-25]) had evidence of COPD, defined as FEV1/FEV6 <0.7 on best-attempt microspirometry, with 39 (95%) being GOLD2 or greater. Of the 41 with detected COPD, only 15 (37%, [22-53]) had a prior diagnosis. In those with evidence of COPD, a high burden of COPD symptoms was present in 63% of participants at enrolment, 40% at 3 months and 45% at 1 year. 20% [9-35] were receiving inhaled corticosteroids at enrolment. 63% [47-78] had eosinophil count ≥100 cells/mm3 and 17% [7-32] ≥300 cells/mm3. Among those with detected COPD, after 1 year 19.5% (95% CI 9-35%) had suffered a respiratory illness requiring prescription of medication, which was numerically but not statistically significantly higher than those without detected COPD (14.3% [10-20%]). In the COPD cohort, death, infection requiring hospitalisation, MI or unplanned coronary revascularisation, and bleeding requiring hospitalisation each occurred on two occasions (4.9%). Conclusions Based on these data, the prevalence of microspirometry-diagnosed COPD of any severity in patients with significant smoking history hospitalised for MI is around 19%. There is a high rate of undiagnosed and untreated disease, a significant burden of symptoms, including during convalescence, and around a 20% incidence of respiratory illness requiring medical treatment at 1 year. Gathering accurate data from this group is helpful in planning research and service improvement. Increasing detection of COPD in patients with MI would lead to improved cardiopulmonary outcomes.

Adverse impacts of corticosteroid treatment on osteoporosis/osteopenia in adult asthmatics: A retrospective ICARUS cohort study

Inhaled corticosteroid (ICS) and oral corticosteroid (OCS) are often used in asthma management. This study evaluated the long-term effect of ICS/OCS on osteoporosis, osteopenia, fractures, and bone metabolism in adult asthmatics in real-world clinical practice. This is a retrospective study investigating de-identified electronic health records from Ajou University Medical Center (Korea). Adult asthmatics receiving maintenance ICS with/without OCS for at least 1 year were enrolled. They were classified into the high/low-dose of ICS or OCS groups. Primary outcomes (incidences of osteoporosis, osteopenia, and fractures) and secondary outcomes (drug prescription and laboratory values related to bone metabolism including albumin and alkaline phosphatase [ALP]) were compared after 5 years of follow-up. After propensity score matching, both high- and low-dose OCS groups included 468 patients, and high/low-dose ICS groups each comprised 1,252 patients. The risk of osteoporosis/major fracture was higher (hazard ratio [95% CI]; 2.00 [1.15-3.57]/3.03 [1.04-11.11]) in the high-dose OCS group (especially in females aged ≥50 years) than in the low-dose group, although the ICS groups showed no significant differences. The high-dose ICS group showed a higher risk of osteopenia (1.92 [1.05-3.70]) than the low-dose ICS group. The linear mixed model of laboratory values showed significantly decreased serum albumin and increased ALP in the high-dose OCS group than in the low-dose OCS group. The results of this study suggest that long-term use of OCS can increase the risk of osteoporosis and osteoporosis-related fractures, while long-term use of ICS may increase the risk of osteopenia in adult asthmatics.

"Achieving Clinical Remission in Asthma with Mepolizumab: A Subanalysis on Vitamin D as a Predictor of Response".

