Exacerbations In Adults Research Articles

Cathepsin C (dipeptidyl peptidase 1) inhibition in adults with bronchiectasis: AIRLEAF®, a Phase II randomised, double-blind, placebo-controlled, dose-finding study.

Bronchiectasis is characterised by uncontrolled neutrophil serine protease (NSP) activity. Cathepsin C (CatC; dipeptidyl peptidase 1) activates NSPs during neutrophil maturation. CatC inhibitors can potentially reduce neutrophil-mediated lung damage. This Phase II, randomised, double-blind, placebo-controlled trial (AIRLEAF®; NCT05238675) evaluated efficacy, safety and optimal dosing of BI 1291583, a novel, reversible CatC inhibitor, in adults with bronchiectasis.In total, 322 participants were randomised (2:1:1:2) to receive one of three oral doses of BI 1291583 (1 mg/2.5 mg/5 mg) or placebo for 24 to 48 weeks. A multiple comparison procedure and modelling approach was used to demonstrate a non-flat dose-response curve based on the time to first pulmonary exacerbation up to Week 48. In addition, efficacy of individual BI 1291583 doses was evaluated based on the frequency of exacerbations, severe exacerbations (fatal or leading to hospitalisation and/or intravenous antibiotic administration), lung function and quality of life.A significant dose-dependent benefit of BI 1291583 over placebo was established based on time to first exacerbation (shape: Emax; adjusted p-value: 0.0448). Treatment with BI 1291583 5 mg and 2.5 mg numerically reduced the risk of an exacerbation compared with placebo (hazard ratios: 0.71 and 0.66, 95% CIs 0.48-1.05 and 0.40-1.08; both p>0.05). BI 1291583 2.5 mg showed numerically better efficacy compared with 5 mg across several endpoints; 1 mg was similar to placebo. The safety profile of BI 1291583 was similar to placebo.Treatment with BI 1291583 resulted in a reduction in the risk of experiencing an exacerbation in adults with bronchiectasis.

796-P: Glucose-Lowering Drugs and Risk of COPD Exacerbations in Adults with Type 2 Diabetes

796-P: Glucose-Lowering Drugs and Risk of COPD Exacerbations in Adults with Type 2 Diabetes

Risk Factors for Acute Asthma Exacerbations in Adults With Mild Asthma

Although individuals with mild asthma account for 30% to 40% of acute asthma exacerbations (AAEs), relatively little attention has been paid to risk factors for AAEs in this population. To identify risk factors associated with AAEs in patients with mild asthma. This was a retrospective cohort study. We used administrative data from a large managed care organization to identify 199,010 adults aged 18 to 85 years who met study criteria for mild asthma between 2013 and 2018. An asthma-coded qualifying visit (index visit) was identified for each patient. We then used information at the index visit or from the year before the index visit to measure potential risk factors for AAEs in the subsequent year. An AAE was defined as either an asthma-coded hospitalization or emergency department visit, or an asthma-related systemic corticosteroid administration (intramuscular or intravenous) or oral corticosteroid dispensing. Poisson regression models with robust SEs were used to estimate the adjusted risk ratios for future AAEs. In the study cohort, mean age was 44 years and 64% were female; 6.5% had AAEs within 1 year after the index visit. In multivariate models, age, sex, race, ethnicity, smoking status, body mass index, prior acute asthma care, and a variety of comorbidities and other clinical characteristics were significant predictors for future AAE risk. Population-based disease management strategies for asthma should be expanded to include people with mild asthma in addition to those with moderate to severe disease.

Brensocatib in non-cystic fibrosis bronchiectasis: ASPEN protocol and baseline characteristics.

