Severe Asthma In Children Research Articles

The role of monocytes and natural killers’ immunophenotypic subsets in bronchial asthma in children

Objective: Childhood bronchial asthma (BA) is a globally significant chronic disease with major health consequences. Recently, focus on the role of the innate immune system has been highlighted. Therefore, this study explores the role of circulating monocytes and natural killer (NK) clusters in childhood asthma. Methods: This case-control study enrolled 50 children with asthma divided equally into severe and mild groups and 26 healthy children. Flow-cytometry analysis was used to identify circulating blood monocytes and natural killers’ subsets. In addition, pulmonary function test (spirometry) for children with asthma was performed. Results: This study showed significant negative correlations between frequency of total circulating, classical, intermediate, and nonclassical monocytes with ratio of forced expiratory volume/forced vital capacity (FEV1/FVC) (r = −0.637, P < 0.001; r = −0.575, P < 0.001; r = −0.657, P < 0.001; r = −0.329, P = 0.004, respectively). Also, there was significant negative correlations between frequency of total NKs and CD56dim CD16+ NK with FEV1/FVC (r = −0.584, P < 0.001) and (r = −0.579, P < 0.001). Significant predictors of childhood asthma severity were frequencies of total monocytes, total NKs, intermediate monocytes, and CD56dimCD16+ NK. Conclusion: Finally, we concluded that the FEV1/FVC is linked to aberrations of monocytes’ and natural killers’ immunophenotypic subsets in children with asthma. The frequencies of total monocytes and NK are significant predictors of severity of childhood asthma. The frequencies of CD14high CD16+ intermediate monocytes and CD56dim CD16+ NK cells are the best independent predictors of severity in children with asthma.

Humidified and standard oxygen therapy in acute severe asthma in children (HUMOX): A pilot randomised controlled trial.

Oxygen (O2) is a mainstay of treatment in acute severe asthma but how it is administered varies widely. The objectives were to examine whether a trial comparing humidified O2 to standard O2 in children is feasible, and specifically to obtain data on recruitment, tolerability and outcome measure stability. Heated humidified, cold humidified and standard O2 treatments were compared for children (2-16 years) with acute severe asthma in a multi-centre, open, parallel, pilot randomised controlled trial (RCT). Multiple outcomes were assessed. Of 258 children screened, 66 were randomised (heated humidified O2 n = 25; cold humidified O2 n = 21; standard O2 n = 20). Median (IQR) length of stay (hours) in hospital was 37.9 (29.1), 52 (35.4) and 49.1 (29.7) for standard, heated humidified and cold humidified respectively and time (hours) on O2 was 15.9 (9.4), 13.6 (14.9) and 13.1 (14.9) for the three groups respectively. The mean (standard deviation) time (hours) taken to step down nebulised to inhaled treatment was 5.6 (14.3), 35.1 (28.2) and 32.7 (20.1). Asthma Severity Score decreased in all three groups similarly, although missing data prevented complete analysis. Humidified O2 was least well tolerated with eight participants discontinuing their randomised treatment early. An important barrier to recruitment was research nurse availability. Although, the results of this pilot study should not be extrapolated beyond the study sample and inferential conclusions should not be drawn from the results, this is the first RCT to compare humidified and standard O2 therapy in acute severe asthmatics of any age. These findings and accompanying screening data show that a large RCT of O2 therapy is feasible. However, challenges associated with randomisation and data collection should be addressed in any future trial design.

The effects of secondhand smoke on respiratory pathology, sensitization and development of allergic diseases in young children (literature review)

The prevalence of active smoking in Ukraine significantly exceeds the worldwide average, which is certainly a risk factor for children to be exposed to secondhand smoke. The article provides literature data and presents a modern view on the problem of secondhand tobacco smoke impact on the child population. In pediatric practice, the pathological impact of secondhand smoke on the child’s health is significant at the stage of its fetal development. Historical data convincingly prove the connection between the antenatal effect of secondhand smoke and the increased risk of perinatal losses and risks of pregnancy — miscarriage, stillbirth, and premature birth. As early as the 1960s and 1970s, scientific evidence was obtained for an association between the effects of tobacco smoke and the risk of sudden infant death syndrome. Children are most vulnerable to the negative effects of tobacco smoke at an early age because they have closer and longer contact with their parents, especially their mothers. Many studies have found an association between the effects of secondhand smoke and airway pathology (bronchitis, pneumonia), as well as an increase in the severity of respiratory syncytial viral infection (bronchiolitis). Numerous literature data indicate an association between the effect of passive smoking and the frequency and severity of oral cavity (dental caries) and middle ear (recurrent and chronic otitis, middle ear effusion) pathology. Many studies have shown the effects of secondhand smoke on the development and severity of bronchial asthma in children, but scientific data on the causal relationship of tobacco smoke with other allergic diseases (atopic dermatitis, allergic rhinitis, and food allergies), which are common in young children and preceded bronchial asthma in the "atopic march, are more limited and contradictory. The literature was searched using the PubMed database.

Caregiver-perceived neighborhood safety and pediatric asthma severity: 2017-2018 National Survey of Children's Health.

To examine the association between caregiver-perceived neighborhood safety and pediatric asthma severity using a cross-sectional, nationally representative sample. Using data from the 2017-2018 National Survey of Children's Health, children aged 6-17 years with primary caregiver report of a current asthma diagnosis were included (unweighted N = 3209; weighted N = 3,909,178). Perceived neighborhood safety, asthma severity (mild vs. moderate/severe), demographic, household, and health/behavioral covariate data were collected from primary caregiver report. Poisson regression with robust error variance was used to estimate the association between perceived neighborhood safety and caregiver-reported pediatric asthma severity. Approximately one-third of children studied had moderate/severe asthma. A total of 42% of children with mild asthma and 52% of children with moderate/severe asthma identified as Hispanic or non-Hispanic Black. Nearly 20% of children with mild asthma and 40% of children with moderate/severe asthma were from families living below the federal poverty level (FPL). Children living in neighborhoods perceived by their caregiver to be unsafe had higher prevalence of moderate/severe asthma compared to those in the safest neighborhoods (adjusted prevalence ratio: 1.34; 95% confidence interval: 1.04-1.74). This association was found to be independent of race/ethnicity, household FPL, household smoking, and child's physical activity level after adjusting for covariates. Children living in neighborhoods perceived by their caregiver to be unsafe have higher prevalence of moderate or severe asthma. Further investigation of geographic context and neighborhood characteristics that influence childhood asthma severity may inform public health strategies to reduce asthma burden and improve disease outcomes.

Small airways targeted treatment with smart nebulizer technology could improve severe asthma in children: a retrospective analysis

Objective Conventional inhaler devices have a low efficacy in targeting small airways. Smart nebulizers can be used to increase deposition to small airways by adjusting the flow and depth of each inhalation based on patients ‘individual inspiratory capacity. We investigated whether targeting of high dose inhaled corticosteroids (ICS) to small airways with a smart nebulizer could reduce exacerbation rate in children with severe asthma (SA). Methods We conducted a retrospective study in children with SA using a smart nebulizer (Akita® Jet nebulizer) for the administration of high dose ICS in our outpatient clinic at the Erasmus MC — Sophia Children’s Hospital. Clinical data before and after start of treatment were collected. The primary outcome was exacerbation rate, defined as: number of asthma exacerbations for which oral corticosteroid courses (OCS) were prescribed. The exacerbation rate 1 year before treatment was compared with the exacerbation rate 1 year after start of treatment. Secondary outcomes were changes in spirometry parameters, hospital admissions and medication use. Results Data on OCS use was available for 28/31 patients. Median number of asthma exacerbations requiring OCS courses 1 year before decreased from 2 (interquartile range(IQR) 2) to 0.5 (IQR 3) 1 year after treatment (p = 0.021). Hospital admission decreased from 1 (IQR 3) to 0 (IQR 1)(p = 0.028). FEV1, FEF25-75 and FEF75 were not significantly improved after one year of treatment with the smart nebulizer (p = 0.191; p = 0.248; p = 0.572). Conclusion Targeting small airways with high dose ICS using a smart nebulizer resulted in a significant reduction in exacerbations requiring OCS after one year of treatment.

Altered Pattern of Macrophage Polarization as a Biomarker for Severity of Childhood Asthma.

