Uncontrolled allergic rhinitis and chronic rhinosinusitis: where do we stand today?

State‐of‐the‐art documents like ARIA and EPOS provide clinicians with evidence‐based treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS), respectively. The currently available medications can alleviate symptoms associated with AR and RS. In real life, a significant percentage of patients with AR and CRS continue to experience bothersome symptoms despite adequate treatment. This group with so‐called severe chronic upper airway disease (SCUAD) represents a therapeutic challenge. The concept of control of disease has only recently been introduced in the field of AR and CRS. In case of poor control of symptoms despite guideline‐directed pharmacotherapy, one needs to consider the presence of SCUAD but also treatment‐related, diagnosis‐related and/or patient‐related factors. Treatment‐related issues of uncontrolled upper airway disease are linked with the correct choice of treatment and route of administration, symptom‐oriented treatment and the evaluation of the need for immunotherapy in allergic patients. The diagnosis of AR and CRS should be reconsidered in case of uncontrolled disease, excluding concomitant anatomic nasal deformities, global airway dysfunction and systemic diseases. Patient‐related issues responsible for the lack of control in chronic upper airway inflammation are often but not always linked with adherence to the prescribed medication and education. This review is an initiative taken by the ENT section of the EAACI in conjunction with ARIA and EPOS experts who felt the need to provide a comprehensive overview of the current state of the art of control in upper airway inflammation and stressing the unmet needs in this domain.     

Seasonal Specificity of Seasonal Allergens and Validation of the ARIA Classification in Korea

Purpose

In Korea, tree pollens are known to be prevalent in spring, grass pollens in summer and weed pollens in autumn. However, few studies have revealed their seasonal specificity for allergic rhinitis symptoms. An ARIA (Allergic Rhinitis and its Impact on Asthma) classification of allergic rhinitis was recently introduced and its clinical validation has not been well proved. The aim of this study was to evaluate the seasonal specificity of seasonal allergens and to validate the ARIA classification with the conventional seasonal and perennial allergic rhinitis (SAR/PAR) classification.

Methods

Two hundred twenty six patients with allergic rhinitis were included in this study. The patients were classified according to the sensitized allergens and the ARIA classifications. A questionnaire survey was performed and the data on the seasonal symptom score, the severity of symptoms and the SNOT (sinonasal outcome test)-20 score was obtained and the data was analyzed and compared between the conventional SAR/PAR classification and the ARIA classification.

Results

Seasonal pollens (tree, grass, weed) were not specific to the pollen peak season and the patients'' symptoms were severe during spring and autumn regardless of the offending pollens. More than 60% of the patients with SAR showed persistent symptoms and 33% of the patients with perennial allergic rhinitis (PAR) had intermittent symptoms, showing the lack of association between the SAR/PAR/PAR+SAR classification and the ARIA classification. The ARIA classification showed better association not only with the symptomatic score, but also with the SNOT-20 score, which showed better validity than the conventional SAR/PAR classifications.

Conclusions

Seasonal pollens were not specific to their season of prevalence in terms of the severity of symptoms, and the ARIA classification showed better representation of allergic symptoms and quality of life (SNOT-20 score) than did the SAR/PAR classification.     

The natural course of allergic rhinitis during 12 years of follow-up

As symptoms of allergic rhinitis are generally thought to disappear with increasing age, we decided to follow up our allergic rhinitis patients to ascertain whether their disease had regressed or progressed, and whether they had developed respiratory symptoms. At our department, between 1979 and 1982, allergic rhinitis was diagnosed in 108 patients. In 1993, 82 of the patients (40 women, 42 men; mean age 36 years), none of whom had received immunotherapy, answered a questionnaire concerning the status of their allergic rhinitis, and any development of the disease during the interim. Of the 82 patients, one was free of allergic symptoms and 39% had become better; symptoms were unchanged in 39% of cases, and worse in 21%. Six percent had suffered from asthma at presentation, 6% had developed asthma in the interim, and 34% reported other lower airways symptoms. Neither sex nor age at diagnosis was a determinant of the course of allergic rhinitis. Thus, in contrast to findings in other studies, the severity of allergic rhinitis seems to have increased among our patients.     

