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Advances in upper airway diseases and allergen immunotherapy

2005; Elsevier BV; Volume: 115; Issue: 4 Linguagem: Inglês

10.1016/j.jaci.2005.01.037

1097-6825

Harold S. Nelson,

Olfactory and Sensory Function Studies

Evidence of an increased prevalence of rhinitis in patients with asthma, and asthma in patients with rhinitis, supports the 1 airway concept. However, there are basic differences between the upper and lower airways, such as the virtual absence of remodeling in the nose compared with the bronchi, despite the presence of similar inflammation. Etiologic factors in chronic rhinosinusitis (CRS) attract increasing interest. Peripheral blood monocytes from patients with CRS release IL-4, IL-13, and IFN-γ on stimulation with fungal antigens, especially those from Alternaria. This is not seen with cells from normal controls. However, a double-blind trial of intranasal amphotericin in CRS was negative. Evidence continues to accumulate of the pivotal role of regulatory T-lymphocytes secretion of IL-10 in the response to allergen immunotherapy. In patients with asthma and house dust mite allergy who are receiving appropriate pharmacotherapy and have instituted environmental controls, house dust mite immunotherapy provides marginal additional benefits in asthma control. Immunotherapy with cat dander extract at a maintenance dose containing 15 μg Fel d 1 produces a more consistent immunologic response than with maintenance doses containing 3.0 μg, whereas doses containing only 0.6 μg are no more effective than placebo. Sublingual immunotherapy for seasonal grass allergy can be safely administered by general practitioners, but symptom relief begins only in the second season of therapy. Sublingual immunotherapy for seasonal grass allergy in children reduced symptoms and onset of new asthma symptoms but, again, beginning only in the second year of treatment. A course of 6 weekly injections of ragweed Amb a 1 bound to cytosine phosphorothionate guanosine containing DNA produced a shift from TH2 to TH1 cytokine release both in peripheral blood cells and in the nose after allergen challenge. No symptom improvement was seen the first year, but symptoms were reduced the second year without further treatment. Evidence of an increased prevalence of rhinitis in patients with asthma, and asthma in patients with rhinitis, supports the 1 airway concept. However, there are basic differences between the upper and lower airways, such as the virtual absence of remodeling in the nose compared with the bronchi, despite the presence of similar inflammation. Etiologic factors in chronic rhinosinusitis (CRS) attract increasing interest. Peripheral blood monocytes from patients with CRS release IL-4, IL-13, and IFN-γ on stimulation with fungal antigens, especially those from Alternaria. This is not seen with cells from normal controls. However, a double-blind trial of intranasal amphotericin in CRS was negative. Evidence continues to accumulate of the pivotal role of regulatory T-lymphocytes secretion of IL-10 in the response to allergen immunotherapy. In patients with asthma and house dust mite allergy who are receiving appropriate pharmacotherapy and have instituted environmental controls, house dust mite immunotherapy provides marginal additional benefits in asthma control. Immunotherapy with cat dander extract at a maintenance dose containing 15 μg Fel d 1 produces a more consistent immunologic response than with maintenance doses containing 3.0 μg, whereas doses containing only 0.6 μg are no more effective than placebo. Sublingual immunotherapy for seasonal grass allergy can be safely administered by general practitioners, but symptom relief begins only in the second season of therapy. Sublingual immunotherapy for seasonal grass allergy in children reduced symptoms and onset of new asthma symptoms but, again, beginning only in the second year of treatment. A course of 6 weekly injections of ragweed Amb a 1 bound to cytosine phosphorothionate guanosine containing DNA produced a shift from TH2 to TH1 cytokine release both in peripheral blood cells and in the nose after allergen challenge. No symptom improvement was seen the first year, but symptoms were reduced the second year without further treatment. The concept of 1 airway, with immunological as well as anatomical connections between the upper and lower airway, continues to be a subject of investigation and to gain support (Table I). Data on the coexistence of asthma and rhinitis were collected from subjects age 20 to 44 years as part of the European Community Respiratory Health Survey.1Leynaert B. Neukirch C. Kony S. Guénégou A. Bousquet J. Aubier M. et al.Association between asthma and rhinitis according to atopic sensitization in a population-based study.J Allergy Clin Immunol. 