Increased Stroke Risk Following Herpes Zoster Infection and Protection With Zoster Vaccine.

BACKGROUND: Studies evaluating stroke following varicella zoster virus (VZV) infection are limited, and the utility of zoster vaccination against this phenomenon is unclear. This study aimed to determine the risk of stroke 30 days following zoster infection and to evaluate the impact of zoster vaccinations on the risk of stroke in VZV-infected patients. METHODS: This retrospective case-control study was conducted from January 2010 to January 2020 utilizing nationwide patient data retrieved from the Veterans Affairs' Corporate Data Warehouse. RESULTS: A total of 2 165 505 patients ≥18 years of age who received care at a Veterans Affairs facility were included in the study, of whom 71 911 had a history of zoster infection. Zoster patients were found to have 1.9 times increased likelihood of developing a stroke within 30 days following infection (odds ratio [OR], 1.93 [95% confidence interval {CI}, 1.57-2.4]; P < .0001). A decreased risk of stroke was seen in patients who received the recombinant zoster vaccine (OR, 0.57 [95% CI, .46-.72]; P < .0001) or the live zoster vaccine (OR, 0.77 [95% CI, .65-.91]; P = .002). CONCLUSIONS: Patients had a significantly higher risk of stroke within the first month following recent herpes zoster infection. Receipt of at least 1 zoster vaccination was found to mitigate this increased risk. Vaccination may therefore be viewed as a protective tool against the risk of neurologic postinfection sequelae.

T-regulatory cells and programmed death 1+ T cells contribute to effector T-cell dysfunction in patients with chronic obstructive pulmonary disease.

RATIONALE: Previous studies from our laboratory have shown that peripheral blood mononuclear cells (PBMCs) from patients with chronic obstructive pulmonary disease (COPD) prone to exacerbations with nontypeable Haemophilus influenzae have impaired responses to lipoprotein P6. We hypothesized that an underlying immunosuppressive network could be responsible for the defective antibacterial immunity observed in these patients. We evaluated T regulatory cells (Tregs), myeloid-derived suppressor cells (MDSC), and exhausted T effector cells (programmed death 1 [PD-1](+)) in patients with COPD, because these cells are known to play a pivotal role in suppressing immune responses. OBJECTIVES: We performed an in-depth characterization of Tregs, T effector cells, and MDSC in COPD and correlated their levels and function with disease severity. METHODS: Treg, effector T cell, and MDSC frequency from patients with COPD and healthy subjects' PBMCs were analyzed by flow cytometry. Treg immunosuppressive capacity was measured by in vitro suppression assay. The frequency of interferon-γ producing T cells and T-cell proliferation were measured after blocking CTLA-4 and PD-1. Plasma proinflammatory and immunosuppressive cytokine levels were measured. MEASUREMENTS AND MAIN RESULTS: Significantly increased levels of Tregs, MDSC, and PD-1(+) exhausted effector T cells were present in patients with COPD compared with healthy subjects. Tregs from patients with COPD suppressed P6-specific T-cell proliferation to a greater extent than Tregs from healthy subjects. Plasma levels of Treg-generated cytokines, IL-10, and transforming growth factor-ß were elevated. Blockade of CTLA-4 resulted in significant augmentation of T-cell IFN-γ production in patients with COPD. CONCLUSIONS: Functionally suppressive Tregs, MDSCs, and exhausted PD-1(+) T cells contribute to effector T-cell dysfunction in COPD.

Effects of bacterial infection on airway antimicrobial peptides and proteins in COPD.

BACKGROUND: Pathogenic bacteria colonize the airways of 30% to 40% of patients with COPD and cause approximately 50% of exacerbations. New strains of nontypeable Haemophilus influenzae (NTHI) and Moraxella catarrhalis are associated with exacerbations. Antimicrobial protein/peptides (AMPs) play important roles in innate lung defense against pathogens. To our knowledge, the changes in AMP baseline levels in respiratory secretions during bacterial colonization and exacerbation have not been described. The objective of this study was to elucidate the effects of the acquisition of a new strain of pathogenic bacteria on the airway levels of AMPs in patients with COPD. METHODS: One hundred fifty-three samples from 11 patients were selected from COPD sputum samples collected prospectively over 6 years. Samples were grouped as culture-negative (no pathogenic bacteria), colonization, and exacerbation due to new strains of NTHI and M catarrhalis. Levels of lysozyme, lactoferrin, LL-37, and secretory leukocyte protease inhibitor (SLPI) were measured by enzyme-linked immunosorbent assay and compared among groups by paired analysis. RESULTS: Compared with baseline, sputum lysozyme levels were significantly lower during colonization and exacerbation by NTHI (P = .001 and P = .013, respectively) and M catarrhalis (P = .007 and P = .018, respectively); SLPI levels were lower with exacerbation due to NTHI and M catarrhalis (P = .002 and P = .004, respectively), and during colonization by M catarrhalis (P = 032). Lactoferrin levels did not change significantly; LL-37 levels were higher during exacerbation by NTHI and M catarrhalis (P = .001 and P = .018, respectively). CONCLUSIONS: Acquisition of NTHI and M catarrhalis is associated with significant changes in airway levels of AMPs, with larger changes in exacerbation. Airway AMP levels are likely to be important in pathogen clearance and clinical outcomes of infection in COPD.