PMID- 22852485 OWN - NLM STAT- MEDLINE DCOM- 20120904 LR - 20131121 IS - 1041-5505 (Print) IS - 1041-5505 (Linking) IP - 165 DP - 2012 Feb TI - Allergic inflammation in the human lower respiratory tract affected by exposure to diesel exhaust. PG - 5-43; discussion 45-64 AB - To improve understanding of human health risks from exposure to diesel exhaust particles (DEP*), we tested whether immunologic effects previously observed in the human nose also occur in the lower airways. Our overall hypothesis was that cell influx and production of cytokines, chemokines, immunoglobulin E (IgE), and other mediators, which would be measurable in sputum and blood, occur in people with asthma after realistic controlled exposures to diesel exhaust (DE). In Phase 1 we tested for direct effects of DE in subjects with clinically undifferentiated mild asthma. In Phase 2 we tested whether DE exposure would exacerbate response to inhaled cat allergen in subjects with both asthma and cat sensitivity. The exposure facility was a controlled-environment chamber supplied with DE from an idling medium-duty truck with ultra-low-sulfur fuel and no catalytic converter. We exposed volunteers for 2 hours with intermittent exercise to exhaust with DEP mass concentration near 100 microg/m3. Exposures to nitrogen dioxide (NO2) near 0.35 ppm (similar to its concentration in DE) and to filtered air (FA) served as controls. Blood was drawn before exposure on day 1 and again the next morning (day 2). Sputum was induced only on day 2. Bronchial reactivity was measured -1 hour after exposure ended. Supplementary endpoints included measures of blood coagulation status, cardiopulmonary physiology, and symptoms. Each phase employed 15 subjects with asthma; 3 subjects participated in both phases. In Phase 1, airway reactivity was measured with inhaled methacholine; in Phase 2, with inhaled cat allergen. We found little biologic response to DE exposure compared with exposure to control atmospheres. In Phase 1, interleukin 4 (IL-4) in sputum showed an estimated 1.7-fold increase attributable to DE exposure, which was close to statistical significance; airway resistance increased modestly but significantly on day 2 after DE exposure; and nonspecific symptom scores increased significantly during DE exposure. In Phase 2, indicators of airway inflammation in sputum showed a possibly meaningful response: polymorphonuclear leukocytes (PMNs) and eosinophils increased after DE exposure, whereas macrophages decreased. IgE in sputum and the bronchoconstrictive response to cat allergen varied significantly between atmospheres, but not in patterns consistent with our primary hypothesis. Symptom score changes relatable to DE exposure were smaller than those in Phase 1 and not statistically significant. Controlled exposures, lasting 2 hours with intermittent exercise, to diluted DE at a particle mass concentration of 100 microg/m3 did not evoke clear and consistent lower-airway or systemic immunologic or inflammatory responses in mildly asthmatic subjects, with or without accompanying challenge with cat allergen. Likewise, these DE exposures did not significantly increase nonspecific or allergen-specific bronchial reactivity. A few isolated statistically significant or near-significant changes were observed during and after DE exposure, including increases in nonspecific symptoms (e.g., headache, nausea) suggestive of subtle, rapid-onset systemic effects. It is possible the lower respiratory tract is more resistant than the nose to adjuvant effects of diesel particles on allergic inflammation, so that no meaningful effects occur under exposure conditions like these. Alternatively, the experimental conditions may have been near a threshold for finding effects. That is, important lower respiratory effects may occur but may be detectable experimentally with slightly higher DEP concentrations, longer exposures, more invasive testing (e.g., bronchoalveolar lavage), or more susceptible subjects. However, ethical and practical barriers to such experiments are considerable. FAU - Riedl, Marc A AU - Riedl MA AD - Department of Allergy and Immunology, University of California-Los Angeles, 90095, USA. mriedl@mednet.ucla.edu FAU - Diaz-Sanchez, David AU - Diaz-Sanchez D FAU - Linn, William S AU - Linn WS FAU - Gong, Henry Jr AU - Gong H Jr FAU - Clark, Kenneth W AU - Clark KW FAU - Effros, Richard M AU - Effros RM FAU - Miller, J Wayne AU - Miller JW FAU - Cocker, David R AU - Cocker DR FAU - Berhane, Kiros T AU - Berhane KT CN - HEI Health Review Committee LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Res Rep Health Eff Inst JT - Research report (Health Effects Institute) JID - 8812230 RN - 0 (Air Pollutants) RN - 0 (Particulate Matter) RN - 0 (Vehicle Emissions) RN - S7G510RUBH (Nitrogen Dioxide) SB - IM MH - Adult MH - Air Pollutants/analysis/*toxicity MH - Air Pollution/*adverse effects/analysis MH - Female MH - Humans MH - Inhalation Exposure/adverse effects MH - Male MH - Middle Aged MH - Nitrogen Dioxide/analysis/toxicity MH - Particulate Matter/analysis/*toxicity MH - Respiratory Hypersensitivity/*chemically induced MH - Saliva/chemistry MH - Time Factors MH - Vehicle Emissions/analysis/*toxicity MH - Young Adult EDAT- 2012/08/03 06:00 MHDA- 2012/09/05 06:00 CRDT- 2012/08/03 06:00 PHST- 2012/08/03 06:00 [entrez] PHST- 2012/08/03 06:00 [pubmed] PHST- 2012/09/05 06:00 [medline] PST - ppublish SO - Res Rep Health Eff Inst. 2012 Feb;(165):5-43; discussion 45-64.