The burden of allergic rhinitis and allergic rhinoconjunctivitis on adolescents: A literature review.

OBJECTIVE: To evaluate the literature regarding the burden of allergic rhinitis (AR) and allergic rhinoconjunctivitis (ARC) in adolescents (aged 10-19 years). DATA SOURCES: Searches were performed in MEDLINE, Embase, Health Technology Assessment Database, and National Health Service Economic Evaluation Database for studies that evaluated concepts of symptoms, quality of life (QOL), daily activities, sleep, examination performance, school absenteeism and presenteeism, and treatment burden in adolescents with AR or ARC. STUDY SELECTIONS: English-language journal articles indexed in the last 15 years describing noninterventional, population-based studies. Records were assessed by 2 independent reviewers. RESULTS: A total of 27 articles were identified; outcomes evaluated were symptoms (n = 6 studies), QOL (n = 9), daily activities (n = 5), emotional aspects (n = 3), sleep (n = 6), education (n = 7), and treatment burden (n = 2). AR symptoms rated most bothersome were rhinorrhea, nasal congestion, and itchy eyes. QOL was worse in adolescents with AR vs controls regardless of QOL instrument used. Nasal symptoms and nasal obstruction were more likely to be associated with poor QOL in adolescents than in adults or younger children, respectively. Daily functioning and sleep were also negatively affected by AR. In addition, a detrimental effect on absenteeism, school productivity, and academic performance was reported. CONCLUSION: Although AR and ARC are sometimes perceived as trivial conditions, this review indicates that their effect on adolescent life is negative and far-reaching. It is critical that clinicians gain a greater understanding of the unique burden of AR and ARC in adolescents to ensure they receive prompt and appropriate care and treatment to improve clinical and academic outcomes.

Influence of MP 29-02 on ciliary beat frequency in human epithelial cells in vitro.

PURPOSE: MP 29-02, which contains fluticasone propionate and azelastine hydrochloride, is used as a topical nasal application for the treatment of seasonal and perennial allergic rhinitis. Although a multitude of data is available on the clinical symptom reduction and treatment safety of MP 29-02, the effect of MP 29-02 on ciliary beat frequency (CBF) has not been evaluated thus far. METHODS: MP 29-02-containing solution was applied at concentrations of 2.5, 5, 10, and 20% to 14 healthy subjects, and nasal ciliated epithelial cells were then visualized using a phase-contrast microscope. CBF was measured after the application of MP 29-02. For a comparison, fluticasone propionate was used. CBF measurements were then performed for 15 min at 22 °C. Ringer's solution was applied as a negative control. RESULTS: MP 29-02 significantly reduced CBF at all the tested concentrations compared with that of the control group within the observation time. At a 2.5% concentration, MP 29-02 significantly reduced CBF from 6.81 Hz (SD ± 1.35 Hz) at baseline to 4.88 Hz (SD ± 1.52 Hz, p < 0.001) after 15 min. In contrast, for fluticasone propionate, a significant reduction was observed only with the 20% concentration after 5, 10, and 15 min. CONCLUSIONS: MP 29-09 significantly reduced CB, with an almost linear relationship between the MP 29-09 concentration and reduction in CBF. For fluticasone propionate, a significant reduction of CBF was observed only at the highest analyzed concentration. The findings have implications for the long-term use of the MP 29-02. Yet, further clinical studies are needed to confirm these results in vivo, especially in patients with seasonal or perennial allergic rhinits.

Pathways through which asthma risk factors contribute to asthma severity in inner-city children.

