Impaired alveolar macrophage response to Haemophilus antigens in chronic obstructive lung disease.

RATIONALE: Interactions of nontypeable Haemophilus influenzae (NTHI) with macrophages are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the immunologic mechanisms that mediate NTHI-macrophage inflammation are poorly understood. Outer membrane protein (OMP) P6 and lipooligosaccharide (LOS) of NTHI are potent immunomodulators. We theorized that alveolar macrophages in COPD possess fundamental immune defects that permit NTHI to evade host responses. OBJECTIVE: To test this hypothesis, we obtained human alveolar and blood macrophages from exsmokers with COPD, exsmokers without COPD, and nonsmokers. METHODS: Alveolar and blood macrophages from each donor were incubated with purified LOS and OMP P6 and with OMP P2 and the total outer membrane preparation (0.1-1 microg/ml). MEASUREMENTS: Supernatants (24 h) were assayed for IL-1beta, TNF-alpha, IL-10, IL-12, and IL-8 by multianalyte multiplexed flow cytometry. RESULTS: Comparative induction of COPD and non-COPD alveolar macrophages by LOS and OMP P6 revealed diminished IL-8, TNF-alpha, and IL-1beta responses of COPD alveolar macrophages (p < or = 0.03 for each). COPD alveolar macrophages also had diminished responses to total outer membrane (p < or = 0.03 for each). In contrast, COPD blood macrophages had no significant differences among donor groups in IL-8, TNF-alpha, or IL-1beta responsiveness to NTHI antigens. Diminished IL-12 responses of COPD blood macrophages to NTHI antigens, compared with nonsmokers, could not be independently dissociated from group differences in age and pack-years. CONCLUSIONS: These findings support a paradigm of defective immune responsiveness of alveolar macrophages, but not blood macrophages, in COPD.

Selective optimization with compensation: a model for elder health programming.

The members of the independent and active baby boom generation entering their retirement years may put clinical nurse specialists (CNS) in greater demand than ever before as educators, consultants, researchers, and case managers. Community-based educational programming to promote health and to monitor and manage chronic health conditions of elders is a recognized method for the CNS to meet these growing demands. The application and utilization of Baltes and Baltes' theoretical model of Selective Optimization With Compensation (SOC) in senior health programming holds promise for CNSs to assume more integral roles in optimizing health promotion for and self-actualization in community-living elders. Senior centers serve older adults who want to stay active, involved with others their age, and current, including learning how to promote their health. The CNS can readily infuse the SOC model into the planning and organizing of health programming for older adults at senior centers, which will in turn aid elders in maintaining independent functioning, autonomy, and quality of life. A detailed template for developing such theory-driven programming with an example program focused on nutrition is provided. Finally, a variety of topics for additional SOC-guided program development are presented.

Impaired phagocytosis of nontypeable Haemophilus influenzae by human alveolar macrophages in chronic obstructive pulmonary disease.

BACKGROUND: Interactions of nontypeable Haemophilus influenzae (NTHI) with human alveolar macrophages are implicated in the persistence of NTHI in chronic obstructive pulmonary disease (COPD). However, the immunologic mechanisms that mediate NTHI-induced macrophage responses are poorly understood. We hypothesized that immunologic responses of alveolar macrophages to NTHI are impaired in COPD. METHODS: Blood and alveolar macrophages--obtained from ex-smokers with COPD (n = 14), ex-smokers without COPD (n = 15), and nonsmokers (n = 9)--were incubated with 3 distinct NTHI strains obtained from patients with COPD. Phagocytosis of 3H-NTHI, expressed as a percentage of the mean total radioactivity, and of intracellular viability, assessed as a percentage of viable cell-associated NTHI, were measured. RESULTS: Alveolar macrophages from donors with COPD, compared with those from donors without COPD, had impaired phagocytosis (median [interquartile range]) for each NTHI strain: 14P13H5, 0.26 (0.08-0.61) versus 1.36 (0.69-1.95); 6P5H1, 0.92 (0.32-1.82) versus 1.90 (1.32-2.68); and 14P14H1, 0.79 (0.23-1.32) versus 2.13 (1.13-2.40) (P < or = .01 for each). However, phagocytosis of all NTHI strains by blood macrophages from donors with COPD was indistinguishable from that of blood macrophages from donors without COPD and from nonsmokers. The intracellular killing of NTHI was not impaired in alveolar macrophages from donors with COPD. CONCLUSIONS: These results support a paradigm of impaired phagocytosis by alveolar macrophages, but not blood macrophages, in COPD and provide an immunologic basis for persistence of NTHI in the airways of adults with COPD.