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351 Residential exposures asosciated with asthma in U.S. children
Abstracts
J ALLERGY CLIN IMMUNOL VOLUME 105, NUMBER 1, PART 2
CSF and IL-4. Their migratory behaviour was analyzed in the SCID mouse model. At day 0, SCID mice were injected intraperitoneally with I x I06 monocyte-derived DC and at day 4, were exposed or not to the aeroallergen Dermatophagoides pteronyssinus (Dpt). At day 7, mice were sacrificed and the presence of the markers CD I a, CD 14. CD68 was investigated by immunohistochemistry on frozen or paraffin sections of thymus, lungs and spleen. Only CDla-positive DC were detectable in the thymus, the lungs and the spleen of reconstituted SCID mice. After exposure to Dpt, the number of CDla+ DC increased in the lymphoid organs and decreased in the lungs, suggesting a selective DC traffic. Indeed, Der p I. the major allergen of Dpt, was only detected in the spleen of mice exposed to Dpt. This migration capacity could be dependent on two factors: the adhesion molecule CD 1Ic and TNFa, both highly expressed by DC in vitro exposed to Der p I. Moreover, when SCID mice reconstituted with PBMC from allergic patients were previously injected with DC from the same donor, the IgE production was highly increased compared to the IgG production. In contrast, with cells from healthy donors, an opposite effect was observed. In addition, DC were also detected in SCID mice only reconstituted with PBMC from allergic patients and producing human IgE and developping an inflammatory pulmonary infiltrate. At least one month after the Dpt exposure, DC were located in the alveolar spaces and walls of the lungs and preferentially expressed the phenotype of mature DC. Taken together, all these results suggest that in SCID mice, human DC may play a role in the development of the allergic reaction in response to Dpt. aaaaaaa 351 Residential Exposures Associated with Asthma in U.S. Children Bruce Lunphear, Michael Weirzmon
Andrew
Al&e,
Peggy
Auingec
Robert
Byrd,
CONTEXT. Residential exposures such as indoor allergens and environmental tobacco smoke are recognized risk factors for asthma, but the contribution of such exposures to asthma in U.S. children is unknown. OBJECTIVE. To estimate the population attributable risk of residential exposures to doctor-diagnosed asthma for U.S. children younger than 6 years of age. DESIGN. Cross-sectional survey conducted from 1988 to 1994. Setting and Participants. A total of 8,257 children less than 6 years of age who participated in the Third National Health and Nutrition Examination Survey, a survey of the health and nutritional status of children and adults in the United States. MAIN OUTCOME MEASURE. Doctor-diagnosed asthma, as reported by the parent. RESULTS. Six percent of children had doctor-diagnosed asthma. The prevalence of asthma was higher among boys (6.7%) than girls (5. I %), and higher among Black children (8.9%) than White children (5.2%). Independent predictors of doctor-diagnosed asthma included a family history of atopy (OR=2.2, 95%CI=1.5, 3.1). child’s history of allergy to a pet (08=24.2,95%CI=8.4,69.5), exposure to environmental tobacco smoke (OR=l.8. CI=1.2-2.6). use of a gas stove or oven for heat OR=1.8 (CI=l.O2-3.2) and presence of a dog in the household (OR= 1.6, CI=I. I, 2.3). The population attributable fraction of z I or more residential exposure for doctor-diagnosed asthma in U.S. children c 6 years of age was 39%. or an estimated 532,972 excesscases.In contrast, having a family history of atopy accounted for 300,CKKlexcesscases. CONCLUSIONS. The elimination of identified residential exposures - if causally associated with asthma - would result in a 40% decline in doctor-diagnosed asthma among U.S. children younger than 6 years of age. 352 Hypersensitivity Pneumonitis From Pezizia Domiciliana: A Case of El Nifio Lung 24 Dyer; RS Wright, MI Liebhaber Sansum-Santa Barbara Medical Foundation Clinic, Santa Barbara, CA
S117
We present an unusual case of extrinsic allergic alveolitis in the home setting. An unprecedented high rainfall during the 1998 El Nigo season and the flooding of a domestic residence provided the conditions for an unusual caseof hypersensitivity pneumonitis in the Santa Ynez Mountains near Santa Barbara, California. A previously healthy 54 year-old woman developed severe dyspnea over a three month period and was found to have restrictive lung disease on pulmonary function testing with evidence of alveolitis. Her diffusing capacity was markedly reduced at 14% predicted. A high-resolution chest tomogram showed ground-glass haziness and small ce.ntriIobular nodules. An open lung biopsy revealed extrinsic allergic alveolitis with moderate lymphoplasmacytic infiltrate and non-necrotizing granulomas (hypersensitivity pneumonitis). The etiology was not initially apparent. A home inspection showed an unusual mushroom identified as Pezizia donziciliana (a Discomycete) growing in the basement. Volumetric air sampling and serum precipitins, obtained specific for fungal samples in the home, confirmed that Pezizia domiciliana was the likely cause of hypersensitivity pneumonitis. The patient subsequently improved with avoidance measures and a course of steroid therapy. This is the first described case.of hypersensitivity pneumonitis due to Pezizia domiciliana. We speculate that the unprecedented rainfall and flooding in her basement due to the El Niilo rains produced ideal factors for the growth of this fungus. The home visit led to mitigating the exposure and prevention of disease progression.
