Novel Noninvasive Techniques to Study Neutrophil Airway Inflammation in an Ozone Challenge Model

Inclusion Criteria: * Able and willing to give written informed consent * Healthy male and female nonsmokers, aged 18 to 55 years, with a history of less than 1 packyear having been nonsmokers for at least the last five years, FEV1 ≥ 80 % of predicted, FEV1/FVC ≥ 70 % * Available to complete all study measurements * Women will be considered for inclusion if they are: * Not pregnant, as confirmed by pregnancy test, and not nursing * Of non-child bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is pre-menarchial or post-menopausal, with documented proof of hysterectomy or tubal ligation, or meet clinical criteria for menopause and has been amenorrhoeic for more than 1 year prior to the screening visit) * Of childbearing potential and using a highly effective method of contraception during the entire study (vasectomised partner, sexual abstinence - the lifestyle of the female should be such that there is complete abstinence from intercourse from two weeks prior to the study until at least 72 hours after the end of the study -, implants, injectables, combined oral contraceptives, hormonal IUDs) * Subjects must be able to produce adequate sputum * Subjects must be responsive to ozone in a screening challenge (250 ppb, 3h) defined by a ≥ 10 % increase in sputum neutrophils 6 h after the start of ozone exposure Exclusion Criteria: * Upper or lower respiratory tract infection in the last four weeks prior to screening * Subjects with a positive skin prick test to common aeroallergens will be excluded * Past or present disease, which as judged by the investigator, may affect the outcome of the study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, hematological disease, neurological disease, psychiatric disease, endocrine disease, infectious disease, inflammatory disease or pulmonary disease (including but not confined to asthma, tuberculosis, bronchiectasis or cystic fibrosis) * Regular intake of any prescribed or over the counter medication. Exceptions include paracetamol for pain relief, oral contraceptive medication, hormonal replacement therapy, dietary and vitamin supplements * Participation in another clinical trial 30 days prior to enrolment * Administration of corticosteroids within the last 4 weeks prior to screening * History of drug or alcohol abuse * Suspected inability to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study