Evaluation of airway reactivity and immune characteristics as risk factors for wheezing early in life.
BACKGROUND
Childhood asthma is most often characterized by recurrent wheezing, airway hyperreactivity, and atopy; however, our understanding of these relationships from early in life remains unclear. Respiratory tract illnesses and atopic sensitization early in life might produce an interaction between innate and acquired immune responses, leading to airway inflammation and heightened airway reactivity.


OBJECTIVE
We hypothesized that premorbid airway reactivity and immunologic characteristics of infants without prior episodes of wheezing would be associated with subsequent wheezing during a 1-year follow-up.


METHODS
One hundred sixteen infants with chronic dermatitis were enrolled before episodes of wheezing. Airway reactivity, allergen-specific IgE levels, cytokine production by stimulated PBMCs, and percentages of dendritic cells were measured on entry, and airway reactivity was reassessed at the 1-year follow-up. Linear regression models were used to evaluate a predictor's effect on continuous outcomes.


RESULTS
Milk sensitization, egg sensitization, or both were associated with heightened airway reactivity before wheezing and after the onset of wheezing; however, these factors were not associated with an increased risk of wheezing. There was an interaction between initial airway reactivity and wheezing as a determinant of airway reactivity at follow-up. In addition, cytokine production by stimulated PBMCs was a risk factor for wheezing, whereas increased percentages of conventional dendritic cells were protective against wheezing.


CONCLUSIONS
Our data in a selected cohort of infants support a model with multiple risk factors for subsequent wheezing that are independent of initial airway reactivity; however, the causative factors that produce wheezing very early in life might contribute to heightened airway reactivity.
Yao
Weiguo
W
Department of Pediatrics, James Whitcomb Riley Hospital for Children, Herman B Wells Center for Pediatric Research, Indianapolis, Ind 46202-5225, USA.
Barbé-Tuana
Florencia M
FM
Llapur
Conrado J
CJ
Jones
Marcus H
MH
Tiller
Christina
C
Kimmel
Risa
R
Kisling
Jeffrey
J
Nguyen
Evelyn T
ET
Nguyen
James
J
Yu
Zhangsheng
Z
Kaplan
Mark H
MH
Tepper
Robert S
RS
D017668:Age of Onset; D001249:Asthma / Q000453:epidemiology / Q000276:immunology* / Q000503:physiopathology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D005512:Food Hypersensitivity / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D012129:Respiratory Function Tests; D012135:Respiratory Sounds / Q000276:immunology*; D012307:Risk Factors
D016207:Cytokines; D007073:Immunoglobulin E
Pediatr Pulmonol. 1992 May;13(1):6-10
1589316
Eur Respir J. 2002 May;19(5):899-905
12030731
Chest. 2001 Mar;119(3):685-90
11243943
Clin Exp Allergy. 1999 Jul;29(7):905-11
10383590
J Allergy Clin Immunol. 2007 Oct;120(4):835-41
17689598
Allergy. 2005 Jan;60(1):113-6
15575941
Lancet. 2008 Sep 20;372(9643):1100-6
18805338
J Allergy Clin Immunol. 2005 Nov;116(5):1067-72
16275378
J Allergy Clin Immunol. 2008 Oct;122(4):760-765
18760452
N Engl J Med. 1995 Jan 19;332(3):133-8
7800004
Am J Respir Crit Care Med. 2004 Jan 1;169(1):70-6
14525803
Am J Respir Crit Care Med. 1995 May;151(5):1434-40
7735597
Allergy. 2002 Mar;57(3):267-8
11906351
Am J Respir Crit Care Med. 2008 Oct 1;178(7):667-72
18565953
J Allergy Clin Immunol. 2009 Oct;124(4):707-13.e2
19733903
Am J Respir Crit Care Med. 2009 Feb 1;179(3):205-11
18996999
Am J Respir Crit Care Med. 2005 Jan 1;171(1):78-82
15502114
J Allergy Clin Immunol. 2001 Nov;108(5):709-14
11692093
Am J Respir Crit Care Med. 2009 Jan 15;179(2):98-104
18990677
Clin Exp Allergy. 2003 Sep;33(9):1226-31
12956743