PurposeAsthma causes a substantial morbidity and mortality burden in children and the pathogenesis of childhood asthma is not completely understood. Macrophages are heterogeneous with divergent M1/M2 polarization phenotypes in response to various stimulations during the inflammatory process. We aimed to investigate the pattern of macrophage polarization and its association with severity and exacerbation in asthmatic children.Patients and MethodsNormal and asthmatic children aged 4–18 years were enrolled for 12 months. Children with asthma were further subgrouped according to their severity and the requirement for hospitalization during exacerbations. Clinical data were obtained from medical records. Peripheral blood samples were collected to analyze macrophage polarization, including M1, M2, and subsets, by flow cytometry.ResultsFifty-one asthmatic cases and 27 normal controls were included in this study. The level of PM-2K+CD14+ but not PM-2K+CD14− was decreased in asthmatic children. The levels of M2a (CCR7−CXCR1+), M2b (CCR7−CD86+), and M2c (CCR7−CCR2+) subsets, but not M1 (CCR7+CD86+), were increased in asthmatic children. The levels of M1 were decreased, but the levels of M2c were increased, in children with moderate asthma compared to those with mild asthma. The levels of PM-2K+CD14+ cells and M1 subsets were decreased, but the M2c subset cells were increased in asthmatic children requiring hospitalization during exacerbations.ConclusionMacrophage polarization may be involved in the pathogenesis of childhood asthma and is a potential biomarker of childhood asthma disease severity.

MiRNA-21 Regulates Bronchial Epithelial Cell Proliferation by Activating Tgfβ1/Smad Signaling Pathway and Its Correlation with Asthma Severity in Children

Background:This research was designed to probe into the role of miRNA-21 in the pathogenesis of childhood asthma and its correlation with the severity.Methods:Fifty-four children with bronchial asthma admitted to the Third Affiliated Hospital of Qiqihar Medical University from Jun 2018 to Dec 2019 were included. Forty nine healthy children underwent physical examination at this time period were also enrolled. The miR-21 expression in peripheral blood serum was analyzed by qRT-PCR. The relationship between the expression and severity of asthma in children was explored by Spearman correlation analysis and ROC curve. Bronchial epithelial cell lines were cultured in vitro and divided into blank control group, negative control group and miR-21 inhibition and activation group. The changes of cell proliferation after treatment were detected by CCK-8 test in different groups. The expression of TGF-β1/Smad signaling pathway protein in cells was assessed by Western blot (WB).Results:Compared with that of healthy children, the miR-21 expression in peripheral blood serum of asthmatic children was higher (P<0.001). MiR-21 expression was positively correlated with the severity of illness (r=0.853, P<0.001). The results of cell experiments in vitro signified that miR-21 can promote the proliferation of bronchial epithelial cells, and may be involved in regulating the expression of TGF-β1/Smad3 signaling pathway, thus affecting cell proliferation.Conclusion:miRNA-21 regulates the proliferation of bronchial epithelial cells by activating TGFβ1/Smad signaling pathway. And it is positively correlated with the severity of asthma in children.

Benefits and risks of bronchoalveolar lavage in severe asthma in children.

BackgroundAlthough bronchoscopy can be part of the exploration of severe asthma in children, the benefit of bronchoalveolar lavage (BAL) is unknown. The present study aimed to decipher whether systematic BAL during a flexible bronchoscopy procedure could better specify the characteristics of severe asthma and improve asthma management.Material and methodsThe study took place in two departments of a university hospital in Paris. Children who underwent flexible bronchoscopy for the exploration of severe asthma between April 2017 and September 2019 were retrospectively included.ResultsIn total, 203 children were included, among whom 107 had a BAL. BAL cell count was normal in most cases, with an increasing number of eosinophils with age, independently from the atopic status of the patients. Compared with bronchial aspiration only, BAL increased the rate of identified bacterial infection by 1.5. Nonatopic patients had more bacterial infections (p<0.001). BAL induced a therapeutic modification only for azithromycin and omalizumab prescriptions. The practice of a BAL decreased bronchoscopy tolerance (p=0.037), especially in the presence of tracheobronchial malacia (p<0.01) and when performed in a symptomatic patient (p=0.019).Discussion and conclusionAlthough BAL may provide interesting information in characterising severe asthma, in most cases its impact on the patient's management remains limited. Moreover, BAL can be poorly tolerated and should be avoided in the case of tracheobronchial malacia or current asthma symptoms.

