Publications

Asthma is a chronic inflammatory disorder of the airways with the proven role of Th2 cells in its pathogenesis. The role and characteristic of different subsets of CD4(+) cells is much less known.The aim of the study was to analyze the incidence of different subsets of CD4(+) T cells, in particular different subsets of CD4(+) cells with the co-expression of different cytokines.Twenty five stable asthmatic and twelve age-matched control subjects were recruited to the study. Bronchoscopy and bronchoalveolar lavage (BAL) were performed in all study subjects. CD4(+) T cells were isolated from BAL fluid by positive magnetic selection. After stimulation simultaneous expression of TGF-β, FoxP3, CD25, IFN-γ, IL-4, TNF-α (set 1); IL-10, FoxP3, CD25, IFN-γ, IL-4, MIP-1β (set 2); IL-17A, IL-8, IFN-γ, IL-4, MIP-1β (set 3) were measured by flow cytometry.The percentage of CD4(+) cells co-expressing Foxp3 and TGF-β (CD4(+)Foxp3(+)TGF-β(+) cells) was significantly lower (P = 0.03), whereas the percentage of CD4(+)IL-17(+) cells (P = 0.008), CD4(+)IL-17(+) IFN-γ(+) cells (P = 0.047) and CD4(+)IL-4(+) cells (P = 0.01) were significantly increased in asthmatics compared with that seen in healthy subjects. A significantly higher percentage of CD4(+)Foxp3(+) cells from asthma patients expressed IFN-γ (P = 0.01), IL-4 (P = 0.004) and CD25 (P = 0.04), whereas the percentage of CD4(+)IL-10(+) cells expressing Foxp3 was significantly decreased in asthmatics (P = 0.03). FEV1% predicted correlated negatively with the percentage of CD4(+)IL-17(+) cells (r = -0.33; P = 0.046) and positively with CD4(+)Foxp3(+)TGF-β(+) cells (r = 0.43; P = 0.01).Our results suggest that in the airways of chronic asthma patients there is an imbalance between increased numbers of CD4(+)IL-17(+) cells and Th2 cells and decreased number of CD4(+)Foxp3(+)TGF-β(+).

Opioid receptors have been demonstrated on sensory fibres in the vagus nerve. Non‐cholinergic (NC) neural bronchoconstriction in guinea‐pig is due to release of neuropeptides from sensory nerve endings. We have therefore studied the effect of opioids on this NC bronchoconstriction in the anaesthetized guinea‐pig. Bilateral vagal stimulation (5 V, 5 ms, 10 Hz) caused reproducible bronchoconstriction in guinea‐pigs which was reduced by atropine (1 mg kg −1 ), but the NC component was unaffected by hexamethonium (10 mg kg −1 ). NC bronchoconstriction was reduced by morphine in a dose‐dependent manner (ED 50 = 132 μg kg −1 with a maximal inhibition of 79 ± 2.1% at 1 mg kg −1 ). Yohimbine (0.5 mg kg −1 ) did not alter the inhibitory effect of morphine (1 mg kg −1 ). The inhibitory effect of morphine was completely reversed by naloxone (1 mg kg −1 ) which had no effect on NC bronchoconstriction. Propranolol (1 mg kg −1 ) significantly increased the NC bronchoconstrictor response but did not significantly alter the inhibition by morphine. The selective μ‐opioid receptor agonist Tyr‐( d ‐Ala)‐Gly‐(N‐Me‐Phe)‐Glyol (DAGOL) was significantly more potent than morphine with an ED 50 of 5.4 μg kg −1 and complete inhibition at 100 μg kg −1 . The δ‐agonist Tyr‐( d ‐Pen)‐Gly‐Phe‐( d ‐Pen) (DPDPE) was less potent than DAGOL with an ED 50 of 28 μg kg −1 and a maximal inhibition of only 50 ± 5% at 100 μg kg −1 . The κ‐receptor agonist, U‐50,488H had no inhibitory effect on the NC bronchoconstrictor response. The bronchoconstrictor responses to exogenous substance P (25 μg kg −1 ) or acetylcholine (25 μg kg −1 ) were unaffected by morphine (500 μg kg −1 ). We conclude that opioids inhibit the NC bronchoconstrictor response to vagal stimulation via an action on μ‐opioid receptors localized to sensory nerve endings in the airway.

