Discordant results have been observed regarding the associations of chronic obstructive pulmonary diseases with secretor, Lewis, and ABO histo-blood groups, which are defined by glycosyltransferases. These enzymes build up oligosaccharide structures that play a role in the adhesion of environmental factors to epithelial cells. The objectives of the present study were to assess the role of all three systems, Lewis (Le), salivary ABH secretor (Se), and red cell blood group ABO, on lung function, wheezing, and asthma in a cohort of 228 coal miners studied cross-sectionally, considering the potential modifying effect of environmental factors on these associations. Asthma was significantly related to nonsecretor phenotype. Significantly lower lung function and higher prevalences of wheezing and asthma were observed in Lewis-negative or nonsecretor subjects of blood group O. Very low lung function values were observed in the small group of Lewis-negative nonsecretors who lack both Le and Se controlled fucoses (1% of Caucasians). Lewis-positive, salivary ABH secretors who have these two fucoses represent 70% of Caucasians. Among these subjects, lower lung function was observed in blood group A, and in a lesser extent in blood group B, i.e., with terminal alpha GaINAc or alpha Gal respectively, than in blood group O subjects. ABO, Lewis, and secretor phenotypes did not account for the potential genetic heterogeneity of subjects toward smoking, but alcohol consumption appeared to exert a protective effect on lung function in Lewis-negative subjects (10% of Caucasians). If confirmed in other populations, the magnitude of the effects observed regarding low lung function in Lewis-negative ABH nonsecretors, and the protective effect of Lewis negative on the deleterious effect of alcohol, may be of clinical importance. Further studies of the combined effects of various histo-blood group genetic systems seem worthwhile, particularly for airflow limitation, wheezing, and asthma, possibly with reference to susceptibility to infectious agents.