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.     

Stronger nasal responsiveness to cold air in individuals with rhinitis and asthma, compared with rhinitis alone

BACKGROUND: We have previously proposed that, compared with rhinitis alone, the constellation of upper and lower airway allergic disease is a manifestation of a more severe form of a syndrome affecting the entire airway. If this is correct, not only the lower, but also the upper airways of patients with asthma and rhinitis should demonstrate more abnormalities compared with patients with rhinitis alone, including higher sensitivity to irritant factors. Objective To test the hypothesis that, a previously well-studied natural nasal stimulus, cold, dry air (CDA), produces a stronger response in subjects with allergic rhinitis (AR) and asthma compared with subjects with AR alone. METHODS: We performed nasal provocation with CDA on 24 individuals with asthma and rhinitis and 17 with rhinitis alone. Prior to and after the challenge, nasal symptoms were recorded using visual analogue scales and nasal lavages were performed to determine histamine and lysozyme levels. RESULTS: The two groups reacted differently to CDA: after the challenge, patients with rhinitis and asthma reported significantly higher scores for nasal congestion, rhinorrhea and lacrimation. Also in this group, significant increases in histamine and in lysozyme levels in nasal lavage fluids were induced by CDA. In subjects with rhinitis alone, CDA failed to increase histamine or lysozyme levels above baseline. The CDA-induced change from baseline in histamine was significantly higher in the patients with rhinitis and asthma, compared with the rhinitis-only group. CONCLUSION: Patients with AR and asthma have stronger nasal responsiveness to CDA compared with patients with rhinitis alone. This observation is consistent with the notion that compared with rhinitis alone, the presence of asthma and rhinitis signifies a higher degree of functional abnormality of the entire airway.     

Allergic rhinitis and its impact on otorhinolaryngology

Allergic rhinitis (AR) is a disease with growing impact on everyday medical practice, as its prevalence has steadily increased during the last decades. Immunoglobulin-E (IgE)-mediated airway inflammation may manifest itself as AR, asthma or both. Allergic inflammation in upper and lower airways is now considered as one airway disease, with manifestation of symptoms in upper, lower or global airway. This insight into allergic inflammation of the whole respiratory tract has consequences for the diagnostic and therapeutic approach of affected patients, as highlighted in the ARIA document. In contrast to asthma, the link between AR and associated conditions in the upper airways like rhinosinusitis, nasal polyps, recurrent viral infections, adenoid hypertrophy, tubal dysfunction, otitis media with effusion and laryngitis remains less explored. It is however of utmost importance to consider the aetiological role of IgE-mediated inflammation of the nasal mucosa in several diseases of the upper respiratory tract, as they represent a large body of patient population seen by the general practitioner as well as the paediatrician, allergologist and otorhinolaryngologist. We here aim at reviewing the current literature on the relationship between AR and conditions in upper airways frequently encountered in everyday clinical practice, and highlight the need for further studies exploring the role of allergic inflammation in the development of these diseases.     

Therapeutic points of intervention and clinical implications: role of desloratadine

Desloratadine, a potent, once-daily, orally active, nonsedating, histamine H₁-receptor antagonist, inhibits the release of histamine and other inflammatory mediators. Once-daily desloratadine therapy rapidly reduces the symptoms of perennial allergic rhinitis and seasonal allergic rhinitis (SAR), reduces the use of inhaled albuterol by patients with SAR and concomitant asthma, and improves symptoms and quality of life in patients with chronic idiopathic urticaria. An open-label, observational study in SAR patients revealed that desloratadine therapy significantly reduced nasal, ocular, dermal, asthma, and total symptoms, and enabled half of the patients with concomitant asthma to reduce their use of asthma medications. Globally, more than 91% of patients and physicians judged desloratadine to have excellent or good efficacy, and more than 98% judged it to have excellent or good tolerability. Furthermore, desloratadine therapy improved quality of life, decreasing by more than 10-fold the percentage of patients whose daily activities and/or sleep were moderately or severely affected by SAR. Allergic rhinitis, a major chronic airway disease that is a risk factor for asthma, warrants extended diagnostic procedures and well-tolerated therapy that encompasses the entire airway, addresses multiple steps in the allergic inflammatory cascade, and is effective on nasal, ocular, dermal, asthma, and total symptoms.     

