Inhaled Corticosteroids Users Research Articles

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.

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.

Exploring the Relationship between Inhaled Corticosteroid Usage, Asthma Severity, and Sleep-Disordered Breathing: A Systematic Literature Review.

(1) Background: Sleep-disordered breathing and asthma are often interrelated. Children and adults with asthma are more susceptible to sleep apnea. Inhaled corticosteroids effectively reduce inflammation and prevent structural changes in the airways. Objective: to explore the existing literature to determine whether inhaled corticosteroids play a role in sleep-disordered breathing in patients with asthma. (2) Methods: We conducted a thorough search of the PubMed, Scopus, and Web of Science databases for English-language articles published up to 12 May 2024. We utilized the ROBINS-E tool to assess the risk of bias. (4) Conclusions: 136 articles were discerned upon conducting the literature search. A total of 13 articles underwent exhaustive full-text scrutiny, resulting in 6 being considered non-relevant. The remaining seven articles, assessed for eligibility, were incorporated into the final analysis. Five studies were identified in adults and two in children. In adult patients, inhaled corticosteroids, especially at high doses, appear to increase the risk of sleep apnea in a dose-dependent manner. Moreover, the properties of inhaled corticosteroids, such as particle size, may impact the risk of developing sleep apnea. In children, the severity of asthma is a key factor affecting the prevalence of sleep apnea, whereas inhaled corticosteroids appear to be a less significant risk factor compared to adults. All of the studies reviewed were classified as having a high risk of bias or some concerns regarding bias. Each study revealed at least one type of bias that raised notable concerns. This research highlights a complex interaction between the use of inhaled corticosteroids, the severity of asthma, and the onset of sleep apnea. Additional research is necessary to investigate these relationships further.

Survival benefit of inhaled corticosteroids in patients with chronic obstructive pulmonary disease: a nationwide cohort study

The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) is debated. We investigated whether the administration of ICS could lower the mortality risk in patients with COPD. We utilized the Korean National Health Insurance Service-National Sample Cohort database from 2002 to 2019. We included patients who had claim codes for COPD and inhalation respiratory medicine at least twice a year. A time-dependent Cox regression model was employed to estimate the association between ICS usage and survival. The cumulative dose of ICS was classified into three groups, and the mortality risk was compared among these groups. Of 16,463 included patients, there were 4395 (26.7%) deaths during the mean follow-up period of 5.0 years. The time-dependent Cox regression model demonstrated that ICS users had a significantly lower mortality risk compared to non-users (adjusted hazard ratio, 0.89; 95% CI, 0.83–0.94; p < 0.001), particularly among individuals aged ≥ 55 years, women, never smokers, and those with history of asthma or coronary heart disease. Higher cumulative dose groups were associated with a lower mortality risk compared to the lowest cumulative dose group. In conclusion, the administration of ICS seemed to be associated with a lower mortality risk in patients with COPD.

Inhaled Corticosteroids and the Risk of Nontuberculous Mycobacterial Infection in Chronic Airway Disease: A Nationwide Population-Based Study.

Chronic airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are increasingly being treated with inhaled corticosteroid (ICS). However, ICSs carry potential infection risks, particularly nontuberculous mycobacteria (NTM). This study investigated the association between ICS use and NTM infection risk using national insurance data, particularly for individuals with chronic airway diseases. We conducted a nationwide population-based study using data from the National Health Insurance Service-National Sample Cohort in South Korea from 2002 to 2019. The cohort included 57,553 patients diagnosed with COPD or asthma. To assess the risk of NTM infection, we used Cox proportional hazards models and propensity score-based inverse probability of treatment weighting (IPTW) to ensure a balanced analysis of covariates. Of the 57,553 patients (mean age 56.0 years, 43.2% male), 16.5% used ICS and 83.5% did not. We identified 63 NTM infection cases, including nine among ICS users and 54 among non-users. Before and after IPTW, ICS use was associated with a higher risk of NTM infection (adjusted hazard ratio [HR], 4.01; 95% confidence interval [CI], 1.48 to 15.58). Higher risks were significant for patients ≥65 years (adjusted HR, 6.40; 95% CI, 1.28 to 31.94), females (adjusted HR, 10.91; 95% CI, 2.24 to 53.20), never-smokers (adjusted HR, 6.31; 95% CI, 1.49 to 26.64), systemic steroid users (adjusted HR, 50.19; 95% CI, 8.07 to 312.19), and those with higher comorbidity scores (adjusted HR, 6.64; 95% CI, 1.19 to 37.03). ICS use in patients with chronic airway diseases might increase the risk of NTM infection, particularly in older females, never-smokers, and systemic steroid users.

