Antigenic Proteins Involved in Occupational Rhinitis 1 and Asthma Caused by Obeche Wood (Triplochiton Scleroxylon)

Background Obeche wood dust is a known cause of occupational asthma where an IgE-mediated mechanism has been demonstrated. Objective To characterize the allergenic profile of obeche wood dust and evaluate the reactivity of the proteins by in vitro, ex vivo and in vivo assays in carpenters with confirmed rhinitis and/or asthma Materials and methods An in-house obeche extract was obtained, and two IgE binding bands were purified (24 and 12 kDa) and sequenced by N-terminal identity. Specific IgE and IgG, basophil activation tests and skin prick tests (SPTs) were performed with whole extract and purified proteins. CCD binding was analyzed by ELISA inhibition studies. Results Sixty-two subjects participated: 12 with confirmed occupational asthma/rhinitis (ORA+), 40 asymptomatic exposed (ORA−), and 10 controls. Of the confirmed subjects, 83% had a positive SPT to obeche. There was a 100% recognition by ELISA in symptomatic subjects vs. 30% and 10% in asymptomatic exposed subjects and controls respectively (p<0.05). Two new proteins were purified, a 24 kDa protein identified as a putative thaumatin-like protein and a 12 kDa gamma-expansin. Both showed allergenic activity in vitro, with the putative thaumatin being the most active, with 92% recognition by ELISA and 100% by basophil activation test in ORA+ subjects. Cross-reactivity due to CCD was ruled out in 82% of cases. Conclusions Two proteins of obeche wood were identified and were recognized by a high percentage of symptomatic subjects and by a small proportion of asymptomatic exposed subjects. Further studies are required to evaluate cross reactivity with other plant allergens.

The effects of storage duration, temperature and cultivar on the severity of garlic clove rot caused by Fusarium proliferatum.

Diseases that affect garlic during storage can lead to severe economic losses for farmers worldwide. One causal agent of clove rot is Fusarium proliferatum. Here, the progress of clove rot caused by F. proliferatum and its dependence on different storage conditions and cultivar type were studied. The effect of temperature on mycelial growth, conidial viability, and fungal survival during garlic commercial storage was documented. Samples of 50 bulbs from a randomized field trial with three different clonal generations for purple garlic (F3, F4 and F5) and the F4 clonal generation for white garlic were labeled and stored for two months (short-term storage). In addition, another sample of the F5 clonal generation of purple garlic was stored for 6 months after harvest (long-term storage). The presence of the pathogen and the percentage of symptomatic cloves were evaluated. A notable difference in the rot severity index (RSI) of different garlic varieties was observed. In all studied cases, clove rot increased with storage time at 20 ◦ C, and the white garlic variety had a higher index of rot severity after two months of storage. Additionally, there were clear differences between the growth rates of F. proliferatum isolates. Studies conducted on the temperature responses of the pathogen propagules showed that expo- sure for at least 20 min at 50 ◦ C was highly effective in significantly reducing the viability of fungal conidia. Pathogenicity studies showed that the fungus is pathogenic in all commercial varieties. However, there were significant differences in varietal susceptibility between Chinese and white garlic type cultivars (81.84 ± 16.44% and 87.5 ± 23.19% symptomatic cloves, respectively) and purple cultivars (49.06 ± 13.42% symptomatic cloves)

