Effectiveness of Mepolizumab in Patients with Severe Eosinophilic Asthma with/without Nasal Polyposis: A Real-Life Study.

INTRODUCTION: Asthma is one of the most common chronic diseases and affects around 334 million people worldwide. The estimated prevalence of severe asthma is 3-10% of the asthmatic population. Mepolizumab has demonstrated efficacy in reducing exacerbations, oral corticosteroid use, and improving quality of life, asthma control, and lung function in patients with severe eosinophilic asthma (SEA). Our study aimed to check the response to mepolizumab in a series of severe asthma patients regarding exacerbations, oral corticosteroid use, asthma control, quality of life, and lung function and to compare the response between patients with and without nasal polyps. METHOD: This is a retrospective, multicenter study of RE-ASGRAMUR (Register of Severe Asthma of the Region of Murcia) performed in eight hospitals of the Region of Murcia (Spain) under routine clinical practice conditions. We included patients diagnosed with SEA who completed at least 1 year of treatment with mepolizumab. We analyzed clinical characteristics, drug tolerance, and effectiveness: exacerbations, ACT, miniAQLQ, forced expiratory volume in 1 s (FEV1), and use of oral corticosteroids. We also compared the results between patients with and without nasal polyps. RESULTS: The median of exacerbations before treatment was 3 and decreased to 0 after treatment (mean decrease of 77.4%). The median diary oral prednisone intake was 15 mg before treatment and 5 mg after treatment (mean 56% reduction). We have obtained a significant improvement in other variables: ED visits and hospitalizations, asthma control (ACT), quality of life (miniAQLQ), and lung function (FEV1). Thirty-four out of 70 patients (48.57%) fulfilled the criteria of super-responder, and 17 out of 70 (24.29%) had a complete response. More patients in the group with nasal polyps fulfilled the criteria of super-responder and complete response to mepolizumab. CONCLUSIONS: Mepolizumab is a safe and effective treatment for SEA patients, improving exacerbations, oral corticosteroid intake, asthma control, quality of life, and lung function. In patients with associated nasal polyposis, there is a statistically significant higher proportion of super-responders and complete responders.

Infection with SARS-CoV-2 among children with asthma: evidence from Global Asthma Network.

BACKGROUND: Clinical presentations of coronavirus disease 2019 (COVID-19) among children with asthma have rarely been investigated. This study aimed to assess clinical manifestations and outcome of COVID-19 among children with asthma, and whether the use of asthma medications was associated with outcomes of interest. METHODS: The Global Asthma Network (GAN) conducted a global survey among GAN centers. Data collection was between November 2020 and April 2021. RESULTS: Fourteen GAN centers from 10 countries provided data on 169 children with asthma infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 was asymptomatic in 58 (34.3%), mild in 93 (55.0%), moderate in 14 (8.3%), and severe/critical in 4 (2.4%). Thirty-eight (22.5%) patients had exacerbation of asthma and 21 (12.4%) were hospitalized for a median of 7 days (interquartile range 3-16). Those who had moderate or more severe COVID-19 were significantly more likely to have exacerbation of asthma as compared to those who were asymptomatic or had mild COVID-19 (adjusted odds ratio (adjOR) 3.97, 95% CI 1.23-12.84). Those who used inhaled bronchodilators were significantly more likely to have a change of asthma medications (adjOR 2.39, 95% CI 1.02-5.63) compared to those who did not. Children who used inhaled corticosteroids (ICS) did not differ from those who did not use ICS with regard to being symptomatic, severity of COVID-19, asthma exacerbation, and hospitalization. CONCLUSIONS: Over dependence on inhaled bronchodilator may be inappropriate. Use of ICS may be safe and should be continued in children with asthma during the pandemic of COVID-19.

Analysis of response of severe eosinophilic asthmatic patients to benralizumab.