ObjectiveMepolizumab, an anti-IL-5 monoclonal antibody, has shown promise in reducing exacerbations and steroid dependency in severe eosinophilic asthma. This study aims to evaluate the effectiveness of mepolizumab in achieving clinical remission in asthma over 12 months and explore Vitamin D levels as a predictor of response.MethodWe assessed Asthma Control Questionnaire (ACQ) scores, spirometry, number of exacerbations, oral corticosteroid (OCS) use, and inhaled corticosteroid (ICS) use in 32 patients, observing significant clinical improvements. Data were collected 1 year prior to starting mepolizumab and one year after starting mepolizumab. Nasal ployps were not seen in all the patients, and computed tomography of para-nasal sinuses are not available for all the patients, so nasal polyps status are not evaluated to avoid any bias.ResultOur results indicate that 12 patients achieved clinical remission after starting mepolizumab, with a strong correlation between higher Vitamin D levels and positive treatment outcomes. This suggests that optimizing Vitamin D levels could enhance the response to mepolizumab in asthma patients, and help in achieving better asthma control.ConclusionMepolizumab is an effective treatment for severe eosinophilic asthma, significantly improving clinical outcomes and reducing corticosteroid use. This study highlights the importance of Vitamin D as a predictor of response to mepolizumab, suggesting that higher Vitamin D levels may enhance treatment efficacy.

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.

Effect and mechanism of allergen-specific immunotherapy on small airway dysfunction in children with asthma.

The purpose of this study was to investigate the effectiveness of allergen-specific immunotherapy (AIT) on small airway dysfunction (SAD) and the underlying mechanism with a special focus on basophils. Sixty-five children with mild to moderate asthma who were under regular inhaled corticosteroid (ICS) treatment for more than 1 year but whose FEF75 remained below 65% of the predicted value and had positive results for serum Der p or Der f were enrolled. Children with asthma underwent house dust mite (HDM) subcutaneous immunotherapy (SCIT) treatment for 1 year. Clinical symptoms and lung function were evaluated every 3 months during HDM SCIT treatment. Basophil activation test (BAT) was carried out before and after HDM SCIT treatment. RNA sequencing was performed in isolated basophils from peripheral blood after 6 months of HDM SCIT treatment, followed by GO term and KEGG pathway enrichment analysis between patients with and without HDM SCIT treatment. HDM AIT treatment ameliorated clinical symptoms while concurrently improved lung function parameters, such as FEV1/FVC, FEF75, FEF50 and MMEF (p < .05). It is worth noting that FEF75 values showed a highly significant, gradual and persistent increase (from 49.55 ± 1.27% at baseline to 71.89 ± 2.64% after 1 year of therapy) and 22 of 35 patients no longer had SAD after 1 year of treatment. BAT results revealed that AIT treatment significantly reduced basophil activity to the inhalant allergen mixtures containing HDM in vitro challenge from baseline. GO term and KEGG pathway enrichment analysis of basophils revealed that downregulated genes were mainly involved in immune cell activation, antigen presentation, and Th2 cell differentiation. Our study demonstrated that HDM AIT not only improved SAD related lung function parameters, but also reduced basophil activity. RNA sequencing revealed the inhibition of phagocytosis and the phagosome pathway in basophils which may affect the polarization of Th2 cell differentiation after HDM AIT.

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.

High-CBD Extract (CBD-X) in Asthma Management: Reducing Th2-Driven Cytokine Secretion and Neutrophil/Eosinophil Activity.

Asthma is a chronic inflammatory disorder of the airways affecting over 10% of the global population. It is characterized by airway inflammation, mucus hypersecretion, and bronchial hyperresponsiveness, driven predominantly by type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s) in a subset of patients. However, a significant portion of asthmatic individuals present with "type 2-low" asthma that is often refractory to standard inhaled corticosteroid (ICS) therapy. Therefore, developing innovative therapeutic strategies has become essential. Recent studies have highlighted cannabidiol (CBD) as a promising anti-inflammatory agent capable of modulating immune responses. This study investigates the therapeutic potential of a high-CBD extract (CBD-X) in asthma. We evaluated the effects of CBD-X on cells involved in asthma pathogenesis using primary human Th2 cells, neutrophils, and asthma mouse model. Our findings indicate that CBD-X extract inhibits Th2 differentiation and reduces the secretion of IL-5 and IL-13, which are crucial cytokines in asthma. Additionally, CBD-X significantly reduces pro-inflammatory cytokines IL-8 and IL-6 in neutrophils and impairs their migration, a critical step in airway inflammation. In a murine asthma model, CBD-X administration led to marked downregulation of IgE and pro-asthmatic cytokines, along with reduced leukocyte, eosinophil, and neutrophil infiltration in lung tissues. These results suggest that CBD-X extract could offer a novel and complementary approach to managing both type 2-high and type 2-low asthma by targeting key inflammatory pathways and modulating immune cell behavior.

