Efficacy of a Non-Pharmacological Intervention in Seasonal Allergic Rhinitis Symptoms.

BACKGROUND: Patients suffering from allergic rhinitis seek for several therapeutic symptomatic options, including nonconventional treatments, to control their symptoms. OBJECTIVES: Through the present proof-of-concept study, we prospectively investigated the potential role of Puressentiel® nasal protection spray (SNPA) in patients suffering from cypress pollen allergic rhinitis. METHODS: In 15 adults, we performed two nasal provocation tests, with a cypress pollen extract, with a 15-day interval, with and without previous randomized administration of SNPA, and evaluated a nasal symptom score, the nasal inspiratory peak flow, and the concentration of inflammatory cytokines in the nasal lavage after the procedures. RESULTS: Comparing results in patients challenged with and without the SNPA spray before the nasal challenge, we found a 57% mean decrease in symptoms, and a 62% average difference in inspiratory peak flow, after the use of the spray. CONCLUSIONS: Puressentiel® SNPA is effective in reducing nasal symptoms, as assessed by nasal symptoms score and nasal inspiratory peak flow, and could be a valid natural non-pharmacological option in patients suffering from allergic rhinitis.

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. Clinical parameters were compared at baseline and 12 months after BT, and hallmarks of airway inflammation and remodeling were analyzed by immunohistochemistry in bronchial biopsy specimens before and 3 months after BT. RESULTS: At baseline, the BT responders were around 8 years younger than the BT partial responders (P = .02) and they had a greater incidence of atopy, higher numbers of blood eosinophils (both P = .03) and IgE levels, higher epithelial IFN-α expression, and higher numbers of mucosal eosinophils and IL-33-positive cells (P ≤ .05). A reduction in blood eosinophil count, serum IgE level, type 2 airway inflammation, and numbers of mucosal IL-33-positive cells and mast cells associated with augmented epithelial MUC5AC and IFN-α/ß immunostaining was noted after BT in responders, whereas the numbers of mucosal IL-33-positive cells were augmented in BT partial responders. Most of these changes were correlated with clinical parameters. Subepithelial membrane thickening and airway smooth muscle area were similar in the 2 patient groups at baseline and after BT. CONCLUSION: By reducing allergic type 2 inflammation and increasing epithelial MUC5AC and anti-viral IFN-α/ß expression, BT may enhance host immune responses and thus attenuate exacerbations and symptoms in BT responders. Instead, targeting IL-33 may provide a clinical benefit in BT partial responders.

CCR10+ ILC2s with ILC1-like properties exhibit a protective function in severe allergic asthma.

BACKGROUND: We previously showed that patients with severe allergic asthma have high numbers of circulating ILC2s expressing CCR10. METHOD: Herein, CCR10+ ILC2s were further analyzed in the blood of healthy individuals or patients with allergic and non-allergic asthma. Characteristics of human CCR10+ and CCR10- ILC2s were assessed by flow cytometry as well as single-cell multiplex RT-qPCR. The role of CCR10+ ILC2s in asthma pathophysiology was studied in allergen-treated mice. RESULTS: When compared to healthy controls, CCR10+ ILC2s are enriched in the blood of both allergic and non-allergic severe asthmatic patients, and these cells are recruited to the lungs. Plasma concentrations of the CCR10 ligand CCL27 are significantly increased in severe asthmatics when compared to non-asthmatic patients. CCR10+ ILC2s secrete little TH 2 cytokines, but exhibit ILC1-like properties, including a capacity to produce IFN-γ. Also, single-cell analysis reveals that the CCR10+ ILC2 subset is enriched in cells expressing amphiregulin. CCR10+ ILC2 depletion, as well as blocking of IFN-γ activity, exacerbates airway hyperreactivity in allergen-challenged mice, providing evidence for a protective role of these cells in allergic inflammation. CONCLUSIONS: Frequencies of circulating CCR10+ ILC2s and CCL27 plasma concentrations represent candidate markers of asthma severity. The characterization of CCR10+ ILC2s in human samples and in mouse asthma models suggests that these cells downregulate allergic inflammation through IFN-γ production.

