Search

Background In about 5% of patients with hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) no mutation in the SERPING1 gene is detected. Methods C1-INH-HAE cases with no mutation in the coding region of SERPING1 after conventional genotyping were examined for defects in the intronic or untranslated regions of the gene. Using a next-generation sequencing (NGS) platform targeting the entire SERPING1, 14 unrelated C1-INH-HAE patients with no detectable mutations in the coding region of the gene were sequenced. Detected variants with a global minor allele frequency lower than the frequency of C1-INH-HAE (0.002%), were submitted to in silico analysis using ten different bioinformatics tools. Pedigree analysis and examination of their pathogenic effect on the RNA level were performed for filtered in variants. Results In two unrelated patients, the novel mutation c.-22-155G > T was detected in intron 1 of the SERPING1 gene by the use NGS and confirmed by Sanger sequencing. All bioinformatics tools predicted that the variant causes a deleterious effect on the gene and pedigree analysis showed its co-segregation with the disease. Degradation of the mutated allele was demonstrated by the loss of heterozygosity on the cDNA level. According to the American College of Medical Genetics and Genomics 2015 guidelines the c.-22-155G > T was curated as pathogenic. Conclusions For the first time, a deep intronic mutation that was detected by NGS in the SERPING1 gene, was proven pathogenic for C1-INH-HAE. Therefore, advanced DNA sequencing methods should be performed in cases of C1-INH-HAE where standard approaches fail to uncover the genetic alteration.

Hereditary angioedema (HAE) is becoming much more genetically complex than was initially considered. Thus, the role of HAE genetics is expanding beyond research laboratories, and the genotyping of subjects suffering from HAE has become diagnostically indispensable in clinical practice. The synthesis and interpretation of the clinical and biochemical analyses to facilitate appropriate genetic test selection has thus also become significantly more complex. With this in mind, an international multidisciplinary group of 14 experts in HAE genetics and disease management was convened in October 2018. The objective was to develop clear, actionable, evidence- and consensus-based statements aiming to facilitate the communication between physicians treating patients with HAE and clinical geneticists, and thus promote the effective use of genetics in the management of the disease. Eleven consensus statements were generated, encompassing considerations regarding the clinical indications for genotyping patients with angioedema, the methods of detection of HAE-causative variants, the variant pathogenicity curation, the genotyping of patients with HAE in the clinic, and genetic counseling. These statements are intended both to guide clinicians and to serve as a framework for future educational and further genetic testing developments as the field continues to evolve rapidly.

Background Pollen food allergy syndrome (PFAS) is a frequently underdiagnosed disease due to diverse triggers, clinical presentations, and test results. This is especially relevant in geographic areas with a broad spectrum of pollen sensitization, such as Southern Europe. Objectives To elucidate similarities and differences of PFAS in nine Southern European centers and identify associated characteristics and unique markers of PFAS. Methods As part of the @IT.2020 Multicenter Study, 815 patients with seasonal allergic rhinitis (SAR), aged 10-60 years, were recruited in seven countries. They completed questionnaires regarding SAR, comorbidities, family history, and PFAS, and underwent skin prick testing (SPT) and serum IgE testing. Results Of the 815 patients, 167 (20.5%) reported PFAS reactions. Most commonly, eliciting foods were kiwi (58, 34.7%), peach (43, 25.7%), and melon (26, 15.6%). Reported reactions were mostly local (216/319, 67.7%), occurring within 5 min of contact with elicitors (209/319, 65.5%). Associated characteristics included positive IgE to at least one panallergen (profilin, PR-10, or nsLTP) (p = 0.007), maternal PFAS (OR: 3.716, p = 0.026), and asthma (OR: 1.752, p = 0.073). Between centers, heterogeneity in prevalence (Marseille: 7.5% vs. Rome: 41.4%, p < 0.001) and of clinical characteristics was apparent. Cypress played a limited role, with only 1/22 SPT mono-sensitized patients reporting a food reaction (p < 0.073). Conclusions PFAS is a frequent comorbidity in Southern European SAR patients. Significant heterogeneity of clinical characteristics in PFAS patients among the centers was observed and may be related to the different pollen sensitization patterns in each geographic area. IgE to panallergen(s), maternal PFAS, and asthma could be PFAS-associated characteristics., EAACI Fellowship Award of the European Academy of Allergology and Clinical Immunology; Euroimmun [118583], SA was supported by the EAACI Fellowship Award of the European Academy of Allergology and Clinical Immunology. The study has been supported by an unrestricted grant from Euroimmun (grant number 118583). The ESEP assay has been provided by Euroimmun. The Informatics Platform AllergyCARD (TM) and the app AllergyMonitor (R) have been provided by TPS Production.