Diagnosis and Management of Grain-Induced Asthma

Grain-induced asthma is a frequent occupational allergic disease mainly caused by inhalation of cereal flour or powder. The main professions affected are bakers, confectioners, pastry factory workers, millers, farmers, and cereal handlers. This disorder is usually due to an IgE-mediated allergic response to inhalation of cereal flour proteins. The major causative allergens of grain-related asthma are proteins derived from wheat, rye and barley flour, although baking additives, such as fungal α-amylase are also important. This review deals with the current diagnosis and treatment of grain-induced asthma, emphasizing the role of cereal allergens as molecular tools to enhance diagnosis and management of this disorder. Asthma-like symptoms caused by endotoxin exposure among grain workers are beyond the scope of this review. Progress is being made in the characterization of grain and bakery allergens, particularly cereal-derived allergens, as well as in the standardization of allergy tests. Salt-soluble proteins (albumins plus globulins), particularly members of the α-amylase/trypsin inhibitor family, thioredoxins, peroxidase, lipid transfer protein and other soluble enzymes show the strongest IgE reactivities in wheat flour. In addition, prolamins (not extractable by salt solutions) have also been claimed as potential allergens. However, the large variability of IgE-binding patterns of cereal proteins among patients with grain-induced asthma, together with the great differences in the concentrations of potential allergens observed in commercial cereal extracts used for diagnosis, highlight the necessity to standardize and improve the diagnostic tools. Removal from exposure to the offending agents is the cornerstone of the management of grain-induced asthma. The availability of purified allergens should be very helpful for a more refined diagnosis, and new immunomodulatory treatments, including allergen immunotherapy and biological drugs, should aid in the management of patients with this disorder.

Component-resolved diagnosis of wheat flour allergy in baker's asthma.

Baker's asthma is one of the most common types of occupational asthma and its prevalence is increasing in the last years. Diagnosis of occupational asthma is complex. The poor specificity of current diagnostic approaches may be associated with insufficient purity of wheat extracts or lack of inclusion of major allergens in them. In this work, we use microarray technology to characterize the allergenic profiles of baker's asthma patients from three regions in Spain and to analyze the influence of other environmental allergens on the sensitization pattern.

Characteristics of patients making serious inhaler errors with a dry powder inhaler and association with asthma-related events in a primary care setting

Acknowledgements The iHARP database was funded by unrestricted grants from Mundipharma International Ltd and Research in Real-Life Ltd; these analyses were funded by an unrestricted grant from Teva Pharmaceuticals. Mundipharma and Teva played no role in study conduct or analysis and did not modify or approve the manuscript. The authors wish to direct a special appreciation to all the participants of the iHARP group who contributed data to this study and to Mundipharma, sponsors of the iHARP group. In addition, we thank Julie von Ziegenweidt for assistance with data extraction and Anna Gilchrist and Valerie L. Ashton, PhD, for editorial assistance. Elizabeth V. Hillyer, DVM, provided editorial and writing support, funded by Research in Real-Life, Ltd.

Impacts of coexisting bronchial asthma on severe exacerbations in mild-to-moderate COPD : results from a national database

Acknowledgments The authors would like to thank Kyungjoo Kim for the confident statistical analyses in this work. This study was supported by a grant (2014P3300300) from the Korea Centers for Disease Control and Prevention. The abstract of this paper was presented at the Asian Pacific Society of Respirology 20th Congress as an oral presentation with interim findings. The poster’s abstract was published in “Poster Abstracts” in Respirology

Effectiveness of initiating extrafine-particle versus fine-particle inhaled corticosteroids as asthma therapy in the Netherlands

Acknowledgements Gokul Gopalan (a Senior Global Medical Director [Respiratory], at Teva Pharmaceuticals, Frazer, PA, US, at the time of this study), assisted with study design. Funding Funds to acquire the dataset from the Pharmo Institute for Drug Outcomes Research (Utrecht, the Netherlands) were provided by RiRL. The study received institutional support from Teva Pharmaceuticals Europe B.V. Gokul Gopalan, a Senior Global Medical Director (Respiratory), at Teva Pharmaceuticals, Frazer, PA, US, at the time of this study, assisted with study design, but neither Teva Pharmaceuticals Europe B.V. nor Teva Pharmaceuticals, Frazer, PA, US, contributed, either in part or in whole, to the collection, analysis, or interpretation of study data, manuscript writing, or the decision to submit the manuscript for publication. Erratum The original version of this article unfortunately contained errors that have since been corrected. The word “pharmo” has been fully capitalised to “PHARMO” throughout the article. The reference to Table 2 in the first and second sentence under the Outcomes heading has been replaced with Fig. 3. Under the Abbreviations heading ‘extrafine-particle’ was repeated, this has been corrected to ‘EF-HFA-BDP [Qvar®]: extrafine-particle hydrofluoroalkane beclomethasone dipropionate’. The competing interests of Nicolas Roche and Theresa Guibert have been amended. Academic affiliations for Dirkje S. Postma (2), Richard J. Martin (3), Ron M.C. Herrings (4), Jetty Overbeek (4), and Nicolas Roche (7) have been corrected. Figure 3 in the online and pdf version did not match, this been amended

