Aims: To determine the predictability of the MARKO questionnaire and/or its domains, individually or in combination with other markers and characteristics (age, gender, smoking history, lung function, 6-min walk test (6 MWT), exhaled breath temperature (EBT), and hsCRP for the incident chronic obstructive pulmonary disease (COPD) in subjects at risk over 2 years follow-up period).Participants and Methods: Patients, smokers/ex-smokers with >20 pack-years, aged 40-65 years of both sexes were recruited and followed for 2 years. After recruitment and signing the informed consent at the GP, a detailed diagnostic workout was done by the pulmonologist; they completed three self-assessment questionnaires-MARKO, SGRQ and CAT, detailed history and physical, laboratory (CBC, hsCRP), lung function tests with bronchodilator and EBT. At the 2 year follow-up visit they performed: the same three self-assessment questionnaires, history and physical, lung function tests and EBT.Results: A sample of 320 subjects (41.9% male), mean (SD) age 51.9 (7.4) years with 36.4 (17.4) pack-years of smoking was reassessed after 2.1 years. Exploratory factor analysis of MARKO questionnaire isolated three distinct domains (breathlessness and fatigue, "exacerbations", cough and expectorations). We have determined a rate for incident COPD that was 4.911/100 person-years (95% CI [3.436-6.816]). We found out that questions about breathlessness and "exacerbations", and male sex were predictive of incident COPD after two years follow-up (AUC 0.79, 95% CI [0.74-0.84], p < 0.001). When only active smokers were analyzed a change in EBT after a cigarette (Delta EBT) was added to a previous model (AUC 0.83, 95% CI [0.78-0.88], p < 0.001).Conclusion: Our preliminary data shows that the MARKO questionnaire combined with EBT (change after a cigarette smoke) could potentially serve as early markers of future COPD in smokers.