Proteomic profiling of serum identifies a molecular signature that correlates with clinical outcomes in COPD.

Objective: Novel biomarkers related to main clinical hallmarks of Chronic obstructive pulmonary disease (COPD), a heterogeneous disorder with pulmonary and extra-pulmonary manifestations, were investigated by profiling the serum levels of 1305 proteins using Slow Off-rate Modified Aptamers (SOMA)scan technology.

Methods: Serum samples were collected from 241 COPD subjects in the multicenter French Cohort of Bronchial obstruction and Asthma to measure the expression of 1305 proteins using SOMAscan proteomic platform. Clustering of the proteomics was applied to identify disease subtypes and their functional annotation and association with key clinical parameters were examined.

Hypoxia Promotes a Mixed Inflammatory-Fibrotic Macrophages Phenotype in Active Sarcoidosis.

Background: Macrophages are pivotal cells in sarcoidosis. Monocytes-derived (MD) macrophages have recently been demonstrated to play a major role especially in pulmonary sarcoidosis. From inflammatory tissues to granulomas, they may be exposed to low oxygen tension environments.

Essential role of smooth muscle Rac1 in severe asthma-associated airway remodelling.

Background: Severe asthma is a chronic lung disease characterised by inflammation, airway hyperresponsiveness (AHR) and airway remodelling. The molecular mechanisms underlying uncontrolled airway smooth muscle cell (aSMC) proliferation involved in pulmonary remodelling are still largely unknown. Small G proteins of the Rho family (RhoA, Rac1 and Cdc42) are key regulators of smooth muscle functions and we recently demonstrated that Rac1 is activated in aSMC from allergic mice.

Clinical and histopathologic predictors of therapeutic response to bronchial thermoplasty in severe refractory asthma.

Background: Phenotypes and endotypes predicting optimal response to bronchial thermoplasty (BT) in patients with severe asthma remain elusive.

Objective: Our aim was to compare the clinical characteristics and hallmarks of airway inflammation and remodeling before and after BT in responder and partial responder patients with severe asthma refractory to oral steroids and to omalizumab.

Methods: In all, 23 patients with severe refractory asthma were divided into BT responders (n = 15) and BT partial responders (n = 8), according to the decrease in asthma exacerbations at 12 months after BT.

Is CCL18 a potential biomarker of type-2 asthma endotypes?

This exploratory cross-sectional study aimed to evaluate the associations between the chemokine ligand 18 (CCL18) blood level and phenotypic characteristics of asthma. We evaluated in a sample of 173 asthmatic adult patients from the Cohort of Bronchial obstruction and Asthma (63.4% women; median age 50 ± interquartile range 27.

IL-33-ST2 axis regulates myeloid cell differentiation and activation enabling effective club cell regeneration.

Evidence points to an indispensable function of macrophages in tissue regeneration, yet the underlying molecular mechanisms remain elusive. Here we demonstrate a protective function for the IL-33-ST2 axis in bronchial epithelial repair, and implicate ST2 in myeloid cell differentiation. ST2 deficiency in mice leads to reduced lung myeloid cell infiltration, abnormal alternatively activated macrophage (AAM) function, and impaired epithelial repair post naphthalene-induced injury.

Penetration of the Human Pulmonary Epithelium by Aspergillus fumigatus Hyphae.

Background: The airway epithelium is the first barrier interacting with Aspergillus fumigatus conidia after their inhalation, suggesting that this structure functions as point of entry of this fungus to initiate pulmonary aspergillosis.

Methods: To study epithelial entry by A fumigatus, primary human reconstituted pseudostratified epithelium cultured in air-liquid interface as well as bronchial epithelial cell monolayers were infected with conidia.

Results: Under these experimental conditions, we found that A fumigatus hyphae traversed the bronchial epithelium through a mechanism involving the recruitment of actin, which formed a tunnel that allows hyphae to enter the cells without disturbing their integrity.

Donor Club Cell Secretory Protein G38A Polymorphism Is Associated With a Decreased Risk of Primary Graft Dysfunction in the French Cohort in Lung Transplantation.

Background: Club Cell Secretory Protein (CCSP) G38A polymorphism has recently been involved in lung epithelial susceptibility to external injuries. Lung transplantation (LT) is currently limited by ischemia-reperfusion injury leading to primary graft dysfunction (PGD). We thus hypothesized that donor CCSP G38A polymorphism might impact the risk of PGD after LT.

Clinical and biological characteristics of the French COBRA cohort of adult subjects with asthma.

The COhort of BRonchial obstruction and Asthma (COBRA) is a longitudinal cohort that involves 12 French academic institutions. DNA, serum samples and clinical data are collected at entry and every 6 months thereafter.Of 1080 patients with asthma recruited between 2007 and 2015, 401 had mild/moderate and 613 had severe asthma.

