Overuse of diagnostic tools and medications in acute rhinosinusitis in Spain: a population-based study (the PROSINUS study).

Objectives Acute rhinosinusitis (ARS) has a high incidence. Diagnosis is clinical, and evolution is mostly self-limited. The aim of this study was to describe the sociodemographic characteristics and use of diagnostic tools and medications in patients with ARS. Design This is a prospective observational study in real-life clinical practice. Setting Patients with clinical diagnosis of ARS (n=2610) were included from ear, nose and throat clinics in Spain. A second visit at resolution was done. Participants Patients were classified according to the duration of symptoms: viral ARS (≤10 days), postviral ARS (>10 days, ≤12 weeks) and chronic rhinosinusitis (>12 weeks). Main outcome measures Sociodemographic characteristics, symptoms, disease severity, quality of life (Sino-Nasal Outcome Test-16), used diagnostic tools and medications, and the management performed by primary care physicians (PCPs) and by otorhinolaryngologists (ORLs) were assessed. Results Of the patients 36% were classified as having viral ARS, 63% postviral ARS and 1% as chronic rhinosinusitis. Working in a poorly air-conditioned environment was a risk factor (OR: 2.26, 95% CI 1.27 to 4.04) in developing postviral ARS. A higher number of diagnostic tools (rhinoscopy/endoscopy: 80% vs 70%; plain X-ray: 70% vs 55%; CT scan: 22% vs 12%; P<0.0001) were performed in postviral than viral cases. PCPs performed more X-rays than ORLs (P<0.0001). Patients, more those with postviral than viral ARS, received a high number of medications (oral antibiotics: 76% vs 62%; intranasal corticosteroids: 54% vs 38%; antihistamines: 46% vs 31%; mucolytic: 48% vs 60%; P<0.0001). PCPs prescribed more antibiotics, antihistamines and mucolytics than ORLs (P<0.0068). More patients with postviral than viral ARS reported symptoms of potential complications (1.5% vs 0.4%; P=0.0603). Independently of prescribed medications, quality of life was more affected in patients with postviral (38.7±14.2 vs 36.0±15.3; P=0.0031) than those with viral ARS. ARS resolution was obtained after 6.04 (viral) and 16.55 (postviral) days, with intranasal corticosteroids being associated with longer (OR: 1.07, 95% 1.02 to 1.12) and phytotherapy with shorter (OR: 0.95, 95% CI 0.91 to 1.00) duration. Conclusions There is a significant overuse of diagnostic tools and prescribed medications, predominantly oral antibiotics, by PCPs and ORLs, for viral and postviral ARS

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. Methods: Fibroblasts were isolated from NM of 5 AIA patients (AIA-NM) and 5 control subjects (control-NM). Cells were treated with 10 ng/ml IL-1b for up to 72 hours. Prostaglandin E2 (PGE2) production was measured by ELISA, expression of COX-1 protein by Western blot, and COX-2 protein by ELISA, Western blot and immunofluorescence techniques. Results: IL-1b increased PGE2 production and COX-1 protein expression in control-NM fibroblasts, but no changes were found in AIA-NM. IL-1b provoked a significant timedependent increase in COX-2 protein expression in control-NM fibroblasts but had a very mild effect on COX-2 protein expression in AIA-NM. Conclusions: Our data suggest that abnormalities in the COX pathway are not a phenomenon exclusive to nasal polyp mucosa as they are also present in all the nasal mucosa of AIA patients. These anomalies may be involved in the pathogenesis of airway inflammation and NSAID intolerance in asthma patients with chronic rhinosinusitis and nasal polyposis

Management of Mechanical Nasal Obstruction Isolated or Associated to Upper Airway Inflammatory Diseases in Real Life: Use of both Subjective and Objective Criteria

Purpose of review: Mechanical nasal obstruction (MNO) is a prevalent condition with a high impact on patient's quality-of-life (QoL) and socio-economic burden. The aim of this study was to determine the usefulness of both subjective and objective criteria in the appropriate management of MNO, either alone or associated to upper airway inflammatory diseases such as allergic rhinitis (AR) or chronic rhinosinusitis with nasal polyps (CRSwNP). Recent findings: A long debate persists about the usefulness of subjective and objective methods for making decisions on the management of patients with nasal obstruction. Establishing standards and ranges of symptom scales and questionnaires is essential to measure the success of an intervention and its impact on QoL. To our knowledge this is the first real-life study to describe the management of MNO using both subjective and objective criteria in MNO isolated or associated to upper airway inflammatory diseases (AR or CRSwNP). Medical treatment (intranasal corticosteroids) has a minor but significant improvement in MNO subjective outcomes (NO, NOSE, and CQ7) with no changes in loss of smell and objective outcomes. After surgery, all MNO patients reported a significant improvement in both subjective and objective outcomes, this improvement being higher in CRSwNP. We concluded that in daily clinical practice, the therapeutic recommendation for MNO should be based on both subjective and objective outcomes, nasal corrective surgery being the treatment of choice in MNO, either isolated or associated to upper airway inflammatory diseases, AR or CRSwNP