Correlation between Gene Polymorphisms of Prostaglandin D Correlation between Gene Polymorphisms of Prostaglandin D

Background: Patients, their families and the community suffer a heavy burden when it comes to asthma because it is both common and possibly life-threatening. It has been postulated that arachidonic acid's most prevalent cyclooxygenase metabolite, prostaglandin D2 (PGD2), is a mast cell activation marker in asthma. Objective: To evaluate association between PGDR-441 polymorphism with risk factors, laboratory characteristics, and severity of asthma in children. Methods: In this cross-sectional study, Forty Egyptian children were genotyped using allele specific polymerase chain reaction (AS-PCR) to assess single nucleotide polymorphism of PTGDR2 receptors. Selected cases were classified according to GINA guidelines and spirometrically assessed to evaluate pulmonary functions. Results: There is significant difference between mild, moderate and severe asthma regarding total IgE level(P1<0.001). 68.0% of the studied patients had Homogenous PGDR2(TT) and 32% had Heterozygous PGDR2(TC). There were no statistically significant associations between PGDR2 Polymorphisms and both of asthma risk factors and laboratory characteristics. There was a statistically significant difference between PGDR2 Polymorphisms and bronchial asthma severity of the studied patients. Heterozygous PGDR2 was associated with more severe bronchial asthma. Conclusion: Our study showed a strong relationship between polymorphism of PTGDR2 receptor and severity of bronchial asthma.

Exclusive Breastfeeding Duration and Allergic Asthma Severity in Children

Introduction: Asthma is a disease marked by bronchial hyperresponsivity. It is commonly seen in children and often affects their quality of life. Many factors affect asthma, including breastfeeding. Bioactive and immunological components of maternal milk have a protective effect on allergic asthma. However, some studies denied this, stating that it had no significant association to asthma. This study aimed to analyze the correlation between breastfeeding duration and the severity of allergic asthma described by the frequency of asthma attacks, sleep disorder, and activity limitation.Methods: This analytic observational study used a cross sectional approach. The subjects were pediatric outpatients aged 1 – 5 years old with allergic asthma at Pediatric Clinic of Dr. Soetomo General Hospital Surabaya and Private Pediatric Clinic from September 2019 to July 2020. Subjects were assessed based on the history of exclusive breastfeeding duration, frequency of asthma attacks, sleep disorder, and activity limitation through an interview using questionnaire.Results: Through the data obtained from 62 respondents, duration of exclusive breastfeeding showed no significant relation to the frequency of asthma attack (rs = -0.227, p = 0.076), sleep disorder (rs = -0.214, p = 0.095), and activity limitation (rs = -0.055, p = 0.672).Conclusion: There was no correlation between the duration of exclusive breastfeeding and the frequency of asthma attack, sleep disorder, and activity limitation.

Effect of vitamin D3 supplementation on severe asthma exacerbations in children with asthma and low vitamin D levels: the VDKA randomized clinical trial

