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Lower Airway Immune Response to Di-Butyl Phthalate (DBP) and Allergen Co-Exposure
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A1908 - Lower Airway Immune Response to Di-Butyl Phthalate (DBP) and Allergen Co-Exposure
Author Block: D. Maestre-Batlle1, R. D. Huff1, D. Wooding1, A. K. Bølling2, C. Carlsten1; 1Respiratory Medicine, University of British Columbia, Vancouver, BC, Canada, 2Norwegian Institute of Public Health, Oslo, Norway.
RATIONALE
Allergic asthma is a complex disease associated with an underlying Th2 cell-mediated inflammatory response resulting in airway eosinophilia, allergen-specific immunoglobulins and bronchial hyperresponsiveness. Phthalates are plastic softeners used in common commercial products that leak from their carrier plastic and become environmental contaminants. Epidemiological studies suggest that phthalate exposure is associated with development and/or worsening of airway diseases like allergic asthma. DBP, a type of phthalate found in high concentrations in indoor air, was found to have high inflammatory potential in vitro. In our study, we hypothesize that DBP inhalation prior to allergen inhalation will affect lung function and recruit and activate immune cells in the lower airway.
METHODS
Allergen-sensitized volunteers were enrolled in our double-blinded, randomized, controlled crossover study. Subjects were exposed to DBP or control air for 3 hours followed by an inhaled allergen challenge. Subjects underwent a methacholine test the following day. Dose-response curves to methacholine were examined, the slope (DRS) was obtained and the provocative concentration that caused a 20% fall in FEV1 (PC20) was calculated. Forced exhaled nitric oxide (FeNO) was measured pre- and post-exposure. Bronchoalveolar lavage (BAL) was acquired 24 hours post-exposure and the cellular fraction was stained immediately for immunophenotyping using flow cytometry. Data was analyzed using a linear mixed effects model.
RESULTS
Preliminary data from 4 volunteers is as follows: FeNO, a measurement of airway inflammation, was increased after DBP exposure relative to control air at 20 hours post-exposure (p=0.10). The area under the curve (allergen challenge) and the DRS (methacholine challenge) trended to increase with DBP exposure, while the methacholine PC20 trended to decrease with DBP. In BAL, DBP exposure increased the percentage of macrophages (p=0.05) and their expression of CD206 (p=0.03), a receptor that aids phagocytosis and antigen presentation. DBP also increased the ratios of M2/M1 macrophages and Th2/Th1 cells (p=0.10 and p=0.19, respectively). Furthermore, the Th1 population was significantly reduced (p=0.03) as was its expression of CD183 (p=0.03), a marker of Th1 cell maturation.
CONCLUSIONS
Our results indicate DBP increases allergen-induced airway inflammation and hyper-responsiveness, and modulates the recruitment and activation of immune cells in the lung. These preliminary results support our hypothesis and will be re-examined upon study completion (n=20).
Author Block: D. Maestre-Batlle1, R. D. Huff1, D. Wooding1, A. K. Bølling2, C. Carlsten1; 1Respiratory Medicine, University of British Columbia, Vancouver, BC, Canada, 2Norwegian Institute of Public Health, Oslo, Norway.
RATIONALE
Allergic asthma is a complex disease associated with an underlying Th2 cell-mediated inflammatory response resulting in airway eosinophilia, allergen-specific immunoglobulins and bronchial hyperresponsiveness. Phthalates are plastic softeners used in common commercial products that leak from their carrier plastic and become environmental contaminants. Epidemiological studies suggest that phthalate exposure is associated with development and/or worsening of airway diseases like allergic asthma. DBP, a type of phthalate found in high concentrations in indoor air, was found to have high inflammatory potential in vitro. In our study, we hypothesize that DBP inhalation prior to allergen inhalation will affect lung function and recruit and activate immune cells in the lower airway.
METHODS
Allergen-sensitized volunteers were enrolled in our double-blinded, randomized, controlled crossover study. Subjects were exposed to DBP or control air for 3 hours followed by an inhaled allergen challenge. Subjects underwent a methacholine test the following day. Dose-response curves to methacholine were examined, the slope (DRS) was obtained and the provocative concentration that caused a 20% fall in FEV1 (PC20) was calculated. Forced exhaled nitric oxide (FeNO) was measured pre- and post-exposure. Bronchoalveolar lavage (BAL) was acquired 24 hours post-exposure and the cellular fraction was stained immediately for immunophenotyping using flow cytometry. Data was analyzed using a linear mixed effects model.
RESULTS
Preliminary data from 4 volunteers is as follows: FeNO, a measurement of airway inflammation, was increased after DBP exposure relative to control air at 20 hours post-exposure (p=0.10). The area under the curve (allergen challenge) and the DRS (methacholine challenge) trended to increase with DBP exposure, while the methacholine PC20 trended to decrease with DBP. In BAL, DBP exposure increased the percentage of macrophages (p=0.05) and their expression of CD206 (p=0.03), a receptor that aids phagocytosis and antigen presentation. DBP also increased the ratios of M2/M1 macrophages and Th2/Th1 cells (p=0.10 and p=0.19, respectively). Furthermore, the Th1 population was significantly reduced (p=0.03) as was its expression of CD183 (p=0.03), a marker of Th1 cell maturation.
CONCLUSIONS
Our results indicate DBP increases allergen-induced airway inflammation and hyper-responsiveness, and modulates the recruitment and activation of immune cells in the lung. These preliminary results support our hypothesis and will be re-examined upon study completion (n=20).
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