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

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.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.NP (n = 12) and NM fibroblasts (n = 10) were in vitro pre-incubated with LPS (24 hours) prior to the addition of dexamethasone. Cytokine/chemokine secretion was measured by ELISA and Cytometric Bead Array. GR?, GR?, mitogen-activated protein-kinase phosphatase-1 (MKP-1) and glucocorticoid-induced leucine zipper (GILZ) expression was measured by RT-PCR and immunoblotting, GR? nuclear translocation by immunocytochemistry, and GR? localization by immunoblotting. The role of MKP-1 and GILZ on dexamethasone-mediated cytokine inhibition was analyzed by small interfering RNA silencing.Pre-incubation of nasal fibroblasts with LPS enhanced the secretion of IL-6, CXCL8, RANTES, and GM-CSF induced by FBS. FBS-induced CXCL8 secretion was higher in NP than in NM fibroblasts. LPS effects on IL-6 and CXCL8 were mediated via activation of p38?/? MAPK and IKK/NF-?B pathways. Additionally, LPS pre-incubation: 1) reduced dexamethasone's capacity to inhibit FBS-induced IL-6, CXCL8 and RANTES, 2) reduced dexamethasone-induced GR? nuclear translocation (only in NM fibroblasts), 3) did not alter GR?/GR? expression, 4) decreased GILZ expression, and 5) did not affect dexamethasone's capacity to induce MKP-1 and GILZ expression. MKP-1 knockdown reduced dexamethasone's capacity to suppress FBS-induced CXCL8 release.The bacterial product LPS negatively affects GR function in control NM and NP fibroblasts by interfering with the capacity of the activated receptor to inhibit the production of pro-inflammatory mediators. This study contributes to the understanding of how bacterial infection of the upper airways may limit the efficacy of glucocorticoid treatment

Signal transduction pathways (MAPKS, NF-kB, 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). Methods Fibroblasts were isolated from specimens of nasal mucosa (NM, N = 5) and nasal polyps (NP, N = 5). After IL-1β (1 ng/ml) incubation, COX-2 and phosphorylated forms of ERK, JNK and p38 MAPK were measured by Western blot. MAPK's role in IL-1β-induced COX-2 expression was assessed by treating cells with ERK (PD98059), JNK (SP600125) and p38 MAPK (SB203580) inhibitors (0.1-10 µM) prior to IL-1β exposure. NF-κB and C/EBP nuclear translocation was measured by Western blot and TransAM® after IL-1β (10 ng/ml) exposure. Results No differences were observed in the MAPK phosphorylation time-course between NM and NP-AIA fibroblasts. The p38 MAPK inhibitor at 10 µM significantly reduced IL-1β-induced COX-2 expression in NM fibroblasts (85%). In NP-AIA fibroblasts the COX-2 inhibition (65%) at 1 and 10 µM was not statistically significant compared to non-treated cells. ERK and JNK inhibitors had no significant effect in either the NM or NP-AIA cultures. The effect of IL-1β on NF-κB and C/EBP subunits' nuclear translocation was similar between NM and NP-AIA fibroblasts. Conclusions These results suggest that p38 MAPK is the only MAPK involved in IL-1β-induced COX-2 expression. NM and NP-AIA fibroblasts have similar MAPK phosphorylation dynamics and nuclear factor translocation (NF-κB and C/EBP). COX-2 downregulation observed in AIA patients appears not to be caused by differences in MAPK dynamics or transcription factor translocation

When the Nose Meets the Lab: Histopathological Analysis in Chronic Rhinosinusitis with Nasal Polyps for Routine Clinical Practice

Purpose of review: We aimed to review the latest evidence regarding the value of tissue histopathological analysis in chronic rhinosinusitis with nasal polyps (CRSwNP) and to facilitate tissue analysis by proposing a pragmatic checklist for clinical settings. Recent findings: CRSwNP is a chronic inflammatory disease that severely impairs the patient's quality of life. The severity of the disease can be correlated with nasal polyps enriched in eosinophils/IL-5 and, although ≥ 10 eosinophils per high power field are considered enough to determine an eosinophilic CRS, this cut-off value, the biopsy method, and the sampling location are still a matter of debate. Besides, tissue eosinophil values might also have some added value when combined with other cellular counts (e.g., eosinophil-to-lymphocyte ratio, Charcot-Leyden crystals). Structured histopathology analysis of sinonasal tissue including, for instance, tissue remodelling biomarkers, fibrosis, and eosinophilic aggregates has proven to be a valuable tool for healthcare professionals to identify different pheno-endotypes of CRSwNP and to improve the prioritisation of candidates to targeted therapies. Patients with CRSwNP are treated according to their severity with corticosteroids (intranasal and systemic), endoscopic sinus surgery, and/or biological therapy. Summary: A panel of expert ear, nose, and throat specialists and pathologists proposed a pragmatic checklist to improve the clinical practice around tissue analysis in CRSwNP, to facilitate communication between hospital-based healthcare professionals, and to standardize the evaluation of inflammatory biomarkers