Epidemiological characterization of the intermittent and persistent types of allergic rhinitis

BACKGROUND: A new classification of allergic rhinitis (AR) has been proposed by the allergic rhinitis and its impact on asthma (ARIA) workgroup. The validity of this new classification is still largely unknown, especially the extent to which it differs from the classical seasonal/perennial (SAR/PAR) classification, and how and whether intermittent and persistent types of AR, as defined by ARIA, differ from each other. METHODS: Two-step cross-sectional, population-based, in six Western Europe countries; telephone interview followed by clinical diagnosis [including specific immunoglobulin E (IgE) measurements] in a selected subset. RESULTS: Within the population with AR, 29% of the subjects had persistent AR. There was no association between the intermittent/persistent and the SAR/PAR classifications. Subjects with persistent AR had more severe symptoms, and higher rate of self-awareness and previous diagnosis of AR; they were also clearly distinct in their sensitization pattern and medication use. CONCLUSIONS: The classic types of SAR/PAR cannot be used interchangeably with the new classification of intermittent/persistent, as they do not represent the same stratum of disease. There is also evidence that the persistent type describes a distinct group with characteristics that differentiates them from intermittent AR. These results support the validity of the new ARIA classification.     

Clinical advantages of dual activity in allergic rhinitis

Symptoms of allergic rhinitis include sneezing; itching of the eyes, nose, and throat; nasal obstruction; and rhinorrhoea; they may be seasonal or perennial, depending on the causative allergen. The major symptom of perennial allergic rhinitis is nasal obstruction. Sneezing and rhinorrhoea are often present, but are less troublesome than in seasonal allergic rhinitis. Symptom relief is a priority in allergic rhinitis because patients have a severely impaired quality of life. The nasal vascular system is complex. Histamine acts on postcapillary venules during both the immediate and late phase of reactivity and causes plasma extravasation. Other inflammatory mediators can also induce this reaction. Thus, histamine antagonists that also have some additional antiallergic properties have advantages in the treatment of allergic rhinitis. Mizolastine is a second-generation antihistamine that has been shown, in experimental studies, to possess 5-lipoxygenase inhibitory properties in addition to its H₁-receptor antagonistic activity. In the treatment of seasonal allergic rhinitis, mizolastine 10 mg/day has been shown to be effective in reducing nasal and ocular symptoms. It has been shown to be significantly more effective than placebo with a greater percentage of responders. Another study has shown that symptoms of seasonal allergic rhinitis in mizolastine-treated patients were reduced more significantly than in cetirizine-treated patients on the second and third days of treatment. In perennial allergic rhinitis, mizolastine significantly improved symptoms of nasal obstruction compared with placebo and also significantly reduced nasal membrane colour, nasal secretions, and mucosal swelling as shown by rhinoscopy. These effects were maintained over a 5-month treatment period. Mizolastine has also been shown to be at least as effective as loratadine, and in one trial even superior in the treatment of perennial allergic rhinitis.     

Differences between allergic and nonallergic rhinitis in a large sample of adolescents and adults