2004; 113: 86-93Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar On the basis of a postal questionnaire completed by 3000 respondents, asthma was present at the various centers in between 1.0% and 6.0% of respondents without rhinitis and between 7.6% and 22.6% of respondents with rhinitis. Rhinitis prevalence at the various centers ranged between 10.5% and 36.2% for respondents without asthma and between 50.0% and 77.1% for respondents with asthma. Among 600 of the respondents who underwent further testing, asthma was present in 2.0% of those without rhinitis and 13.4% of those with rhinitis (odds ratio, 6.63). In respondents with rhinitis, there was a 3-fold increase in bronchial hyperresponsiveness compared with respondents without rhinitis. The risks for both asthma and rhinitis were significantly associated with a parental history of asthma, levels of total IgE, and atopic sensitization. However, after adjusting for these and other confounding factors, rhinitis remained significantly associated with a higher risk of asthma and for bronchial hyperresponsiveness in subjects without asthma. Thus, the association between rhinitis and asthma does not appear to be explained fully by a common atopic predisposition.Table IKey advances in upper airway disease1. Data from a large European study confirmed the increased prevalence of rhinitis in patients with asthma and asthma in patients with rhinitis. The association could not be completely explained by coexistent atopy.2. Supporting a possible role of an immunologic reaction to fungi in CRS, peripheral blood monocytes from patients with CRS, on exposure to fungal extracts, particularly Alternaria, released IL-4, IL-13, and IFN-γ, whereas the cells of normal individuals did not.3. Not supporting a possible role of an immunologic reaction to fungi in CRS was a double-blind study of intranasal amphotericin that showed no benefit in patients with CRS.4. Studies in allergic rhinitis suggest that quality of life is affected by patients' confidence that they can cope with the disease as well as by the symptoms.5. Inability to concentrate and daytime drowsiness in allergic rhinitis may be part of the pathophysiology of the disease rather than a result of interference with sleep.6. In a large, 8-year follow-up study from Denmark, 17% who had had symptoms of allergic rhinitis had remitted. Open table in a new tab The similarities and differences between rhinitis and asthma were explored from the standpoint of remodeling.2Bousquet J. Jacquot W. Vignola A.M. Bachert C. Van Cauwsenberge P. Allergic rhinitis: a disease remodeling the upper airways?.J Allergy Clin Immunol. 2004; 113: 43-49Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar Even though inflammation is similar in rhinitis and asthma, there is far less remodeling seen in the nose in rhinitis than in the bronchi in patients with asthma. Epithelial damage is minimal, and the reticular basement membrane does not have the pseudothickening characteristic of asthma. Two possible explanations were offered for the differences between remodeling in the nose and lung: changes in the bronchi may be a result of cytokine production by smooth muscle cells, or differences may relate to the differing embryonic origin, because the nose is of ectodermal origin, and the bronchi are of endodermal origin. Otitis media with effusion (OME) is a common, chronic inflammatory disease of the middle ear space. Epidemiologically, patients with OME have an increased prevalence of atopic conditions such as allergic rhinitis, eczema, and asthma. To explore the possibility that OME may have an inflammation similar to that found in rhinitis, specimens were obtained of middle ear effusion, and of adenoidal and eustachian tube tissue during adenoidectomy from 45 children with OME (age 2-18 years).3Nguyen L.H.P. Manoukian J.J. Sobol S.E. Tewfik T.L. Mazer B.D. Schloss M.D. et al.Similar allergic inflammation in the middle ear and the upper airway: evidence linking otitis media with effusion to the united airways concept.J Allergy Clin Immunol. 2004; 114: 1110-1115Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar Eleven (24%) of the children were atopic as defined by at least 1 positive skin prick test result. In these atopic children, the middle ear effusions had significantly higher levels of eosinophils, T lymphocytes, and IL-4 mRNA+ cells and significantly lower levels of neutrophils and IFN-γ mRNA+ cells compared with nonatopic patients. Similar differences were found in the eustachian and adenoidal tissue. The authors concluded that their data support the concept that the middle ear may be part of the united airway in atopic individuals. Rhinitis therapy has been reported to improve subjective and objective measures of asthma. To examine the effect of rhinitis treatment on asthma exacerbations, patient data were analyzed from a large managed care organization.4Corren J. Manning B.E. Thompson S.F. Hennessy S. Strom B.L. Rhinitis therapy and the prevention of hospital care for asthma: a case-control study.J Allergy Clin Immunol. 