BACKGROUND: Although both smoking and respiratory complaints are very common, tools to improve diagnostic accuracy are scarce in primary care. This study aimed to reveal what inflammatory patterns prevail in clinically established diagnosis groups, and what factors are associated with eosinophilia. METHOD: Induced sputum and blood plasma of 59 primary care patients with COPD (n = 17), asthma (n = 11), chronic bronchitis (CB, n = 14) and smokers with no respiratory complaints ('healthy smokers', n = 17) were collected, as well as lung function, smoking history and clinical work-up. Patterns of inflammatory markers per clinical diagnosis and factors associated with eosinophilia were analyzed by multiple regression analyses, the differences expressed in odds ratios (OR) with 95% confidence intervals. RESULTS: Multivariately, COPD was significantly associated with raised plasma-LBP (OR 1.2 [1.04-1.37]) and sTNF-R55 in sputum (OR 1.01 [1.001-1.01]), while HS expressed significantly lowered plasma-LBP (OR 0.8 [0.72-0.95]). Asthma was characterized by higher sputum eosinophilic counts (OR 1.3 [1.05-1.54]), while CB showed a significantly higher proportion of sputum lymphocytic counts (OR 1.5 [1.12-1.9]). Sputum eosinophilia was significantly associated with reversibility after adjusting for smoking, lung function, age, gender and allergy. CONCLUSION: Patterns of inflammatory markers in a panel of blood plasma and sputum cells and mediators were discernable in clinical diagnosis groups of respiratory disease. COPD and so-called healthy smokers showed consistent opposite associations with plasma LBP, while chronic bronchitics showed relatively predominant lymphocytic inflammation compared to other diagnosis groups. Only sputum eosinophilia remained significantly associated with reversibility across the spectrum of respiratory disease in smokers with airway complaints.