Serum amyloid a is a biomarker of acute exacerbations of chronic obstructive pulmonary disease.

RATIONALE: Much of the total disease burden and cost of chronic obstructive pulmonary disease (COPD) is associated with acute exacerbations of COPD (AECOPD). Serum amyloid A (SAA) is a novel candidate exacerbation biomarker identified by proteomic screening. OBJECTIVES: To assess SAA as a biomarker of AECOPD. METHODS: Biomarkers were assessed (1) cross-sectionally (stable vs. AECOPD; 62 individuals) and (2) longitudinally with repeated measures (baseline vs. AECOPD vs. convalescence; 78 episodes in 37 individuals). Event severity was graded (I, ambulatory; II, hospitalized; III, respiratory failure) based on consensus guidelines. MEASUREMENTS AND MAIN RESULTS: Presumptively newly acquired pathogens were associated with onset of symptomatic AECOPD. In the cross-sectional study, both SAA and C-reactive protein (CRP) were elevated at AECOPD onset compared with stable disease (SAA median, 7.7 vs. 57.6 mg/L; P < 0.01; CRP median, 4.6 vs. 12.5 mg/L; P < 0.01). Receiver operator characteristics analysis was used to generate area-under-curve values for event severity. SAA discriminated level II/III events (SAA, 0.88; 95% confidence interval, 0.80-0.94 vs. CRP, 0.80; 95% confidence interval, 0.70-0.87; P = 0.05). Combining SAA or CRP with major symptoms (Anthonisen criteria, dyspnea) did not further improve the prediction model for severe episodes. IL-6 and procalcitonin were not informative. CONCLUSIONS: SAA is a novel blood biomarker of AECOPD that is more sensitive than CRP alone or in combination with dyspnea. SAA may offer new insights into the pathogenesis of AECOPD.

Phenotyping of cytochrome P450 2E1 in vitro and in vivo.

The aim of the present study was to develop and improve methods for phenotyping of CYP2E1, an important enzyme in the biotransformation of many industrial chemicals, therapeutic drugs and endogenous substances. The possibility to measure CYP2E1 activity in lymphocytes by using p-nitrophenol as a substrate and CYP2E1 protein levels by flow cytometry were studied in vitro. Further, the conventional chlorzoxazone method for in vivo phenotyping was studied by adjusting the dose to body weight in 10 healthy volunteers. Finally, the possibility to obtain the chlorzoxazone metabolic ratio in saliva samples was investigated. No CYP2E1 protein in lymphocytes was detected by using flow cytometry. Some enzyme activity was found in the experiments with p-nitrophenol, however, it could not be verified that it was catalyzed by CYP2E1. Chlorzoxazone and 6-hydroxychlorzoxazone were not detectable in saliva samples. The present in vivo experiments, combined with our previous data (in total 356 experiments in 50 subjects) show that the metabolic ratio increases with decreasing absorbed dose, expressed as the sum of chlorzoxazone and 6-hydroxychlorzoxazone in plasma at 2 h. The increase becomes pronounced at sum concentrations below 100 microM. In conclusion, chlorzoxazone metabolism in vivo remains the only available method for CYP2E1 phenotyping. The administered dose as well as the absorption of the probe influences the chlorzoxazone ratio. We suggest that a dose of 10 mg chlorzoxazone per kg body weight is used to estimate the CYP2E1 phenotype. Further, metabolic ratios should be disregarded if the sum of plasma chlorzoxazone and 6-hydroxychlorzoxazone is below 100 microM (blood sampled after 2 h).

Airborne cat allergen reduction in classrooms that use special school clothing or ban pet ownership.

BACKGROUND: Allergens from furred animals are brought to school mainly via clothing of pet owners. Asthmatic children allergic to cat have more symptoms when attending a class with many cat owners, and some schools allocate specific resources to allergen avoidance measures. OBJECTIVE: The aim of the current study was to evaluate the effect of school clothing or pet owner-free classes compared with control classes on airborne cat allergen levels and to investigate attitudes and allergic symptoms among the children. METHODS: Allergen measurements were performed prospectively in 2 classes with school clothing, 1 class of children who were not pet owners, and 3 control classes during a 6-week period in 2 consecutive years. Portable pumps and petri dishes were used for collection of airborne cat allergen, and a roller was used for sampling on children's clothes. Cat allergen (Fel d 1) was analyzed with enzyme-linked immunoassay and immunostaining. Both years, questionnaires were administered to the children. RESULTS: We found 4-fold to 6-fold lower airborne cat allergen levels in intervention classes compared with control classes. Levels of cat allergen were 3-fold higher on clothing of cat owners than of children without cats in control classes. Pet ownership ban seemed less accepted than school clothing as an intervention measure. CONCLUSION: For the first time, it has been shown that levels of airborne cat allergen can be reduced by allergen avoidance measures at school by using school clothing or pet ownership ban, and that both measures are equally efficient. The clinical effect of these interventions remains to be evaluated.

Reduction of exposure to laboratory animal allergens in a research laboratory.

OBJECTIVES: The purpose of this study was to determine exposure levels in the laboratory during different tasks and evaluate the effectiveness of safety equipment used to reduce personal exposure. METHODS: Personal and stationary air samples were collected during different tasks in a laboratory animal facility in which several allergen reduction strategies had been implemented. Mouse urinary allergen concentrations were measured using a polyclonal sandwich enzyme-linked immunosorbent assay. Sera from the personnel (n = 29) were analysed every 6 months for the presence of specific antibodies against mouse and rat urinary allergens, and the staff answered questionnaires on work-related symptoms, exposure and use of respiratory protection. RESULTS: The highest airborne mouse allergen levels were measured during manual emptying of cages, during changing of cages on an unventilated table and during handling of male animals on an unventilated table. Automatic emptying and cleaning of cages resulted in low airborne allergen levels in the working room. Using a ventilated cage-changing wagon reduced the allergen exposure level from 77 to 17 ng/m3. The housing of animals in ventilated cabinets, with air exhausted through the cabinet, effectively prevented the release of allergens into the ambient air. The handling of animals on ventilated benches and the use of a centralized vacuum cleaner resulted in a low exposure level. Only two subjects developed specific immunoglobulin E of > 0.35 kU/l, of whom one was reduced to negative after increased use of respiratory protection. CONCLUSIONS: Effective reduction of exposure to allergens can be achieved by several strategies, which together appear to minimize sensitization to rodents.