Previous data suggested the potential treatment effect of a proprietary quail eggs-based blend on allergic rhinitis (AR) symptoms, induced by allergen challenge. We herein aimed to investigate the efficacy and safety of a similar dietary supplement, comprising the bioactive ingredients of quail eggs and the zinc mineral, in the setting of active AR. Adult patients (

eMass project aims to digitalize the medical examination procedure of recruitment phase of conscripts in the Hellenic Navy. eMass integrates recruits' Electronic Health Record (EHR), while allows a pre-screening test, through portable telemedicine equipment. The data will be exploited to assess the individual's cardiovascular risk through appropriate digital tools and algorithms. The eMass digital platform, will be accessible to health experts involved in the recruitment procedure for further assessment and processing. Recruits' personal data is stored in the database encrypted using Advanced Encryption Standard (AES). eMass solution contributes to beneficial management and medical data analysis, preventing inessential physical or medical examinations minimizing danger of possible errors and reducing time-consuming processes. Moreover, eMass exploits Electronic Health Record data through a machine-learning based cardiovascular risk assessment tool.

Background The analysis of mobile health (mHealth) data has generated innovative insights into improving allergic rhinitis control, but additive information is needed. A cross-sectional real-world observational study was undertaken in 17 European countries during and outside the estimated pollen season. The aim was to collect novel information including the phenotypic characteristics of the users. Methods The Allergy Diary–MASK-air–mobile phone app, freely available via Google Play and App, was used to collect the data of daily visual analogue scales (VASs) for overall allergic symptoms and medication use. Fluticasone Furoate (FF), Mometasone Furoate (MF), Azelastine Fluticasone Proprionate combination (MPAzeFlu) and eight oral H1-antihistamines were studied. Phenotypic characteristics were recorded at entry. The ARIA severity score was derived from entry data. This was an a priori planned analysis. Results 9037 users filled in 70,286 days of VAS in 2016, 2017 and 2018. The ARIA severity score was lower outside than during the pollen season. Severity was similar for all treatment groups during the pollen season, and lower in the MPAzeFlu group outside the pollen season. Days with MPAzeFlu had lower VAS levels and a higher frequency of monotherapy than the other treatments during the season. Outside the season, days with MPAzeFlu also had a higher frequency of monotherapy. The number of reported days was significantly higher with MPAzeFlu during and outside the season than with MF, FF or oral H1-antihistamines. Conclusions This study shows that the overall efficacy of treatments is similar during and outside the pollen season and indicates that medications are similarly effective during the year.

The genetic alteration underlying the great majority of primary angioedema with normal C1 inhibitor (nl-C1-INH-HAE) cases remains unknown. To search for variants associated with nl-C1-INH-HAE, we genotyped 133 unrelated nl-C1-INH-HAE patients using a custom next-generation sequencing platform targeting 55 genes possibly involved in angioedema pathogenesis. Patients already diagnosed with F12 alterations as well as those with histaminergic acquired angioedema were excluded. A variant pathogenicity curation strategy was followed, including a comparison of the results with those of genotyping 169 patients with hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE), and only filtered-in variants were studied further. Among the examined nl-C1-INH-HAE patients, carriers of neither the ANGPT1 p.Ala119Ser nor the KNG1 p.Met379Lys variant were found, whereas the PLG p.Lys330Glu was detected in four (3%) unrelated probands (one homozygote). In total, 182 different variants were curated, 21 of which represented novel mutations. Although the frequency of variants per gene was comparable between nl-C1-INH-HAE and C1-INH-HAE, variants of the KNG1 and XPNPEP1 genes were detected only in nl-C1-INH-HAE patients (six and three, respectively). Twenty-seven filtered variants in 23 different genes were detected in nl-C1-INH-HAE more than once, whereas 69/133 nl-C1-INH-HAE patients had compound heterozygotes of filtered variants located in the same or different genes. Pedigree analysis was performed where feasible. Our results indicate the role that alterations in some genes, like KNG1, may play in disease pathogenesis, the complex trait that is possibly underlying in some cases, and the existence of hitherto unrecognized disease endotypes.