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. Immunostained sections were assessed for airway smooth muscle (ASM) area, subepithelial basement membrane thickness, nerve fibers, and epithelial neuroendocrine cells. Histopathologic findings were correlated with clinical parameters. RESULTS: BT significantly improved asthma control and quality of life at both 3 and 12 months and decreased the numbers of severe exacerbations and the dose of oral corticosteroids. At 3 months, this clinical benefit was accompanied by a reduction in ASM area (median values before and after BT, respectively: 19.7% [25th-75th interquartile range (IQR), 15.9% to 22.4%] and 5.3% [25th-75th IQR], 3.5% to 10.1%, P < .001), subepithelial basement membrane thickening (4.4 µm [25th-75th IQR, 4.0-4.7 µm] and 3.9 µm [25th-75th IQR, 3.7-4.6 µm], P = 0.02), submucosal nerves (1.0 ‰ [25th-75th IQR, 0.7-1.3 ‰] immunoreactivity and 0.3 ‰ [25th-75th IQR, 0.1-0.5 ‰] immunoreactivity, P < .001), ASM-associated nerves (452.6 [25th-75th IQR, 196.0-811.2] immunoreactive pixels per mm2 and 62.7 [25th-75th IQR, 0.0-230.3] immunoreactive pixels per mm2, P = .02), and epithelial neuroendocrine cells (4.9/mm2 [25th-75th IQR, 0-16.4/mm2] and 0.0/mm2 [25th-75th IQR, 0-0/mm2], P = .02). Histopathologic parameters were associated based on Asthma Control Test scores, numbers of exacerbations, and visits to the emergency department (all P ≤ .02) 3 and 12 months after BT. CONCLUSION: BT is a treatment option in patients with severe therapy-refractory asthma that downregulates selectively structural abnormalities involved in airway narrowing and bronchial reactivity, particularly ASM, neuroendocrine epithelial cells, and bronchial nerve endings.

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. In cross-sectional analyses, compared with patients with milder disease, patients with severe asthma had more symptoms, exacerbations, hospitalisations and visits to the emergency department during the preceding 12 months, higher numbers of blood eosinophils, and more comorbidities. More than 60% of patients with severe asthma were therapy-uncontrolled at entry, and 152 of them were being treated with omalizumab. In addition, patients with asthma who had the highest eosinophilia levels (>300/mm3) had shorter asthma duration, lower lung function, and higher rates of severe exacerbations and unacceptable asthma control than patients with lower eosinophil counts.Longitudinal analyses performed in 427 patients with asthma with at least three differential blood cell counts demonstrated that both eosinophil numbers and eosinophil increase over time were associated with the number of exacerbations occurring until the next visit and with Juniper score.Studies with the COBRA cohort will help to improve knowledge concerning the risk and biological factors associated with asthma severity and to better understand their influence on the disease trajectory.

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.Unenhanced chest CT was performed the day after each BT session in 13 patients with severe asthma, leading to the examination of 38 treated lobes. A total of 15 BT-treated lobes were evaluated in 11 patients at 1 month. The first two patients also underwent CT at 1 week.No symptoms suggestive of pulmonary infection were noted following BT in any patient. Peribronchial consolidations and ground-glass opacities were observed in all treated lobes on day 1, with three lower lobes showing complete collapse. Mild involvement of an adjacent untreated lobe was observed in 12 out of 38 (32%) cases. Opacities had decreased in 5 out of 15 (33%) and disappeared in 10 out of 15 (67%) at 1 month.BT induced early pulmonary peribronchial hyperdensities in all treated lobes. These alterations were unrelated to clinical symptoms and spontaneously decreased or disappeared after 1 month.

[18F]FDG PET/CT predicts progression-free survival in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by an unpredictable course. Prognostic markers and disease activity markers are needed. The purpose of this single-center retrospective study was to evaluate the prognostic value of lung fluorodeoxyglucose ([18F]-FDG) uptake assessed by standardized uptake value (SUV), metabolic lung volume (MLV) and total lesion glycolysis (TLG) in patients with IPF. METHODS: We included 27 IPF patients (IPF group) and 15 patients with a gastrointestinal neuroendocrine tumor without thoracic involvement (control group). We quantified lung SUV mean and SUV max, MLV and TLG and assessed clinical data, high-resolution CT (HRCT) fibrosis and ground-glass score; lung function; gender, age, physiology (GAP) stage at inclusion and during follow-up; and survival. RESULTS: Lung SUV mean and SUV max were higher in IPF patients than controls (p <0.00001). For patients with IPF, SUV mean, SUV max, MLV and TLG were correlated with severity of lung involvement as measured by a decline in forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO) and increased GAP score. In a univariate and in a multivariate Cox proportional-hazards model, risk of death was increased although not significantly with high SUV mean. On univariate analysis, risk of death was significantly associated with high TLG and MLV, which disappeared after adjustment functional variables or GAP index. Increased MLV and TLG were independent predictors of death or disease progression during the 12 months after PET scan completion (for every 100-point increase in TLG, hazard ratio [HR]: 1.11 (95% CI 1.06; 1.36), p = 0.003; for every 100-point increase in MLV, HR: 1.20 (1.04; 1.19), p = 0.002). On multivariable analysis including TLG or MLV with age, FVC, and DLCO or GAP index, TLG and MLV remained associated with progression-free survival (HR: 1.1 [1.03; 1.22], p = 0.01; and 1.13 [1.0; 1.2], p = 0.005). CONCLUSION: FDG lung uptake may be a marker of IPF severity and predict progression-free survival for patients with IPF.

