Cigarette Smoke Nasal and Whole Blood Challenge in Patients With COPD

Introduction Chronic obstructive pulmonary disease (COPD) is a common respiratory disease that causes widespread morbidity and mortality, the Global Burden of Disease Study estimating COPD to be currently the sixth most common cause of death worldwide. Decades of cigarette smoking is by far the major contributing factor, and this causes a range of respiratory disorders; including chronic bronchitis, obstructive bronchiolitis, emphysema, and pulmonary vascular disease. Medical treatment of COPD is largely palliative; involving smoking cessation, use of inhaled bronchodilators, and long term oxygen therapy for respiratory failure. Recently, it has been recognised that those smokers who develop COPD have amplification of inflammation compared with "healthy smokers", and that there is the urgent need to develop new challenge models to assess why COPD develops in some heavy smokers.

Cigarette Smoke Nasal Challenge Model The nose is an accessible part of the respiratory system, from which it is possible to obtain tissue exudates and cell brushings in a non-invasive manner. A comprehensive review of the extensive clinical research experience with these nasal methodologies has recently been published. There is also the insight that patients with COPD commonly have inflammation of both the airways and nasal passages, with a similar type of inflammatory infiltrate in lower and upper airways. In COPD the inflammation is predominantly involving neutrophils and macrophages, as opposed to the increase in mast cells and eosinophils characteristic of asthma.

It has long been recognised that there is a strong functional and immunological relationship between the nose and bronchi, especially in terms of infiltrating leukocytes and inflammatory mediators when comparing allergic rhinitis and allergic asthma. The upper and lower airways have related respiratory epithelium and similar responses to allergen challenge.

The nasal and bronchial mucosa of smokers with COPD have been demonstrated to be infiltrated with CD8+ T lymphocytes and neutrophils. This corresponds to the presence of nasal symptoms during exacerbations of COPD, and sputum and nasal levels of IL-8 are correlated in COPD.

In order to sample nasal exudates for allergic inflammatory mediators, the classical methods of nasal lavage are those described by Naclerio et al., the nasal pool method of Greiff et al., and the use of a Foley's catheter by Grünberg and colleagues. Lavage is performed with saline at volumes of between 1 and 10ml. The repeatability and validity of different nasal lavage methods have been compared.