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BACKGROUND: Limited data exist on the relative impact of moderate and severe exacerbations on asthma control and impairment. OBJECTIVE: To explore data from the CAPTAIN trial to evaluate the relationship between first moderate or severe exacerbation and changes in lung function, symptoms, physical activity limitation scores, and short-acting ß2-agonist (SABA) usage to determine the clinical relevance of moderate events. METHODS: CAPTAIN was a phase IIIA 24- to 52-week, multicenter, international, randomized controlled trial evaluating efficacy and safety of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI in patients with uncontrolled asthma on inhaled corticosteroid/long-acting ß2-agonist. Outcomes reported include first postrandomization exacerbation event by severity (wk 1-52), frequency and duration of moderate and severe exacerbations, and time course of changes over ± 14-day peri-exacerbation period for lung function, symptoms, limitations, and SABA use. RESULTS: Of the intent-to-treat population (n = 2,436), 550 patients (23%) continued to 52 weeks. There were 529 moderate and 546 severe exacerbations. Lung function changes were similar, but symptom, physical activity limitation scores, and SABA use were higher, for severe versus moderate exacerbations. Lung function decline preceded increases in symptom, physical activity limitation scores, and SABA use, irrespective of exacerbation severity. Lung function variables, limitation scores, and SABA use returned to pre-exacerbation baseline after approximately 8 to 12 days for both exacerbation severities. CONCLUSIONS: Whereas severe events were associated with greater impact on symptoms, physical activity limitations, and SABA use, onset and time to resolution were generally similar for moderate and severe events. Both exacerbation severities represent clinically important deteriorations comprising clinical and functional changes.

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INTRODUCTION: Despite adherence to inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) therapy, many patients with asthma experience moderate exacerbations. Data on the impact of moderate exacerbations on the healthcare system are limited. This study assessed the frequency and economic burden of moderate exacerbations in patients receiving ICS/LABA. METHODS: Retrospective, longitudinal study analyzed data from Optum's de-identified Clinformatics® Data Mart Database recorded between October 1, 2015, and December 31, 2019. Eligibility criteria included patients ≥18 years of age with ≥1 ICS/LABA claim and ≥1 medical claim for asthma in the 12 months pre-index (first ICS/LABA claim). Primary objectives included describing moderate exacerbation frequency, and associated healthcare resource utilization (HRU) and costs. A secondary objective was assessing the relationship between moderate exacerbations and subsequent risk of severe exacerbations. Patients were stratified by moderate exacerbation frequency in the 12 months post index. Moderate exacerbations were identified using a newly developed algorithm. RESULTS: In the first 12 months post index 61.6% of patients experienced ≥1 moderate exacerbation. Mean number of asthma-related visits was 4.1 per person/year and median total asthma-related costs was $3544. HRU and costs increased with increasing exacerbation frequency. Outpatient and inpatient visits accounted for a similar proportion of these costs. Moderate exacerbations were associated with an increased rate and risk of future severe exacerbations (incidence rate ratio, 1.56; hazard ratio, 1.51 [both p < 0.001]). CONCLUSIONS: This study highlighted that a high proportion of patients continue to experience moderate exacerbations despite ICS/LABA therapy and subsequently experience increased economic burden and risk of future severe exacerbations.

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BACKGROUND: Exacerbation frequency strongly influences treatment choices in patients with severe asthma. RESEARCH QUESTION: What is the extent of the variability of exacerbation rate across countries and its implications in disease management? STUDY DESIGN AND METHODS: We retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients aged ≥ 18 years who did not initiate any biologics prior to baseline visit. A severe exacerbation was defined as the use of oral corticosteroids for ≥ 3 days or asthma-related hospitalization/ED visit. A series of negative binomial models were applied to estimate country-specific severe exacerbation rates during 365 days of follow-up, starting from a naive model with country as the only variable to an adjusted model with country as a random-effect term and patient and disease characteristics as independent variables. RESULTS: The final sample included 7,510 patients from 17 countries (56% from the United States), contributing to 1,939 severe exacerbations (0.27/person-year). There was large between-country variation in observed severe exacerbation rate (minimum, 0.04 [Argentina]; maximum, 0.88 [Saudi Arabia]; interquartile range, 0.13-0.54), which remained substantial after adjusting for patient characteristics and sampling variability (interquartile range, 0.16-0.39). INTERPRETATION: Individuals with similar patient characteristics but coming from different jurisdictions have varied severe exacerbation risks, even after controlling for patient and disease characteristics. This suggests unknown patient factors or system-level variations at play. Disease management guidelines should recognize such between-country variability. Risk prediction models that are calibrated for each jurisdiction will be needed to optimize treatment strategies.

