Immune dysregulation in the aging human lung.

Abstract

Aging has been associated with diminished lung function and increased susceptibility to lung infection. To determine whether changes suggestive of immune dysregulation and inflammation appear in the lungs of clinically normal individuals as a function of advancing age, we performed bronchoalveolar lavage (BAL) on discontinuous age groups (20-36, 45-55, and 65-78 yr old) of clinically normal volunteer subjects. We measured immunoglobulin (IgG, IgA, IgM), albumin, interleukin-6 (IL-6), and interleukin-10 concentrations in BAL fluid. Bronchoalveolar cell profiles, cell surface antigen expression, and superoxide anion production were also measured. A significant increase in total cell concentration, neutrophils, and BAL immunoglobulin content was observed in the oldest age group compared with the youngest age group. Mean lymphocyte subset (CD4+/CD8+) ratios were significantly increased in blood (2.6 +/- 0.4 versus 1.6 +/- 0.1; p<0.03) and to a greater degree in BAL (4.8 +/- 1.0 versus 1.9 +/- 0.2; p<0.01) for the oldest versus youngest age groups. Similarly, BAL-derived cells displayed significantly increased phorbol myristate acetate-stimulated release of superoxide anion (8.8 +/- 1.3 versus 4.5 +/- 0.7 nmol/5 x 10 5 cells/h; p<0.01) for the oldest versus youngest subject group, and mean BAL IL-6 concentrations were significantly elevated in the oldest age group (0.86 +/- 0.13 ng/ml) compared with the youngest age group (0.53 +/- 0.03 ng/ml; p<0.01). Our observations suggest that altered inflammatory cell profiles and low-grade inflammation exist in the lower respiratory tracts of many asymptomatic, clinically normal volunteers of advanced age.

Airways inflammation in chronic bronchitis: the effects of smoking and alpha1-antitrypsin deficiency

“…The current data shows that inflammation in the larger airways is increased in the a 1 ATD subjects despite more using inhaled steroids (which would be expected to have a beneficial effect) [23] and the subjects being younger (which would also be associated with less inflammation in the larger airways) [31,32]. MPO concentrations were higher, as was the chemoattractant LTB 4 .…”

Differential susceptibility according to gender in the association between air pollution and mortality from respiratory diseases

“…The increased susceptibility of elderly to particulate matter may also be to due lifelong exposure to environmental substances that are harmful to health, as well as to previous respiratory infections, as observed by Meyer et al 35 in a study of healthy non-smokers from 65 to 78 years of age. The authors observed an increase in neutrophils, immunoglobulins (IgG, IgA, and IgM), and interleukin-6 (IL-6) in fluid from bronchoalveolar lavage, as compared to samples from individuals 20 to 36 years of age.…”

Bronchoalveolar lavage, sputum and exhaled clinically relevant inflammatory markers: values in healthy adults

“…Focusing on studies on normal values, nine studies specifically designed to provide data on BAL cellular normal reference values in adult subjects, fulfilling the current literature search criteria, have been published as observational studies (table 2) [26, [28][29][30][31][32][33][34][35]. Eight of these were performed in North America and only one in Europe [35].…”

“…Most of the subjects were male, nonsmokers and aged ,50 yrs. Only four studies specifically evaluated the influence of age on BAL characteristics [26,[33][34][35], and most of the subjects concerned were nonsmokers. Since the vast majority of the studies were from North America, in particular the USA, it is not surprising that in some cases volunteers were reimbursed for participation.…”