Chronic hypersensitivity pneumonitis: high resolution computed tomography patterns and pulmonary function indices as prognostic determinants

Objectives

To investigate high resolution computed tomography (HRCT) and pulmonary function indices (PFTs) for determining prognosis in patients with chronic fibrotic hypersensitivity pneumonitis (CHP).

Methods

Case records, PFTs (FEV₁, FVC and DLco) and HRCTs of ninety-two patients with chronic hypersensitivity pneumonitis were evaluated. HRCT studies were scored by two observers for total disease extent, ground-glass opacification, fine and coarse reticulation, microcystic and macrocystic honeycombing, centrilobular emphysema and consolidation. Traction bronchiectasis within each pattern was graded. Using Cox proportional hazards regression models the prognostic strength of individual HRCT patterns and pulmonary function test variables were determined.

Results

There were forty two deaths during the study period. Increasing severity of traction bronchiectasis was the strongest predictor of mortality (HR 1.10, P?P?=?0.02, 95%CI 1.00-1.03), microcystic honeycombing (HR 1.09, P?=?0.019, 95%CI 1.01-1.17) and macrocystic honeycombing (HR 1.06, P?<?0.01, 95%CI 1.01-1.10) were also independent predictors of mortality. In contrast, no individual PFT variable was predictive of mortality once HRCT patterns were accounted for.

Conclusion

HRCT patterns, in particular, severity of traction bronchiectasis and extent of honeycombing are superior to pulmonary function tests for predicting mortality in patients with CHP.

Key Points

? HRCT is increasingly used to assess chronic fibrotic hypersensitivity pneumonitis. ? HRCT patterns are superior to pulmonary function tests for predicting mortality. ? Extensive traction bronchiectasis strongly predicts poor survival in chronic hypersensitivity pneumonitis.     

Increased toll-like receptor (TLR) 2 and TLR4 expression in monocytes from patients with type 1 diabetes: further evidence of a proinflammatory state

CONTEXT: Type 1 diabetes (T1DM) is associated with increased cardiovascular mortality. It is a pro-inflammatory state as evidenced by increased circulating biomarkers and monocyte activity. The toll-like receptors (TLRs) are pattern recognition receptors, expressed abundantly on monocytes. TLR2 and TLR4 are important in atherosclerosis. However, there is a paucity of data examining TLR2 and TLR4 expression in T1DM and examining its contribution to the proinflammatory state. OBJECTIVE: Thus, we examined TLR2 and TLR4 expression in monocytes from T1DM patients compared with controls (n = 31 per group). SETTING: The study was performed at the University of California Davis Medical Center. PATIENTS: Healthy controls (n = 31) and T1DM patients (n = 31) were included in the study. RESULTS: TLR2 and TLR4 surface expression and mRNA were significantly increased in T1DM monocytes compared with controls. Downstream targets of TLR, nuclear factor kappaB, myeloid differentiation factor 88, Trif, and phosphorylated IL-1 receptor-associated kinase were significantly up-regulated in T1DM. Finally, the release of IL-1beta and TNF-alpha was significantly increased in monocytes from T1DM compared with controls and correlated with TLR2 and TLR4 expression (P < 0.005). In addition, TLR2 and TLR4 expression was significantly correlated to glycosylated hemoglobin, carboxymethyllysine, and nuclear factor kappaB (P < 0.02). CONCLUSION: Thus, we make the novel observation that TLR2 and TLR4 expression and signaling are increased in T1DM and contribute to the proinflammatory state.     

Validation of the human activity profile in stroke: A comparison of observed,proxy and self-reported scores

Purpose. To assess the concurrent validity of the Human Activity Profile (HAP) with stroke and healthy control individuals, when reported by the subject or a proxy and compared to observed performance, used as gold standard; factors related to discrepancies; as well as to determine variables that could best predict physical activity levels.

Methods. A total of 24 stroke and 23 healthy control subjects took part in the study. Functional outcome measures included personal/demographic factors, HAP, the 10-meter walk, and cognition.

Results. Strong relationships were found between self-reported and observed scores for both groups (r = 0.89 – 0.99). The relationships between proxy and observed scores were acceptable for stroke (r = 0.80 – 0.87) but lower for control subjects (r = 0.65 – 0.75), with intraclass correlation coefficients (ICCs) ranging from 0.69 – 0.89. Significant differences were found between proxy and observed scores for stroke, but not for control subjects. Discrepancies between scores showed little predictability from selected variables. For stroke subjects, the strongest variable explaining physical activity levels was walking speed (r² = 43%) and the best combination of variables was walking speed plus cognition (r² = 55%).

