Use Of Inhaled Corticosteroids Research Articles

Asthma and coronavirus disease 2019–related outcomes in hospitalized patients: A single-center experience

BackgroundSeveral chronic conditions have been associated with a higher risk of severe coronavirus disease 2019 (COVID-19), including asthma. However, there are conflicting conclusions regarding risk of severe disease in this population. ObjectiveTo understand the impact of asthma on COVID-19 outcomes in a cohort of hospitalized patients and whether there is any association between asthma severity and worse outcomes. MethodsWe identified hospitalized patients with COVID-19 with confirmatory polymerase chain reaction testing with (n = 183) and without asthma (n = 1319) using International Classification of Diseases, Tenth Revision, codes between March 1 and December 30, 2020. We determined asthma maintenance medications, pulmonary function tests, highest historical absolute eosinophil count, and immunoglobulin E. Primary outcomes included death, mechanical ventilation, intensive care unit (ICU) admission, and ICU and hospital length of stay. Analysis was adjusted for demographics, comorbidities, smoking status, and timing of illness in the pandemic. ResultsIn unadjusted analyses, we found no difference in our primary outcomes between patients with asthma and patients without asthma. However, in adjusted analyses, patients with asthma were more likely to have mechanical ventilation (odds ratio, 1.58; 95% confidence interval [CI], 1.02-2.44; P = .04), ICU admission (odds ratio, 1.58; 95% CI, 1.09-2.29; P = .02), longer hospital length of stay (risk ratio, 1.30; 95% CI, 1.09-1.55; P < .003), and higher mortality (hazard ratio, 1.53; 95% CI, 1.01-2.33; P = .04) compared with the non-asthma cohort. Inhaled corticosteroid use and eosinophilic phenotype were not associated with considerabledifferences. Interestingly, patients with moderate asthma had worse outcomes whereas patients with severe asthma did not. ConclusionAsthma was associated with severe COVID-19 after controlling for other factors.

Inhaled corticosteroid use for asthma is linked to adrenal suppression.

Inhaled corticosteroid use for asthma is linked to adrenal suppression.

Changes after 12 years of follow-up severe asthma patients cohort: higher obstruction and comorbidities, but significant better quality of life

Background The Brazilian Cohort of Asthma São Paulo (BRASASP) had a well-characterized severe asthmatic in Brazil, with 12 years of follow-up under standard treatment. Methods Sequential assessment of patients with uncontrolled asthma from BRASASP cohort was carried out with 12 years of follow-up, performing exams and comparing with previous measurements. Results 50 from the 60 initial patients were reevaluated. Twelve years later, FEV1 and the FEV1/FVC ratio have significantly decreased, with a rate of loss of lung function of 11.8 and 14%, respectively, and worsening in small airway parameters such as RV/TLC. BMI, The Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ) scores haven’t changed. However, exacerbations decreased by 56%. Mean daily inhaled corticosteroid use was similar over time, but daily oral corticosteroid use decreased, in addition to a significant reduction in induced sputum eosinophilic and neutrophilic profile and serum IgE. Rhinitis, sinusitis, and GERD were the main comorbidities. In quality of life according to respiratory questionnaire SGRQ, total score showed a huge improvement (62% of patients). Conclusions There was significant decrease in FEV1 and FEV1/FVC. Data of pulmonary functional small airway characteristics show globally affected airways. Although higher doses of medications, patients were still uncontrolled, but with reduction of exacerbations, daily use of oral corticosteroid, less eosinophils and neutrophils in induced sputum and lower levels of IgE. Improvement in quality of life in 62% of patients.

Height and bone mineral content after inhaled corticosteroid use in the first 6 years of life

BackgroundInfants and young children might be particularly susceptible to the potential side effects from inhaled corticosteroid (ICS) on height and bone mineral content (BMC), but this has rarely been studied...

Oral Candidiasis as a Local Adverse Effect of Inhaled Corticosteroids: What the Dental Practitioner Should Know

Inhaled corticosteroids are increasingly recommended at all stages of asthma in all age groups as a first-line treatment for controlling symptoms and minimizing oral corticosteroid dependence in chronic asthma owing to their anti-inflammatory and immunosuppressive effects. Despite the fact that they are highly effective, their use can be accompanied by systemic and local adverse effects. Systemic adverse effects are infrequent, but oral candidiasis, the most common oral fungal infection, is a frequently observed local adverse effect of inhaled corticosteroid use. This adverse effect may lead to discomfort and cause reduced patient compliance. In this review, clinical findings of oral candidiasis, potential pathogenity mechanisms following such therapy along with the specific prophylactic measures that should be undertaken to minimize this adverse effect are discussed extensively. Understanding the factors leading to increased risk can give the opportunity of focusing on the patients who need timely intervention.