INTRODUCTION: Clinical trials and real-life studies have been published showing effectiveness of benralizumab in severe eosinophilic asthmatic patients. The aim of the present study is to describe super-responders to benralizumab in a series of 79 patients who completed at least 1 year of treatment, and to compare super-responders with non super-responders. METHODS: This is a multicenter study of the Register of Severe Asthma of the Region of Murcia (RE-ASGRAMUR) Group performed in eight hospitals under the conditions of routine clinical practice. Patients with zero exacerbations and no oral corticosteroid therapy for asthma were considered super-responders. We analyzed clinical, functional, and inflammatory parameters of selected patients. RESULTS: In all, 50 of the 79 patients (63%) met the super-responder criteria. In addition, 36% of the patients (26/71) were considered as complete responders to treatment (super--responder + Asthma Control Test [ACT] ≥ 20 + forced expiratory volume in 1 s [FEV1] ≥ 80%). The super--responders were significantly older in age (P = 0.0029), had higher eosinophils count (P = 0.0423), higher proportion of nasal polyps (P = 0.036), and they had less severe disease at baseline. After 1 year of treatment, the super-responders had higher levels of ACT questionnaire (23 vs 19, P = 0.0007) and better percentage of FEV1 (83 vs 75, P = 0.0359). CONCLUSION: Almost two of the three patients treated with benralizumab were super--responders after 1 year of treatment and 36% had a complete response. Super-responders were associated with older age, higher eosinophils count, had nasal polyposis as comorbidity, and had less severe disease at baseline. This data illustrated the good real-life response of patients with severe eosinophilic asthma to the treatment with benralizumab.

Microbiome and Asthma: Microbial Dysbiosis and the Origins, Phenotypes, Persistence, and Severity of Asthma.

The importance of the microbiome, and of the gut-lung axis in the origin and persistence of asthma, is an ongoing field of investigation. The process of microbial colonisation in the first three years of life is fundamental for health, with the first hundred days of life being critical. Different factors are associated with early microbial dysbiosis, such as caesarean delivery, artificial lactation and antibiotic therapy, among others. Longitudinal cohort studies on gut and airway microbiome in children have found an association between microbial dysbiosis and asthma at later ages of life. A low α-diversity and relative abundance of certain commensal gut bacterial genera in the first year of life are associated with the development of asthma. Gut microbial dysbiosis, with a lower abundance of Phylum Firmicutes, could be related with increased risk of asthma. Upper airway microbial dysbiosis, especially early colonisation by Moraxella spp., is associated with recurrent viral infections and the development of asthma. Moreover, the bacteria in the respiratory system produce metabolites that may modify the inception of asthma and is progression. The role of the lung microbiome in asthma development has yet to be fully elucidated. Nevertheless, the most consistent finding in studies on lung microbiome is the increased bacterial load and the predominance of proteobacteria, especially Haemophilus spp. and Moraxella catarrhalis. In this review we shall update the knowledge on the association between microbial dysbiosis and the origins of asthma, as well as its persistence, phenotypes, and severity.

Quality of life in children with diseases causing central airway obstruction: Reliability and validity of the TAPQOL questionnaire.

INTRODUCTION: The aim of this study was to analyse the psychometric performance (reliability and validity) of the TAPQOL questionnaire in measuring the global quality of life in children with central airway obstruction (CAO), which encompasses pathologies with a low prevalence that have a common anatomical or functional affectation. METHOD: The study population consisted of 109 patients with CAO attended in a national reference airway unitafter signing informed consent. The TAPQOL questionnaire was used to measure the global quality of life and its psychometric characteristics were analysed. The reliability was determined using Cronbach's α statistic and the validity was determined by means of a principal component analysis. RESULTS: The mean age was 4.8 years and there was no predominant sex. The most frequent diagnosis was laryngomalacia (24.5%), followed bysubglotticstenosis (20.2%). The lowest score in the TAPQOL questionnaire was obtained for the scales of anxiety (66.2 ± 23.7), respiratory (67.9 ± 29.6), and conduct 68.2 ± 21.4). The Cronbach's α was above 0.7 in the majority of the scales and the validity study by principal component analysis with a total variance of 76.7% fits the original 12-component model. CONCLUSIONS: TAPQOL is a valid tool to measure the health-related quality of life in patients with CAO. Measuring it in these patients indicates which fields are most affected, highlighting therapeutic needs that have not been resolved but which can be approached in normal clinical practice.

