Inhalation of ozone in normal subjects causes a neutrophilic inflammatory response in the airways. Pretreatment with inhaled corticosteroids reduces the inflammatory response to inhaled ozone in dogs. We undertook a double-blind, randomized, placebo-controlled, crossover study to investigate the effects of 2 wk of treatment with inhaled budesonide 800 microg twice daily or placebo prior to ozone exposure in humans. Fifteen (six male; mean age, 31.1 +/- 2.1 yr) healthy nonsmokers were exposed to 400 parts per billion (ppb) ozone for 2 h with intermittent exercise. Spirometry, exhaled carbon monoxide (CO) and nitric oxide (NO) levels, measurement of methacholine reactivity, and collection of exhaled air condensate and induced sputum samples were performed at baseline, preexposure, and at intervals up to 24 h postexposure. Ozone exposure led to significant decreases in spirometry and increased methacholine reactivity and sputum neutrophils and myeloperoxidase (MPO). There were no changes in exhaled NO and CO levels, or exhaled breath nitrite after ozone exposure. There were no differences in any of the parameters after treatment with budesonide compared with placebo, and no differences in the response to ozone between treatment groups. We conclude that a high dose of inhaled corticosteroid does not protect against the effects of ozone exposure in normal subjects.
Histamine, which has long been implicated as a mediator of allergic airway disease, has multiple effects on airways which are mediated by at least three histamine receptors. H1-receptors mediate bronchoconstriction, vasoconstriction and dilatation, microvascular leak and activation of sensory nerves. H2-receptors mediate vasodilatation in some species and mucus secretion. H3-receptors mediate vasodilatation in some species and mucus secretion. H3-receptors modulate cholinergic neurotransmission, the release of neuropeptides from sensory nerves and allergen-induced bronchoconstriction.
No abstract is provided for this article.
With the high initial success rates for coronary angioplasty that are reported regularly, it has become increasingly difficult to demonstrate methods or techniques that are able to provide more beneficial early results than can be achieved by conventional angioplasty. On the other hand, the incidence of late restenosis has remained much the same over the 10 years that angioplasty has been part of clinical practice, and there is still no proved intervention that modifies the restenosis process. Therefore, the problem of restenosis has assumed increasing relevance in determining the clinical value of coronary angioplasty and, accordingly, studies that address the problem of restenosis need to become more exacting. Although numerous articles have addressed the problem of restenosis in the clinical setting, many defining certain factors associated with restenosis and possible interventions to reduce the incidence of restenosis, there is surprisingly little consensus. Most of the discrepancies can be attributed to three factors: 1) the selection of patients, 2) the method of analysis, and 3) the definition of restenosis employed. This review shows how these three factors influence the outcome and conclusions of restenosis studies.
<h3>Background</h3> Transarterial chemoembolization (TACE) is the therapy which have chosen in 50-60% of patients with Hepatocellular carcinoma (HCC). Recently, Hepatoma Arterial Embolization (HAP) score stratifies patients who will benefit from the first TACE. We conducted a survey to investigate the value of HAP score in the prognosis of HCC treated with TACE in Vietnam. <h3>Methods</h3> Prospective cohort study in patients with HCC and first TACE at the Department of Internal Medicine, Hanoi Medical University Hospital, Vietnam, from January 2017 to June 2021. The HAP score (serum albumin 0.9 mg/dl, alpha-foetoprotein >400 ng/ml, and tumor size >7 cm), and ALBI score was applied before first TACE, mortality and survival were observed with a follow-up of 54 months. <h3>Results</h3> We included 106 patients with age of 62.8 ± 10.1 years. In this population, HCC risk factor was mainly hepatitis B with 75.5% (80/106). The HAP score classified 19, 41, 31 and 15 patients as HAP A, B, C and D, respectively, (IDDF2021-ABS-0070 Table 1). The median follow–up time was 37.5±1.2 months for HAP A, 40.8±2.9 months for HAP B, 24.0±2.5 months for HAP C and 20.4±4.1 months for HAP D. There were no deaths at the first year in HAP A. The cumulative proportion surviving at first years for HAP B, C, D was 97.4; 77.9 and 66.7, respectively. At 36 months, this percentage for HAP A, B, C and D was 92.3; 72.5; 31.1 and 27.1, respectively, (IDDF2021-ABS-0070 Table 2). Survival of all subgroups differed significantly from each other (each p < 0.05) (IDDF2021-ABS-0070 Figure 2. Kaplan-Meier curve for HAP score). Area under the curve for receiver operating characteristic of HAP score was 0.71 and higher than this of ALBI grade (0.57) (IDDF2021-ABS-0070 Figure 3. ROC curves for HAP score and ALBI grade), indicating a significant performance of HAP score compared with ALBI grade in prognosis of HCC treated with TACE. <h3>Conclusions</h3> HAP is a useful score to assist for the management decisions of patients with HCC requiring TACE due to its value in predicting mortality and survival.