Noninvasive methods for the detection of upper and lower airway inflammation in atopic children

BACKGROUND: Exhaled nitric oxide (FE(NO)) and exhaled breath condensate (EBC) are noninvasive methods to assess inflammation. OBJECTIVE: To investigate the role of the FE(NO) and of the EBC pH and IL-5 levels in atopic children. METHODS: We evaluated oral and nasal FE(NO) and the pH and IL-5 of oral and nasal EBC in children with atopic dermatitis (AD; n = 18), allergic rhinitis (AR; n = 18), intermittent asthma (n = 21), moderate persistent asthma (n = 18), and healthy controls (HCs; n = 16). RESULTS: Oral FE(NO) was significantly increased in asthma, whereas the nasal values were increased in AR and asthma in comparison with HCs. The pH of oral EBC was lower in AD and asthma than in AR and HCs, whereas the nasal levels were lower in AD, AR, and asthma than in HCs. The oral IL-5 was higher in AD, AR, and asthma in comparison with HCs, whereas the nasal IL-5 concentrations were higher in asthma and AR than in HCs. In AR, the nasal FE(NO) correlated with the IL-5 values and with the disease duration. In intermittent asthma, oral and nasal pH inversely correlated with the exacerbations, whereas in moderate asthma, the nasal IL-5 positively correlated with exacerbations. In AD, the oral and nasal IL-5 positively correlated with the serum IgE. CONCLUSION: These markers of nasal and bronchial inflammation, accessible with noninvasive techniques, might be useful to identify patients with uncontrolled diseases and to verify the usefulness of new therapeutic approaches. CLINICAL IMPLICATIONS: These markers are useful tools to monitor the upper and lower airway inflammation in atopic children.     

Atopic march: link to upper airways

PURPOSE OF REVIEW: This review examines the role of the upper airways in the atopic march. Evidence examining the theory that allergic rhinitis precedes asthma will be discussed. In addition, the role of allergic rhinitis as an end point in the atopic march will be reviewed. RECENT FINDINGS: Ciprandi and colleagues found that nasal symptoms, airflow and markers of inflammation (eosinophils, cytokine levels) directly correlated with lower airway markers. This confirms previous studies finding that many patients with allergic rhinitis have lower airway hyperreactivity or bronchial hyperresponsiveness and the link between upper and lower airways. Leynaert and colleagues questioned over 90 000 individuals and found that patients with rhinitis have increased risk for asthma and lower airway reactivity compared with patients without rhinitis. In the German Multicenter Atopy Study, a longitudinal study of 1300 children, patients with atopic dermatitis were found to have increased risk for asthma at 7 years of age. Patients with atopic dermatitis and no wheezing in the first 3 years, however, did not have an increased risk for developing current wheezing or bronchial hyperresponsiveness at 7 years of age. It was proposed that atopic dermatitis and asthma are linked, but atopic dermatitis does not precede asthma. SUMMARY: Allergic rhinitis is a risk factor for asthma and can precede asthma in the atopic march.     

Effect of nasal triamcinolone acetonide on lower airway inflammatory markers in patients with allergic rhinitis

BACKGROUND: Allergic rhinitis (AR) and asthma are commonly associated, and similar underlying inflammatory processes link both diseases. AR, even in the absence of asthma, is associated with increased levels of exhaled nitric oxide (ENO) and hydrogen peroxide (H(2)O(2)) in exhaled breath condensate, 2 noninvasive markers of lower airway inflammation. OBJECTIVE: We sought to evaluate the effect of treatment with the nasal steroid triamcinolone acetonide on ENO and exhaled H(2)O(2) in subjects with AR. METHODS: We allocated 23 subjects in a randomized, double-blind, parallel-controlled fashion to 4-week treatment with triamcinolone acetonide (220 microg/d) or matching placebo. RESULTS: ENO levels were greater in the subgroup with concomitant asthma (16/23 subjects) and decreased significantly with triamcinolone acetonide treatment in this subgroup of patients in comparison with patients receiving placebo. Breath condensate levels of H(2)O(2) were higher in patients with AR without asthma than in those with asthma but decreased significantly with triamcinolone acetonide treatment in both subgroups. No changes were observed in bronchial hyperresponsiveness, nasal and asthma symptoms, or peak expiratory flow with active treatment or placebo. CONCLUSION: We conclude that treatment of AR with triamcinolone acetonide results in decrease of 2 noninvasive markers of lower airway inflammation, ENO and H(2)O(2), supporting that upper and lower airway inflammation should be seen as a continuum in subjects with AR with and without asthma. ENO might be a more specific marker of the lower airway inflammation present in asthma.     