Severe Asthma and Biological Therapies: Now and the Future.

Recognition of phenotypic variability in pediatric asthma allows for a more personalized therapeutic approach. Knowledge of the underlying pathophysiological and molecular mechanisms (endotypes) of corresponding biomarkers and new treatments enables this strategy to progress. Biologic therapies for children with severe asthma are becoming more relevant in this sense. The T2 phenotype is the most prevalent in childhood and adolescence, and non-T2 phenotypes are usually rare. This document aims to review the mechanism of action, efficacy, and potential predictive and monitoring biomarkers of biological drugs, focusing on the pediatric population. The drugs currently available are omalizumab, mepolizumab, benralizumab, dupilumab, and 1ezepelumab, with some differences in administrative approval prescription criteria between the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Previously, we described the characteristics of severe asthma in children and its diagnostic and therapeutic management.

Pediatric asthma: The REGAP consensus.

Asthma is one of the main chronic diseases in childhood, due to its high prevalence and its social and health costs. This document is a summary of a consensus guideline approved by 6 Spanish pediatric societies related to asthma and endorsed by the Spanish Pediatric Association. Asthma is easily identifiable by clinical criteria in most patients. Spirometry and other tests are helpful for diagnosis, especially in atypical cases. Asthma exacerbation is a frequent manifestation of the disease and must be identified and treated promptly. When asthma symptoms are frequent and the quality of life is affected, maintenance treatment must be instituted to achieve control of the disease. Low-dose inhaled corticosteroids are effective and safe for long-term use. Education of the patient with asthma is essential for good control. The main reason for poor asthma control is non-compliance with treatment, either due to its erratic and insufficient administration, or due to poor application technique of inhaled drugs. If control is not obtained despite adequate treatment, the diagnosis must be reconsidered, as well as the factors or comorbidities that make control difficult. Other drugs can be added to avoid high doses of inhaled corticosteroids, notably montelukast or long-acting ß2 adrenergic agonists. Severe or difficult-to-control asthma, which does not respond to the usual treatments, should be managed in specialized units.

Asthma and rhinoconjunctivitis comorbidity: united airway disease or inherited target organs?

The idea of a united airway disease for asthma and rhinoconjunctivitis is supported by clinical and epidemiological data. However, many asthmatics do not have rhinoconjunctivitis and vice versa. The aim of this study was to investigate if the family history of a specific organ involvement is associated with the implication of the same organ in the allergic child. According to the organ involvement in either or both parents, the family history of 739 children who were skin prick positive to either Dermatophagoides pteronyssinus or D. farinae or both was defined as: asthma and rhinoconjunctivitis positive; asthma and rhinoconjunctivitis negative; asthma negative and rhinoconjunctivitis positive; and asthma positive and rhinoconjunctivitis negative. Asthma and rhinoconjunctivitis in the children were defined according to the International Study of Asthma and Allergies in Childhood questionnaire. Associations between each type of family history and the presence of asthma and/or rhinoconjunctivitis in the children were calculated and adjusted for usual confounders. Adjusted odds ratio of children having asthma, when family history included asthma, was 2.48 (1.38-4.45) when it also included rhinoconjunctivitis; and 2.13 (1.12-4.05) when it did not. However, family history of rhinoconjunctivitis was not associated with asthma in the child. Conversely, the odds ratio of children having rhinoconjunctivitis when family history included rhinoconjunctivitis was 1.84 (1.05-3.21) when it also included asthma; and 1.89 (1.23-2.89) when it did not. Family history of asthma was not associated with rhinoconjunctivitis in the child. In a population of children sensitized to mites, the organ or organs (nose and/or lung) which are implicated in parents tend to be also involved in their children.

Impact of Self-Efficacy on The Quality of Life of Children With Asthma and Their Caregivers. / Impacto de la autoeficacia en la calidad de vida de niños con asma y sus cuidadores.