353 Effect of Cigarette
Smoke (CS) on Intracelhlar Reduced-Glutathione Levels of Primary Cultures of Human Bronchial Epithelial Cells of Never-Smokers, Smokers and Patients with COPD C Rusznak*t, PR Mills*. JL Devalia*, RJ Sapsford*. RJ Davies*, S Lozewicz* *Academic Department of Respiratory Medicine, St. Bartholomew’s and the Royal London School of Medicine and Dentistry, London, UK tA1lergy Center, Vanderbilt University Medical Center, Nashville, TN, USA Although cigarette smoking is of paramount importance in the development of chronic obstructive pulmonary disease.(COPD), only a small proportion of smokers develop the disease. We have recently demonstrated, that primary cultures of epithelial cells from patients with COPD have a greater susceptibility to the effects of CS causing increased permeability and release of pro-inflammatory mediators such asIL- IO; and sICAM- I. To investigate the putative underlying mechanisms responsible for the observed differences, we established primary explant cultures of human bronchial epithelial cells (HBEC) from biopsy material obtained from never-smokers, who had normal pulmonary function, smokers with normal pulmonary function and smokers with COPD. The HBEC cultures were exposed for 20 minutes to CS or air, and intracellular reduced glutathione (GSH) levels measured after 24 hour incubation. Levels of intracellular GSH following exposure to air were significantly higher in cultures of HBEC derived from both smokers with normal pulmonary function and COPD patients, than in cultures from healthy never-smokers. Exposure to CS significantly decreased the concentration of intracellular GSH in all cultures when compared to exposure to air. The fall in intracellular GSH was significantly greater in cells from smokers with COPD (mean 72.9% decrease) than in cells from smokers with normal pulmonary function (mean 43.9% decrease, p=O.O2) or cells from never-smokers (mean 50.6% decrease,p=O.O48).These results suggest that whereas smokers with and without COPD demonstrate increased levels of GSH within bronchial epithelial cell cultures, those with COPD have a greater susceptibility to the effect of CS in reducing intracellular GSH levels. Whether in patients with COPD the greater susceptibility of bronchial epithelial cells to CS exposure contributes to the develop ment ofCOPD, or is a secondary characteristic of this condition, need to be determined.
J ALLERGY CLIN IMMUNOL VOLUME 105, NUMBER 1, PART 2
CSF and IL-4. Their migratory behaviour was analyzed in the SCID mouse model. At day 0, SCID mice were injected intraperitoneally with I x I06 monocyte-derived DC and at day 4, were exposed or not to the aeroallergen Dermatophagoides pteronyssinus (Dpt). At day 7, mice were sacrificed and the presence of the markers CD I a, CD 14. CD68 was investigated by immunohistochemistry on frozen or paraffin sections of thymus, lungs and spleen. Only CDla-positive DC were detectable in the thymus, the lungs and the spleen of reconstituted SCID mice. After exposure to Dpt, the number of CDla+ DC increased in the lymphoid organs and decreased in the lungs, suggesting a selective DC traffic. Indeed, Der p I. the major allergen of Dpt, was only detected in the spleen of mice exposed to Dpt. This migration capacity could be dependent on two factors: the adhesion molecule CD 1Ic and TNFa, both highly expressed by DC in vitro exposed to Der p I. Moreover, when SCID mice reconstituted with PBMC from allergic patients were previously injected with DC from the same donor, the IgE production was highly increased compared to the IgG production. In contrast, with cells from healthy donors, an opposite effect was observed. In addition, DC were also detected in SCID mice only reconstituted with PBMC from allergic patients and producing human IgE and developping an inflammatory pulmonary infiltrate. At least one month after the Dpt exposure, DC were located in the alveolar spaces and walls of the lungs and preferentially expressed the phenotype of mature DC. Taken together, all these results suggest that in SCID mice, human DC may play a role in the development of the allergic reaction in response to Dpt. aaaaaaa 351 Residential Exposures Associated with Asthma in U.S. Children Bruce Lunphear, Michael Weirzmon
Andrew
Al&e,
Peggy
Auingec
Robert
Byrd,
CONTEXT. Residential exposures such as indoor allergens and environmental tobacco smoke are recognized risk factors for asthma, but the contribution of such exposures to asthma in U.S. children is unknown. OBJECTIVE. To estimate the population attributable risk of residential exposures to doctor-diagnosed asthma for U.S. children younger than 6 years of age. DESIGN. Cross-sectional survey conducted from 1988 to 1994. Setting and Participants. A total of 8,257 children less than 6 years of age who participated in the Third National Health and Nutrition Examination Survey, a survey of the health and nutritional status of children and adults in the United States. MAIN OUTCOME MEASURE. Doctor-diagnosed asthma, as reported by the parent. RESULTS. Six percent of children had doctor-diagnosed asthma. The prevalence of asthma