Non‐allergic rhinitis: Position paper of the European Academy of Allergy and Clinical Immunology

This EAACI position paper aims at providing a state‐of‐the‐art overview on nonallergic rhinitis (NAR). A significant number of patients suffering from persistent rhinitis are defined as nonallergic noninfectious rhinitis (NANIR) patients, often denominated in short as having NAR. NAR is defined as a symptomatic inflammation of the nasal mucosa with the presence of a minimum of two nasal symptoms such as nasal obstruction, rhinorrhea, sneezing, and/or itchy nose, without clinical evidence of endonasal infection and without systemic signs of sensitization to inhalant allergens. Symptoms of NAR may have a wide range of severity and be either continuously present and/or induced by exposure to unspecific triggers, also called nasal hyperresponsiveness (NHR). NHR represents a clinical feature of both AR and NAR patients. NAR involves different subgroups: drug‐induced rhinitis, (nonallergic) occupational rhinitis, hormonal rhinitis (including pregnancy rhinitis), gustatory rhinitis, senile rhinitis, and idiopathic rhinitis (IR). NAR should be distinguished from those rhinitis patients with an allergic reaction confined to the nasal mucosa, also called “entopy” or local allergic rhinitis (LAR). We here provide an overview of the current consensus on phenotypes of NAR, recommendations for diagnosis, a treatment algorithm, and defining the unmet needs in this neglected area of research.     

How should nasal symptoms be investigated in asthma? A comparison of radiologic and endoscopic findings

BACKGROUND: To improve asthma control, the management of rhinosinusitis often leads the physician to perform sinonasal imaging and/or nasal endoscopy, but their respective contributions are still insufficiently understood. OBJECTIVE: To evaluate the potential contribution of a symptoms questionnaire, sinus radiography (SR) and computed tomography (CT) scan to the diagnosis of nasal diseases in asthmatic patients when compared with ENT examination. METHODS: A total of 124 patients completed a questionnaire on nasal symptoms administered by the chest physician. Then, they underwent ENT examination. On the same day, SR and CT scans were performed independently. RESULTS: Patients (80.3%) had nasal symptoms during the month preceding the consultation. The ENT examination was normal in 8.1% (n = 10) and revealed rhinitis in 57.3% (n = 71), rhinosinusitis in 14.5% (n = 18) and nasal polyposis in 20.2% (n = 25). For rhinitis, the negative predictive value of bilateral nasal obstruction was 87.8%. Both SR and CT had low sensitivity and specificity. For rhinosinusitis, the negative predictive value of nasal symptoms varied from 85.4 to 95.2%. Sinus CT was at least as accurate as SR for the diagnosis of rhinosinusitis. In a multivariate analysis, only the CT scan (score > or =12) appeared to be significantly associated with the diagnosis of nasal polyposis. CONCLUSION: In asthmatic patients, physicians need to enquire systematically about the existence of nasal symptoms by using this simple questionnaire which is sensitive for rhinitis, and has good negative predictive value for excluding rhinosinusitis and nasal polyposis.     

Topical nasal lysine aspirin in aspirin-sensitive and aspirin-tolerant chronic rhinosinusitis with nasal polyposis

Chronic rhinosinusitis patients with nasal polyps can be aspirin sensitive or aspirin tolerant. The majority belong to the latter group. They tolerate intake of aspirin or other non-steroidal anti-inflammatory drugs, whereas aspirin-sensitive patients have an adverse reaction (asthma, rhinitis and/or urticaria). Diagnosis of aspirin sensitivity is important for the patient, but is rarely undertaken in routine ENT or respiratory medicine practice. Treatment of nasal polyps is by a combination of medical therapy and surgery. Oral and topical steroids form the mainstay of medical therapy, which is aimed at reducing inflammation and symptom improvement. Surgery helps with polyps causing severe nasal obstruction. Despite these therapies, recurrences are common in aspirin sensitive patients. Any adjunctive therapy to prevent or prolong recurrence would be welcome. One such possibility is topical nasal lysine-aspirin. This is an area under current debate and this non-systematic review aims to provide evidence of its use, to date, in aspirin sensitive and aspirin tolerant nasal polyp patients.     

