Future Research Directions in Asthma. An NHLBI Working Group Report

Levy, Bruce D.; Noël, Patricia; Freemer, Michelle; Cloutier, Michelle M.; Georas, Steve N.; Jarjour, Nizar N.; Ober, Carole; Woodruff, Prescott G.; Barnes, Kathleen C.; Bender, Bruce G.; Camargo, Carlos A.; Chupp, G.L.; Denlinger, Loren C.; Fahy, John V.; Fitzpatrick, Anne M.; Fuhlbrigge, Anne L.; Gaston, B.; Hartert, Tina V.; Kolls, Jay K.; Lynch, Susan V.; Moore, Wendy C.; Morgan, Wayne J.; Nadeau, Kari; Ownby, Dennis R.; Solway, Julian; Szefler, Stanley J.; Wenzel, Sally E.; Wright, Rosalind J.; Smith, Robert A.; Erzurum, Serpil C.

doi:10.1164/rccm.201505-0963ws

Cited by 85 publications

(56 citation statements)

References 44 publications

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“…4,5 Young children are particularly diverse with numerous and variable phenotypic presentations in early life that correspond to different outcomes, 6-9 yet they are incompletely studied and significant treatment gaps remain. 10,11 Even among young children who warrant treatment with daily inhaled corticosteroids (ICS) , the response to ICS is inconsistent, 12 perhaps due to differences in symptom presentation and/or persistence 13 or other underlying inflammatory features.…”

Section: Introductionmentioning

confidence: 99%

Individualized therapy for persistent asthma in young children

Fitzpatrick

Jackson

Mauger

et al. 2016

Journal of Allergy and Clinical Immunology

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218

217

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Background Phenotypic presentations in young children with asthma are varied and may contribute to differential responses to asthma controller medications. Methods The Individualized Therapy for Asthma in Toddlers (INFANT) study was a multicenter, randomized, double-blind, double-dummy, clinical trial in children age 12-59 months (n=300) with asthma necessitating treatment with daily controller (Step 2) therapy. Participants completed a 2-8 week run-in period followed by three crossover periods with daily inhaled corticosteroid (ICS), daily leukotriene receptor antagonist (LTRA), and as-needed ICS treatment co-administered with albuterol. The primary outcome was differential response to asthma medication based on a composite measure of asthma control. The primary analysis involved two stages: determination of differential response, and assessment of whether three pre-specified features (aeroallergen sensitization, previous exacerbations, sex) predicted differential response. Results 74% (170 of 230) of children with analyzable data had a differential response to the three treatment strategies. Within differential responders, the probability of best response was highest for daily ICS and was predicted by aeroallergen sensitization, but not exacerbation history or sex. The probability of best response to daily ICS was further increased in children with both aeroallergen sensitization and blood eosinophils ≥300/μL. In these children, daily ICS was associated with more asthma control days and fewer exacerbations compared to the other treatments. Conclusions In young children with asthma necessitating Step 2 treatment, phenotyping with aeroallergen sensitization and blood eosinophils is useful for guiding treatment selection and identifies children with a high exacerbation probability for whom treatment with daily ICS is beneficial despite possible risks of growth suppression.

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Section: Introductionmentioning

confidence: 99%

Individualized therapy for persistent asthma in young children

Fitzpatrick

Jackson

Mauger

et al. 2016

Journal of Allergy and Clinical Immunology

Self Cite

218

217

View full text Add to dashboard Cite

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“…Traditional asthma therapies, although effective for many patients, provide only temporary symptomatic alleviation [103]. Moreover, even with these interventions, some patients still experience exacerbations and progressive deterioration of pulmonary function [5, 12].…”

Section: Resultsmentioning

confidence: 99%

PPARs: Key Regulators of Airway Inflammation and Potential Therapeutic Targets in Asthma

Banno

Reddy

Lakshmi

et al. 2018

Nuclear Receptor Research

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Asthma affects approximately 300 million people worldwide, significantly impacting quality of life and healthcare costs. While current therapies are effective in controlling many patients’ symptoms, a large number continue to experience exacerbations or treatment-related adverse effects. Alternative therapies are thus urgently needed. Accumulating evidence has shown that the peroxisome proliferator-activated receptor (PPAR) family of nuclear hormone receptors, comprising PPARα, PPARβ/δ, and PPARγ, is involved in asthma pathogenesis and that ligand-induced activation of these receptors suppresses asthma pathology. PPAR agonists exert their anti-inflammatory effects primarily by suppressing pro-inflammatory mediators and antagonizing the pro-inflammatory functions of various cell types relevant to asthma pathophysiology. Experimental findings strongly support the potential clinical benefits of PPAR agonists in the treatment of asthma. We review current literature, highlighting PPARs’ key role in asthma pathogenesis and their agonists’ therapeutic potential. With additional research and rigorous clinical studies, PPARs may become attractive therapeutic targets in this disease.

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“…Layer in the global interest in personalized medicine and existing asthma clinical network efforts to categorize specific asthma populations based on their underlying pathology (Levy, et al, 2015), and it is not difficult to envision an expanded repertoire of asthma drugs, or drug combinations tailored to better manage specific asthmatic subpopulations. Perhaps most encouraging (for the treatment of all diseases) is the promise of biased ligand pharmacology, which now has a strong foundation built on multiple basic science disciplines and will likely find wide spread clinical application once industry expands its platforms and strategies to accommodate the reality that ligands have much greater capacity to manipulate GPCRs than previously thought.…”

Section: What We Can Expect In the Near (And Not-so-near) Futurementioning

confidence: 99%

Bronchoprotection and bronchorelaxation in asthma: New targets, and new ways to target the old ones

Pera

Penn

2016

Pharmacology & Therapeutics

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Despite over 50 years of inhaled beta-agonists and corticosteroids as the default management or rescue drugs for asthma, recent research suggests that new therapeutic options are likely to emerge. This belief stems from both an improved understanding of what causes and regulates airway smooth muscle (ASM) contraction, and the identification of new targets whose inhibition or activation can relax ASM. In this review we discuss the recent findings that provide new insight into ASM contractile regulation, a revolution in pharmacology that identifies new ways to “tune” G protein-coupled receptors to improve therapeutic efficacy, and the discovery of several novel targets/approaches capable of effecting bronchoprotection or bronchodilation.

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Future Research Directions in Asthma. An NHLBI Working Group Report

Cited by 85 publications

References 44 publications

Individualized therapy for persistent asthma in young children

Individualized therapy for persistent asthma in young children

PPARs: Key Regulators of Airway Inflammation and Potential Therapeutic Targets in Asthma

Bronchoprotection and bronchorelaxation in asthma: New targets, and new ways to target the old ones

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