Evidence for 2 clusters among patients with noneosinophilic asthma

BackgroundAlthough asthma is often seen as an eosinophilic disease associated with atopy, patients with noneosinophilic asthma represent a substantial part of the population with asthma. ObjectiveTo apply an unsupervised clustering method in a cohort of 588 patients with noneosinophilic asthma (sputum eosinophils < 3%) recruited from an asthma clinic of a secondary care center. MethodsOur cluster analysis of the whole cohort identified 2 subgroups as cluster 1 (n = 417) and cluster 2 (n = 171). ResultsCluster 1 comprised a predominantly female group with late disease onset, a low proportion of atopy (24%), and a substantial smoking history (53%). In this cluster, treatment burden was low (<50% of inhaled corticosteroid users); asthma control and quality of life were poor, with median Asthma Control Test, Asthma Control Questionnaire, and Asthma Quality of Life scores of 16, 1.7, and 4.5, respectively, whereas lung function was preserved with a median postbronchodilation forced expiratory volume in 1 second of 93% predicted. Cluster 2 was a predominantly male group, almost exclusively comprising patients with atopy (99%) with early disease onset and a moderate treatment burden (median inhaled corticosteroids dose 800 µg/d equivalent beclomethasone). In cluster 2, asthma was partially controlled, with median Asthma Control Test and Asthma Control Questionnaire scores reaching 18 and 1.3, respectively, and lung function well preserved with a median postbronchodilation of 95% predicted. Although systemic and airway neutrophilic inflammation was the dominant pattern in cluster 1, cluster 2 essentially comprised paucigranulocytic asthma with moderately elevated fraction exhaled nitric oxide. ConclusionNoneosinophilic asthma splits into 2 clusters distinguishing by disease onset, atopic status, smoking history, systemic and airway inflammation, and disease control and quality of life.

Inhaled Corticosteroids May Not Affect the Clinical Outcomes of Pneumonia in Patients with Chronic Obstructive Pulmonary Disease.

Although inhaled corticosteroids (ICS) is reportedly associated with a higher risk of pneumonia in chronic obstructive pulmonary disease (COPD), the clinical implications of ICS have not been sufficiently verified to determine their effect on the prognosis of pneumonia. The electronic health records of patients hospitalized for pneumonia with underlying COPD were retrospectively reviewed. Pneumonia was confirmed using chest radiography or computed tomography. The clinical outcomes of pneumonia in patients with COPD who received ICS and those who received long-acting bronchodilators other than ICS were compared. Among the 255 hospitalized patients, 89 met the inclusion criteria. The numbers of ICS and non-ICS users were 46 and 43, respectively. The CURB-65 (confusion, uremia, respiratory rate, blood pressure, age ≥65 years) scores at the initial presentation of pneumonia were comparable between the two groups. The proportions of patients with multilobar infiltration, pleural effusion, and complicated pneumonia in the radiological studies did not vary between the two groups. Additionally, the defervescence time, proportion of mechanical ventilation, intensive care unit admission, length of hospital stays, and mortality rate at 30 and 90 days were not significantly different between the two groups. ICS use and blood eosinophils count were not associated with all pneumonia outcomes and mortality in multivariate analyses. The clinical outcomes of pneumonia following ICS use in patients with COPD did not differ from those in patients treated without ICS. Thus, ICS may not contribute to the severity and outcomes of pneumonia in patients with COPD.