Background: In view of the large heterogeneity in the clinical presentation of hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE), great efforts are being made towards detecting measurable biological determinants of disease severity that can help to improve the management of the disease. Considering the central role that plasma kallikrein plays in bradykinin production, we investigated the contribution of the functional polymorphism KLKB1-428G/A to the disease phenotype. Methods: We studied 249 C1-INH-HAE patients from 114 European families, and we explored possible associations of C1-INH-HAE clinical features with carriage of KLKB1-428G/A, combined or not with that of the functional F12-46C/T polymorphism. Results: Carriers of the G allele of the KLKB1-428G/A polymorphism exhibited a significantly delayed disease onset (i.e., by 4.1 years [p < 0.001], depending on the zygocity status), while carriers of both the KLKB1-428G/A and the F12-46C/T polymorphism displayed an 8.8-year delay in disease onset (p < 0.001) and a 64% lower probability of needing long-term prophylactic treatment (p = 0.019). Conclusions: These findings support our initial hypothesis that functional alterations in genes of proteins involved in bradykinin metabolism and function affect the clinical phenotype and possibly contribute to the pathogenesis of C1-INH-HAE. Given that an earlier onset of symptoms is inversely correlated with the subsequent course of the disease and, eventually, the need for long-term prophylaxis, these polymorphisms may be helpful prognostic biomarkers of disease severity.

BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) causes swelling in the skin and upper airways and pain in the abdomen because of mucosal swelling. C1-INH-HAE is frequently misdiagnosed, leading to delays in diagnosis, inadequate treatment, and unnecessary procedures.OBJECTIVE: To evaluate the history of misdiagnosis in patients participating in the Icatibant Outcome Survey (IOS).METHODS: The IOS is an observational study in which safety and effectiveness of icatibant have been evaluated since 2009. As part of the IOS, patients record any misdiagnoses received before being diagnosed as having C1-INH-HAE.RESULTS: In January 2016, a total of 418 of 633 IOS patients with C1-INH-HAE type I or II had provided misdiagnosis data. Of these, 185 of 418 (44.3%) received 1 or more prior misdiagnoses. The most common misdiagnoses were allergic angioedema (103 of 185) and appendicitis (50 of 185). A variety of other misdiagnoses were reported, including a substantial number of gastrointestinal disorders (excluding appendicitis). Misdiagnosis rates were similar between males (41.1%) and females (46.5%) and between C1-INH-HAE type I (43.7%) and type II (51.6%). Patients with family members diagnosed as having C1-INH-HAE were significantly less likely to be misdiagnosed than patients without a family history (140 of 366 [41.7%] vs 38 of 58 [65.5%], respectively; P = .001). Patients with a prior misdiagnosis had longer median delay to C1-INH-HAE diagnosis (13.3 years) than patients without (1.7 years; P < .001).CONCLUSION: From this large database, approximately 50% of patients with C1-INH-HAE type I or II have previously had their conditions misdiagnosed, most commonly as allergic angioedema or appendicitis. Misdiagnosis results in marked delays in receiving the correct diagnosis, during which time patients cannot access effective, lifesaving treatment.TRIAL REGISTRATION: ClinicalTrials.gov: NCT01034969.