Inhaled Corticosteroid Use Among COPD Patients in Primary Care in Spain.

PurposeInhaled corticosteroids (ICS) are frequently used to treat chronic obstructive pulmonary disease (COPD) outside the current recommendations. Our aim was to describe ICS use in COPD patients and to identify factors associated with ICS use among COPD patients treated within primary care in Spain.Patients and MethodsThis was a cross-sectional, non-interventional and multicenter study of patients with COPD treated in primary care. Patient characteristics and exacerbations were described in terms of ICS use among the overall cohort, and among those with spirometry confirmed COPD (post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] ratio <70%). Multivariable logistic regression was used to identify factors associated with ICS use.ResultsA total of 901 patients were included, of which 47.9% (n = 432) were treated with ICS. A total of 240 patients (26.6%) experienced moderate/severe exacerbations in the prior year, while 309 (34.3%) during the previous two years. History of asthma totaled 11.6% (n = 105). The most frequent phenotype was non-exacerbator (51.6%), and the proportion of patient with moderate or severe exacerbations was significantly higher among ICS treated patients compared to non-treated: 37.5% versus 16.6% during the previous year (p < 0.001), and 46.8% versus 22.8% during the previous 2-years (p < 0.001), respectively. Patient characteristics were similar among spirometry confirmed patients and the overall population. Factors significantly associated with ICS use were a history of asthma (OR = 4.39, 95% CI: 2.67–7.26), the presence of moderate or severe exacerbations in the last year (OR = 2.52, 95% CI: 1.81–3.49), followed by higher mMRC and higher CAT score.ConclusionNearly half of patients in primary care in Spain are treated with ICS, despite most of them being non-exacerbators. History of asthma, exacerbations, and worse dyspnea and CAT scores are associated with ICS use.

Association Between Bedroom Particulate Matter Filtration and Changes in Airway Pathophysiology in Children With Asthma

To identify the measurable physiologic changes in the small airways of children with asthma, when employing a 2.5 µm particulate matter (PM2.5) filtration device in their bedrooms.The population enrolled includes children with mild or moderate asthma who live in a suburb of Shanghai, China, during a low-ozone season. A total of 43 children (5–13 years old; 60% boys) are included in the analysis.Patients are randomly assigned into either arm of a double-blind crossover study design with 3 consecutive 14 day periods of true filtration-washout-sham filtration or the reverse order. Impulse oscillometry, spirometry, and fractional exhaled nitric oxide (FeNO) were measured before and after each intervention, and peak flow was measured twice per day at home.PM2.5 concentrations were moderately high (28.6-69.8 μ g/m3) among the enrollees. A decrease in PM2.5 concentration by 63.4% was noted in true filtration bedrooms, when compared with sham filtration. True filtration was associated with improved airway mechanics, as measured by impulse oscillometry (a 22% to 43% decrease in resonant frequency, small airway resistance, and total airway resistance and 73% increase in airway reactance), FeNO, (27.6% decrease) and peak flow measurement (1.6% increase). These airway parameters were significantly associated with bedroom particulate matter reduction. Statistical significance was only noted in children without eosinophilic airway inflammation at the baseline (an absolute eosinophil count of 450 cells per μL and FeNO >35 parts per billion). No large airway parameters (forced expiratory volume in 1 second, forced vital capacity, and forced expiratory volume in 1 second to forced vital capacity) differed after 14 days of true filtration.PM2.5 filtration in the bedroom may improve airway mechanics and inflammation in pediatric patients with asthma who do not have eosinophilic inflammation.With this study, the authors expand on previous work by the same group that revealed 1 night of HEPA air filtration improved airway mechanics in healthy adults. The results after 2 weeks indicate a promising intervention for children with noneosinophilic asthma. The authors carefully controlled for a number of confounders, including intercurrent illness, asthma exacerbations, seasonal variation, ozone levels, inhaled corticosteroid use, and secondhand smoke exposure. In future studies, researchers should address patients in different environmental conditions with a larger sample size, for a longer intervention period, before formal recommendations can be made.

