Reference values for methacholine reactivity (SAPALDIA study)

BACKGROUND: The distribution of airway responsiveness in a general population of non-smokers without respiratory symptoms has not been established, limiting its use in clinical and epidemiological practice. We derived reference equations depending on individual characteristics (i.e., sex, age, baseline lung function) for relevant percentiles of the methacholine two-point dose-response slope. METHODS: In a reference sample of 1567 adults of the SAPALDIA cross-sectional survey (1991), defined by excluding subjects with respiratory conditions, responsiveness during methacholine challenge was quantified by calculating the two-point dose-response slope (O'Connor). Weighted L1-regression was used to estimate reference equations for the 95(th ), 90(th ), 75(th )and 50(th )percentiles of the two-point slope. RESULTS: Reference equations for the 95(th ), 90(th ), 75(th )and 50(th )percentiles of the two-point slope were estimated using a model of the form a + b* Age + c* FEV(1 )+ d* (FEV(1))(2 ), where FEV(1 )corresponds to the pre-test (or baseline) level of FEV(1). For the central half of the FEV(1 )distribution, we used a quadratic model to describe the dependence of methacholine slope on baseline FEV(1). For the first and last quartiles of FEV(1), a linear relation with FEV(1 )was assumed (i.e., d was set to 0). Sex was not a predictor term in this model. A negative linear association with slope was found for age. We provide an Excel file allowing calculation of the percentile of methacholine slope of a subject after introducing age – pre-test FEV(1 )– and results of methacholine challenge of the subject. CONCLUSION: The present study provides equations for four relevant percentiles of methacholine two-point slope depending on age and baseline FEV(1 )as basic predictors in an adult reference population of non-obstructive and non-atopic persons. These equations may help clinicians and epidemiologists to better characterize individual or population airway responsiveness

Distinguishing Asthma Phenotypes Using Machine Learning Approaches.

Asthma is not a single disease, but an umbrella term for a number of distinct diseases, each of which are caused by a distinct underlying pathophysiological mechanism. These discrete disease entities are often labelled as asthma endotypes. The discovery of different asthma subtypes has moved from subjective approaches in which putative phenotypes are assigned by experts to data-driven ones which incorporate machine learning. This review focuses on the methodological developments of one such machine learning technique-latent class analysis-and how it has contributed to distinguishing asthma and wheezing subtypes in childhood. It also gives a clinical perspective, presenting the findings of studies from the past 5 years that used this approach. The identification of true asthma endotypes may be a crucial step towards understanding their distinct pathophysiological mechanisms, which could ultimately lead to more precise prevention strategies, identification of novel therapeutic targets and the development of effective personalized therapies

The drivers of tropical speciation

© 2014 Macmillan Publishers Limited. All rights reserved. Since the recognition that allopatric speciation can be induced by large-scale reconfigurations of the landscape that isolate formerly continuous populations, such as the separation of continents by plate tectonics, the uplift of mountains or the formation of large rivers, landscape change has been viewed as a primary driver of biological diversification. This process is referred to in biogeography as vicariance. In the most species-rich region of the world, the Neotropics, the sundering of populations associated with the Andean uplift is ascribed this principal role in speciation. An alternative model posits that rather than being directly linked to landscape change, allopatric speciation is initiated to a greater extent by dispersal events, with the principal drivers of speciation being organism-specific abilities to persist and disperse in the landscape. Landscape change is not a necessity for speciation in this model. Here we show that spatial and temporal patterns of genetic differentiation in Neotropical birds are highly discordant across lineages and are not reconcilable with a model linking speciation solely to landscape change. Instead, the strongest predictors of speciation are the amount of time a lineage has persisted in the landscape and the ability of birds to move through the landscape matrix. These results, augmented by the observation that most species-level diversity originated after episodes of major Andean uplift in the Neogene period, suggest that dispersal and differentiation on a matrix previously shaped by large-scale landscape events was a major driver of avian speciation in lowland Neotropical rainforests

The relation between paracetamol use and asthma:a GA2LEN European case-control study