Impact of exacerbation history on future risk and treatment outcomes in chronic obstructive pulmonary disease patients: A prospective cohort study based on Global Initiative for Chronic Obstructive Lung Disease (GOLD) A and B classifications.

In this study, we aimed to explore the impact of exacerbation history on future exacerbation and mortality with different inhaled drugs in chronic obstructive pulmonary disease (COPD) patients based on a Global Initiative Chronic Obstructive Lung Disease (GOLD) A and B classifications. This observational study was based on the cohort study Real World Research of Diagnosis and Treatment of COPD (RealDTC). We collected data from COPD patients in China from 1 July 2017 to 31 December 2022. Patients were followed up until December 2023 or death. Further, we separated GOLD A and B patients into GOLD A0 and B0, who had no exacerbation during the previous year, and GOLD A1 and B1, who had only one exacerbation during the previous year. Study outcomes included moderate-to-severe exacerbation, hospitalisation, frequent exacerbation in the first year and all-cause mortality during total follow-up. Of the 8318 eligible patients, GOLD E group of patients suffered from a greater risk of exacerbation in the first year and death than patients in the GOLD A and B groups. GOLD A1 group had a higher risk of moderate-to-severe exacerbation (hazard ratio (HR) = 2.087; 95% confidence interval (CI) = 1.419-3.068), hospitalisation (HR = 1.704; 95% CI = 1.010-2.705) and frequent exacerbation (HR = 1.983; 95% CI = 1.046-3.709) compared to GOLD A0. GOLD B1 group had a risk of moderate-to-severe exacerbation (HR = 1.321; 95% CI = 1.105-1.679) and mortality (HR = 1.362; 95% CI = 1.026-1.963) that exceeded the risk in GOLD B0 group. The treatment outcome of different inhaled drugs had no statistical differences in GOLD A0 group. In GOLD A1 group, only inhaled corticosteroids (ICS), in addition to long-acting β-2 agonist (LABA) and long-acting muscarinic antagonist (LAMA), reduced the risk of moderate-to-severe exacerbation in the first year compared to only LAMA. As for the GOLD B0 group, LABA and LAMA decreased the odds of moderate-to-severe exacerbation, hospitalisation, frequent exacerbation and mortality compared to only LAMA. ICS, LABA, and LAMA in GOLD B0 also down-regulated the risk of frequent exacerbation, compared to only LAMA. In addition, GOLD B1 patients treated with LABA and LAMA or ICS, LABA, and LAMA had a lower risk of moderate-to-severe exacerbation and hospitalisation. Meanwhile, ICS, LABA, and LAMA also reduced the risk of frequent exacerbation and mortality, compared to only LAMA in the multivariate Cox analysis. Compared to the GOLD A or B group without exacerbation history, GOLD A patients with exacerbation history had a higher risk of future exacerbation, and GOLD B patients with exacerbation history had a higher risk of future exacerbation and mortality and benefited more from triple inhaler therapy.

Effect of continuous inhaled corticosteroids on glycated hemoglobin in asthmatic children: a pilot study