Paediatric Barcelona Olfactory Test-6 (pBOT-6): Validation of a Combined Odour Identification and Threshold Screening Test in Healthy Spanish Children and Adolescents

Background: Few odour tests have been created for children. Objectives: The aim of the present study was to develop and validate a simple and quick olfactory test, suitable for the evaluation of odour identification and threshold in a Spanish paediatric population, the paediatric Barcelona Olfactory Test-6 (pBOT-6).The pBOT-6 consisted in a set of 6 odorants for a forced-choice identification test (IT), and a 6 dilutions phenyl ethyl alcohol geometric series for the threshold test (TT). The pBOT-6 was compared with the U-sniff test (a validated international paediatric smell test) in 131 Spanish healthy volunteers aged 6-17 years. A Bland-Altman plot was used to determine the agreement between two tests. Reliability was analyzed in fifteenvolunteers using the intraclass correlation coefficient (ICC). Normative data was obtained and 8 children diagnosed with subjective smell loss were tested for validation.Bland-Altman analysis demonstrated a minimal bias of -1.71% with upper and lower limit of agreement of -31.1% and 27.6%, respectively. The ICC was 0.83 (95% CI 0.6-0.96) for the IT and 0.73 (95% CI 0.36-0.9) for the TT, showing excellent and good consistency between measurements over time. Mean pBOT-6 scores were significantly higher in healthy volunteers compared with patients with smell loss. Discrimination between normosmia and smell loss was achieved with a sensitivity of 96.9% and a specificity of 100%.The pBOT-6 offers an effectiveand fast method useful in clinical routine to distinguish, with high sensitivity and specificity, between paediatric patients with normosmia and those with smell dysfunction

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. Methods: Nasal mucosal epithelial cells and peripheral blood eosinophils were obtained from human volunteers. Epithelial cells were stimulated with 10% fetal bovine serum (FBS) in the presence of MP-AzeFlu, AZE, or FP (1:102 to 1:105 dilution). Concentrations of interleukin (IL)-6, IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured by ELISA. Eosinophils were incubated in 10% human epithelial cell-conditioned medium (HECM) and survival assessed by trypan blue dye exclusion. Results are expressed as mean ± SEM percentage secretion/survival compared with FBS/HECM (respectively). Results: FP and MP-AzeFlu (all dilutions) and AZE (1:102) significantly reduced IL-6 secretion and eosinophil survival compared with positive controls. At 1:102 dilution, IL-6 secretion was significantly lower with MP-AzeFlu (38.3 ± 4.2%, compared with FBS = 100%) than with AZE (76.1 ± 4.9%) or FP (53.0 ± 4.9%). At 1:102 dilution, eosinophil survival was significantly lower with MP-AzeFlu at day 3 (17.5 ± 3.0%) and day 4 (2.4 ± 1.4%, compared with HECM = 100%) than with AZE (day 3: 75.2 ± 7.2%; day 4: 44.0 ± 9.7%) or FP (day 3: 38.5 ± 3.5%; day 4: 14.6 ± 4.0%). Conclusion: Greater reductions in cytokine secretion and eosinophil survival observed with MP-AzeFlu in vitro may underlie MP-AzeFlu's superior clinical efficacy vs. AZE or FP alone observed in AR patients

Evaluating the Quality and Safety of In-Office Rhinologic Procedures: A YO-IFOS Pilot Study

The primary objective of this pilot study was to identify which aspects of in-office rhinologic procedures (IORPs) warrant further attention and investigation in the future. The secondary objectives were to survey which IORPs are most common and to identify needs for education and training. A cross-sectional study was carried out following the Consensus-Based Checklist for Reporting of Survey Studies (CROSS). The survey collected demographic, organizational, quality, and safety aspects of IORPs and was electronically distributed to YO-IFOS members across five continents. A total of 194 surgeons completed the survey, and 172 respondents (88%) performed IORPs. Ninety-nine responders (51.5%) worked in an academic setting. Common procedures included powered polypectomy (48, 28.4%) and turbinate reduction (93, 54.1%). The main concerns were about patients’ tolerance (116, 76.3%) and about the safety of the procedure (102, 67.1%). The most important barriers to the diffusion of IORPs are concerns about the tolerance and safety of these procedures. It would be convenient to establish protocols for this type of procedure to ensure the greatest patient comfort based on evidence