Idiopathic rhinitis, the ongoing quest

The term rhinitis in daily practice is used for nasal dysfunction causing symptoms-like nasal itching, sneezing, rhinorrhea and or nasal blockage. Chronic rhinitis can roughly be classified into allergic, infectious or nonallergic/noninfectious. When allergy, mechanical obstruction and infections have been excluded as the cause of rhinitis, a number of poorly defined nasal conditions of partly unknown aetiology and pathophysiology remain. The differential diagnosis of nonallergic noninfectious rhinitis is extensive. Although the percentage of patients with nonallergic noninfectious rhinitis with a known cause has increased the last decades, still about 50% of the patients with nonallergic noninfectious rhinitis has to be classified as suffering from idiopathic rhinitis (IR), or rather e causa ignota. Specific immunological, clinical and sometimes radiological and functional tests are required to distinguish known causes. Research to the underlying pathophysiology of IR has moved from autonomic neural dysbalans to inflammatory disorders (local allergy), the nonadrenergic noncholinergic (NANC) sensory peptidergic neural system and central neural hyperaesthesia, still without solid ground or proof. This review summarizes the currently known causes for nonallergic noninfectious rhinitis and possible treatments. Also possible pathophysiological mechanisms of IR are discussed.     

Occupational upper airway disease: how work affects the nose

Chronic inflammation of the upper airways is common and can arbitrarily be divided into rhinitis and rhinosinusitis. Infection and allergy represent two well‐characterized and most frequently diagnosed etiologies of upper airway inflammation. Persistent upper airway inflammation caused by agents inhaled in the work environment represents a diagnostic challenge in clinical practice, and its pathophysiology has been little studied. Occupational rhinitis is a recognized medical condition with diagnostic and therapeutic guidelines. In contrast, only limited evidence is available about the relationship between work exposures and rhinosinusitis. This review aims at providing a comprehensive overview of the available literature on occupational upper airway disease with a focus on pathophysiological mechanisms and with an emphasis on the current unmet needs in work‐related upper airway disease.     

Natural history and clinical features of aspirin-exacerbated respiratory disease

Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome characterized by chronic rhinosinusitis, nasal polyposis, asthma and precipitation of asthma, and rhinitis attacks after ingestion of aspirin (ASA) and most other nonsteroidal antiinflammatory drugs (NSAIDs). Although precipitation of asthma attacks by ingestion of ASA and other NSAIDs is considered a hallmark of the syndrome, the respiratory mucosal inflammatory disease process begins and continues in the absence of ongoing or even intermittent exposure to ASA or NSAIDs. The typical patient with AERD is an adult who develops refractory chronic rhinitis in the third or fourth decade of life. The chronic rhinitis evolves into chronic eosinophilic rhinosinusitis with associated nasal polyposis. Anosmia appears in most patients. CT of the sinuses most often demonstrates pansinusitis and patients often undergo multiple sinus operations resulting in only limited temporary benefit. During the evolution of the sinus disease persistent asthma develops. Finally, if patients are exposed to ASA or NSAIDs acute respiratory reactions begin to occur. Despite subsequent avoidance of ASA and other NSAIDs, the respiratory mucosal inflammatory disease persists, often requiring systemic corticosteroids for control of both upper- and lower-respiratory tract symptoms. Adequate control of asthma can often only be accomplished with the simultaneous control of the associated rhinosinusitis. With few exceptions, once AERD develops it remains for the remainder of the patient’s life. Formerly Scripps Clinic and Green Hospital, La Jolla, CA     