Brensocatib is an investigational, oral, reversible inhibitor of dipeptidyl peptidase-1 shown to prolong time to first exacerbation in adults with bronchiectasis. Outlined here are the clinical trial design, and baseline characteristics and treatment patterns of adult patients enrolled in the phase 3 ASPEN trial (NCT04594369). The ASPEN trial is a global study enrolling patients with a clinical history consistent with bronchiectasis (cough, chronic sputum production and/or recurrent respiratory infections), diagnosis confirmed radiologically and ≥2 exacerbations in the prior 12 months. It was designed to evaluate the impact of two brensocatib doses (10 mg and 25 mg) on exacerbation rate over a 52-week treatment period versus placebo. Comprehensive clinical data, including demographics, disease severity, lung function, Pseudomonas aeruginosa status and quality of life, were collected at baseline. 1682 adults from 35 countries were randomised from December 2020 to March 2023. Mean age was 61.3 years and 64.7% were female. ∼70% had moderate-to-severe Bronchiectasis Severity Index (BSI) scores, 29.3% had ≥3 exacerbations in the prior 12 months and 35.7% were positive for P. aeruginosa. Mean BSI scores were highest in Australia/New Zealand (8.3) and lowest in Latin America (5.9). Overall, the most common aetiology was idiopathic (58.4%). In P. aeruginosa-positive versus P. aeruginosa-negative patients, lung function was lower, with greater long-term macrolide (21.5% versus 14.0%) and inhaled corticosteroid use (63.5% versus 53.9%). There was wide regional variation in long-term antibiotic use in patients with bronchiectasis and P. aeruginosa. ASPEN baseline characteristics and treatment profiles were representative of a global bronchiectasis population.

A RCT to explore the effectiveness of supporting adherence to nebuliser medication in adults with cystic fibrosis: fidelity assessment of study interventions

BackgroundA multi-component self-management intervention ‘CFHealthHub’ was developed to reduce pulmonary exacerbations in adults with Cystic Fibrosis (CF) by supporting adherence to nebuliser medication. It was evaluated in a randomized controlled trial (RCT) involving 19 CF centres, with 32 interventionists, 305 participants in the intervention group, and 303 participants in the standard care arm. Ensuring treatment fidelity of intervention delivery was crucial to ensure that the intervention produced the expected outcomes.MethodsFidelity of the CFHealthHub intervention and standard care was assessed using different methods for each of the five fidelity domains defined by the Borrelli framework: study design, training, treatment delivery, receipt, and enactment. Study design ensured that the groups received the intended intervention or standard care. Interventionists underwent training and competency assessments to be deemed certified to deliver the intervention. Audio-recorded intervention sessions were assessed for fidelity drift. Receipt was assessed by identifying whether participants set Action and Coping Plans, while enactment was assessed using click analytics on the CFHealthHub digital platform.ResultsDesign: There was reasonable agreement (74%, 226/305) between the expected versus actual intervention dose received by participants in the CFHealthHub intervention group. The standard care group did not include focused adherence support for most centres and participants. Training: All interventionists were trained. Treatment delivery: The trial demonstrated good fidelity (overall fidelity by centre ranged from 79 to 97%), with only one centre falling below the mean threshold (> 80%) on fidelity drift assessments. Receipt: Among participants who completed the 12-month intervention, 77% (205/265) completed at least one action plan, and 60% (160/265) completed at least one coping plan. Enactment: 88% (268/305) of participants used web/app click analytics outside the intervention sessions. The mean (SD) number of web/app click analytics per participant was 31.2 (58.9). Additionally, 64% (195/305) of participants agreed to receive notifications via the mobile application, with an average of 53.6 (14.9) notifications per participant.ConclusionsThe study demonstrates high fidelity throughout the RCT, and the CFHealthHub intervention was delivered as intended. This provides confidence that the results of the RCT are a valid reflection of the effectiveness of the CFHealthHub intervention compared to standard care.Trial registrationISRCTN registry: ISRCTN55504164 (date of registration: 12/10/2017).

How do immunostimulants compare with placebo for preventing exacerbations in adults with chronic bronchitis or chronic obstructive pulmonary disease (COPD)?

How do immunostimulants compare with placebo for preventing exacerbations in adults with chronic bronchitis or chronic obstructive pulmonary disease (COPD)?

