We investigated the impact of cigarette smoke exposure on respiratory immune defense mechanisms. Mice were exposed to two cigarettes daily, 5 d/wk, for 2–4 mo. Tobacco smoke decreased the number of dendritic cells (DCs) in the lung tissue. Furthermore, smoke exposure dramatically reduced the percentage of B7.1-expressing DCs. Because DCs are believed to be indispensable to the initiation of adaptive immune responses, we investigated the impact of cigarette smoke on immune responsiveness toward adenovirus. Mice were exposed to two cigarettes for 2–4 mo and inoculated with 2 × 108 pfu of a replication-deficient adenovirus on three occasions, 2 wk apart, during the last month of tobacco smoke exposure. Smoke exposure specifically prevented the expansion and maximal activation of CD4 T cells and reduced the number of both activated CD4 and CD8 T cells. Consequently, smoke exposure shifted the activated CD4:CD8 T cell ratio from 3 to 1.5 when compared with sham exposure. Significant decreases were also observed in serum adenovirus-specific pan IgG, IgG1, and IgG2a immunoglobulin levels, which was associated with diminished viral neutralization capacity. We demonstrate that chronic tobacco smoke exposure impairs the immune response against adenovirus. This may, in part, explain the increased prevalence of viral infections in chronic obstructive pulmonary disease.

Although Weber type B ankle fractures are often considered benign with a good prognosis, evidence from observational studies suggests that 17% to 24% of such patients may have less satisfactory outcomes. Although the explanation for variability in outcomes remains unclear, previous studies of other surgical procedures have suggested nonsurgery-related causes account for much of the variability in outcomes. We conducted a prospective observational cohort study to evaluate health-related quality of life in 30 patients with unstable ankle fractures who were otherwise healthy. Only patients from 2 university-affiliated hospitals sustaining unstable type B Weber injury patterns requiring surgery were eligible. Patients provided detailed baseline information regarding alcohol consumption, smoking habits, and educational level. Patients completed the short form 36 questionnaire and a visual analogue pain scale at regular follow-up intervals. The average patient age was 51.6 years (SD 15.2 years), and 57% (17 out of 30) were male. The majority of fractures were the result of a fall (67%, 20 out of 30), and all were closed injuries. Almost half of all patients were smokers (47%, 14 out of 30), whereas 43% consumed alcohol on a weekly basis (13 out of 30). Forty-three percent of patients (13 out of 30) had obtained an elementary or high school level of education. Patients experienced significant improvements in all domains of the SF-36 questionnaire (P < 0.001), except general health, which remained essentially normal over the 24-month period. Study patients achieved scores similar to age-matched U.S. normative data across 6 of the 8 domains (Role Emotional, Social Function, Mental Health, Bodily Pain, Vitality, and General Health). However, patients' physical function and role physical scores remained significantly lower than US norms at 24 months (21.8 and 20.7 points lower on a 100-point scale, respectively; P < 0.001). Smoking history (P = 0.02), presence of a medial malleolar fracture (P = 0.02), and lower levels of education (P = 0.01) were significant independent predictors of lower physical function up to 3 months postoperation. Lower mental health domain scores were significantly associated with alcohol use (P = 0.02) and increasing age (P = 0.04). As is the case in many other areas, social factors may be important determinants of outcome in patients with traumatic fractures. Optimal orthopedic care may involve attention to modifiable risk factors, including smoking and alcohol consumption.

The purpose of this study was to investigate the impact of mainstream cigarette smoke exposure (MTS) on allergic sensitization and the development of allergic inflammatory processes. Using two different experimental murine models of allergic airways inflammation, we present evidence that MTS increased cytokine production by splenocytes in response to OVA and ragweed challenge. Paradoxically, MTS exposure resulted in an overall attenuation of the immune inflammatory response, including a dramatic reduction in the number of eosinophils and activated (CD69⁺) and Th2-associated (T1ST2⁺) CD4 T lymphocytes in the lung. Although MTS did not impact circulating levels of OVA-specific IgE and IgG1, we observed a striking reduction in OVA-specific IgG2a production and significantly diminished airway hyperresponsiveness. MTS, therefore, plays a disparate role in the development of allergic responses, inducing a heightened state of allergen-specific sensitization, but dampening local immune inflammatory processes in the lung.

In population studies, the relative survival in chronic lymphocytic leukemia (CLL) decreases with age. In this study, we demonstrated in a cohort of 189 patients from a CLL clinic that overall survival was lower in the sub-cohort of patients aged ≥ 70 years, but causes of death were similar for all age groups, being progressive CLL, secondary malignancies and infections. As normal individuals age, the plasma levels of inflammatory cytokines, such as interleukin-6 (IL-6) and IL-8, can increase. In our patients with CLL, IL-6, IL-8 and tumor necrosis factor-α (TNF-α) levels increased with age to a greater degree than in normal individuals, and the levels correlated closely with plasma β₂-microglobulin and with one another. In addition, in patients ≥ 70 years, IL-6 was found to be a better prognostic marker than immunoglobulin variable heavy chain gene (IgV_H) status. In vitro studies demonstrated that IL-6 and IL-8 could enhance the binding of CLL cells to stromal cells, suggesting that their clinical activity may be mediated through their effects on the microenvironment. Thus, plasma IL-6 is an important prognostic marker for the elderly with CLL, and this study highlights that the utility of prognostic markers may depend on patient age.