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Introduction Wheezing is common in preschool-aged children, affecting about half of all children within their first six years of life. Children who have recurrent wheezing experience disease-related morbidity, including increased emergency visits and hospitalizations. Early-life lower respiratory tract viral infections are linked to recurrent wheezing and eventual asthma onset. Identifying high-risk children is crucial, with the frequency and severity of wheezing episodes being good predictors of long-term outcomes. Aim To identify predictors of severe exacerbations in children with recurrent wheezing. Methods We conducted a retrospective cohort study involving 168 pediatric patients with recurrent wheezing followed up at our outpatient clinic. The outcome of interest was the occurrence of a severe exacerbation, defined as any exacerbation requiring hospitalization and the need for supplemental oxygenation or ventilatory support. Results The median age of the first wheezing exacerbation was five months, with a predominance of the male gender. Approximately two-thirds of the patients had a family history of atopy. Comorbid allergic rhinitis and atopic dermatitis were present in 15.4% and 16.7% of patients, respectively. Twenty percent of patients had a severe wheezing exacerbation as the first form of presentation, and 30% presented at least one severe exacerbation from the first presentation to the last follow-up. Patients with severe exacerbations were younger at the first episode (median age 4 months, IQR 2-7, versus 7 months, IQR 4-12, p=0.027) and more frequently had a family history of atopy (71.7% versus 55.6%, p=0.050). In this cohort, patients who initially presented with a severe episode are at increased risk of incident severe exacerbations during follow-up, HR 2.24 (95%CI 1.01-4.95). Conclusions We know that the severity of exacerbations in children with recurrent wheezing correlates with the long-term outcomes of the disease. Therefore, preventing severe exacerbations can positively impact the prognosis of these patients. In this analysis, we found independent predictors of severe exacerbations to be the first clinical episode before the age of three months and a family history of atopy. We also found that patients whose initial presentation was severe have a higher risk of new severe exacerbations. Therefore, these subgroups of patients should be closely monitored by pediatricians.

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Chronic obstructive pulmonary disease (COPD) affects more than 200 million people worldwide. The chronic course of COPD is frequently worsened by acute exacerbations (AECOPD). Mortality in patients hospitalized for severe AECOPD remains dramatically high, and the underlying mechanisms are poorly understood. Lung microbiota is associated with COPD outcomes in nonsevere AECOPD, but no study specifically investigated severe AECOPD patients. The aim of this study is thus to compare lung microbiota composition between severe AECOPD survivors and nonsurvivors. Induced sputum or endotracheal aspirate was collected at admission from every consecutive severe AECOPD patient. After DNA extraction, the V3-V4 and ITS2 regions were amplified by PCR. Deep-sequencing was performed on a MiSeq sequencer (Illumina); the data were analyzed using DADA2 pipeline. Among 47 patients admitted for severe AECOPD, 25 (53%) with samples of sufficient quality were included: 21 of 25 (84%) survivors and 4 of 25 (16%) nonsurvivors. AECOPD nonsurvivors had lower α-diversities indices than survivors for lung mycobiota but not for lung bacteriobiota. Similar results were demonstrated comparing patients receiving invasive mechanical ventilation (n = 13 [52%]) with those receiving only noninvasive ventilation (n = 12 [48%]). Previous systemic antimicrobial therapy and long-term inhaled corticosteroid therapy could alter the lung microbiota composition in severe AECOPD patients. In acidemic AECOPD, lower lung mycobiota α-diversity is linked to the severity of the exacerbation, assessed by mortality and the requirement for invasive mechanical ventilation, whereas lung bacteriobiota α-diversity is not. This study encourages a multicenter cohort study investigating the role of lung microbiota, especially fungal kingdom, in severe AECOPD. IMPORTANCE In AECOPD with acidemia, more severe patients-i.e., nonsurvivors and patients requiring invasive mechanical ventilation-have lower lung mycobiota α-diversity than survivors and patients receiving only noninvasive ventilation, respectively. This study encourages a large multicenter cohort study investigating the role of lung microbiota in severe AECOPD and urges investigation of the role of the fungal kingdom in severe AECOPD.