2004; 113: 415-419Abstract Full Text Full Text PDF PubMed Scopus (194) Google Scholar To be eligible, patients were identified as having both asthma and rhinitis. Records were searched for emergency department visits or hospitalizations. A nested case control analysis was then conducted of 361 subjects and 1444 control patients. Patients who used nasal corticosteroids had a significantly lower risk of both asthma-related emergency department treatment and hospitalization (adjusted odds ratios, 0.75 and 0.56, respectively). Nonsedating antihistamine use was associated with a nonsignificant trend toward reduced visits. However, patients using both nasal corticosteroids and antihistamines had a further reduction over patients using nasal corticosteroids alone in the risk for both emergency department visits and hospitalizations. A combined faculty of allergist/immunologists, infectious disease specialists, radiologists, and otolaryngologists met in a workshop to discuss rhinosinusitis research and patient care.5Meltzer E.O. Hamilos D.L. Hadley J.A. Lanza D.C. Marple B.F. Nicklas R.A. Rhinosinusitis: establishing definitions for clinical research and patient care.J Allergy Clin Immunology. 2004; 114: S156-S212Google Scholar The resulting document, Rhinosinusitis: Establishing Definitions for Clinical Research and Patient Care, appeared as a supplement to the December 2004 issue of the Journal and in the December 2004 issue of Otolaryngology—Head and Neck Surgery. This report first addressed the causative factors in rhinosinusitis: bacterial, fungal, allergic/immunologic, and nonimmunologic. There was a discussion of the histological features of chronic rhinosinusitis (CRS) and of nasal polyps. The article then addressed the approach to the diagnosis and assessment of rhinosinusitis that should be used in future studies, including symptoms, quality of life assessments, rhinoscopy, imaging, and challenges. Guidelines were provided for future studies of intervention in rhinosinusitis, including precise definitions of the disease state being studied. An editorial accompanying the workshop report highlights the importance of CRS: 18 million cases, 30 million courses of antibiotics, and 40,000 patients per year undergoing sinus surgery.6Platts-Mills T.A.E. Rosenwasser L.J. Chronic sinusitis consensus and the way foreword.J Allergy Clin Immunol. 2004; 114: 1359-1361Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar Thus, the importance that future research address the role of bacterial infection and the indications for surgery in this eosinophilic inflammatory disease. The etiology of CRS was addressed in an article from the Mayo Clinic.7Shin S.-H. Ponikau J.U. Sherris D.A. Congdon D. Frigas E. Homburger H.A. et al.Chronic rhinosinusitis: an enhanced immune response to ubiquitous airborne fungi.J Allergy Clin Immunol. 2004; 114: 1369-1375Abstract Full Text Full Text PDF PubMed Scopus (246) Google Scholar The authors noted that antibiotics and surgery are usually ineffective in long-term treatment; that the histological hallmark is a chronic inflammatory infiltrate of lymphocytes, plasma cells, and eosinophils similar to that in the bronchial mucosa of patients with asthma; and that the patients have increased numbers of CD4+ T lymphocytes positive for cytokines such as IL-5, IL-13, and IFN-γ in their sinus mucosa, suggesting an immunologic mechanism. However, less than 40% of patients with CRS are atopic. Pursuing previous suggestions of a role of common fungi in the etiology of this disease, the authors cultured PBMCs with extracts of 4 common fungi: Alternaria, Cladosporium, Aspergillus, and Penicillium. The PBMCs of patients with CRS showed increased cytokine production compared with normal controls on exposure to Alternaria, Cladosporium, and Aspergillus. Most striking was the response to Alternaria, to which PBMCs from 16 of 18 CRS patients produced IL-5, compared with 0 of 15 normals. PBMCs from all of the CRS patients produced IL-13 on stimulation with Alternaria compared with none of the controls, and they produced 5.5 times as much IFN-γ. On the other hand, only 28% of the patients with CRS had specific IgE directed toward Alternaria. Because fungal antigens can be isolated from the nasal secretions of most patients with CRS and the cytokines released by stimulation of patients' PBMCs with these fungi are the same as those expressed in the airways of patients with CRS, the authors suggest that the response to these ubiquitous airborne fungi may explain both the chronic airways inflammation and the concomitant asthma symptoms in patients with CRS. Two uncontrolled studies had reported that treatment of patients with CRS with intranasal washes containing amphotericin had resulted in the disappearance of nasal polyps and a decrease in symptoms.8Ricchetti A. Landis B.N. Maffioli A. Giger R. Zeng C. Lacroix J.S. Effect of anti-fungal nasal lavage with amphotericin B on nasal polyposis.J Laryngol Otol. 2002; 116: 261-263Crossref PubMed Scopus (119) Google Scholar, 9Ponikau J.U. Sherris D.A. Kita H. Kern E.R. Intranasal antifungal treatment in 51 patients with chronic rhinosinusitis.J Allergy Clin Immunol. 