BACKGROUND: The aim of this study was to describe differences between allergic rhinitis (AR) and nonallergic rhinitis (NAR) in a large community-based sample of Danish adolescents and adults. METHODS: A total of 1,186 subjects, 14-44 years of age, who in a screening questionnaire had reported a history of airway symptoms suggestive of asthma and/or allergy, or who were taking any medication for these conditions were clinically examined. All participants were interviewed about respiratory symptoms and furthermore skin test reactivity, lung function and airway responsiveness were measured using standard techniques. RESULTS: A total of 77% of the subjects with rhinitis had AR, whereas 23% had NAR. Subjects with NAR were more likely to be females, OR = 2.05 (1.31-3.20), P = 0.002, to have persistent symptoms within the last 4 weeks, OR = 1.88 (1.23-2.89), P = 0.003, and to have recurring headaches, OR = 1.94, (1.12-3.37), P = 0.019. On the other hand, subjects with NAR were less likely to have airway hyperresponsiveness, OR = 0.40, (0.24-0.66), P < 0.001, food allergy, OR = 0.40, (0.19-0.36), P = 0.009 and to have been treated with antihistamines in the last 4 weeks, OR = 0.22, (0.13-0.38), P < 0.001 compared with subjects with AR. Subjects with AR were symptomatically worse within their season in terms of sneezing (P < 0.001) and itchy eyes (P < 0.001), compared to subjects with NAR, whereas nasal congestion and rhinorrhea were equally frequent in the two groups (P = 0.901 and P = 0.278, respectively). CONCLUSIONS: The proportion of subjects with NAR in an adolescent and adult population with rhinitis is around one-fourth. Women have NAR twice as often as men. In general, subjects with NAR have more persistent but equally severe symptoms compared to subjects with AR. However, subjects with AR have more sneezing and itchy eyes within their particular season of allergy compared to subjects with NAR.     

Seasonal and perennial allergic rhinitis: is this classification adherent to real life?

BACKGROUND: Allergic rhinitis is traditionally subdivided into seasonal (SAR) and perennial (PAR), although the new definitions of persistent and intermittent were recently proposed. We assessed the validity of the traditional classification in a large group of subjects suffering from allergic rhinitis alone. METHODS: Young males referred to a Navy Military Hospital for routine fitness visit, and reporting symptoms of rhinitis alone were selected. According to the sensitization they were subdivided into (i) sensitized to pollens only (seasonal, SAR), (ii) to perennial allergens only (perennial, PAR) and (iii) to both (mixed, MAR). Spirometry, methacholine challenge, severity and characteristics of symptoms were assessed in all participants. RESULTS: Of 19 325 subjects, 2347 had allergic rhinitis. Seventy-two percent of the subjects had MAR, 17% SAR and 11% PAR. Ocular involvement and irritative symptoms were more frequent in SAR (P < 0.03), whereas obstruction was predominant in PAR (P < 0.01). Nasal symptoms varied according to the period of the year in SAR (P < 0.01) and PAR (P < 0.03). An overt bronchial obstruction was detected in 12% of PAR patients, in 7.8% of MAR, and in 4.2% of SAR. forced expiratory volume/1 s was significantly lower during season in SAR patients only (P < 0.05). The FEF25-75 was impaired in 22.5% MAR patients, 21% PAR, and 14% SAR, with a seasonal change in SAR (P < 0.05) and PAR (P < 0.001). Bronchial hyperreactivity was present in 82.2% of PAR, 73.6% of MAR, and 53.5% of SAR, with a seasonal change in SAR (P < 0.001) and MAR (P < 0.05). CONCLUSIONS: This study provides evidence that up to 80% of allergic rhinitics have a mixed form, and SAR and PAR definitions are poorly adherent to real life. Lung involvement is frequent in patients reporting nose symptoms alone.     

A 12‐week, placebo‐controlled study of the efficacy and safety of ebastine, 10 and 20 mg once daily, in the treatment of perennial allergic rhinitis