BACKGROUND: Pathway analyses can be used to determine how host and environmental factors contribute to asthma severity. OBJECTIVE: To investigate pathways explaining asthma severity in inner-city children. METHODS: On the basis of medical evidence in the published literature, we developed a conceptual model to describe how 8 risk-factor domains (allergen sensitization, allergic inflammation, pulmonary physiology, stress, obesity, vitamin D, environmental tobacco smoke [ETS] exposure, and rhinitis severity) are linked to asthma severity. To estimate the relative magnitude and significance of hypothesized relationships among these domains and asthma severity, we applied a causal network analysis to test our model in an Inner-City Asthma Consortium study. Participants comprised 6- to 17-year-old children (n = 561) with asthma and rhinitis from 9 US inner cities who were evaluated every 2 months for 1 year. Asthma severity was measured by a longitudinal composite assessment of day and night symptoms, exacerbations, and controller usage. RESULTS: Our conceptual model explained 53.4% of the variance in asthma severity. An allergy pathway (linking allergen sensitization, allergic inflammation, pulmonary physiology, and rhinitis severity domains to asthma severity) and the ETS exposure pathway (linking ETS exposure and pulmonary physiology domains to asthma severity) exerted significant effects on asthma severity. Among the domains, pulmonary physiology and rhinitis severity had the largest significant standardized total effects on asthma severity (-0.51 and 0.48, respectively), followed by ETS exposure (0.30) and allergic inflammation (0.22). Although vitamin D had modest but significant indirect effects on asthma severity, its total effect was insignificant (0.01). CONCLUSIONS: The standardized effect sizes generated by a causal network analysis quantify the relative contributions of different domains and can be used to prioritize interventions to address asthma severity.

Efficacy and safety of beclomethasone dipropionate nasal aerosol in children with perennial allergic rhinitis.

BACKGROUND: Beclomethasone dipropionate (BDP) nasal aerosol (non-aqueous) is approved for management of seasonal and perennial allergic rhinitis (PAR) in adolescents and adults. OBJECTIVE: To evaluate the efficacy and safety of BDP nasal aerosol at 80 µg/day in children with PAR. METHODS: This 12-week, phase 3, double-blinded, placebo-controlled, parallel-group study randomized 547 children (4-11 years old) with PAR to once-daily BDP nasal aerosol at 80 µg/day or placebo. The primary end point was change from baseline in average morning and evening reflective total nasal symptom score (rTNSS) during the first 6 weeks of treatment in patients 6 to 11 years old. Changes from baseline in average morning and evening instantaneous TNSS (iTNSS) in children 6 to 11 years old and average rTNSS and iTNSS in children 4 to 11 years old were assessed during the first 6 weeks of treatment. RESULTS: Improvements were significantly greater with BDP nasal aerosol than with placebo during the first 6 weeks of treatment in children 6 to 11 years old in average morning and evening rTNSS and iTNSS (mean treatment difference -0.66 [P = .002] and -0.58 [P = .004], respectively). Improvements in average morning and evening rTNSS and iTNSS also were significantly greater in patients 4 to 11 years receiving BDP nasal aerosol than with placebo during the first 6 weeks of treatment (P = .002 and P = .004, respectively). Similar improvements were seen during 12 weeks of treatment. The safety profile of BDP nasal aerosol was comparable to that of placebo. CONCLUSION: The BDP nasal aerosol at 80 µg/day in children 4 to 11 years old was well tolerated and effective in controlling nasal symptoms of PAR. TRIAL REGISTRATION: www.clinicaltrials.gov, identifier NCT01783548.

No hypothalamic-pituitary-adrenal function effect with beclomethasone dipropionate nasal aerosol, based on 24-hour serum cortisol in pediatric allergic rhinitis.

BACKGROUND: Intranasal corticosteroids are the mainstay of allergic rhinitis (AR) treatment. Their potential to suppress the hypothalamic-pituitary-adrenal axis should be evaluated, especially after long-term daily use in children. OBJECTIVE: To evaluate the effects of treatment with non-aqueous beclomethasone dipropionate (BDP) nasal aerosol on hypothalamic-pituitary-adrenal axis function in children with perennial AR. METHODS: In this double-blinded, placebo-controlled, parallel-group study, patients (6-11 years old) with perennial AR were randomized (2:1) to BDP nasal aerosol at 80 µg/day (n = 67) or placebo (n = 32). The primary end point was change from baseline in 24-hour serum cortisol (SC) weighted mean for BDP nasal aerosol and placebo after 6 weeks of treatment, which was analyzed in the per-protocol population. RESULTS: The per-protocol population included 97 patients (BDP nasal aerosol, n = 66; placebo, n = 31). Baseline geometric mean SC weighted mean values were similar in the 80-µg/day BDP nasal aerosol and placebo groups (5.97 and 6.47 µg/dL, respectively). After 6 weeks' treatment, geometric mean values were 6.19 and 7.13 µg/dL, respectively, with no decrease from baseline in either group. Geometric mean SC ratio of BDP nasal aerosol at 80 µg/day to placebo was 0.91 (95% confidence interval 0.81-1.03), indicating predefined noninferiority. SC concentration-time profiles were similar for the placebo and 80-µg/day BDP nasal aerosol groups at baseline and week 6. BDP nasal aerosol at 80 µg/day was generally well tolerated. CONCLUSION: In pediatric patients with perennial AR, 24-hour SC profiles were comparable for BDP nasal aerosol and placebo, indicating that once-daily BDP nasal aerosol treatment did not significantly affect hypothalamic-pituitary-adrenal axis function. TRIAL REGISTRATION: ClinicalTrials.gov; NCT01697956.

