Mucus Plugs and Emphysema in the Pathophysiology of Airflow Obstruction and Hypoxemia in Smokers

Abstract

Rationale:The relative roles of mucus plugs and emphysema in mechanisms of airflow limitation and hypoxemia in smokers with chronic obstructive pulmonary disease (COPD) are uncertain.Objectives: To relate image-based measures of mucus plugs and emphysema to measures of airflow obstruction and oxygenation in patients with COPD.Methods: We analyzed computed tomographic (CT) lung images and lung function in participants in the Subpopulations and Intermediate Outcome Measures in COPD Study. Radiologists scored mucus plugs on CT lung images, and imaging software automatically quantified emphysema percentage. Unadjusted and adjusted relationships between mucus plug score, emphysema percentage, and lung function were determined using regression.Measurements and Main Results: Among 400 smokers, 229 (57%) had mucus plugs and 207 (52%) had emphysema, and subgroups could be identified with mucus-dominant and emphysema-dominant disease.Only 33% of smokers with high mucus plug scores had mucus symptoms. Mucus plug score and emphysema percentage were independently associated with lower values for FEV 1 and peripheral oxygen saturation (P , 0.001). The relationships between mucus plug score and lung function outcomes were strongest in smokers with limited emphysema (P , 0.001). Compared with smokers with low mucus plug scores, those with high scores had worse COPD Assessment Test scores (17.4 6 7.7 vs. 14.4 6 13.3), more frequent annual exacerbations (0.75 6 1.1 vs. 0.43 6 0.85), and shorter 6-minute-walk distance (329 6 115 vs. 392 6 117 m) (P , 0.001). Conclusions: Symptomatically silent mucus plugs are highly prevalent in smokers and independently associate with lung function outcomes. These data provide rationale for targeting patients with mucus-high/emphysema-low COPD in clinical trials of mucoactive treatments.Clinical trial registered with www.clinicaltrials.gov (NCT01969344).

Comparison of demographic, clinical, spirometry, and radiological parameters between smoking and non-smoking COPD patients in rural Gujarat, India

“…[ 7 ] In our study, almost equal number of smokers and never smokers reported production of mucus or phlegm, which correlates with a well-known fact that smoke is a primary cause of goblet cell hyperplasia and resultant mucus hypersecretion in the pathophysiology of COPD. [ 8 ] This could explain the reason for increase mucus production reported by non-smoker COPD patients in our study as biomass fuel exposure is present in a majority of these patients. [ 9 ]…”

“…The chronic inflammatory process induced by tobacco smoking promotes thickening and narrowing of the small conducting airways, as well as destruction of the parenchyma and reduced alveolar-bronchiolar attachments. [ 8 11 12 ] More severe expiratory airflow obstruction in smokers could be secondary to these additional changes.…”

Mucus, Microbiomes and Pulmonary Disease

“…During an exacerbation event, mucin overproduction and its associated inflammation leads to airway obstruction, contributing to poorer lung function. Detecting and quantifying mucus plugs using multidetector CT in asthma and COPD is linked to airflow obstruction and poorer lung function outcomes [113,114]. Importantly, the prevalence of mucus hypersecretion is similar in patients with high and low mucus plug scores, highlighting the difficulties in using symptoms as a main surrogate for disease classification.…”

Mucus plugging on computed tomography and chronic bronchitis in chronic obstructive pulmonary disease

“…Radiologically, MP has been linked to severity of airflow obstruction, eosinophilic inflammation, and interleukin-4 blood levels in asthma [ 5 , 7 ]. In two smaller studies, MP was associated with worse lung function and health-related quality of life in smokers with and without COPD, but neither CB nor eosinophilia [ 3 , 8 ]. To date, this is the first study finding a significant association between mucus plugging and CB in a large cohort of COPD subjects.…”

“…More mucus plugs have been found in COPD subjects with worse airflow obstruction; additionally, more emphysema is seen in COPD patients with worse airflow obstruction. Previous smaller studies in smokers with and without COPD have found weak but significant correlations between mucus plugging scores and percent emphysema [ 3 , 8 ]. Our analysis was restricted to those with COPD, and we found statistically different amounts of percent emphysema between those with and without mucus plugs but the difference was not great.…”