Assessing the risk of intentional self-harm in montelukast users: an updated Sentinel System analysis using ICD-10 coding

Background Montelukast prescribing information includes a Boxed Warning issued in March 2020 regarding neuropsychiatric adverse events. A previous Sentinel System study of asthma patients from 2000 to 2015 did not demonstrate an increased risk of intentional self-harm measured using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, with montelukast compared to inhaled corticosteroids (ICS). Methods Using a new user cohort study design, we examined intentional self-harm events in patients aged 10 years and older who were incident users of either montelukast or ICS as monotherapy, with a diagnosis of asthma, between October 1, 2015, to June 30, 2022, in the Sentinel System. We measured intentional self-harm using ICD-10-CM codes, which may have better accuracy for capturing suicide attempts than ICD-9-CM codes. We used inverse probability of treatment weighting to balance baseline covariates. We performed subgroup analyses by age group, sex, psychiatric history, and pre/post Boxed Warning era and conducted sensitivity analyses varying type of care setting of the outcome and exposure episode gaps. Results Among 752,230 and 724,855 patients in the montelukast and ICS exposure groups respectively, we found no association between montelukast use and self-harm compared to ICS use [Hazard Ratio (95% Confidence Interval): 0.96 (0.85, 1.08)]. This finding was consistent across all subgroups, and sensitivity analyses. Conclusion Our results cannot exclude other neuropsychiatric idiosyncratic reactions to montelukast. Compared to the previous Sentinel study, this study identified about double the rate of self-harm events, suggesting a greater sensitivity of ICD-10 codes for measuring self-harm than ICD-9.

Inhaled corticosteroid for patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

The efficacy of inhaled corticosteroid (ICS) in the treatment of patients with COVID-19 has been evaluated in randomized controlled trials (RCTs), however, their findings are not consistent. PubMed, Embase, Cochrane Library, ClinicalTrials.gov, Scopus, Web of Science and Google Scholar were searched to June 10, 2023. Only RCTs that investigated the clinical efficacy and safety of ICS for patients with COVID-19 were included. Eleven RCTs were included. ICS users had significantly higher rate of symptom alleviation at day 14 than the control group (risk ratio [RR], 1.13; 95% CI, 1.04-1.23; I2=42%). Additionally, no significant difference between the ICS users and the control group was observed in the composite outcome of urgent care, emergency department (ED) visit or hospitalization (RR, 0.43; 95% CI, 0.08-2.48; I2=85%) and hospitalization or death (RR, 0.85; 95% CI, 0.64-1.12; I2=0%). Finally, ICS user had a non-significantly lower risk of death at day 28 than the control group (0.63% vs 0.99%; RR, 0.82; 95% CI, 0.43-1.56; I2=0%). Additional ICS use, particularly inhaled budesonide may help symptom relief in patients with COVID-19. However, ICS use did not help reduce the risk of urgent care, ED visit, hospitalization, or death.

Inhaled corticosteroids and adverse outcomes among chronic obstructive pulmonary disease patients with community-acquired pneumonia: a population-based cohort study.

While inhaled corticosteroids (ICS) may increase pneumonia risk in patients with chronic obstructive pulmonary disease (COPD), the impact of ICS on pneumonia outcomes is debated. We examined whether ICS use is associated with adverse outcomes among COPD patients with community-acquired pneumonia (CAP). Population-based cohort study of all COPD patients with an incident hospitalization for CAP between 1997 and 2013 in Northern Denmark. Information on medications, COPD severity, comorbidities, complications, and death was obtained from medical databases. Adjusted risk ratios (aRRs) for pleuropulmonary complications, intensive care unit (ICU) admissions, and 30-day mortality in current and former ICS users were compared with those in non-users, using regression analyzes to handle confounding. Of 11,368 COPD patients with CAP, 6,073 (53.4%) were current ICS users and 1,733 (15.2%) were former users. Current users had a non-significantly decreased risk of pleuropulmonary complications [2.6%; aRR = 0.82 (0.59-1.12)] compared to non-users (3.2%). This was also observed among former users [2.5%; aRR = 0.77 (0.53-1.12)]. Similarly, decreased risks of ICU admission were observed among current users [aRR = 0.77 (0.57-1.04)] and among former users [aRR = 0.81 (0.58-1.13)]. Current ICS users had significantly decreased 30-day mortality [9.1%; aRR = 0.72 (0.62-0.85)] compared to non-users (12.6%), with a stronger association observed among patients with frequent exacerbations [0.58 (0.39-0.86)]. No significant association was observed among former ICS users [0.89 (0.75-1.05)]. Our results suggest a decreased risk of death with ICS use among COPD patients admitted for CAP.