Mepolizumab in children and adolescents with severe eosinophilic asthma not eligible for omalizumab: a single Center experience

Background Mepolizumab is an anti-interleukin-5 monoclonal antibody shown to reduce asthma exacerbations in adults and adolescents with severe eosinophilic asthma. Aim To assess the impact of mepolizumab on children and adolescents over 12 months by examining steroid usage, asthma-related hospitalizations, Asthma Control Test (ACT) scores, fractional exhaled nitric oxide concentration (FeNO), forced expiratory volume in 1 s (FEV1), mid expiratory flow (FEF25–75%), and blood eosinophil count. Methods Retrospective analysis performed between October 2015 and December 2022. Data was reviewed 12 months before and after commencing mepolizumab. Mepolizumab was offered if the patient had severe eosinophilic asthma and were unresponsive to or ineligible for omalizumab. Results Sixteen participants (age 7–17, 8 males, 8 females) received subcutaneous mepolizumab monthly with no serious adverse reactions. Incidence of hospital admissions fell significantly (IRR 0.33, p = 0.007). Among the 11 patients receiving daily oral corticosteroids, 3 were weaned off daily oral steroids and 3 patients’ daily dose was significantly reduced (mean Δ-0.095 ± 0.071 mg/kg, p = 0.0012). Eosinophil count was decreased (mean Δ-0.85 x 109/L, p < 0.001). There was no significant change in mean overall steroid burden per patient (mean Δ-1445.63 ± 1603.18 mg, p = 0.10), ACT scores (mean Δ2.88 ± 6.71, p = 0.17), FEV1 z-scores (mean Δ-0.99 ± 1.88, p = 0.053), FEF25–75% z-scores (mean Δ-0.65 ± 1.61, p = 0.13), FeNO (mean Δ-20.09 ± 80.86, p = 0.34), or number of courses of oral steroids given for asthma attacks (IRR 0.71, p = 0.09). Conclusion Among children and adolescents with severe eosinophilic asthma ineligible for or not responsive to omalizumab, mepolizumab therapy exhibited significant reduction in rate of asthma-related hospitalizations and significant decrease in daily steroid dosage.

Influenza Vaccine Effectiveness Pre-pandemic Among Adults Hospitalized With Congestive Heart Failure or Chronic Obstructive Pulmonary Disease and Older Adults.

Data are limited on influenza vaccine effectiveness (VE) in the prevention of influenza-related hospitalizations in older adults and those with underlying high-risk comorbidities. We conducted a prospective, test-negative, case-control study at 2 US hospitals from October 2018-March 2020 among adults aged ≥50 years hospitalized with acute respiratory illnesses (ARIs) and adults ≥18 years admitted with congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD) exacerbations. Adults were eligible if they resided in 1 of 8 counties in metropolitan Atlanta, Georgia. Nasopharyngeal and oropharyngeal swabs were tested using BioFire FilmArray (bioMérieux, Inc.) respiratory panel, and standard-of-care molecular results were included when available. Influenza vaccination history was determined from the Georgia vaccine registry and medical records. We used multivariable logistic regression to control for potential confounders and to determine 95% confidence intervals (CIs). Among 3090 eligible adults, 1562 (50.6%) were enrolled. Of the 1515 with influenza vaccination history available, 701 (46.2%) had received vaccination during that season. Influenza was identified in 37 (5.3%) vaccinated versus 78 (9.6%) unvaccinated participants. After adjustment for age, race/ethnicity, immunosuppression, month, and season, pooled VE for any influenza-related hospitalization in the eligible study population was 63.1% (95% CI, 43.8-75.8%). Adjusted VE against influenza-related hospitalization for ARI in adults ≥50 years was 55.9% (29.9-72.3%) and adjusted VE against influenza-related CHF/COPD exacerbation in adults ≥18 years was 80.3% (36.3-93.9%). Influenza vaccination was effective in preventing influenza-related hospitalizations in adults aged ≥50 years and those with CHF/COPD exacerbations during the 2018-2020 seasons.

Percent Recovery Index Predicts Poor Asthma Control and Exacerbation in Adults.

