Rebecca Simms

Effects of Helicobacter pylori, geohelminth infection and selected commensal bacteria on the risk of allergic disease and sensitization in 3-year-old Ethiopian children

Background Epidemiological studies have suggested that gastro‐intestinal infections including Helicobacter pylori, intestinal microflora (commensal bacteria) and geohelminths may influence the risk of asthma and allergy but data from early life are lacking.

Pseudomonas aeruginosa quorum sensing molecules correlate with clinical status in cystic fibrosis

Pseudomonas aeruginosa produces quorum sensing signal molecules that are potential biomarkers for infection. A prospective study of 60 cystic fibrosis patients with chronic P. aeruginosa, who required intravenous antibiotics for pulmonary exacerbations, was undertaken. Clinical measurements and biological samples were obtained at the start and end of the treatment period. Additional data were available for 29 of these patients when they were clinically stable. Cross-sectionally, quorum sensing signal molecules were detectable in the sputum, plasma and urine of 86%, 75% and 83% patients, respectively. They were positively correlated between the three biofluids. Positive correlations were observed for most quorum sensing signal molecules in sputum, plasma and urine, with quantitative measures of pulmonary P. aeruginosa load at the start of a pulmonary exacerbation. Plasma concentrations of 2-nonyl-4-hydroxy-quinoline (NHQ) were significantly higher at the start of a pulmonary exacerbation compared to clinical stability (p<0.01). Following the administration of systemic antibiotics, plasma 2-heptyl-4-hydroxyquinoline (p=0.02) and NHQ concentrations (p<0.01) decreased significantly. In conclusion, quorum sensing signal molecules are detectable in cystic fibrosis patients with pulmonary P. aeruginosa infection and are positively correlated with quantitative measures of P. aeruginosa. NHQ correlates with clinical status and has potential as a novel biomarker for P. aeruginosa infection. P. aeruginosa QS molecules correlate with clinical status in cystic fibrosis and are biomarkers for infection http://ow.ly/MhzZp

Target renal damage: the microvascular associations of increased aortic stiffness in patients with COPD

BackgroundAlthough renal impairment has been described in COPD, there is opportunity to evaluate further to determine nature and consider optimal management. Increased aortic stiffness, as seen in COPD, leads to reduced buffering of pulsatile flow. We hypothesised that urinary albumin creatinine ratio (UACR) would reflect glomerular damage related to aortic stiffness.MethodsPatients with COPD and controls underwent spirometry, blood pressure, arterial stiffness - aortic pulse wave velocity (PWV) and provided a spot urine sample for UACR, with other renal biomarkers measured.ResultsThe UACR was increased in patients (n = 52): 0.80 mg/mmol compared to controls (n = 34): 0.46 mg/mmol, p < 0.05. Aortic PWV was related to log10 UACR in all subjects (r = 0.426, p < 0.001) and COPD patients alone. Aortic PWV was a significant variable for UACR with oxygen saturations, after accounting for potential confounders. Eight subjects (7 patients) reached a defined clinical microalbuminuria threshold, with aortic PWV greater in these patients compared to those patients without, although albuminuria is a continuum. Proximal tubular damage biomarkers, unlike the glomerular marker, were not different between patients and controls.ConclusionsThere is glomerular damage in patients with COPD evidenced by increased UACR, related to increased aortic stiffness. Besides the macrovascular prognostic implications of increased aortic stiffness, the microvascular state in COPD management should be considered.

Glutamine supplementation in cystic fibrosis: A randomized placebo‐controlled trial

Pulmonary infection and malnutrition in cystic fibrosis are associated with decreased survival. Glutamine has a possible anti‐microbial effect, with a specific impact against Pseudomonas aeruginosa. We aimed to test the hypothesis that oral glutamine supplementation (21 g/day) for 8 weeks in adults with cystic fibrosis would decrease pulmonary inflammation and improve clinical status.

Assessment of a rapid liquid-based cytology method for measuring sputum cell counts

Differential sputum cell counting is not widely available despite proven clinical utility in the management of asthma. We compared eosinophil counts obtained using liquid-based cytology (LBC), a routine histopathological processing method, and the current standard method. Eosinophil counts obtained using LBC were a strong predictor of sputum eosinophilia (≥3%) determined by the standard method suggesting LBC could be used in the management of asthma.

S129 Decreased cAMP Production in Lung Fibroblasts from Patients with Idiopathic Pulmonary Fibrosis

Rationale Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with unknown aetiology and no effective therapy. Myofibroblasts are the primary effector cells in the pathogenesis of IPF and differentiation from fibroblasts is a major source of myofibroblasts. Prostaglandin E2 (PGE2) inhibits fibroblast to myofibroblast differentiation via the E Prostanoid 2 (EP2) receptor and cAMP, suggesting cAMP is a key regulator of myofibroblast differentiation. The aim of the present study was to evaluate the effect of different cAMP elevating agents on myofibroblast differentiation. Methods Fibroblasts from lungs of patients with IPF (F-IPF) and from non-fibrotic lungs (F-NL) were used. TGF-β1 (2ng/ml 3d) was used to induce myofibroblast differentiation. The effect of PGE2, β2-agonists Salmeterol and Formoterol, the direct adenylyl cyclase activator Forskolin and the phosphodiesterase 4 (PDE4) inhibitor Roflumilast (all 1µm, 3d) was evaluated. IL-1β (2ng/ml, 24hr) was used for cyclooxygenase 2 (COX-2) induction. α-smooth muscle actin (α-SMA, a myofibroblast marker), COX-2, EP2, EP4 and β2-receptor expression was analysed by Western blotting and immunocytochemistry, respectively. Adenylyl cyclase mRNA was measured by qPCR and cAMP was measured by radioimmunoassay. Results F-IPF showed increased α-SMA and collagen expression and repressed COX-2 expression compared to F-NL. PGE2 treatment prevented TGF-β1-induced α-SMA expression and COX-2 repression in F-NL, which was mimicked by β2-agonists and Forskolin. PGE2 also reduced α-SMA expression and increased COX-2 expression in F-IPF despite that it induced significantly less cAMP than in F-NL But this effect on F-IPF was not mimicked by β2-agonists and Forskolin as they induced even less cAMP than PGE2 in these cells. TGF-β-treated F-NL also produced less cAMP than untreated cells in response to these cAMP. stimulants. However, the expression of EP2, EP4, β2-adrenoceptors and adenylyl cyclase isoforms was similar in F-NL and F-IPF. Furthermore, combination of PGE2 with Roflumilast showed greater effect than PGE2 alone on α-SMA reduction and COX-2 expression in F-IPF and F-NL, whereas Roflumilast alone had no effect. Conclusions cAMP is a key anti-fibrotic regulator of myofibroblast differentiation. However, cAMP production in myofibroblasts is defective, probably due to increased degradation by PDE4.