title: Effects of ultrafine particles on the allergic inflammation in the lung of asthmatics: results of a double-blinded randomized cross-over clinical pilot study.
abstract: BACKGROUND
  Epidemiological and experimental studies suggest that exposure to ultrafine particles (UFP) might aggravate the allergic inflammation of the lung in asthmatics.
  
  
  METHODS
  We exposed 12 allergic asthmatics in two subgroups in a double-blinded randomized cross-over design, first to freshly generated ultrafine carbon particles (64 μg/m³; 6.1 ± 0.4 × 10⁵ particles/cm³ for 2 h) and then to filtered air or vice versa with a 28-day recovery period in-between. Eighteen hours after each exposure, grass pollen was instilled into a lung lobe via bronchoscopy. Another 24 hours later, inflammatory cells were collected by means of bronchoalveolar lavage (BAL). (
  
  
  BACKGROUND
  NCT00527462) RESULTS: For the entire study group, inhalation of UFP by itself had no significant effect on the allergen induced inflammatory response measured with total cell count as compared to exposure with filtered air (p = 0.188). However, the subgroup of subjects, which inhaled UFP during the first exposure, exhibited a significant increase in total BAL cells (p = 0.021), eosinophils (p = 0.031) and monocytes (p = 0.013) after filtered air exposure and subsequent allergen challenge 28 days later. Additionally, the potential of BAL cells to generate oxidant radicals was significantly elevated at that time point. The subgroup that was exposed first to filtered air and 28 days later to UFP did not reveal differences between sessions.
  
  
  CONCLUSIONS
  Our data demonstrate that pre-allergen exposure to UFP had no acute effect on the allergic inflammation. However, the subgroup analysis lead to the speculation that inhaled UFP particles might have a long-term effect on the inflammatory course in asthmatic patients. This should be reconfirmed in further studies with an appropriate study design and sufficient number of subjects.
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Str. 1a, 30625, Hannover, Germany. Frank.Schaumann@mps-hamburg.com.
authors.forename: Frank
authors.initials: F
authors.lastname: Schaumann
authors.affiliation: Hannover Medical School, Hannover, Germany. Cornelia.Froemke@tiho-hannover.de.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Frömke
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Str. 1a, 30625, Hannover, Germany. dijkstra.dorothea@mh-hannover.de.|Hannover Medical School, Hannover, Germany. dijkstra.dorothea@mh-hannover.de.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Dijkstra
authors.affiliation: Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Member of the German Center for Lung research (DZL), Munich, Germany, Munich, Germany. franci@helmholtz-muenchen.de.
authors.forename: Francesca
authors.initials: F
authors.lastname: Alessandrini
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Str. 1a, 30625, Hannover, Germany. horst.windt@item.fraunhofer.de.
authors.forename: Horst
authors.initials: H
authors.lastname: Windt
authors.affiliation: Cooperationgroup Comprehensive Molecular Analytics (CMA), Joint Mass Spectrometry Centre (JMSC), Helmholtz Zentrum München, Munich, Germany. karg@helmholtz-muenchen.de.
authors.forename: Erwin
authors.initials: E
authors.lastname: Karg
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Str. 1a, 30625, Hannover, Germany. meike.mueller@item.fraunhofer.de.
authors.forename: Meike
authors.initials: M
authors.lastname: Müller
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Str. 1a, 30625, Hannover, Germany. carla.winkler@astrazeneca.com.|Hannover Medical School, Hannover, Germany. carla.winkler@astrazeneca.com.
authors.forename: Carla
authors.initials: C
authors.lastname: Winkler
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Str. 1a, 30625, Hannover, Germany. armin.braun@item.fraunhofer.de.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research, Hannover, Germany. armin.braun@item.fraunhofer.de.
authors.forename: Armin
authors.initials: A
authors.lastname: Braun
authors.affiliation: Hannover Medical School, Hannover, Germany. koch.armin@mh-hannover.de.
authors.forename: Armin
authors.initials: A
authors.lastname: Koch
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Str. 1a, 30625, Hannover, Germany. jens.hohlfeld@item.fraunhofer.de.|Hannover Medical School, Hannover, Germany. jens.hohlfeld@item.fraunhofer.de.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research, Hannover, Germany. jens.hohlfeld@item.fraunhofer.de.
authors.forename: Jens Michael
authors.initials: JM
authors.lastname: Hohlfeld
authors.affiliation: Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Member of the German Center for Lung research (DZL), Munich, Germany, Munich, Germany. heidrun.behrendt@lrz.tu-muenchen.de.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Behrendt
authors.affiliation: Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München, Member of the German Center for Lung Research, Munich, Germany. otmar.schmid@helmholtz-muenchen.de.
authors.forename: Otmar
authors.initials: O
authors.lastname: Schmid
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Str. 1a, 30625, Hannover, Germany. wolfgang.koch@item.fraunhofer.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koch
authors.affiliation: Institute of Epidemiology I, Helmholtz Zentrum München, Munich, Germany. schulz@helmholtz-muenchen.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Schulz
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Str. 1a, 30625, Hannover, Germany. norbert.krug@item.fraunhofer.de.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research, Hannover, Germany. norbert.krug@item.fraunhofer.de.
authors.forename: Norbert
authors.initials: N
authors.lastname: Krug
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D001249:Asthma / Q000150:complications* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D002244:Carbon / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D052638:Particulate Matter / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D010865:Pilot Projects; D011014:Pneumonia / Q000139:chemically induced* / Q000150:complications / Q000276:immunology / Q000503:physiopathology; D012130:Respiratory Hypersensitivity / Q000150:complications / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D012720:Severity of Illness Index
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D002244:Carbon