Demoly, Pascal/0000-0001-7827-7964; Chavannes, Niels/0000-0002-8607-9199; Basagana, Xavier/0000-0002-8457-1489; N.G., Papadopoulos/0000-0002-4448-3468; Almeida, Rute/0000-0001-7755-5002; Pereira, Ana Margarida/0000-0002-5468-0932; Gemicioglu, Bilun/0000-0001-5953-4881; Bedard, Annabelle/0000-0002-7842-8889; Anto, J M/0000-0002-4736-8529; Fonseca, Joao Almeida/0000-0002-0887-8796; Rodo, Xavier/0000-0003-4843-6180; stelmach, rafael/0000-0002-5132-1934; J, Garcia-Aymerich/0000-0002-7097-4586; orlando, valentina/0000-0002-8209-8878; Cardona, Victoria/0000-0003-2197-9767; yorgancioglu, arzu/0000-0002-4032-0944; Bindslev-Jensen, Carsten/0000-0002-8940-038X; VENTURA, Maria Teresa/0000-0002-2637-4583; O'Hehir, Robyn/0000-0002-3489-7595; Costa, Elisio/0000-0003-1158-1480; Malva, Joao/0000-0002-5438-4447; Pugin, Benoit/0000-0001-7132-9477; Psarros, Fotis/0000-0002-2928-150X; Kuna, Piotr/0000-0003-2401-0070 WOS:000473432800017 PubMed ID: 30951790 Background: Mobile health can be used to generate innovative insights into optimizing treatment to improve allergic rhinitis (AR) control. Objectives: A cross-sectional real-world observational study was undertaken in 22 countries to complement a pilot study and provide novel information on medication use, disease control, and work productivity in the everyday life of patients with AR. Methods: A mobile phone app (Allergy Diary, which is freely available on Google Play and Apple stores) was used to collect the data of daily visual analogue scale (VAS) scores for (1) overall allergic symptoms; (2) nasal, ocular, and asthma symptoms; (3) work; and (4) medication use by using a treatment scroll list including all allergy medications (prescribed and over-the-counter) customized for 22 countries. The 4 most common intranasal medications containing intranasal corticosteroids and 8 oral H-1-antihistamines were studied. Results: Nine thousand one hundred twenty-two users filled in 112,054 days of VASs in 2016 and 2017. Assessment of days was informative. Control of days with rhinitis differed between no (best control), single (good control for intranasal corticosteroid-treated days), or multiple (worst control) treatments. Users with the worst control increased the range of treatments being used. The same trend was found for asthma, eye symptoms, and work productivity. Differences between oral H-1-antihistamines were found. Conclusions: This study confirms the usefulness of the Allergy Diary in accessing and assessing behavior in patients with AR. This observational study using a very simple assessment tool (VAS) on a mobile phone had the potential to answer questions previously thought infeasible. Sanofi AventisSanofi-Aventis; GlaxoSmithKlineGlaxoSmithKline; North Portugal Regional Operational Programme; European Regional Development Fund (ERDF)European Union (EU); Mundipharm; Teva Pharma; AstraZenecaAstraZeneca; Boehringer IngelheimBoehringer Ingelheim; Chiesi; MEDA Pharma; Sao Paulo Research FoundationFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); NovartisNovartis; Chiesi, DBV Technologies; UCBUCB Pharma SA; SanofiSanofi-Aventis; Adamed; FAES, Berlin Chemie; ALK-Abello; Allergopharma, Allergy Therapeutics; ServierServier; ASIT biotech; Hulka; Leti and Stallergenes; Roxall, Atmos, Bionorica; ALK-Abello, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics; Biomay, Nuvo, Circassia; Novartis Pharma; Mundipharma; RocheRoche Holding; Erkko Foundation; Hal Allergy B. V.; Teva; Meda, Stallergenes; Cipla; Mundipharma, Mylan; Sanofi-AventisSanofi-Aventis P. Devillier reports personal fees from Sanofi Aventis, GlaxoSmithKline, AstraZeneca, Chiesi, Meda Pharma, and Menarini outside the submitted work. R. Almeida reports grants from Project NORTE-01-0145-FEDER-000016 (NanoSTIMA) by the North Portugal Regional Operational Programme (NORTE 2020) under the Portugal 2020 Partnership Agreement and through the European Regional Development Fund (ERDF) during the conduct of the study. A. Todo-Bom reports grants and personal fees from GlaxoSmithKline, Mundipharm, and Novartis; personal fees from Teva Pharma and AstraZeneca; and grants from Leti and Bial outside the submitted work. A. A. Cruz reports grants and personal fees from AstraZeneca; grants from GlaxoSmithKline; personal fees from Boehringer Ingelheim, Chiesi, Novartis, Eurofarma, MEDA Pharma, and Boston Scientific outside the submitted work. R. Stelmach reports grants from the Sao Paulo Research Foundation and MSD; grants and personal fees from Novartis, grants, personal fees, and nonfinancial support from AstraZeneca and Chiesi; and personal fees and nonfinancial support from Boehringer Ingelheim outside the submitted work. D. Larenas-Linnemann reports personal fees from Armstrong, AstraZeneca, Boehringer Ingelheim, Chiesi, DBV Technologies, Grunenthal, GlaxoSmithKline, MEDA, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, and UCB and grants from Sanofi, AstraZeneca, Novartis, UCB, GlaxoSmithKline, TEVA, Boehringer Ingelheim, and Chiesi outside the submitted work. V. Kvedariene has received payment for consultancy from GlaxoSmithKline and for lectures from StallergensGreer and Berlin-Chemie outside the submitted work. P. Kuna reports personal fees from Adamed, Boehringer Ingelheim, AstraZeneca, Chiesi, FAES, Berlin Chemie, Novartis, Polpharma, and Allergopharma outside the submitted work. R. Mosges reports personal fees from ALK-Abello, Allergopharma, Allergy Therapeutics, Hexal, Servier, Klosterfrau, Stada, UCB, and Friulchem; grants from ASIT biotech, Nuvo, Bayer, FAES, GlaxoSmithKline, MSD, Johnson & Johnson, Meda, Optima, Ursapharm, BitopAG, and Hulka; grants and personal fees from Bencard; grants from Leti and Stallergenes; grants, personal fees and nonfinancial support from Lofarma; nonfinancial support from Roxall, Atmos, Bionorica, Otonomy, and Ferrero; and personal fees and nonfinancial support from Novartis outside the submitted work. O. Pfaar reports grants and personal fees from ALK-Abello, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, and Lofarma; grants from Biomay, Nuvo, Circassia, and GlaxoSmithKline; and personal fees from Novartis Pharma, MEDA Pharma, Indoor Biotechnologies, and Pohl-Boskamp outside the submitted work. T. Haahtela reports personal fees from Mundipharma, Novartis, and Orion Pharma outside the submitted work. S. Toppila-Salmi reports other support from Biomedical Systems and Roche and grants from the Erkko Foundation outside the submitted work. N. G. Papadopoulos reports grants from Gerolymatos and personal fees from Hal Allergy B. V., Novartis Pharma AG, Menarini, Hal Allergy B. V., and Mylan outside the submitted work. S. Bosnic-Anticevich reports personal fees from Teva, Boehringer Ingelheim, Sanofi, GlaxoSmithKline, and AstraZeneca outside the submitted work. C. Bachert reports personal fees from Meda, Stallergenes, and ALK-Abello (speaker). I. J. Ansotegui reports personal fees from Hikma, Roxall, AstraZeneca, Menarini, UCB, Faes Farma, Sanofi, and Mundipharma outside the submitted work. D.; Wallace reports other from Mylan Pharmaceutical Company outside the submitted work being co-chair of the AAAAI/ACAAI Joint Task Force on Practice Parameters. J. Bousquet reports personal fees and other support from Chiesi, Cipla, Hikma, Menarini, Mundipharma, Mylan, Novartis, Sanofi-Aventis, Takeda, Teva, and Uriach outside the submitted work and other support from Kyomed. The rest of the authors declare that they have no relevant conflicts of interest.

