Benefits and harm of systemic steroids for short- and long-term use in rhinitis and rhinosinusitis: an EAACI position paper.

Because of the inflammatory mechanisms of most chronic upper airway diseases such as rhinitis and chronic rhinosinusitis, systemic steroids have been used for their treatment for decades. However, it has been very well documented that-potentially severe-side-effects can occur with the accumulation of systemic steroid courses over the years. A consensus document summarizing the benefits of systemic steroids for each upper airway disease type, as well as highlighting the potential harms of this treatment is currently lacking.

Superior effect of MP-AzeFlu than azelastine or fluticasone propionate alone on reducing inflammatory markers.

Background: MP-AzeFlu, intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP), is superior to AZE or FP alone for treatment of allergic rhinitis (AR). However, the precise anti-inflammatory mechanism of action of MP-AzeFlu has not been characterized.

Objective: To investigate the anti-inflammatory effects of MP-AzeFlu compared with AZE or FP alone in an established in vitro model of eosinophilic inflammation.

Low E-prostanoid 2 receptor levels and deficient induction of the IL-1β/IL-1 type I receptor/COX-2 pathway: Vicious circle in patients with aspirin-exacerbated respiratory disease.

Background: We hypothesized that the 2 reported alterations in aspirin-exacerbated respiratory disease (AERD), reduced expression/production of COX-2/prostaglandin (PG) E2 and diminished expression of E-prostanoid (EP) 2 receptor, are closely linked.

Objective: We sought to determine the mechanisms involved in the altered regulation of the COX pathway in patients with AERD.

Methods: Fibroblasts were obtained from nasal mucosa; samples of control subjects (NM-C, n = 8) and from nasal polyps from patients with aspirin-exacerbated respiratory disease (NP-AERD, n = 8).

Clinical and biological markers of difficult-to-treat severe chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the upper airways of which two major phenotypes exist, CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP). Some patients with CRS have suboptimal response to current guideline treatments. These patients remain severe and uncontrolled by treatment and have a poor quality of life.

Effect of lipopolysaccharide on glucocorticoid receptor function in control nasal mucosa fibroblasts and in fibroblasts from patients with chronic rhinosinusitis with nasal polyps and asthma.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the upper airways frequently associated with asthma. Bacterial infection is a feature of CRSwNP that can aggravate the disease and the response to glucocorticoid treatment.

Objective: We examined whether the bacterial product lipopolysaccharide (LPS) reduces glucocorticoid receptor (GR) function in control nasal mucosa (NM) fibroblasts and in nasal polyp (NP) fibroblasts from patients with CRSwNP and asthma.

Corticosteroid treatment regulates mucosal remodeling in chronic rhinosinusitis with nasal polyps.

Objectives/hypothesis: To investigate the effect of oral plus intranasal corticosteroid (CS) treatment on nasal polyp (NP) mucosa remodeling from patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP).

Study Design: Case series, retrospective study.

Methods: Patients (n = 18) with severe CRSwNP were treated with oral prednisone for 2 weeks and intranasal budesonide for 12 weeks.

Fluticasone furoate inhibits cytokine secretion from nasal epithelial cells and reduces eosinophil survival in an in vitro model of eosinophilic inflammation.

Background: Fluticasone furoate (FF) is an intranasal corticosteroid indicated for the treatment of allergic rhinitis (AR). However, the anti-inflammatory effects of FF in the nasal mucosa have yet to be investigated thoroughly. The aim of this study was to investigate the effect of FF on eosinophil survival and cytokine secretion from nasal mucosa epithelial cells.

Oral plus nasal corticosteroids improve smell, nasal congestion, and inflammation in sino-nasal polyposis.

Objectives/hypothesis: To assess the effect of oral plus intranasal corticosteroids on subjective outcomes (smell and nasal congestion) and objective outcomes (tissue eosinophilia and nitric oxide) in severe nasal polyposis (NP).

Study Design: After a 4-week steroid washout period (w0), severe NP were randomized into a treatment group (n = 67) that receive oral prednisone for 2 weeks (w2) plus intranasal budesonide for 12 weeks (w12), and a control group (n = 22) that received no steroid treatment.

