Synergistic effects of fluticasone propionate and salmeterol on in vitro T-cell activation and apoptosis in asthma

In asthma T cells are characterized by an increased activation state and by reduced apoptosis

Airway cell composition at rest and after an all-out test in competitive rowers

Med Sci Sports Exerc. 2004 Oct;36(10):1723-9. Airway cell composition at rest and after an all-out test in competitive rowers. Morici G, Bonsignore MR, Zangla D, Riccobono L, Profita M, Bonanno A, Paternò A, Di Giorgi R, Mirabella F, Chimenti L, Benigno A, Vignola AM, Bellia V, Amato G, Bonsignore G. SourceDepartment of Experimental Medicine Italian National Research Council (CNR), Palermo, Italy. Abstract PURPOSES: This study was designed to assess: a) whether rowing affects airway cell composition, and b) the possible relationship between the degree of ventilation during exercise and airway cells. SUBJECTS AND METHODS: In nine young, nonasthmatic competitive rowers (mean age +/- SD: 16.2 +/- 1.0 yr), induced sputum samples were obtained at rest and shortly after an all-out rowing test over 1000 m (mean duration: 200 +/- 14 s), during which ventilatory and metabolic variables were recorded breath-by-breath (Cosmed K4b, Italy). RESULTS: At rest, induced sputum showed prevalence of neutrophils (60%) over macrophages (40%); after exercise, total cell and bronchial epithelial cell (BEC) counts tended to increase. In the last minute of exercise, mean VE was 158.0 +/- 41.5 L x min(-1), and VO2 x kg(-1) 62 +/- 11 mL x min(-1). Exercise VE correlated directly with postexercise total cell (Spearman rho: 0.75, P < 0.05) an dmacrophage (rho: 0.82, P < 0.05) counts. A similar trend was observed for exercise VE and changes in BEC counts from baseline to postexercise (rho: 0.64, P = 0.11). Exercise VE did not correlate with airway neutrophil counts at rest or after exercise. Expression of adhesion molecules by airway neutrophils, macrophages, and eosinophils decreased after the all-out test. CONCLUSION: Similar to endurance athletes, nonasthmatic competitive rowers showed increased neutrophils in induced sputum compared with values found in sedentary subjects. The trend toward increased BEC postexercise possibly reflected the effects of high airflows on airway epithelium. Airway macrophages postexercise were highest in rowers showing tile most intense exercise hyperpnea, suggesting early involvement of these cells during exercise. However, the low expression of adhesion molecules by all airway cell types suggests that intense short-lived exercise may be associated with a blunted response of airway cells in nonasthmatic well-trained rowers. PMID:15595293[PubMed - indexed for MEDLINE

Vessel-Associated Transforming Growth Factor-Beta1 (TGF-β1) Is Increased in the Bronchial Reticular Basement Membrane in COPD and Normal Smokers

BACKGROUND: Transforming growth factor-beta1 (TGF-β1) is a multipotential cytokine with angiogenic activity. There are only limited data about its role in airway remodeling in COPD. We have previously shown that the reticular basement membrane (Rbm) is hypervascular in the airways of current smokers either with or without chronic obstructive pulmonary disease (COPD). This study evaluated TGF-β1 immunostaining in the Rbm and its relationship to vascularity in smokers with or without COPD. METHODOLOGY/PRINCIPAL FINDINGS: Bronchial biopsies from 15 smokers with normal lung function, 19 current and 14 ex-smokers with COPD were immunostained for TGF-β1 antibody and compared to 17 healthy controls. The percentage area of tissue and also number and area of vessels staining positively for TGF-β1 were measured and compared between groups. Some bronchial biopsies from current smoking COPD subjects were also stained for phosphorylated (active) Smad2/3. Epithelial TGF- β1 staining was not different between COPD current smokers and normal controls. TGF-β1 stained vessels in the Rbm were increased in smokers with normal lung function, current smoking COPD and ex-smokers with COPD compared to controls [median (range) for number of vessels/mm Rbm 2.5 (0.0-12.7), 3.4 (0.0-8.1) and 1.0 (0.0-6.3) vs. 0.0 (0.0-7.0), p<0.05]. Percentage of vessels stained was also increased in these clinical groups. Preliminary data suggest that in current smoking COPD subjects endothelial cells and cells in the Rbm stain positively for phosphorylated Smad2/3 suggesting TGF-β1 is functionally active in this situation. CONCLUSIONS/SIGNIFICANCE: Vessel-associated TGF-β1 activity is increased in the bronchial Rbm in smokers and especially those with COPD

Palaeoecological data indicates land-use changes across Europe linked to spatial heterogeneity in mortality during the Black Death pandemic

