Dual Effect of Neutrophils on pIgR/Secretory Component in Human Bronchial Epithelial Cells: Role of TGF-β

Neutrophils have a dual affect on epithelial pIgR/SC, the critical receptor for transcellular routing of mucosal IgA, but mechanisms of pIgR/SC upregulation remain elusive. Requirements of cytokine, redox, and signalling pathways for pIgR/SC production were assessed in human bronchial epithelial (Calu-3) cells cocultured with increasing numbers of blood neutrophils. Increased SC production was observed after incubation for 48 hrs with intermediate neutrophil numbers (1.25 to 2.5 × 106), was favoured by the elastase inhibitor SLPI, and correlated with increased TGF-β production. Exogenous TGF-β stimulated SC production with a maximal effect at 48 hrs and both TGF-β- and neutrophil-driven SC upregulation were dependent on redox balance and p38 MAP-kinase activation. This paper shows that activated neutrophils could upregulate epithelial pIgR/SC production through TGF-β-mediated activation of a redox-sensitive and p38 MAPK-dependent pathway. An imbalance between the two neutrophil-driven opposite mechanisms (SC upregulation and SC degradation) could lead to downregulation of pIgR/SC, as observed in severe COPD

Severe asthma: oral corticosteroid alternatives and the need for optimal referral pathways

Peer reviewe

A belgian survey on the diagnosis of asthma– COPD overlap syndrome

INTRODUCTION: Patients with chronic airway disease may present features of both asthma and COPD, commonly referred to as asthma-COPD overlap syndrome (ACOS). Recommendations on their diagnosis are diffuse and inconsistent. This survey aimed to identify consensus on criteria for diagnosing ACOS. METHODS: A Belgian expert panel developed a survey on ACOS diagnosis, which was completed by 87 pulmonologists. Answers chosen by >/=70% of survey respondents were considered as useful criteria for ACOS diagnosis. The two most frequently selected answers were considered as major criteria, others as minor criteria. The expert panel proposed a minimal requirement of two major criteria and one minor criterion for ACOS diagnosis. Respondents were also asked which criteria are important for considering inhaled corticosteroids prescription in a COPD patient. RESULTS: To diagnose ACOS in COPD patients, major criteria were "high degree of variability in airway obstruction over time (change in forced expiratory volume in 1 second >/=400 mL)" and "high degree of response to bronchodilators (>200 mL and >/=12% predicted above baseline)". Minor criteria were "personal/family history of atopy and/or IgE sensitivity to >/=1 airborne allergen", "elevated blood/sputum eosinophil levels and/or increased fractional exhaled nitric oxide", "diagnosis of asthma /=10 pack-years for (ex-)smokers"; minor criteria were "lack of response on acute bronchodilator test"; "reduced diffusion capacity"; "limited variability in airway obstruction"; "age >40 years"; "emphysema on chest computed tomography scan". CONCLUSION: Specific criteria were identified that may guide physicians to a more uniform diagnostic approach for ACOS in COPD or asthma patients. These criteria are largely similar to those used to prescribe inhaled corticosteroids in COPD

Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA)

BACKGROUND: Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) working group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies.METHODS: COMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult, and paediatric clinicians, pharmaceutical representatives and health regulators from across Europe. Evidence included a systematic review of development, validity, and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients' and carers' views about outcome measures. It was discussed using a modified GRADE Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria.RESULTS: Both adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire, and Asthma Control Test (ACT) or Childhood-ACT while the adult COM includes the Severe Asthma Questionnaire and the Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately).CONCLUSIONS: This patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.</p

Cent scientifiques répliquent à SEA (Suppression des Expériences sur l’Animal vivant) et dénoncent sa désinformation

La lutte contre la maltraitance animale est sans conteste une cause moralement juste. Mais elle ne justifie en rien la désinformation à laquelle certaines associations qui s’en réclament ont recours pour remettre en question l’usage de l’expérimentation animale en recherche

Efficacité de l’immunothérapie dans l’asthme : comparaison des voies sous-cutanée et sublinguale☆

Allergen-specific immunotherapy (IT) represents an effective treatment in allergic asthma and rhinitis. Seven studies have directly compared the sublingual route (SLIT) to conventional, subcutaneous IT (SCIT). The efficacy of SCIT versus SLIT on asthma and rhinitis symptom and medication scores was not significantly different, although a tendency for greater benefit with SCIT was often reported. Comparison of SCIT and SLIT meta-analyses confirmed this trend, except that the effect of SLIT seemed to increase over time. Improved lung function and bronchial reactivity threshold were observed in some but not all studies of SCIT and SLIT. The long term benefit documented for two to three years of SCIT needs to be confirmed for SLIT, assuming that both treatments probably affect the natural course of these patients toward polysensitization and (in pollen allergy) the development of asthma. The most striking difference between SCIT and SLIT is the risk of a severe allergic reaction to the vaccine, which is limited to SCIT, limiting its benefit/risk ratio in chronic asthma. Before additional comparative data are available, the choice of SCIT versus SLIT should rely on the assessment of the balance of efficacy over risk, taking into account the documented effects of these treatments and the patient's phenotype. (C) 2009 Elsevier Masson SAS. All rights reserved

Secretory immunity and polymorphonuclear neutrophilis in Chronic Obstrutive Pulmonary Disease

Thèse de doctorat en sciences biomédicales (immunologie des muqueuses) (SBIM 3)--UCL, 200

Role of exosomes in allergic asthma: Signaling platforms between the epithelium and type 2 immunity.

No abstract availabl