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Abstract Background In cystic fibrosis (CF) patients, it has been suggested that systemic inflammation may be an important risk factor for poor health outcomes. The relationship of plasma inflammatory biomarkers to lung function and hospitalization history remains largely unexplored. Methods This cross-sectional study included 58 consecutive, clinically stable adults from the CF Clinic at St. Paul's Hospital (Vancouver, Canada). Blood levels of interleukin (IL)-6, IL-1β, C-reactive protein (CRP), interleukin (IL)-6, IL-1β, granzyme B (GzmB), chemokine C-C motif ligand 18 (CCL18/PARC), surfactant protein D (SP-D), lipopolysaccharide (LPS)-binding protein, and soluble cluster of differentiation 14 (sCD14) were measured using enzyme-linked immunosorbent assays, and LPS levels were measured using a Limulus amebocyte lysate assay. Spirometry was also performed. Multivariable linear regression analysis was used to assess relationships of the blood biomarkers to lung function. Results Lung function impairment was independently associated with elevated plasma levels of CRP (P < 0.01), IL-6 (P = 0.04), IL-1β (P < 0.01), and LBP (P < 0.01). Increasing age (P < 0.01), reduced body mass index (P = 0.02), prior hospitalizations (P = 0.03), and presence of Pseudomonas aeruginosa in sputum cultures (P < 0.01) were also associated with reduced lung function. Elevated concentrations of LPS in plasma were associated with a previous history of hospitalization (P < 0.05). There was a trend towards an increase in plasma IL-6 (P = 0.07) and IL-1β (P = 0.06) levels in patients who were previously hospitalized. Conclusions IL-6 and IL-1β are promising systemic biomarkers for lung function impairment and history of hospitalization in adult patients with CF.

Purpose: Mitomycin C (MMC) plus standard 5‐fluorouracil (FU) infusion in weeks 1 and 5 often contributes to radiotherapy interruptions and possibly less‐than‐ideal outcomes in anal cancer. This study was to evaluate alternative strategies for chemotherapy delivery that might be less toxic or more efficacious, and outcomes of patient‐initiated treatment interruption for severe acute toxicity. Materials and methods: This was a prospective, nonrandomized study for patients with T1‐4N0‐3M0 anal squamous carcinoma. Radiotherapy of 54 Gy in 30 fractions over 6 weeks was given with infusion FU 300 mg/m2/day for 96 hours/week for 6 weeks plus bolus MMC at 10 mg/m2 on D1. Results: Fifty patients were recruited (72% female). Median age was 60.5 years (35–84). Forty‐seven patients (94%) received 54 Gy. Median duration of chemoradiation was 39 days (37–105). Grade 3 and 4 acute toxicity were observed in 66%. Thirty‐one percent with severe acute toxicity developed severe late toxicity. Of those who experienced severe late skin toxicity, 29% did not have severe acute toxicity. Disease‐free survival at 5 years was 74% (95% confidence interval [CI], 60–84), and at 9 years 61% (95% CI, 46–74). Overall survival at 5 years was 84% (95% CI, 71–92), and at 9 years 67% (95% CI, 50–81). Colostomy‐free survival at 5 years was 70% (95% CI, 56–81), and at 9 years 57% (95% CI, 40–72). Conclusion: It is feasible to deliver chemoradiation with bolus MMC and protracted infusion FU for anal cancer. Efficacy and toxicity of this regimen seem similar to conventional chemoradiation with FU/MMC. Acute skin toxicity is not a reliable predictor of severe late skin toxicity. [ABSTRACT FROM AUTHOR]

Aims Although surfactant protein-D (SP-D) is a pneumoprotein that is predominantly synthesized by type II epithelial cells in the lung, individuals with increased circulating levels of SP-D are at an elevated risk of mortality from ischemic heart disease. Whether SP-D contributes directly to atherosclerosis is unknown. We determined the effects of SP-D gene deletion in a mouse model of atherosclerosis. Methods and results SP-D knockout (KO) mice were crossed with hyperlipidemic and atherosclerosis-prone apolipoprotein E (ApoE) KO mice to generate SP-D/ApoE double knockout (DKO) mice. Mice were placed on a high-fat diet for 12 weeks beginning at 8 weeks of age. Compared with ApoE KO mice, SP-D/ApoE DKO mice had significantly less atherosclerosis with reduced macrophage accumulation, decreased local macrophage proliferation, and increased smooth muscle cell coverage in plaques. Interestingly, SP-D deficiency worsened hypercholesterolemia and induced obesity and insulin resistance but suppressed plasma interleukin-6 (IL-6) levels. SP-D deficiency also reduced blood monocytes and neutrophils counts in ApoE KO mice. Conclusion SP-D deficiency reduces atherosclerosis in part by decreasing the accumulation and proliferation of macrophages and by reducing IL-6 levels systemically. SP-D is a promising therapeutic target for cachectic COPD patients with elevated circulating SP-D levels who are at increased risk of cardiovascular morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background and objective CD8+ cell infiltration and apoptosis of airway epithelial cells are increased in chronic obstructive pulmonary disease ( COPD). CD8+ T cells induce apoptosis by releasing granzymes, which can also cause extracellular matrix degradation and remodelling. Granzyme B levels and T cells expressing granzyme B are increased in bronchoalveolar lavage fluid of COPD patients, which suggests that granzyme B may contribute to the pathogenesis of COPD. This study provides quantitation of granzyme B-positive cells in relation to CD8+ cells in the small airway walls of emphysema. Methods Antibodies against CD8 and granzyme B were used to identify CD8+ and granzyme B+ cells. Volume fraction ( Vv) of CD8+ and granzyme B+ cells were quantitated by the point counting method in the small airways of 13 non-smoker control subjects and 46 emphysema patients (14 panlobular emphysema ( PLE) and 32 centrilobular emphysema ( CLE) lungs). Immunohistochemical detection of macrophage scavenger receptor was also performed in randomly selected cases. Results The Vv of CD8+ and granzyme B+ cells in CLE was greater than those in control and PLE (both P < 0.001) subjects. The Vv of granzyme B+ cells was greater than that of CD8+ cells ( P = 0.006), and not all CD8+ cells were positive for granzyme B in CLE subjects. Monocytes expressing both granzyme B and macrophage scavenger receptor and granulocytes expressing granzyme B were identified. Conclusions Upregulation of granzyme B in CD8+ and non- CD8+ cells is an early phenomenon of small airway wall remodelling in centrilobular emphysema and suggests its possible role in the pathogenesis of COPD. [ABSTRACT FROM AUTHOR]