BackgroundAsthma is a prevalent chronic disease with significant impact on patients, families, and communities. Inhaled corticosteroids (ICS) are the mainstay of treatment for persistent and uncontrolled asthma. However, concerns remain about the potential adverse effects of ICS, including HbA1c level. This study aims to evaluate the influence of ICS on Hemoglobin A1c (HbA1c) levels in children with bronchial asthma.MethodsThis prospective cohort study included 48 pediatric asthma patients aged 2 to 15 years who had been using ICS for at least 6 months. Comprehensive clinical assessments and measurements of HbA1c levels were conducted at the start of recruitment and after 6 months of ICS use. The types and doses of ICS used followed the guidelines provided by the Global Initiative for Asthma (GINA).ResultsThe initial HbA1c levels ranged from 4.46 to 6.11, with a mean of 5.32 ± 0.35. Three patients (6.3%) had persistent prediabetes status after 6 months. There was no significant relationship between glycemic status and the characteristics of ICS. The duration of ICS therapy and the doses used did not significantly affect HbA1c levels. A weak positive correlation was observed between initial and subsequent HbA1c levels.ConclusionThe study found no significant difference in HbA1c levels among asthmatic children using ICS after six months of treatment. Additionally, there was no significant difference in HbA1c levels between patients using different types of ICS. Regular monitoring of HbA1c levels is recommended, particularly for children on high doses or prolonged use of inhaled Fluticasone.

7432 Secondary Adrenal Insufficiency Caused By Concurrent Treatment With Budesonide And Itraconazole

Abstract Disclosure: F. Anjum: None. M.G. Jakoby: None. Introduction: Inhaled corticosteroids (ICS) are unlikely to affect corticotroph axis function even at high doses due to low systemic absorption. However, co-treatment with drugs that reduce hepatic clearance of ICS may predispose patients to secondary adrenal insufficiency (AI). We report a case of secondary AI that occurred during concurrent treatment with budesonide and itraconazole. Case presentation: A 42-year-old female with longstanding asthma managed with inhaled budesonide (160 μg twice daily) was started on itraconazole (200 mg twice daily) for management of pulmonary histoplasmosis. Over the next three months, she experienced severe fatigue, and laboratory evaluation was notable for an undetectable (&amp;lt; 0.4 μg/dL) 8 AM cortisol level. Serum sodium (140 mM, 136-145) and potassium (4.6 mM, 3.5-5.1) were unremarkable, and a diagnosis of drug induced secondary AI was made. Treatment with hydrocortisone (15 mg in the morning, 5 mg in the evening) was started, and the patient’s infectious disease specialist stopped itraconazole, substituting posaconazole (300 mg daily) for an additional six months. Her pulmonologist substituted fluticasone (250 μg twice daily) for budesonide. After an approximate two-month hydrocortisone taper, 8 AM ACTH level was easily detectable (37.2 pg/mL, 7.2-63.3), though 30 min stimulated cortisol level was subnormal (11.1 μg/dL, expected &amp;gt; 18). Hydrocortisone was successfully tapered off over an additional two-months (30 min stimulated cortisol 23.4 μg/dL). Discussion: The literature on ICS induced secondary AI is generally case reports and series, and the incidence is very low (1.1/10,000 patient-years at risk). Limited oral bioavailability, high deposition in lungs, extensive protein binding, and robust hepatic clearance are factors that minimize the effects of ICS on corticotroph axis function. However, concurrent treatment with potent CYP3A4 inhibitors like itraconazole can significantly reduce hepatic clearance of ICS and predispose to systemic effects, including Cushing syndrome when high dose ICS are prescribed or secondary AI at lower doses. In a series of 25 cystic fibrosis patients co-treated with itraconazole and budesonide, 11/25 (44%) developed secondary AI. Our patient likely developed secondary AI but not Cushing syndrome due to treatment with low dose budesonide. This case illustrates the importance that endocrinologists recognize CY3A4 inhibiting drugs as a risk factor for secondary AI in patient treated with ICS. Presentation: 6/3/2024

Comparative Risk of Neuropsychiatric Adverse Events Associated With Leukotriene-Receptor Antagonists Versus Inhaled Corticosteroids