Determinants and impact of suboptimal asthma control in Europe : The INTERNATIONAL CROSS-SECTIONAL AND LONGITUDINAL ASSESSMENT ON ASTHMA CONTROL (LIAISON) study

Acknowledgements We are grateful to THERAmetrics for the study management, data collection and analysis. The authors would like to thank the following investigators for their contribution (>30 patients enrolled): F. Fohler, A.G. Haider, J. Hesse-Tonsa, J. Messner, W. Pohl (Austria); G. Joos, J.L. Halloy, R. Peche, H. Simonis, P. Van den Brande (Belgium); B. Bugnas, J.M. Chavaillon, P. Debove, S. Dury, L. Mathieu, O. Lagrange, A. Prudhomme, S. Verdier (France); A. Benedix, O. Kestermann, A. Deimling, G. Eckhardt, M. Gernhold, V. Grimm-Sachs, M. Hoefer, G. Hoheisel, C. Stolpe, C. Schilder, M. John, J. Uerscheln, K.H. Zeisler (Germany); A. Chaniotou, P. Demertzis, V. Filaditaki-Loverdou, A. Gaga, E. Georgatou-Papageorgiou, S. Michailidis, G. Pavkalou, M. Toumpis (Greece); K. Csicsari, K. Hajdu, M. Póczi, M. Kukuly, T. Kecskes, C. Hangonyi, J. Schlezak, E. Takács, M. Szabo,G. Szabó, C. Szabo (Hungary); G.W. Canonica, W. Castellani, A. Cirillo, M.P. Foschino Barbaro, M. Gjomarkaj, G. Guerra, G. Idotta, D. Legnani, M. Lo Schiavo, R. Maselli, F. Mazza, S. Nutini, P. Paggiaro, A. Pietra, O. Resta, S. Salis, N.A. Scichilone, M.C. Zappa, A. Zedda (Italy); M. Goosens, R. Heller, K. Mansour, C. Meek, J. van den Berg (The Netherlands); A. Antczak, M. Faber, D. Madra-Rogacka, G. Mincewicz, M. Michnar, D. Olejniczak, G. Pulka, Z. Sankowski, K. Kowal, I. Krupa-Borek, B. Kubicka Kozik, K. Kuczynska, P. Kuna, A. Kwasniewski, M. Wozniak (Poland); F. Casas Maldonado, C. Cisneros, J. de Miguel Díez, L.M. Entrenas Costa, B. Garcìa-Cosio, M.V. Gonzales, L. Lores, M. Luengo, C. Martinez, C. Melero, I. Mir, X. Munoz, A. Pacheco, V. Plaza, J. Serra, J. Serrano, J.G. Soto Campos (Spain); T. Bekci, R. Demir, N. Dursunoglu, D. Ediger, A. Ekici, O. Goksel, H. Gunen, I.K. Oguzulgen, Z.F. Ozseker, (Turkey); L. Barnes, T. Hall, S. Montgomerie, J. Purohit, J. Ryan (United Kingdom). The authors would also like to thank P. Galletti (THERAMetrics S.p.A., Sesto San Giovanni, Italy) and K. Stockmeyer (THERAMetrics GmbH, Essen, Germany) for providing editorial assistance in the preparation of this manuscript. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Are pharmacological randomised controlled clinical trials relevant to real-life asthma populations? : A protocol for an UNLOCK study from the IPCRG

Funding The IPCRG provided funding for this research project as an UNLOCK Group study for which the funding was obtained through an unrestricted grant by Novartis AG, Basel, Switzerland. Novartis has no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. This study will include data from the Optimum Patient Care Research Database and is undertaken in collaboration with Optimum Patient Care and the Respiratory Effectiveness Group.