An Analysis of Demographics and Inhaled Corticosteroid Use on COVID-19 Outcomes Among Hospitalized Adult Asthmatics: An Early Experience at a NY Hospital System

PurposeIt is unclear whether asthma is a risk factor for the development of COVID-19; however, severe asthma is a risk factor for morbidity and mortality. While systemic corticosteroids are beneficial during the inflammatory phase of COVID-19, the impact of inhaled corticosteroids (ICS) is unclear. We sought to characterize asthmatics admitted with COVID-19 early in the pandemic, determine if baseline factors are associated with more severe COVID-19 disease, and if the use of ICS may mitigate the severity of COVID-19.Patients and MethodsA retrospective chart review of hospitalized asthma patients >18 years testing positive for SARS-CoV2 from March to June 2020 was performed. Baseline demographic and asthma variables were collected. COVID-19 outcomes and laboratory values were extracted and compared between sex, race, ethnicity, and ICS use.ResultsOf the 906 patient charts reviewed, 787 asthmatics were confirmed to be admitted for symptomatic COVID-19. Sex differences were found in hospitalization and intubation. Non-Hispanic patients had a significantly greater number of days on ventilator. Patients on ICS were 1.6 times more likely to be discharged on supplemental oxygen compared to patients not on ICS (p = 0.01).ConclusionWhile our findings confirm trends observed by others with respect to risk factors among asthmatics with COVID-19, differences based on sex, ethnicity and ICS use in asthmatics were observed. Our finding that ICS use was associated with discharge with oxygen is novel. Future research is needed to study the trajectory of asthmatics from diagnosis to outcomes.

Association between Inhaled Corticosteroid Use and SARS-CoV-2 Infection: A Nationwide Population-Based Study in South Korea.

BackgroundAlthough it is known that inhaled corticosteroid (ICS) use may increase the risk of respiratory infection, its influence on the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. Thus, the aim of this study was to investigate the association between ICS use and the positivity of SARS-CoV-2 infection among patients with chronic respiratory diseases.MethodsNationwide data of 44,968 individuals with chronic respiratory diseases tested for SARS-CoV-2 until May 15, 2021 were obtained from the Ministry of Health and Welfare and Health Insurance Review and Assessment Service in Korea. The positivity of SARS-CoV-2 infection was retrospectively analysed according to the prescription, type, and dose of ICS taken one year before SARS-CoV-2 test.ResultsAmong 44,968 individuals tested, 931 (2.1%) were positive for SARS-CoV-2. A total of 7,019 patients (15.6%) were prescribed ICS one year prior to being tested for SARS-CoV-2. Low, medium, and high doses of ICS were prescribed in 7.5%, 1.6%, and 6.5% of total cases, respectively. Among types of ICS, budesonide, fluticasone, beclomethasone, and ciclesonide were prescribed in 3.7%, 8.9%, 2.3%, and 0.6% of total cases, respectively. A multivariate analysis showed no significant increase in infection with ICS use (odds ratio, 0.84; 95% confidence interval, 0.66–1.03). Moreover, there were no associations between the positivity of infection and the dose or type of ICS prescribed.ConclusionPrior ICS use did not increase the positivity for SARS-CoV-2 infection. Moreover, different doses or types of ICS did not affect this positivity.

A real-world study of inhaled corticosteroid use in patients with severe eosinophilic asthma treated with mepolizumab