Importance Severe asthma exacerbations cause significant morbidity and costs. Whether vitamin D3supplementation reduces severe childhood asthma exacerbations is unclear. Objective To determine whether vitamin D3supplementation improves the time to a severe exacerbation in children with asthma and low vitamin D levels. Design, Setting, and Participants The Vitamin D to Prevent Severe Asthma Exacerbations (VDKA) Study was a randomized, double-blind, placebo-controlled clinical trial of vitamin D3supplementation to improve the time to severe exacerbations in high-risk children with asthma aged 6 to 16 years taking low-dose inhaled corticosteroids and with serum 25-hydroxyvitamin D levels less than 30 ng/mL. Participants were recruited from 7 US centers. Enrollment started in February 2016, with a goal of 400 participants; the trial was terminated early (March 2019) due to futility, and follow-up ended in September 2019. Interventions Participants were randomized to vitamin D3, 4000 IU/d (n = 96), or placebo (n = 96) for 48 weeks and maintained with fluticasone propionate, 176 μg/d (6-11 years old), or 220 μg/d (12-16 years old). Main Outcomes and Measures The primary outcome was the time to a severe asthma exacerbation. Secondary outcomes included the time to a viral-induced severe exacerbation, the proportion of participants in whom the dose of inhaled corticosteroid was reduced halfway through the trial, and the cumulative fluticasone dose during the trial. Results Among 192 randomized participants (mean age, 9.8 years; 77 girls [40%]), 180 (93.8%) completed the trial. A total of 36 participants (37.5%) in the vitamin D3group and 33 (34.4%) in the placebo group had 1 or more severe exacerbations. Compared with placebo, vitamin D3supplementation did not significantly improve the time to a severe exacerbation: the mean time to exacerbation was 240 days in the vitamin D3group vs 253 days in the placebo group (mean group difference, −13.1 days [95% CI, −42.6 to 16.4]; adjusted hazard ratio, 1.13 [95% CI, 0.69 to 1.85];P = .63). Vitamin D3supplementation, compared with placebo, likewise did not significantly improve the time to a viral-induced severe exacerbation, the proportion of participants whose dose of inhaled corticosteroid was reduced, or the cumulative fluticasone dose during the trial. Serious adverse events were similar in both groups (vitamin D3group, n = 11; placebo group, n = 9). Conclusions and Relevance Among children with persistent asthma and low vitamin D levels, vitamin D3supplementation, compared with placebo, did not significantly improve the time to a severe asthma exacerbation. The findings do not support the use of vitamin D3supplementation to prevent severe asthma exacerbations in this group of patients. Trial Registration ClinicalTrials.gov Identifier:NCT02687815

English

BACKGROUND Bronchial asthma is a major public health concern especially in the paediatric population. An elevated immunoglobulin E (IgE) level is considered as an objective marker of allergy. Because IgE is a mediator of allergic response, quantitative measurement of IgE together with other clinical markers, can provide useful information for the differentiation between atopic and non-atopic diseases. In this study, we wanted to determine serum IgE and absolute eosinophil count (AEC) levels and correlate both levels with severity of asthma in children in the age group of 2 - 15 years admitted in the paediatric department. METHODS This is a descriptive cross-sectional study. After taking the informed consent from the parent or guardian, relevant information on asthmatic symptoms and severity, other associated manifestations, precipitating factors, and family history of asthma were recorded in a pre-designed proforma. A total of 65 children (age group 2 – 15 years old) with bronchial asthma were studied. Investigations such as hemogram and serum IgE levels were determined. Asthma severity was assessed according to global initiative for asthma (GINA) guidelines. RESULTS Among 65 children, 69.2 % were boys. Receiver operating characteristic curve (ROC) analysis showed that total IgE cut-off concentration of 168 IU/ml, distinguishes children with intermittent asthma from those with mild persistent disease. IgE cut-off concentration of 989 IU/ml distinguishes mild persistent from those with moderate persistent asthma. Both showed adequate or good diagnostic efficacy. Cut off value of 168 IU/ml may prove useful in practice, indicating that 75 % of children in intermittent group will have serum concentration of total IgE &lt; 168 IU/ml. No association was observed between AEC and increasing severity of asthma. Only atopic dermatitis with asthma showed increasing trend of IgE levels. CONCLUSIONS Asthmatic children with higher asthma severity have a higher serum total IgE concentration (168 IU/ml and 989 IU/ml are the cut off values for differentiating intermittent from mild persistent and mild persistent from moderate persistent). KEYWORDS Serum IgE, Absolute Eosinophil Count, Childhood Asthma, Asthma Severity