Intranasal Steroids in the Treatment of Allergy-Induced Rhinorrhea

While nasal congestion has been identified as one of the most bothersome and prevalent symptoms of allergic rhinitis, it is underappreciated that many patients find rhinorrhea also to be bothersome. Rhinorrhea as a symptom of allergic rhinitis virtually never occurs alone; about 97% of patients with allergic rhinitis suffer from at least two symptoms, a finding that underscores the advantage of treating a broad range of symptoms with a single medication. Along with sneezing and nasal obstruction, rhinorrhea is a classic acute symptom of allergic rhinitis; it appears as a late-phase symptom as well. In this review, the characterization and epidemiology of rhinorrhea, the pathophysiology of rhinorrhea in allergic rhinitis, the roles played by mediators in early- and late-phase rhinorrhea, the prevalence and impact of this symptom, and the efficacy and safety of available treatment options are all discussed in context of relevant literature. A review of the clinical studies assessing the efficacy of intranasal corticosteroids (INS) for rhinorrhea is presented. Many clinical studies and several meta-analyses conclusively demonstrate that, in addition to being safe and well-tolerated, INS are more effective than other agents (including oral and intranasal antihistamines) across the spectrum of AR symptoms, including rhinorrhea and nasal congestion.     

Diagnosis and management of NSAID‐Exacerbated Respiratory Disease (N‐ERD)—a EAACI position paper

NSAID‐exacerbated respiratory disease (N‐ERD) is a chronic eosinophilic, inflammatory disorder of the respiratory tract occurring in patients with asthma and/or chronic rhinosinusitis with nasal polyps (CRSwNP), symptoms of which are exacerbated by NSAIDs, including aspirin. Despite some progress in understanding of the pathophysiology of the syndrome, which affects 1/10 of patients with asthma and rhinosinusitis, it remains a diagnostic and therapeutic challenge. In order to provide evidence‐based recommendations for the diagnosis and management of N‐ERD, a panel of international experts was called by the EAACI Asthma Section. The document summarizes current knowledge on the pathophysiology and clinical presentation of N‐ERD pointing at significant heterogeneity of this syndrome. Critically evaluating the usefulness of diagnostic tools available, the paper offers practical algorithm for the diagnosis of N‐ERD. Recommendations for the most effective management of a patient with N‐ERD stressing the potential high morbidity and severity of the underlying asthma and rhinosinusitis are discussed and proposed. Newly described sub‐phenotypes and emerging sub‐endotypes of N‐ERD are potentially relevant for new and more specific (eg, biological) treatment modalities. Finally, the document defines major gaps in our knowledge on N‐ERD and unmet needs, which should be addressed in the future.     

Exercise-induced rhinitis: a common disorder that adversely affects allergic and nonallergic athletes.

BACKGROUND: Exercise is a well-established trigger for allergic disorders such as asthma, urticaria, and anaphylaxis, but the effect of exercise on rhinitis has not been well described. OBJECTIVE: To survey individuals with and without nasal allergy who exercise regularly to determine the prevalence and nature of nasal symptoms induced by indoor exercise. METHODS: An original, self-administered questionnaire to evaluate exercise-induced rhinitis (EIR) was distributed to adults who were receiving allergy immunotherapy at a community allergy practice and to members of a community athletic club. Nasal symptoms that occur indoors (runny nose, nasal congestion, postnasal drip) were primarily evaluated. Comparisons with outdoor EIR were determined. The perception of adverse effects of rhinitis on exercise was evaluated. RESULTS: Sixty-six (40%) of the 164 patients indicated that their indoor EIR adversely affected athletic performance, and this finding occurred more frequently in patients with nasal allergy vs unaffected individuals (53.1% vs 27.7%; P = .009). Of the 61.0% who reported increased rhinitis with indoor exercise, rhinorrhea was the most common symptom experienced (48.8%). Indoor EIR occurred more frequently in patients with nasal allergy vs unaffected individuals (69.1% vs 53.0%; P = .04). Outdoor EIR occurred in 56.1% of the total population, and patients with nasal allergy reported significantly more rhinitis with outdoor exercise compared with unaffected individuals (71.6% vs 41.0%; P < .001). CONCLUSIONS: Exercise-induced rhinitis, predominantly rhinorrhea, commonly occurs in athletes regardless of underlying nasal allergy. A history specific to indoor and outdoor exercise triggers needs to be part of the complete rhinitis history so that specific treatment can be directed.     

