Pathophysiology of airway hyperresponsiveness in patients with nasal polyposis

It has been hypothesized that airway hyperresponsiveness (AHR) is characterized by sensitivity (strength of stimulus) and reactivity (responsiveness to stimulus); the latter could be the intrinsic characteristic of AHR. The underlying mechanisms leading to AHR could be 1) airway inflammation, 2) reduction of forces opposing bronchoconstriction, and 3) structural airway changes/geometric factors.

Our main objective was to assess the relationships between reactivity in patients with nasal polyposis and these three mechanisms using measurements of 1) bronchial and bronchiolar/alveolar NO, 2) bronchomotor response to deep inspiration, and 3) forced expiratory flows and an index of airway to lung size, i.e. FEF(25-75%)/FVC.

Patients underwent spirometry, multiple flow measurement of exhaled NO (corrected for axial diffusion), assessment of bronchomotor response to deep inspiration by forced oscillation technique and methacholine challenge allowing the calculation of reactivity (slope of the dose-response curve) and sensitivity (PD(10)).

One hundred and thirty-two patients were prospectively enrolled of whom 71 exhibited AHR. Airway reactivity was correlated with alveolar NO concentration (rho = 0.35; p = 0.017), with airflow limitation (FEF(25-75%): rho = -0.40; p = 0.003) and with an index of airway size to lung size (FEF(25-75%)/FVC: rho = -0.38; p = 0.005), of which only alveolar NO remained the only independent factor in a stepwise multiple regression analysis (variance 25%). Airway sensitivity was not correlated with any pulmonary function or exhaled NO parameter.

In patients with nasal polyposis, alveolar NO is associated with airway reactivity, suggesting that bronchiolar/alveolar lung inflammation may constitute one intrinsic characteristic of increased responsiveness.