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: T cell & Asthma. 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.

Azithromycin or montelukast as inhaled corticosteroid-sparing agents in moderate-to-severe childhood asthma study

Abstract: Background Clinical trials in children with moderate-to-severe persistent asthma are limited. Objective We sought to determine whether azithromycin or montelukast are inhaled corticosteroid sparing. Methods The budesonide dose (with salmeterol [50 μg] twice daily) necessary to achieve control was determined in children 6 to 17 years of age with moderate-to-severe persistent asthma. After a budesonide-stable period of 6 weeks, children were randomized in a double-masked, parallel, multicenter study to receive once-nightly azithromycin, montelukast, or matching placebos plus the established controlling dose of budesonide (minimum, 400 μg twice daily) and salmeterol twice daily. Primary outcome was time from randomization to inadequate asthma control after sequential budesonide dose reduction. Results Of 292 children screened, only 55 were randomized. Inadequate adherence to study medication (n = 80) and improved asthma control under close medical supervision (n = 49) were the major reasons for randomization failure. A futility analysis was requested by the Data Safety Monitoring Board. In data available for analyses, no differences were noted for either treatment compared with placebo in time to inadequate control status (median: azithromycin, 8.4 weeks [95% confidence limit, 4.3-17.3]; montelukast, 13.9 weeks [95% confidence limit, 4.7-20.6]; placebo, 19.1 weeks [95% confidence limit, 11.7-infinity]), with no difference between the groups (log-rank test, P = .49). The futility analysis indicated that even if the planned sample size was reached, the results of this negative study were unlikely to be different, and the trial was prematurely terminated. Conclusion Based on these results, neither azithromycin nor montelukast is likely to be an effective inhaled corticosteroid–sparing alternative in children with moderate-to-severe persistent asthma.

Statins and Pulmonary Fibrosis: The Potential Role of NLRP3 Inflammasome Activation

Abstract: Rationale: The role of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) in the development or progression of interstitial lung disease (ILD) is controversial.Objectives: To evaluate the association between statin use and ILD.Methods: We used regression analyses to evaluate the association between statin use and interstitial lung abnormalities (ILA) in a large cohort of smokers from COPDGene. Next, we evaluated the effect of statin pretreatment on bleomycin-induced fibrosis in mice and explored the mechanism behind these observations in vitro.Measurements and Main Results: In COPDGene, 38% of subjects with ILA were taking statins compared with 27% of subjects without ILA. Statin use was positively associated in ILA (odds ratio, 1.60; 95% confidence interval, 1.03–2.50; P = 0.04) after adjustment for covariates including a history of high cholesterol or coronary artery disease. This association was modified by the hydrophilicity of statin and the age of the subject. Next, we demonstrate ...

Inhibition of phosphodiesterase 4 attenuates airway hyperresponsiveness and airway inflammation in a model of secondary allergen challenge.

Abstract: We compared for the first time the therapeutic potential of a specific phosphodiesterase 4 (PDE4) inhibitor, rolipram, with anti-VLA-4 and anti-IL-5 in a model of secondary allergen exposure of previously sensitized and challenged mice. To address these issues, mice were sensitized and challenged with ovalbumin (OVA) (primary challenge). Six weeks later, sensitized/challenged mice were reexposed to OVA (secondary challenge) and airway response (resistance [RL] and dynamic compliance [Cdyn]) to inhaled methacholine was monitored. After secondary OVA challenge, RL significantly increased as did the number of lung inflammatory cells and IL-4 and IL-5 production in bronchoalveolar lavage fluid (BALF). Administration of rolipram, in a dose-dependent manner, significantly prevented both changes in RL and Cdyn, as well as eosinophil, lymphocyte, and neutrophil accumulation in the BALF; IL-4 and IL-5 levels in BALF were also significantly reduced. In contrast, treatment with anti-VLA-4 and anti-IL-5 only prevented changes in RL and eosinophil numbers and IL-5 production in BALF. Further, goblet cell hyperplasia was suppressed only by treatment with rolipram. None of the treatments affected OVA-specific antibody levels. These studies confirm that IL-5 dependent eosinophilic inflammation plays an essential role in the development of certain aspects of airway function after rechallenge of sensitized mice and that lymphocytes and neutrophils are also important in the development of altered airway function. The use of agents that inhibit PDE4 may have an important role in the treatment of asthma in previously sensitized mice.

First do no harm: Managing antihistamine impairment in patients with allergic rhinitis

Abstract: Antihistamines are effective medications that have been used for decades in the management of allergic rhinitis; however, they may be administered or selected in an inappropriate fashion and may be the source of drug-related morbidity. Our objective is to present relevant background information and an expert consensus statement on the use of antihistamines in treatment of allergic rhinitis. In July 2002, 14 experts in allergy, clinical immunology, pharmacology, and impairment assessment were invited to participate in a roundtable conference to present current concepts and develop a consensus statement on the clinical management of allergic rhinitis with antihistamines. Many of the antihistamines used to treat allergic rhinitis, as well as the disease itself, may produce sedation, impairment, and reduced quality of life. Allergic rhinitis is more appropriately managed with the relatively nonimpairing second-generation antihistamines (eg, loratadine, desloratadine, cetirizine, and fexofenadine), because older agents (eg, diphenhydramine, chlorpheniramine, and brompheniramine) produce sedation and impairment and worsen sleep architecture. Although there is some debate surrounding the varying degrees of efficacy of second-generation antihistamines, it is known that some agents may produce varying levels of drowsiness or impairment, especially at higher than recommended doses. The differences with regard to safety among the second-generation antihistamines are smaller than are the differences between the first and second generations. A nonsedating, nonimpairing (even at higher than recommended doses), second-generation antihistamine is preferred for all patients, particularly those with a higher risk for the development of adverse effects. We recommend that primary care and specialist physicians, nurse practitioners, physician assistants, pharmacists, and all other health professionals involved in the diagnosis and treatment of allergic rhinitis follow this consensus document and share this information with patients for whom antihistamine therapy is recommended. In addition, further epidemiologic studies on the effects of antihistamines should be performed.

The Failure of STAT6-deficient Mice to Develop Airway Eosinophilia and Airway Hyperresponsiveness Is Overcome by Interleukin-5

Abstract: While signal transducer and activator of transcription protein 6 (STAT6) is important in interleukin-4 (IL-4)-induced commitment of CD4(+) T cells to the T helper cell, type 2 (Th2) phenotype and IgE isotype switching in B cells, its role in other IL-4-mediated events and their impact upon the allergic response is less evident. In the present study we demonstrate the critical role of STAT6 in the development of allergic airway eosinophilia and airway hyperresponsiveness (AHR) after allergen sensitization and challenge. STAT6-deficient (STAT6-/-) mice did not develop a Th2 cytokine response or an allergen-specific IgE response. Further, STAT6-/- mice had a reduced constitutive and allergen-induced expression of CD23 as well as lower mucus production in the airway epithelium. Critically, we show that IL-5 alone can reconstitute airway eosinophilia and AHR in sensitized and challenged STAT6-/- mice. This emphasizes the essential nature of the IL-4-dependent signaling of T cells to the Th2 phenotype and secretion of IL-5, resulting in the airway eosinophilia and AHR. These observations underscore the importance of targeting this pathway in new antiallergic asthma drug development.