Early computed tomography modifications following bronchial thermoplasty in patients with severe asthma.

Bronchial thermoplasty (BT) is a recent, promising and well-tolerated technique for the treatment of severe asthma. By delivering thermal energy to the airway wall, this procedure can induce early pulmonary opacities seen on computed tomography (CT). We aimed to examine early CT modifications induced by BT and to determine their association with respiratory symptoms.

Inhibition of T Cell Alloreactivity by Bronchial Epithelium Is Impaired in Lung Transplant Recipients, Through Pathways Involving TGF-β, IL-10 and HLA-G.

Background: Bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx) results from bronchial epithelial cell (BECs) damages, thought to be orchestrated by T cells primed by antigen-presenting cell presenting alloantigens. In this cell cross-talk, BECs are also suspected to play a pivotal immunosuppressive role in T cell alloreactivity. We studied the immunomodulating role of BECs in a human ex vivo model of allogeneic T cell response, both in healthy subjects and LTx recipients.

Effectiveness of bronchial thermoplasty in patients with severe refractory asthma: Clinical and histopathologic correlations.

Background: The effectiveness of bronchial thermoplasty (BT) has been reported in patients with severe asthma, yet its effect on different bronchial structures remains unknown.

Objective: We sought to examine the effect of BT on bronchial structures and to explore the association with clinical outcome in patients with severe refractory asthma.

Methods: Bronchial biopsy specimens (n = 300) were collected from 15 patients with severe uncontrolled asthma before and 3 months after BT.

Perip7lakin is a target for autoimmunity in asthma.

The role of autoimmunity targeting epithelial antigens in asthma has been suggested, in particular in non-atopic and severe asthma. Periplakin, a desmosomal component, is involved in epithelial cohesion and intracellular signaling. We detected anti-periplakin IgG antibodies in 47/260 (18 %) patients with asthma, with no association with severity or atopy.

Airway smooth muscle enlargement is associated with protease-activated receptor 2/ligand overexpression in patients with difficult-to-control severe asthma.

Background: Asthma is a complex disease with heterogeneous features of airway inflammation and remodeling. The increase in airway smooth muscle (ASM) mass is an essential component of airway remodeling in patients with severe asthma, yet the pathobiological mechanisms and clinical outcomes associated with ASM enlargement remain elusive.

Objective: We sought to compare ASM area in control subjects and patients with mild-to-moderate or severe asthma and to identify specific clinical and pathobiological characteristics associated with ASM enlargement.

Obstructive Sleep Apnoea Modulates Airway Inflammation and Remodelling in Severe Asthma.

Background: Obstructive sleep apnoea (OSA) is frequently observed in severe asthma but the causal link between the 2 diseases remains hypothetical. The role of OSA-related systemic and airway neutrophilic inflammation in asthma bronchial inflammation or remodelling has been rarely investigated. The aim of this study was to compare hallmarks of inflammation in induced sputum and features of airway remodelling in bronchial biopsies from adult patients with severe asthma with and without OSA.

Expression of high-mobility group box 1 and of receptor for advanced glycation end products in chronic obstructive pulmonary disease.

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation and remodeling. High-mobility group box 1 (HMGB1), a nuclear protein that is released during inflammation and repair, interacts with proinflammatory cytokines and with the receptor for advanced glycation end products (RAGE), which is highly expressed in the lung.

Objectives: To determine whether HMGB1 is augmented in COPD and is associated with IL-1beta and RAGE.

Lung chitinolytic activity and chitotriosidase are elevated in chronic obstructive pulmonary disease and contribute to lung inflammation.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation and emphysematous alveolar destruction. In this study, we have investigated whether chitotriosidase (ChTRase) and acidic mammalian chitinase, two chitinases with chitinolytic activity, are selectively augmented in COPD and contribute to its pathogenesis. We found that smokers with COPD, but not asthmatics, had higher chitinolytic activity and increased levels of ChTRase in bronchoalveolar lavage, more ChTRase-positive cells in bronchial biopsies, and an elevated proportion of alveolar macrophages expressing ChTRase than smokers without COPD or never-smokers.

A role for Bid in eosinophil apoptosis and in allergic airway reaction.

Bid, a proapoptotic member of Bcl-2 family, is involved in Fas receptor signaling. Fas activation promotes human eosinophil cell death and is believed to accelerate the resolution of pulmonary Th2-driven allergic reaction in mice. We hypothesized that Bid would regulate eosinophil apoptosis and Ag-induced airway inflammation, particularly eosinophilia.