Severe asthma in children

Bush, Andy; Fleming, Louise; Saglani, Sejal

doi:10.1111/resp.13085

Cited by 91 publications

(84 citation statements)

References 97 publications

(80 reference statements)

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“…Faced with a child or adolescent with a possible severe asthma diagnosis, clinicians need to consider possibilities, which are more fully described elsewhere and summarized here: Is this asthma?…”

Section: Introductionmentioning

confidence: 99%

Severe asthma in children—a review of definitions, epidemiology, and treatment options in 2019

Ahmed

Turner

2019

Pediatric Pulmonology

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Severe asthma is a relatively uncommon condition in children but one which causes morbidity, occasionally mortality, and is a challenging condition to manage. There are several definitions of severe asthma, which have a common theme of poor control despite high dose inhaled corticosteroid treatment. Depending on the definition chosen, the prevalence of severe childhood asthma may be up to 5% within populations with asthma. Collectively, there is some evidence that the treatments used in severe asthma are beneficial, but a solid evidence‐base is lacking for many treatments and some treatments have recognized side effects. Evidence supporting the use of maintenance oral prednisolone and intramuscular triamcinolone is weak. Response to systemic corticosteroids is heterogeneous and recognizing phenotypes or endotypes may identify those most likely to gain maximal benefit from treatment. For children aged 6 to 11 years, the anti‐IgE biologic omalizumab is effective and anti‐IL‐5 agent (mepolizumab) has recently been licenced in Europe (but not the US). Biologics, which are licenced for >11 year olds include omalizumab, mepolizumab, benralizumab, reslizumab, and dupilumab. There is plenty that the clinician can offer to the child and adolescent with severe asthma in 2019, including nontherapeutic and therapeutic interventions. To manage severe asthma, practitioners from broad specialities must establish and maintain a close therapeutic relationship with patients. Looking beyond 2019, more treatment options will emerge for severe childhood asthma, and clinical teams will need to continue weighing up benefits and harms.

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Section: Introductionmentioning

confidence: 99%

Severe asthma in children—a review of definitions, epidemiology, and treatment options in 2019

Ahmed

Turner

2019

Pediatric Pulmonology

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“…104 Secondly, long-term colonization or infection of the airways with allergenic fungi could provide a persistent source of allergen exposure and trigger proinflammatory host defence mechanisms. 9 It has even been reported that chronic fungal infection of the skin and nails can exacerbate asthma, with improvement in asthma symptoms and lung function on treatment of the infection. 24,104-106 SAFS is typically associated with worse inflammation than other phenotypes of STRA despite more asthma treatment.…”

Section: Mouldsmentioning

confidence: 99%

“…50 • Management of coexisting food allergy including avoidance advice, personal management plan for allergic reactions and access to self-injectable adrenaline. 9,95,131 3. Antifungal therapy may need to be considered though evidence for itraconazole and voriconazole in children is weak and may be associated with significant side-effects.…”

Section: Box 2 An Approach To Identify and Manage Stra And Allergic Tmentioning

confidence: 99%

“…Some children have asthma that is difficult to treat despite high doses of ICS and additional controller medications due to modifiable factors, commonly poor adherence to ICS or persistent exposure to environmental triggers. [4][5][6][7][8][9] These children have "severe therapy-resistant asthma" (STRA) (Box 1). 3 However, 2%-5% of children with asthma remain symptomatic despite addressing modifiable factors and treatment with high-dose ICS, long-acting β2-receptor agonists, leukotriene receptor antagonists and occasionally systemic corticosteroids.…”

Section: Introductionmentioning

confidence: 99%

“…10 Despite the low prevalence of STRA, it accounts for significant morbidity and almost 50% of total asthma-related expenditure. 17 It is also necessary to minimize exposure to environmental allergens where possible, 2 avoid pollutants including cigarette smoke 13 and manage comorbidities including obesity, 9 dysfunctional breathing and vocal cord dysfunction, allergic rhinitis and food allergy. 12 This involves confirming the diagnosis of asthma by demonstrating variable and reversible airflow obstruction, [13][14][15] ensuring adherence to treatment by checking general practitioner prescription records and that the appropriate inhalers are available on the home visit 2,16 and checking the child's inhaler technique.…”

Section: Introductionmentioning

confidence: 99%

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Does allergy explain why some children have severe asthma?

