Altered gene expression profiles in nasal respiratory epithelium reflect stable versus acute childhood asthma.
BACKGROUND
Asthma is the most common chronic disease of childhood and has a strong genetic component.


OBJECTIVE
To identify gene expression signatures that reflect asthma-related processes and to determine whether these genes were similar or distinct between stable asthma and acute exacerbations in childhood, we profiled gene expression patterns in nasal respiratory epithelial cells.


METHODS
Children who had stable asthma (asthma-S; n = 10) and children experiencing an asthma exacerbation (asthma-E; n = 10) were recruited along with nonatopic children without asthma (n = 10). RNA was prepared from nasal respiratory epithelial cells isolated from each child, initially analyzed as pooled samples from the 3 groups, and further validated by using microarrays and RT-PCR with individual patient samples.


RESULTS
Distinct gene clusters were identifiable in individual and pooled asthma-S and asthma-E samples. Asthma-E samples demonstrated the strongest and most reproducible signatures, with 314 genes of 34,886 measured as present on the chip demonstrating induction or repression of greater than 2-fold with P < .05 in each of 4 individual samples. Asthma-S-regulated genes encompassed genes that overlapped with those of asthma-E but were fewer (166) and less consistent with respect to their behavior across the asthma-E patient samples.


CONCLUSIONS
Exacerbated asthma status is readily distinguished based on the occurrence of strong gene expression signatures in nasal epithelial samples. Stable asthma status also exhibits differential signatures. The results suggest that there are independent gene expression signatures reflective of cells and genes poised or committed to activation by an asthma attack.
Guajardo
Jesus R
JR
Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Schleifer
Kathleen W
KW
Daines
Michael O
MO
Ruddy
Richard M
RM
Aronow
Bruce J
BJ
Wills-Karp
Marsha
M
Hershey
Gurjit K Khurana
GK
D000208:Acute Disease; D001249:Asthma / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D005810:Multigene Family; D009297:Nasal Mucosa / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction