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Sputum induction with nebulized hypertonic saline is increasingly being used to evaluate airway inflammation. We investigated the procedure-associated risk in 16 asthmatics that were still symptomatic despite on high doses of regular corticosteroid (CS) therapy (7 on daily inhaled CS > or = 800 microg budesonide or equivalent; 9 on additional daily oral CS)(More)
BACKGROUND Interleukin-5 (IL-5) is essential for the formation of eosinophils, which are thought to have a major role in the pathogenesis of asthma and other allergic diseases. We aimed to assess the effects of monoclonal antibody to IL-5 on blood and sputum eosinophils, airway hyper-responsiveness, and the late asthmatic reaction to inhaled allergen in(More)
BACKGROUND The combination of salmeterol and fluticasone propionate (SFC) and tiotropium bromide (TIO) are commonly used treatments in chronic obstructive pulmonary disease (COPD) but there are few data on their effectiveness when used together. We compared the effects of SFC 50/500 microg twice daily in addition to TIO 18 microg once daily with the(More)
We have developed a critical test of the chromatin accessibility model of Ig isotype determination in which local unfolding of chromatin higher order structure (chromatin accessibility) in the region of specific germline genes in the H chain locus determines the Ab class to be expressed in the B cell. We show that multiple germline genes are constitutively(More)
Bronchiectasis is characterized by chronic inflammation in one or more bronchi, but the extent of inflammation is difficult to monitor. The concentration of nitric oxide (NO) in exhaled air is increased in asthmatic patients, possibly as a result of the chronic inflammatory process. We have measured exhaled NO in patients with documented bronchiectasis and(More)
BACKGROUND Analysis of bronchoalveolar lavage fluid has improved our understanding of the pathogenesis of asthma. Safety issues and access to expert resources limit this techniques as a research tool. Induced sputum is a non-invasive method of collecting airway fluid which is applicable to subjects with a range of severity of airflow obstruction. The method(More)
Thymic stromal lymphopoietin (TSLP) is said to increase expression of chemokines attracting Th2 T cells. We hypothesized that asthma is characterized by elevated bronchial mucosal expression of TSLP and Th2-attracting, but not Th1-attracting, chemokines as compared with controls, with selective accumulation of cells bearing receptors for these chemokines.(More)
Antagonizing the effect of interleukin (IL)-5 is a potential new treatment strategy in allergic disorders. We evaluated the safety, biological activity, and pharmacokinetics of SCH55700, a humanized anti-human IL-5 antibody, in subjects with severe persistent asthma treated with oral or high doses of inhaled steroids. In a double-blind, randomized,(More)
Indirect challenges act by causing the release of endogenous mediators that cause the airway smooth muscle to contract. This is in contrast to the direct challenges where agonists such as methacholine or histamine cause airflow limitation predominantly via a direct effect on airway smooth muscle. Direct airway challenges have been used widely and are well(More)
BACKGROUND Inhaled glucosteroids and oral theophylline are widely used to treat asthma. We compared the benefits of adding theophylline to inhaled glucosteroid with those of doubling the dose of inhaled glucosteroid in patients with persistent symptoms despite the use of inhaled glucosteroid. METHODS In a double-blind, placebo-controlled trial, we(More)