Publications

Nuclear Factor-κB — A Pivotal Transcription Factor in Chronic Inflammatory Diseases

In chronic inflammatory diseases, such as asthma, rheumatoid arthritis, inflammatory bowel disease, and psoriasis, several cytokines recruit activated immune and inflammatory cells to the site of lesions, thereby amplifying and perpetuating the inflammatory state.1 These activated cells produce many other mediators of inflammation.What causes these diseases is still a mystery, but the disease process results from an interplay of genetic and environmental factors. Genes, such as those for atopy in asthma and for HLA antigens in rheumatoid arthritis and inflammatory bowel disease, may determine a patient's susceptibility to the disease and the disease's severity, but environmental factors, often unknown, . . .

The low‐chloride cough response is not inhibited by a single, high dose of aspirin.

The effect of a single, high dose of aspirin has been assessed against low chloride cough challenge. The drug does not affect the cough response, suggesting that airway prostaglandin generation is not responsible for the tussive activity of low chloride solution.

Intravascular ultrasound: An evolving rival for quantitative coronary angiography

No abstract is provided for this article.

Individualized Assessment for Percutaneous or Surgical Revascularization

No abstract is provided for this article.

The association between trimethylamine N-oxide levels and coronary microvascular dysfunction and prognosis in patients with ST-elevation myocardial infarction

Background and aims Coronary microvascular dysfunction (CMD) is common after ST-elevation myocardial infarction (STEMI), leading to adverse clinical outcomes. However, its diagnosis remains difficult, and mechanisms elusive. This study explores the role of Trimethylamine N-oxide (TMAO), a gut microbiota metabolite, as a potential biomarker for diagnosing CMD in STEMI patients. Methods This prospective, observational study enrolled 210 STEMI patients with multivessel coronary artery disease who underwent primary percutaneous coronary intervention (PCI). TMAO levels were measured at baseline, 3 months, and 12 months post-PCI, whilst coronary physiology was assessed at 3 months. The primary endpoint was the incidence of CMD at 3 months, with the secondary endpoint being major adverse cardiovascular and cerebrovascular events (MACCE) at 12 months. An additional 59 consecutive patients were enrolled for validation. Results TMAO levels varied from baseline to 3 months, then stabilised. The areas under the ROC curve for baseline TMAO and TMAO at 3-month were 0.55 (95 % CI 0.46–0.64; p = 0.426), and 0.80 (95 % CI 0.73–0.87; p < 0.001), respectively. The optimal cut-off for TMAO at 3-month to diagnose CMD was 3.91, with similar sensitivity and specificity in the derivation and validation cohort. The incidence of MACCE was higher in patients with TMAO≥3.91 (41.4 % vs 10.7 %; p < 0.001). The addition of 3-month TMAO improved the diagnostic performance of traditional risk factors. Conclusion TMAO is a robust biomarker for CMD and is significantly associated with the incidence of MACCE. TMAO has the potential in guiding clinical decision-making and suggests an interplay between gut microbiota and CMD.

Volume 4 Number 2

Aims and

Small airway fibroblasts from COPD patients are senescent and pro-fibrotic

<b>Background:</b> Progressive small airway fibrosis is a key feature of early COPD. In COPD, cellular senescence levels are increased and may relate to disease progression. Peripheral parenchymal fibroblasts are pro-inflammatory and dysfunctional in COPD, but the role of small airway fibroblasts (SAF) and the impact of senescence are unknown. <b>Aim:</b> Compare senescence and pro-fibrotic markers of SAF from COPD patients to age-matched controls. <b>Method:</b> SAF were isolated from non-smoker and COPD surgical lung resections. Gene expression was measured by qPCR, protease activity by zymography, cell proliferation using iCELLigence impedance and senescence cells by senescence-associated β-galactosidase (SA-βGal) staining, p16^INK4a and p21^Waf1 expression. <b>Results:</b> COPD SAF displayed reduced proliferation (n=4-5, Fig. 1), increased SA-βGal staining (n=6), and elevated p21 (34%) and p16 (12%) expression compared to control non-smoker SAF. Whilst gene expression of MMP2/9 was unchanged (n=3-7), pro-MMP2 was significantly increased (102%, p=0.02) in COPD SAF and similarly trends in elevated pro- and active-MMP2/9 (15-28%). COPD SAF also displayed trends in increased αSMA (25%), COL1A1 (40%) and COL3A1 (20%, n=5) expression. <b>Conclusion:</b> This suggests COPD SAF show cellular senescence, have elevated MMPs and pro-fibrotic markers compared to non-smoker. Elucidating the mechanism underlying this phenotype could lead to future targets of airway fibrosis and COPD.