Inhaled Corticosteroids and the Risk of Nontuberculous Mycobacterial Pulmonary Disease in Chronic Obstructive Pulmonary Disease: Findings from a Nationwide Population-Based Study.

Studies have shown increased nontuberculous mycobacterial pulmonary disease (NTM) incidence with inhaled corticosteroid (ICS) use in patients with chronic respiratory diseases; however, this association in chronic obstructive pulmonary disease (COPD) remains insufficiently studied. Using a nationwide population-based database of the Korean National Health Insurance Service, newly diagnosed COPD patients (2005-2018) treated with inhaled bronchodilators were selected. An NTM case was defined by the presence of the first diagnostic code following inhaled bronchodilator use. Results indicated that ICS users did not have an increased risk of NTM disease compared to non-ICS users (hazard ratio (HR), 1.121; 95% confidence interval (CI), 0.950-1.323; p = 0.176). However, in a subgroup analysis, the highest quartile of the cumulative ICS dose was associated with the development of NTM (1.200, 0.950-1.323, p = 0.050). Medium (1.229, 1.008-1.499, p = 0.041) and high daily doses of ICS (1.637, 1.241-2.160, p < 0.001) were associated with an increased risk of NTM disease. There was no difference in the risk of NTM according to ICS type. ICS use may increase the risk of developing NTM disease in patients with COPD. Physicians should weigh the potential benefits and risks of ICS, especially when using high doses and prolonged durations.

The Impact of Inhaled Corticosteroids on the Prognosis of Chronic Obstructive Pulmonary Disease.

A comprehensive analysis of the effects of inhaled corticosteroids (ICS) on COPD in a real-world setting is required due to safety concerns regarding ICS in COPD. This study aimed to explore the impact of ICS on the prognosis of Asian COPD patients in the real-life world. We examined 978 COPD patients registered in the Korean National Health and Nutrition Examination Survey (KNHANES) database and with their data linked to Health Insurance and Review Assessment (HIRA) data. The outcome measures were ascertained by HIRA from January 1, 2009, to December 31, 2012. This study enrolled two arms; ICS users (N = 85, mean age = 66.7 ± 8.9 years) and non-ICS users (N = 893, mean age = 63.7 ± 9.7 years). Compared to the non-ICS users, the ICS users had a higher rate of pneumonia, tuberculosis, and acute exacerbations (P<0.05). Hospitalization due to respiratory causes was also higher among ICS users (P<0.05). Multivariate analysis showed that acute exacerbation was independently associated with the development of pneumonia (P<0.05), whereas ICS therapy had a tendency to be associated with pneumonia. Another multivariate analysis demonstrated that old age, FEV1, ICS therapy, and pneumonia were independently associated with the occurrence of acute exacerbation (P<0.05). The concomitant pneumonia (HR = 3.353, P = 0.004) was independently associated with higher mortality (P<0.05). Our data demonstrated that the ICS users had a higher rate of pneumonia and tuberculosis and the concomitant pneumonia was independently associated with higher mortality, highlighting the importance of cautious and targeted administration of ICS in COPD.

Blood eosinophil percentage as a predictor of response to inhaled corticosteroid in bronchiectasis.

The role of inhaled corticosteroid (ICS) among patients with bronchiectasis remains controversial. There is limited evidence of using baseline eosinophil count (absolute and percentage) as a marker to predict the role of ICS among patients with bronchiectasis. A retrospective case-control study was conducted in a major regional hospital and tertiary respiratory referral centre in Hong Kong, including 140 Chinese patients with noncystic fibrosis (CF) bronchiectasis, to investigate the exacerbation risks of bronchiectasis among ICS users and nonusers with different baseline eosinophil counts. ICS user had significantly lower risk to develop bronchiectasis exacerbation with adjusted odds ratio (OR) of 0.461 (95% confidence interval [CI] 0.225-0.945, p-value 0.035). Univariate logistic regression was performed for different cut-offs of blood eosinophil count (by percentage) from 2% to 4% (with a 0.5% grid each time). Baseline eosinophil 3.5% was found to be the best cut-off among all with adjusted OR of 0.138 (95% CI = 0.023-0.822, p-value = 0.030). Baseline eosinophil count of 3.5% might serve as a marker to predict the benefits of ICS on exacerbation risk among patients with non-CF bronchiectasis.