Studies from the UK and USA suggest that frequent use of paracetamol (acetaminophen) may increase the risk of asthma, but data across Europe are lacking. As part of a multicentric case-control study organised by the Global Allergy and Asthma European Network (GA(2)LEN), it was examined whether or not frequent paracetamol use is associated with adult asthma across Europe. The network compared 521 cases with a diagnosis of asthma and reporting of asthma symptoms within the last 12 months with 507 controls with no diagnosis of asthma and no asthmatic symptoms within the last 12 months across 12 European centres. All cases and controls were selected from the same population, defined by age (2045 yrs) and place of residence. In a random effects meta-analysis, weekly use of paracetamol, compared with less frequent use, was strongly positively associated with asthma after controlling for confounders. There was no evidence for heterogeneity across centres. No association was seen between use of other analgesics and asthma. These data add to the increasing and consistent epidemiological evidence implicating frequent paracetamol use in asthma in diverse populations

Study on Occupational Allergy Risks (SOLAR II) in Germany: Design and methods

<p>Abstract</p> <p>Background</p> <p>SOLAR II is the 2^ndfollow-up of a population-based cohort study that follows the participants of ISAAC Phase Two recruited in Munich and Dresden in 1995/6. A first follow-up study was conducted 2002 and 2003 (SOLAR I). The aims of SOLAR II were to investigate the course of atopic diseases over puberty taking environmental and occupational risk factors into account. This paper describes the methods of the 2^ndfollow-up carried out from 2007 to 2009 and the challenges we faced while studying a population-based cohort of young adults.</p> <p>Methods</p> <p>Wherever possible, the same questionnaire instruments were used throughout the studies. They included questions on respiratory and allergic diseases, domestic and occupational exposure and work related stress. Furthermore, clinical examinations including skin prick tests, spirometry and bronchial challenge with methacholine, exhaled nitric oxide (FeNO) and blood samples were employed at baseline and 2^ndfollow-up. As information from three studies was available, multiple imputation could be used to handle missing data.</p> <p>Results</p> <p>Of the 3053 SOLAR I study participants who had agreed to be contacted again, about 50% had moved in the meantime and had to be traced using phone directories and the German population registries. Overall, 2904 of these participants could be contacted on average five years after the first follow-up. From this group, 2051 subjects (71%) completed the questionnaire they received via mail. Of these, 57% participated at least in some parts of the clinical examinations. Challenges faced included the high mobility of this age group. Time constraints and limited interest in the study were substantial. Analysing the results, selection bias had to be considered as questionnaire responders (54%) and those participating in the clinical part of the study (63%) were more likely to have a high parental level of education compared to non-participants (42%). Similarly, a higher prevalence of parental atopy (e.g. allergic rhinitis) at baseline was found for participants in the questionnaire part (22%) and those participating in the clinical part of the study (27%) compared to non-participants (11%).</p> <p>Conclusions</p> <p>In conclusion, a 12-year follow-up from childhood to adulthood is feasible resulting in a response of 32% of the baseline population. However, our experience shows that researchers need to allocate more time to the field work when studying young adults compared to other populations.</p

A Manifesto Concerning the Legal Protection of Computer Programs

Rationale: There is conflicting evidence on whether patients with asthma experience an accelerated decline in lung function with age. We examined the association between postbronchodilator lung function, asthma, chronic rhinosinusitis (CRS), and atopy with age using a large European sample. Methods: In 17 centers in 11 European countries, case control studies were nested within representative cross-sectional surveys of adults aged less than 75 years. Representative samples of participants with asthma, CRS or both and controls were assessed for postbronchodilator ventilatory function, smoking history, atopy, and treatment. Multiple regression was used to assess the interactive effects of age and diagnostic group on decline in postbronchodilator ventilatory function. Results: A total of 3337 participants provided adequate data (778 with asthma, 399 with CRS, 244 with both asthma and CRS and 1916 controls who had neither asthma nor CRS). Participants with asthma had lower FEV1/FVC (-4.09% (95% CI: -5.02, -3.15, P &lt; 0.001) and a steeper slope of FEV1/FVC against age (-0.14%/annum [95%CI: -0.19, -0.08]) equivalent to smoking 1-2 packs of cigarettes per day. Those with atopy had a slope equivalent to controls. Conclusions: People with asthma have a steeper decline in postbronchodilator lung function with age, but neither CRS nor atopy alone were associated with such decline