Hormonal factors and incident asthma and allergic rhinitis during puberty in girls.

BACKGROUND: Accumulating evidence is indicating that hormonal factors play a role in new-onset allergic rhinitis and asthma after puberty. OBJECTIVE: To determine whether age at menarche and use of hormonal contraceptives predict new-onset allergic rhinitis and asthma after puberty in young German women. METHODS: A prospective community-based cohort study followed 1,191 girls 9 to 11 years old to early adulthood (19-24 years old). Self-administrated questionnaires concerning age at menarche, use of hormonal contraceptives, and status and age at onset of physician-diagnosed allergic rhinitis and asthma were collected at 16 to 18 and 19 to 24 years of age. Logistic regression models were used to analyze the incidence of asthma and allergic rhinitis after puberty and pooled estimates were obtained from the final model. RESULTS: Eleven percent of girls developed allergic rhinitis after menarche and 3% reported new-onset asthma. Late menarche (>13 years of age) was statistically significantly inversely related to allergic rhinitis (adjusted odds ratio [OR] 0.32, 95% confidence interval [CI] 0.14-0.74) but did not reach the level of statistical significance for asthma (OR 0.32, 95% CI 0.07-1.42). Use of hormonal contraceptives was inversely associated with new-onset allergic rhinitis (OR 0.14, 95% CI 0.08-0.23) and asthma (OR 0.27, 95% CI 0.12-0.58) after puberty. CONCLUSION: This study shows that girls with late onset of menarche are less likely to develop allergic rhinitis after puberty compared with those who have menarche at an average age. These findings also suggest that, in addition to endogenous hormones, hormonal contraceptives play a role and might protect young women from allergies and asthma.

Follow-up study in local allergic rhinitis shows a consistent entity not evolving to systemic allergic rhinitis.

BACKGROUND: Local allergic rhinitis (LAR) is a common disease that affects 25.7% of the rhinitis population and more than 47% of patients previously diagnosed with nonallergic rhinitis. Whether LAR is the first step in the natural history of allergic rhinitis (AR) with systemic atopy or a consistent entity is unknown. OBJECTIVE: The aim was to evaluate the natural history of a population with LAR of recent onset and the development of AR and asthma. METHODS: A prospective 10-year follow-up study with initial cohorts of 194 patients with LAR of recent onset and 130 healthy controls is being undertaken. A clinical-demographic questionnaire, spirometry, skin prick test, and specific IgE to aeroallergens were done yearly. Nasal allergen provocation tests with Dermatophagoides pteronyssinus, Alternaria alternata, Olea europea, and a mix of grass pollen were performed at baseline and after 5 years. RESULTS: At disease onset, most of the patients with LAR had moderate-to-severe persistent-perennial rhinitis; conjunctivitis and asthma were the main comorbidities (51.1% and 18.8%, respectively), and D pteronyssinus was the most relevant aeroallergen (51.1%). After 5 years of follow-up, a worsening of rhinitis was detected in 26.2%, with an increase in symptom persistence and severity, and new associations with conjunctivitis and asthma. Atopy was detected by skin prick test and/or serum specific-IgE in patients with LAR (6.81%) and in controls (4.5%). CONCLUSIONS: This study shows a similar rate of development of systemic atopy in LAR and controls, which suggests that LAR is an entity well differentiated from AR. To determine the natural course of LAR more precisely, this study is in progress to complete 10 years of follow-up.

Obesity and adiposity indicators, asthma, and atopy in Puerto Rican children.

