Neutrophilic Steroid-Refractory Recurrent Wheeze and Eosinophilic Steroid-Refractory Asthma in Children

Guiddir, Tamazoust; Saint‐Pierre, Philippe; Purenne-Denis, Elsa; Lambert, Nathalie; Laoudi, Yacine; Couderc, Rémy; Gouvis-Echraghi, Rahelé; Amat, Flore; Just, Jocelyne

doi:10.1016/j.jaip.2017.02.003

Cited by 73 publications

(66 citation statements)

References 47 publications

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“…In 27 studies this was by skin prick test, or specific IgE or total IgE; while in seven studies atopy was evaluated by total IgE or clinically; and in three studies only on clinical criteria . Sixteen studies recorded the presence of previous asthma attacks. Twenty‐nine studies recorded current asthma medications …”

Section: Resultsmentioning

confidence: 99%

“…Sixteen studies recorded the presence of previous asthma attacks. Twenty‐nine studies recorded current asthma medications …”

Section: Resultsmentioning

confidence: 99%

“…Fourteen studies had a control group defined as non‐asthmatic/wheezing children (two also included adults); in 11 studies there was no control group; in six studies the control group was defined as upper airways symptoms; in six studies the control group was defined as lower respiratory problems but non‐asthma; and one study compared children that in the future developed asthma (positive vs negative athma predictive index [API]) (Table ).…”

Section: Resultsmentioning

confidence: 99%

“…Airway inflammation was determined in 20 studies . Significant airway eosinophilia was reported in seven studies (in BAL alone, in biopsy alone, and in both); while eosinophilic cationic protein (ECP) in BAL was elevated in three studies, but not in one .…”

Section: Resultsmentioning

confidence: 99%

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The relationship between inflammation and remodeling in childhood asthma: A systematic review

Castro-Rodriguez

Saglani

Rodríguez‐Martínez

et al. 2018

Pediatric Pulmonology

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Section: Resultsmentioning

confidence: 99%

“…Sixteen studies recorded the presence of previous asthma attacks. Twenty‐nine studies recorded current asthma medications …”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

The relationship between inflammation and remodeling in childhood asthma: A systematic review

Castro-Rodriguez

Saglani

Rodríguez‐Martínez

et al. 2018

Pediatric Pulmonology

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show abstract

“…12,17 • Early sensitization to multiple allergens, but also molecular allergens, conveys a higher risk of asthma exacerbations. [33][34][35][36][37] • Patients with the persistent eosinophilic phenotype have a greater risk of asthma exacerbations. [33][34][35][36][37] • Patients with the persistent eosinophilic phenotype have a greater risk of asthma exacerbations.…”

Section: Discussionmentioning

confidence: 99%

Clinical phenotypes in asthma during childhood

Just

Bourgoin‐Heck

Amat

2017

Clin Experimental Allergy

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Asthma is a heterogeneous disease characterized by numerous phenotypes relating to age of onset, triggers, comorbidities, severity (assessed by multiple exacerbations, lung function pattern) and finally the inflammatory cells involved in the pathophysiologic pathway. These phenotypes can vary over time in relation to changes in the principal triggers involved in the aetiology of the disease. Nevertheless, in a patient with multiple allergies and early-onset disease (defined as multiple sensitizations and allergic comorbidities), the prognosis of asthma is poor with a high risk of persistence and severity of the disease during childhood. Future research will focus on classifying phenotypes into groups based on pathophysiologic mechanisms (endotypes) and the biomarkers attached to these endotypes, which could predict prognosis and lead to targeted therapy. Currently, these biomarkers are related to inflammatory cells associated with the asthma endotype, essentially eosinophils and neutrophils (and related cytokines) attached to Th-2 and non Th-1 pathways, respectively. The most severe asthma (refractory asthma) is linked to neutrophil-derived inflammation (frequently associated with female sex, obesity and possibly disorganized airway microbiota) encountered in very young children or teenagers. Severe asthma is also linked to or a marked eosinophil inflammatory process (frequently associated with multiple atopy and, more rarely, with non-atopic hypereosinophilic asthma in children) and frequently encountered in teenagers. Severe phenotypes of asthma could also play a role in the origin of chronic obstructive pulmonary disease in adult life.

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Subcutaneous mepolizumab in children aged 6 to 11 years with severe eosinophilic asthma

Gupta

Pouliquen²,

Austin³

et al. 2019

Pediatric Pulmonology

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Objectives There are no published reports for anti‐interleukin‐5 therapy in children <12 years with asthma. The primary objective of this study was to characterize the pharmacokinetics and pharmacodynamics of mepolizumab following subcutaneous (SC) administration in children 6 to 11 years‐of‐age with severe eosinophilic asthma. Hypothesis Mepolizumab SC pharmacokinetics and pharmacodynamics in children with severe eosinophilic asthma are comparable with adults. Study Design Multinational, nonrandomised, open‐label (NCT02377427). Patient Selection Children 6 to 11 years‐of‐age with severe eosinophilic asthma (blood eosinophil count ≥150 cells/µL at screening or ≥300 cells/µL <12 months of screening) and ≥2 exacerbations in the prior year. Methodology Children received mepolizumab SC 40 mg (bodyweight <40 kg) or 100 mg (≥40 kg) every 4 weeks for 12 weeks. Results Thirty‐six children received mepolizumab (40 mg, n = 26; 100 mg, n = 10). Mepolizumab exposures were higher and apparent clearance lower than predicted based on prior existing data. Derived mepolizumab exposures normalized to mean bodyweight for the 40 mg and 100 mg dose groups were 454 μg * day/mL and 675 μg * day/mL, respectively. At week 12, blood eosinophils were reduced by 89% and 83% from baseline to 42 and 55 cells/µL, respectively. Mepolizumab was well tolerated; no new safety signals were observed compared with previous adult/adolescent studies. Conclusion In children 6 to 11 years‐of‐age with severe eosinophilic asthma, mepolizumab SC 40 or 100 mg provided bodyweight‐adjusted drug exposure within twofold of target adult exposure as well as marked reductions to blood eosinophil counts similar to adults, and although not designed to evaluate efficacy outcomes, demonstrated a positive clinical profile.

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Neutrophilic Steroid-Refractory Recurrent Wheeze and Eosinophilic Steroid-Refractory Asthma in Children

Abstract: Inflammation pathway of asthma and recurrent wheeze are related to eosinophil cells in older children and neutrophil cells in younger children. These results could improve personalized treatments.

Cited by 73 publications

References 47 publications

The relationship between inflammation and remodeling in childhood asthma: A systematic review

The relationship between inflammation and remodeling in childhood asthma: A systematic review

Clinical phenotypes in asthma during childhood

Subcutaneous mepolizumab in children aged 6 to 11 years with severe eosinophilic asthma

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