Nasal mucosa secretion exudation response to cold air in bronchial asthma patients

Background. Combined airway hyper responsiveness to cold and hypoosmotic stimuli in asthma patients results in impairment of lung respiration function and poor disease control compared to patients with isolated airway hyper responsiveness to only one of the stimuli or without such responsiveness that can be connected with edema or mucus hypersecretion.

Aim. The purpose of the study is the estimation of the processes of mucin secretion, plasma exudation and oxidative stress in response to cold air in asthma patients with combined airway responsiveness to cold and hypoosmotic stimuli using nasal mucosa as a model.

Materials and methods. 23 patients with asthma participated in the study. For the nasal lavage procedure, a nasal cavity was pre-washed at least three times in 5-min intervals with 5 ml saline solution (~36 °C). A control nasal lavage was done 5 min after the last washing with a dwelling time of 1 min in the nasal cavity. Directly after the control lavage, a cold air nasal challenge was done: a participant was asked to breathe deeply at the pace of a metronome to ensure hyperventilation inhaling cold air (–20 °C) through the nose and exhaling through the mouth for 5 min. Nasal lavages were taken at 1 min, 15, and 30 min after the challenge. Mucin secretion was estimated on the basis of total protein (TP) content, total carbohydrates (TC), and water-soluble forms of mucins MUC5AC and MUC5B in the lavage fluids. For the estimation of plasma exudation, the concentration of α2-macroglobulin (α2-MG) was measured. Oxidative stress was estimated by the content of thiobarbituric acid-reactive substances (TBARS) in lavage fluid. Lung function and airway responsiveness were studied by the forced expiration spirometry method and the bronchial challenge tests with isocapnic cold air hyperventilation (CAHV) and distilled water inhalation (DWI).

Results. According to the bronchial challenge tests, the patients were divided into groups: 1) without airway responsiveness to the cold and osmotic stimuli (n = 6); 2) combined airway responsiveness to both stimuli (drop in FEV1 by 10% or more after CAHV and DWI) (n = 11); 3) isolated airway responsiveness to only one of the stimuli (n = 6). In the total group of asthma patients, the mean content of TP, TC, α2-MG, and TBARS increased by 63%, 109, 47, and 68%, respectively, after the cold air nasal challenge, whereas MUC5AC and MUC5B decreased by 15 and 20%, respectively. Secretion and exudation in the nasal mucosa were more pronounced in asthma patients of group 2 in comparison with other groups. Oxidative stress was lower in group 1. There were two interesting correlations between bronchi responsiveness to CAHV and DWI and changes in the content of the biomarkers after the cold air nasal challenge in group 2: 1) ∆FEV1 after CAHV and TC level at 15 min (r = –0,65; р = 0,0401) and at 30 min (r = –0,82; р = 0,0034); 2) ∆FEV1 after DWI and the change of α2-MG at 1 min after the cold air nasal challenge (r = –0,67; р = 0,0242).

Conclusion. In accordance with the unified airway model, the found correlations may indicate that prolonged mucin secretion after cold air breathing is a negative factor for the bronchi response to cold air, whereas enhanced plasma exudation determines the bronchi responsiveness to a hypoosmotic stimulus. Nasal mucosa is a promising model for the simultaneous investigation of molecular processes of airway secretion, exudation and oxidative response in asthma patients. 

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