Upper and lower airway pathology in young children with allergic- and non-allergic rhinitis

Allergic- and non-allergic rhinitis are very common diseases in childhood in industrialized countries. Although these conditions are widely trivialized by both parents and physicians they induce a major impact on quality of life for the affected children and a substantial drainage of health care resources. Unfortunately, diagnostic specificity is hampered by nonspecific symptom history and lack of reliable diagnostic tests which may explain why the pathology behind such diagnoses is poorly understood. Improved understanding of the pathophysiology of allergic- and non-allergic rhinitis in young children may contribute to the discovery of new mechanisms involved in pathogenesis and help direct future research to develop correctly timed preventive measures as well as adequate monitoring and treatment of children with rhinitis. Asthma is a common comorbidity in subjects with allergic rhinitis and epidemiological surveys have suggested a close connection between upper and lower airway diseases expressed as the "united airways concept". Furthermore, an association between upper and lower airway diseases also seems to exist in non-atopic individuals. Nevertheless, the nature of this association is poorly understood and there is a paucity of data objectivizing this association in young children. The aim of this thesis was to describe pathology in the upper and lower airways in young children from the COPSAC birth cohort with investigator-diagnosed allergic- and non-allergic rhinitis. Nasal congestion is a key symptom in both allergic- and non-allergic rhinitis, and eosinophilic inflammation is a hallmark of the allergic diseases. In paper I, we studied nasal eosinophilia and nasal airway patency assessed by acoustic rhinometry in children with allergic rhinitis, non-allergic rhinitis and healthy controls. Allergic rhinitis was significantly associated with nasal eosinophilia and irreversible nasal airway obstruction suggesting chronic inflammation and structural remodeling of the nasal mucosa in children already at age 6 years. Non-allergic rhinitis exhibited no change in the nasal airway patency, but some nasal eosinophilia albeit less than children with allergic rhinitis. These findings suggest different pathology in allergic- and non-allergic rhinitis which may have important clinical implications for early pharmacological treatment of rhinitis in young children. In paper II, we utilized the nasal airway patency end-points derived from paper I to examine whether upper and lower airway patency are associated. Upper airway patency was assessed by acoustic rhinometry before and after intranasal α-agonist and lower airway patency by spirometry before and after inhaled β2-agonist. Upper and lower airway patencies were strongly associated and independent of body size, rhinitis and asthma. The association was consistent for both baseline values and for decongested nasal airway patency and post-β2 FEV1. Blood and nasal eosinophilia were also associated with nasal airway obstruction. This suggests generalized diminished airway dimensions as a novel susceptibility factor for concurrent symptoms of asthma and rhinitis in early childhood and supports the notion of a common pathophysiology in asthma and rhinitis. The clinical interpretation of these findings is that all children presenting either rhinitis or asthma should be considered inflamed in the entire respiratory tract. In paper III, we aimed to describe asthma and intermediary asthma end-points associated with allergic- and non-allergic rhinitis in preschool-aged children. At age 7 years, we evaluated prevalence of asthma, eczema, food sensitization, and filaggrin mutations; levels of total IgE, FeNO, and blood-eosinophils; lung function and bronchial responsiveness to cold dry air. We found that asthma was similarly associated with allergic- and non-allergic rhinitis suggesting a link between upper and lower airway diseases beyond an allergy associated inflammation. Only children with allergic rhinitis had increased bronchial responsiveness and elevated FeNO suggesting different endotypes of asthma symptoms in young children with allergic- and non-allergic rhinitis. We also found bronchial hyperresponsiveness and raised values of FeNO in children with allergic rhinitis without asthma suggesting sub-clinical bronchial inflammation and supporting the allergic disease process to involve both upper and lower airways. In conclusion, these observations objectively show marked differences in nasal pathology in young children with allergic- and non-allergic rhinitis and lend support to a close connection between upper and lower airway diseases partly from an allergy driven process, but equally from non-allergic mechanisms.     