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Background: To evaluate the association of elevated blood glucose with the risk of acute exacerbations in patients with chronic obstructive pulmonary disease (COPD). Methods: Totally 526 consecutive patients with COPD recruited between Jan. 2018 and July 2019 were included in this study. Based on the American Diabetes Association's Standards of Care, these patients were divided into three groups according to HbA1c level: low HbA1c level (HbA1c <5.7%, n=204), moderate HbA1c level (HbA1c 5.7-6.4%, n=165), and high HbA1c level (HbA1c ≥6.5%, n=157). All subjects were followed up for 18 months. Multivariate Cox regression analysis was used to evaluate the predicting value of HbA1c for the time of the next COPD severe exacerbation. Results: Totally 141 (26.8%) patients in the study had at least 1 severe exacerbation. The proportion of patients suffering from at least 1 severe exacerbation was significantly higher (P<0.01) for patients with high (36.3%) and moderate HbA1c levels (25.5%) compared to those with low HbA1c levels (20.6%). Multivariate Cox regression analysis indicated that high (HR=2.74, 95% CI: 1.70-4.41; P<0.01) and moderate HbA1c levels (HR=2.19, 95% CI: 1.39-3.46; P<0.01) were significantly associated with a higher risk of the next severe exacerbation compared with low HbA1c level, after controlling for potential confounders including age, gender, body mass index (BMI), smoking status, disease duration of COPD, frequency of hospitalization due to acute exacerbation of COPD (AECOPD) in the past 12 months, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages, COPD assessment test (CAT) score, corticosteroids use, hypertension, and cardiovascular diseases. Subgroup analyses also indicated a significant association between HbA1c levels and risk of the next severe exacerbation in different GOLD stages and diabetes status. Conclusion: Elevated blood glucose, no matter with or without diabetes, is significantly associated with a higher risk of the next severe exacerbation for patients with COPD.

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Background: Long-acting beta-agonists (LABA) and long-acting muscarinic antagonists (LAMA) combination therapy improved lung function and health-related quality-of-life and reduced exacerbation rates and dyspnea in symptomatic chronic obstructive pulmonary disease (COPD) patients. We compared the real-world effects of three fixed-dose LABA/LAMA combinations for COPD in Taiwan. Methods: This multicenter, retrospective study evaluated 1-year outcomes after LABA/LAMA combination therapy in patients with symptomatic COPD. Exacerbations and symptoms of COPD, lung functions, and therapy escalation were compared among patients using tiotropium/olodaterol, umeclidinium/vilanterol and indacaterol/glycopyrronium. Propensity score matching (PSM) was applied to balance the baseline characteristics. Results: Data of 1,617 patients were collected. After PSM, time to first moderate-to-severe COPD exacerbation was comparable among three groups, while the annualized rates of the exacerbation (episodes/patient/year) in patients receiving tiotropium/olodaterol (0.19) or umeclidinium/vilanterol (0.17) were significantly lower than those receiving indacaterol/glycopyrronium (0.38). COPD-related symptoms were stable over the treatment period, and there was no significant difference in the changes of symptom scores including CAT and mMRC among three groups at the end of the study period. Conclusion: This study presented valuable real-world outcome in terms of exacerbation and treatment response of COPD patients treated with fixed-dose LABA/LAMA regimens in Taiwan. The annualized rates of moderate-to-severe exacerbation in patients receiving tiotropium/olodaterol or umeclidinium/vilanterol were significantly lower than those receiving indacaterol/glycopyrronium, though the time to first moderate-to-severe exacerbation was similar among different fixed-dose LABA/LAMA combinations.