Previous studies indicate that the percent recovery index (PRI: the percentage increase from the maximally reduced FEV1 after bronchodilator inhalation), one of the indexes of methacholine bronchial provocation, may predict acute asthma exacerbations in childhood and elderly asthmatics. It is known that childhood (<12) and elder (>60) asthmatics may be different to adult patients in many aspect including prognosis. However, in adults, a research for predicting value of PRI to exacerbation is still absence. Besides exacerbation, predicting value of PRI to poor asthma control is also unknown. We try to detect whether PRI can predict poor asthma control and exacerbation in adults in this research. Meanwhile, we try to detect whether treatment can influence PRI. In 61 adults with asthma, baseline PRI was measured during enrollment. And then baseline PRI was evaluated as a predictor of exacerbation or poor asthma control at an upcoming 3-month follow-up. The covariates included age, sex, BMI, previous exacerbation, smoking status and baseline lung function. After treatment for 3 months, PRI was measured again and compared with baseline PRI. After the 3-month follow-up, we found that baseline PRI was significantly related to asthma exacerbation (P = 0.023), poor asthma control (ACT at 3 months, P = 0.014), decreased quality of life (decrease of MiniAQLQ, P = 0.010) and cumulative number of EDHO at 3 months (P = 0.039). Meanwhile, no significant correlation was observed between baseline PRI and inflammation factors (FENO, CaNO, and EOS). Finally, PRI was dramatically reduced after standard treatment for 3 months. PRI is efficient in the prediction of poor asthma control and exacerbation in adults. The predictive value of PRI may rely on the inherent property of asthmatic airway smooth muscle (ASM) independent of inflammation factors. Effective treatment can alleviate PRI dramatically and that indicate PRI may also be valuable in evaluation of curative effect.

The association of varying treatment thresholds of mepolizumab on asthma exacerbations in adults

Background. Asthma has a high healthcare burden globally, with up to 10% of the asthma population suffering from severe disease. Biologic agents are a newer class of asthma treatments for severe asthma, with good evidence for efficacy in clinical trials. Nevertheless, real-world studies of its impact on clinical outcomes are limited. Methods. This is an observational cohort study using administrative claims data. The study population consisted of patients aged ≥18 years who had a diagnosis of asthma and initiated mepolizumab after November 4, 2015 and had continuous medical and drug coverage in both the 365 days prior to and following mepolizumab initiation. In patients treated with mepolizumab, we described clinically significant asthma exacerbations by minimum continuous treatment thresholds following initiation of mepolizumab, medication switching patterns and chronic oral corticosteroid (≥28 days) use. Results. We identified 2,536 adults with asthma who initiated mepolizumab. There was an association toward reduction in severe asthma-related events over the first one year of exposure. We observed associations with reduced dispensings of oral corticosteroids over the first year after mepolizumab initiation. Very few patients switched to other biologics during the study period. Conclusions. Treatment with mepolizumab may be associated with fewer asthma-related events in the first year. Over the first one year after initiating mepolizumab, we found associations with decreased concomitant dispensings of oral corticosteroids and medium to high dose ICS/LABA. Additionally, most patients who initiated mepolizumab did not switch to other biologics.

Clinical and immune-related factors associated with exacerbation in adults with well-controlled generalized myasthenia gravis.

To describe the clinical predictors and immune-related factors for exacerbation in adults with well-controlled generalized myasthenia gravis (GMG). We conducted a retrospective analysis of 585 adults with well-controlled GMG from our institution to explore the risk factors for exacerbation. Furthermore, propensity score matching (PSM) was used to compare the proportions of lymphocyte subsets, and the levels of immunoglobulin, complement, and anti-acetylcholine receptor antibody (AChR-ab) in the peripheral blood of 111 patients with exacerbations and 72 patients without exacerbations. A total of 404 patients (69.1%) experienced at least one exacerbation, and the median (interquartile range) time to the first exacerbation was 1.5 years (0.8-3.1 years). Multivariable Cox regression analysis showed that age at onset, disease duration before enrollment, Myasthenia Gravis Foundation of America classification (MGFA) class III vs. class II, MGFA class IV-V vs. class II, AChR-ab levels, anti-muscle specific kinase antibody levels, thymus hyperplasia, prednisone plus immunosuppressants vs. prednisone treatment, and thymectomy were independent predictors for exacerbations [hazard ratio (HR) = 1.011, 1.031, 1.580, 1.429, 2.007, 2.033, 1.461, 0.798, and 0.651, respectively]. Propensity-matched analysis compared 51 patient pairs. After PSM, the peripheral blood proportions of CD3-CD19+ B cells, ratios of CD3+CD4+/CD3+CD8+ T cells, and AChR-ab levels were significantly increased, and the peripheral blood proportions of CD3+CD8+ T and CD4+CD25+CD127low+ regulatory T cells (Tregs) were significantly lower in patients with exacerbation than in those without exacerbation (all p < 0.05). Myasthenia gravis (MG) exacerbations were more frequent in those patients with older onset age, longer disease duration, more severe MGFA classification, positive AChR-ab, and lack of combined immunotherapy or thymectomy treatment. On the other hand, CD3-CD19+ B cells, CD3+CD8+ T cells, Tregs, and AChR-ab in peripheral blood may be involved in the course of GMG exacerbation.