BackgroundMepolizumab is a humanized anti-interleukin-5, monoclonal antibody approved for the treatment of patients with severe eosinophilic asthma (SEA). There is limited evidence that mepolizumab can reduce inhaled corticosteroid (ICS) use in these patients. ObjectiveTo investigate changes in ICS use and clinical outcomes in patients with SEA who initiated mepolizumab treatment. MethodsThis retrospective cohort study (GlaxoSmithKline identification: 212695/HO-20-19951) used administrative claims data from the IBM Watson Health MarketScan Database (identification period: November 2015 to March 2018). Eligible patients had SEA and were receiving high-dose ICS and mepolizumab. Use of ICS, oral corticosteroid (OCS), and short-acting β2-agonist and exacerbation frequency were analyzed quarterly during the 12-month follow-up period after mepolizumab initiation. ResultsIn total, 351 patients were included. The proportion of patients using high-dose ICS decreased in quarters 1 to 4 after mepolizumab initiation (79.8%, 74.6%, 68.9%, 65.5%, respectively); 49.0% of patients reduced or discontinued ICS for one or more quarter. Comparing patients who discontinued ICS vs those who remained on high-dose ICS, a lower proportion had chronic OCS use (3.4%–9.2% vs 13.9%–16.8%) and OCS burst use (15.4%–20.8% vs 19.7%–26.1%) in quarters 1 to 4; similarly in quarters 3 and 4, a lower proportion of patients had exacerbations (16.9% and 20.3% vs 27.2% and 27.7%) and short-acting β2-agonist claims (35.4% and 39.2% vs 43.3% and 49.0%, respectively). ConclusionIn patients with SEA on high-dose ICS, a reduction in both ICS and OCS use was observed after initiating mepolizumab. These findings have important implications for clinical outcomes and follow-up care in this patient population.

Diagnosis and management of cough-variant asthma

Abstract Cough is a natural defence mechanism of the lungs to prevent aspiration and to keep the airway clean. Cough, wheezing and shortness of breath are common symptoms of asthma. Cough-variant asthma is one of the phenotypes of asthma with the main symptom of cough without shortness of breath and wheezing. Cough-variant asthma is largely observed in patients with bronchial hyperresponsiveness who experience cough due to innocuous stimuli, and it is associated with a family history and seasonal allergy. In the present study, in patients with cough-variant asthma, no abnormalities were found during the lung function test, particularly forced expiratory flow in the first second (FEV1) or peak expiratory flow (PEF), although these values were lower than those in normal individuals. A bronchial provocation test using methacholine is needed to assess airway hyperresponsiveness, and depending on the outcome of the test, an assessment can be made as to the probability of the patient requiring a diagnosis of cough-variant asthma. Administration of inhalation therapy with bronchodilators and corticosteroids is the mainstay of management in patients with cough-variant asthma presenting with the symptom of persistent cough. Until now, there have been no specific guidelines for drug selection, dose and duration of inhaled corticosteroid use in cough-variant asthma. If symptoms do not resolve with inhaled corticosteroid monotherapy, consideration may be given to increase the inhalation dose or to add other drugs such as long-acting B2 agonists, slow-release theophylline or leukotriene receptor antagonist (LTRA).

Uncontrolled asthma from childhood to young adulthood associates with airflow obstruction.

IntroductionLung function development from childhood to young adulthood is important for lung health later in life. We investigated the association between asthma control and lung function from 8 to 24 years of age.MethodsA total of 668 participants from the population-based BAMSE cohort study, with persistent or incidental asthma and between 8 and 24 years of age, were included. Asthma was defined as controlled or uncontrolled at each examination based on the Global Initiative for Asthma (GINA) criteria. Dynamic spirometry was performed at 8, 16 and 24 years of age. Associations between uncontrolled asthma and pre-bronchodilation forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio were evaluated with a generalised estimating equation model, as overall associations and at each examination. Unadjusted and adjusted (for sex, current asthma, allergic sensitisation, body mass index, smoking, smoke exposure, inhaled corticosteroid use) analyses were done; and were thereafter stratified by sex, elevated blood eosinophils (≥0.3×109 cells·µL−1), elevated FENO (≥25 ppb), allergic sensitisation and ever/never smoking.ResultsUncontrolled asthma was associated with a lower overall FEV1/FVC z-score from 8 to 24 years of age (adjusted regression coefficient −0.11; 95% CI (−0.20 to −0.02; p=0.016). After stratification, this association was primarily seen among females (adjusted regression coefficient −0.170; 95% CI (−0.298 to −0.044; p=0.009) and participants with elevated FENO (regression coefficient −0.207; 95% CI −0.342 to −0.073; p=0.002), in contrast to males and participants with normal FENO.ConclusionUncontrolled asthma is associated with airflow obstruction from childhood to young adulthood. This highlights the importance of active management of asthma during growth.

Association between inhaled corticosteroid use and COVID-19 outcomes.

