The influence of individual characteristics and non‐respiratory diseases on blood eosinophil count

BackgroundBlood eosinophil (B‐Eos) count is an emerging biomarker in the management of respiratory disease but determinants of B‐Eos count besides respiratory disease are poorly described. Therefore, we aimed to evaluate the influence of non‐respiratory diseases on B‐Eos count, in comparison to the effect on two other biomarkers: fraction of exhaled nitric oxide (FeNO) and C‐reactive protein (CRP), and to identify individual characteristics associated with B‐Eos count in healthy controls.MethodsChildren/adolescents (<18 years) and adults with complete B‐Eos data from the US National Health and Nutritional Examination Surveys 2005–2016 were included, and they were divided into having respiratory diseases (n = 3333 and n = 7,894, respectively) or not having respiratory disease (n = 8944 and n = 15,010, respectively). After excluding any respiratory disease, the association between B‐Eos count, FeNO or CRP, and non‐respiratory diseases was analyzed in multivariate models and multicollinearity was tested. After excluding also non‐respiratory diseases independently associated with B‐Eos count (giving healthy controls; 8944 children/adolescents and 5667 adults), the independent association between individual characteristics and B‐Eos count was analyzed.ResultsIn adults, metabolic syndrome, heart disease or stroke was independently associated with higher B‐Eos count (12%, 13%, and 15%, respectively), whereas no associations were found with FeNO or CRP. In healthy controls, male sex or being obese was associated with higher B‐Eos counts, both in children/adolescents (15% and 3% higher, respectively) and adults (14% and 19% higher, respectively) (p < 0.01 all). A significant influence of race/ethnicity was also noted, and current smokers had 17% higher B‐Eos count than never smokers (p < 0.001).ConclusionsNon‐respiratory diseases influence B‐Eos count but not FeNO or CRP. Male sex, obesity, certain races/ethnicities, and current smoking are individual characteristics or exposures that are associated with higher B‐Eos counts. All these factors should be considered when using B‐Eos count in the management of respiratory disease.     

Source analysis of epileptic discharges using multiple signal classification analysis

Multiple signal classification is an alternative to the traditional dipole fitting source analysis methods. Our aim was to assess the clinical usefulness of this algorithm and to compare the localization of the epileptiform electroencephalography discharges with the regions of altered cerebral blood flow in 10 patients with complex partial seizures undergoing preoperative investigation. We performed multiple signal classification analysis of ictal and interictal discharges, and registered single-photon emission computed tomography. Localization of the ictal, but not the interictal discharges, as determined by multiple signal classification analysis was consistent with the regions showing perfusion changes on the single-photon emission computed tomography. Multiple signal classification analysis is a promising tool in localizing foci in patients with complex partial seizures and may contribute to the preoperative evaluation.     

Differential bronchial and pulmonary vascular responses to vagal stimulation in the pig.

The pulmonary and bronchial vascular responses and changes in bronchial tone upon vagal stimulation (240 impulses at 2 Hz or 10 Hz) were studied in anaesthetized pigs paralyzed with pancuronium. The acetylcholine-evoked vasodilatation in the tracheobronchial circulation had the same magnitude when using pancuronium or succinylcholine as skeletal muscle relaxants. Atropine-sensitive bradycardia, hypotension and bronchoconstriction were observed upon vagal stimulation. A vasoconstrictor response in the pulmonary vascular bed and clear-cut vasodilatation in the bronchial circulation supplied by the bronchial artery also occurred upon vagal stimulation. The vagally-evoked increase in pulmonary vascular resistance was markedly reduced after atropine while the bronchial vasodilatation was unchanged. This suggests that the vagally-induced increase in bronchial blood flow was not secondary to changes in the pulmonary circulation. Furthermore, the pulmonary vasoconstrictor response caused by vagal stimulation under control conditions is probably explained by reflex sympathetic activation due to the fall in systemic blood pressure. These data indicate selective vagal non-cholinergic influence of blood flow in the bronchial vascular bed compared to the pulmonary circulation.     

Resistance to activated protein C: A common inherited cause of venous thrombosis

Resistance to activated protein C (RAPC) is a newly recognized hypercoagulable state that was first described in 1993. It has become apparent that RAPC is even more common than deficiencies in protein C, protein S, or antithrombin III (AT-III) and affects an estimated 5% of the general population. The majority of patients with RAPC have an abnormality in factor V (Arg506Gln), which renders factor Va resistant to degradation by activated protein C. Studies in 75 patients referred to the Hematology Laboratory at Walter Reed Army Institute of Research (WRAIR) over a 14-month period for evaluation of venous thromboembolism were reviewed to determine the percentage of those with RAPC. Of the 75 patients in the study, one was deficient in protein S, one was deficient in protein C, and none was deficient in AT-III. In contrast, 27 (36%) patients tested positive for RAPC. Blood was available for DNA analysis in 15 patients with RAPC. Of these 15 patients, nine (60%) tested positive for the Arg506Gln mutation in factor V. Six other patients with RAPC did not have the factor V mutation. Additional risk factors for thrombosis were immobility, obesity, use of oral contraceptives, and pregnancy. The majority of patients had deep venous thrombosis of the lower extremities; 71% had a recurrence if not placed on chronic anticoagulation therapy. Thus RAPC is a significant risk factor for venous thrombosis. Evaluation for inherited hypercoagulable states should include testing for this newly described condition.Supported in part by NIH grant R37-HL52246.Presented at the Twentieth Annual Meeting of the Peripheral Vascular Surgery Society, New Orleans, La., June 10, 1995.The opinions contained herein do not necessarily reflect the opinions of the U.S. Department of the Army or Department of Defense.     

Transcutaneous immunization with bacterial ADP-ribosylating exotoxins, subunits, and unrelated adjuvants

We have recently described a needle-free method of vaccination, transcutaneous immunization, consisting of the topical application of vaccine antigens to intact skin. While most proteins themselves are poor immunogens on the skin, we have shown that the addition of cholera toxin (CT), a mucosal adjuvant, results in cellular and humoral immune responses to the adjuvant and coadministered antigens. The present study explores the breadth of adjuvants that have activity on the skin, using diphtheria toxoid (DTx) and tetanus toxoid as model antigens. Heat-labile enterotoxin (LT) displayed adjuvant properties similar to those of CT when used on the skin and induced protective immune responses against tetanus toxin challenge when applied topically at doses as low as 1 microg. Interestingly, enterotoxin derivatives LTR192G, LTK63, and LTR72 and the recombinant CT B subunit also exhibited adjuvant properties on the skin. Consistent with the latter finding, non-ADP-ribosylating exotoxins, including an oligonucleotide DNA sequence, as well as several cytokines (interleukin-1beta [IL-1beta] fragment, IL-2, IL-12, and tumor necrosis factor alpha) and lipopolysaccharide also elicited detectable anti-DTx immunoglobulin G titers in the immunized mice. These results indicate that enhancement of the immune response to topical immunization is not restricted to CT or the ADP-ribosylating exotoxins as adjuvants. This study also reinforces earlier findings that addition of an adjuvant is important for the induction of robust immune responses to vaccine antigens delivered by topical application.