Nasal allergies and beyond: a clinical review of the pharmacology, efficacy, and safety of mometasone furoate

Mometasone furoate nasal spray (MFNS; Nasonex^®, Schering-Plough Corporation, Kenilworth, NJ, USA) is an effective and well-tolerated intranasal corticosteroid approved for the prophylactic treatment of seasonal allergic rhinitis, and the treatment of perennial allergic rhinitis. MFNS is a potent molecule with a rapid onset of action and excellent safety and efficacy profiles. Having recently received approval for the treatment of nasal polyposis, data indicate that MFNS may also be effective in rhinosinusitis.     

Allergic vs nonallergic rhinitis: which is more predisposing to chronic rhinosinusitis?

BACKGROUND: The impact of allergy on chronic rhinosinusitis (CRS) is controversial. OBJECTIVE: To evaluate whether a history of CRS is more prevalent in patients with allergic rhinitis than in those with nonallergic persistent rhinitis. METHODS: A total of 115 patients (78 females; mean age, 31.9 years; age range, 14-64 years) with persistent rhinitis were included in the study. A 7-point analog scale was used to report the severity of individual and global CRS symptoms and to determine the impact of rhinosinusitis symptoms on quality of life. The allergic status of the patients was evaluated using skin prick tests for common inhalant allergens, and asthma was evaluated by means of history, physical examination, and respiratory function tests. Rhinoscopy and paranasal sinus computed tomography were used to determine CRS. RESULTS: Asthma and CRS were not significantly different in allergic and nonallergic patients. Nasal polyps were found equally in both groups (8 patients). However, mean Lund-Mackay staging scores, postnasal drainage, dental pain, and global CRS scores were significantly higher in patients with nonallergic rhinitis (P = .045, P = .001, P = .02, and P = .01, respectively). No significant correlations, except for dental pain (correlation coefficient, 0.250; P = .008), were found between Lund-Mackay scores and CRS symptoms. In rhinoscopy, the only conspicuous difference was nasal purulence in allergic patients (P = .002). CONCLUSION: Allergic and nonallergic rhinitis may contribute similarly to the development of CRS.     

Olopatadine nasal spray for the treatment of allergic rhinitis

Olopatadine hydrochloride nasal spray (Patanase^® Nasal Spray, Alcon Laboratories, TX, USA) was approved by the US FDA in 2008, and is indicated for the relief of symptoms of seasonal allergic rhinitis (SAR), also referred to as allergic rhinosinusitis. Olopatadine is an antihistamine with selective H₁-receptor antagonist activity. Clinical trials of olopatadine nasal spray have demonstrated safety and efficacy in the treatment of SAR patients. With an onset of action of 30 min, olopatadine nasal spray has also been shown to improve quality of life, ability to perform work and the conduct of usual activities in SAR patients.     

Chronic rhinosinusitis: epidemiology and medical management

Chronic rhinosinusitis (CRS) affects 12.5% of the US population. On epidemiologic grounds, some association has been found between CRS prevalence and air pollution, active cigarette smoking, secondhand smoke exposure, perennial allergic rhinitis, and gastroesophageal reflux. The majority of pediatric and adult patients with CRS are immune competent. Data on genetic associations with CRS are still sparse. Current consensus definitions subclassify CRS into CRS without nasal polyposis (CRSsNP), CRS with nasal polyposis (CRSwNP), and allergic fungal rhinosinusitis (AFRS). Evaluation and medical management of CRS has been the subject of several recent consensus reports. The highest level of evidence for treatment for CRSsNP exists for saline lavage, intranasal steroids, and long-term macrolide antibiotics. The highest level of evidence for treatment of CRSwNP exists for intranasal steroids, systemic glucocorticoids, and topical steroid irrigations. Aspirin desensitization is beneficial for patients with aspirin-intolerant CRSwNP. Sinus surgery followed by use of systemic steroids is recommended for AFRS. Other modalities of treatment, such as antibiotics for patients with purulent infection and antifungal drugs for patients with AFRS, are potentially useful despite a lack of evidence from controlled treatment trials. The various modalities of medical treatment are reviewed in the context of recent consensus documents and the author's personal experience.     