was higher among boys (6.7%) than girls (5. I %), and higher among Black children (8.9%) than White children (5.2%). Independent predictors of doctor-diagnosed asthma included a family history of atopy (OR=2.2, 95%CI=1.5, 3.1). child’s history of allergy to a pet (08=24.2,95%CI=8.4,69.5), exposure to environmental tobacco smoke (OR=l.8. CI=1.2-2.6). use of a gas stove or oven for heat OR=1.8 (CI=l.O2-3.2) and presence of a dog in the household (OR= 1.6, CI=I. I, 2.3). The population attributable fraction of z I or more residential exposure for doctor-diagnosed asthma in U.S. children c 6 years of age was 39%. or an estimated 532,972 excesscases.In contrast, having a family history of atopy accounted for 300,CKKlexcesscases. CONCLUSIONS. The elimination of identified residential exposures - if causally associated with asthma - would result in a 40% decline in doctor-diagnosed asthma among U.S. children younger than 6 years of age. 352 Hypersensitivity Pneumonitis From Pezizia Domiciliana: A Case of El Nifio Lung 24 Dyer; RS Wright, MI Liebhaber Sansum-Santa Barbara Medical Foundation Clinic, Santa Barbara, CA
S117
We present an unusual case of extrinsic allergic alveolitis in the home setting. An unprecedented high rainfall during the 1998 El Nigo season and the flooding of a domestic residence provided the conditions for an unusual caseof hypersensitivity pneumonitis in the Santa Ynez Mountains near Santa Barbara, California. A previously healthy 54 year-old woman developed severe dyspnea over a three month period and was found to have restrictive lung disease on pulmonary function testing with evidence of alveolitis. Her diffusing capacity was markedly reduced at 14% predicted. A high-resolution chest tomogram showed ground-glass haziness and small ce.ntriIobular nodules. An open lung biopsy revealed extrinsic allergic alveolitis with moderate lymphoplasmacytic infiltrate and non-necrotizing granulomas (hypersensitivity pneumonitis). The etiology was not initially apparent. A home inspection showed an unusual mushroom identified as Pezizia donziciliana (a Discomycete) growing in the basement. Volumetric air sampling and serum precipitins, obtained specific for fungal samples in the home, confirmed that Pezizia domiciliana was the likely cause of hypersensitivity pneumonitis. The patient subsequently improved with avoidance measures and a course of steroid therapy. This is the first described case.of hypersensitivity pneumonitis due to Pezizia domiciliana. We speculate that the unprecedented rainfall and flooding in her basement due to the El Niilo rains produced ideal factors for the growth of this fungus. The home visit led to mitigating the exposure and prevention of disease progression.
353 Effect of Cigarette
Smoke (CS) on Intracelhlar Reduced-Glutathione Levels of Primary Cultures of Human Bronchial Epithelial Cells of Never-Smokers, Smokers and Patients with COPD C Rusznak*t, PR Mills*. JL Devalia*, RJ Sapsford*. RJ Davies*, S Lozewicz* *Academic Department of Respiratory Medicine, St. Bartholomew’s and the Royal London School of Medicine and Dentistry, London, UK tA1lergy Center, Vanderbilt University Medical Center, Nashville, TN, USA Although cigarette smoking is of paramount importance in the development of chronic obstructive pulmonary disease.(COPD), only a small proportion of smokers develop the disease. We have recently demonstrated, that primary cultures of epithelial cells from patients with COPD have a greater susceptibility to the effects of CS causing increased permeability and release of pro-inflammatory mediators such asIL- IO; and sICAM- I. To investigate the putative underlying mechanisms responsible for the observed differences, we established primary explant cultures of human bronchial epithelial cells (HBEC) from biopsy material obtained from never-smokers, who had normal pulmonary function, smokers with normal pulmonary function and smokers with COPD. The HBEC cultures were exposed for 20 minutes to CS or air, and intracellular reduced glutathione (GSH) levels measured after 24 hour incubation. Levels of intracellular GSH following exposure to air were significantly higher in cultures of HBEC derived from both smokers with normal pulmonary function and COPD patients, than in cultures from healthy never-smokers. Exposure to CS significantly decreased the concentration of intracellular GSH in all cultures when compared to exposure to air. The fall in intracellular GSH was significantly greater in cells from smokers with COPD (mean 72.9% decrease) than in cells from smokers with normal pulmonary function (mean 43.9% decrease, p=O.O2) or cells from never-smokers (mean 50.6% decrease,p=O.O48).These results suggest that whereas smokers with and without COPD demonstrate increased levels of GSH within bronchial epithelial cell cultures, those with COPD have a greater susceptibility to the effect of CS in reducing intracellular GSH levels. Whether in patients with COPD the greater susceptibility of bronchial epithelial cells to CS exposure contributes to the develop ment ofCOPD, or is a secondary characteristic of this condition, need to be determined.