Effect of improved home ventilation on asthma control and house dust mite allergen levels

The warm, humid environment in modern homes favours the dust mite population, but the effect of improved home ventilation on asthma control has not been established. We tested the hypothesis that a domestic mechanical heat recovery ventilation system (MHRV), in addition to allergen avoidance measures, can improve asthma control by attenuating re-colonization rates. We conducted a randomized double-blind placebo-controlled parallel group trial of the installation of MHRV activated in half the homes of 120 adults with asthma, allergic to Dermatophagoides pteronyssinus. All homes had carpets steam cleaned and new bedding and mattress covers at baseline. The primary outcome was morning peak expiratory flow (PEF) at 12 months. At 12 months, the primary end-point; change in mean morning PEF as compared with baseline, did not differ between the MHRV group and the control group (mean difference 13.5 l/min, 95% CI: −2.6 to 29.8, P = 0.10). However, a secondary end-point; evening mean PEF, was significantly improved in the MHRV group (mean difference 24.5 l/min, 95% CI: 8.9-40.1, P = 0.002). Indoor relative humidity was reduced in MHRV homes, but there was no difference between the groups in Der p 1 levels, compared with baseline. The addition of MHRV to house dust mite eradication strategies did not achieve a reduction in mite allergen levels, but did improve evening PEF

IL-33 promotes the egress of group 2 innate lymphoid cells from the bone marrow

Group 2 innate lymphoid cells (ILC2s) are effector cells within the mucosa and key participants in type 2 immune responses in the context of allergic inflammation and infection. ILC2s develop in the bone marrow from common lymphoid progenitor cells, but little is known about how ILC2s egress from the bone marrow for hematogenous trafficking. In this study, we identified a critical role for IL-33, a hallmark peripheral ILC2-activating cytokine, in promoting the egress of ILC2 lineage cells from the bone marrow. Mice lacking IL-33 signaling had normal development of ILC2s but retained significantly more ILC2 progenitors in the bone marrow via augmented expression of CXCR4. Intravenous injection of IL-33 or pulmonary fungal allergen challenge mobilized ILC2 progenitors to exit the bone marrow. Finally, IL-33 enhanced ILC2 trafficking to the lungs in a parabiosis mouse model of tissue disruption and repopulation. Collectively, these data demonstrate that IL-33 plays a critical role in promoting ILC2 egress from the bone marrow

Mechanism of cigarette smoke condensate-induced acute inflammatory response in human bronchial epithelial cells

BACKGROUND: To demonstrate the involvement of tobacco smoking in the pathophysiology of lung disease, the responses of pulmonary epithelial cells to cigarette smoke condensate (CSC) — the particulate fraction of tobacco smoke — were examined. METHODS: The human alveolar epithelial cell line A549 and normal human bronchial epithelial cells (NHBEs) were exposed to 0.4 μg/ml CSC, a concentration that resulted in >90% cell survival and <5% apoptosis. Changes in gene expression and signaling responses were determined by RT-PCR, western blotting and immunocytofluorescence. RESULTS: NHBEs exposed to CSC showed increased expression of the inflammatory mediators sICAM-1, IL-1β, IL-8 and GM-CSF, as determined by RT-PCR. CSC-induced IL-1β expression was reduced by PD98059, a blocker of mitogen-actived protein kinase (MAPK) kinase (MEK), and by PDTC, a NFκB inhibitor. Analysis of intracellular signaling pathways, using antibodies specific for phosphorylated MAPKs (extracellular signal-regulated kinase [ERK]-1/2), demonstrated an increased level of phosphorylated ERK1/2 with increasing CSC concentration. Nuclear localization of phosphorylated ERK1/2 was seen within 30 min of CSC exposure and was inhibited by PD98059. Increased phosphorylation and nuclear translocation of IκB was also seen after CSC exposure. A549 cells transfected with a luciferase reporter plasmid containing a NFκB-inducible promoter sequence and exposed to CSC (0.4 μg/ml) or TNF-α (50 ng/ml) had an increased reporter activity of approximately 2-fold for CSC and 3.5-fold for TNF-α relative to untreated controls. CONCLUSION: The acute phase response of NHBEs to cigarette smoke involves activation of both MAPK and NFκB

The same analysis approach: Practical protection against the pitfalls of novel neuroimaging analysis methods

Standard neuroimaging data analysis based on traditional principles of experimental design, modelling, and statistical inference is increasingly complemented by novel analysis methods, driven e.g. by machine learning methods. While these novel approaches provide new insights into neuroimaging data, they often have unexpected properties, generating a growing literature on possible pitfalls. We propose to meet this challenge by adopting a habit of systematic testing of experimental design, analysis procedures, and statistical inference. Specifically, we suggest to apply the analysis method used for experimental data also to aspects of the experimental design, simulated confounds, simulated null data, and control data. We stress the importance of keeping the analysis method the same in main and test analyses, because only this way possible confounds and unexpected properties can be reliably detected and avoided. We describe and discuss this Same Analysis Approach in detail, and demonstrate it in two worked examples using multivariate decoding. With these examples, we reveal two sources of error: A mismatch between counterbalancing (crossover designs) and cross-validation which leads to systematic below-chance accuracies, and linear decoding of a nonlinear effect, a difference in variance