Inhaled Corticosteroids in Patients with Chronic Obstructive Pulmonary Disease and Risk of Acquiring Streptococcus pneumoniae Infection. A Multiregional Epidemiological Study.

Inhaled corticosteroids (ICS) are associated with an increased risk of clinical pneumonia among patients with chronic obstructive pulmonary disease (COPD). It is unknown whether the risk of microbiologically verified pneumonia such as pneumococcal pneumonia is increased in ICS users. The study population consists of all COPD patients followed in outpatient clinics in eastern Denmark during 2010-2017. ICS use was categorized into four categories based on accumulated use. A Cox proportional hazard regression model was used adjusting for age, body mass index, sex, airflow limitation, use of oral corticosteroids, smoking, and year of cohort entry. A propensity score matched analysis was performed for sensitivity analyses. A total of 21,438 patients were included. Five hundred and eighty-two (2.6%) patients acquired a positive lower airway tract sample withS. pneumoniaeduring follow-up. In the multivariable analysis ICS-use was associated with a dose-dependent risk ofS. pneumoniae as follows:low ICS dose: HR 1.11, 95% CI 0.84 to 1.45, p = 0.5; moderate ICS dose: HR 1.47, 95% CI 1.13 to 1.90, p = 0.004; high ICS dose: HR 1.77, 95% CI 1.38 to 2.29, p < 0.0001, compared to no ICS use. Sensitivity analyses confirmed these results. Use of ICS in patients with severe COPD was associated with an increased and dose-dependent risk of acquiringS. pneumoniae, but only for moderate and high dose. Caution should be taken when administering high dose of ICS to patients with COPD. Low dose of ICS seemed not to carry this risk.

Impact of COVID-19 pandemic on control of bronchial asthma in children attending the asthma clinic in a tertiary care centre in Kerala

Abstract BACKGROUND: COVID-19 pandemic led to widespread change in the life of people across the globe, including children, with far-reaching consequences. When control of disease is considered among children with asthma, a positive impact is to be expected. This study aimed to assess the impact of the COVID-19 pandemic on disease control among children with asthma. OBJECTIVES: The main objectives are (1) to compare the level of asthma control pre-COVID versus during the COVID pandemic in terms of exacerbations and short-acting beta agonist (SABA) usage and (2) to compare the use of inhaled corticosteroids (ICS) pre-COVID versus during the COVID pandemic. MATERIALS AND METHODS: Hospital-based study was conducted among children aged 5–15 years attending the asthma clinic of Government TD Medical College, Alappuzha, during the period May 2021–January 2022. Asthma control in terms of SABA usage, emergency visits, hospitalizations, and ICS usage was compared pre-COVID (before March 2020) to Complete lockdown (March 2020–May 2020), phased reopening (June 2020–May 2021) and after the lifting of major restrictions (June 2021–January 2022). Statistical analysis was done using IBM SPSS Statistics v.26. RESULTS: In total, 139 children were included in the study. A decrease was observed in the number of children requiring SABA as reliever therapy, with 18%, 25.9%, and 33.1% not requiring SABA during the complete lockdown, during phased reopening, and after the lifting of major restrictions, respectively, when compared to pre-COVID. A statistically significant decrease in hospitalizations and visits to the emergency department due to asthma exacerbations were also observed during various phases of the pandemic. ICS was stopped in 15.1%, 30.2%, and 35.3% of the study subjects during various phases of the pandemic without further exacerbations. CONCLUSION: There was a significant impact on asthma control during the pandemic, which was sustained during various phases of lifting restrictions.

