Clinical issues of mucus accumulation in COPD

Figures & data

Figure 1 Causes of excessive mucus in COPD.

Notes: Reprinted with permission of the American Thoracic Society. Copyright © 2013 American Thoracic Society. Kim V, Criner GJ, 2013, Chronic bronchitis and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 187(3):228–237.⁷ Official journal of the American Thoracic Society.
Abbreviations: PEF, peak expiratory flow; COPD, chronic obstructive pulmonary disease.

Figure 2 MM and smooth muscle hypertrophy in a small airway from a COPD patient.

Note: Hematoxylin and eosin stain.

Abbreviations: MM, mucous metaplasia; SMH, smooth muscle hypertrophy; COPD, chronic pulmonary disease.

Figure 3 Goblet cell hyperplasia.

Notes: Periodic acid Schiff–Alcian Blue stain. Higher magnification of a small airway quadrant is shown here. Goblet cells appear in an intense blue–purple color with periodic acid Schiff–Alcian Blue stain.

Table 1 Selected studies on chronic bronchitis and outcomes

Outcome	Study	Subjects	Important findings
Lung function	Sherman et al^Citation35	3,948	Adjusted FEV1 decline: 4.5±2 mL per year (SE) in males;* 1.7±1.5 mL per year (SE) in females
	Vestbo et al^Citation36	9,435	Adjusted FEV1 decline: 22.8 mL/year (95% CI: 8.2–37.4) in males;* 12.6 mL/year (95% CI: 0.7–24.6) in females
	Lindberg et al^Citation39	963	FEV1/FVC <0.7 and FEV1 <80% predicted, OR: 2.56 (95% CI: 1.32–4.95)*
	de Marco et al^Citation37	5,002	FEV1/FVC <0.7, IRR: 1.85 (95% CI: 1.17–2.93)*
	Guerra et al^Citation38	1,412	FEV1/FVC <0.7, HR: 2.2 (95% CI: 1.3–3.8) in <50 years;* 0.9 (95% CI: 0.6–1.4) in ≥50 years
Health-related quality of life	Agusti et al^Citation25	2,164	CB+ versus CB−: GOLD II: SGRQ total 50.3±18 versus 38.9±20.5;* mMRC 1.5±1 versus 1.3±1* GOLD III: SGRQ total 58.8±17.6 versus 51.2±18.2;* mMRC 1.8±1 versus 1.8±1.1 GOLD IV: SGRQ total 65±16.5 versus 59.4±15.2;* mMRC 2.4±1 versus 2.3±1
	Kim et al^Citation24	1,061	CB+ versus CB−: SGRQ total 49.9±19.7 versus 36.6±20* SGRQ respiratory 62.5±19 versus 38±22.4* mMRC, median (interquartile range) 3(2–4) versus 2(1–3)*
	de Oca et al^Citation26	759	CB+ versus CB−: Short Form-12 physical score 44.6±1.01 versus 49.5±0.36* Limitation due to physical health 39 (40.6) versus 148 (22.4)*
COPD exacerbation and hospitalization	Vestbo et al^Citation36	9,435	COPD-related hospitalization, RR: 2.4 (95% CI: 1.3–4.5) in males;* 2.6 (95% CI: 1.2–5.3) in females*
	Burgel et al^Citation40	433	All exacerbations: OR: 4.15 (95% CI: 2.43–7.08)* Moderate exacerbations: OR: 4.65 (95% CI: 2.54–8.48)* Severe exacerbations: OR: 4.08 (95% CI: 1.18–14.09)*
	Agusti et al^Citation25	2,164	CB+ versus CB−, exacerbations in past year: GOLD II: 0.7±1.1 versus 0.6±1 GOLD III: 1±1.2 versus 1±1.4 GOLD IV: 1.2±1.6 versus 1.2±1.3
	Kim et al^Citation24	1,061	CB+ versus CB−, exacerbations in past year: Total, number/patient: 1.21±1.62 versus 0.63±1.12* Severe, %: 26.6 versus 20*
	de Oca et al^Citation26	759	CB+ versus CB−, exacerbations in past year: 5.3±3.83 versus 2.1±0.95
Mortality	Annesi and Kauffmann^Citation43	1,061	All-cause, RR: 1.35±0.111*
	Speizer et al^Citation27	8,427	COPD-related, OR: 3.75 (95% CI: 1.28–11) in males;* 11.04 (95% CI: 2.52–48.5) in females* All-cause, OR: 1.37 (95% CI: 1.09–1.72) in males;* 0.98 (95% CI: 0.68–1.41) in females
	Tockman and Comstock^Citation44	884	All cause, RR: 1.65 (95% CI: 0.95–2.89)
	Lange et al^Citation42	13,756	All-causes, RR: 1.3 (95% CI: 1.1–1.4) in males* and 1.1 (95% CI: 0.9–1.3) in females
	Prescott et al^Citation41	14,223	COPD-related with pulmonary infection, RR: 3.5 (95% CI: 1.8–7.1)* COPD-related without pulmonary infection, RR: 0.9 (95% CI: 0.5–1.8)
	Mannino et al^Citation45	5,542	All-cause, RR: 1.2 (95% CI: 0.97–1.4)
	Pelkonen et al^Citation31	1,711	Respiratory-related, HR: 2.54 (95% CI: 1–6.46)* All-cause, HR: 1.64 (95% CI: 1.23–2.19)*
	Guerra et al^Citation38	1,412	All-cause mortality, HR: 2.2 (95% CI: 1.3–3.8) in <50 years;* 1 (95% CI: 0.7–1.3) in ≥50 years

Notes:

* Statistically significant. Data are presented as mean ± SD or number (percentage), except as indicated. IRR, OR, RR, and HR are all from multivariate analyses with adjustments for covariates.

Abbreviations: FEV₁, forced expiratory volume in 1 second; SE, standard error; CI, confidence interval; FVC, forced vital capacity; OR, odds ratio; IRR, incidence rate ratio; HR, hazard ratio; CB+, group with chronic bronchitis; CB−, group without chronic bronchitis; GOLD, Global initiative for chronic Obstructive Lung Disease; SGRQ, St George’s Respiratory Questionnaire; mMRC, modified Medical Research Council; RR, relative risk; SD, standard deviation; COPD, chronic obstructive pulmonary disease.

Table 2 Summary of therapeutic interventions for chronic bronchitis

Intervention	Mechanism of action
Smoking cessation	Improves mucociliary function, decreases goblet cell hyperplasia
Physical measures (chest PT, HFCWO, flutter valve)	Augments shear stresses to improve mucociliary clearance
Expectorants	Vagally mediated increase in airway secretions
Mucolytics (hypertonic saline, dornase alpha)	Rehydration of airway mucus, hydrolysis of mucus DNA
Methylxanthines	Improves lung function, increases ciliary beat frequency
SABA	Improves lung function, increases ciliary beat frequency
LABA	Improves lung function, increases ciliary beat frequency, reduces hyperinflation, improves PEF
Anticholinergics	Improves lung function, decreases mucus secretion
Glucocorticoids	Reduces inflammation and mucus production
PDE-4 inhibitors	Reduces inflammation, improves lung function
Antioxidants	Breaks down mucin polymers, reduces mucus production
Macrolides	Reduces inflammation, reduces goblet cell secretion

Abbreviations: PT, physiotherapy; HFCWO, high frequency chest wall oscillation; DNA, deoxyribonucleic acid; SABA, short-acting beta agonist; LABA, long-acting beta agonist; PEF, peak expiratory flow; PDE-4, phosphodiesterase-4.

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