BackgroundRecent evidence has established a beneficial effect of systemic corticosteroids for treatment of moderate‐to‐severe COVID‐19.ObjectiveTo determine if inhaled corticosteroid use is associated with COVID‐19 outcomes.MethodsIn a nationwide cohort of hospitalized SARS‐CoV‐2 test‐positive individuals in Denmark, we estimated the 30‐day hazard ratio of intensive care unit (ICU) admission or death among users of inhaled corticosteroids (ICS) compared with users of bronchodilators (β2‐agonist/muscarinic‐antagonists), and non‐users of ICS overall, with Cox regression adjusted for age, sex, and other confounders. We repeated these analyses among influenza test‐positive patients during 2010–2018.ResultsAmong 6267 hospitalized SARS‐CoV‐2 patients, 614 (9.8%) were admitted to ICU and 677 (10.8%) died within 30 days. ICS use was associated with a hazard ratio of 1.09 (95% CI [CI], 0.67 to 1.79) for ICU admission and 0.78 (95% CI, 0.56 to 1.11) for death compared with bronchodilator use. Compared with no ICS use overall, the hazard ratio of ICU admission or death was 1.17 (95% CI, 0.87–1.59) and 1.02 (95% CI, 0.78–1.32), respectively. Among 10 279 hospitalized influenza patients, of which 951 (9.2%) were admitted to ICU and 1275 (12.4%) died, the hazard ratios were 1.43 (95% CI, 0.89–2.30) and 1.11 (95% CI, 0.85–1.46) for ICU admission, and 0.80 (95% CI, 0.63–1.01) and 1.03 (95% CI, 0.87–1.22) for death compared with bronchodilator use and no ICS use overall, respectively.ConclusionOur results do not support an effect of inhaled corticosteroid use on COVID‐19 outcomes, however we can only rule out moderate‐to‐large reduced or increased risks.Study registrationThe study was pre‐registered at encepp.eu (EUPAS35897).

The Role of Pediatric Health-care Providers in Promoting Students' Asthma Health.

The Role of Pediatric Health-care Providers in Promoting Students' Asthma Health.

Dynamics of inhaled corticosteroid use are associated with asthma attacks

Inhaled corticosteroids (ICS) suppress eosinophilic airway inflammation in asthma, but patients may not adhere to prescribed use. Mean adherence—averaging total doses taken over prescribed—fails to capture many aspects of adherence. Patients with difficult-to-treat asthma underwent electronic monitoring of ICS, with data collected over 50 days. These were used to calculate entropy (H) a measure of irregular inhaler use over this period, defined in terms of transitional probabilities between different levels of adherence, further partitioned into increasing (Hinc) or decreasing (Hdec) adherence. Mean adherence, time between actuations (Gapmax), and cumulative time- and dose-based variability (area-under-the-curve) were measured. Associations between adherence metrics and 6-month asthma status and attacks were assessed. Only H and Hdec were associated with poor baseline status and 6-month outcomes: H and Hdec correlated negatively with baseline quality of life (H:Spearman rS = − 0·330, p = 0·019, Hdec:rS = − 0·385, p = 0·006) and symptom control (H:rS = − 0·288, p = 0·041, Hdec: rS = − 0·351, p = 0·012). H was associated with subsequent asthma attacks requiring hospitalisation (Wilcoxon Z-statistic = − 2.34, p = 0·019), and Hdec with subsequent asthma attacks of other severities. Significant associations were maintained in multivariable analyses, except when adjusted for blood eosinophils. Entropy analysis may provide insight into adherence behavior, and guide assessment and improvement of adherence in uncontrolled asthma.

Blood Eosinophils and Clinical Outcomes in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Propensity Score Matching Analysis of Real-World Data in China.