Methods: Barcelona Smell Test 24 (BAST-24), nasal congestion, tissue eosinophilia, and nasal nitric oxide (nNO) were assessed.

Lung myofibroblasts are characterized by down-regulated cyclooxygenase-2 and its main metabolite, prostaglandin E2.

Background: Prostaglandin E2 (PGE2), the main metabolite of cyclooxygenase (COX), is a well-known anti-fibrotic agent. Moreover, myofibroblasts expressing α-smooth muscle actin (α-SMA), fibroblast expansion and epithelial-mesenchymal transition (EMT) are critical to the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our aim was to investigate the expression of COX-2 and PGE2 in human lung myofibroblasts and establish whether fibroblast-myofibroblast transition (FMT) and EMT are associated with COX-2 and PGE2 down-regulation.

Differential expression of remodeling markers by tissue structure in nasal polyposis.

Background: Data on the expression and role of matrix metalloproteinases (MMPs) and their tissue inhibitors (tissue inhibitor of metalloproteinases [TIMPs]) in chronic rhinosinusitis with nasal polyps (CRSwNPs) are contradictory, partly because or the use of different techniques of tissue analysis. The aim of this study was to establish a qualitative/semiquantitative method of analysis on the expression of these remodeling markers in different tissue structures and eosinophils in both NPs and nasal mucosa (NM).

Methods: NP tissues were obtained from patients undergoing endoscopic sinus surgery for severe CRSwNPs (n = 33) and NM tissues from patients undergoing nasal corrective surgery (n = 12).

Low prostaglandin E2 and cyclooxygenase expression in nasal mucosa fibroblasts of aspirin-intolerant asthmatics.

Background And Objective: Anomalies in the regulation of cyclooxygenase (COX)-1 and -2 have been described in nasal polyps of aspirin-induced asthma (AIA). Whether these anomalies are specific to nasal polyps or affect all the nasal mucosa (NM) of upper airways is still unclear. The objective of this study was to compare the COX pathway in NM of AIA patients with the NM of control subjects.

Signal transduction pathways (MAPKs, NF-κB, and C/EBP) regulating COX-2 expression in nasal fibroblasts from asthma patients with aspirin intolerance.

Background: Recent studies have revealed that cyclooxygenase-2 (COX-2) expression is down-regulated in aspirin-induced asthma (AIA). Various signal pathways (MAPKs, NF-κB and C/EBP) are involved in COX-2 regulation.

Objective: To investigate the regulation of COX-2 expression through MAP-kinase pathway activation and nuclear factor translocation in aspirin-induced asthma (AIA).

Proteasome inhibition reduces proliferation, collagen expression, and inflammatory cytokine production in nasal mucosa and polyp fibroblasts.

Proteasome inhibitors, used in cancer treatment for their proapoptotic effects, have anti-inflammatory and antifibrotic effects on animal models of various inflammatory and fibrotic diseases. Their effects in cells from patients affected by either inflammatory or fibrotic diseases have been poorly investigated. Nasal polyposis is a chronic inflammatory disease of the sinus mucosa characterized by tissue inflammation and remodeling.

Impact of cell culture methods on the outcomes of the in vitro inflammatory response in nasal polyps.

Background: In vitro culture of nasal polyp cells is frequently used in the investigation of inflammatory mechanisms and effect of treatments in nasal polyposis. Research outcomes may, however, be influenced by the culture methodology used.

Methods: Nasal polyp and nasal mucosa in vitro fibroblast cultures were pre-treated with foetal bovine serum (FBS)-free culture medium or medium supplemented with either FBS or charcoal-stripped (cs) FBS.

[Cyclooxigenase-2 levels are increased in the lung tissue and bronchial tumors of patients with chronic obstructive pulmonary disease].

Introduction: The expression of cyclooxygenase 2 (COX-2) is usually increased in inflammation and cancer. This study examines the expression of COX-2 in the lung of chronic obstructive pulmonary disease (COPD) patients with lung cancer.

Methods: We studied 44 male patients with bronchial cancer (27 squamous carcinoma and 17 adenocarcinoma).

Reduced expression of COXs and production of prostaglandin E(2) in patients with nasal polyps with or without aspirin-intolerant asthma.

