National Jewish Health

About: National Jewish Health is a healthcare organization based out in Denver, Colorado, United States. It is known for research contribution in the topics: Asthma & T cell. The organization has 883 authors who have published 833 publications receiving 79201 citations. The organization is also known as: National Jewish Medical and Research Center.

Significant variability in response to inhaled corticosteroids for persistent asthma

Abstract: Background: A clinical model is needed to compare inhaled corticosteroids (ICSs) with respect to efficacy. Objective: The purpose of this investigation was to compare the relative beneficial and systemic effects in a dose-response relationship for 2 ICSs. Methods: A 24-week, parallel, open-label, multicenter trial examined the benefit-risk ratio of 2 ICSs in persistent asthma. Benefit was assessed by improvements in FEV 1 and PC 20 ; risk was assessed by overnight plasma cortisol suppression. Thirty subjects were randomized to either beclomethasone dipropionate (BDP) 168, 672, and 1344 μg/day (n = 15) or fluticasone propionate (FP) 88, 352, and 704 μg/day (n = 15), both administered by means of a metered dose inhaler (MDI) with chlorofluorocarbon propellant via a spacer, in 3 consecutive 6-week intervals; this was followed by 3 weeks of FP dry powder inhaler (DPI) 2000 μg/day. Results: Maximum FEV 1 response occurred with the low dose for FP-MDI and the medium dose for BDP-MDI and was not further increased by treatment with FP-DPI. Near-maximum methacholine PC 20 improvement occurred with the low dose for FP-MDI and the medium dose for BDP-MDI. Both BDP-MDI and FP-MDI caused dose-dependent cortisol suppression. Responsiveness to ICS treatment was found to vary markedly among subjects. Good (>15%) FEV 1 response, in contrast to poor ( 1 /forced vital capacity ratio (0.63 vs 0.73) before treatment. Excellent (>3 doubling dilutions) improvement in PC 20 , in contrast to poor ( Conclusions: Near-maximal FEV 1 and PC 20 effects occurred with low-medium dose for both ICSs in the subjects studied. High-dose ICS therapy did not significantly increase the efficacy measures that were evaluated, but it did increase the systemic effect measure, overnight cortisol secretion. Significant intersubject variability in response occurred with both ICSs. It is possible that higher doses of ICSs are necessary to manage more severe patients or to achieve goals of therapy not evaluated in this study, such as prevention of asthma exacerbations. (J Allergy Clin Immunol 2002;109:410-8.)

CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus

Abstract: Angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV, the novel coronavirus that causes severe acute respiratory syndrome [Li, W. Moore, M. J., Vasilieva, N., Sui, J., Wong, S. K., Berne, M. A., Somasundaran, M., Sullivan, J. L., Luzuriaga, K., Greenough, T. C., et al. (2003) Nature 426, 450–454]. We have identified a different human cellular glycoprotein that can serve as an alternative receptor for SARS-CoV. A human lung cDNA library in vesicular stomatitis virus G pseudotyped retrovirus was transduced into Chinese hamster ovary cells, and the cells were sorted for binding of soluble SARS-CoV spike (S) glycoproteins, S590 and S1180. Clones of transduced cells that bound SARS-CoV S glycoprotein were inoculated with SARS-CoV, and increases in subgenomic viral RNA from 1–16 h or more were detected by multiplex RT-PCR in four cloned cell lines. Sequencing of the human lung cDNA inserts showed that each of the cloned cell lines contained cDNA that encoded human CD209L, a C-type lectin (also called L-SIGN). When the cDNA encoding CD209L from clone 2.27 was cloned and transfected into Chinese hamster ovary cells, the cells expressed human CD209L glycoprotein and became susceptible to infection with SARS-CoV. Immunohistochemistry showed that CD209L is expressed in human lung in type II alveolar cells and endothelial cells, both potential targets for SARS-CoV. Several other enveloped viruses including Ebola and Sindbis also use CD209L as a portal of entry, and HIV and hepatitis C virus can bind to CD209L on cell membranes but do not use it to mediate virus entry. Our data suggest that the large S glycoprotein of SARS-CoV may use both ACE2 and CD209L in virus infection and pathogenesis.