Background and Objective: Elevated eosinophils in chronic obstructive pulmonary disease (COPD) are recognized as a biomarker to guide inhaled corticosteroids use, but the value of blood eosinophils in hospitalized exacerbations of COPD remains controversial. This study aimed to evaluate the accuracy of eosinophils in predicting clinical outcomes in acute exacerbation of COPD (AECOPD).Methods: We analyzed data from the acute exacerbation of chronic obstructive pulmonary disease inpatient registry (ACURE) study, which is an ongoing nationwide multicenter, observational real-world study in patients admitted for AECOPD. Data collected between January 2018 and December 2019 in 163 centers were first reviewed. The eligible patients were divided into eosinophilic and non-eosinophilic groups, according to blood eosinophil with 2% of the total leukocyte count as the threshold. Propensity score (PS) matching was performed to adjust for confounders.Results: A total of 1,566 patients (median age: 69 years; 80.3% male) were included and 42.7% had an eosinophilic AECOPD. Eosinophil count <2% was associated with the development of respiratory failure and pneumonia. After PS matching, 650 pairs in overall patients, 468 pairs in patients with smoking history and 177 pairs in patients without smoking were selected, respectively. Only in patients with smoking history, the non-eosinophilic AECOPD was associated with longer median hospital stays (9 vs. 8 days, P = 0.034), higher dosage of corticosteroid use, higher economic burden of hospitalization, and poorer response to corticosteroid therapy compared to the eosinophilic AECOPD. No significant difference was found in patients without smoking. Eosinophil levels had no relationship with the change of COPD Assessment Test scores and readmissions or death after 30 days.Conclusion: Elevated eosinophils were associated with better short-term outcomes only in patients with a smoking history. Eosinophil levels cannot be confidently used as a predictor alone for estimating prognosis.

Characterization of COPD Admissions During the First COVID-19 Outbreak.

PurposeExacerbations of COPD (ECOPD) are a frequent cause of hospitalization that seemed to ameliorate during the COVID outbreak. We aimed to evaluate the clinical characteristics of COPD-related hospital admissions and mortality in relation to the presence of COVID-19.Patients and MethodsWe conducted a case–control study of patients admitted in four teaching hospitals throughout Spain between March 15 and April 30, 2020. Hospital admissions of respiratory cause with and without PCR-proven SARS-CoV-2 infection in patients with COPD were evaluated. Baseline and episode-related clinical characteristics were analyzed. Logistic regression analysis was performed to evaluate the risk for mortality.ResultsDuring the study period, 2101 patients were admitted for respiratory worsening, 1200 (57.1%) with COVID-19. A total of 228 (10.8%) were admitted due to COPD worsening, of whom 52 (22.8%) tested positive for COVID-19. COPD patients with COVID-19, when compared to those without COVID-19, were more frequently males with better lung function (FEV1 postbronchodilator 71% vs 46% respectively, p<0.001) and had higher mortality (44.9% vs 13.6% respectively, p<0.001) despite similar age, comorbidities, total days of hospitalization and admission to intensive care unit. COVID-19 and eosinopenia were the strongest risk factors for mortality in the multivariate analysis in the overall COPD population. Inhaled corticosteroid use was not associated to mortality.ConclusionHospitalizations for ECOPD without COVID-19 were more frequent than COPD with COVID-19 during the first outbreak, but the latter were associated with higher mortality and low eosinophil counts that warrant further analysis.

Impact of COVID-19 pandemic on asthma symptoms and management: A prospective analysis of asthmatic children in Ecuador

BackgroundAsthma affects up to 33% of children in Latin American settings. The ongoing COVID-19 pandemic has had a significant impact on access to and use of health services. We aimed to evaluate the impact of the COVID-19 lockdown on asthma exacerbations, medical facility visits, and use of asthma medications in children. MethodsWe used data from a prospective cohort of 213 children aged 5–17 years in 3 Ecuadorian cities and analysed the impact of the COVID-19 lockdown on asthma. Outcomes (asthma exacerbations, emergency room [ER] visits, planned and unplanned outpatient visits, and use of inhaled corticosteroids and Beta-2 agonists) were analysed using repeated Poisson counts (ie, number of events per participant before and during the COVID-19 lockdown). ResultsDuring compared to before lockdown: a) the number of asthma exacerbations remained constant (IRR, 0.87; 95% CI: 0.72–1.05; p = 0.152); b) outpatient visits (IRR 0.26, 95% CI 0.14–0.47, p < 0.001) declined 74% while ER visits declined 89% (IRR 0.11, 95% CI 0.04–0.32, p < 0.001); and c) there was no change in inhaled corticosteroids use (IRR 1.03, 95% CI 0.90–1.16, P = 0.699) while Beta-2 agonist use increased (IRR 1.32, 95% CI 1.10–1.58, P = 0.003). ConclusionsIn a cohort of Ecuadorian children with asthma, health services attendance decreased dramatically after COVID-19 lockdown, but asthma exacerbations and use of inhaled corticosteroids were unchanged. Future analyses will address the question of the effect of SARS-CoV-2 infection on asthma exacerbations and control in this paediatric population.