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OBJECTIVE: Uncontrolled asthma is associated with higher risk of hospital admissions and death. Low adherence to inhaled corticosteroid (ICS), the cornerstone of asthma therapy, is well-documented. Our aim was to investigate if hospital admission with an acute exacerbation of asthma changes ICS adherence. METHODS: This retrospective cohort study comprises 241 patients hospitalized with an asthma exacerbation over 12 months (May 2019-April 2020). The primary outcome was proportion of ICS adherent patients, defined as Medication Possession Ratio (MPR) ≥80%, in the six-month period before and after admission. RESULTS: The pre- to post-admission proportion of ICS adherent patients increased from 10% to 13% (p = 0.25) and the mean ICS MPR increased from 34% to 42% (p < 0.001). Different patterns of post-discharge adherence were observed, as adherent patients remained adherent, while patients with poor pre-admission adherence increased their adherence during two months after discharge followed by a decline in MPR. Co-variates such as sex, age, body mass index (BMI), GINA 2020-treatment step did not predict improvement in adherence after discharge. CONCLUSIONS: Admission with an asthma exacerbation did not increase the proportion of patients adherent with controller medication, primarily ICS. Although an improvement in adherence was initially seen primarily in previously poorly adherent patients, this increase was transient as it decreased over time post-discharge.

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Objetivo: Estimar en una cohorte de pacientes diagnosticados de EPOC y diabetes la incidencia de hospitalizaciones por exacerbación grave de la EPOC y sus factores asociados. Diseño: Estudio prospectivo de cohorte. Emplazamiento: Centros de Atención Primaria de Lleida ciudad (en total 7 centros). Participantes: Se estudiaron 761 pacientes codiagnosticados de EPOC y diabetes. Los criterios de inclusión fueron pacientes de ambos sexos, igual o mayores de 40 años, residentes en el área geográfica de Lleida ciudad, con el diagnóstico de EPOC según los criterios de la guía GOLD, con espirometría reciente y una fracción FEV1/FVC <0,7; diagnosticados de DM2 según la guía de la International Diabetes Federation. Los criterios de exclusión fueron padecer alguna enfermedad física o psíquica grave. Mediciones principales: Las variables del estudio fueron: el sexo, la edad, su área básica de salud en Lleida, índice de masa corporal, perímetro de cintura, hábito tabáquico y enólico, hipertensión arterial, insuficiencia cardiaca, insuficiencia renal crónica, FEV1, FEV1/FVC, categorización GOLD, HbA1c. Se registró la vacuna antigripal y antineumocócica. La variable dependiente fue la exacerbación grave. En el análisis estadístico la asociación de la variable dependiente con las variables independientes se determinó mediante el cálculo de la hazard ratio (HR) con el intervalo de confianza del 95%. La HR se estimó de forma ajustada mediante modelos de regresión de Cox no condicional. Resultados: La incidencia de hospitalización por exacerbación grave de la EPOC fue del 9,98%; se objetivó un aumento del riesgo de exacerbación grave en pacientes diagnosticados de insuficiencia cardiaca (HR=2,27; p=0,002), y con una menor fracción de FEV1/FVC. La vacuna antigripal y antineumocócica presentaron un papel protector débil sin ser estadísticamente significativa.(AU)

Objective: To estimate the incidence of hospitalizations for severe exacerbation of chronic obstructive pulmonary disease (COPD) and its associated factors in a cohort of patients diagnosed with COPD and diabetes type 2. Design: Prospective cohort study. Site: Primary care centres of Lleida city (7 centres totally). Participants: Based on a sample of 716 patients diagnosed by COPD and diabetes. The inclusion criteria was carried out by patients of both genders, equal to or older than 40 years, ordinarily residents in the geographical area of Lleida city, with the diagnosis of COPD according to GOLD guideline, with recent spirometry and FEV1/FVC ratio <0.7; diagnosed with diabetes type 2 according to the guidelines of the International Diabetes Federation. The exclusion criteria were suffering from a serious physical or mental illness. Main measurements: The study variables were comprised by gender, age, primary care centre of Lleida, body mass index, waist circumference, smoking and enolic habit, blood pressure, heart failure, chronic renal failure, FEV1, FEV1/FVC, GOLD categorization, glycosylated haemoglobin (HbA1c). There were registered by influenza and pneumococcal vaccine. The dependent variable was severe exacerbation. In statistical analysis, the association of the dependent variable with the independent variables was determined by calculating the Hazard ratio (HR) with the 95% confidence interval. HR was estimated in an adjusted way by using unconditional Cox regression model. Results: The incidence for severe exacerbation of COPD was 9.98%; that means that an increased risk of severe exacerbation was registered in patients diagnosed with heart failure (HR=2.27; p=.002), and with lower FEV1/FVC ratio. The influenza and pneumococcal vaccines provided weak protection to prevent exacerbations, however it was not statistically significant.(AU)