Alveolar Tissue Inflammation in Asthma

Abstract: As physiologic and autopsy evidence suggests that peripheral airways and parenchyma are involved in asthma, we hypothesized that significant alveolar tissue inflammation is present in patients with stable, chronic asthma. Eleven patients with nocturnal asthma (NA) and 10 patients with non-nocturnal asthma (NNA) were studied. Each subject underwent two bronchoscopies with proximal airway endobronchial and distal alveolar tissue transbronchial biopsy in a random order at 4:00 P.M. and 4:00 A.M. Morphometric analysis was used to determine the number per volume (Nv) of inflammatory cells. Between-group comparisons showed that the Nv of eosinophils was greater in the NA alveolar tissue 4:00 A.M. compared with the subjects with NNA (40.2 x 10(3) [26.4-57.1 x 10(3), IQ] versus 15.7 x 10(3) [2.1-35.2 x 10(3), IQ], p = 0.05). In regard to the airway biopsies, no difference in the inflammatory and epithelial cells between the two groups was seen at either time. The NA group exhibited greater eosinophils and macrophages in the alveolar tissue at 4:00 A.M. compared with 4:00 P.M. (40.2 x 10(3) [26.4-57.1 x 10(3), IQ] versus 10.3 x 10(3) [2.7-16.8 x 10(3), IQ], p = 0.016 for eosinophils and 215.1 x 10(3) [129.9-356.1 x 10(3), IQ] versus 166.3 x 10(3) [150.7-212.6 x 10(3), IQ], p = 0.031 for macrophages). Only alveolar tissue eosinophils, not proximal airway tissue eosinophils, correlated with the nocturnal decrement in lung function (r = -0.54, p = 0.03). These findings suggest that eosinophils and macrophages accumulate to a greater extent in the alveolar tissue and these changes contribute more to the variation in lung function compared with inflammation in the more proximal tissue.

Practice parameters for the clinical evaluation and treatment of circadian rhythm sleep disorders. An American Academy of Sleep Medicine report.

Abstract: The expanding science of circadian rhythm biology and a growing literature in human clinical research on circadian rhythm sleep disorders (CRSDs) prompted the American Academy of Sleep Medicine (AASM) to convene a task force of experts to write a review of this important topic. Due to the extensive nature of the disorders covered, the review was written in two sections. The first review paper, in addition to providing a general introduction to circadian biology, addresses "exogenous" circadian rhythm sleep disorders, including shift work disorder (SWD) and jet lag disorder (JLD). The second review paper addresses the "endogenous" circadian rhythm sleep disorders, including advanced sleep phase disorder (ASPD), delayed sleep phase disorder (DSPD), irregular sleep-wake rhythm (ISWR), and the non-24-hour sleep-wake syndrome (nonentrained type) or free-running disorder (FRD). These practice parameters were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the AASM to present recommendations for the assessment and treatment of CRSDs based on the two accompanying comprehensive reviews. The main diagnostic tools considered include sleep logs, actigraphy, the Morningness-Eveningness Questionnaire (MEQ), circadian phase markers, and polysomnography. Use of a sleep log or diary is indicated in the assessment of patients with a suspected circadian rhythm sleep disorder (Guideline). Actigraphy is indicated to assist in evaluation of patients suspected of circadian rhythm disorders (strength of recommendation varies from "Option" to "Guideline," depending on the suspected CRSD). Polysomnography is not routinely indicated for the diagnosis of CRSDs, but may be indicated to rule out another primary sleep disorder (Standard). There is insufficient evidence to justify the use of MEQ for the routine clinical evaluation of CRSDs (Option). Circadian phase markers are useful to determine circadian phase and confirm the diagnosis of FRD in sighted and unsighted patients but there is insufficient evidence to recommend their routine use in the diagnosis of SWD, JLD, ASPD, DSPD, or ISWR (Option). Additionally, actigraphy is useful as an outcome measure in evaluating the response to treatment for CRSDs (Guideline). A range of therapeutic interventions were considered including planned sleep schedules, timed light exposure, timed melatonin doses, hypnotics, stimulants, and alerting agents. Planned or prescribed sleep schedules are indicated in SWD (Standard) and in JLD, DSPD, ASPD, ISWR (excluding elderly-demented/nursing home residents), and FRD (Option). Specifically dosed and timed light exposure is indicated for each of the circadian disorders with variable success (Option). Timed melatonin administration is indicated for JLD (Standard); SWD, DSPD, and FRD in unsighted persons (Guideline); and for ASPD, FRD in sighted individuals, and for ISWR in children with moderate to severe psychomotor retardation (Option). Hypnotic medications may be indicated to promote or improve daytime sleep among night shift workers (Guideline) and to treat jet lag-induced insomnia (Option). Stimulants may be indicated to improve alertness in JLD and SWD (Option) but may have risks that must be weighed prior to use. Modafinil may be indicated to improve alertness during the night shift for patients with SWD (Guideline).

Interleukin-5 expression in the lung epithelium of transgenic mice leads to pulmonary changes pathognomonic of asthma.

Abstract: We have generated transgenic mice that constitutively express murine interleukin (IL)-5 in the lung epithelium. Airway expression of this cytokine resulted in a dramatic accumulation of peribronchial eosinophils and striking pathologic changes including the expansion of bronchusassociated lymphoid tissue (BALT), goblet cell hyperplasia, epithelial hypertrophy, and focal collagen deposition. These changes were also accompanied by eosinophil infiltration of the airway lumen. In addition, transgenic animals displayed airway hyperresponsiveness to methacholine in the absence of aerosolized antigen challenge. These findings demonstrate that lung-specific IL-5 expression can induce pathologic changes characteristic of asthma and may provide useful models to evaluate the efficacy of potential respiratory disease therapies or pharmaceuticals.