Chronic mucus hypersecretion in COPD and asthma: Involvement of microRNAs and stromal cell-epithelium crosstalk

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide, especially in the elderly, while asthma is the most common chronic disease among children. Many COPD and asthma patients suffer from chronic cough with phlegm, a symptom called chronic mucus hypersecretion (CMH). Patients with CMH have a lower quality of life, more breathing difficulty, and a higher risk of death. CMH is attributed to excessive mucus production in the airways and impaired mucus clearance.

In this thesis, we hypothesized that microRNAs (small molecules that regulate translation of genes into proteins) are involved in CMH by influencing 1) mucus production and 2) communication between mucus-producing cells in the airways and the cells in the underlying connective tissues.

Through extensive profiling of miRNAs and transcribed genes in airway biopsies, new microRNAs and genes that potentially play a role in the development of CMH were identified. MicroRNA-31-5p was associated with CMH in both COPD and asthma, suggesting a similar mechanism that contributes to CMH in both diseases. Furthermore, we showed that the cells in the underlying connective tissues communicate with mucus-producing cells in the airway, and this communication promotes mucus production. It was also shown that microRNAs, including miRNA-146a-5p, are also involved in this communication.

The findings in this thesis provide more insight into mechanisms that play a role in CMH in the contexts of both COPD and asthma. The translation of these discoveries to the clinic may lead to the development of new treatment strategies for CMH.