2002; 110: 862-866Abstract Full Text Full Text PDF PubMed Scopus (190) Google Scholar A randomized, placebo-controlled study was undertaken in Ulm, Germany, to assess the response of patients with CRS to this treatment.10Weschta M. Rimek D. Formanek M. Polzehi D. Podbielski A. Riechelmann H. Topical antifungal treatment of chronic rhinosinusitis with nasal polyps: a randomized, double-blind clinical trail.J Allergy Clin Immunol. 2004; 113: 1122-1128Abstract Full Text Full Text PDF PubMed Scopus (195) Google Scholar Seventy-eight patients with nasal polyps, symptoms, and positive sinus computed tomography were randomized to receive 200-μL nasal sprays with either amphotericin solution or saline 4 times daily for 8 weeks. Sixty completed the study (6 in the amphotericin group discontinued because of intolerance of the medication). There was no difference between active and placebo groups in the follow-up sinus CT scores, whereas the median posttreatment symptom score was significantly worse in the amphotericin group than in subjects who had received placebo. The authors concluded that treatment with amphotericin was ineffective and was not indicated in patients with severe CRS. It should be noted, however, that in this study, amphotericin was administered as a 200-μL spray rather than as a 20-mL wash, which had been used in the studies reporting a favorable response to amphotericin. Polymorphic MHC class II molecules on the surface of antigen-presenting cells have been implicated in the immunopathogenesis of several chronic inflammatory diseases, including rheumatoid arthritis, type I diabetes, multiple sclerosis, and celiac disease. Recently, allergic bronchopulmonary aspergillosis has been reported to have HLA–MHC class II associations. This led to a study of MHC class II associations with allergic fungal sinusitis (AFS; n = 44) and chronic hypertrophic rhinosinusitis (HRS; n = 30).11Schubert M.S. Hutcheson P.S. Graff R.J. Santiago L. Slavin R.G. J Allergy Clin Immunol. 2004; 114: 1376-1383Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar Patients with AFS and HRS were similar in having increased prevalence of HLA-DQBI∗03 alleles over normal. Although 66% of patients with AFS and 50% of patients with HRS had positive results for at least 1 allele, the 2 groups differed in their frequency of DQBI∗03 allelic variants. These findings suggest potential roles for MHC class II molecules in the immunopathogenesis of both chronic HRS and AFS. Nasal polyps are almost always a manifestation of CRS, and like CRS, they are characterized histologically by an inflammatory cell infiltration of eosinophils, lymphocytes, and plasma cells. DNA microarray technology consists of a matrix with attached sequences that allow simultaneous analysis of expression of panels of human genes. Comparison of profiles of genes expressed by diseased and healthy tissues often highlights the involvement of both expected and unsuspected pathologic pathways. In a study from Johns Hopkins, expression microarrays containing approximately 10,500 genes were used to compare gene profiles of nasal polyp tissue from 10 patients and normal sphenoid mucosal samples from 4 patients who had undergone pituitary surgery.12Liu Z. Kim J. Sypek J.P. Wang I.-M. Horton H. Oppenheim F.G. et al.Gene expression profiles in human nasal polyp tissues studied by means of DNA microarray.J Allergy Clin Immunol. 2004; 114: 783-790Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar Compared with normal sinus tissue, 192 genes were upregulated at least 2-fold and 156 genes were downregulated by at least 50% in the nasal polyp samples. It is hoped that this information will ultimately prove useful in providing new insight into the pathogenesis and treatment of nasal polyps and CRS. It had been previously shown that an ongoing allergic response in the nose augmented bacterial sinusitis in a mouse model. To eliminate the possible contribution of the injected alum, studies were repeated with passive sensitization with TH2 lymphocytes followed by nasal allergen challenge.13Yu X. Sperling A. Blair C. Thompson K. Naclerio R. Antigen stimulation of TH2 cells augments acute bacterial sinusitis in mice.J Allergy Clin Immunol. 2004; 114: 328-334Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar Mice who were passively sensitized and intranasally challenged with allergen followed by infection showed an increase in the number of recovered bacteria and an increase in sinus inflammation compared with those given infection alone or those passively sensitized with TH1 lymphocytes, followed by intranasal allergen challenge and infection. The results suggest that the release of TH2 cytokines or the subsequent response of cells such as eosinophils interferes with the ability of the mouse to clear an infection during an ongoing allergic reaction. The occurrence rate of remissions in patients with allergic rhinitis was studied in Copenhagen, Denmark.14Bodtger L. Linneberg A. Remission of allergic rhinitis: an 8-year observational study.J Allergy Clin Immunol. 