BACKGROUND: Whether adiposity indicators other than body mass index (BMI) should be used in studies of childhood asthma is largely unknown. The role of atopy in "obese asthma" is also unclear. OBJECTIVES: To examine the relationship among adiposity indicators, asthma, and atopy in Puerto Rican children, and to assess whether atopy mediates the obesity-asthma association. METHODS: In a study of Puerto Rican children with (n = 351) and without (n = 327) asthma, we measured BMI, percent of body fat, waist circumference, and waist-to-hip ratio. The outcomes studied included asthma, lung function, measures of atopy, and, among cases, indicators of asthma severity or control. We performed mediation analysis to assess the contribution of atopy to the relationship between adiposity and asthma. RESULTS: BMI, percent of body fat, and waist circumference were associated with increased odds of asthma. Among cases, all 3 measures were generally associated with lung function, asthma severity/control, and atopy; however, there were differences depending on the adiposity indicator analyzed. Atopy considerably mediated the adiposity-asthma association in this population: allergic rhinitis accounted for 22% to 53% of the association with asthma, and sensitization to cockroach mediated 13% to 20% of the association with forced vital capacity and 29% to 42% of the association with emergency department visits for asthma. CONCLUSIONS: Adiposity indicators are associated with asthma, asthma severity/control, and atopy in Puerto Rican children. Atopy significantly mediates the effect of adiposity on asthma outcomes. Longitudinal studies are needed to further investigate the causal role, if any, of adiposity distribution and atopy on "obese asthma" in childhood.

ALLERGIC DISEASES AND ASTHMA IN ADOLESCENTS.

The goal of our research was to find out, whether asthma phenotyping, based on presence of accompanying allergic diseases is significant for asthma classification or not. Research was conducted on the basis of questioning of random and representative cohorts of Tbilisi children's population, by cross-section method of epidemiological research. Special extended screening questionnaire was developed for epidemiological study of allergic diseases. Diagnostic criterion for allergy was analyzed and representative cohort was selected. Research was conducted in 2010-2014 period. Studied population included 1450 children from 2 to 17 years age representing Tbilisi general population (of them, 850 girls and 600 boys). As a result of research the following findings were made: asthma was confirmed where at least two of the listed was present: diagnosis of asthma made by doctor, asthma symptoms and consumption of drugs against asthma. Allergic rhinitis was confirmed, where more than one of the listed symptoms was present and children should not have caught cold, rhinorrhea, nasal obstruction or snore, combined or IgE with some inhalation allergen. Atopic dermatitis was confirmed if the subject had atopic dermatitis at a time of interview or clinical study. Markers of asthma severity were based on number of asthma episodes and number of symptoms, or regular consumption of corticosteroids, number of missed days at school and answer of subjects to the question: for the past year what was the degree of discomfort attributable to asthma ("very high" - "absolutely not"). Allergic sensitization was assessed based on the skin prick-test and test of specific immunoglobulin E in serum and was deemed positive where the average diameter of blebs in skin prick tests was 3 mm larger than negative control and IgE-0,35kU/l. Lung function was assessed by means of respirometers, by evaluating maximal forced expiration data and flow-volume curves. Allergic rhinitis was regarded as the most common accompanying disease. Subjects with non-specific hyperresponsiveness of bronchi and asthma before age of 12, were classified only as being in remission and having accompanying allergic disease and subjects without obstruction and asthma were classified as absence of asthma and were designated as independent group. Population was divided into "active" (indicate presence of symptoms or are subjected to treatment) and "ever" (diagnosis was made before involvement into the study) groups. Main finding is identification of correlation between airways inflammation and phenotype accompanying asthma in children of age from 2 to 16. Research showed than of 860 children (398 males and 462 females) of age from 2 to 8, 62 children had asthma (17 females and 45 males) with at least accompanying disease. Of 590 children (311 males and 279 females) of age from 9 to 17, 81 children had asthma (26 females and 55 males) with at least accompanying allergic disease. The most common asthma phenotype was only asthma, in 32.8%, further asthma and allergic rhinitis (27.9%), asthma with allergic rhinitis and atopic dermatitis (13%), asthma with atopic dermatitis (4.9%). Asthma phenotypes did not differ significantly, with respect of asthma severity and need of anti-inflammation medication. Gender was notably correlated with only one phenotype of asthma; boys are more susceptible to asthma and allergic rhinitis, compared with the girls (9.5% boys and 4.9% girls) p=0.001. Lung function is significantly correlated with hyperresponsiveness of bronchi associated with asthma phenotype with the lowest FEV 2% data - in case of asthma, allergic rhinitis and atopic dermatitis. Our research showed than asthma in adults is accompanied with allergic rhinitis or atopic dermatitis (approximately 14.9%). In puberty, asthma phenotypes with allergic rhinitis was mostly associated with non-specific hyperresponsiveness of bronchi and airways inflammation (p>0.05). In the combinations of allergic diseases the association of the phenotypes with gender was mostly found in males (p=0.001).