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. METHODS: Bronchial biopsy specimens from 12 control subjects, 24 patients with mild-to-moderate asthma, and 105 patients with severe asthma were analyzed for ASM area, basement membrane thickness, vessels, eosinophils, neutrophils, T lymphocytes, mast cells, and protease-activated receptor 2 (PAR-2). In parallel, the levels of several ASM mitogenic factors, including the PAR-2 ligands, mast cell tryptase, trypsin, tissue factor, and kallikrein (KLK) 5 and KLK14, were assessed in bronchoalveolar lavage fluid. Data were correlated with asthma severity and control both at inclusion and after 12 to 18 months of optimal management and therapy. RESULTS: Analyses across ASM quartiles in patients with severe asthma demonstrated that patients with the highest ASM quartile (median value of ASM area, 26.3%) were younger (42.5 vs ≥50 years old in the other groups, P ≤ .04) and had lower asthma control after 1 year of optimal management (P ≤ .006). ASM enlargement occurred independently of features of airway inflammation and remodeling, whereas it was associated with PAR-2 overexpression and higher alveolar tryptase (P ≤ .02) and KLK14 (P ≤ .03) levels. CONCLUSION: Increase in ASM mass, possibly involving aberrant expression and activation of PAR-2-mediated pathways, characterizes younger patients with severe asthma with poor asthma control.

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. In addition, anti-periplakin IgE antibodies were detected in 12 of 138 tested patients (8.7 %) and were more frequently observed in patients with than without nasal polyposis. This study identifies a new autoimmune epithelial target in asthma. Whether periplakin autoimmunity (both IgG and IgE auto-antibodies) is involved in asthma pathogenesis remains to be studied during the disease course of these patients.

Severe, chronic cough caused by pulmonary arteriovenous malformations in a patient with hereditary haemorrhagic telangiectasia: case report.

BACKGROUND: Patients with pulmonary arteriovenous malformations usually complain of dyspnoea upon exertion, fatigue or migraine, or may be asymptomatic. We describe a patient with an unreported manifestation of a pulmonary arteriovenous malformation: a severe chronic cough. CASE PRESENTATION: A 51-year old Caucasian non-smoking female police officer presented with a chronic cough. She had been diagnosed with hereditary haemorrhagic telangiectasia in 1992. She complained of a severe, dry cough at the time of the diagnosis and a pulmonary arteriovenous malformation in the upper left lobe as demonstrated by CT of the chest. The fistula was occluded and the cough disappeared rapidly but resumed in 1994. Recanalisation of the fistula led to a new embolisation procedure, and the cough disappeared. Similar episodes occurred in 1998 and 2004, leading to embolisation of a fistula in the right lower lobe and reperfused fistula in the upper left lobe, respectively. The patient was referred to our research team in 2010 because of reappearance of her dry cough that was more pronounced during exercise and exposure to volatile irritants, and absent during the night. Despite extensive investigations, no cause was found other than reperfusion of the fistula in the left upper lobe. The malformation was not accessible to embolisation, leading us to recommend surgical excision of the malformation. A surgeon undertook atypical resection of the left upper lobe in 2012. The cough disappeared immediately after surgery and has not recurred. CONCLUSION: Physicians caring for patients with pulmonary arteriovenous malformations should know that a severe, chronic cough can be caused by the malformation. A cough associated with a pulmonary arteriovenous malformation can be treated effectively by embolisation but may resume in cases of reperfusion of the malformation. In our case, the severity of the cough led to surgical excision because embolisation was not possible. The mechanism of action of this cough remains to be determined.

[Asbestos: An up-to-date general review]. / L'amiante: le point en 2014.

Major risks associated with asbestos exposure (mesothelioma, lung cancer and asbestosis) have been knownfor a long time. Various clinical and epidemiological studies, which include assessment of risk of developing cancer after discovering atypical computer-tomography (CT) images or pleural plaques in persons who had been exposed to asbestos, are still ongoing, however. This short report updates the risk of occupational exposure in 2014, the consequences of the former occupational exposures, the scale of compensation and recent legal dispositions intended to reduce the risk of occupational and non-professional exposure in France.

