Nonatopic children with multitrigger wheezing have airway pathology comparable to atopic asthma.
BACKGROUND
Epidemiologic studies have shown that, in atopic children, wheezing is more likely to persist into adulthood, eventually becoming asthma, whereas it appears to resolve by adolescence in nonatopic children.


OBJECTIVE
To investigate whether among children with multitrigger wheeze responsive to bronchodilators the airway pathology would be different in nonatopic wheezers, who are often considered nonasthmatic, compared with atopic wheezers, who are more frequently diagnosed as having asthma.


METHODS
Bronchial biopsies were obtained from 55 children undergoing bronchoscopy for appropriate clinical indications: 18 nonatopic children with multitrigger wheeze (median age, 5 yr; range, 2-10 yr), 20 atopic children with multitrigger wheeze (medan age, 5 yr; range, 2-15 yr), and 17 control children with no atopy or wheeze (median age, 4; range, 2-14 yr). By histochemistry and immunohistochemistry, we quantified epithelial loss, basement membrane thickness, angiogenesis, inflammatory cells, IL-4(+,) and IL-5(+) cells in subepithelium.


RESULTS
Unexpectedly, all pathologic features examined were similar in atopic and nonatopic wheezing children. Compared with control subjects, both nonatopic and atopic wheezing children had increased epithelial loss (P = 0.03 and P = 0.002, respectively), thickened basement membrane (both P < 0.0001), and increased number of vessels (P = 0.003 and P = 0.03, respectively) and eosinophils (P < 0.0001 and P = 0.002, respectively). Moreover, they had increased cytokine expression, which was highly significant for IL-4 (P = 0.002 and P = 0.0001, respectively) and marginal for IL-5 (P = 0.02 and P = 0.08, respectively).


CONCLUSIONS
This study shows that the airway pathology typical of asthma is present in nonatopic wheezing children just as in atopic wheezing children. These results suggest that, when multitrigger wheezing responsive to bronchodilators is present, it is associated with pathologic features of asthma even in nonatopic children.
Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova, Padova, Italy.
Graziella
G
Turato
Angelo
A
Barbato
Simonetta
S
Baraldo
Maria Elena
ME
Zanin
Erica
E
Bazzan
Kim
K
Lokar-Oliani
Fiorella
F
Calabrese
Cristina
C
Panizzolo
Deborah
D
Snijders
Piero
P
Maestrelli
Renzo
R
Zuin
Leonardo M
LM
Fabbri
Marina
M
Saetta
D000293:Adolescent; D001249:Asthma / Q000503:physiopathology*; D001485:Basement Membrane / Q000276:immunology / Q000473:pathology; D001980:Bronchi / Q000098:blood supply / Q000276:immunology / Q000473:pathology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004804:Eosinophils / Q000378:metabolism; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000503:physiopathology; D007150:Immunohistochemistry; D007249:Inflammation; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008297:Male; D009389:Neovascularization, Pathologic; D020545:Respiratory Mucosa / Q000276:immunology / Q000473:pathology; D012135:Respiratory Sounds / Q000503:physiopathology*; D018418:Th2 Cells / Q000378:metabolism
D015848:Interleukin-5; D015847:Interleukin-4