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A large proportion of asthmatic patients are treated with protocols resulting from data obtained by randomized controlled trials (RCTs) for which they would not have been eligible. Therefore, the aim of this study was to undertake a quantitative synthesis on real-world evidence comparing single inhaled corticosteroid (ICS)/formoterol maintenance and reliever therapy (SMART) and maintenance ICS/long-acting ß2-adrenoceptor agonist (LABA) + as-needed short-acting ß2-adrenoceptor agonist (SABA). A network meta-analysis of real-world studies was performed to compare SMART with ICS/LABA + as-needed SABA therapies in asthmatic patients. The surface under the cumulative ranking curve analysis was used to rank efficacy. The posterior probability distribution was reported as 95% credible interval (95%CrI). Data of 11,360 asthmatic patients were extracted from 6 studies. SMART including an ICS at medium-dose (MD) was more effective than MD ICS/LABA FDC + as-needed SABA (RR 0.54 95%CrI 0.42-0.69; P < 0.001) and low-dose (LD) SMART (RR 0.82 95%CrI 0.70-0.95; P < 0.05) against severe asthma exacerbation. MD SMART improved the Asthma Control Questionnaire score more than MD ICS/LABA FDC + as-needed SABA (delta effect -0.33 95%CrI -0.62 to -0.01; P < 0.05). The efficacy rank was: MD SMART > LD SMART > ICS + LABA free combination + as-needed SABA > ICS/LABA FDC + as-needed SABA > MD ICS/LABA FDC + as-needed SABA. The findings of this network meta-analysis of real-world evidence, and concordance with the effect estimates resulting from previous meta-analyses of RCTs, suggest that SMART may represent the preferred therapeutic option to reduce the risk of severe exacerbation in adults with moderate to severe asthma.

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PURPOSE: Chronic obstructive pulmonary disease (COPD) is a risk factor for acquiring multiple drug resistant bacteria. The main objective of this analysis was to question a beneficial outcome in the routine use of antipseudomonal antibiotics in the empiric treatment of severe AECOPD in Intensive Care Unit patients. MATERIAL AND METHODS: We report a retrospective, observational cohort study in adult patients with severe AECOPD admitted to ICU at a tertiary care university hospital. Antibiotic treatment on admission as well as microbiology samples were analyzed. The influence of SOFA score at admission, age, sex and antibiotic choice upon survival was investigated by multivariable analysis. RESULTS: 437 patients were included. Mean age was 68 years (±10), 46.5% were female. 271/437 patients (62%) were initially treated with antibiotics covering Pseudomonas aeruginosa. Overall, positive microbiology samples were found in 107 patients (24.5%). P. aeruginosa was only found in 3.7%. There was no significant difference in 30-day ICU mortality after adjusting for age, sex and severity of illness (20.4% ± 11.6 in patients with Pseudomonas inactive antibiotics versus 29.3% ± 10.8 in patients with PAA, p=0.113). CONCLUSIONS: Empiric use of antipseudomonal antibiotics did not result in improved ICU survival in this retrospective analysis.

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OBJECTIVE: To estimate the incidence of hospitalizations for severe exacerbation of chronic obstructive pulmonary disease (COPD) and its associated factors in a cohort of patients diagnosed with COPD and diabetes type 2. DESIGN: Prospective cohort study. SITE: Primary care centres of Lleida city (7 centres totally). PARTICIPANTS: Based on a sample of 716 patients diagnosed by COPD and diabetes. The inclusion criteria was carried out by patients of both genders, equal to or older than 40 years, ordinarily residents in the geographical area of Lleida city, with the diagnosis of COPD according to GOLD guideline, with recent spirometry and FEV1/FVC ratio <0.7; diagnosed with diabetes type 2 according to the guidelines of the International Diabetes Federation. The exclusion criteria were suffering from a serious physical or mental illness. MAIN MEASUREMENTS: The study variables were comprised by gender, age, primary care centre of Lleida, body mass index, waist circumference, smoking and enolic habit, blood pressure, heart failure, chronic renal failure, FEV1, FEV1/FVC, GOLD categorization, glycosylated haemoglobin (HbA1c). There were registered by influenza and pneumococcal vaccine. The dependent variable was severe exacerbation. In statistical analysis, the association of the dependent variable with the independent variables was determined by calculating the Hazard ratio (HR) with the 95% confidence interval. HR was estimated in an adjusted way by using unconditional Cox regression model. RESULTS: The incidence for severe exacerbation of COPD was 9.98%; that means that an increased risk of severe exacerbation was registered in patients diagnosed with heart failure (HR=2.27; p=.002), and with lower FEV1/FVC ratio. The influenza and pneumococcal vaccines provided weak protection to prevent exacerbations, however it was not statistically significant. CONCLUSION: It documents a significant incidence of exacerbation in patients diagnosed with DM2 and COPD. Heart failure and a lower FEV1/FVC could increase the exacerbation risk.

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PURPOSE: Frequent exacerbators are a specific phenotype of chronic obstructive pulmonary disease (COPD), whose clinical characteristics and prognostic biomarkers during severe acute exacerbation (AECOPD) have not yet been fully elucidated. The aim of this study was to investigate the clinical features of severe AECOPD in frequent exacerbators and explore the predictive value of the neutrophil-to-lymphocyte ratio (NLR) for outcome in this phenotype during severe exacerbation. PATIENTS AND METHODS: A total of 604 patients with severe AECOPD were retrospectively included in the study. Subjects were defined as frequent exacerbators if they experienced two or more exacerbations in the past year. Clinical characteristics and worse outcome (ICU admission, or invasive ventilation, or in-hospital mortality) during severe AECOPD were compared between frequent exacerbators and non-frequent ones. Furthermore, the relationship between NLR and worse outcome in frequent exacerbators was analyzed using logistic regression and receiver operating characteristic (ROC). RESULTS: Among 604 patients with severe AECOPD, 282 (46.69%) were frequent exacerbators and 322 (53.31%) were non-frequent exacerbators. Compared with the non-frequent ones, frequent exacerbators presented higher levels of NLR (5.93 [IQR, 3.40-9.28] vs 4.41 [IQR, 2.74-6.80]; p<0.001), and more worse outcome incidence (58 [20.57%] vs 38 [11.80%]; p=0.003). Moreover, among the frequent exacerbators, NLR levels in the patients with worse outcome were much higher than in those without worse outcome (11.09 [IQR, 7.74-16.49] vs 5.28 [IQR, 2.93-7.93]; p<0.001). Increased NLR was significantly associated with a higher risk of worse outcome in frequent exacerbators (OR, 1.43; 95% CI, 1.28-1.64; p<0.001). Furthermore, ROC analysis revealed that a cut-off value of 10.23, NLR could predict worse outcome of severe AECOPD in frequent exacerbators (sensitivity 62.1%, specificity 92.0%, AUC 0.833). CONCLUSION: Frequent exacerbators exhibited an increased level of NLR and a higher proportion of worse outcome during severe AECOPD. NLR is expected to be a promising predictive biomarker for the prognosis of severe AECOPD in frequent exacerbators.

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AIM: Patients with mild asthma may experience severe exacerbations. This analysis was conducted to investigate regional peculiarities of mild asthma population in Russia. MATERIALS AND METHODS: The SYGMA2 is a double-blind multinational study involving adult patients with mild asthma (n=4176). We conducted an open-label descriptive analysis of the baseline characteristics of the Russian group (n=579) of SYGMA2 trial comparing to SYGMA2 population from other countries. The subanalysis was descriptive only, and no hypothesis were tested. RESULTS: The Russian population of patients with mild asthma was comparable to the rest of countries in terms of demographic characteristics, smoking status and duration of asthma. The spirometric parameters in the Russian group was slightly worse than in the other population. At the study entry 48% of Russian patients had symptom control on maintenance therapy, but 52% were uncontrolled on short-acting bronchodilators. While in other countries this ratio was inverse (55/45%). More patients with mild asthma in the Russian group had at least one severe exacerbation in the previous year (30.1% vs 20.7% in other countries). CONCLUSION: We revealed a delayed prescription of controller therapy and overuse of short-acting bronchodilators in the Russian group of mild asthma patients, that may increase risk of asthma non-control and severe exacerbation.