Conclusions. Self-reported HAP was an excellent measure both for stroke and control subjects and related well to observed performance. Proxy reports appear to be valid for stroke subjects. HAP was significantly related to measures of walking speed.     

Induction and expression of GST-Pi foci in the liver of Cyclophosphamide-administered rats

Anticancer drug Cyclophosphamide (CY) is metabolized to phosphoramide mustard and acrolein by the hepatic P450 enzymes. GST-Pi is a biochemical feature which occurs in carcinogen induced preneoplastic foci and it plays an important role in the detoxification pathway of acrolein metabolism. Administration of CY induces GST-Pi positive single cells and foci expression in rat liver and these can be considered as precursors of preneoplastic foci leading to hepatocarcinogenesis. The expression of GST-Pi in CY-treated rats on different days of treatment was confirmed by immunohistochemistry, immunoblot, RT-PCR and by ELISA. We also advocate that epigenetic mechanism could be accounted for the GST-Pi induction in the hepatocytes of CY-treated rats.     

Effect of the food flavour cinnamaldehyde on the antioxidant status of rat kidney

Cinnamaldehyde, a food flavour, has a high potential for human consumption in India. In this study, we evaluated the effect of cinnamaldehyde on the antioxidant status of the rat kidney. Rats were given cinnamaldehyde orally by gavage at dose levels of 2.14, 6.96, 22.62 and 73.5 mg/kg body weight/day for the period of 10, 30 and 90 days. The non-enzymatic antioxidants ascorbic acid, alpha-tocopherol and reduced glutathione were decreased while the antioxidant enzymes, superoxide dismutase, glutathione peroxidase and glutathione-s-transferase were increased. Catalase was decreased and thiobarbituric acid-reactive substances were increased only in the kidney of rats treated with cinnamaldehyde at the dose level of 73.5 mg/kg body weight/day during an exposure period of 90 days and not in the kidney of other cinnamaldehyde-treated rat groups. Thus, cinnamaldehyde has an effect on the antioxidant status of rat kidney and its effect is time- and dose-dependent.     

Reduced-calorie orange juice beverage with plant sterols lowers C-reactive protein concentrations and improves the lipid profile in human volunteers

BACKGROUND: Dietary plant sterols effectively reduce LDL cholesterol when incorporated into fat matrices. We showed previously that supplementation with orange juice containing plant sterols (2 g/d) significantly reduced LDL cholesterol. Inflammation is pivotal in atherosclerosis. High-sensitivity C-reactive protein (hs-CRP), the prototypic marker of inflammation, is a cardiovascular disease risk marker; however, there is a paucity of data on the effect of plant sterols on CRP concentrations. OBJECTIVE: The aim of this study was to examine whether plant sterols affect CRP concentrations and the lipoprotein profile when incorporated into a reduced-calorie (50 calories/240 mL) orange juice beverage. DESIGN: Seventy-two healthy subjects were randomly assigned to receive a reduced-calorie orange juice beverage either without (Placebo Bev) or with (1 g/240 mL; Sterol Bev) plant sterols twice a day with meals for 8 wk. Fasting blood was obtained at baseline and after 8 wk of Placebo Bev or Sterol Bev supplementation. RESULTS: Sterol Bev supplementation significantly reduced total cholesterol (5%; P < 0.01) and LDL cholesterol (9.4%; P < 0.001) compared with both baseline and Placebo Bev (P < 0.05). HDL cholesterol increased significantly with Sterol Bev (P < 0.02). No significant changes in triacylglycerol, glucose, or liver function tests were observed with Sterol Bev. Sterol Bev supplementation resulted in no significant change in vitamin E and carotenoid concentrations. Sterol Bev supplementation resulted in a significant reduction of CRP concentrations compared with baseline and Placebo Bev (median reduction: 12%; P < 0.005). CONCLUSION: Supplementation with a reduced-calorie orange juice beverage containing plant sterols is effective in reducing CRP and LDL cholesterol and could be incorporated into the dietary portion of therapeutic lifestyle changes.