A randomized controlled trial to assess adherence to allergic rhinitis treatment following a daily short message service (SMS) via the mobile phone.

BACKGROUND: Short message service (SMS) has been suggested as an effective method to improve adherence to medical therapy in some chronic diseases. However, data on the effects of SMS interventions to allergic rhinitis (AR) treatment is limited at present. We aimed to assess whether a daily SMS reminder could improve AR patients' adherence to medication and treatment outcomes. METHODS: Fifty outpatients with AR were randomized to either receive (SMS group) or not (control group) a daily SMS reminder on their cell phone to take intranasal corticosteroid treatment for 30 days. The primary study outcomes were self-reported adherence to medication, clinic attendance rate, and severity of AR symptoms using a visual analogue scale (VAS). Secondary outcomes were changes in nasal patency (minimum cross-sectional area, nasal cavity volume, and nasal airway resistance) and exhaled nasal nitric oxide levels. RESULTS: Self-reported adherence to medication in the SMS group (15/25, 60%), was significantly higher than in the control group (7/25, 28%, p = 0.02). Similarly, the clinic attendance rate in the SMS group (72%) was significantly higher than in the control group (40%, p = 0.02). Although the VAS score improved significantly from baseline in both study groups, the improvement in the SMS group was significantly greater than in the control group (4.38 ± 4.38 vs. 8.74 ± 6.54, p = 0.031). No significant differences were observed between the two groups for the secondary outcomes. CONCLUSIONS: A daily SMS reminder may be an effective intervention to improve adherence to medication and treatment outcomes in AR patients.

Prevalence and clinical relevance of allergic rhinitis in patients with classic asthma and cough variant asthma.

BACKGROUND: A clinically relevant relationship between classic asthma and allergic rhinitis has been reported. However, the possible link between cough variant asthma (CVA) and allergic rhinitis remains unknown. OBJECTIVES: To clarify the prevalence and clinical relevance of perennial allergic rhinitis or seasonal allergic rhinitis in CVA patients compared to classic asthma patients. METHODS: We retrospectively studied adult patients with classic asthma (n = 190) and those with CVA (n = 83). The prevalence of perennial allergic rhinitis or seasonal allergic rhinitis and associations of concomitant perennial or seasonal allergic rhinitis with asthma severity, forced expiratory volume in 1 s (% predicted), fractional exhaled nitric oxide (FeNO) levels, and eosinophil proportions in sputum and blood were analyzed in the two groups. RESULTS: The prevalence of perennial allergic rhinitis and/or seasonal allergic rhinitis was significantly higher in classic asthma patients than in CVA patients (all p < 0.05). Concomitant perennial allergic rhinitis was associated with higher FeNO levels and eosinophil proportions in sputum and blood in classic asthma patients (p = 0.035, p = 0.036, and p = 0.008, respectively) and with higher asthma severity, FeNO levels, and sputum eosinophil proportions in CVA patients (p = 0.031, p = 0.007, and p = 0.010, respectively). Concomitant seasonal allergic rhinitis was only associated with higher sputum eosinophil proportions in CVA patients with active rhinitis symptoms during the sensitized pollen season (p = 0.025). CONCLUSIONS: Perennial allergic rhinitis may be relevant for CVA patients as well as classic asthma patients by consistently augmenting eosinophilic lower airway inflammation.

The effect of high altitude on olfactory functions.

It is known that high-altitude trips cause nasal congestion, impaired nasal mucociliary transport rate, and increased nasal resistance, due to decreased partial oxygen pressure and dry air. It is also known that olfactory perception is affected by barometric pressure and humidity. The aim of the present study was to investigate whether olfactory function changes in relation to high altitude in a natural setting. The present study included 41 volunteers with no history of chronic rhinosinusitis or nasal polyposis. The study group consisted of 31 men (76 %) and 10 women (24 %); the mean age of the study population was 38 ± 10 years. Olfactory testing was conducted using "Sniffin' Sticks" at a high altitude (2,200 ms) and at sea level. Odor test scores for threshold and identification were significantly better at sea level than at high altitude (p < 0.001). The major finding of this investigation was that olfactory functions are decreased at high altitudes.

