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

Effects on nasal nitric oxide production of 2 mechanisms of vasoconstriction

Background: Vasoconstrictor drugs reduce nitric oxide (NO) production in vitro by inhibiting the enzyme involved in the regulation of inducible and constitutive NO synthases (iNOS and cNOS). Intranasal vasoconstrictors also decrease nasal NO concentration in vivo. It is as yet unclear if this last finding is due to the effects of the drug on the enzyme or on the vessels. Physical exercise also induces nasal vasoconstriction and reduces nasal resistance. Objectives: The aim of this study was to clarify the mechanisms involved in xylometazoline-induced reduction of nasal NO concentration. Methods: We compared 2 randomized groups of patients with moderate-severe persistent allergic rhinitis. The fi rst group (n=24) underwent a physiological nasal vasoconstrictor stimulus (exercise) whereas the second group (n=29) was treated with a nasal vasoconstrictor drug (topical xylometazoline). Nasal volume and NO were determined at baseline and 15 to 20 minutes after the end of each stimulus using acoustic rhinometry and chemiluminescence, respectively. Results: Baseline values of nasal volume and NO did not differ between the 2 groups. Nasal volume increased by 57% (P = .0001) after exercise and 71% (P = .0001) after xylometazoline. Nasal NO decreased (25%, P = .001) after xylometazoline, but not after exercise. Conclusion: Physical exercise and topical xylometazoline cause vasoconstriction and similar effects on nasal volume. In contrast nasal NO decreased with xylometazoline but not after exercise. These fi ndings suggest that vasoconstrictor drugs reduce nasal NO by mechanisms other than vasoconstriction

Allergic rhinitis: continuous or on demand antihistamine therapy?

Allergic rhinitis is an inflammatory disease of the nasal mucosa, caused by an IgE-mediated reaction after exposure to the allergen to which the patient is sensitized. Histamine is the most important preformed mediator released in the early stage of the allergic reaction, and also contributes to the late phase of the latter, exhibiting proinflammatory effects. Minimal persistent inflammation is a physiopathological phenomenon induced by the presence of an inflammatory cell infiltrate, together with ICAM-1 expression in the epithelial cells of the mucosa exposed to the allergen to which they are sensitized, in the absence of clinical symptoms. This molecule is considered to be an allergic inflammatory marker. The priming effect first described by Connell in 1968 consists of the reduction in the allergen concentration required to elicit a nasal hyper-response when performing a daily nasal exposure test. This implies that with natural exposure to inhaled allergens, small amounts of environmental allergen will maintain the patient symptoms, and thus of course minimal persistent inflammation. Considering the above, it is questionable whether antihistamines should be administered on a continuous basis or upon demand. The antihistamines, and fundamentally the second-generation drugs, have been shown to exert an antiinflammatory effect, and this effect is greater when the drug is administered continuously than when administered upon demand. Likewise, a reduction in treatment cost and an improvement in quality of life among patients treated on a continuous basis has been documented. However, no studies have been specifically designed to clarify the indication of treatment on a continuous basis or upon demand, as occurs in the GINA. As a result, the individualization of treatment according to the concrete characteristics of each patient seems to be the best approach, at least for the time being

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

Use of antihistamines in pediatrics

Drugs with antihistamine action are among the most commonly prescribed medicines in pediatrics. According to the International Medical Statistics (IMS), almost two million antihistamine units (in solution) for pediatric use were sold in Spain during 2006 - at a cost of nearly 6 million euros. Of this amount, 34% corresponded to first-generation (or sedating) antihistamines. The difficulties inherent to research for drug development increase considerably when the pediatric age range is involved. The use of any medication in this age group must adhere to the strictest safety criteria, and must offer the maximum guarantees of effi cacy. For this reason, detailed knowledge of the best scientific evidence available in relation to these aspects is essential for warranting drug use. The first-generation antihistamines have never been adequately studied for pediatric age groups, though they are still widely used in application to such patients. In contrast, studies in children have been made with the second-generation antihistamines, allowing us to know their safety profile, and such medicines are available at pediatric dosages that have been well documented from the pharmacological perspective. The present review affords an update to our most recent knowledge on antihistamine use in children, based on the best scientific evidence available