Leukotriene-receptor antagonists (LTRA) and inhaled corticosteroids (ICS) are common controller medications for asthma, but limited studies examine their comparative risks on neuropsychiatric adverse events (NAEs) in asthma patients. To investigate the comparative risks of LTRA versus ICS on seven distinct categories of NAEs in asthma patients at a nationwide level. We conducted a nationwide cohort study during 2010-2021. Incident NAEs and its clinical subgroups (e.g., psychotic disorders, anxiety disorders, movement disorders, behavioral and emotional disorders, mood disorders, sleep-related disorders, and personality disorders) were assessed. Cox proportional hazards regressions were employed to quantify the comparative risks. There were 1,249,897 asthma patients aged 6-64 years. Incidence rates for NAEs were 25.10 per 1000 person-years among patients treated with LTRA, and 23.46 per 1000 person-years among those treated with ICS. The incidence rate difference was 1.64 [95%CI: 0.30-2.98] per 1000 person-years. Positive associations of NAEs and three clinical subgroups were found in patients treated with LTRA compared to ICS (hazard ratios (HR): 1.06 [95%CI: 1.00-1.12] for NAEs; HR: 1.88 [95%CI: 1.24-2.84] for psychotic disorders; HR: 1.10 [95%CI: 1.01-1.20] for anxiety disorders; and HR: 1.27 [95%CI: 1.02-1.58] for behavioral and emotional disorders), but not for movement disorders, mood disorders, sleep-related disorders, and personality disorders. This nationwide cohort study identified heightened risks, ranging from 6% to 88%, of NAEs and three clinical subgroups in asthma patients treated with LTRA compared to ICS. These findings underscore the necessity for clinicians to communicate with patients regarding potential neuropsychiatric harms when prescribing LTRA.

Identifying the predictive value of fractional exhaled nitric oxide (FeNO) for uncontrolled asthma in 3-7-year-old Thai children.

Fractional exhaled nitric oxide (FeNO) is the method for monitoring airway inflammation. However, a singular FeNO value cutoff may not adequately represent the control status across different ages and demographics. This study aimed to evaluate the correlation between FeNO values and asthma control levels, identifying an optimal cutoff point for children aged 3 to 7 years. This cross-sectional study was conducted at Naresuan University Hospital from April 1, 2023 to July 31, 2023. Inclusion criteria were asthmatic patients aged 3 to 7 years who were capable of following commands. Exclusion criteria included children who had a coronavirus disease 2019 (COVID-19) infection, those experiencing difficulty breathing, or unable to perform the FeNO measurement. Eligible patients were classified according to their level of asthma control and underwent FeNO testing. Out of 108 participants who successfully completed FeNO measurements, a significant difference in FeNO values was observed across controlled, partially controlled, and uncontrolled asthma groups, with uncontrolled asthma presenting significantly higher values. The optimal FeNO cutoff point for predicting uncontrolled asthma was identified as ≥15 ppb with a sensitivity 46.7%, specificity 86.0%, positive predictive value (PPV) 35.0%, negative predictive value (NPV) 90.9%. This study established a significant correlation between FeNO levels and uncontrolled asthma, FeNO cutoff point ≥15 ppb as the optimal value in predicting uncontrolled asthma in Thai children aged 3-7 years. Factors such as uncontrolled allergic rhinitis, symptoms at onset, smoking exposure, treatment compliance, and inhaled corticosteroid (ICS) usage were associated with FeNO values. The application of FeNO measurement should be integrated with clinical assessments and consideration of these associated factors.

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.

FLUTICASONE FUROATE AND VILANTEROL (FF/VI) VERSUS FLUTICASONE PROPRIONATE AND FORMOTEROL (FP/FM) AS MAINTENANCE THERAPY IN STABLE ASTHMATIC PATIENTS- A COMPARATIVE STUDY