Bonner

Roberts

2018

Clin Experimental Allergy

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Asthma is a common disease in childhood with a minority of affected children having severe therapy-resistant asthma (STRA). Children with STRA can be differentiated from those with mild-moderate disease by greater allergic sensitization, increased eosinophilic airway inflammation, increased airway remodelling and reduced corticosteroid responsiveness. The aetiology of STRA in children is multifactorial but allergy seems to play a key role. Many children with asthma have coexisting allergic disease, and severe rhinitis seems to be an important driver of STRA in children. Allergies to foods, moulds, pollen and pets have also been associated with severe asthma exacerbations. Identifying allergens that are driving asthma symptoms in children with STRA may provide additional strategies for improving their disease control. Avoidance strategies may be possible. Additional monoclonal antibody therapy with Omalizumab or Mepolizumab may be helpful in children with clinically important polysensitization.

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Flavonoids as Cytokine Immunomodulators to Reduce Airway Inflammation via Inhibition of the NF‐κB Signalling Pathway: A Systematic Overview

Gandhi¹,

Dhanabalan²,

Vasconcelos³

et al. 2020

Encyclopedia of Life Sciences

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Asthma is a chronic inflammatory respiratory disease with increasing prevalence which has been linked to the interaction of genetic and environmental factors. Specific types of infections and environmental exposure, alongside a predisposed set of genes, can lead to a systemic propensity for allergic T‐helper (Th) type 2 cells to induce cytokine responses, resulting in allergic airway inflammation. The key event in the pathogenesis of asthma is infiltration of inflammatory cells into the airways and lungs, resulting in mucus hypersecretion and intermittent obstructive events. Cytokines play a vital role in the pathogenesis of immune responses and also have a complex mode of action in inflammatory processes. Peer‐reviewed articles investigating flavonoids with therapeutic evidence for the management of asthma were acquired from Pubmed, Embase, Scopus and Web of Science. We provide an extensive overview of the modulation of cytokines by flavonoids to assess how these natural products trigger immune responses, modulate immunity and lower airway inflammation. Seventeen flavonoids were reported as cytokine modulators of nuclear transcription factor kappa B (NF‐κB) signalling in the identified articles. These flavonoids predominantly modulated the release of the production and expressions of the pro‐ and anti‐inflammatory cytokines TNF‐α, IL‐1β, IL‐8, Th17 (IL‐17), Th1 (IFN‐γ, IL‐2 and IL‐12) and Th2 (IL‐4, IL‐5, IL‐6 and IL‐13), inhibited eosinophil infiltration and decreased the activity and expression of NF‐κB. Key Concepts Bronchial asthma is a chronic inflammatory airway syndrome which endangers human health. Corticosteroids and β2‐agonists are effective drugs for asthma; however, their prolonged use is associated with side effects such as drug tolerance, osteoporosis and immune suppression. Asthma increases the number of inflammatory cells such as eosinophils and lymphocytes in peripheral blood, bronchoalveolar lavage fluid (BALF) and lung tissue and immunoglobulin E (IgE). Flavonoids are plant‐derived active compounds reputed to have therapeutic potential. The use of flavonoids in experimentally induced asthma models is associated with lower levels of Th2 cytokines such as IL‐4, IL‐5, IL‐6 and IL‐13 and modulation of pro‐inflammatory cytokines such as TNF‐α, IL‐1β and IL‐8. Flavonoids generally inhibit pulmonary nuclear transcription factor kappa‐B (NF‐κB) or mitogen‐activated protein kinase (MAPK) signalling pathways and reduce airway inflammation in experimental models. Flavonoids reduce airway hyperresponsiveness, mucus cell hyperplasia and fixed airway flow obstruction. Flavonoids demonstrated significant in vitro and in vivo properties in animal models on homeostasis within the immune system and on the inflammatory response.

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Severe asthma in children

Cited by 91 publications

References 97 publications

Severe asthma in children—a review of definitions, epidemiology, and treatment options in 2019

Severe asthma in children—a review of definitions, epidemiology, and treatment options in 2019

Does allergy explain why some children have severe asthma?

Flavonoids as Cytokine Immunomodulators to Reduce Airway Inflammation via Inhibition of the NF‐κB Signalling Pathway: A Systematic Overview

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