Background: Researchers have debated whether regulation of the COX enzymes (COX-1 and COX-2), which mediate production of prostaglandins (PGs), affects the pathogenesis of nasal polyps (NPs) and aspirin-intolerant asthma (AIA).

Objective: We investigated the roles of PGE(2), COX-1 and COX-2, and PGE(2) receptors in the development of NPs and AIA by measuring their expression in fibroblasts derived from nasal mucosa (NM) and NPs.

Methods: Fibroblasts were isolated from the NM of subjects without asthma who had septal deviation, turbinate hypertrophy, or both (control subjects, n = 7); NPs of aspirin-tolerant nonasthmatic patients (n = 7); and NPs of patients with asthma who were intolerant of aspirin (n = 7).

Mometasone and desloratadine additive effect on eosinophil survival and cytokine secretion from epithelial cells.

Background: Although antihistamines and topical corticosteroids are used in combination to treat allergic rhinitis, their additive effect has not been yet demonstrated. The aim was investigate the antiinflammatory additive effect of mometasone and desloratadine on cytokine and sICAM-1 secretion by epithelial cells, and on eosinophil survival stimulated by human epithelial cells secretions from nasal mucosa and polyps.

Methods: Epithelial cells obtained from nasal mucosa or polyps were stimulated with 10% fetal bovine serum in presence of mometasone (10(-11) M-10(-5) M) with/without desloratadine (10(-5) M).

Nuclear translocation of the glucocorticoid receptor in fibroblasts of asthmatic patients with nasal polyposis insensitive to glucocorticoid treatment.

Background: Nasal polyposis (NP) is treated with topical glucocorticoids (GC). Some patients require endoscopic nasal surgery because GC treatment is ineffective. To exert its function, the GC needs to bind with the GC receptor (GR) and the GC-GR complex moves to the cell nucleus.

The importance of smell in patients with bronchiectasis.

Background: The aim of the study was to evaluate the sense of smell in patients with bronchiectasis.

Methods: Prospective controlled study was performed on 91 patients with bronchiectasis. Bronchiectasis patients were sub-classified depending on: the presence of chronic rhinosinusitis, with or without nasal polyps, and the bronchiectasis ethiology.

Lower sensitivity of nasal polyp fibroblasts to glucocorticoid anti-proliferative effects.

Background: Treatment with glucocorticoids (GCs) is the cornerstone of nasal polyp (NP) therapy, but some patients respond poorly to them. Fibroblasts are involved in both inflammation and remodelling of NP. We aimed to evaluate whether NP fibroblasts are less sensitive to GCs' anti-proliferative and anti-inflammatory effects, compared to nasal mucosa (NM) fibroblasts.

Importance of glucocorticoid receptors in upper and lower airways.

Glucocorticoids (GCs) are the most common and effective drugs for treating inflammatory airway diseases, but some patients respond poorly to them. GC effects are mediated through the glucocorticoid receptor (GR). We present an update on the GR gene, the GR alpha and GR beta splicing variants, their translational and post-translational modifications, as well as their alterations in disease.

Corticosteroid treatment in chronic rhinosinusitis: the possibilities and the limits.

Chronic rhinosinusitis, including nasal polyps, is an inflammatory disease of the nose and sinuses. The medical treatment, mainly topical intranasal and oral corticosteroids, constitutes its first line of therapy. Long-term treatment with corticosteroid nasal spray reduces inflammation and nasal polyp size, and improves nasal symptoms such as nasal blockage, rhinorrea, and the loss of smell.

Activity of the cyclooxygenase 2-prostaglandin-E prostanoid receptor pathway in mice exposed to house dust mite aeroallergens, and impact of exogenous prostaglandin E2.

Background: Prostaglandin E2 (PGE2), experimentally administered to asthma patients or assayed in murine models, improves allergen-driven airway inflammation. The mechanisms are unknown, but fluctuations of the endogenous cyclooxygenase (COX)-2/prostaglandin/E prostanoid (EP) receptor pathway activity likely contribute to the clinical outcome. We analyzed the activity of the pathway in mice sensitized to aeroallergens, and then studied its modulation under exogenous PGE2.