2004; 114: 1384-1388Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar Fifteen hundred eighty-one subjects, half selected randomly and half selected because they reported rhinitis or asthma symptoms on allergen exposure, were queried regarding nasal symptoms on exposure to plants, animals, or house dust mites (HDMs). If they reported symptoms within the previous 12 months and had at least a class II RAST to the relevant allergen, they were diagnosed as having allergic rhinitis. Eight years later, 734 (69%) of those eligible were re-evaluated by using the same questionnaire. In 1990, allergic rhinitis was reported by 198 subjects, with a total of 257 cases. On follow-up in 1998, 36 subjects had remission in 43 cases. Remission rates were 12% for pollen, 19% for animals, and 38% for HDMs, for a mean rate of 17%. In 78% of subjects experiencing symptom remission, the specific IgE remained stable. Overall, 22% of the remitting subjects and 7% of the nonremitting subjects had a decline in specific IgE. Immunotherapy had no effect on the rate of remission. Thus, for the most part, allergic rhinitis is a persisting disease. Symptoms may not fully reflect the effect of rhinitis on an individual's health-related quality of life (HRQOL). The elements contributing to the Rhinosinusitis Disability Index, a measure of HRQOL in rhinosinusitis, were evaluated in a telephone interview with 106 randomly selected individuals with a physician diagnosis of allergic rhinitis, sinusitis, or chronic postnasal drip.15Chen H. Katz P.P. Eisner M.D. Yelin E.H. Blanc P.D. Health-related quality of life in adult rhinitis: the role of perceived control of disease.J Allergy Clin Immunol. 2004; 114: 845-850Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar In a multivariate model, 3 components were found to be independent predictors of the HRQOL. They were a Rhinitis Symptom Score consisting of 11 questions pertaining to eye, nose, and sinus symptoms, each graded 0 to 4; a Perceived Control of Rhinitis Questionnaire consisting of 8 questions regarding an individual's perception of their ability to deal with rhinitis, graded 1 to 4; and the Center for Epidemiologic Studies Depression Scale, with 20 items intended to assess depression and psychological distress. These 3 questionnaires accounted for 62% of the variance in the HRQOL (symptom score, 36%; the other 2 together, 26%). The Medical Outcomes Study Short Form (SF) 12 (an abbreviated SF-36) and medication use were not independent contributors to the rhinosinusitis HRQOL. It was concluded that disease severity accounts for only a portion of the variation observed in rhinitis-specific HRQOL. Psychological factors appear to play a nearly equal role, particularly the individual's perceived ability to deal with the condition. This emphasizes the importance of educating patients to cope with their rhinitis effectively. Strategies to achieve this include teaching patients environmental controls and proper use of their medication (especially timing). In addition to the classical ocular/rhinitis symptoms, patients with allergic rhinitis often complain of impairment of their daytime performance, daytime sleepiness, and diminished quality of life. These latter symptoms are often attributed to impairment of sleep because of rhinitis, but this has not often been studied. Twenty-five subjects with seasonal allergic rhinitis and 25 normal subjects were followed with assessment of symptoms, daytime sleepiness, and quality of life (SF-36) during the pollen season and polysomnography before and during the season.16Stuck B.A. Czajkowski J. Hagner A.-E. Klimek L. Verse T. Hörmann K. et al.Changes in daytime sleepiness, quality of life and objective sleep patterns in seasonal allergic rhinitis: a controlled clinical trail.J Allergy Clin Immunol. 2004; 113: 663-668Abstract Full Text Full Text PDF PubMed Scopus (158) Google Scholar During the pollen season, the subjects with allergic rhinitis had significant increases in their sleepiness scores and deterioration in the physical function and role physical parameters of the quality of life assessments. These changes were largely limited to subjects with moderate or severe rhinitis symptoms. Statistically significant differences between groups were also found for selected parameters of the sleep studies, but the changes were minimal, and all values were within normal ranges. Thus, daytime sleepiness seems to be related to rhinitis itself rather than to an impairment of nocturnal sleep. A somewhat different conclusion was reached in the supplement to the November 2004 issue of the Journal, Allergic Rhinitis After Hours: The Relevance and Consequence of Nighttime Symptoms.17Craig T.J. McCann J.L. Gurevich F. Davies M.J. The correlation between allergic rhinitis and sleep disturbance.J Allergy Clin Immunol. 