Biologics in the Treatment of Severe Uncontrolled Asthma in Children

Asthma is the most common chronic disease in children, currently affecting about 7 million children. Severe uncontrolled asthma is rare in children with a prevalence of about 2.1% to 5%, but inflicts a disproportionate health burden. Children with severe asthma have increased risk of life threatening exacerbations, frequent hospitalization, worsening health-related quality of life, and impaired physical activity. Severe asthma in childhood is associated with long-term morbidities, such as bronchiolitis obliterans, impaired airway development, and development of chronic obstructive pulmonary disease in adulthood. Childhood asthma like adult-onset asthma, is classified into four cellular inflammatory phenotypes using induced sputum cytometry. The four phenotypes of asthma include eosinophilic asthma, neutrophilic asthma, paucigranulocytic asthma, and mixed cellularity asthma. The pathophysiological mechanisms of asthma involve airway inflammation and remodeling. Inflammatory mediators such as cytokines, chemokines, adhesion molecules, and growth factors play a key role in orchestration airway remodeling. During airway inflammation, cytokines secreted by type 2 helper (Th2) lymphocytes, such as interleukin-5 (IL-5), IL-4, IL-13, IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) play a key role in the pathogenesis of eosinophilic asthma. Whereas, the Th17 axis cytokines, including IL-17, IL-23, and IL-8 are responsible for the pathophysiology of neutrophilic asthma. The airway structural changes due to airway remodeling lead to thickening of the airway wall, narrowing of the bronchiolar lumen, airway obstruction, and decline in pulmonary function. Most of the children with asthma respond to low and medium inhaled corticosteroids, however a significant proportion still have severe asthma uncontrolled on the standard of care. The most common asthma phenotype in children is eosinophilic asthma, which responds superbly to biologic therapy. Children with severe asthma require add-on targeted interleukin antagonists (ILA), such as mepolizumab (anti-IL-5), benralizumab (anti-IL-5Rα), and dupilumab (anti-4Rα). ILAs have been shown to ameliorate asthma symptoms, reduce moderate and severe exacerbations, and improve pulmonary function. Additionally, ILAs have been demonstrated to improve the health-related quality of life, and have steroid sparing effect.

A Comprehensive Analysis of Immune Constituents in Blood and Bronchoalveolar Lavage Allows Identification of an Immune Signature of Severe Asthma in Children

BackgroundTargeted approaches may not account for the complexity of inflammation involved in children with severe asthma (SA), highlighting the need to consider more global analyses. We aimed to identify sets of immune constituents that distinguish children with SA from disease-control subjects through a comprehensive analysis of cells and immune constituents measured in bronchoalveolar lavage (BAL) and blood.MethodsTwenty children with SA and 10 age-matched control subjects with chronic respiratory disorders other than asthma were included. Paired blood and BAL samples were collected and analyzed for a large set of cellular (eosinophils, neutrophils, and subsets of lymphocytes and innate lymphoid cells) and soluble (chemokines, cytokines, and total antibodies) immune constituents. First, correlations of all immune constituents between BAL and blood and with demographic and clinical data were assessed (Spearman correlations). Then, all data were modelled using supervised multivariate analyses (partial least squares discriminant analysis, PLS-DA) to identify immune constituents that significantly discriminate between SA and control subjects. Univariate analyses were performed (Mann-Whitney tests) and then PLS-DA and univariate analyses were combined to identify the most discriminative and significant constituents.ResultsConcentrations of soluble immune constituents poorly correlated between BAL and blood. Certain constituents correlated with age or body mass index and, in asthmatics, with clinical symptoms, such as the number of exacerbations in the previous year, asthma control test score, or forced expiratory volume. Multivariate supervised analysis allowed construction of a model capable of distinguishing children with SA from control subjects with 80% specificity and 100% sensitivity. All immune constituents contributed to the model but some, identified by variable-important-in-projection values > 1 and p < 0.1, contributed more strongly, including BAL Th1 and Th2 cells and eosinophilia, CCL26 (Eotaxin 3), IgA and IL-19 concentrations in blood. Blood concentrations of IL-26, CCL13, APRIL, and Pentraxin-3 may also help in the characterization of SA.ConclusionsThe analysis of a large set of immune constituents may allow the identification of a biological immune signature of SA. Such an approach may provide new leads for delineating the pathogenesis of SA in children and identifying new targets for its diagnosis, prediction, and personalized treatment.

Biologic Therapy and Severe Asthma in Children.

Severe asthma is a heterogeneous, complex and chronic disease widespread in the pediatric population. According to the recent findings about the different endotypes of asthma in children, each one characterized by specific intracellular molecular pathways, several innovative biologic therapies have been developed. Due to their precise ability to target specific inflammatory type 2 mediators, biologics have revolutionized the care of chronic allergic diseases in the pediatric and adult population. In this review, we aim to provide the latest evidence about the use, indications, efficacy and safety of biologic therapies to treat severe asthma in children and adolescents.

Factors Associated with Persistence of Severe Asthma from Late Adolescence to Early Adulthood.