Portal vein thrombosis following laparoscopic cholecystectomy complicated by dengue viral infection: a case report

<p>Abstract</p> <p>Introduction</p> <p>Portal vein thrombosis is an uncommon post-operative complication following abdominal surgery. Although therapeutic anticoagulation is recommended, this treatment may be questionable when the patient has an associated bleeding diathesis.</p> <p>Case presentation</p> <p>We report a case of a 63-year-old woman of Asian Indian ethnicity who developed portal vein thrombosis following an uneventful laparoscopic cholecystectomy for symptomatic gallstones. Her condition was further complicated by dengue viral infection in the post-operative period, with thrombocytopenia immediately preceding the diagnosis of portal vein thrombosis. The etiological connections between dengue viral infection with thrombocytopenia, laparoscopic cholecystectomy, portal vein thrombosis as well as the treatment dilemmas posed in treating a patient with portal vein thrombosis with a bleeding diathesis are discussed.</p> <p>Conclusion</p> <p>When portal vein thrombosis occurs in patients with contraindications to anticoagulation, there is a role for initial conservative management without aggressive anticoagulation therapy and such patients must be approached on an individualized basis.</p

GSTM1 and GSTP1 Polymorphisms as Potential Factors for Modifying the Effect of Smoking on Inflammatory Response

Inflammation has been known to be an important underlying condition for development of various diseases including cancer. The aims of this study were to investigate whether tobacco smoke exposure increases the level of inflammation biomarkers and the GSTM1 and GSTP1 gene polymorphisms are associated with inflammatory response due to tobacco smoke exposure. We measured urinary cotinine level in 300 healthy university students. Total serum TNF-α levels and blood WBC counts were determined to evaluate inflammatory response. Allelic loss of the GSTM1 and the GSTP1 (Ile105Val) polymorphism were determined by PCR and RFLP. Tobacco smoke exposure was found to be associated with increase of both TNF-α level and WBC count. Particularly, smokers with combination of GSTM1 null and GSTP1 AG or GG genotypes showed higher TNF-α level than those with the other genotype combinations (p=0.07). This result suggests that smoking may induce inflammation measured as TNF-α level or WBC count and combinations of the GSTM1 and GSTP1 polymorphisms may modify the effect of smoking on serum TNF-α level

Allergies respiratoires, pollens et polluants

National audienceFor 30 years, an increased incidence of respiratory allergy and asthma has been observed, particularly in children and young people living in urban areas of developed countries. A genetic origin is unlikely due to the rapidity of this increase and environmental factors (diet, lifestyle, exposure to xenobiotics...) should be involved. Epidemiological studies have shown that atmospheric pollutants may play a role. They could have an effect on the respiratory tract by inducing irritation, inflammation, airway hyperresponsiveness or enhancing respiratory allergies (adjuvant effect) or they could have an effect on the aeroallergens, in particular the pollens. Experimental studies have shown that pollen exposure to pollutants induce enhanced deformation or fracture of the external envelope linking to an enhanced liberation of intracytoplasmic allergenic granules and induce also a qualitative and quantitative modification of allergens. However, few experimental studies have shown that pollutant-exposed pollens are more allergenic that "clean" pollens. One important point to consider is the enhanced granule liberation by exposed pollens. Due to the small size of the granules, the allergen bioavailability may increase, leading to higher incidence of respiratory allergies.Depuis 30 ans, une incidence accrue des allergies respiratoires est observée, notamment chez les enfants et les adolescents vivant dans les zones urbaines des pays industrialisés. Il est admis que cette augmentation est trop rapide pour être liée à des facteurs génétiques et que d'autres facteurs, notamment environnementaux (alimentation, mode de vie, contact avec des xénobiotiques...) sont impliqués. Les études épidémiologiques montrent que les polluants de l'air en particulier semblent jouer un rôle important dans l'incidence des allergies. Ils peuvent agir soit par action au niveau du système respiratoire, en provoquant une irritation, une inflammation, une augmentation de l'hyperréactivité bronchique non spécifique ou en potentialisant une réponse allergique pré-existante (effet adjuvant), soit par action au niveau des aéroallergènes, dont les pollens représentent la majeure partie. Les principaux effets observés expérimentalement sont une augmentation des déformations et fractures de l'enveloppe externe conduisant à une libération accrue de granules intracytoplasmiques, eux-mêmes allergisants et une modification quantitative et qualitative des allergènes. Peu de travaux ont toutefois clairement mis en évidence une augmentation du potentiel allergisant des pollens après exposition aux polluants. Une piste à explorer reste la libération plus importante des granules intrapolliniques qui, de part leur petite taille, pourraient augmenter la biodisponibilité des allergènes et donc la fréquence et la gravité des allergies respiratoires