2004; 114: S139-S148Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar Evidence was reviewed supporting the conclusion that the pathophysiology of allergic rhinitis often disrupts sleep, leading to fatigue, irritability, memory deficits, excessive daytime somnolence, and depression, thereby further reducing the quality of life. Allergic rhinitis is characterized by the epithelial layer accumulation of mast cells and eosinophils linked to the local generation and release of chemotactic factors. Those of relevance to the tissue eosinophil accumulation have been extensively studied, but scant attention has been given to those factors relevant to epithelial mast cell accumulation. To address this need, immunohistochemical analysis of the expression of mast cell chemoattractants and their receptors was made in nasal biopsies from symptomatic atopic patients with perennial and seasonal allergic rhinitis.18Salib R.J. Kumar S. Wilson S.J. Howarth P.H. Nasal mucosal immunoexpression of the mast cell chemoattractants TGF-β, eotaxin, and stem cell factor and their receptors in allergic rhinitis.J Allergy Clin Immunol. 2004; 114: 799-806Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar Mast cells were significantly increased in the epithelium of both rhinitis groups. Immunoreactivity for TGF-β1, TGF-β2, and TGF-β3 was observed, predominantly localized to the superficial columnar epithelial cells. It was significantly increased in both rhinitis groups. Similarly, immunoreactivity for the receptors TGF-βRI, TGF-βRII, and TGF-βRIII was significantly increased predominantly in the epithelial layer of both rhinitis groups. The number of epithelial mast cells significantly correlated with immunoreactivity levels for TGF-β1, TGF-β2, TGF-βRI, and TGF-βRII. Immunoreactivity for eotaxin was increased in the perennial rhinitis group, and C-kit positive cells were increased in the seasonal group, whereas CCR3 and stem cell factor were not increased in the patients with rhinitis. These results are consistent with the involvement of TGF-β in either the recruitment or retention of mast cells within the epithelium in patients with allergic rhinitis. Levocetirizine is the R or active enantiomer of cetirizine, which is itself an active metabolite of hydroxyzine, a first-generation antihistamine. Levocetirizine is reported to have less cerebral histamine receptor binding than the racemic compound, which would result in reduced central nervous system side effects. A 6-month placebo-controlled study of levocetirizine was conducted in Europe in 551 subjects with allergic rhinitis.19Bachert C. Bousquet J. Canonica G.W. Durham S.R. Klimek L. Mullol J. et al.Levocetirizine improves quality of life and reduces costs in long-term management of persistent allergic rhinitis.J Allergy Clin Immunol. 2004; 114: 838-844Abstract Full Text Full Text PDF PubMed Scopus (198) Google Scholar The symptomatic response to active treatment was rapid and sustained. At 4 weeks, reduction in total nasal symptom score with levocetirizine (including congestion) was 18% more than that in the placebo group, despite the use of less rescue medication. The Juniper rhinitis-specific quality of life score also improved by 0.48 compared with placebo (0.50 is considered a clinically meaningful change). Improvement in individual symptoms generally paralleled total symptom score except for nasal congestion, which improved significantly in the levocetirizine group only from 3 months on. The only difference in side effects was with somnolence, which was reported by 1.8% of the placebo and 6.8% of the levocetirizine subjects. However, further analysis revealed that the total duration of combined fatigue, asthenia, and somnolence in the 2 groups was similar, 3.26 days per 100 days in the placebo group and 3.72 days per 100 days in the levocetirizine group. Levocetirizine was compared with desloratadine and placebo in a crossover nasal challenge study in 24 subjects.20Deruaz C. Leimgruber A. Berney M. Pradervand E. Spertini F. Levocetirizine better protects than desloratadine in a nasal provocation with allergen.J Allergy Clin Immunol. 2004; 113: 669-676Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar Single doses of each drug were administered, followed by a nasal challenge with increasing doses of grass pollen extract. Both antihistamines were more effective than placebo (P < .001). Desloratadine increased the threshold by 1.93 allergen doses, whereas levocetirizine increased it by 2.63 doses (P = .02, levocetirizine vs desloratadine). Neither drug had any effect on nasal congestion or IL-5, IL-8, eotaxin, or eosinophil cationic protein levels in nasal lavage fluid at 24 hours after challenge. The monoclonal anti-IgE, omalizumab, has been shown to be effective in the treatment of allergic asthma and allergic rhinitis. A study using nasal allergen challenges was undertaken to determine the time to onset of action.21Lin H. Boesel K.M. Griffith D.T. Pru