Profile of MUC5AC and MUC5B mucins expression in asthma patients under cold exposure

Abstract

Introduction. Cold airway hyperresponsiveness (CAH) is a common condition in patients with asthma, which worsens the clinical course of the disease and the patients’ quality of life. MUC5AC and MUC5B are the main secreted mucins in the respiratory tract, which are involved in normal mucociliary clearance, but also capable of provoking the development of pathological changes in case of dysregulation of their balanced production.Aim. The aim of this study was to determine the dynamics of MUC5AC and MUC5B expression during experimental cooling in patients with asthma depending on the status of CAH.Materials and methods. The study enrolled 98 subjects including 26 patients with chronic non-obstructive bronchitis without exacerbation (control group) and 72 patients with asthma. The expression of MUC5AC, MUC5B and TRPM8 was determined in the upper respiratory tract by quantitative reverse transcription PCR. The production of MUC5AC and MUC5B was also measured in sputum by ELISA. All patients underwent a bronchoprovocation test with isocapnic cold air hyperventilation to detect CAH, and a similar nasal challenge was performed to assess the effect of cooling on the expression of the studied genes.Results. Patients with asthma had 4.22-fold increase in the expression of MUC5AC (p=0.02) in the nasal epithelium as compared with the control group. CAH was associated with an initial 7.33-fold upregulation of MUC5AC (p=0.008) as well as with further increase in MUC5AC expression but a decrease in MUC5B in response to cooling, which was not observed in asthma patients without CAH. Basal TRPM8 expression was associated with baseline level of MUC5AC (ρ=0.41, p=0.04), MUC5B (ρ=0.55, p<0.001) and amount of sputum produced after the cold bronchoprovocation.Conclusion. Asthma patients with CAH demonstrate a more pronounced imbalance in the production of mucins, which is aggravated by cold exposure. This, in turn, can lead to a number of pathological disorders associated with a more severe course of the disease.