[Cross-talk between differentiated cells in different tissues: the example of asthma]. / Informations croisées entre cellules différenciées de tissus différents: l'exemple de l'asthme.

Asthma is a chronic inflammatory airway disorder that leads to symptoms such as coughing, wheezing and chest tightness. Typical features of asthma are chronic airway inflammation and remodeling, leading to airway obstruction. The airway epithelium is considered as an essential controller of inflammatory, immunological and regenerative responses to allergens. Abnormal molecular crosstalk between bronchial epithelial and immune cells plays an important role in driving chronic inflammation and airway remodeling. Drugs that selectively inhibit crucial aspects of epithelial-immune or epithelial-mesenchymal interactions could potentially prevent these processes.

[Health impact of diesel particles: between myth and reality?]. / Impact sanitaire des particules diesel: entre mythe et réalité?

Exposure to particulate air pollution produced by traffic, and especially diesel particles, is accused of having multiple deleterious effects on human health. While some such effects are undeniable, such as the aggravation of respiratory allergies, many questions remain as to their impact on mortality, lung cancer and cardiovascular events.

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. Cluster findings were revalidated during a follow-up visit, and compared to those obtained in a group of 47 COPD patients included in the Melbourne Longitudinal COPD Cohort. RESULTS: Unsupervised clustering identified two clusters within COPD subjects at inclusion. Cluster 1 showed elevated levels of factors contributing to tissue injury, whereas Cluster 2 had higher expression of proteins associated with enhanced immunity and host defense, cell fate, remodeling and repair and altered metabolism/mitochondrial functions. Patients in Cluster 2 had a lower incidence of exacerbations, unscheduled medical visits and prevalence of emphysema and diabetes. These protein expression patterns were conserved during a follow-up second visit, and substanciated, by a large part, in a limited series of COPD patients. Further analyses identified a signature of 15 proteins that accurately differentiated the two COPD clusters at the 2 visits. CONCLUSIONS: This study provides insights into COPD heterogeneity and suggests that overexpression of factors involved in lung immunity/host defense, cell fate/repair/ remodelling and mitochondrial/metabolic activities contribute to better clinical outcomes. Hence, high throughput proteomic assay offers a powerful tool for identifying COPD endotypes and facilitating targeted therapies.

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. ChTRase accounted for approximately 80% of bronchoalveolar lavage chitinolytic activity, while acidic mammalian chitinase was undetectable. Bronchoalveolar lavage chitinolytic activity and ChTRase were associated with airflow obstruction and emphysema and with the levels of interleukin (IL)-1beta, IL-8, tumor-necrosis factor (TNF)-alpha, and its type II soluble receptor. Tumor necrosis factor-alpha stimulated ChTRase release only from alveolar macrophages from smokers with COPD, and exposure of these cells to ChTRase promoted the release of IL-8, monocyte-chemoattractant protein-1, and metalloproteinase-9. Finally, ChTRase overexpression in the lung of normal mice promoted macrophage recruitment and the synthesis of the murine homologue of IL-8, keratinocyte-derived cytokine, and of monocyte-chemoattractant protein-1. We conclude that pulmonary ChTRase overexpression may represent a novel important mechanism involved in COPD onset and progression.

Idiopathic interstitial lung disease with anti-SSA antibody.

OBJECTIVES: Consensus is lacking on the immunological tests to perform for diagnosis of interstitial lung diseases (ILDs). In particular, the value of detecting anti-SSA antibody in this context is unknown. We aimed to determine whether the detection of anti-SSA antibody in patients with ILD can identify a subgroup of patients with CTD. METHODS: We compared the characteristics of patients with newly diagnosed apparently idiopathic ILD with anti-SSA antibody [anti-SSA(+) group] and without anti-SSA antibody (control group). RESULTS; Anti-SSA(+) patients (n = 15) more often had extra-respiratory signs (xerostomia and ocular dryness), auto-immune features, a CT scan pattern of non-specific interstitial pneumonia and more severe lung function alteration than controls (n = 30). Of patients who were anti-SSA(+), 2 met the criteria for SS and 13 (86%) of 15 met the criteria for the diagnosis of undifferentiated CTD. CONCLUSIONS: Our results suggest that identification of anti-SSA antibody in patients with early ILD can reveal a specific subgroup of patients with more ground glass opacity and more severe lung function impairment than those without anti-SSA antibody.