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Bronchiectasis is characterized by systemic inflammation and multiple comorbidities. This study aimed to investigate the clinical outcomes based on the bronchiectasis etiology comorbidity index (BACI) score in patients hospitalized for severe bronchiectasis exacerbations. We included non-cystic fibrosis patients hospitalized for severe bronchiectasis exacerbations between January 2008 and December 2016 from the Chang Gung Research Database (CGRD) cohort. The main outcome was the 1-year mortality rate after severe exacerbations. We used the Cox regression model to assess the risk factors of 1-year mortality. Of 1,235 patients who were hospitalized for severe bronchiectasis exacerbations, 641 were in the BACI < 6 group and 594 in the BACI ≥ 6 group. The BACI ≥ 6 group had more previous exacerbations and a lower FEV1. Pseudomonas aeruginosa (19.1%) was the most common bacterium, followed by Klebsiella pneumoniae (7.5%). Overall, 11.8% of patients had respiratory failure and the hospital mortality was 3.0%. After discharge, compared to the BACI < 6 group, the BACI ≥ 6 group had a significantly higher cumulative incidence of respiratory failure and mortality in a 1-year follow-up. The risk factors for 1-year mortality in a multivariate analysis include age [hazard ratio (HR) 4.38, p = 0.01], being male (HR 4.38, p = 0.01), and systemic corticosteroid usage (HR 6.35, p = 0.001), while airway clearance therapy (ACT) (HR 0.50, p = 0.010) was associated with a lower mortality risk. An increased risk of respiratory failure and mortality in a 1-year follow-up after severe exacerbations was observed in bronchiectasis patients with multimorbidities, particularly older age patients, male patients, and patients with a history of systemic corticosteroid use. ACT could effectively improve the risk for 1-year mortality.

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PURPOSE: Asthma exacerbations are inflammatory events that rarely result in full hospitalization following an ER visit. Unfortunately, certain patients require prolonged support, including occasional external lung support through ECMO or ECCOR (with subsequent further exposure to other life-threatening issues), and some die. In parallel, biologics are revolutionizing severe asthma management, mostly in T2 high patients. METHODS: We extensively reviewed the current unmet needs surrounding ICU-admitted asthma exacerbations, with a focus on currently available drugs and the underlying biological processes involved. We explored whether currently available T2-targeting drugs can reasonably be seen as potential players not only for relapse prevention but also as candidate drugs for a faster resolution of such episodes. The patient's perspective was also sought. RESULTS: About 30% of asthma exacerbations admitted to the ICU do not resolve within five days. Persistent severe airway obstruction despite massive doses of corticosteroids and maximal pharmacologically induced bronchodilation is the main cause of treatment failure. Previous ICU admission is the main risk factor for such episodes and may eventually be considered as a T2 surrogate marker. Fatal asthma cases are hallmarked by poorly steroid-sensitive T2-inflammation associated with severe mucus plugging. New, fast-acting T2-targeting biologics (already used for preventing asthma exacerbations) have the potential to circumvent steroid sensitivity pathways and decrease mucus plugging. This unmet need was confirmed by patients who reported highly negative, traumatizing experiences. CONCLUSIONS: There is room for improvement in the management of ICU-admitted severe asthma episodes. Clinical trials assessing how biologics might improve ICU outcomes are direly needed.

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BACKGROUND: The French Emergency Medicine Society, the French Intensive Care Society and the Pediatric Intensive Care and Emergency Medicine French-Speaking Group edited guidelines on severe asthma exacerbation (SAE) in adult and pediatric patients. RESULTS: The guidelines were related to 5 areas: diagnosis, pharmacological treatment, oxygen therapy and ventilation, patients triage, specific considerations regarding pregnant women. The literature analysis and formulation of the guidelines were conducted according to the Grade of Recommendation Assessment, Development and Evaluation methodology. An extensive literature research was conducted based on publications indexed in PubMed™ and Cochrane™ databases. Of the 21 formalized guidelines, 4 had a high level of evidence (GRADE 1+/-) and 7 a low level of evidence (GRADE 2+/-). The GRADE method was inapplicable to 10 guidelines, which resulted in expert opinions. A strong agreement was reached for all guidelines. CONCLUSION: The conjunct work of 36 experts from 3 scientific societies resulted in 21 formalized recommendations to help improving the emergency and intensive care management of adult and pediatric patients with SAE.

