Accelerated Lung Function Decline and Mucus–Microbe Evolution in Chronic Obstructive Pulmonary Disease

• Published in: American journal of respiratory and critical care medicine Vol. 210; no. 3; pp. 298 - 310
• Main Authors: Meldrum, Oliver W., Donaldson, Gavin C., Narayana, Jayanth Kumar, Xaverius Ivan, Fransiskus, Jaggi, Tavleen K., Mac Aogáin, Micheál, Finney, Lydia J., Allinson, James P., Wedzicha, Jadwiga A., Chotirmall, Sanjay H.
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01.08.2024
• Subjects: Achromobacter; Aged; Aged, 80 and over; Airway management; Chronic obstructive pulmonary disease; Disease Progression; Female; Forced Expiratory Volume; Humans; Klebsiella; Longitudinal Studies; Lung cancer; Lung diseases; Male; Microbiota; Middle Aged; Mucin 5AC - metabolism; Mucin-5B - metabolism; Mucus - microbiology; Original; Pathology; Prospective Studies; Pulmonary Disease, Chronic Obstructive - microbiology; Respiratory Function Tests; Sputum - microbiology; rheology; lung function decline; metagenomics; COPD; mucus
• ISSN: 1073-449X; 1535-4970; 1535-4970
• DOI: 10.1164/rccm.202306-1060OC

Progressive lung function loss is recognized in chronic obstructive pulmonary disease (COPD); however, no study concurrently evaluates how accelerated lung function decline relates to mucus properties and the microbiome in COPD. Longitudinal assessment of mucus and microbiome changes accompanying accelerated lung function decline in patients COPD. This was a prospective, longitudinal assessment of the London COPD cohort exhibiting the greatest FEV decline (  = 30; accelerated decline; 156 ml/yr FEV loss) and with no FEV decline (  = 28; nondecline; 49 ml/yr FEV gain) over time. Lung microbiomes from paired sputum (total 116 specimens) were assessed by shotgun metagenomics and corresponding mucus profiles evaluated for biochemical and biophysical properties. Biochemical and biophysical mucus properties are significantly altered in the accelerated decline group. Unsupervised principal component analysis showed clear separation, with mucus biochemistry associated with accelerated decline, whereas biophysical mucus characteristics contributed to interindividual variability. When mucus and microbes are considered together, an accelerated decline mucus-microbiome association emerges, characterized by increased mucin (MUC5AC [mucin 5AC] and MUC5B [mucin 5B]) concentration and the presence of and . As COPD progresses, mucus-microbiome shifts occur, initially characterized by low mucin concentration and transition from viscous to elastic dominance accompanied by the commensals , , , and (Global Initiative for Chronic Obstructive Lung Disease [GOLD] A and B) before transition to increased mucus viscosity, mucins, and DNA concentration together with the emergence of pathogenic microorganisms including , , and (GOLD E). Mucus-microbiome associations evolve over time with accelerated lung function decline, symptom progression, and exacerbations affording fresh therapeutic opportunities for early intervention.