Background Currently, no data are available on the direct comparison between the Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) and conventional metallic drug-eluting stents. Methods The ABSORB II study is a randomized, active-controlled, single-blinded, multicenter clinical trial aiming to compare the second-generation Absorb BVS with the XIENCE everolimus-eluting metallic stent. Approximately 501 subjects will be enrolled on a 2:1 randomization basis (Absorb BVS/XIENCE stent) in approximately 40 investigational sites across Europe and New Zealand. Treated lesions will be up to 2 de novo native coronary artery lesions, each located in different major epicardial vessels, all with an angiographic maximal luminal diameter between 2.25 and 3.8 mm as estimated by online quantitative coronary angiography (QCA) and a lesion length of ≤48 mm. Clinical follow-up is planned at 30 and 180 days and at 1, 2, and 3 years. All subjects will undergo coronary angiography, intravascular ultrasound (IVUS) and IVUS–virtual histology at baseline (pre–device and post–device implantation) and at 2-year angiographic follow-up. The primary end point is superiority of the Absorb BVS vs XIENCE stent in terms of vasomotor reactivity of the treated segment at 2 years, defined as the QCA quantified change in the mean lumen diameter prenitrate and postnitrate administration. The coprimary end point is the noninferiority (reflex to superiority) of the QCA-derived minimum lumen diameter at 2 years postnitrate minus minimum lumen diameter postprocedure postnitrate by QCA. In addition, all subjects allocated to the Absorb BVS group will undergo multislice computed tomography imaging at 3 years. Conclusions The ABSORB II randomized controlled trial (ClinicalTrials.gov NCT01425281) is designed to compare the safety, efficacy, and performance of Absorb BVS against the XIENCE everolimus-eluting stent in the treatment of de novo native coronary artery lesions.
No abstract is provided for this article.
Exacerbations of asthma are likely to be due to an increase in airway inflammation. We have studied noninvasive markers of airway inflammation in asthma exacerbations induced by reducing the dose of inhaled corticosteroids. Following a 2-wk run-in period, mild exacerbations were induced in subjects with stable asthma controlled with medium- to high-dose inhaled corticosteroids (beclomethasone dipropionate ⩾ 800 μ g or equivalent daily) by switching them to budesonide 200 μ g daily given from a dry-powder inhaler (Turbohaler). Fifteen subjects were enrolled and were seen twice weekly for 8 wk after steroid reduction. At each visit, exhaled nitric oxide (NO), and methacholine airway responsiveness were measured and spirometry and sputum induction were performed. Mild exacerbation was defined as: (1) a decrease in morning peak expiratory flow (PEF) of ⩾ 20% but < 30% on at least two consecutive days as compared with the mean for the last 7 d of the run-in period; (2) awakening on two consecutive nights because of asthma; or (3) increased use of a short-acting β2-agonist to eight or more puffs daily. Eight subjects did not develop exacerbations during the 8-wk study, whereas seven subjects developed mild exacerbations at Week 4 (n = 1), Week 6 (n = 1), and Week 8 (n = 5). The only significant difference between these two groups at baseline was a higher baseline sputum eosinophil count in subjects with subsequent exacerbations (p < 0.05). The increases in sputum eosinophils and exhaled NO were correlated with decreases in airway function, including decreases in morning PEF and FEV1. However, multiple regression analysis suggested that the change in sputum eosinophils is a potentially useful marker in predicting loss of asthma control reflected by loss of airway function. Jatakanon A, Lim S, Barnes PJ. Changes in sputum eosinophils predict loss of asthma control.
There is increasing evidence for the development of tolerance to the bronchoprotective effects of inhaled beta 2-agonists against bronchoconstrictor stimuli in asthma. With short-acting beta 2-agonists, this is more readily demonstrable using indirectly acting agents such as adenosine monophosphate (AMP), which may act via mast cell degranulation, than using methacholine (MCh), implying more rapid mast cell than smooth muscle desensitization. Desensitization may be greater with the long-acting beta 2-agonist, salmeterol, given its greater duration of receptor occupancy. In a double-blind, placebo-controlled crossover study, we investigated the effect of regular salmeterol on the protection conferred by albuterol using MCh- and AMP-induced bronchoconstriction. Sixteen mild asthmatic subjects not using inhaled glucocorticoids were randomized to treatment for 2 wk with inhaled salmeterol (50 micrograms b.i.d. via diskhaler) or identical placebo. Provocative concentrations of MCh and AMP causing a 20% fall in FEV1 (PC20) were measured 15 min after 200 micrograms albuterol, both before and after treatment. Mean MCh PC20 after albuterol decreased significantly after 2 wk of salmeterol treatment (mean 2.2 mg/ml before to 1.1 +/- 1.2 mg/ml after) compared with placebo (2.9 +/- 1.3 mg/ml before to 2.6 +/- 1.3 mg/ml after; p < 0.05), but this fell just short of statistical significance when analyzed as change in doubling dilutions (1.1 +/- 0.4 versus 0.18 +/- 0.4; p = NS). Mean PC20 to AMP was not significantly affected (mean 27.5 +/- 1.5 mg/ml prior to salmeterol treatment and 9.5 +/- 1.5 mg/ml after treatment; p = NS compared with placebo). Thus, regular salmeterol treatment led to loss of bronchoprotection by albuterol to MCh but not to AMP challenge, implying an absence of mast cell beta 2-adrenoceptor downregulation with regular salmeterol therapy.