Asthma control and care among six public health clinic attenders in Malaysia: A cross-sectional study.

Asthma is common in Malaysia but neglected. Achieving optimal asthma control and care is a challenge in the primary care setting. In this study, we aimed to identify the risk factors for poor asthma control and pattern of care among adults and children (5-17 years old) with asthma attending six public health clinics in Klang District, Malaysia. We conducted a cross-sectional study collecting patients' sociodemographic characteristics, asthma control, trigger factors, healthcare use, asthma treatment, and monitoring and use of asthma action plan. Descriptive statistics and stepwise logistic regression were used in data analysis. A total of 1280 patients were recruited; 85.3% adults and 14.7% children aged 5-17 years old. Only 34.1% of adults had well-controlled asthma, 36.5% had partly controlled asthma, and 29.4% had uncontrolled asthma. In children, 54.3% had well-controlled asthma, 31.9% had partly controlled, and 13.8% had uncontrolled asthma. More than half had experienced one or more exacerbations in the last 1 year, with a mean of six exacerbations in adults and three in children. Main triggers for poor control in adults were haze (odds ratio [OR] 1.51; 95% confidence interval [CI] 1.13-2.01); cold food (OR 1.54; 95% CI 1.15-2.07), extreme emotion (OR 1.90; 95% CI 1.26-2.89); air-conditioning (OR 1.63; 95% CI 1.20-2.22); and physical activity (OR 2.85; 95% CI 2.13-3.82). In children, hot weather (OR 3.14; 95% CI 1.22-8.11), and allergic rhinitis (OR 2.57; 95% CI 1.13-5.82) contributed to poor control. The majority (81.7% of adults and 64.4% of children) were prescribed controller medications, but only 42.4% and 29.8% of the respective groups were compliant with the treatment. The importance of an asthma action plan was reported less emphasized in asthma education. Asthma control remains suboptimal. Several triggers, compliance to controller medications, and asthma action plan use require attention during asthma reviews for better asthma outcomes.

Short-term exposure to ozone and asthma exacerbation in adults: A longitudinal study in China.

The relationships between short-term ozone exposure and the acute exacerbations of asthma in adults have not been fully studied. Existing studies commonly ignored the effects of ozone on mild or early asthma exacerbations. To investigate the associations between short-term ozone exposure and asthma exacerbations in Chinese adults. We administered health management for adult asthma patients through the Respiratory Home Platform and required them to monitor their lung function every morning and evening by themselves. Finally, a total of 4,467 patients in 18 Chinese cities were included in the current analyses, with 79,217 pairs of lung function records. The maximum daily 8-h average ozone concentrations were collected from fixed-site air quality monitoring stations. We calculated diurnal peak expiratory flow (PEF) variation using morning and evening measurements of PEF and then defined different severity of asthma exacerbations with diurnal PEF variations >10, 15, and 20%, respectively. A binomial distributed generalized additive mixture model combined with distribution non-linear models was applied to examine the association of ozone with asthma exacerbations. We further conducted stratified analyses by sex, age, season of lung function tests, and region. We found that short-term ozone exposure was independently associated with an elevated risk of asthma exacerbations defined by lung function and the effects could last for about 2 days. At lag 0-2 days, each 10 μg/m3 increment in ozone concentration was associated with odds ratios of 1.010 [95% confidence interval (CI): 1.003, 1.017], 1.014 (95% CI: 1.005, 1.023), and 1.017 (95% CI: 1.006, 1.028) for asthma exacerbations that were defined by diurnal PEF variation over 10, 15, and 20%, respectively. The associations remained significant after adjusting for other pollutants, and became unstable when using 24-h average ozone concentration. We also found that the associations were relatively stronger in males, those aged 45 years and older, and in the warm season. Our results suggest that short-term ozone exposure can increase the risk of asthma exacerbations, even in the early stage of exacerbation. Male and older asthma patients may be more vulnerable to ozone air pollution, especially in the warm season.