Background: Fluticasone furoate (FF) is a novel long-acting inhaled corticosteroid (ICS). Vilanterol (VI) is a long‐acting beta2‐agonist (LABA) that binds to the beta2‐adrenoceptor on the airway smooth muscle, producing bronchodilation. The corticosteroid fluticasone propionate (FP)and the long-acting β₂-adrenoceptor agonist (LABA) formoterol fumarate (FM) have been combined in a single, pressurized, metered-dose, aerosol inhaler for the maintenance treatment of patients aged ≥12 years with persistent asthma.This study evaluated the efficacy and safety of Fluticasone furoate 100 mcgandVilanterol 6 mcg versus Fluticasone proprionate 250 mcg and Formoterol 25 mcg for 12 weeks in patients with persistent asthma as maintenance therapy. Methods and Materials: A hospital based comparative study was conducted among stable asthmatic patients attended to Santhiram Medical College and General Hospital, Nandyal during January 2024 to June 2024(6months) by using convenient sampling method with sample size 60. Study tool was pre-designed, pre-tested, asthma control questionnaire5 (ACQ5),asthma control test (ACT) and Ask 12 adherence barrier survey. Results: Among 60 patients, 30 patients (Group1) were given Fluticasone furoate and Vilanterol and another 30 patients (Group 2) were given Fluticasone proprionate and Formoterol. All the patients (both the treatment groups) completed the 12 weeks treatment period. Improvements from baseline in 0- to 24-h wmFEV1 were observed with both FF/VI (376 mL) and FP/FM (353 mL) the adjusted mean treatment difference was not statistically significant. There were no differences between 0- to 4-h serial wmFEV1, asthma control test, ACQ5 and Ask 12 adherence barrier survey. There was no difference in reported exacerbations between treatments. Adverse events reported in the present study were not significant. Both treatments were well tolerated. Conclusion: The present study shows that the efficacy of once daily Fluticasone furoate and Vilanterol was not inferior as compared to the efficacy of twice daily Fluticasone proprionate and Formoterol as maintenance therapy in stable asthmatic patients. Howevertreatment with once daily FF/VI has the advantage of forgetfulness and inconvenience of inhalation.Henceonce daily FF/VI can be also useful for stable asthmatic patients as maintenance therapy as FF/VI DPI treatment.

Exploring the Impact of Inhaled Corticosteroids on Endothelial Function in Chronic Obstructive Pulmonary Disease Patients Undergoing Pulmonary Rehabilitation.

Background: Chronic obstructive pulmonary disease (COPD) is associated with subclinical atherosclerosis and endothelial dysfunction, which can be assessed non-invasively through flow-mediated dilation (FMD). In this study, we evaluated the potential impact of inhaled corticosteroid (ICS) therapy on FMD of COPD patients undergoing pulmonary rehabilitation (PR). Methods: Medical records of COPD patients undergoing FMD assessment upon admission to our Pulmonary Rehabilitation Unit were reviewed in this retrospective post hoc analysis. Results: A total of 46 patients with COPD (median age 71.5 years, 28.3% postmenopausal females) were included in the final analysis. Among these, 27 participants were currently receiving ICS therapy, while 19 were not. At baseline, the two groups showed no difference in the main clinical and functional variables. Similarly, no significant difference was observed in vascular reactivity parameters, with a median FMD of 3.12% (IQR: 2.23-4.45) in ICS users and 3.39% (IQR: 2.45-4.08) in ICS nonusers (p = 0.544). After PR, a significant improvement in the main rehabilitation and patient-reported outcomes was observed in all groups, with a significant improvement in FMD documented in both patients treated with steroids (from 3.12%; IQR: 2.23-4.45 to 4.77%; IQR: 3.25-5.63, p = 0.022) and in those who were not (from 3.39%; IQR: 2.45-4.08 to 5.04%; IQR: 3.98-6.06, p = 0.005). FMD changes were of comparable magnitude among groups. Conclusions: Our preliminary findings do not indicate a significant impact of medications containing ICS on the endothelial function of COPD patients, suggesting that the potential beneficial effect of PR on this surrogate marker of cardiovascular risk is independent of inhaled therapy.

Inhaled budesonide and pulmonary sarcoidosis revisited.

