We read with interest the article by Thomas et al1(December 2004) on the influence of age on induced sputum in normal subjects. We think that the discussion on the possible physiopathologic mechanisms could be deepened. Although an influence of advancing age on lung cellularity in healthy subjects has been already described,2 reference values for cell counts in induced sputum in healthy adults > 50 years old are not available. The possible explanations of the results found by Thomas et al1 could be an impairment in humoral lung immunity in older healthy subjects compared with younger healthy subjects,3and the presence of a low-grade inflammation in the lower respiratory tracts of many asymptomatic, older subjects.4 In particular, a previous study2 has reported in BAL fluid of the older healthy individuals an increase in CD4+/CD8+ lymphocytes ratio probably due to a repeated antigenic stimulation or irritation by environmental substances of the immune cells in the lower respiratory tract during the years. The recurrent antigen stimulation on the immune cells in the lung could be demonstrated by the decreasing with age of CD19+ B lymphocytes that represent the B cells not yet differentiated into antibody-secreting cells, suggesting that B cells on mucosal surface of airways in older subjects has been driven to differentiate by previous repeated antigen stimulations. The low-grade inflammation in the airways observed in older subjects might be related to the decline in the lung function that starts in the fourth to fifth decade of life in normal never-smoker humans. The mechanism by which neutrophils are recruited to within the airways in older healthy subjects is still unclear. A number of neutrophil chemoattractants can be secreted by inflammatory cells that reside in the airways, and epithelial cells can release cytokines, such as IL-8, which have a potent chemoattractant activity for neutrophils.5 Low-grade persistent inflammation may occur because of the loss of factors that normally down-regulate the inflammatory response to pollutants or repetitive antigenic stimulations, combined with advancing age. Epithelial cells could be a significant source of neutrophil chemoattractants, which contributes to a low-grade inflammation in older subjects. Persistent, low-grade inflammation could damage elastin and perhaps lead to the age-associated loss of elastin fibers. Therefore, considering that many patients affected by asthma or COPD who increasingly perform induced sputum are often > 50 years old, these findings deserve further investigations.