Beliefs about medicines and adherence to asthma medications during pregnancy

Objective Discontinuation of, and non-adherence to, inhaled corticosteroids (ICS) for asthma treatment is a significant issue in pregnancy. This study characterized beliefs about medicines in pregnant women with asthma and investigated associations with ICS adherence. Methods Pregnant women with relatively mild asthma (n = 302) were grouped according to ICS use and self-reported adherence (≥80% doses taken). They completed questions about dislike of asthma medications and the validated Beliefs about Medicines Questionnaire (BMQ), which consists of ten questions about asthma medicines (“necessity” questions about maintaining health, or “concern” questions about adverse effects), and eight general medicine questions, scored on five-point Likert scales. The Necessity Concerns differential (N-C) was calculated, with positive scores indicating that the patient perceives the benefits of medicines to outweigh the risks. Results ICS was used by 87 (29%) women, with 49 (56%) self-reporting adherence. Of the 22% who disliked taking asthma medications during pregnancy, 20% had the belief that the medication was unsafe. ICS users had a significantly higher BMQ necessity score and higher necessity-concern differential score than nonusers; when adjusted for covariates, ICS non-adherence was associated with a lower necessity score (p = 0.015). Women adherent to ICS were more likely to agree to “my health at present depends on my asthma medication” compared to non-adherent ICS users. Conclusions ICS non-adherence was not associated with having relatively more concerns about asthma medicines; however, ICS users were more likely to perceive that the benefits of medication use outweighed any risks. Interventions to improve asthma medication adherence in pregnancy are needed.

Relationships between Airway Remodeling and Clinical Characteristics in COPD Patients.

Background: Airway remodeling is a cardinal feature of chronic obstructive pulmonary disease (COPD) pathology. However, inconsistent findings have been reported regarding the nature of proximal airway remodeling in COPD. This is likely due to the heterogeneity of COPD. This study investigated the histopathological features of airway remodeling in bronchial biopsies of COPD patients compared to smoking controls (S). We tested the hypothesis that histopathological features in bronchial biopsies relate to clinical characteristics in COPD patients, focusing on smoking status, symptom burden, lung function, exacerbation risk and inhaled corticosteroid (ICS) use. Methods: We recruited 24 COPD patients and 10 S. We focused on reticular basement membrane thickness (RBM), surface immunoglobulin A (IgA) expression, goblet cell numbers (periodic acid-Schiff [PAS]+), sub-mucosal remodeling markers including collagen 4, 6 and laminin expression, and inflammatory cell counts (CD45+). Results: RBM thickness was increased in frequent exacerbators, IgA expression was reduced in COPD patients with worse lung function, and goblet cell numbers were increased in COPD patients compared to S but with no difference between the COPD subgroups. Collagen 4 expression was associated with higher symptom burden and worse quality of life. Sub-mucosal inflammatory cell counts were increased in COPD non-inhaled corticosteroid (ICS) users compared to ICS users and S. Conclusion: We observed relationships between the histopathological features of airway remodeling and clinical characteristics in COPD patients. Our data highlight the influence of clinical heterogeneity on diverse patterns of airway remodeling in COPD patients.

Risk of Tuberculosis Caused by Fluticasone Propionate versus Budesonide in Chronic Obstructive Pulmonary Disease: A Nationwide Population-Based Study.

Background: In chronic obstructive pulmonary disease (COPD), inhaled corticosteroids (ICSs) are recommended for use by patients with frequent exacerbations and blood eosinophilia. However, ICSs are often inappropriately prescribed and overused. COPD studies have reported an increased risk of tuberculosis among ICS users. This study aimed to compare the risk of tuberculosis according to the different ICS components. Methods: This study was conducted using a nationwide, population-based cohort. Patients newly diagnosed with COPD between 2005 and 2018, and treated with either fluticasone propionate or budesonide, were selected. The patients were followed up until the development of tuberculosis. Results: After propensity score matching, 16,514 fluticasone propionate and 16,514 budesonide users were identified. The incidence rate of tuberculosis per 100,000 person-years was 274.73 for fluticasone propionate and 214.18 for budesonide. The hazard ratio of tuberculosis in fluticasone propionate compared with budesonide was 1.28 (95% confidence interval 1.05–1.60). The risk of tuberculosis for fluticasone propionate increased with higher ICS cumulative doses: 1.01 (0.69–1.48), 1.16 (0.74–1.81), 1.25 (0.79–1.97), and 1.82 (1.27–2.62) from the lowest to highest quartiles, respectively. Conclusion: Fluticasone propionate is associated with a higher risk of tuberculosis than budesonide. ICS components can differently affect the risk of tuberculosis in patients with COPD.

