Asthma and Corticosteroid Responses in Childhood and Adult Asthma

Ramadan, Amira; Gaffin, Jonathan M.; Israel, Elliot; Phipatanakul, Wanda

doi:10.1016/j.ccm.2018.10.010

Cited by 42 publications

(35 citation statements)

References 131 publications

(134 reference statements)

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“…At the same time, corticosteroid resistance in asthma is a very complex problem. Current research shows that the mechanism of corticosteroid resistance may be related to genetic variation, epigenetics, asthma phenotypes, race and the airway microbiome [60].…”

Section: Nthi Infection and Corticosteroid-resistant Asthmamentioning

confidence: 99%

The role of NTHi colonization and infection in the pathogenesis of neutrophilic asthma

et al. 2020

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Asthma is a complex heterogeneous disease. The neutrophilic subtypes of asthma are described as persistent, more severe and corticosteroid-resistant, with higher hospitalization and mortality rates, which seriously affect the lives of asthmatic patients. With the development of high-throughput sequencing technology, an increasing amount of evidence has shown that lower airway microbiome dysbiosis contributes to the exacerbation of asthma, especially neutrophilic asthma. Nontypeable Haemophilus influenzae is normally found in the upper respiratory tract of healthy adults and is one of the most common strains in the lower respiratory tract of neutrophilic asthma patients, in whom its presence is related to the occurrence of corticosteroid resistance. To understand the pathogenic mechanism by which nontypeable Haemophilus influenzae colonization leads to the progression of neutrophilic asthma, we reviewed the previous literature on nontypeable Haemophilus influenzae colonization and subsequent aggravation of neutrophilic asthma and corticosteroid resistance. We discussed nontypeable Haemophilus influenzae as a potential therapeutic target to prevent the progression of neutrophilic asthma.

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Section: Nthi Infection and Corticosteroid-resistant Asthmamentioning

confidence: 99%

The role of NTHi colonization and infection in the pathogenesis of neutrophilic asthma

et al. 2020

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“…Furthermore, not only interindividual differences in ICS response have been described, but also differences among different populations and ethnic groups [ 4 , 8 ]. These differences have been evidenced to be the result of the interaction of several factors, including comorbidities, environmental exposures, and the clinical characteristics of the disease, among others [ 9 ]. For instance, the type of asthma (e.g., atopic or non-atopic) could partly contribute to the responsiveness to ICS therapy in some patients.…”

Section: Introductionmentioning

confidence: 99%

Identification of ROBO2 as a Potential Locus Associated with Inhaled Corticosteroid Response in Childhood Asthma

Hernandez‐Pacheco

Gorenjak

et al. 2021

JPM

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Inhaled corticosteroids (ICS) are the most common asthma controller medication. An important contribution of genetic factors in ICS response has been evidenced. Here, we aimed to identify novel genetic markers involved in ICS response in asthma. A genome-wide association study (GWAS) of the change in lung function after 6 weeks of ICS treatment was performed in 166 asthma patients from the SLOVENIA study. Patients with an improvement in lung function ≥8% were considered as ICS responders. Suggestively associated variants (p-value ≤ 5 × 10−6) were evaluated in an independent study (n = 175). Validation of the association with asthma exacerbations despite ICS use was attempted in European (n = 2681) and admixed (n = 1347) populations. Variants previously associated with ICS response were also assessed for replication. As a result, the SNP rs1166980 from the ROBO2 gene was suggestively associated with the change in lung function (OR for G allele: 7.01, 95% CI: 3.29–14.93, p = 4.61 × 10−7), although this was not validated in CAMP. ROBO2 showed gene-level evidence of replication with asthma exacerbations despite ICS use in Europeans (minimum p-value = 1.44 × 10−5), but not in admixed individuals. The association of PDE10A-T with ICS response described by a previous study was validated. This study suggests that ROBO2 could be a potential novel locus for ICS response in Europeans.

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“…Pediatric asthma is a heterogeneous chronic inflammatory disease of the airways, characterized by a large number of observable characteristics (phenotypes) related to a complex combination of underlying pathophysiological and/or molecular mechanisms (endotypes), which involve several cell types, mediators and immune pathways [ 1 , 2 , 3 ]. Endotypes differ across the spectrum of asthma, providing a variable response to standard anti-inflammatory therapy with inhaled corticosteroids (ICS) [ 4 , 5 ], which are presently the mainstream of asthma treatment [ 6 , 7 , 8 ]. Furthermore, different regulatory mechanisms, such as release of a variety of cytokines, chemokines and other mediators, may influence airway epithelium responses [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Breathomics in Asthmatic Children Treated with Inhaled Corticosteroids

et al. 2020

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Background: “breathomics” enables indirect analysis of metabolic patterns underlying a respiratory disease. In this study, we analyze exhaled breath condensate (EBC) in asthmatic children before (T0) and after (T1) a three-week course of inhaled beclomethasone dipropionate (BDP). Methods: we recruited steroid-naive asthmatic children for whom inhaled steroids were indicated and healthy children, evaluating asthma control, spirometry and EBC (in asthmatics at T0 and T1). A liquid-chromatography–mass-spectrometry untargeted analysis was applied to EBC and a mass spectrometry-based target analysis to urine samples. Results: metabolomic analysis discriminated asthmatic (n = 26) from healthy children (n = 16) at T0 and T1, discovering 108 and 65 features relevant for the discrimination, respectively. Searching metabolomics databases, seven putative biomarkers with a plausible role in asthma biochemical–metabolic processes were found. After BDP treatment, asthmatic children, in the face of an improved asthma control (p < 0.001) and lung function (p = 0.01), showed neither changes in EBC metabolomic profile nor in urinary endogenous steroid profile. Conclusions: “breathomics” can discriminate asthmatic from healthy children, with prostaglandin, fatty acid and glycerophospholipid as putative markers. The three-week course of BDP—in spite of a significant clinical improvement—was not associated with changes in EBC metabolic arrangement and urinary steroid profile.

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Asthma and Corticosteroid Responses in Childhood and Adult Asthma

Cited by 42 publications

References 131 publications

The role of NTHi colonization and infection in the pathogenesis of neutrophilic asthma

The role of NTHi colonization and infection in the pathogenesis of neutrophilic asthma

Identification of ROBO2 as a Potential Locus Associated with Inhaled Corticosteroid Response in Childhood Asthma

Breathomics in Asthmatic Children Treated with Inhaled Corticosteroids

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