Rhinitis in adults

Rhinitis is a very common disorder caused by inflammation or irritation of nasal mucosa. Dominant symptoms are nasal obstruction; however, in some patients, runny nose, excessive sneezing or nasal itch may be the most bothersome symptoms. The most common causes of nasal inflammation are viral infections and allergic response to airborne allergens. Response to irritants may cause similar symptoms, although signs of inflammation may not always be present. Viral rhinitis is lasting up to 10 days and it is part of the common cold syndrome. In short-lived rhinitis, lasting for 7 to 10 days, sometimes it is not easy to differentiate between the potential causes of the disorder, if general symptoms of infection like fever and malaise are not present. In long-living rhinitis, it is important to differentiate between infectious, allergic, non-allergic non-infectious rhinitis, and chronic rhinosinusitis. Itch and ocular symptoms are more common in allergic rhinitis, while other symptoms like nasal obstruction, rhinorrhea and sneezing may affect patients with allergic and non-allergic rhinitis. Patients with allergic rhinitis often have symptoms after exposure to irritants, temperature and humidity changes, like patients with non-allergic rhinitis, and such exposure may sometimes cause more severe symptoms than exposure to allergens. Sensitivity to a non-specific trigger is usually called non-specific nasal hyperreactivity. Allergic rhinitis occurs due to immunoglobulin E (IgE) interaction with allergen in contact with nasal mucosa in a sensitized patient. Sensitization to certain airborne allergen, like pollens, dust, molds, animal dander, etc. usually occurs in families with allergy background, which is helpful in making diagnosis in patients who have rhinitis in a certain period of the year, or aggravation of nasal symptoms occurs in the environment typical of certain allergen. The diagnosis is clinically confirmed by proving sensitivity to certain allergen on skin prick test, and by proving specific antibody IgE in patient serum. Allergic rhinitis is categorized according to sensitivity to allergens that occur seasonally, like pollens, or to allergens that are present all year round, like house dust mite, molds and animal dander, into seasonal and perennial allergic rhinitis. Allergy to pollens causes the same mechanism of inflammation in response to allergens, which is the result of allergen binding to specific IgE antibody; however, patients with pollen allergy usually complain more of sneezing and runny nose, whereas patients with allergy to perennial allergens more often complain of obstruction, with the episodes of sneezing and runny nose occurring only when exposed to higher concentrations of allergens (house cleaning, around pets). Treatment includes avoidance of allergens, medical treatment and immunotherapy (allergy vaccines, tablets with allergens). Avoidance of allergens means reduction of environmental allergen load to the respiratory system including workplace, which is not easy to accomplish. Medical treatment is usually necessary to control symptoms, and it includes antihistamines, nasal or in tablets, and nasal glucocorticoids (steroids). Antihistamines should be second generation, which do not cause sedation, and such treatment shows more efficacy on runny nose, sneezing and nasal itch than on nasal stuffiness. Nasal steroids are more potent in improving nasal patency than antihistamines, and are at least as potent in the control of all other nasal and ocular symptoms. Nasal patency may be improved by nasal or oral decongestants, but such treatment should be reduced to as short period as possible, since after several days of using nasal decongestants rebound congestion may occur and patients will need nasal decongestants to improve nasal airways even when allergens are not around anymore.     

Local allergic rhinitis: Implications for management

A significant proportion of rhinitis patients without systemic IgE‐sensitisation tested by skin prick test and serum allergen‐specific IgE (sIgE) display nasal reactivity upon nasal allergen provocation test (NAPT). This disease phenotype has been termed local allergic rhinitis (LAR). LAR is an underdiagnosed entity affecting children and adults from different parts of the world, with moderate‐to‐severe symptoms, impairment of quality of life and rapid progression to symptom worsening. LAR is a stable phenotype and not merely an initial state of AR. Allergic rhinitis and LAR share many clinical features including a positive NAPT response, markers of type 2 nasal inflammation including sIgE in nasal secretions and a significant rate of asthma development. LAR should be considered as a differential diagnosis in those subjects of any age with symptoms suggestive of AR but no evidence of systemic atopy. Although LAR pathophysiology is partially unknown, in some patients sIgE can be demonstrated directly in the nasal secretions and/or indirectly via positive responses in basophil activation test (BAT). LAR can coexist with other rhinitis phenotypes, especially AR. The diagnosis currently relies on the positivity of NAPT to a single or multiple allergens. NAPT has high sensitivity, specificity and reproducibility, and it is considered the gold standard. BAT and the measurement of nasal sIgE can also contribute to LAR diagnosis. LAR patients benefit from the same therapeutic strategies than AR individuals, including the avoidance of allergen exposure and the pharmacotherapy. Moreover, several recent studies support the effectiveness and safety of allergen immunotherapy for LAR, which opens a window of treatment opportunity in these patients.     

