Chronic obstructive lung disease (COPD) is a worldwide leading and still increasing cause of chronic morbidity and mortality. The important issue of COPD is its delayed diagnosis. Previous studies have found that accelerated loss of forced expiratory volume in 1 second (FEV1.0) in an individual is considered an indicator of developing COPD. This functional predictive system, due to lower sensitivity, is very difficult to discover high-risk population and earlier stage of the disease. The inflammation occurs earlier than the lung function impairment. Therefore, early detection of the inflammation may theoretically predict the occurrence of COPD and thus may guide early intervention.

Proteomics techniques and protein chip techniques provides us high throughput screening method to figure out characteristic inflammatory or metabolic markers of a diseases. It can be used for searching the biomarkers relating to lung function loss. EBC is collected from exhaled gas and is a good non-invasive method for exploring the pathologic process of the airways.

Thus we designed this study to identify potential biomarkers associated with rapid lung function decline. This study is divided into two parts: 1) screening potential biomarkers between stable COPD and healthy individuals; 2) verifying significant biomarkers of first part in a community-based nested case-control population for 2 years.

Thus we designed this study. This study is divided into two parts: screening target biomarkers and identifying biomarkers.

1. The FIRST STEP is a Case-control study to find target biomarkers. 20 COPD patients and 20 controls are to be enrolled in the study and their EBC and blood are collected. Proteomics techniques and protein chip techniques are to be used to screen COPD specific biomarkers in EBC.
2. The SECOND STEP is a community-based nested case-control study to make sure whether the significant biomarkers in first part can predict rapid decline of lung function. The study will be a community based, multicenter prospective cohort designed, which including a total of 2,400 study subjects. EBC and blood are collected at the baseline and followed up for two years. Case group is defined as subjects with rapid decline of lung function and new COPD patients. Control group is selected according to 1:1 matching with age and gender.

1. FIRST STEP:

1. Case Group:

   Inclusion criteria

   1. age from 40 to 75 year olds; gender is not limited.
   2. Stable COPD
   3. Sign the informed consent with willingness of obeying the protocol. Exclusion criteria
   1. with known other chronic respiratory diseases except COPD (such as asthma, tuberculosis, bronchiectasis, interstitial lung disease, occupational lung diseases, sarcoidosis, lung cancer, et al);
   2. had been accepted lung lobectomy or transplantation;
   3. be ill with severe, or uncontrolled systemic diseases other than COPD (such as psychiatry diseases, chronic liver diseases, heart failure, auto-immunity diseases, chronic renal diseases, et al );
   4. Alcoholism, drug or solvents addition;
   5. Acute exacerbation COPD patients (AECOPD)

2. Control group:

Inclusion criteria According to age (+ / - 5 years), gender and smoking, to match healthy volunteers as the control group.

1. age from 40 to 75 year olds; gender is not limited.
2. FEV1 /forced vital capacity (FVC)> 70% after inhaling bronchodilators;
3. Sign the informed consent with willingness of obeying the protocol. Exclusion criteria

a. with known other chronic respiratory diseases except COPD (such as asthma, tuberculosis, bronchiectasis, interstitial lung disease, occupational lung diseases, sarcoidosis, lung cancer, et al); b. had been accepted lung lobectomy or transplantation; c. be ill with severe, or uncontrolled systemic diseases other than COPD (such as psychiatry diseases, chronic liver diseases, heart failure, auto-immunity diseases, chronic renal diseases, et al ); d. Alcoholism, drug or solvents addition; e. Acute respiratory infection in 4 weeks (rhinitis, pharyngitis, acute tracheobronchitis, pneumonia, etc.)

2.SECOND STEP: nested case-control study Inclusion criteria

1. age from 40 to 75 year olds; gender is not limited.
2. have been living in the community for more than 1 years and no plan to move in the near 3 years
3. FEV1 / FVC > 70% after inhaling bronchodilators;
4. Sign the informed consent with willingness of obeying the protocol.

Exclusion criteria

1. with known other chronic respiratory diseases except COPD (such as asthma, tuberculosis, bronchiectasis, interstitial lung disease, occupational lung diseases, sarcoidosis, lung cancer, et al);
2. had been accepted lung lobectomy or transplantation;
3. be ill with severe, or uncontrolled systemic diseases other than COPD (such as psychiatry diseases, chronic liver diseases, heart failure, auto-immunity diseases, chronic renal diseases, et al );
4. Alcoholism, drug or solvents addition;

The FIRST STEP of study will be a outpatient based case-control study. 20 stable COPD patients and 20 healthy individuals will be recruited.

The SECOND STEP of study will be a community based, multi-center，prospective nested case-control designed, which including a total of 24OO study subjects, it will focus on two different communities, which are Shi Cha Hai community, De Sheng Community in Beijing