Airway responses to NO2 and allergen in asthmatics
Nitrogen dioxide (N02), a gas produced by combustion, is a common environmental air pollutant. Individuals with asthma are more sensitive to N02 exposure than healthy subjects, according to results from controlled human-exposure studies. N02 can enhance the asthmatic response to inhaled allergen. The mechanisms for N02's enhancing effect on the asthmatic reaction to allergen appear to be related to an increased inflammatory reaction in the airways.
The general aim of the studies I-III was to examine whether an ambient level of an air pollutant, nitrogen dioxide, interacts with pollen allergens so as to enhance the allergic inflammation in the upper and lower airways. Efforts were made to mimic real exposure situations with ambient doses of air pollutants and allergen.
The aim of study IV was to evaluate a simplified method to study intra-individual changes in eosinophil cationic protein (ECP) in induced sputum.
I. Thirteen subjects with mild asthma and allergy were exposed at rest to 500 µg/m3 N02 or purified air for 30 minutes, followed four hours later by an allergen inhalation challenge. Bronchoscopy was performed 19 hours after the allergen challenge. This single 1/2-hour exposure to N02 followed by allergen gave an increase in the number of neutrophilic cells both in the bronchial and the bronchoalveolar lavage fluid. The levels of ECP were higher in bronchial wash after N02+allergen. No alteration was seen in symptoms or pulmonary function between N02+allergen and purified air+allergen exposure.
II. We used the same exposure protocol as in study 1 but on sixteen subjects who had asthma and rhinitis. The aim was to investigate if similar changes occurred in the upper airways. Nasal lavage was made before exposure, before nasal allergen challenge, and one, four and 18 hours after allergen challenge. No such priming effect of ambient N02 exposure on subsequent allergic response in the upper airways (activation of inflammatory cells and mediators) was noticeable.
III. Eighteen subjects with mild asthma were exposed to 500 µg/m 3 N02 or purified air for 15 minutes on day 1 and 2x1 5 minutes on day 2. Four hours after the exposure (day 1), and the two exposures (day 2) an allergen dose was inhaled. Sputum was induced and daily blood samples were taken. ECP in both sputum and blood increased after the 3 repeated exposures but not after a single brief exposure. No alteration was seen in symptoms or pulmonary function between N02+allergen and purified air+allergen exposure.
IV. In thirteen mild asthmatics sputum was induced before and 24 hours after allergen challenge. The entire sputum sample was incubated and divided into 2 parts. One part was processed according to the conventional method, and released ECP levels in the supernatant were measured. The second part was treated with a lysing reagent, and total ECP (intracellular and extracellular) was measured. We found a good correlation between total ECP levels in the entire sputum sample and released ECP levels in the supernatant before and 24 hours after allergen challenge. The changes in total and released ECP after the allergen challenge also correlated. Total ECP seems to reflect the eosinophilic inflammatory changes in asthma, and might be a useful tool in monitoring asthma in clinical practise and in exposure studies.
These studies (I-III) show for the first time that there is an interactive effect of the air pollutant N02 and allergen on the inflammatory reaction in the bronchi of persons with asthma. N02 has an enhancing effect on the eosinophilic inflammation by increasing the release of ECP. This was found both in bronchial lavage fluid, induced sputum and peripheral blood. There was also an increase of the neutrophilic cells in the airways. These N02 effects on eosinophilic and neutrophilic leukocytes were found in the lower but not in the upper airways. The N02 concentrations and allergen doses were comparable to the levels you can encounter in the outdoor environment. This data suggests that ambient N02 can enhance the allergic inflammatory reaction in the airways without causing symptoms or pulmonary dysfunction.
List of scientific papers
I. Barck C, Sandstrom T, Lundahl J, Hallden G, Svartengren M, Strand V, Rak S, Bylin G (2002). Ambient level of NO2 augments the inflammatory response to inhaled allergen in asthmatics. Respir Med. 96(11): 907-17.
https://doi.org/10.1053/rmed.2002.1374
II. Barck C, Lundahl J, Holmstrom M, Bylin G (2005). Does nitrogen dioxide affect inflammatory markers after nasal allergen challenge? [Submitted]
III. Barck C, Lundahl J, Hallden G, Bylin G (2005). Brief exposures to NO2 augment the allergic inflammation in asthmatics. Environ Res. 97(1):58-66.
https://doi.org/10.1053/rmed.2002.1374
IV. Barck C, Lundahl J, Hallden G, Bylin G (2005). Total eosinophil cationic protein levels in induced sputum as a marker of changes in eosinophilic inflammation in patient with allergic asthma. [Accepted]
https://doi.org/0.1016/S1081-1206(10)61193-3
History
Defence date
2005-04-29Department
- Department of Medicine, Huddinge
Publication year
2005Thesis type
- Doctoral thesis
ISBN-10
91-7140-273-XNumber of supporting papers
4Language
- eng