The factors influencing the heterogeneous clinical manifestation of hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) represent one of the oldest unsolved problems of the disease. Considering that factor XII (FXII) levels may affect bradykinin production, we investigated the contribution of the functional promoter polymorphism F12-46C/T in disease phenotype. We studied 258 C1-INH-HAE patients from 113 European families, and we explored possible associations of F12-46C/T with clinical features and the SERPING1 mutational status. Given that our cohort consisted of related subjects, we implemented generalized estimating equations (GEEs), an extension of the generalized linear model accounting for the within-subject correlation. F12-46C/T carriers exhibited a significantly delayed disease onset (P

SERPING1 genotyping of subjects suspicious for hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) is important for clinical practice as well as for research reasons. Conventional approaches towards the detection of C1-INH-HAE-associated SERPING1 variants are cumbersome and time-demanding with many pitfalls. To take advantage of the benefits of next-generation sequencing (NGS) technology, we developed and validated a custom NGS platform that, by targeting the entire SERPING1 gene, facilitates genetic testing of C1-INH-HAE patients in clinical practice. In total, 135 different C1-INH-HAE-associated SERPING1 variants, out of the approximately 450 reported, along with 115 negative controls and 95 randomly selected DNA samples from affected family members of C1-INH-HAE index patients, were included in the forward and reverse validation processes of this platform. Our platform's performance, i.e. analytical sensitivity of 98.96%, a false negative rate of 1.05%, analytical specificity 100%, a false positive rate equal to zero, accuracy of 99.35%, and repeatability of 100% recommends its implementation as a first line approach for the genetic testing of C1-INH-HAE patients or as a confirmatory method. A noteworthy advantage of our platform is the concomitant detection of single nucleotide variants and copy number variations throughout the whole length of the SERPING1 gene, moreover providing information about the size and the localization of the latter. During our study, 15 novel C1-INH-HAE-related SERPING1 variants were detected.

Background Immune responses to rhinovirus (RV) as well as direct effects of RV on respiratory epithelium may contribute to the induction of asthma exacerbations. Objective To evaluate the effect of the environment resulting from an atopic immune response on RV-induced epithelial inflammation, replication and cytotoxicity. Methods Peripheral blood mononuclear cells (PBMC) from atopic asthmatic subjects and matched controls (12 pairs) were isolated and stimulated by RVs. Human bronchial epithelial (BEAS-2B) cells were infected with RV in the presence of conditioned media from RV-stimulated PBMC cultures. IL-6, IL-8, RANTES and TGF-beta1 levels were measured by ELISA, RV-induced cytotoxicity by a colorimetric method and RV titres on Ohio-HeLa cells. Results RV-induced epithelial production of IL-6, IL-8 and RANTES was significantly lower, while TGF-beta1 was higher when cells were exposed to conditioned media from atopic asthmatic subjects compared with those from normal controls. Exposure to the 'atopic' environment also resulted in elevated RV titres and increased RV-induced cytotoxicity. Conclusions Under the influence of an atopic environment, the epithelial inflammatory response to RV is down-regulated, associated with increased viral proliferation and augmented cell damage, while TGF is up-regulated. These changes may help explain the propensity of atopic asthmatic individuals to develop lower airway symptoms after respiratory infections and indicate a mechanism through which viral infections may promote airway remodelling.

Background: No published data presently exist concerning hereditary angioedema (HAE) in Greece. The aim of this study was to present the results from patients recorded by the Greek Hereditary Angioedema Registry over the last 3 years (July 2010 to June 2013). Methods: A systematic recording of HAE cases was undertaken following a physician awareness campaign and confirmation of diagnosis. A questionnaire was also used for the assessment of key parameters of the patients' disease-specific quality of life. Results: One hundred and sixteen patients from 41 non-related families were recorded. There were 33 (80.5%) families with type I HAE, 7 (17%) with type II HAE and 1 (2.5%) with non-C1 inhibitor (C1-INH), non-FXII HAE. Two further non-C1-INH, non-FXII HAE sporadic cases were recorded. An investigation of non-symptomatic family members revealed another 6 asymptomatic individuals with C1-INH deficiency. The average delay in diagnosis was 16.5 years and the incidence of death in the families of patients was 1 for every 2 families. The use of newer therapeutic agents seems to fall significantly short of the existing needs. HAE was found to affect the quality of life slightly in 14%, greatly in 63% and significantly in 23% of the patients. Conclusion: Until recently, there has been a significant degree of underdiagnosis of HAE in Greece. Very low compliance with the provisions of the applicable international guidelines and consensus positions, with adverse consequences on the patients' quality of life, was also observed. The centralized model we used to uncover the patients could be effective in other countries presenting with comparable disease characteristics. © 2014 S. Karger AG, Basel