Application of Peak Nasal Inspiratory Flow reference values in the treatment of allergic rhinitis.

OBJECTIVE: To assess the applicability of the Peak Nasal Inspiratory Flow (PNIF) curves in follow-up of children in the treatment of allergic rhinitis. METHODS: Prospective study of 40 patients with AR, grouped in corticosteroid spray versus physiological saline solution use. Follow up for 10 weeks through clinical score and PNIF percentages in relation to the reference curves, with was-out at week 8. Statistical assessment of the effect of treatment on variation of PNIF and clinical score was calculated by ANOVA model and Multiple Comparison of Means Test - Least Significant Difference. RESULTS: There was a statistically significant influence of the group, time and interaction between time and group on PNIF percentages. Throughout follow up, patients from the treatment group had mean PNIF percentages significantly higher than the placebo group. Clinical score results also demonstrated a statistically significant influence between the groups, time and interaction between time and group. CONCLUSION: Increase in PNIF percentage values observed in children treated with intranasal corticosteroids revealed the applicability of PNIF curves in their follow up.

[Some features of development and course of bronchial asthma in children in azerbaijan].

According to the international "ISAAC" program, we studied the peculiarities of bronchial asthma in children at the age of 13-14 years, in various climatic and geographic regions of Azerbaijan. At the first stage of investigation, 14693 eighth class pupils of high school from the four various regions were surveyed: the I region (n=4979) - an industrial city, placed in a semi-desert area; the II region (n=3010) - rural areas, located in a semi-desert climatic zone; the III region (n=3133) - areas, located in a subtropical climatic zone; the IV region (n=3571) - an ecologically clean mountainous region, located along southern slopes of the Greater Caucasian ridge. At the second stage of the investigation allergological, clinical-functional examinations were carried out in children with symptoms of allergic diseases. It was established that prevalence of BA was reliably more frequent in the industrial city (4,6%) than in other three, especially rural areas. In subtropical climatic area 2,8%, in rural semi-desert area - 2,5%, in mountainous region - 1,8% of examined children were suffering from BA. Study of the clinical course of diseases in children with allergic diseases and their allergic status revealed that structure and expressiveness of sensitization to domestic, pollen, fungous and food allergens depends on residing area.

Dampness and moulds in relation to respiratory and allergic symptoms in children: results from Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC Phase Two).

BACKGROUND: Many studies report that damp housing conditions are associated with respiratory symptoms. Less is known about mechanisms and possible effect modifiers. Studies of dampness in relation to allergic sensitization and eczema are scarce. OBJECTIVE: We study the influence of damp housing conditions world-wide on symptoms and objective outcomes. METHODS: Cross-sectional studies of 8-12-year-old children in 20 countries used standardized methodology from Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC). Symptoms of asthma, rhinitis and eczema, plus residential exposure to dampness and moulds, were ascertained by parental questionnaires (n = 46 051). Skin examination, skin prick tests (n = 26 967) and hypertonic saline bronchial challenge (n = 5713) were performed. In subsamples stratified by wheeze (n = 1175), dust was sampled and analysed for house dust mite (HDM) allergens and endotoxin. RESULTS: Current exposure to dampness was more common for wheezy children (pooled odds ratio 1.58, 95% CI 1.40-1.79) and was associated with greater symptom severity among wheezers, irrespective of atopy. A significant (P < 0.01) adverse effect of dampness was also seen for cough and phlegm, rhinitis and reported eczema, but not for examined eczema, nor bronchial hyperresponsiveness. HDM sensitization was more common in damp homes (OR 1.16, 1.03-1.32). HDM-allergen levels were higher in damp homes and were positively associated with HDM-sensitization, but not wheeze. CONCLUSION: A consistent association of dampness with respiratory and other symptoms was found in both affluent and non-affluent countries, among both atopic and non-atopic children. HDM exposure and sensitization may contribute, but the link seems to be related principally to non-atopic mechanisms.

Specialist-based treatment reduces the severity of allergic rhinitis.