Asthma severity in children generally starts mild but may progress and stay severe for unknown reasons. Identify factors in childhood that predict persistence of severe asthma in late adolescence and early adulthood. The Childhood Asthma Management Program is the largest and longest asthma trial in 1041 children aged 5-12 years with mild to moderate asthma. We evaluated 682 participants from the program with analyzable data in late adolescence (age 17-19) and early adulthood (age 21-23). Severe asthma was defined using criteria from the American Thoracic Society and the National Asthma Education and Prevention Program to best capture severe asthma. Logistic regression with stepwise elimination was used to analyze clinical features, biomarkers, and lung function predictive of persistence of severe asthma. In late adolescence and early adulthood 12% and 19% of the patents had severe asthma, respectively; only 6% were severe at both time periods. For every 5% decrease in post bronchodilator FEV1/FVC in childhood, the odds of persistence of severe asthma increased 2.36-fold (95% CI: 1.70-3.28; p <0.0001), for participants with maternal smoking during pregnancy odds of persistence of severe asthma increased 3.17-fold (95% CI: 1.18-8.53, p=0.02). Reduced growth lung function trajectory was significantly associated with persistence of severe asthma compared to normal growth. Lung function and maternal smoking during pregnancy were significant predictors of severe asthma from late adolescence to early adulthood. Interventions to preserve lung function early may prevent disease progression.

Treatment for Severe Asthma in Children: What About Biologics?

Asthma is the most common pulmonary disease in children age 5 to 17 years. Asthma is characterized by chronic airway inflammation and heterogeneous clinical phenotypes. A small proportion of patients (approximately 5% to 10%) diagnosed with severe asthma are unable to achieve asthma control even with intensive therapy. Severe asthma in children is characterized by poor asthma control, uncontrolled symptoms, poor quality of life, disrupted school-related activities and increased risk of exacerbations, health care use, and morbidities due to asthma. Several new biologic agents targeting the mediators of asthma inflammation that are now approved are likely to improve asthma outcomes in children with severe asthma. This article outlines the various biologic agents currently approved for use in children. [Pediatr Ann. 2021;50(5):e206-e213.].

Biological Therapies in Children and Adolescents with Severe Uncontrolled Asthma: A Practical Review.

Severe uncontrolled asthma is a complex and heterogeneous disease. A multidisciplinary assessment is required to correctly identify and manage children and adolescents with severe asthma because they may require strict monitoring and additional treatment with advanced targeted therapies. Recent research efforts have focused on identifying epidemiologic, clinical, and molecular mechanisms that underlie severe asthma, leading to the recognition of different phenotypes and endotypes and identifying biomarkers able to predict the response to biologic therapies. Additional progress has occurred by introducing biological therapies that have revolutionized the care of chronic allergic diseases in the adult and pediatric population. In this review, we briefly summarized the current literature on biological therapies to treat severe asthma in children and adolescents.

Precision Medicine for Paediatric Severe Asthma: Current Status and Future Direction.

Asthma is a heterogeneous disease, characterised by different phenotypes and endotypes. Precision medicine in asthma refers to the implementation of a targeted therapy for each individual child, based on the identification of treatable traits, including environmental, immunological and genetic factors. Severe asthma in children is associated with increased hospitalisation rates, a lower quality of life, increased healthcare costs and an increased mortality. In the era of new molecular biologics treatments, it is essential to improve deep phenotyping of children with severe asthma in order to deliver the most effective treatment to each individual child. In this review, we discuss the personalised approach to the assessment and management of severe asthma. We explore the indications and use of the currently licensed biologics, as well as the potential of other emerging treatments.

Contemporary diagnosis and management of childhood asthma

Asthma is a chronic heterogeneous inflammatory disorder/syndrome of the airways that affects more than 300 Million people worldwide. Asthma often starts in childhood (Allergic Asthma phenotype).Co morbidities often trigger asthma exacerbations. It’s often difficult to diagnose asthma in young children. Objective tests of lung function aid in the diagnosis of asthma in children &gt; six years of age. Asthma has phenotypes and endotypes. Biomarkers Ex. Fractional excretion of Nitric Oxide aid in the diagnosis of severe asthma in children and adults. Management of Severe Asthma has undergone a revolution. Asthma is responsible for considerable global morbidity and health-care costs. Substantial progress was made against key outcomes such as hospital admissions with asthma and mortality in the 1990s and early 2000s, but little improvement has been observed in the past 10 years, despite escalating treatment costs.