Persistent Wheezing in Very Young Children Is Associated with Lower Respiratory Inflammation

Abstract

Despite advances in understanding the pathophysiology of asthma, morbidity and mortality in pediatrics continue to rise. Little is known about the initiation and chronicity of inflammation resulting in asthma in this young population. We evaluated 20 "wheezing" children (WC) (median age 14.9 mo) with a minimum of two episodes of wheezing or prolonged wheezing > or = 2 mo in a 6-mo period with bronchoscopy and bronchoalveolar lavage (BAL). Comparisons were made with six normal controls (NC) (median age 23.3 mo) undergoing general anesthesia for elective surgery. BAL fluid cell counts and differentials were determined. The eicosanoids, leukotriene (LT) B(4), LTE(4), prostaglandin (PG)E(2), and 15-hydroxyeicosatetraenoic acid (HETE) and the mast cell mediators, beta-tryptase and PGD(2), were evaluated by enzyme immunoassay (EIA). WC had significant elevations in total BAL cells/ml (p = 0.01), as well as, lymphocytes (LYMPH, p = 0.007), macrophages/monocytes (M&M, p = 0.02), polymorphonuclear cells (PMN, p = 0.02), epithelial cells (EPI, p = 0.03), and eosinophils (EOS, p = 0.04) compared with NC. Levels of PGE(2) (p = 0.0005), 15-HETE (p = 0.002), LTE(4) (p = 0.04), and LTB(4) (p = 0.05) were also increased in WC compared with NC, whereas PGD(2) and beta-tryptase were not. This study confirms that inflammation is present in the airways of very young WC and may differ from patterns seen in adults with asthma.

Challenges and Opportunities for Respiratory Syncytial Virus Vaccines

“…One such study compared the BAL findings in 6 healthy children compared to 20 subjects with recurrent wheezing or prolonged wheezing of greater than 2 months over a 6 month period. (Krawiec et al, 2001) In this report, the average age of the healthy children was 23 months compared to 15 months for the wheezing subjects. The wheezing subjects had a significantly greater number of total cells, lymphocytes, epithelial cells, neutrophils, and eosinophils compared to controls.…”

“…Wheezing subjects also had increased BAL levels of leukotriene (LT)B 4 and LTE 4 than control subjects. (Krawiec et al, 2001) LTB 4 is a neutrophil chemotactic factor. (Wenzel, 1997) LTE 4 is the final metabolite in the cysteinyl leukotriene pathway and has been shown to be an important mucus secretagogue, induce smooth muscle constriction, and be an eosinophil chemotactic factor.…”

Asthma Therapies Revisited: What Have We Learned?

“…To design appropriate strategies, it is important to determine when relevant pathophysiologic elements of the disease begin to be expressed. From the standpoint of airway inflammation, recent work using both bronchoalveolar lavage in wheezing preschool children (14) and bronchial biopsy in infants (15) and young children (16) have demonstrated that both inflammatory cell infiltration and structural alterations (thickening of subepithelial reticular membrane) can be demonstrated by 2 to 3 years of life. Loss of lung function, predominantly noted in the persistent wheezing phenotype, occurs within the first 6 years of life (17).…”

Wheezing in infancy: epidemiology, investigation, and treatment

“…A asma é uma entre as várias causas de sibilância nessa faixa etária 10 . Metade das crianças que sibilam no início da vida deixam de fazê-lo aos 6 anos de idade; são os chamados sibilantes transitórios, nos quais existe relação com a redução do calibre das vias aeríferas, infecções virais de vias aéreas superiores, tabagismo materno e fatores genéticos.…”