Abstract
Obstructive lung diseases, such as chronic obstructive pulmonary disease, asthma, or non-cystic fibrosis bronchiectasis, share some major pathophysiological features: small airway involvement, dysregulation of adaptive and innate pulmonary immune homeostasis, mucus hyperproduction, and/or hyperconcentration. Mucus regulation is particularly valuable from a therapeutic perspective given it contributes to airflow obstruction, symptom intensity, disease severity, and to some extent, disease prognosis in these diseases. It is therefore crucial to understand the mucus constitution of our patients, its behavior in a stable state and during exacerbation, and its regulatory mechanisms. These are all elements representing potential therapeutic targets, especially in the era of biologics. Here, we first briefly discuss the composition and characteristics of sputum. We focus on mucus and mucins, and then elaborate on the different sample collection procedures and how their quality is ensured. We then give an overview of the different direct analytical techniques available in both clinical routine and more experimental settings, giving their advantages and limitations. We also report on indirect mucus assessment procedures (questionnaires, high-resolution computed tomography scanning of the chest, lung function tests). Finally, we consider ways of integrating these techniques with current and future therapeutic options. Cystic fibrosis will not be discussed given its monogenic nature.
Highlights
No increases in mucin gene expression have been found [51], suggesting that mucus is in a dehydrated state triggered potentially by local hypoxic inhibitions of cystic fibrosis transmembrane conductance regulator (CFTR) activity [52], or by fluid absorption enhanced by human neutrophil elastase (HNE) activity [53]
Mucus dysregulation could be considered as the be-all and end-all of certain obstructive lung diseases, such as asthma, Chronic obstructive pulmonary disease (COPD), or non-CF bronchiectasis
Despite the wide range of available methods for assessing mucus production and secretion, as well as the biophysical and biochemical properties of mucus, daily clinical practice has relied for years on clinical evaluation, chest high-resolution computed tomography (HRCT), cytology, and microbiology
Summary
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