Association between cold weather, influenza infection, and asthma exacerbation in adults in Hong Kong.

Despite a conspicuous exacerbation of asthma among patients hospitalized due to influenza infection, no study has attempted previously to elucidate the relationship between environmental factors, influenza activity, and asthma simultaneously in adults. In this study, we examined this relationship using population-based hospitalization records over 22 years. Daily numbers of hospitalizations due to asthma in adults of 41 public hospitals in Hong Kong during 1998-2019 were obtained. The data were matched with meteorological records and air pollutant concentrations. We used type-specific and all-type influenza-like illness plus (ILI+) rates as proxies for seasonal influenza activity. Quasi-Poisson generalized additive models together with distributed-lag non-linear models were used to examine the association. A total of 212,075 hospitalization episodes due to asthma were reported over 22 years. The cumulative adjusted relative risk (ARR) of asthma hospitalizations reached 1.15 (95 % confidence interval [CI], 1.12-1.18) when the ILI+ total rate increased from zero to 20.01 per 1000 consultations. Compared with the median temperature, a significantly increased risk of asthma hospitalization (cumulative ARR = 1.10, 95 % CI, 1.05-1.15) was observed at the 5th percentile of temperature (i.e., 14.6 °C). Of the air pollutants, oxidant gas was significantly associated with asthma, but only at its extreme level of concentrations. In conclusion, cold conditions and influenza activities are risk factors to asthma exacerbation in adult population. Influenza-related asthma exacerbation that appeared to be more common in the warm and hot season, is likely to be attributable to influenza A/H3N2. The heavy influence of both determinants on asthma activity implies that climate change may complicate the asthma burden.

Immunostimulants versus placebo for preventing exacerbations in adults with chronic bronchitis or chronic obstructive pulmonary disease.

Immunostimulants versus placebo for preventing exacerbations in adults with chronic bronchitis or chronic obstructive pulmonary disease.

Effects of COVID-19 and Social Distancing on Rhinovirus Infections and Asthma Exacerbations.

Since their discovery in the 1950s, rhinoviruses (RVs) have been recognized as a major causative agent of the "common cold" and cold-like illnesses, accounting for more than 50% of upper respiratory tract infections. However, more than that, respiratory viral infections are responsible for approximately 50% of asthma exacerbations in adults and 80% in children. In addition to causing exacerbations of asthma, COPD and other chronic lung diseases, RVs have also been implicated in the pathogenesis of lower respiratory tract infections including bronchiolitis and community acquired pneumonia. Finally, early life respiratory viral infections with RV have been associated with asthma development in children. Due to the vast genetic diversity of RVs (approximately 160 known serotypes), recurrent infection is common. RV infections are generally acquired in the community with transmission occurring via inhalation of aerosols, respiratory droplets or fomites. Following the outbreak of coronavirus disease 2019 (COVID-19), exposure to RV and other respiratory viruses was significantly reduced due to social-distancing, restrictions on social gatherings, and increased hygiene protocols. In the present review, we summarize the impact of COVID-19 preventative measures on the incidence of RV infection and its sequelae.

265 Predicting exacerbation in adults with cystic fibrosis using a 1-minute sit-to-stand test

265 Predicting exacerbation in adults with cystic fibrosis using a 1-minute sit-to-stand test

Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2): a randomised, double-blind, placebo-controlled, parallel-group trial