Impact of Inhaled and Intranasal Corticosteroids Exposure on the Risk of Ocular Hypertension and Glaucoma: A Systematic Review and Meta-Analysis.

PurposeStarting in 2019, the Global Initiative for Asthma recommended the use of inhaled corticosteroids (ICS) as part of reliever combination therapy in patients 12 years of age and older, thus dramatically increasing the population exposure to ICS. ICS and intranasal corticosteroids (INS) are commonly used for a variety of respiratory diseases. Chronic steroid use is a well-known risk factor for elevated intraocular pressure (IOP) and glaucoma regardless of route of administration. This study aimed to determine the reported risk of glaucoma, ocular hypertension (OHT) and IOP elevation associated with ICS and INS use.Materials and MethodsSystematic literature search in MEDLINE, EMBASE, Cochrane, CINAHL, BIOSIS, and Web of Science databases from the date of inception identified studies that assess ocular outcomes related to glaucoma in ICS and INS users. Study selection, risk of bias assessment and data extraction were done independently in duplicate. Meta-analysis assessed glaucoma incidence, OHT incidence and IOP changes in patients using ICS and INS. Study adhered to PRISMA guidelines. Study protocol was registered with PROSPERO: CRD42020190241.ResultsQualitative and quantitative analyses included 65 and 41 studies, respectively. Incidence of glaucoma was not significantly different in either ICS or INS users compared to control over 45,457 person-years of follow-up. Similarly, no significant difference in OHT incidence over 4431 person-years was detected. In studies reporting IOP, a significantly higher IOP was observed (0.69 mmHg) in 857 ICS or INS users compared to 615 controls. However, no significant increase in IOP was observed within ICS or INS users when compared to pre-treatment baseline.ConclusionOverall, use of ICS or INS does not significantly increase the incidence of glaucoma or OHT. However, ICS and INS patients had significantly higher IOPs compared to untreated patients. Awareness of these findings is significant in care of patients with additional risk factors for glaucoma.

Association betweenInhaledβ2-agonistsInitiation and Risk of Major Adverse Cardiovascular Events: A Population-based Nested Case-Control Study.

PurposeDespite ample evidence underpinning the efficacy of β2-agonists in asthma and chronic obstructive pulmonary disease (COPD), the occurrence of β1- and β2-adrenoceptors in the heart suggests that β2-agonists may have deleterious cardiac effects. We investigated the association between new users of long-or short-acting β2-agonists (LABA or SABA) or ICS (inhaled corticosteroids)/LABA and major adverse cardiovascular events (MACE).MethodsA nested case–control analysis was conducted using the UK Clinical Practice Research Datalink of patients with asthma, COPD or asthma–COPD overlap with initial treatment of LABA, SABA, ICS/LABA, ICS, long-or short-acting muscarinic antagonist (LAMA or SAMA) between 01 January 1998 and 31 July 2018. The primary outcome was MACE, defined as the first occurrence of stroke, heart failure, myocardial infarction, arrhythmia, or cardiovascular death. Each case was matched with up to 10 controls on age, sex, date of cohort-entry, and duration of follow-up. The risk of MACE associated with β2-agonists was estimated using conditional logistic regression after controlling for potential confounders.ResultsThe cohort included 180,567 new users of β2-agonists, ICS, SAMA, or LAMA. Among asthmatics, β2-agonists were not associated with the risk of MACE (SABA vs ICS: HR 1.29 [0.96–1.73]; ICS/LABA vs ICS, HR 0.75 [0.33–1.73]). In contrast, among COPD patients, LABA (HR, 2.38 [1.04–5.47]), SABA (HR, 2.02 [1.13–3.59]) and ICS/LABA (HR, 2.08 [1.04–4.16]) users had an increased risk of MACE compared with SAMA users. Among patients with asthma–COPD overlap, SABA (HR, 2.57 [1.26–5.24]) was associated with an increased risk of MACE compared with ICS.ConclusionIn conclusion, initiation of LABA, SABA, or ICS/LABA in COPD or SABA in asthma–COPD overlap is associated with increased risk of MACE. No associations were observed among patients with asthma.