Publications (3)34.43 Total impact
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ABSTRACT: Early in life, natural exposure to microbial components (eg, endotoxin) may mitigate allergy and asthma development in childhood. Bacterial DNA is a potent stimulus for the innate immune system; its immune stimulatory potential in dust is unknown. We sought to quantify bacterial DNA and endotoxin content in dust from urban homes, rural homes, farm homes, and farm barns and to determine if dust DNA is immune-stimulatory. Total DNA, bacterial DNA, and endotoxin were measured in 32 dust samples. To measure bacterial DNA content, a quantitative polymerase chain reaction assay specific for bacterial ribosomal DNA was developed. Peripheral blood mononuclear cells from 5 adults were stimulated with endotoxin-free dust DNA with/without lipopolysaccharide (LPS) from selected dust samples. IL-12p40, IL-10, and tumor necrosis factor-alpha were measured in cell supernatants by enzyme-linked immunosorbent assay. Bacterial DNA in dust correlated with endotoxin (r = 0.56, P <.001) and total DNA content (r = 0.51, P =.003). The highest bacterial DNA levels were measured in farm barns (mean, 22.1 microg/g dust; range, 1.3 to 56.2), followed by rural homes (6.3 microg/g; 0.2 to 20), farm homes (2.2 microg/g; 0.1 to 9.1), and urban homes (0.6 microg/g; 0.1 to 1.2). Farm barn DNA significantly potentiated (P < or =.05) LPS-induced IL-10 and IL-12 p40 but not tumor necrosis factor-alpha release (13-fold, 3-fold, and 1.5-fold increases, respectively). DNA from 6 urban homes did not demonstrate this LPS-potentiating effect. Endotoxin is a marker for bacterial DNA, which is also higher in locales of lower asthma and allergy prevalence. DNA from farm barn dust augments the immune modulatory effects of endotoxin and may combine with exposure to other such naturally occurring microbial components to mitigate allergy and asthma development.
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ABSTRACT: Objective lung function measurements are routinely used to diagnose and manage asthma, but their utility for young children has not been defined. Bronchodilator responses were measured by means of impulse oscillometry (IOS) and compared with conventional spirometry to determine the value of lung function measures in 4-year-old asthma-prone children. The study participants were in the Childhood Asthma Prevention Study (National Institute of Health/National Institute of Allergy and Infectious Diseases) and at risk for asthma. At age 4 years, concurrent asthma was determined by using a previously validated modified American Thoracic Society questionnaire. Children performed IOS and spirometry before and after albuterol administration and underwent skin prick testing to 13 common allergens to assess atopy. IOS measures were as follows: airways resistance at 5 Hz and 10 Hz, airways reactance at 5 Hz and 10 Hz, and resonant frequency. Asthmatic patients versus nonasthmatic patients significantly differed in their IOS-assessed bronchodilator responses through Delta resistance at 5 Hz (medians, 27% vs 17%; P =.02) and Delta resistance at 10 Hz (24% vs 16%; P =.03). Because atopic children who have frequent wheezing are at risk for persistent asthma, the data were analyzed in regard to atopic patients with or without asthma. IOS strongly distinguished atopic asthmatic children through Delta resistance at 5 Hz (36% vs 13%, P =.007), Delta resistance at 10 Hz (25% vs 11%, P =.02), and Delta reactance at 10 Hz (47% vs 12%, P =.03). Conventional spirometry did not establish similar statistically significant findings. IOS bronchodilator responses are remarkably abnormal in 4-year-old children, who are most likely to have persistent asthma. IOS is a useful diagnostic tool in early asthma development and might be a helpful objective outcome measure of early interventions.