A multivariate analysis of serum nutrient levels and lung function

<p>Abstract</p> <p>Background</p> <p>There is mounting evidence that estimates of intakes of a range of dietary nutrients are related to both lung function level and rate of decline, but far less evidence on the relation between lung function and objective measures of serum levels of individual nutrients. The aim of this study was to conduct a comprehensive examination of the independent associations of a wide range of serum markers of nutritional status with lung function, measured as the one-second forced expiratory volume (FEV₁).</p> <p>Methods</p> <p>Using data from the Third National Health and Nutrition Examination Survey, a US population-based cross-sectional study, we investigated the relation between 21 serum markers of potentially relevant nutrients and FEV₁, with adjustment for potential confounding factors. Systematic approaches were used to guide the analysis.</p> <p>Results</p> <p>In a mutually adjusted model, higher serum levels of antioxidant vitamins (vitamin A, beta-cryptoxanthin, vitamin C, vitamin E), selenium, normalized calcium, chloride, and iron were independently associated with higher levels of FEV₁. Higher concentrations of potassium and sodium were associated with lower FEV₁.</p> <p>Conclusion</p> <p>Maintaining higher serum concentrations of dietary antioxidant vitamins and selenium is potentially beneficial to lung health. In addition other novel associations found in this study merit further investigation.</p

A comparision of GHG emissions from UK field crop production under selected arable systems with reference to disease control

Crop disease not only threatens global food security by reducing crop production at a time of growing demand, but also contributes to greenhouse gas (GHG) emissions by reducing efficiency of N fertiliser use and farm operations and by driving land use change. GHG emissions associated with adoption of reduced tillage, organic and integrated systems of field crop production across the UK and selected regions are compared with emissions from conventional arable farming to assess their potential for climate change mitigation. The reduced tillage system demonstrated a modest (<20%) reduction in emissions in all cases, although in practice it may not be suitable for all soils and it is likely to cause problems with control of diseases spread on crop debris. There were substantial increases in GHG emissions associated with the organic and integrated systems at national level, principally due to soil organic carbon losses from land use change. At a regional level the integrated system shows the potential to deliver significant emission reductions. These results indicate that the conventional crop production system, coupled to reduced tillage cultivation where appropriate, is generally the best for producing high yields to minimise greenhouse gas emissions and contribute to global food security, although there may be scope for use of the integrated system on a regional basis. The control of crop disease will continue to have an essential role in both maintaining productivity and decreasing GHG emissions.Peer reviewe

Inducible Nitric Oxide Synthase (iNOS) and Nitric Oxide (NO) are Important Mediators of Reflux-induced Cell Signalling in Esophageal Cells

Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) has been implicated in both DNA damage induction and aberrant cell signalling in various tissue and cell backgrounds. We investigated here the role of iNOS and NO in DNA damage induction and nuclear factor-kappa B (NF-κB) signalling in esophageal cells in vitro. As esophageal adenocarcinoma develops in a background of Barrett’s esophagus secondary to reflux disease, it is possible that inflammatory mediators like NO may be important in esophageal cancer development. We show that reflux components like stomach acid and bile acids [deoxycholic acid (DCA)] can induce iNOS gene and protein expression and produce NO generation in esophageal cells, using real-time PCR, western blotting and NO sensitive fluorescent probes, respectively. This up-regulation of iNOS expression was not dependent on NF-κB activity. DCA-induced DNA damage was independent of NF-κB and only partially dependent on iNOS and NO, as measured by the micronucleus assay. These same reflux constituents also activated the oncogenic transcription factor NF-κB, as measured by transcription factor enzyme-linked immunosorbent assay and gene expression studies with NF-κB linked genes (e.g. interleukin-8). Importantly, we show here for the first time that basal levels of NF-κB activity (and possibly acid and DCA-induced NF-κB) are dependent on iNOS/NO and this may lead to a positive feedback loop whereby induced iNOS is upstream of NF-κB, hence prolonging and potentially amplifying this signalling, presumably through NO activation of NF-κB. Furthermore, we confirm increased protein levels of iNOS in esophageal adenocarcinoma and, therefore, in neoplastic development in the esophagus