Chest
Translating Basic Research Into Clinical PracticeSecretory Hyperresponsiveness and Pulmonary Mucus Hypersecretion
Section snippets
Physiology of Mucus Hypersecretion
In health, mucus is secreted to coat the airway, prevent water loss, and trap inhaled material, which is removed by mucociliary clearance. Normal mucus is a mixture of mucin glycoproteins, electrolytes, water, and secreted lipids and peptides. Mucins are linearly linked core proteins encoded by mucin (MUC) genes. These core mucin proteins are heavily glycosylated. Of the identified human MUC genes, 11 are expressed in the airway at the messenger RNA or protein level. The principal airway
IL-13 and Mucus Hypersecretion in Asthma
Patients with asthma who have chronic cough and sputum production have worse clinical control as measured by the Asthma Control Questionnaire (ACQ) and more frequent exacerbations19; additionally, there is dramatic mucus obstruction in the airways of patients with asthma who are dying.20, 21 Helper T-cell type 2 cytokines, including IL-13, are implicated in mucus production and goblet cell hyperplasia in asthma,22 and IL-13 induces goblet cell hyperplasia with mucus hypersecretion in the mouse
Allergic Bronchopulmonary Aspergillosis
Fungi in the genus Aspergillus are ubiquitous. They can be found wherever there is decomposing organic matter and on surfaces that get wet. Spores from some species in this genus, particularly Aspergillus fumigatus, can cause human disease. The spores are 2 to 3 μm in diameter, small enough to reach the alveoli in humans. Host defenses are normally able to clear Aspergillus spores without disease but hosts with propensity for airway mucus plugging, such as patients with asthma, are susceptible
Summary
Mucus hypersecretion is a distinct component of many airway diseases including inflammatory diseases and some forms of airway cancer. Although mucus secretion is an effective airway defense, secretory hyperresponsiveness can lead to airway obstruction and poor clearance. Therapy targeted at inflammation may be less effective in decreasing pathologic hypersecretion. There is a need for effective mucoregulatory medications to treat secretory hyperresponsiveness.
Acknowledgments
Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts: Dr Rubin holds patents for the use of aerosol surfactant as mucokinetic medications and aerosolized Dapsone as a mucoregulatory therapy in airway hyperinflation. VCU has licensed this to InspiRx. Dr Rubin also holds research grants from the Cystic Fibrosis Foundation and the Denny Hamlin Foundation for studying mucus clearance as well as research grants from Fisher & Paykel, GlaxoSmithKline, and
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2022, Advanced Drug Delivery ReviewsCitation Excerpt :The main reasons are the overproduction of biomolecules and the decrease of mucociliary clearance. In the mucus of CF patients, although the content of water and mucins is reduced by the serine proteases degradation, increase of the content of DNA and actin with high MW induces mucus accumulation in the airway [73,74]. The pore size of mucus mesh also reduces to 140 ± 50 nm in CF [75].
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Dr Henke is currently at Asklepios Fachkliniken München-Gauting, Comprehensive Pneumology Center, Member of the German Center for Lung Research (Gauting, Germany)