Prevalence and severity of allergic rhinitis in house dust mite-allergic patients with bronchial asthma or atopic dermatitis

BACKGROUND: Allergic rhinitis, asthma and atopic dermatitis are closely associated. Although population-based studies report a high prevalence of rhinitis among asthma patients, less is known of the association between rhinitis and atopic dermatitis and the severity of concomitant rhinitis. OBJECTIVES: We aimed to determine the prevalence and severity of allergic rhinitis among asthmatics and patients with atopic dermatitis and assessed whether age and comorbidity influence the severity of rhinitis signs and symptoms. METHODS: Three hundred and twenty-five patients recruited for a multicentre trial to study the effect of encasings of mattresses, pillows and duvets on signs and symptoms of allergic rhinitis and/or asthma and/or atopic dermatitis recorded visual analogue scores (VAS) and daily symptom scores and underwent nasal challenge tests with house dust mite (HDM). RESULTS: Based on history and clinical symptoms 92% of the 164 asthmatic patients and 85% of the 86 patients with atopic dermatitis could be diagnosed as having rhinitis. Inclusion of a positive provocation to HDM did not result in a substantial lower prevalence of rhinitis. Subjects reported moderate symptoms, with mean rhinitis VAS scores ranging from 40.0 to 55.0. Presence of atopic dermatitis was associated with lower rhinitis VAS and symptoms scores, whereas in multivariate analysis the presence of asthma was positively associated with nasal responsiveness to HDM. CONCLUSION: The prevalence of nasal symptoms in patients with bronchial asthma or atopic dermatitis and sensitized to house dust mites is high. Although the majority of patients experience mild to moderate symptoms, the presence of nasal disease needs to be examined in all patients with atopic disorders.     

Nasal eosinophilic inflammation contributes to bronchial hyperresponsiveness in patients with allergic rhinitis

There are increasing evidences that allergic rhinitis (AR) may influence the clinical course of asthma. We conducted methacholine challenge test and nasal eosinophils on nasal smear to patients with allergic rhinitis in order to investigate the mechanism of connecting upper and lower airway inflammation in 35 patients with AR during exacerbation. The methacholine concentration causing a 20% fall in FEV1 (PC20) was used as thresholds of bronchial hyperresponsiveness (BHR). Thresholds of 25 mg/dL or less were assumed to indicate BHR. All patients had normal pulmonary function. Significant differences in BHR were detected in the comparison of patients with cough or postnasal drip and without cough or postnasal drip. There were significant differences of PC20 between patients with cough or postnasal drip and those without cough or postnasal drip (3.41+/-3.59 mg/mL vs 10.2+/-1.2 mg/mL, p=0.001). The levels of total IgE were higher in patients with seasonal AR than in patients with perennial AR with exacerbation (472.5+/-132.5 IU/L vs. 389.0+/-70.9 IU/L, p<0.05). Nasal eosinophils were closely related to log PC20 (r=-0.65, p<0.01). These findings demonstrated that nasal eosinophilic inflammation might contribute to BHR in patients with AR.     

The link between allergic rhinitis and allergic asthma: a prospective population-based study. The Copenhagen Allergy Study

BACKGROUND: It has been hypothesized that allergic rhinitis and allergic asthma are manifestations of the same disease entity. We aimed to investigate the relationship between allergic rhinitis and allergic asthma. METHODS: Participants in a population-based study of 15-69-year-olds in 1990 were invited to a follow-up in 1998. A total of 734 subjects were examined on two occasions eight years apart. Allergic rhinitis to pollen was defined as a history of nasal symptoms on exposure to pollens and IgE specific to pollen. Allergic asthma to pollen was defined as a history of lower airway symptoms on exposure to pollens and IgE specific to pollen. Similarly, diagnoses of allergic rhinitis and allergic asthma to animals or mite were defined. RESULTS: At follow-up, all subjects with allergic asthma to pollen (n = 52) had in addition allergic rhinitis to pollen. In the longitudinal analysis, there were a total of 28 new (incident) cases of allergic asthma to pollen. They all had allergic rhinitis to pollen at baseline, or had developed allergic rhinitis to pollen at follow-up. Accordingly, allergic rhinitis to animals and mite were ubiquitous in subjects with allergic asthma to animals and mite, respectively. CONCLUSIONS: The results support the hypothesis that allergic rhinitis and allergic asthma are manifestations of the same disease entity.     

Prevalence and risk factors for allergic rhinitis and atopic eczema among schoolchildren in Israel: results from a national study.

