Advances in asthma in 2016: Designing individualized approaches to management

Anderson, William C.; Apter, Andrea J.; Dutmer, Cullen M.; Searing, Daniel A.; Szefler, Stanley J.

doi:10.1016/j.jaci.2017.06.015

Cited by 25 publications

(14 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among numerous pathogenic components for asthma, we tested two major players-Th2 cytokines and RV infection-for their effects on SCGB1A1 reduction. Th2 cytokines are classical players in regulating the "Th2-high" asthma endotype (60,61), and human RV is the major contributor to asthma exacerbations and severe asthma (62,63). We have demonstrated the causal link between Th2 cytokines/RV and SCGB1A1 reduction in asthmatic airways.…”

Section: Discussionmentioning

confidence: 72%

The Club Cell Marker SCGB1A1 Downstream of FOXA2 is Reduced in Asthma

Zhu¹,

An²,

Ran³

et al. 2019

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Human SCGB1A1 protein has been shown to be significantly reduced in BAL, sputum, and serum from humans with asthma as compared with healthy individuals. However, the mechanism of this reduction and its functional impact have not been entirely elucidated. By mining online datasets, we found that the mRNA of SCGB1A1 was significantly repressed in brushed human airway epithelial cells from individuals with asthma, and this repression appeared to be associated with reduced expression of FOXA2. Consistently, both Scgb1A1 and FoxA2 were downregulated in an ovalbumin-induced mouse model of asthma. Furthermore, compared with wild-type mice, Scgb1a1 knockout mice had increased airway hyperreactivity and inflammation when they were exposed to ovalbumin, confirming the antiinflammatory role of Scgb1a1 in protection against asthma phenotypes. To search for potential asthma-related stimuli of SCGB1A1 repression, we tested T-helper cell type 2 cytokines. Both IL-4 and IL-13 repressed epithelial expression of SCGB1A1 and FOXA2. Importantly, infection of epithelial cells with human rhinovirus similarly reduced expression of these two genes, which suggests that FOXA2 may be the common regulator of SCGB1A1. To establish the causal role of reduced FOXA2 in SCGB1A1 repression, we demonstrated that FOXA2 was required for SCGB1A1 expression at baseline. FOXA2 overexpression was sufficient to drive promoter activity and expression of SCGB1A1 and was also able to restore the repressed SCGB1A1 expression in IL-13-treated or rhinovirus-infected cells. Taken together, these findings suggest that low levels of epithelial SCGB1A1 in asthma are caused by reduced FOXA2 expression.

show abstract

Section: Discussionmentioning

confidence: 72%

The Club Cell Marker SCGB1A1 Downstream of FOXA2 is Reduced in Asthma

Zhu¹,

An²,

Ran³

et al. 2019

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

show abstract

“…Similarly, Teague et al concluded that “in 32% of children evaluated, BAL revealed corticosteroid‐refractory eosinophilic infiltration amenable to anti‐T H 2 biological therapies.” While data from these studies are insufficient to routinely inform treatment changes at present, ongoing investigations may identify a larger role in the assessment of lower airway inflammation in clinical care. Indeed, recent reports suggest that analysis of inflammatory patterns in bronchial biopsies may be useful in predicting future lung function …”

Section: Back To the Future: The Re‐emergence Of Bronchoscopy In Clinmentioning

confidence: 99%

Bronchoscopy in severe childhood asthma: Irresponsible or irreplaceable?

Januska

Goldman

Webley

et al. 2019

Pediatric Pulmonology

View full text Add to dashboard Cite

For children with severe asthma, guideline‐based management focuses on the escalation of anti‐inflammatory and bronchodilatory medications while addressing comorbid conditions. Bronchoscopy, in this context, has been relegated to ruling out asthma mimickers. More recently, however, there have been questions surrounding the clinical utility of bronchoscopy in severe childhood asthma. In this solicited lecture summary, we discuss the past, present, and potential future applications of bronchoscopy in severe childhood asthma.

show abstract

“…The 2011 American Thoracic Society guidelines [ 6 ] recommended <20 ppb in children for low FeNO and > 35 ppb in children for high FeNO as the most useful cutoffs to make the determination that eosinophilic inflammation and response to corticosteroids would be unlikely or likely, respectively. Although different varieties of lower airway inflammation found in asthma have already been discussed, the fact remains that atopy is a significant risk factor in most childhood asthma [ 7 ]. Thus, FeNO measurement is likely to be particularly useful in diagnosis and management of asthma in children and adolescents.…”

Section: New In the Diagnosis Of Asthma – The Diagnostic Accuracy Ofmentioning

confidence: 99%

What is New in the Management of Childhood Asthma?

2018

View full text Add to dashboard Cite

Asthma still causes considerable morbidity and mortality globally and minimal improvement has been seen in key outcomes over the last decade despite increasing treatment costs. This review summarizes recent advances in the management of asthma in children and adolescents. It focuses on the need for personalized treatment plans based on heterogenous asthma pathophysiology, the use of the terminology ‘asthma attack’ over exacerbation to instill widespread understanding of severity, and the need for every attack to trigger a structured review and focused strategy. The authors discuss difficulties in diagnosing asthma, accuracy and use of Fractional exhaled nitric oxide both as second line test and as a method to monitor treatment adherence or guide the choice of pharmacotherapy. The authors discuss acute and long-term management of asthma. Asthma treatment goals are to minimize symptom burden, prevent attacks and (where possible) reduce risk and impact of progressive pathophysiology and adverse outcomes. The authors discuss pharmacological management; optimal use of short acting β2 agonists, long acting muscarinic antagonist (tiotropium), use of which is relatively new in pediatrics, allergen specific immunotherapy, biological monoclonal antibody treatment, azalide antibiotic azithromycin, and the use of vitamin D. They also discuss electronic monitoring and adherence devices, direct observation of therapy via mobile device, temperature controlled laminar airflow device, and the importance of considering when symptoms may actually result from dysfunctional breathing rather than asthma.

show abstract

Advances in asthma in 2016: Designing individualized approaches to management

Cited by 25 publications

References 92 publications

The Club Cell Marker SCGB1A1 Downstream of FOXA2 is Reduced in Asthma

The Club Cell Marker SCGB1A1 Downstream of FOXA2 is Reduced in Asthma

Bronchoscopy in severe childhood asthma: Irresponsible or irreplaceable?

What is New in the Management of Childhood Asthma?

Contact Info

Product

Resources

About