Early (before 6 months), late (6-12 months) and very late (after 12 months) angiographic scaffold restenosis in the ABSORB Cohort B trial

The long-term follow-up of the first-in-man ABSORB Cohort B trial showed that angiographic binary restenosis can occur early, late or very late after implantation of the Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS). Since the mechanical support of the scaffold decreases during bioresorption, the mechanism of in-segment restenosis (ISR) of the Absorb BVS might be different from that of metallic stents. The objective of the current analysis was to review the multimodality imaging of cases with binary restenosis to elucidate the mechanism of ISR after Absorb BVS implantation.The ABSORB Cohort B trial enrolled 101 patients with a maximum of two de novo coronary lesions. At the three-year imaging and clinical follow-up, there were six cases of in-segment binary restenosis: two early ISR (<6 months), one late ISR (6-12 months) and three very late ISR (>12 months). Three of these ISR cases seemed to be induced by anatomical or procedural factors. In the other three cases, intravascular imaging (IVUS/OCT) demonstrated that the main mechanism of restenosis was significant intra-scaffold tissue growth, while the structural circularity and diameter of the scaffold were not affected.Early and late restenosis after implantation of the Absorb bioresorbable scaffold could be related to anatomical or procedural factors. In this small cohort of patients late or very late restenosis seems to be attributed to pure intra-scaffold tissue growth without extrinsic encroachment of the scaffold.

Use of 'Low-Dose' Theophylline to Reduce Exacerbations of COPD: A Pragmatic Multicentre Randomised Placebo Controlled Trial

This abstract is funded by: National Institute for Health Research Health Technology Assessment Presented at mini symposium: B14. LATE BREAKING CLINICAL TRIALS AND FIRST REPORTS IN ASTHMA AND COPD Monday 21st May 2018

Coronary stenting in small vessels: reply

We deeply appreciate the interest of Moreno et al. on our meta-analysis and we welcome the continuous debate regarding this issue. Unfortunately, we partially disagree with Moreno et al. on their response1 to our previous letter2 to the editor published in the Journal of the American College of Cardiology , and on their present criticisms. In particular, concerning their previous reply letter in the Journal of the American College of Cardiology ,1 we believe that they did not sufficiently evaluate the importance of statistical heterogeneity among trials, present both in our and their meta-analyses. Although a quantitative estimate may be obtained also in the case of statistical heterogeneity, using the random effect model, …

Alveolar macrophage-mediated elastolysis: roles of matrix metalloproteinases, cysteine, and serine proteases

Chronic obstructive pulmonary disease (COPD) is a common lung disease with cigarette smoking as the major etiological factor, but only 15% of smokers develop COPD. Destruction of lung elastin observed in COPD is mediated by many enzymes, including cysteine, serine, and matrix metalloproteinases (MMP). The contribution of these enzymes to the lung elastolytic load, released from alveolar macrophages collected from nonsmokers, healthy smokers, and COPD patients, was examined by radiolabeled elastin as substrate in the presence of specific enzyme inhibitors. The activity of MMP was further examined by zymography and Western blotting. COPD macrophages degraded more elastin than either of the other groups. Elastolysis was greatest in the initial 24 h. Through the 72-h culture period, the contribution to elastolysis of serine elastases decreased, MMP increased, and cysteine elastases remained constant. The increased release of elastolytic enzymes in COPD subjects may explain why some smokers develop COPD. This difference may be due to unknown susceptibility factors. Serine proteases play a significant role; however, other enzymes, particularly the MMP, deserve further investigation.

Table of Contents

Lung cancer: practice and epidemiology

Healing of a coronary artery dissection detected by intravascular ultrasound and optical coherence tomography

No abstract is provided for this article.

Corticosteroid resistance in chronic obstructive pulmonary disease: inactivation of histone deacetylase

Aneurysm of the Abdominal Aorta

A 76-year-old man was admitted to the intensive care unit with unstable angina pectoris of Braunwald class IIIB. He was known to have hypertension, which was poorly controlled with medication. Physical examination revealed a pulsating mass in the lower abdomen that was suggestive of an aortic aneurysm. An echocardiographic study with a small, hand-held ultrasound device (SonoHeart, SonoSite Inc) showed an abdominal aortic aneurysm containing thrombotic material (Figure 1). His troponin T level was elevated, and he underwent coronary arteriography, which showed a high-grade stenosis at the bifurcation of left anterior descending artery and the first diagonal branch. The lesion was dilated during the same session, with direct stenting of both branches. Figure 1. Transverse image of the aneurysm of the abdominal aorta (56 mm in diameter), which contains a large thrombus (TR). The …