Results of a few controlled clinical studies have been reported with inhaled corticosteroids (ICS) in patients with pulmonary sarcoidosis. Some evidence of efficacy has been observed, but mainly with the ICS budesonide (BUD). These clinically important and statistically significant results are restricted to maintenance therapy with BUD after induction of treatment with systemic corticosteroids for a few weeks or months. Positive results have also been described in patients with relapses after earlier treatment with oral corticosteroids. A possible explanation for BUD's efficacy in patients with parenchymal lesions could be that inhaled BUD is rapidly absorbed into systemic circulation, creating plasma peaks which result in systemic anti-inflammatory activity in both peripheral airways and lung tissue. At airway level this steroid activity is furthermore prolonged because a BUD fraction is intracellularly, reversibly transformed into lipophilic BUD-oleate. These mechanisms have been proposed to explain the theoretically unexpected similar efficacy of BUD compared with more lipophilic ICSs in patients with asthma and COPD. In this review we summarize the results of clinical studies with ICSs in patients with pulmonary sarcoidosis. It is obvious that current ICSs, including BUD, cannot generally be recommended as such for treatment of sarcoidosis. However, using BUD as a model substance further pharmacologic and kinetic studies could possibly define a kinetic profile giving optimal partitioning between airway and systemic activity with less adverse systemic risks. Such a substance could replace or reduce oral corticosteroids in the treatment of airway and pulmonary parenchymal diseases.

Asthma control and use of short-acting beta-2-agonists for symptom relief in Africa – A narrative review

More than 100 million people in Africa live with Asthma. With appropriate treatment, predominantly inhaled corticosteroids (ICSs), asthma is controllable in most people. However, in Africa, multiple factors constrain the accessibility, availability, and quality of asthma services, which lead to underdiagnosis and sub-optimal treatment of the disease. These constraints include weak healthcare systems and inadequate knowledge of healthcare providers on asthma diagnosis and treatment. There is also a poor awareness of asthma as a long-term disease in the general population. There are several myths and misconceptions about asthma as a disease. There is also poor access to ICSs, the most effective controller medicines for asthma. This is mostly due to the high cost. Furthermore, the non-use or delays in initiating treatment with inhaled steroids commonly leads to overuse and overreliance on rapid relievers of asthma symptoms, and in particular, short-acting beta-2-agonists (SABAs), both in oral and inhaled forms. This practice is very common and contributes to the sub-optimal treatment and resultant poor control of asthma, which is highly prevalent in Africa. In this paper, we highlight the burden of asthma in Africa, the effects of overuse/overreliance of SABA use on asthma control and provide suggestions to reduce the dependency on SABAs to improve asthma treatment and enhance asthma control on the African continent.

The Analysis Study of Comparison of Effectiveness and Safety of Inhalers in Mild-to Moderate Asthma in Adults: A Comprehensive Systematic Review

Background: Asthma, a prevalent and potentially debilitating chronic disease, is traditionally managed using reliever medications such as short-acting β2-agonists (SABA) or low-dose inhaled corticosteroids (ICS). Recent evidence, however, indicates that a combination of as-needed ICS and a rapid-acting long-acting β2-agonist (LABA) provides superior outcomes compared to SABA alone. Furthermore, this combination therapy is at least as effective as regular ICS in mitigating the risk of exacerbations. This emerging evidence highlights a significant shift in treatment strategies for mild asthma, underscoring the potential for enhanced management and improved patient outcomes with the new therapeutic approach. Methods: Following PRISMA 2020 guidelines, this systematic review focused exclusively on full-text articles published in English between 2014 and 2024. Result: The study conducted a comprehensive review of over 400 publications sourced from reputable databases, including ScienceDirect, SagePub, and PubMed. Folowing an initial screening, eight publications were identified as warranting more in-depth analysis. Conclusion: The study found that as-needed ICS/LABA is effective in preventing exacerbations in mild-to-moderate asthma patients, but less effective than regular ICS in improving FEV1 and ACQ scores. Combining ICS/LABA with SMART regimen was highest for severe exacerbations prevention.