The Black Death (1347–1352 CE) is the most renowned pandemic in human history, believed by many to have killed half of Europe’s population. However, despite advances in ancient DNA research that conclusively identified the pandemic’s causative agent (bacterium Yersinia pestis), our knowledge of the Black Death remains limited, based primarily on qualitative remarks in medieval written sources available for some areas of Western Europe. Here, we remedy this situation by applying a pioneering new approach, ‘big data palaeoecology’, which, starting from palynological data, evaluates the scale of the Black Death’s mortality on a regional scale across Europe. We collected pollen data on landscape change from 261 radiocarbon-dated coring sites (lakes and wetlands) located across 19 modern-day European countries. We used two independent methods of analysis to evaluate whether the changes we see in the landscape at the time of the Black Death agree with the hypothesis that a large portion of the population, upwards of half, died within a few years in the 21 historical regions we studied. While we can confirm that the Black Death had a devastating impact in some regions, we found that it had negligible or no impact in others. These inter-regional differences in the Black Death’s mortality across Europe demonstrate the significance of cultural, ecological, economic, societal and climatic factors that mediated the dissemination and impact of the disease. The complex interplay of these factors, along with the historical ecology of plague, should be a focus of future research on historical pandemics.The authors acknowledge the following funding sources: Max Planck Independent Research Group, Palaeo-Science and History Group (A.I., A.M. and C.V.); Estonian Research Council #PRG323, PUT1173 (A.Pos., T.R., N.S. and S.V.); European Research Council #FP7 263735 (A.Bro. and A.Plu.), #MSC 655659 (A.E.); Georgetown Environmental Initiative (T.N.); Latvian Council of Science #LZP-2020/2-0060 (N.S. and N.J.); LLNL-JRNL-820941 (I.T.); NSF award #GSS-1228126 (S.M.); Polish-Swiss Research Programme #013/2010 CLIMPEAT (M.Lam.), #086/2010 CLIMPOL (A.W.); Polish Ministry of Science and Higher Education #N N306 275635 (M.K.); Polish National Science Centre #2019/03/X/ST10/00849 (M.Lam.), #2015/17/B/ST10/01656 (M.Lam.), #2015/17/B/ST10/03430 (M.Sło.), #2018/31/B/ST10/02498 (M.Sło.), #N N304 319636 (A.W.); SCIEX #12.286 (K.Mar.); Spanish Ministry of Economy and Competitiveness #REDISCO-HAR2017-88035-P (J.A.L.S.); Spanish Ministry of Education, Culture and Sports #FPU16/00676 (R.L.L.); Swedish Research Council #421-2010-1570 (P.L.), #2018-01272 (F.C.L. and A.S.); Volkswagen Foundation Freigeist Fellowship Dantean Anomaly (M.B.), Spanish Ministry of Science and Innovation #RTI2018-101714-B-I00 (F.A.S. and D.A.S.), OP RDE, MEYS project #CZ.02.1.01/0.0/0.0/16_019/0000728 (P.P.)Peer reviewe

Methacholine challenge and sputum induction - Reply

AUTHORS\u2019 REPLY We would like to thank Drs Labiris and Hargreave for their interesting comments on our article. They have emphasised the variability in the data and the fact that the p values for neutrophils and macrophages were near significance. Moreover, they have provided the results of a power analysis for paired continuous data showing that the study is underpowered to reach solid conclusions. We agree that their comments are valid both for the variability of the data and that the p value was near significance for neutrophils and macrophages. However, the p value for eosinophils was far from the significance level (p = 0.49). This is important because the aim of the study was to evaluate the influence of methacholine challenge on overall sputum cellularity but, in particular, on eosinophils which are considered the most relevant inflammatory cell in bronchial asthma. We are confident that a methacholine inhalation challenge carried out one hour before sputum induction in asthmatic subjects does not alter the eosinophil count in induced sputum, and that this result is important for both clinical practice and clinical trials involving patients with asthma

Allergic rhinitis, rhinosinusitis, and asthma : one airway disease

Asthma and allergies, including rhinoconjunctivitis and atopic dermatitis, are common throughout the world, with a high burden of morbidity and cost. The nasal and bronchial mucosa present similarities, and most patients with asthma also have rhinitis, suggesting the concept of "one airway, one disease." Not all patients with rhinitis present with asthma, however, and there are differences between rhinitis and asthma. For this article, the authors differentiate between chronic rhinosinusitis and nasal polyposis based on the presence of polyps in the nasal cavity or the sinuses during clinical examination or surgery. This approach neglects an ill-defined group of chronic hyperplastic sinusitis, which might represent a transition phase