Background: Respiratory viruses are the most frequent triggers of acute asthma exacerbations. Herein we investigate costimulatory molecule expression on peripheral blood mononuclear cells (PBMC) during such exacerbations. Methods: Eleven children with atopic asthma were followed prospectively and respiratory symptoms were recorded on diary cards. A blood sample and nasopharyngeal wash (NPW) were obtained at baseline and subsequently during an exacerbation. PBMC were immunophenotyped using flow cytometry. NPW samples were examined for the presence of respiratory viruses by RT-PCR. Results: A virus was detected in 73% of exacerbations and none at baseline. A drop of NK cells and a marginal increase of monocytes were the only changes of cell count during the exacerbation. A significant downregulation of B7-2 on NK cells and of B7-1 on monocytes was also observed during exacerbations. Conclusions: The above observations are in contrast to in vitro findings showing an upregulation of costimulatory molecules after exposure of blood cells to viruses or allergens. It is possible that activated immune cells leave the blood stream to migrate to the inflammation site during acute asthma exacerbations.

Background The relationship between inflammation, air obstruction and lung cancer is complex and there is still great uncertainty regarding their underlying pathophysiology. Our aim was to investigate the inflammation pathways that are implicated in both chronic obstructive pulmonary disease (COPD) and lung cancer. Methods A literature search was performed in PubMed to identify relative studies published until June 2011. Results The pathophysiology of both COPD and lung cancer includes dysregulation of the inflammation process, but the cascade of signaling events is not yet fully understood. Both lung cancer and COPD are associated with cigarette smoking that induces a chronic inflammatory state in the lung by generating reactive oxidant species. It is considered that shared inflammatory pathways involve genetic and epigenetic changes due to chronic tissue injury and abnormal tumor immunity in susceptible hosts. The proposed role of chronic inflammation is based on the 2-stage model of carcinogenesis. According to this model, genotoxic injury is crucial in tumorigenesis, followed by promotional events that result in clonal growth of modulated cells. Research has shown that chronic inflammation creates the necessary environment for the development of lung cancer, acting as a tumor promoter. This environment, in combination with cigarette smoke, induces the upregulation of mediators of the inflammatory response, such as cyclooxygenase-2. This leads to the production of inflammatory cytokines through lymphocytes, such as IL-1, IL-6, IL-8 and IL-10, as well as to the increased formation of chemotactic factors. Some of the latter mediators may suppress cell mediated immune response and promote angiogenesis. They also impact cell growth, resulting in the inhibition of apoptosis. Inflammatory factors promote oxidative stress, contribute to the generation of reactive oxygen, and cause oxidative DNA base modification. COX-2 also plays an important role in promoting epithelial-to-mesenchymal transition, present in both lung cancer and COPD. Thus, chronic inflammation plays a pathogenic role in lung cancer by inducing preneoplastic mutations and cellular damage. Conclusions Additional research is required to understand the cellular and molecular mechanisms that link COPD and lung cancer, in an effort to discover new methods of prevention and treatment.

Background Chest radiation is a common therapeutic approach in the management of lung cancer, as well as in other malignancies, rendering radiation-induced pneumonitis a rather commonly reported adverse event. A large proportion of patients undergoing radiation have underlying chronic obstructive pulmonary disease (COPD). We aim to elucidate the pathogenetic pathways implicated in radiation-induced pneumonitis particularly in this subgroup of patients. Methods A literature search was performed in PubMed to identify relative studies published until June 2011. Results The incidence of radiation-induced pneumonitis after conventional irradiation in COPD is about 7 to 10% in the moderate although symptomatic forms and about 1 to 3% in the severe forms. Radiation-induced pneumonitis seems to be an acute-phase reaction, taking primarily place in the most radiosensitive subunit of the lung, the alveolar/capillary complex. Reactive oxygen species, generated by radiation, initiate a cascade of molecular events that alter the cytokine milieu of the microenvironment, creating inflammation and chronic oxidative stress. COPD is characterized by a chronic inflammatory state in the lung, also generating reactive oxidant species. Biological markers intrinsic to the patient, such as early variations of certain cytokines (IL-6, IL-10, TGF-β) seem to be implicated and studies are under way to determine their role. The standard dose-volume metrics, such as V20, V13 and mean lung dose, are major factors influencing the clinical course of radiation-induced pneumonitis. Conclusions Understanding the underlying pathogenesis of radiation-induced pneumonitis may help improve optimal delivery of treatment plans, minimize the risks and increasing the therapeutic ratio in patients with COPD.