BACKGROUND: Although the treatment of allergic rhinitis (AR) is now well established, its impact on severity has not yet been evaluated. OBJECTIVE: The aim was to analyse specialist-based treatment on AR severity, nasal symptoms and quality of life. METHODS: A longitudinal observational, prospective, multi-centre study with 4 weeks of follow-up was carried out by 141 allergologists and ENT specialists in Spain. Selection criteria were adult patients with AR, clinically diagnosed at least 2 years before, with a total nasal symptom score (TNSS) ≥5, not receiving either antihistamines within the previous week or nasal corticosteroids during the 2 previous weeks. Disease severity using both original Allergic Rhinitis and its Impact on Asthma (o-ARIA) and modified (m-ARIA) classifications, nasal symptoms, and Quality of Life (ESPRINT-15), were measured at baseline and after 4 weeks of treatment. RESULTS: Among the recruited AR patients (n = 707, 58% women), 39.3% were intermittent and 60.7% persistent, 40.2% had asthma and 61.4% conjunctivitis. Most patients were treated with second generation antihistamines in monotherapy (63.2%) or in combination with intranasal corticosteroids (31.5%). While using o-ARIA, 96.9% of patients had 'moderate/severe' AR, the m-ARIA discriminated between 'moderate' (55.4%) and severe (41.5%) AR, at baseline. After 4 weeks of treatment, improvement was found on disease severity (P < 0.0001), TNSS (8.2 ± 1.8 vs. 3.5 ± 2.3, P < 0.0001) and Quality of Life (ESPRINT-15 global score: 3.0 ± 1.2 vs. 1.1 ± 1.0, P < 0.0001). CONCLUSIONS: Specialist-based treatment reduces AR severity, evaluated using the m-ARIA classification for the first time, in addition to the improvement of nasal symptoms and quality of life. CLINICAL RELEVANCE: Specialist-based treatment improves AR severity, in addition to nasal symptoms and quality of life. However, no matter the treatment option some AR patients remain severe and need further follow-up.

Elevated guanylate cyclase and cyclic-guanosine monophosphate-dependent protein kinase levels in nasal mucosae of antigen-challenged rats.

OBJECTIVE: In patients with severe allergic rhinitis, the most serious symptom is rhinostenosis, which is considered to be induced by a dilatation of plexus cavernosum. The vascular relaxing responses to chemical mediators are mainly mediated by the production of nitric oxide (NO). However, the exact mechanism(s) in nasal venoresponsiveness of allergic rhinitis is not fully understood. In the present study, we investigated the roles of soluble guanylate cyclase (sGC) and cyclic-guanosine monophosphate (c-GMP)-dependent protein kinase G (PKG) in venodilatation of nasal mucosae of antigen-challenged rats. METHODS: Actively sensitized rats were repeatedly challenged with aerosolized antigen (2,4-dinitrophenylated Ascaris suum). Twenty-four hours after the final antigen challenge, nasal septum mucosa was exposed surgically and observed directly in vivo under a stereoscopic microscope. The sodium nitroprusside (SNP) and 8-Br-cGMP (a PKG activator) were administered into arterial injection, and the venous diameters of nasal mucosa were observed. RESULTS: The intra-arterial injections of SNP and 8-Br-cGMP-induced venodilatation were significantly augmented in the nasal mucosae of repeatedly antigen-challenged rats. Furthermore, protein expressions of sGC and PKG were significantly increased in nasal mucosae of the antigen-challenged rats. CONCLUSION: The present findings suggest the idea that the promoted cGMP/PKG pathway may be involved in the enhanced NO-induced venodilatation in nasal mucosae of antigen-challenged rats.

Topical treatment targeting sphingosine-1-phosphate and sphingosine lyase abrogates experimental allergic rhinitis in a murine model.

BACKGROUND: Sphingosine-1-phosphate (S1P) plays a crucial role in homeostasis of the immune system by regulating lymphocyte recirculation and inflammatory cell recruitment. The levels of S1P are tightly controlled through regulated production and controlled breakdown by sphingosine-lyase (SL). The S1P analogue FTY720 has been developed as an immunosuppressant in transplantation and tested as a treatment for various inflammatory diseases. FTY720 exploits S1P biology by acting as a S1P1 and S1P 3 agonist and by inhibiting S1P breakdown by SL. OBJECTIVE: Here, we investigate interfering S1P in allergic rhinitis (AR) and its way of action. METHODS: Allergic rhinitis was induced by sensitizing mice to ovalbumin (OVA) and challenging the nose with OVA allergen. At the time of allergen challenge, mice received topical intranasal treatment with FTY720. To address the relative contribution of SL inhibition in mediating its effects, some mice were treated with the SL inhibitor 2-acetyl-4-tetrahydroxybutyl (THI). RESULTS: FTY720 treatment resulted in significantly fewer eosinophils, mast cells and dendritic cells in the nasal mucosa of AR animals, compared with diluent treatment. Levels of IL-4, IL-5, IL-10 and IL-13 produced by lymph node cells fell significantly in FTY720-treated animals. Moreover, FTY720 proved potent enough to suppress inflammation in a model of persistent AR. In vitro and in vivo experiments indicate that FTY720 impaired Th2 differentiation and proliferation important in driving eosinophilia and induced apoptosis in mast cells. CONCLUSION: Our results indicate that interfering with S1P metabolism is a powerful and feasible strategy to develop new topical agents that suppress AR.