INTRODUCTION: Health-related quality of life is an important outcome measurement in the monitoring of asthma control. Self-efficacy is a determinant of self-management behaviors that can contribute to the improvement of asthma control and quality of life. Our objective was to analyze the relationship between self-efficacy and quality of life in children with asthma and their caregivers. METHODS: We included 176 patients aged 6-14 years with asthma, and determined their level of self-efficacy according to three groups (low, medium and high levels). Each child and their main caregiver completed the PAQLQ and PACQLQ questionnaires, respectively. RESULTS: PAQLQ range=1-7: 5.61±1.11; PACQLQ range=1-7: 5.42±1.35; self-efficacy range=0-60: low level 28.44±4.58; average level 37.41±1.7, and high level 47.50±5.5. Significant differences were observed in quality of life according to low-medium vs. high levels of self-efficacy. Specific related domains: PAQLQ emotions and PAQLQ symptoms with self-efficacy in problem-solving skills related to asthma and treatment self-efficacy; PACQLQ emotions with self-efficacy in problem-solving skills related to asthma. CONCLUSIONS: A high level of self-efficacy is associated with a better quality of life for children and their caregivers. Based on these results, the measurement of self-efficacy could be incorporated in the assessment of educational interventions in self-management targeted at the quality of life of the patient and his or her family.

Mediterranean diet as a protective factor for wheezing in preschool children.

OBJECTIVE: To test the hypothesis that the Mediterranean diet can be a protective factor for current wheezing in preschoolers. STUDY DESIGN: Questionnaires were completed by parents of 1784 preschoolers (mean age, 4.08 +/- 0.8 years). Children were stratified according to whether they experienced wheezing (20.0%) or not in the previous year. A Mediterranean diet score was built according to the intake frequency of several foods. RESULTS: Age, birth by cesarean section, low birth weight, exposure to livestock during pregnancy, antibiotic use in the first year of life, acetaminophen consumption in the previous 12 months, rhinoconjunctivitis, eczema, parental asthma and tobacco consumption, maternal educational level, maternal age, physical activity, cat at home, and Mediterranean diet were associated with current wheezing but not with obesity. In the multivariate analysis, eczema, rhinoconjunctivitis, paternal asthma, and acetaminophen consumption remained risk factors for current wheezing (adjusted odds ratio [aOR] = 2.35 [95% confidence interval (CI) = 1.2 to 4.8], 2.78 [95% CI =1.3 to 6.1], 3.89 [95% CI = 1.4 to 10.7], and 2.38 [95% CI = 1.2 to 4.6], respectively). Conversely, Mediterranean diet and older age remained protective factors (aOR = 0.54 [95% CI = 0.3 to 0.9] and 0.67 [95% CI = 0.5 to 0.9], respectively). CONCLUSIONS: The Mediterranean diet is an independent protective factor for current wheezing in preschoolers, irrespective of obesity and physical activity.

[Association between chronic colonization or infection with Pseudomonas aeruginosa and bronchial hyperreactivity in patients with cystic fibrosis]. / Asociación entre colonización-infección crónica por Pseudomonas aeruginosa e hiperreactividad bronquial en pacientes con fibrosis quística.

OBJECTIVE: In patients with cystic fibrosis, bronchial hyperreactivity is a common finding that has not been conclusively associated with atopy. The objective of the present study was to determine the relationship between chronic colonization or infection with Pseudomonas aeruginosa and bronchial hyperreactivity in a group of patients with cystic fibrosis. PATIENTS AND METHODS: A nonspecific histamine bronchial provocation test was administered to a group of 32 cystic fibrosis patients with a mean (SD) age of 11.25 (3.7) years. The presence of atopy and of chronic colonization or infection with P aeruginosa was also studied. RESULTS: Nine of the 32 patients (28.1%) studied showed bronchial hyperreactivity. The clinical status of these 9 patients was significantly worse and all were colonized or infected with P aeruginosa. Atopy was present in 17 of the 32 patients (53.1%) in the study group, but in only 3 of the 9 patients (33.3%) with bronchial hyperreactivity. Bronchial hyperreactivity was significantly associated with colonization or infection with P aeruginosa (P< .001), but not with atopy (P=.12). In the patients without atopy, colonization was significantly associated with bronchial hyperreactivity (P=.017). In the group with normal lung function (forced expiratory volume in 1 second >/=80%) this association was also significant (P=.044), while the association between bronchial hyperreactivity and atopy was not (P=.11). CONCLUSIONS: The results of the present study suggest that in patients with cystic fibrosis, bronchial hyperreactivity may be associated with colonization or infection with P aeruginosa, and that this may be a more important risk factor for bronchial hyperreactivity than atopy.