This double-blind, placebo-controlled, multicentre study investigated the ability of ebastine, 10 and 20 mg once daily, to control symptoms of perennial allergic rhinitis (PAR) over a 12-week period, and assessed additional benefits of the 20-mg dose. Following a 2-week baseline period, patients (12-63 years) were randomized to treatment with ebastine 10 mg (n=88) or 20 mg (n=102), or placebo (n=100). Patients scored symptom severity (0-3) twice daily, and mean changes from baseline scores showed ebastine to be significantly effective in week 1. Control of symptoms persisted over the 12 weeks, the average daily total nasal symptom score for nasal stuffiness plus nasal discharge plus sneezing plus itchy nose being reduced by both doses, with statistical significance at 20 mg (P=0.015 vs placebo) despite decreased usage of sodium cromoglycate rescue medications. Patient and clinician final opinions of treatment also significantly favoured ebastine, both 10 and 20 mg, over placebo. No serious adverse events occurred, and study treatments were well tolerated with a low incidence of central nervous system-related adverse events and headache. In conclusion, ebastine 10 or 20 mg once daily was rapidly effective in relieving symptoms of PAR in adult and adolescent patients; additional benefits of the 20-mg dose became apparent in the longer term.     

A Comparison of Intranasal and Oral Flunisolide in the Therapy of Allergic Rhinitis

Intranasal flunisolide is an effective treatment for allergic rhinitis. Flunisolide has high bioavailability when administered to normal subjects (50% of an intranasal dose reaches the systemic circulation) with minimal systemic effects. Bioavailability in patients with active rhinitis averages 62.4 +/- 15.7%. The oral dose bioequivalent to 100 micrograms intranasally is 500 micrograms. To define the comparative trial and systemic effects of intranasal flunisolide in patients with active allergic rhinitis, a multicenter, randomized, double-blind, placebo-controlled study was conducted during the 1983 ragweed hayfever season. Ninety-nine patients with ragweed hayfever for greater than or equal to 2 years and positive prick skin tests to ragweed were randomly allocated to one of three treatment groups: 0 = oral flunisolide 500 micrograms b.i.d. and intranasal placebo b.i.d.; N = intranasal flunisolide 50 micrograms per nostril b.i.d. and oral placebo b.i.d.; P = intranasal and oral placebo b.i.d. Treatment continued for 4 weeks. Patients kept daily symptom scores. Patients were evaluated by a blinded observer every 2 weeks and were globally evaluated at the study's end. Data were analyzed for each center and pooled. There were no significant differences in symptom severity of sneezing, nasal congestion, and throat itch in the 0 (oral flunisolide) and P (placebo) groups. N (nasal flunisolide) was significantly more effective than O or P (P less than or equal to 0.005) for each symptom for at least one 2-week period. Global evaluation demonstrated control of overall hayfever severity for N (nasal flunisolide) but not for O (oral flunisolide). We conclude that the therapeutic efficacy of flunisolide is achieved by topical and not by systemic action.     

CCL趋化因子与变应性鼻炎

CCL趋化因子在嗜酸性细胞的募集中起着重要的作用,而嗜酸性细胞的募集是变应性鼻炎发生发展的关键.本文综述了CCL趋化因子中Eotaxin、RANTES和MCPs在变应性鼻炎发生中的作用.     

The Quality of Health Information on Allergic Rhinitis,Rhinitis, and Sinusitis Available on the Internet

PurposeThe internet has become one of the most important media outlets used to obtain health information. Therefore, the quality of health information available on the internet is very important. We evaluated the quality of internet-derived health information on allergic rhinitis, rhinitis and sinusitis and compared these results to those of previous studies performed five years ago.MethodsThe terms "allergic rhinitis (AR)", "rhinitis" and "sinusitis" were searched among the four most commonly used search engines in South Korea. These websites were evaluated according to the author, the Journal of the American Medical Association (JAMA) benchmarks, the DISCERN questionnaire and the Allergic rhinitis and its Impact on Asthma (ARIA) 2008 Update.ResultsA total of 120 websites were obtained and analyzed. For all diseases, "Oriental physician" had the largest portion (almost half of all websites), followed by "Western physician". Based on analyses using the JAMA benchmark, "Attribution" and "Disclosure" were ignored in almost all surveyed websites. According to the scores of the DISCERN question, the majority of websites did not supply appropriate references for their health information, and information on the negative aspects of treatment such as risks and uncertainty was not provided in several websites. In an analysis based on the ARIA 2008 Update concepts, 65% of websites pertaining to health information on AR contained unreliable information.ConclusionsThe quality of health information on the internet was not acceptable. Thus, governmental regulation or control to improve the quality of health information is required.     