Important roles of tachykinins in the development of allergic nasal hyperresponsiveness in guinea-pigs

Background Although it has been suggested that the use of tachykinin receptor antagonists might prove to be an effective treatment for allergic rhinitis (AR), they are not used clinically. Therefore, we decided to examine the effects of tachykinin receptor antagonists on AR symptoms in an appropriate experimental model. Objective To evaluate newly developed tachykinin receptor antagonists in a Japanese cedar pollen‐induced AR model and to determine their effect on allergen‐induced sneezing, nasal blockage, and nasal hyperresponsiveness (NHR). Methods Sensitized guinea‐pigs were challenged by forced inhalation of pollen once every week. Sneezing and nasal blockage were observed after pollen challenges. NHR (nasal blockage) to an intranasal application of leukotriene D₄ was assessed 2 days after an antigen challenge. We also evaluated whether intranasal dosing with a tachykinin causes NHR. NK₁ and NK₂ receptor antagonists were administered before an intranasal treatment with antigen or tachykinin. Amounts of tachykinins present in nasal cavity lavage fluid were measured by an enzyme immunoassay. Results Although an NK₁ and NK₂ receptor dual antagonist showed no effect on pollen‐induced sneezing and biphasic nasal blockage, it did completely suppress the development of NHR. Experiments using specific NK₁ or NK₂ receptor antagonists revealed that NK₂ receptor activation was preferentially involved in the development of hyperresponsiveness. Increases in the levels of substance P (SP) and neurokinin A (NKA) in the nasal tissue were noted 20 min–1 h after the challenge. Intranasal instillation of either SP or NKA‐induced NHR, which was almost completely inhibited by NK₂ receptor antagonists and partially inhibited by NK₁ receptor antagonists. Conclusions SP and NKA, which are released early after the challenge, mediate the development of NHR by preferentially activating NK₂ receptors. Therefore, NK₂ receptor antagonists might prove to be effective treatment of AR.     

A double-blind, placebo-controlled comparison of treatment with fluticasone propionate and levocabastine in patients with seasonal allergic rhinitis. FLNCO2 Italian Study Group

Fluticasone propionate aqueous nasal spray (FPANS) is a topically active glucocorticoid which has been successfully used for the treatment of seasonal allergic rhinitis (SAR). Topical levocabastine is a highly selective H1 antagonist which has been proposed as an alternative treatment of SAR. The purpose of this study was to compare the clinical efficacy of two topical nasal treatments, FPANS and levocabastine, in the treatment of SAR. Additionally, the effect of treatments on nasal inflammation was examined during natural pollen exposure. A group of 288 adolescent and adult patients with at least a 2-year history of SAR to seasonal pollens participated in a multicenter, doubleblind, double-dummy, and placebo-controlled study. Patients were treated with either FPANS 200 microg, once daily (n = 97), or topical levocabastine, 200 microg, given twice daily (n = 96), or matched placebo (n = 95) for a period of 6 weeks, starting from the expected beginning of the pollen season. Clinically relevant pollens included Parietaria, olive, and grass. Assessment of efficacy was based on scores of daily nasal symptoms and on nasal cytology of nasal lavage. Nasal lavage was performed immediately before, during, and at the end of treatment in 39 patients. FPANS significantly increased the percentage of symptom-free days for nasal obstruction on waking and during the day, rhinorrhea, sneezing, and itching. FPANS provided a better control for night and day nasal obstruction (P<0.02 and P<0.01) and rhinorrhea (P<0.01) than levocabas tine. In addition, fewer patients treated with FPANS used rescue medication (P<0.025). The percentage of eosinophils in nasal lavage was reduced only during treatment with FPANS. The results of this study indicate that FPANS 200 microg, once daily, provides a better clinical effect than levocabastine 200 microg, twice daily, in patients with SAR. Unlike levocabastine, FPANS significantly attenuates nasal eosinophilia during pollen exposure, a feature which may explain its therapeutic efficacy.     