Insights, attitudes, and perceptions about asthma and its treatment : a multinational survey of patients from Europe and Canada

Acknowledgments Editorial assistance was provided by Ken Kauffman and Patricia Abramo, Adelphi Communications, New York, NY. This assistance was funded by Merck & Co., Inc.

Interleukin 9: A candidate gene for asthma

Asthma is a complex heritable inflammatory disorder of the airways associated with clinical signs of atopy and bronchial hyperresponsiveness. Recent studies localized a major gene for asthma to chromosome 5q31-q33 in humans. Thus, this segment of the genome represents a candidate region for genes that determine susceptibility to bronchial hyperresponsiveness and atopy in animal models. Homologs of candidate genes on human chromosome 5q31-q33 are found in four regions in the mouse genome, two on chromosome 18, and one each on chromosomes 11 and 13. We assessed bronchial responsiveness as a quantitative trait in mice and found it linked to chromosome 13. Interleukin 9 (IL-9) is located in the linked region and was analyzed as a gene candidate. The expression of IL-9 was markedly reduced in bronchial hyporesponsive mice, and the level of expression was determined by sequences within the qualitative trait locus (QTL). These data suggest a role for IL-9 in the complex pathogenesis of bronchial hyperresponsiveness as a risk factor for asthma.

Gene dosage and stochastic effects determine the severity and direction of uniparental ribosomal RNA gene silencing (nucleolar dominance) in Arabidopsis allopolyploids

Nucleolar dominance is an epigenetic phenomenon in which one parental set of ribosomal RNA (rRNA) genes is silenced in an interspecific hybrid. In natural Arabidopsis suecica, an allotetraploid (amphidiploid) hybrid of Arabidopsis thaliana and Cardaminopsis arenosa, the A. thaliana rRNA genes are repressed. Interestingly, A. thaliana rRNA gene silencing is variable in synthetic Arabidopsis suecica F1 hybrids. Two generations are needed for A. thaliana rRNA genes to be silenced in all lines, revealing a species-biased direction but stochastic onset to nucleolar dominance. Backcrossing synthetic A. suecica to tetraploid A. thaliana yielded progeny with active A. thaliana rRNA genes and, in some cases, silenced C. arenosa rRNA genes, showing that the direction of dominance can be switched. The hypothesis that naturally dominant rRNA genes have a superior binding affinity for a limiting transcription factor is inconsistent with dominance switching. Inactivation of a species-specific transcription factor is argued against by showing that A. thaliana and C. arenosa rRNA genes can be expressed transiently in the other species. Transfected A. thaliana genes are also active in A. suecica protoplasts in which chromosomal A. thaliana genes are repressed. Collectively, these data suggest that nucleolar dominance is a chromosomal phenomenon that results in coordinate or cooperative silencing of rRNA genes.

A normal β-globin allele as a modifier gene ameliorating the severity of α-thalassemia in mice

Thalassemia is a heritable human anemia caused by a variety of mutations that affect expression of the α- or the β-chain of hemoglobin. The expressivity of the phenotype is likely to be influenced by unlinked modifying genes. Indeed, by using a mouse model of α-thalassemia, we find that its phenotype is strongly influenced by the genetic background in which the α-thalassemia mutation resides [129sv/ev/129sv/ev (severe) or 129sv/ev/C57BL/6 (mild)]. Linkage mapping indicates that the modifying gene is very tightly linked to the β-globin locus (Lod score = 13.3). Furthermore, the severity of the phenotype correlates with the size of β-chain-containing inclusion bodies that accumulate in red blood cells and likely accelerate their destruction. The β-major globin chains encoded by the two strains differ by three amino acids, one of which is a glycine-to-cysteine substitution at position 13. The Cys-13 should be available for interchain disulfide bridging and consequent aggregation between excess β-chains. This normal polymorphic variation between murine β-globin chains could account for the modifying action of the unlinked β-globin locus. Here, the variation in severity of the phenotype would not depend on a change in the ratio between α- and β-chains but on the chemical nature of the normal β-chain, which is in excess. This work also indicates that modifying genes can be normal variants that—absent an apparent physiologic rationale—may be difficult to identify on the basis of structure alone.