The implantation of a bioresorbable scaffolds (BRSs) is a new approach that provides transient vessel support with drug delivery capability, potentially without the limitations of permanent metallic implants. The potential short- and long-term performance of this technology has been repeatedly investigated with optical coherence tomography (OCT). However, images acquired by OCT after implantation of BRSs are different from those with metallic stents due to the translucency of polymeric materials compared to the opacity of metallic compounds. This chapter presents the potential bias of conventional methodology and the consensus of multiple core labs and expert researchers of OCT on a standard methodology that enables peopel to compare two different devices using an almost identical, methodological language. When the conventional methods are applied for the comparison of the polymeric bioresorbable scaffold and the permanent metallic stents, the methodological discrepancies discussed in the chapter lead to biased res.

No abstract is provided for this article.

Rationale: Neutralization of tumor necrosis factor-α (TNF-α) is an effective antiinflammatory therapy for several chronic inflammatory diseases.Methods and Objectives: We undertook a double-blind, placebo-controlled, parallel-group design study in 38 patients with moderate asthma treated with inhaled corticosteroids but symptomatic during a run-in phase. Infliximab (5 mg/kg) or placebo was administered by intravenous infusion at Weeks 0, 2, and 6. We assessed clinical response by monitoring lung function, symptoms, and inhaled β2-agonist usage using hand-held electronic devices.Results: The primary endpoint, change in morning PEF at Days 50–56 compared with the last 7 d of the run-in, was not significantly different on treatment. However, infliximab was associated with a decrease in mean diurnal variation of PEF at Week 8 (p = 0.02; 95% confidence interval [CI], −8.1 to −0.72). Furthermore, there was a decrease in the number of patients with exacerbations of asthma (p = 0.01; 95% CI, 4.4 to 52.7) and an increased probability of freedom from exacerbation with time (p = 0.03) in patients on infliximab (n = 14) compared with placebo (n = 18). In addition, infliximab decreased levels of TNF-α (p = 0.01) and other cytokines in sputum supernatants. There were no serious adverse events related to the study agent.Conclusions: Treatment with infliximab was well tolerated and caused a decrease in the number of patients with exacerbations in symptomatic moderate asthma. The promising preliminary findings underscore the need to evaluate therapy directed against TNF-α in larger trials enrolling patients with more severe asthma.

No abstract is provided for this article.

Background: Whether revascularization improves prognosis in stable ischemic heart disease is controversial. Methods: Individual patient-level data from 19 prospective, randomized stent trials were pooled. Rates of 5-year major adverse cardiovascular events (MACE; a composite of cardiac death, myocardial infarction, or ischemia-driven target lesion revascularization) were assessed and compared after percutaneous coronary intervention with bare-metal stents (BMS) and first-generation and second-generation drug-eluting stents (DES1 and DES2, respectively). Poisson multivariable regression analysis was performed to identify predictors of adverse events. Results: Among 10 987 patients treated with percutaneous coronary intervention for stable ischemic heart disease, 1550, 2776, and 6661 received BMS, DES1, and DES2, respectively. The 5-year rates of MACE progressively declined with evolution in stent technology (BMS: 24.1% versus DES1: 17.9% versus DES2: 13.4%, P <0.0001). However, MACE rates between 1 and 5 years increased from BMS to DES1, then declined with DES2 (BMS: 7.4% versus DES1: 10.2%, DES2: 8.5%, P =0.02). Conclusions: Patients with stable ischemic heart disease remain at substantial risk for long-term MACE after revascularization with percutaneous coronary intervention, even with contemporary DES. New approaches to reduce the ongoing risk of MACE beyond 1 year after stent implantation are necessary.

For women undergoing drug-eluting stent (DES) implantation, the individual and combined impact of chronic kidney disease (CKD) and diabetes mellitus (DM) on outcomes is uncertain.