Effect of inhaled corticosteroids on bones and growth

Inhaled corticosteroids are recognized as the most effective anti-inflammatory therapy in patients with asthma and their early introduction is recommended by national and international guidelines. Concerns have been raised about potential adverse effects of inhaled corticosteroids on bones and growth, as these appear to be more important clinically than effects on the hypothalamic-pituitary-adrenal axis, which are more commonly measured. This review examines the effects of inhaled corticosteroids on biochemical bone markers, bone density and growth in adults and children with asthma, in view of the recent availability of a substantial amount of new clinical trial data. Examination of relevant retrospective and prospective data, involving 11 studies (1,240 patients) on biochemical bone markers and 14 studies (373 patients) on bone density over a wide dose range, have largely indicated no significant or clinically important effect on these measurements in adults or children with asthma. Markers of bone formation and resorption need to be measured concurrently for a reliable assessment of bone turnover to be made. Knemometry, measuring lower leg growth rate, is a sensitive technique for comparing the systemic activity of different inhaled corticosteroids, but does not relate to long-term growth. The majority of approximately 40 studies on inhaled corticosteroids and statural growth in children, over a wide recommended dose range, including a number of recent long-term, prospective studies, demonstrate little or no effect. Children taking above recommended doses of inhaled corticosteroids should have their growth monitored using stadiometry at least every 6 months by trained personnel. Most of the areas reviewed, particularly the relatively new areas of biochemical bone markers and bone density, require further properly controlled, long-term, prospective investigation, although the long-term value of bone markers appears limited. In summary, the data as it currently stands, suggests that doses of inhaled corticosteroids up to 1,000 microg x day(-1) in adults and 400 microg x day(-1) in children have no significant effect on bones and growth in the large majority of patients with asthma.

Myocardial Contrast Two-Dimensional Echocardiography: Initial Observations during Cardiac Catheterization

Myocardial contrast two-dimensional (2D) echocardiography is a relatively new technique which was developed and validated in animals to determine myocardial perfusion. However, human studies are scarce. Therefore, myocardial contrast 2D echocardiography was performed in 32 patients with suspected coronary artery disease immediately after coronary arteriography. Two milliliters of sonicated iopamidol (microbubbles size 12 ± 4 pm) was injected intracoronarily during continuous recording of échocardiographie apical four-chamber view. Visible myocardial contrast was achieved in 82% of patients (25 patients) and 62% of injections (96 injections). Perfusion defects were detected in 5 of 6 patients with > 90% stenosis without collateral circulation and in none of the 7 patients with collateral flow. Normally contracting segments were opacified in every instance, while this occurred only in 7 of 15 areas with contraction abnormalities. No wall motion abnormalities resulted from intracoronary sonicated iopamidol. Minor transient electrocardiographic changes (ST-T segment changes) were noted, which were similar as seen after routine coronary arteriography. Patients showed no complaints after injection of the echocontrast. Myocardial contrast 2D echocardiography is a potential useful method for the real-time analysis of myocardial perfusion in humans.

Longitudinal Distribution of Plaque Burden and Necrotic Core–Rich Plaques in Nonculprit Lesions of Patients Presenting With Acute Coronary Syndromes

Objectives In this substudy of the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, we examined the longitudinal distribution of atherosclerotic plaque burden, virtual histology–intravascular ultrasound (VH-IVUS) characterized necrotic core (NC) content and VH–thin-cap fibroatheroma (TCFA) distribution in nonculprit lesions of patients presenting with acute coronary syndromes. Background Previous analyses suggested that vulnerable plaques and acute myocardial infarction may occur more frequently in the proximal than the distal coronary tree. Methods A total of 4,234 proximal, mid, and distal 30-mm-long segments of each epicardial coronary artery were compared with each other and to the left main coronary artery (LMCA). Results Combining IVUS data from all 3 arteries, there was a gradient in plaque burden from the proximal (42.4%) to mid (37.6%) to distal (32.6%) 30-mm-long segments (p < 0.0001). Overall, 67.4% of proximal, 41.0% of mid, and 29.7% of distal 30-mm-long segments contained at least 1 lesion (plaque burden >40%). Proportion of NC, however, was similar in the proximal and mid 30-mm-long segments of all arteries (10.3% [interquartile range (IQR): 4.8% to 16.7%] vs. 10.6% [IQR: 5.0% to 18.1%], p = 0.25), but less in the distal 30-mm-long segment (9.1% [IQR: 3.7% to 17.8%], p = 0.03 compared with the proximal segment and p = 0.003 compared with the mid segment). Overall, 17.3% of proximal, 11.5% of mid, and 9.1% of distal 30-mm-long segments had at least 1 lesion that was classified as VH-TCFA (p < 0.0001). Comparing the LMCA with the combined cohort of proximal left anterior descending, left circumflex, and right coronary artery 30-mm-long segments: 1) plaque burden was less (35.4% [IQR: 28.8% to 43.5%] vs. 40.9% [IQR: 33.3% to 48.0%], p < 0.0001); 2) fewer LMCAs contained at least 1 lesion (17.5%, p < 0.0001); 3) there was less NC (6.5% [IQR: 2.9% to 12.2%] vs. 9.3% [IQR: 4.3% to 15.9%], p < 0.0001); and 4) LMCAs rarely contained a VH-TCFA (1.8%, p < 0.0001). Conclusions The current analysis appears to confirm that lesions that are responsible for acute coronary events (large, plaque burden–rich in NC) are somewhat more likely to be present in the proximal than the distal coronary tree, except for the LMCA.