Impact of allergic rhinitis symptoms on quality of life in primary care.

BACKGROUND: Allergic rhinitis (AR) impairs quality of life (QoL), sleep and work. The Allergic Rhinitis and its Impact on Asthma (ARIA) classification is widely used, but the impact of the different symptoms on QoL is not clear. OBJECTIVE: To describe characteristics of patients consulting in primary care for AR and to study the impact of AR symptoms and the ARIA classes on QoL. METHODS: A multicenter prospective observational cross-sectional study assessed the visual analogue scale (VAS) in the management of AR in 990 patients consulting general practitioners for AR. Patients were classified according to the four classes of ARIA. VAS, Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and total symptom score (TSS) for nasal and non-nasal symptoms were evaluated. VAS and TSS measures were compared with RQLQ. RESULTS: Mild intermittent rhinitis was diagnosed in 20% of patients, mild persistent rhinitis in 17%, moderate/severe intermittent rhinitis in 15% and moderate/severe persistent rhinitis in 48%. The presence of treatments did not affect VAS levels. Both severity and duration of rhinitis had an impact on QoL and VAS levels. Ocular symptoms (OR: 2.78, 95% CI: 1.965-3.939) including eyelid edema (OR: 2.07, 95% CI: 1.274-3.360) and asthenia (OR: 2.73, 95% CI: 1.922-3.877) had more impact on RQLQ than nasal obstruction (OR: 1.61, 95% CI: 1.078-2.405) and nasal pruritus (OR 1.45, 95% CI: 1.028-2.042). Sneezing and rhinorrhea did not impact RQLQ. CONCLUSIONS: This study confirmed that ocular symptoms and, to a lesser degree, nasal obstruction and pruritus have a significant impact on QoL.

Effect of nebulized beclomethasone on airway inflammation and clinical status of children with allergic asthma and rhinitis: a randomized, double-blind, placebo-controlled study.

We aimed to evaluate the therapeutic effect of nebulized beclomethasone dipropionate (nBDP) on both allergic asthma and rhinitis. In a randomized, double-blind, placebo-controlled study, 40 children (mean age 10.7 ± 2.1 years) with allergic asthma and rhinitis received either nBDP (daily dose of 800 µg, administered twice daily) or placebo for 4 weeks (with a face mask), after a 2-week run-in period of clinical assessment. Nasal and oral fractional exhaled nitric oxide (FeNO) measurements together with pulmonary function tests, nasal and oral exhaled breath condensate (EBC) collection for pH and interleukin-5 (IL-5) measurements as well as nasal and bronchial symptom scores were obtained at baseline and after 4-week treatment. A significant improvement in oral FeNO, oral and nasal EBC IL-5 and nasal EBC pH was observed in the nBDP group when comparing the values with baseline, together with an improvement in symptom score of the visual analogue scale, nasal obstruction, sneezing, rhinorrhea, breathing difficulty, cough, wheezing and sleep disturbance (nBDP end treatment vs. baseline, Wilcoxon signed-rank test). nBDP was more effective than placebo (ANCOVA test) in improving [difference Δ = response after treatment at the last visit (active or placebo) - value at baseline] nasal pH, oral IL-5, oral FeNO, forced expiratory volume in 1 s, forced expiratory volume in 1 s/forced vital capacity, peek expiratory flow, visual analogue scale, breathing difficulty, cough, wheezing and sleep disturbance scores. No differences were observed between the nBDP and the placebo group for symptom score of rhinitis. nBDP is a useful treatment for airway inflammation and clinical status in children with concomitant allergic asthma and rhinitis.