Vasoactive intestinal peptide in human nasal mucosa

Vasoactive intestinal peptide (VIP), which is present with acetylcholine in parasympathetic nerve fibers, may have important regulatory functions in mucous membranes. The potential roles for VIP in human nasal mucosa were studied using an integrated approach. The VIP content of human nasal mucosa was determined to be 2.84 +/- 0.47 pmol/g wet weight (n = 8) by RIA. VIP-immunoreactive nerve fibers were found to be most concentrated in submucosal glands adjacent to serous and mucous cells. 125I-VIP binding sites were located on submucosal glands, epithelial cells, and arterioles. In short-term explant culture, VIP stimulated lactoferrin release from serous cells but did not stimulate [3H]glucosamine-labeled respiratory glycoconjugate secretion. Methacholine was more potent than VIP, and methacholine stimulated both lactoferrin and respiratory glycoconjugate release. The addition of VIP plus methacholine to explants resulted in additive increases in lactoferrin release. Based upon the autoradiographic distribution of 125I-VIP binding sites and the effects on explants, VIP derived from parasympathetic nerve fibers may function in the regulation of serous cell secretion in human nasal mucosa. VIP may also participate in the regulation of vasomotor tone

Effect of pollutants upon patients with respiratory allergies

Epidemiological studies have revealed an association between pollution and allergic respiratory diseases. The main pollutants in this sense are nitric oxide, ozone, and particulate matter. The present review on one hand addresses the chemical characteristics of each of these three groups of pollutants and their main sources, and on the other examines their effects upon allergic respiratory diseases--placing special emphasis on the effects of diesel exhaust particles. For each of the pollutants, the underlying mechanisms capable of influencing allergic respiratory diseases are commented. Lastly, an evaluation is made of some of the genetic aspects related to the response to pollutants

Dupilumab Improves Nasal Polyp Burden and Asthma Control in Patients With CRSwNP and AERD

In the difficult-to-treat subgroup of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and comorbid aspirin-exacerbated respiratory disease, dupilumab significantly improved CRSwNP disease outcomes, along with asthma control and lung function. This is preliminary evidence of the effect of dupilumab in patients with CRSwNP and comorbid aspirin- exacerbated respiratory disease

Air pollution and allergens

It is well known that the prevalence of allergic diseases has increased in recent decades in the industrialized world. Exposure to environmental pollutants may partially account for this increased prevalence. In effect, air pollution is a growing public health problem. In Europe, the main source of air pollution due to particles in suspension is represented by motor vehicles--particularly those that use diesel fuel. Diesel exhaust particles (DEPs) are composed of a carbon core upon which high-molecular weight organic chemical components and heavy metals deposit. Over 80% of all DEPs are in the ultrafine particle range (< 0.1 pm in diameter). Air pollutants not only have a direct or indirect effect upon the individual, but also exert important actions upon aeroallergens. Pollen in heavily polluted zones can express a larger amount of proteins described as being allergenic. Through physical contact with the pollen particles, DEPs can disrupt the former, leading to the release of paucimicronic particles and transporting them by air--thus facilitating their penetration of the human airways. Climate change in part gives rise to variations in the temperature pattern characterizing the different seasons of the year. Thus, plants may vary their pollination calendar, advancing and prolonging their pollination period. In addition, in the presence of high CO2 concentrations and temperatures, plants increase their pollen output. Climate change may also lead to the extinction of species, and to the consolidation of non-native species--with the subsequent risk of allergic sensitization among the exposed human population. In conclusion, there is sufficient scientific evidence on the effect of air pollution upon allergens, increasing exposure to the latter, their concentration and/or biological allergenic activity