Percent body fat, skinfold thickness or body mass index for defining obesity or overweight, as a risk factor for asthma in schoolchildren: which one to use in epidemiological studies?

None of the epidemiological studies indicating that obesity is a risk factor for asthma in schoolchildren have used the percent body fat (PBF) to define obesity. The present study compares the definition of obesity using body mass index (BMI), PBF and the raw sum of the thickness of four skinfolds (SFT) to evaluate this condition as a risk factor for asthma. All classes of children of the target ages of 6-8 years of all schools in four municipalities of Murcia (Spain) were surveyed. Participation rate was 70.2% and the number of children included in the study was 931. Height, weight and SFT (biceps, triceps, subscapular and suprailiac) were measured according to standard procedures. Current active asthma was defined from several questions of the International Study of Asthma and Allergies in Childhood questionnaire. Obesity was defined using two standard cut-off points for BMI and PBF, and the 85th percentile for BMI, PBF and SFT. The highest quartile of each type of measurement was also compared with the lowest. A multiple logistic regression analysis was made for the various obesity definitions, adjusting for age, asthma in the mother and father and gender. The adjusted odds ratios of having asthma among obese children were different for boys and girls and varied across the different obesity definitions. For the standard cut-off points of BMI they were 1.19 [95% confidence interval (CI) 0.41-3.43] for girls and 2.00 (95% CI 0.97-4.10) for boys; however, for PBF (boys 25%, girls 30%) the corresponding figures were 1.54 (95% CI 0.63-3.73) and 1.20 (95% CI 0.66-2.21). BMI, PBF and SFT showed more consistency between each other when using the other cut-off points. BMI, PBF (except standard cut-off points) and SFT produce relatively comparable results when analysing the interaction between obesity and asthma.

Pediatricians' attitudes and costs of bronchiolitis in the emergency department: a prospective multicentre study.

BACKGROUND: How pediatricians manage bronchiolitis and the derived total costs (direct and indirect) in the emergency department (ED) have not been fully characterized. The aim of the present study is to calculate those costs in a European country. METHODS: A prospective and observational study, including 10 EDs of tertiary hospitals throughout Spain and during the bronchiolitis season 2010-2011, was performed. Every ED recruited children on random days of the week (3 days per week; always including one non-working day per every week). Recruitment aimed at a total sample size of 600 children. Direct (diagnostic procedures, time spent in the ED and medication) and indirect costs (work hours lost by parents, babysitting, travels, and meals) were collected. Comparisons between bronchiolitis caused by respiratory syncytial virus (RSV) and non-RSV bronchiolitis, as well as costs across severity categories were performed with the Kruskal-Wallis test. A multiple regression model was built to assess the influence of several of the studied factors on the total costs, including a RSV positive test and episode severity as independent variables; and gender, age, attending nursery school, preterm birth, low birth weight, smoker mother during pregnancy, and current smoker father as covariates. RESULTS: From the 664 recruited children, direct mean costs were €213.2 ± 91.8 and indirect ones were €35.9 ± 55.3; the total costs being €249.2 ± 122.9. Costs were significantly higher in children positive to RSV and rose with increased severity. Those associations were maintained in the multiple regression analysis. CONCLUSIONS: Although relatively low at the individual level (€249.2, mean total cost) the costs for just the ED expenses of bronchiolitis in Spain would add up to about €20 million per year.