The Presence of Chronic Mucus Hypersecretion across Adult Life in Relation to Chronic Obstructive Pulmonary Disease Development

Abstract

Rationale: Chronic mucus hypersecretion (CMH) is common among smokers and is associated with chronic obstructive pulmonary disease development and progression.

Objectives: To understand how the relationships between smoking, CMH, and chronic obstructive pulmonary disease develop during adult life, and facilitate earlier disease detection and intervention.

Methods: We analyzed data on CMH, smoking, and lung function prospectively collected by the Medical Research Council National Survey of Health and Development, a nationally representative British cohort followed since birth in 1946. We analyzed the longitudinal relationships between smoking and CMH, how symptoms during life related to airflow limitation at 60-64 years, and how CMH duration between ages 43 and 60-64 years related to concurrent FEV1 decline.

Measurements and main results: From 5,362 individuals enrolled at birth, 4,427 contributed data between ages 20 and 64 years (52% male; 63% ever-smoker). Among smokers CMH prevalence escalated between ages 36 and 43 from 7.6 ± 2.0% to 13.0 ± 2.6%. At these ages, symptoms were associated with a higher risk of subsequent airflow limitation (odds ratio [95% confidence interval], 3.70 [1.62-8.45] and 4.11 [1.85-9.13], respectively). Across adult life, CMH followed a dynamic remitting-relapsing course. Symptom prevalence following smoking cessation returned to levels seen among never-smokers. The longer CMH was present across three occasions (ages 43, 53, and 60-64 yr), the greater the concurrent FEV1 decline, corresponding to an additional decrement of 3.6 ± 2.5 ml/yr per occasion that CMH was present (P = 0.005).

Conclusions: CMH among middle-aged smokers represents an early developmental phase of chronic obstructive pulmonary disease. Smoking-related CMH usually resolves following smoking cessation but the longer its duration the greater the FEV1 lost, suggesting the course of CMH across adult life may reflect the underlying course of airway disease activity.

Keywords: COPD; chronic bronchitis; chronic mucus hypersecretion; cough; smoking.

Figure 1.

Timeline of cohort size and data collection during the study between recruitment in 1946 and the most recent data collection in 2006–2011.

Figure 2.

The prevalence of chronic mucus hypersecretion (CMH), chronic sputum expectoration (CS), chronic cough (CC), and cigarette smoking among those individuals providing complete data at all six time points within the National Survey of Health and Development (n = 1,284). (A) Area-proportional Venn diagram (52) representing the overlapping cumulative prevalence (%) of CS, CC, and cigarette smoking. Numbers shown are percentages of the included population (n = 1,284). *Never-smoker, never-CS, and never-CC. (B) Analysis of differences in cumulative-symptom prevalence between ever- and never-smoker groups (P values calculated using chi-square test). (C) Prevalence (%) with 95% CI of CMH, CS, CC, and cigarette smoking at each of six time points between 1966 and 2009. Data from the 2006–2011 survey are plotted at the average date (2009). CI = confidence interval.

Figure 3.

The longitudinal pattern of chronic mucus hypersecretion (CMH) presence among those providing complete data at all six National Survey of Health and Development time points (n = 1,284) and reporting CMH on at least one occasion (156 individuals; 12.1%). At each time point, individuals are classified according to their previous and current reporting of CMH as follows (and in the CMH presence classification box): “not yet” (no current/previous CMH), “incident” (first report of CMH), “ongoing” (persistent CMH since the incident report), “relapse” (CMH currently reported following previous remission), and “remission” (CMH reported previously but absent currently). CMH = chronic cough with concurrent chronic mucus expectoration. Figure E1 displays similar separate plots of chronic sputum expectoration presence and chronic cough presence data.

Figure 4.

The prevalence of chronic mucus hypersecretion (CMH) (with 95% confidence intervals) and median smoking cigarette consumption during five time-periods over adult life within the National Survey of Health and Development according to concurrent cigarette smoking behavior (see Figures E2 and E3 and Tables E2–E4). **P < 0.01; ***P < 0.001, change in symptom prevalence during each period analyzed using McNemar’s test according to smoking behavior group (colored accordingly); ^†Mann-Whitney U tests; ^‡Wilcoxon signed rank tests. IQR = interquartile range.

Figure 5.

The relationship between chronic symptoms (chronic cough and/or chronic sputum expectoration) among smokers and nonsmokers at different ages during adult life and the presence of airflow limitation (FEV₁/FVC less than lower limit of normal) by age 60–64 years. Logistic regression models are adjusted for sex and concurrent smoking cigarette consumption. The log odds ratio (95% confidence intervals [CIs]) of having developed airflow limitation by the time they reached 60–64 years of age among those with chronic symptoms is shown at each age.

Figure 6.

The influence of duration of chronic mucus hypersecretion (CMH) presence on FEV₁ decline between ages 43 and 60–64 years. Estimated FEV₁ decline between 43 and 60–64 years of age calculated using multilevel models (Table 1) including average height and weight is shown for (A) male (height, 176 cm; weight, 79 kg) and (B) female (height, 163 cm; weight, 66 kg) smokers according to the number of occasions CMH was reported across the three time points.