Black and Hispanic children living in urban environments in the USA have an excess burden of morbidity and mortality from asthma. Therapies directed at the eosinophilic phenotype reduce asthma exacerbations in adults, but few data are available in children and diverse populations. Furthermore, the molecular mechanisms that underlie exacerbations either being prevented by, or persisting despite, immune-based therapies are not well understood. We aimed to determine whether mepolizumab, added to guidelines-based care, reduced the number of asthma exacerbations during a 52-week period compared with guidelines-based care alone. This is a randomised, double-blind, placebo-controlled, parallel-group trial done at nine urban medical centres in the USA. Children and adolescents aged 6-17 years, who lived in socioeconomically disadvantaged neighbourhoods and had exacerbation-prone asthma (defined as ≥two exacerbations in the previous year) and blood eosinophils of at least 150 cells per μL were randomly assigned 1:1 to mepolizumab (6-11 years: 40 mg; 12-17 years: 100 mg) or placebo injections once every 4 weeks, plus guideline-based care, for 52 weeks. Randomisation was done using a validated automated system. Participants, investigators, and the research staff who collected outcome measures remained masked to group assignments. The primary outcome was the number of asthma exacerbations that were treated with systemic corticosteroids during 52 weeks in the intention-to-treat population. The mechanisms of treatment response were assessed by study investigators using nasal transcriptomic modular analysis. Safety was assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03292588. Between Nov 1, 2017, and Mar 12, 2020, we recruited 585 children and adolescents. We screened 390 individuals, of whom 335 met the inclusion criteria and were enrolled. 290 met the randomisation criteria, were randomly assigned to mepolizumab (n=146) or placebo (n=144), and were included in the intention-to-treat analysis. 248 completed the study. The mean number of asthma exacerbations within the 52-week study period was 0·96 (95% CI 0·78-1·17) with mepolizumab and 1·30 (1·08-1·57) with placebo (rate ratio 0·73; 0·56-0·96; p=0·027). Treatment-emergent adverse events occurred in 42 (29%) of 146 participants in the mepolizumab group versus 16 (11%) of 144 participants in the placebo group. No deaths were attributed to mepolizumab. Phenotype-directed therapy with mepolizumab in urban children with exacerbation-prone eosinophilic asthma reduced the number of exacerbations. US National Institute of Allergy and Infectious Diseases and GlaxoSmithKline.

Impact and treatment of exacerbations in adults with bronchiectasis.

Exacerbations have a negative impact on inflammatory diseases of the airways and, in patients with bronchiectasis, severe exacerbations are associated with increased morbidity and mortality. Exacerbations are also associated with a decline in quality of life and lung function, greater local and systemic inflammation and clinically more severe forms of the disease. As a consequence, the majority of therapeutic clinical trials carried out in patients with bronchiectasis are aimed at preventing exacerbations, but there is a scarcity of scientific evidence on the best treatment once they occur. All of these elements, combined with the great heterogeneity of bronchiectasis and the influence of geographical and microbiological factors on its clinical presentations and aetiologies, mean that the recommendations of therapeutic guidelines vary. An international group of experts has now reached agreement on the definition of exacerbation in bronchiectasis for the inclusion of patients in clinical trials, although its validity in clinical practice has yet to be demonstrated.

Nebulizer versus metered dose inhaler with space chamber (MDI spacer) for acute asthma and chronic obstructive pulmonary disease (COPD) exacerbation: attitudes of patients and healthcare providers in the COVID-19 era

Objective Short-acting bronchodilators for asthma and chronic obstructive pulmonary disease (COPD) exacerbations are commonly delivered by nebulizers although administration using metered dose inhaler with space chamber (MDI spacer) has been shown to be equally efficacious. There are few studies examining patients’ and healthcare providers’ attitudes on the 2 administration methods in adults. This study explores patients’ and healthcare providers’ attitudes on the use of nebulizer versus MDI spacer for acute asthma and COPD exacerbations in adults. Methods Patients admitted for asthma or COPD exacerbations, doctors and nurses in a university-affiliated hospital were surveyed from 1 April 2021 to 30 Sept 2021 regarding their views on the effectiveness, ease of use, preparation and administration, side effects, and infection risk of the 2 administration methods. Results Ninety-nine patients, 103 doctors and 650 nurses completed the survey. 60.6% of patients perceived nebulizer to be more effective. Patients who found nebulizer more comfortable were more likely to prefer nebulizer (OR 43.97, p = 0.01), while those who associated it with a greater infection risk were less likely to prefer nebulizer (OR 0.15, p = 0.03). 49.5% of doctors and 49.1% of nurses perceived nebulizer to be more effective, compared to 10.7% and 34.5%, respectively, for MDI spacer. Effectiveness and patient comfort influenced doctors’ and nurses’ preference for nebulizer while ease of preparation and administration influenced nurses’ preference only. Conclusions Patients and healthcare providers perceived nebulizer to be more effective. Factors unique to each group influenced their preference for nebulizer.