Specific IgE antibodies in nasal secretion from patients with allergic rhinitis and with negative or weakly positive RAST on the serum

Nasal secretions from eighteen patients with allergic rhinitis with a positive case history, intradermal test and nasal provocation test, but with negative or only weakly positive RAST (radioallergosorbent test) on the serum against a total of thirty-five allergens, were studied. In the RAST an immunosorbent-purified anti-IgE with D?2 specificity was used, which raised the detection limit. Nasal secretion was collected by washing the nasal mucosa with 0.9% and 18% NaCl solution respectively, and the latter secretion was also lyophilized and concentrated. In ten cases RAST was slightly positive on the nasal secretion, and in three of the concentrated secretions the RAST value was higher than on the serum. In none of the serum or nasal secretion samples was RAST positive according to the cut off value for a positive result defined by the reference system used in Phadebas RAST®. From these results it is concluded that RAST analyses of nasal secretion from patients with allergic rhinitis is of no appreciable value in routine clinical allergological diagnosis. However, the increased sensitivity of RAST obtained with isotope-labelled anti-D?2 may be useful in the serological diagnosis of patients with low grade allergy having low levels of IgE antibodies in serum.     

Advances in upper airway diseases and allergen immunotherapy

The purpose of this review is to highlight important articles on upper airway diseases and immunotherapy that appeared during 2006. Studies from Europe continue to examine the usefulness of the Allergic Rhinitis and its Impact on Asthma classification of allergic rhinitis as intermittent or persistent and its levels of severity as mild or moderate/severe. A number of physical agents were shown to effect nasal inflammation: sudden temperature changes in patients with allergic rhinitis increased eosinophilic inflammation; in children with allergic asthma, the personal exposure to particles <2.5 microm air pollution correlated with percent of nasal eosinophils and levels of markers of nasal exudation; and in patients who developed rhinorrhea on exposure to cold and windy weather, nasal challenge with cold dry air caused sloughing of nasal epithelial cells. A 3-month double-blind, placebo-controlled study of nasal washes with amphoteracin B showed no benefit in patients with chronic rhinosinusitis. Studies of immunotherapy with grass and dog dander extracts confirmed the need for doses containing 15 to 20 microg of the major allergen for optimal effectiveness. The protective effect of immunotherapy on the development of asthma in children with allergic rhinitis was shown to still be present 2 years after completion of a 3-year course of treatment. Injection immunotherapy with a moderate dose of house dust mite extract in house dust-sensitive adults with atopic dermatitis reduced symptoms and use of corticosteroids and antihistamines compared with treatment with about 1/1000 of that dose of the same extract. Pretreatment for 9 weeks with the monoclonal anti-IgE antibody omalizumab reduced systemic reactions during rush immunotherapy 5-fold and allowed further build-up at weekly intervals without systemic reactions. A review of sublingual immunotherapy confirmed both efficacy and safety, but evidence for appropriate dosing and for the effectiveness of sublingual immunotherapy employing multiple allergen mixes was still lacking. Two studies with a sublingual grass pollen extract tablet showed a clear dose response and the ability to initiate sublingual immunotherapy without an up-dosing phase. A pilot study with cytosine phosphorothionate quanosine DNA conjugated to the major allergen of ragweed reported impressive improvement in symptoms the first pollen season that persisted during the second pollen season without any further administration of the conjugate. In conclusion, studies on rhinitis and sinusitis explored the pathophysiology of the disease more than offering new therapeutic approaches. Studies on immunotherapy addressed optimal dosing, but also a variety of safer and more convenient approaches such as reduction of IgE with omalizumab, conjugating allergen to immunostimulatory DNA sequences, or administration by the sublingual route.