Defining pediatric asthma: phenotypes to endotypes and beyond

Conrad, Laura A.; Cabana, Michael D.; Rastogi, Deepa

doi:10.1038/s41390-020-01231-6

Cited by 59 publications

(41 citation statements)

References 66 publications

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“…This approach looks at etiologies and clinical biomarkers such as eosinophils, FENO, lung function, Immunoglobulin E, atopy, comorbidities, physiology, and degree of symptomatology and controller therapy. Studies define groups differently with each endotype appearing to be more or less responsive to particular treatments and interventions (Conrad et al, 2020).…”

Section: Diagnosis Of Asthmamentioning

confidence: 99%

Pharmacology Update: Emergency and Controller Medications for Treatment of Asthma

2021

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Asthma is the most common noncommunicable chronic childhood disease, affecting more than 5 million children in the United States. Asthma is the leading cause of school absenteeism. Treatments for asthma are divided into fast-acting medications that are used to relieve symptoms and slower acting (controller) medications that prevent symptoms. Albuterol is the most common fast acting medication for asthma, and it exists in multiple forms, including metered-dose inhaler and nebulized therapy. The use of spacers and holding chambers can further improve medication deposition in the airway. The cornerstone controller therapy for asthma is inhaled corticosteroid. Other medications for asthma include long-acting beta agonists, long-acting antimuscarinics, and antileukotrienes. The newest agents for controller asthma therapies are biologics.

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Section: Diagnosis Of Asthmamentioning

confidence: 99%

Pharmacology Update: Emergency and Controller Medications for Treatment of Asthma

2021

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“…Over the last few decades, there has been a shift in the approach of describing the complex and heterogeneous nature of asthma, which can possibly permit the delivery of precision medicine to pediatric patients. Recent advances have classifiedasthma into phenotypes and endotypes in a commendable attempt to group individuals based on common features, pathophysiology and treatment approaches [ 1 , 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…In light of the multiple shapes of asthma, which present as a diverse entity with multiple underlying mechanisms, patient responses to treatment vary tremendously. Probably the most common and distinctly identified phenotype of the disease is characterized by increased T-helper 2 (TH2) cytokines and mediators, known as allergic or TH2-high asthma [ 2 , 3 ]. Accordingly, TH2-high asthma is defined by the underlying feature of elevated levels of type 2 inflammation in the airways compared with healthy controls [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Biologic Therapies in Pediatric Asthma

Perikleous

Steiropoulos

Nena

et al. 2022

JPM

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Undeniably, childhood asthma is a multifactorial and heterogeneous chronic condition widespread in children. Its management, especially of the severe form refractory to standard therapy remains challenging. Over the past decades, the development of biologic agents and their subsequent approval has provided an advanced and very promising treatment alternative, eventually directing toward a successful precision medicine approach. The application of currently approved add-on treatments for severe asthma in children, namely omalizumab, mepolizumab, benralizumab, dupilumab, and tezepelumab have been shown to be effective in terms of asthma control and exacerbation rate. However, to date, information is still lacking regarding its long-term use. As a result, data are frequently extrapolated from adult studies. Thus, the selection of the appropriate biologic agent, the potential predictors of good asthma response, and the long-term outcome in the pediatric population are still to be further investigated. The aim of the present study was to provide an overview of the current status of the latest evidence about all licensed monoclonal antibodies (mAbs) that have emerged and been applied to the field of asthma management. The innovative future targets are also briefly discussed.

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“…Briefly, the Th2 pathway begins with allergen stimulation of Th2 cytokines (IL-4, IL-5, IL-9, IL-13) which trigger IgE release by B cells, which together promote histamine and leukotriene release by mast cells and eosinophilic inflammation [ 13 ]. General dampening of this inflammatory response by steroids or therapies targeting specific mediators within this pathway, i.e., leukotriene inhibitors and anti-IgE, IL4, or monoclonal antibodies, have been greatly effective for some but also revealed a broad group of pediatric non-responders with seemingly non-atopic and/or non-steroid responsive disease [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…Sputum transcriptomics has linked this type of airway eosinophilia to gene signatures from metabolic, ubiquitination, and mitochondrial function pathways [ 19 ]. The full range of asthma endotypes is beyond the scope of this review and is described in detail elsewhere [ 15 , 20 – 22 ]. Despite the application of multi-omic technologies and related advances in asthma classification and treatment algorithms, therapy-resistant phenotypes persist, and early-life therapies have yet to change the long-term disease trajectory.…”

Section: Introductionmentioning

confidence: 99%

Perinatal origins of chronic lung disease: mechanisms–prevention–therapy—sphingolipid metabolism and the genetic and perinatal origins of childhood asthma

Wasserman

Worgall

2021

Mol Cell Pediatr

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Childhood asthma derives from complex host-environment interactions occurring in the perinatal and infant period, a critical time for lung development. Sphingolipids are bioactive molecules consistently implicated in the pathogenesis of childhood asthma. Genome wide association studies (GWAS) initially identified a link between alleles within the 17q21 asthma-susceptibility locus, childhood asthma, and overexpression of the ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3), an inhibitor of de novo sphingolipid synthesis. Subsequent studies of pediatric asthma offer strong evidence that these asthma-risk alleles correlate with early-life aberrancies of sphingolipid homeostasis and asthma. Relationships between sphingolipid metabolism and asthma-related risk factors, including maternal obesity and respiratory viral infections, are currently under investigation. This review will summarize how these perinatal and early life exposures can synergize with 17q21 asthma risk alleles to exacerbate disruptions of sphingolipid homeostasis and drive asthma pathogenesis.

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Defining pediatric asthma: phenotypes to endotypes and beyond

Cited by 59 publications

References 66 publications

Pharmacology Update: Emergency and Controller Medications for Treatment of Asthma

Pharmacology Update: Emergency and Controller Medications for Treatment of Asthma

Biologic Therapies in Pediatric Asthma

Perinatal origins of chronic lung disease: mechanisms–prevention–therapy—sphingolipid metabolism and the genetic and perinatal origins of childhood asthma

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