Inclusion Criteria:  aged at 40-75 years old; FEV1/FVC>70% after inhaled bronchodilator current smoker (≥ 10 pack-years) rate of FEV1 decline >30ml/y lived in a community for more than 1 years and has no plans to move out in the next 4 years  Exclusion Criteria:  history of asthma, COPD, lung cancer, active pulmonary tuberculosis, bronchiectasis, diffuse lung disease (interstitial pneumonia, pulmonary sarcoidosis, occupational lung disease, sarcoidosis et al) and pleural disease; history of lobectomy and / or lung transplantation; predicted life expectancy less than 3 years; history of severe psychiatric illnesses, mental disorders, neurological disorders, malignant tumors, chronic liver disease, heart failure, autoimmune diseases, chronic kidney disease; Alcoholism, drug abuse or abuse of toxic solvents; Cannot finish long term follow-up or poor compliance; Do not provide consent