RATIONALE: Chronic Mucus Hypersecretion(CMH) is common amongst smokers and is associated with Chronic Obstructive Pulmonary Disease(COPD) development and progression. Understanding how the relationships between smoking, CMH and COPD develop during adult life could facilitate earlier disease detection and intervention. METHODS: We analysed data on CMH, smoking and lung function prospectively collected by the MRC National Survey of Health and Development, a nationally representative British cohort followed since birth in 1946. We analysed 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 to 60-64 years related to concurrent FEV1 decline. RESULTS: From 5362 individuals enrolled at birth, 4427 contributed data between ages 20 and 64 years (52%male;63%ever-smoker). Amongst 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 (OR(95%CI):3.70(1.62-8.45);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 amongst never-smokers. The longer CMH was present across 3 occasions (ages 43, 53 and 60-64), the greater the concurrent FEV1 decline, corresponding to an additional decrement of 3.6±2.5ml/year per occasion that CMH was present(p=0.005). CONCLUSIONS: CMH amongst middle-aged smokers represents an early developmental phase of COPD. 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.