Fexofenadine reduces nasal congestion in perennial allergic rhinitis

BACKGROUND: Nasal congestion is the predominant symptom in perennial allergic rhinitis (PAR), and it seems to be mainly related to the late-phase inflammatory events. The present pilot study aimed to evaluate the therapeutic effect exerted by fexofenadine in patients with PAR due to mite allergy. METHODS: This study was a parallel, double-blind, randomized, three-arm (1:1:1), placebo-controlled study. Thirty-one subjects with PAR were enrolled and received double-blind medication: fexofenadine 120 or 180 mg, or placebo, once a day for 28 days. RESULTS: The total symptom score was reduced by fexofenadine (both dosages) at V2 (P=0.007), whereas placebo did not modify it. Nasal congestion decreased after 1 week of treatment with fexofenadine 120 (P=0.027) and 180 (P=0.01), but not with placebo (P=NS). At V3, fexofenadine (both dosages) significantly reduced nasal congestion (P=0.011 and P=0.007, respectively), by placebo did not show any significant effect. CONCLUSIONS: This pilot study represents the first evidence of the efficacy of fexofenadine in PAR, and also the control of the nasal congestion. We suggest performing larger trials to confirm these preliminary findings.     

High incidence of sensitization to ornamental plants in allergic rhinitis

BACKGROUND: A few indoor plants have been described as potential allergens, in single case reports of allergic rhinitis. There is no data evaluating the prevalence of allergic sensitization to these plants. AIM: The relationship between owning indoor ornamental plants with the risk to be sensitized has been evaluated in atopic rhinitis. METHODS: A group of 59 patients with allergic rhinitis were submitted to skin prick tests (SPT) using both the leafs of their own plant and commercial extracts of the most frequent airborne allergens. A control group of 15 healthy subjects was tested with the same allergens. RESULTS: While no subject from the control group developed a significant SPT to any of the tested plants, 78% of allergic rhinitis had positive SPT to at least one plant, the most frequent sensitization being Ficus benjamina, yucca, ivy and palm tree. CONCLUSION: In allergic rhinitis, indoor plants should be considered as potential allergens.     

Perennial allergic rhinitis and chronic sinusitis: correlation with rhinologic risk factors

BACKGROUND: The reported association of allergy and sinusitis varies greatly between study, and the exact role of allergy in predisposing to sinusitis is not clear. We attempted to determine whether patients with perennial allergic rhinitis are at greater risk of developing sinusitis with respect to a control group, and to determine whether there is a correlation between rhinomanometry, endoscopy, and nasal swab, and computed tomography (CT) findings. METHODS: Forty adult patients with perennial allergic rhinitis underwent CT scans of the paranasal sinuses, and the results were then compared to CTs of the paranasal sinuses of 30 control subjects. All allergic patients underwent nasal endoscopy, nasal swab, and active anterior rhinomanometry, and the results were studied in relation to the CT findings. RESULTS: We found sinusitis in 67.5% of the allergic patients and in 33.4% of the controls, with a statistically significant difference between the two groups (P = 0.017). Twenty-three patients had a positive nasal swab; 22 showed increased nasal resistance on rhinomanometry, and 36 had positive endoscopy, but the association of CT findings with endoscopy, rhinomanometry, or nasal swab was not statistically significant (P = 0.583, P = 1.00, P = 0.506, respectively). CONCLUSIONS: Allergic rhinitis is often associated with sinusitis, but the underlying mechanism has yet to be determined. Evidently, factors other than classical pathogen growth and mechanical factors, such as the association of the various factors and immunologic mechanisms, may contribute to the pathogenesis of chronic sinusitis in allergic patients.