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Date of Award

Fall 2012

Degree Type

Thesis

Degree Name

Master of Health Sciences (MSc)

Department

Medical Sciences (Division of Physiology/Pharmacology)

Supervisor

Parameswaran Nair

Language

English

Abstract

Various studies have shown an association between neutrophilic airway inflammation and severe asthma, but have failed to establish a causal relationship. In these studies airway neutrophilia could be due to high steroid doses, an airway infection, an epiphenomenon of severe asthma or a combination of these. We have examined the role of neutrophils in severe asthma in patients on optimum steroid doses with controlled eosinophilic airway inflammation and chemotactic activity of IL-17 as one potential mechanism of neutrophil recruitment to the airway.

We examined the number, viability and activity of neutrophils in blood and sputum of three groups of asthma subjects divided on the basis of asthma severity. We also compared direct migration of blood neutrophils towards IL-17 between non-asthmatics and severe asthma subjects.

Viability and survival at 24 hours was measured by examining apoptotic and non-apoptotic cells. Activation was examined by measuring the production of hydrogen peroxide and the expression of primary and secondary granule proteins. In migration study, migration of neutrophils towards IL-17 was measured.

Blood neutrophils were increased in severe asthma subjects as compared to moderate and mild asthma subjects. There was no difference in sputum neutrophil numbers. There was no difference in viability, although blood neutrophil 24 hour survival was increased in severe asthma subjects as compared to moderate asthma subjects. There was no difference in the level of activation amongst the three groups.

IL-17 was not a chemotactic stimulus for neutrophils. The study results show that sputum neutrophil numbers and activation are not increased in severe asthma as compared to less severe asthma. Therefore, the study results do not support a causal relationship between airway neutrophilia and severe asthma.

Airway neutrophilia observed in previous studies might be due to airway infections or high doses of steroids taken by study subjects.

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