Background Lung resection is still the only potentially curative therapy for patients with localised non-small lung cancer (NSCLC). However, the presence of cardiovascular comorbities and pulmonary function impairment increase the risk of perioperative death and postoperative complications. Various studies have evaluated the use of different preoperative tests aiming to identify asthma patients at greater risk for complications. Methods A literature search was performed in Pubmed to identify relative studies published until June 2011. Results Postoperative complications are associated with prolonged hospital stays and excessive morbidity and mortality especially in this group of patients. According to the ACCP/BTS guidelines, patients without known underlying lung disease with a preoperative FEV1 in excess of 2 L, generally tolerate pneumonectomy whereas those with FEV1 greater that 1.5 L, tolerate lobectomy. Although spirometric values strongly correlate with the severity of obstruction, they do not provide direct information regarding the degree of gas exchange impairment or the status of cardiovascular function. Cardiopulmonary exercise testing (CPET) is a preoperative test suggested before lung resection in patients with known underlying cardiovascular or lung disease. It is based on the interactions among pulmonary function, cardiovascular function and oxygen absorption from the peripheral tissues. Patients with maximal oxygen consumption (VO2 max)

Background Lung cancer remains the leading cause of cancer-related deaths among men and women in the civilized world. A notable number of patients undergo radiation in various stages of the treatment process and its main respiratory side effect is pneumonitis. Our aim was to investigate the diagnostic and treatment methods of post-radiation pneumonitis particularly in asthma patients. Methods A literature search was performed in Pubmed to identify relative studies published until June 2011. Lung cancer, post-radiation pneumonitis, therapy and asthma were the key words used for the search. Results Post-radiation pneumonitis is a clinical situation demanding early diagnosis in asthma patients, but the latter is often underestimated. Pneumonitis is clinically revealed by dyspnea, cough, fever and usually begins up to 12 weeks after the start of radiation treatment. Radiographically, it appears as diffuse or patchy consolidation and/or ground glass opacities. Pulmonary function decline is correlated to decreased values of forced expiratory volume in the 1st second (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO). The effects on normal tissue may mimic or hide tumor recurrence. Smoking cessation causes changes of total lung capacity and vital capacity and this may have consequences on lung volume results in dose volume histogram analysis, targeting precision, oxygenation changes, tumor biology (gene expression) and prognosis. NCI Common Toxicity Criteria (CTC) V3.0 assessments are usually preformed weekly during radiotherapy and at regular follow-up visits. Complication rates vary with dose, fractionation, schedule duration, technique, photons' energy, irradiated volume, dose escalation, accelerated fractionation schemes, fields, co-morbidities and concurrent chemo-radiotherapy. Conclusions The crucially deteriorating on therapy effect of pneumonitis leads to the realization that alertness and constant attention is not only strongly advised, but compulsory in asthma patients.

Summarization: eMass project aims to digitalize the medical examination procedure of recruitment phase of conscripts in the Hellenic Navy. eMass integrates recruits’ Electronic Health Record (EHR), while allows a pre-screening test, through portable telemedicine equipment. The data will be exploited to assess the individual’s cardiovascular risk through appropriate digital tools and algorithms. The eMass digital platform, will be accessible to health experts involved in the recruitment procedure for further assessment and processing. Recruits’ personal data is stored in the database encrypted using Advanced Encryption Standard (AES). eMass solution contributes to beneficial management and medical data analysis, preventing inessential physical or medical examinations minimizing danger of possible errors and reducing time-consuming processes. Moreover, eMass exploits Electronic Health Record data through a machine-learning based cardiovascular risk assessment tool. Appearing in: Public Health and Informatics