Altered gene expression profiles in nasal respiratory epithelium reflect stable versus acute childhood asthma

Guajardo, Jesus R.; Schleifer, Kathleen W.; Daines, Michael O.; Ruddy, Richard M.; Aronow, Bruce J.; Wills‐Karp, Marsha; Hershey, Gurjit K. Khurana

doi:10.1016/j.jaci.2004.10.032

Cited by 78 publications

(93 citation statements)

References 28 publications

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“…Three studies of small or modest size have profiled gene expression during acute exacerbation in blood or nasal cells, reporting up-regulation of similar pathways related to innate and adaptive immune responses (3)(4)(5). However, these studies focused on expression changes during acute exacerbations and provided no information regarding expression across the broad range of asthma control states that precede exacerbation.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling in Blood Provides Reproducible Molecular Insights into Asthma Control

Croteau‐Chonka¹,

Qiu²,

Martínez

et al. 2017

Am J Respir Crit Care Med

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Rationale: Maintaining optimal symptom control remains the primary objective of asthma treatment. Better understanding of the biologic underpinnings of asthma control may lead to the development of improved clinical and pharmaceutical approaches.Objectives: To identify molecular pathways and interrelated genes whose differential expression was associated with asthma control.Methods: We performed gene set enrichment analyses of asthma control in 1,170 adults with asthma, each with gene expression data derived from either whole blood (WB) or unstimulated CD4 1 T lymphocytes (CD4), and a self-reported asthma control score representing either the preceding 6 months (chronic) or 7 days (acute). Our study comprised a discovery WB cohort (n = 245, chronic) and three independent, nonoverlapping replication cohorts: a second WB set (n = 448, acute) and two CD4 sets (n = 300, chronic; n = 77, acute). Measurements and Main Results:In the WB discovery cohort, we found significant overrepresentation of genes associated with asthma control in 1,106 gene sets from the Molecular Signatures Database (false discovery rate, ,5%). Of these, 583 (53%) replicated in at least one replication cohort (false discovery rate, ,25%). Suboptimal control was associated with signatures of eosinophilic and granulocytic inflammatory signals, whereas optimal control signatures were enriched for immature lymphocytic patterns. These signatures included two related biologic processes related to activation by TREM-1 (triggering receptor expressed on myeloid cells 1) and lipopolysaccharide. Conclusions:Together, these results demonstrate the existence of specific, reproducible transcriptomic components in blood that vary with degree of asthma control and implicate a novel biologic target (TREM-1).

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Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling in Blood Provides Reproducible Molecular Insights into Asthma Control

Croteau‐Chonka¹,

Qiu²,

Martínez

et al. 2017

Am J Respir Crit Care Med

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“…In this study, discrete gene expression profiles were found in acute versus stable asthma, with several immune-regulated genes being upregulated and cilia-related genes being down-regulated. These results suggest that distinct genes are induced during asthma exacerbations as compared with stable asthma (27). Although these results are interesting, it is not yet clear the extent to which gene expression changes in nasal epithelial brushings may provide an early signal for impending exacerbations, or the extent to which they may be confounded by rhinitis, atopy, or other factors.…”

Section: Airway Epithelial Cellsmentioning

confidence: 93%

“…Up-regulated genes included those previously implicated in asthma pathogenesis, such as IL-1␤, IL-8, tumor necrosis factor-␣ (TNF-␣)-induced protein 6, lipocortin-1, as well as novel genes including plasminogen activator inhibitor 2. In another study, nasal epithelial brushings were used as a surrogate for lower airway epithelium to determine gene expression profiles using microarrays in children with stable asthma (n ϭ 10), children experiencing an acute exacerbation (n ϭ 10), and nonatopic control children (n ϭ 10) (27). In this study, discrete gene expression profiles were found in acute versus stable asthma, with several immune-regulated genes being upregulated and cilia-related genes being down-regulated.…”

Section: Airway Epithelial Cellsmentioning

confidence: 99%

Gene Expression Profiling in Human Asthma

Hansel

Diette²

2007

Proceedings of the American Thoracic Society

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Asthma is a chronic inflammatory disease of the lungs, characterized by airway hyperreactivity, mucus hypersecretion, and airflow obstruction. Despite recent advances, the genetic regulation of asthma pathogenesis is still largely unknown. Gene expression profiling techniques are well suited to study complex diseases and hold substantial promise for identifying novel genes and pathways in asthma; however, relatively few studies have been completed in human asthma. The few studies that have been done have identified many novel candidate genes and pathways in asthma pathogenesis, including ALOX15 and serine proteinase inhibitors cathepsin C and G. The interpretation of results of these studies should be cautious, as limitations include small sample sizes and heterogeneity of study populations and tissues sampled. In the future, the promise of gene expression studies would be enhanced by the use of larger sample sizes and attempts to standardize phenotype, sample collection techniques, and analysis. As the field of expression profiling in asthma advances, we hope it will improve our understanding of critical questions about mechanisms involved in susceptibility to the disease, as well as help to personalize care by improving appropriate selection of patients for prevention and treatment strategies.

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“…It offers a rapid and simple way to sample both healthy and diseased children without long, unnecessary, and often painful bronchoscopy procedures that necessitate sedation. Previous studies have found that disease subtypes related to asthma severity can be distinguished in both the nasal mucosa as well as bronchial cell samples taken from asthmatic children, and gene expression between the two tissue types was similar in about 90% of non-ubiquitous genes 22,24 . As a source for iPSCs, NECs offer advantages over other frequently utilized cell types.…”

Section: Introductionmentioning

confidence: 99%

Cultivate Primary Nasal Epithelial Cells from Children and Reprogram into Induced Pluripotent Stem Cells

Ulm

Mayhew

Debley

et al. 2016

JoVE

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Nasal epithelial cells (NECs) are the part of the airways that respond to air pollutants and are the first cells infected with respiratory viruses. They are also involved in many airway diseases through their innate immune response and interaction with immune and airway stromal cells. NECs are of particular interest for studies in children due to their accessibility during clinical visits. Human induced pluripotent stem cells (iPSCs) have been generated from multiple cell types and are a powerful tool for modeling human development and disease, as well as for their potential applications in regenerative medicine. This is the first protocol to lay out methods for successful generation of iPSCs from NECs derived from pediatric participants for research purposes. It describes how to obtain nasal epithelial cells from children, how to generate primary NEC cultures from these samples, and how to reprogram primary NECs into well-characterized iPSCs. Nasal mucosa samples are useful in epidemiological studies related to the effects of air pollution in children, and provide an important tool for studying airway disease. Primary nasal cells and iPSCs derived from them can be a tool for providing unlimited material for patient-specific research in diverse areas of airway epithelial biology, including asthma and COPD research. Video LinkThe video component of this article can be found at

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Altered gene expression profiles in nasal respiratory epithelium reflect stable versus acute childhood asthma

Cited by 78 publications

References 28 publications

Gene Expression Profiling in Blood Provides Reproducible Molecular Insights into Asthma Control

Gene Expression Profiling in Blood Provides Reproducible Molecular Insights into Asthma Control

Gene Expression Profiling in Human Asthma

Cultivate Primary Nasal Epithelial Cells from Children and Reprogram into Induced Pluripotent Stem Cells

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