Dysregulation of COVID-19 related gene expression in the COPD lung

BackgroundChronic obstructive pulmonary disease (COPD) patients are at increased risk of poor outcome from Coronavirus disease (COVID-19). Early data suggest elevated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) receptor angiotensin converting enzyme 2 (ACE2) expression, but relationships to disease phenotype and downstream regulators of inflammation in the Renin-Angiotensin system (RAS) are unknown. We aimed to determine the relationship between RAS gene expression relevant to SARS-CoV-2 infection in the lung with disease characteristics in COPD, and the regulation of newly identified SARS-CoV-2 receptors and spike-cleaving proteases, important for SARS-CoV-2 infection.MethodsWe quantified gene expression using RNA sequencing of epithelial brushings and bronchial biopsies from 31 COPD and 37 control subjects.ResultsACE2 gene expression (log2-fold change (FC)) was increased in COPD compared to ex-smoking (HV-ES) controls in epithelial brushings (0.25, p = 0.042) and bronchial biopsies (0.23, p = 0.050), and correlated with worse lung function (r = − 0.28, p = 0.0090). ACE2 was further increased in frequent exacerbators compared to infrequent exacerbators (0.51, p = 0.00045) and associated with use of ACE inhibitors (ACEi) (0.50, p = 0.0034), having cardiovascular disease (0.23, p = 0.048) or hypertension (0.34, p = 0.0089), and inhaled corticosteroid use in COPD subjects in bronchial biopsies (0.33, p = 0.049). Angiotensin II receptor type (AGTR)1 and 2 expression was decreased in COPD bronchial biopsies compared to HV-ES controls with log2FC of –0.26 (p = 0.033) and − 0.40, (p = 0.0010), respectively. However, the AGTR1:2 ratio was increased in COPD subjects compared with HV-ES controls, log2FC of 0.57 (p = 0.0051). Basigin, a newly identified potential SARS-CoV-2 receptor was also upregulated in both brushes, log2FC of 0.17 (p = 0.0040), and bronchial biopsies, (log2FC of 0.18 (p = 0.017), in COPD vs HV-ES.Transmembrane protease, serine (TMPRSS)2 was not differentially regulated between control and COPD. However, various other spike-cleaving proteases were, including TMPRSS4 and Cathepsin B, in both epithelial brushes (log2FC of 0.25 (p = 0.0012) and log2FC of 0.56 (p = 5.49E−06), respectively) and bronchial biopsies (log2FC of 0.49 (p = 0.00021) and log2FC of 0.246 (p = 0.028), respectively).ConclusionThis study identifies key differences in expression of genes related to susceptibility and aetiology of COVID-19 within the COPD lung. Further studies to understand the impact on clinical course of disease are now required.

Real-life cost-effectiveness of benralizumab in patients with severe asthma

BackgroundAvailability of clinically effective and cost-effective treatments for severe asthma would be beneficial to patients and national healthcare systems. The aim of this study was to evaluate clinical outcomes and healthcare expenditure after incorporating benralizumab into the standard treatment of refractory eosinophilic asthma.MethodsThis was a cross-sectional multicentre study of consecutive patients with refractory eosinophilic asthma who received treatment with benralizumab during at least 12 months. Patient follow-up was performed in specialised severe asthma units. The main effectiveness parameters measured were: the avoidance of one asthma exacerbation, a 3-point increase in the asthma control test (ACT) score, and the difference in utility scores (health-related quality of life) between a 1-year baseline treatment and 1-year benralizumab treatment. The health economic evaluation included direct costs and incremental cost-effectiveness ratios (ICERs).ResultsAfter 1 year of treatment with benralizumab, patients with refractory eosinophilic asthma showed an improvement in all the effectiveness parameters analysed: improvement of asthma control and lung function, and decrease in the number of exacerbations, oral corticosteroid (both as corticosteroid courses and maintenance therapy), and inhaled corticosteroid use. The total annual cost per patient for the baseline and benralizumab treatment periods were €11,544 and €14,043, respectively, reflecting an increase in costs due to the price of the biological agent but a decrease in costs for the remaining parameters. The ICER was €602 per avoided exacerbation and €983.86 for every 3-point increase in the ACT score.ConclusionsAll the pharmacoeconomic parameters analysed show that treatment with benralizumab is a cost-effective option as an add-on therapy in patients with refractory eosinophilic asthma.