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BACKGROUND: Although the guidelines in most countries do not recommend continuous inhalation of l-isoproterenol to treat pediatric patients with acute severe exacerbation of asthma, lower dose of l-isoproterenol has been widely used in Japan. To determine whether the efficacy of low-dose l-isoproterenol was superior to that of salbutamol, we conducted a double-blind, randomized controlled trial. METHODS: Hospitalized patients aged 1-17 years were eligible if they had severe asthma exacerbation defined by the modified pulmonary index score (MPIS). Patients were randomly assigned (1:1) to receive inhalation of l-isoproterenol (10 µg/kg/h) or salbutamol (500 µg/kg/h) for 12 hours via a large-volume nebulizer with oxygen. The primary outcome was the change in MPIS from baseline to 3 hours after starting inhalation. Trial registration number UMIN000001991. RESULTS: From December 2009 to October 2013, 83 patients (42 in the l-isoproterenol group and 41 in the salbutamol group) were enrolled into the study. Of these, one patient in the l-isoproterenol group did not receive the study drug and was excluded from the analysis. Compared with salbutamol, l-isoproterenol reduced MPIS more rapidly. Mean (SD) changes in MPIS at 3 hours were -2.9 (2.5) in the l-isoproterenol group and -0.9 (2.3) in the salbutamol group (difference -2.0, 95% confidence interval -3.1 to -0.9; P < 0.001). Adverse events occurred in 1 (2%) and 11 (27%) patients in the l-isoproterenol and salbutamol groups, respectively (P = 0.003). Hypokalemia and tachycardia occurred only in the salbutamol group. CONCLUSIONS: Low-dose l-isoproterenol has a more rapid effect with fewer adverse events than salbutamol.

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Fresh peripheral blood (PB) samples from 432 outpatients with stable chronic obstructive pulmonary disease (COPD) were examined. Patients were classified into Group A (large SRA+ cells were undetected) and Group B (large SRA+ cells were detected) and followed-up for 1 year. Patients were further subdivided according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. Cox proportional hazard model had shown that Gold, Group, home oxygen therapy (HOT), and treatment were significant predictors of severe exacerbation. Six of 353 patients in Group A and 29 of 79 in Group B developed severe exacerbation. The rates of severe exacerbation were significantly higher in Group B patients, GOLD stage 2 than Group A, GOLD stage 2; in Group B, GOLD stage 3 than Group A, GOLD stage 3; and in all of Group B compared with in all of Group A. The Kaplan-Meier curves of Group B, GOLD stages 1-4, and of all of Group B showed significantly worse rates of severe exacerbation than those of Group A, Gold 1-4, and all of Group A, respectively. The appearance of large SRA+ cells in the PB of patients with stable COPD may represent a useful biomarker for severe COPD exacerbation.

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BACKGROUND: The prognosis in patients with Chronic Obstructive Pulmonary Disease (COPD) depends, in large part, on the frequency of exacerbations. Cardiovascular diseases, including heart failure (HF), are the risk factors for exacerbations. However, the importance of HF type over the exacerbations in COPD patients is unknown. OBJECTIVE: To determine whether right heart failure (RHF) is an independent risk factor for severe exacerbations in patients with COPD. METHODS: A prospective cohort study of 133 patients diagnosed with COPD with a follow-up period from 2010 to 2016. Patients with bronchial hyperreactivity, asthma, or pulmonary embolism were excluded. RESULTS: The mean age was 74.7 ± 8.2 years and 43.6% were men, 69.9% had severe exacerbations during follow-up. Subjects with RHF had lower FEV1 (50.2 ± 19.9 vs 57.4 ± 16.9, P = .006) and greater incidence of stroke (15.4% vs 1.8%, P = .009) compared to those without RHF. Subjects with RHF were at higher risk of severe exacerbations (HR, 2.46; CI 95%, 1.32-4.58, P = .005) compared to those without RHF after adjusting for confounding variables. CONCLUSION: In patients with COPD, RHF is an independent risk factor for suffering severe exacerbations.

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