BACKGROUND: There is growing evidence that the prevalence rates of asthma and allergic diseases are increasing, especially among children. Several risk factors are under investigation. OBJECTIVE: To evaluate the prevalence and risk factors for allergic diseases, including allergic rhinitis (AR) and atopic eczema (AE), among 13- to 14-year-old schoolchildren in Israel. METHODS: A modified version of the International Study of Asthma and Allergies in Childhood written questionnaire was administered to a national sample of schoolchildren 13 to 14 years old in Israel. The questionnaire was completed by the schoolchildren themselves. RESULTS: There were 10,057 complete questionnaires available for analysis. The prevalence of AR symptoms ever and current AR were 41.6% and 9.4%, respectively. Allergic rhinoconjunctivitis symptoms ever were reported by 15.8% of the children. The prevalence rates of 6 months of itchy rash ever and AE were 5.9% and 7.8%, respectively. After adjustment for demographic and environmental factors, current asthma, parental history of asthma, and population group were the most significant risk factors for current AR (odds ratio [OR], 4.47; 95% confidence interval [CI], 3.70-5.40; OR, 1.30; 95% CI, 1.02-1.66; and OR, 1.75; 95% CI 1.45-2.13; respectively) and AE (OR, 2.30; 95% CI, 1.80-2.90; OR, 1.80; 95% CI, 1.40-2.30; and OR, 1.70; 95% CI, 1.40-2.00; respectively). CONCLUSIONS: Israeli children have a low prevalence rate of current AR and a midrange rate of AE. Arabs have lower prevalence rates of allergic diseases than Jews, and the prominent risk factors for those diseases are current asthma and parental history of asthma.     

Overview of comorbid associations of allergic rhinitis

Allergic rhinitis affects approximately 20% of the U.S. population. An association between allergic rhinitis and conditions including asthma, sinusitis, otitis media, nasal polyposis, respiratory infections, and even orthodontic malocclusions has been observed. Clinical research has identified shared pathogenic mechanisms, epidemiologic correlations, and findings from allergy testing to indicate that these conditions represent long-term physical consequences in allergic individuals. The positive response of patients afflicted with these conditions to antiallergic treatment further enhances the association between allergic rhinitis and other airway diseases. The use of nasal corticosteroids in patients with rhinitis and asthma reduces not only rhinitis symptoms but also asthma symptoms and airway reactivity to methacholine challenge. Similarly, antihistamines, with or without decongestants, result in improvement of objective measurements of pulmonary function. In the treatment of acute sinusitis, the combination of an intranasal corticosteroid and an antibiotic provides greater benefit than an antibiotic alone. Treatment strategies for allergic rhinitis should be directed at controlling the symptoms of allergic rhinitis and reducing the development of physical complications in susceptible persons. Three techniques for the treatment of allergic rhinitis are used, including avoidance of offending allergens, selection of appropriate pharmaceuticals, and allergy immunotherapy. Appropriate treatment may spare some patients of related airway diseases and may also reduce the overall cost of care. The broadened scope of allergic rhinitis and increased prevalence of IgE-mediated diseases have heightened awareness regarding the profound consequences of allergic rhinitis and the importance of effective treatment. (J Allergy Clin Immunol 1997;99:S773-80.)     

A comparison of topical budesonide and oral montelukast in seasonal allergic rhinitis and asthma

BACKGROUND: Allergic rhinitis and asthma commonly coexist and are both mediated by similar inflammatory mechanisms. Leukotriene antagonists may therefore be an alternative to corticosteroid therapy. OBJECTIVE: To compare oral montelukast with inhaled plus intranasal budesonide in patients with seasonal allergic rhinitis and asthma. PATIENTS AND METHODS: A single-blind double-dummy placebo-controlled crossover study was performed comparing once daily 10 mg oral montelukast with 400 microg inhaled plus 200 microg intranasal budesonide in 12 patients with allergic rhinitis and asthma: mean (S.E.) age 34.0 years (2.7), forced expiratory volume in 1 s (FEV1) 91.2 (3.8)% predicted. Each treatment was for 2 weeks with a 1-week placebo run-in and washout. Measurements were made after each active treatment and placebo for: adenosine monophosphate bronchial challenge, exhaled and nasal nitric oxide. Patients also recorded their domiciliary peak expiratory flow, nasal peak inspiratory flow, asthma and seasonal allergic rhinitis symptoms. RESULTS: There were no significant differences between the placebos for any measurement. For adenosine monophosphate PC20, geometric mean fold differences (95% confidence interval (CI) for difference) were 6.4 (2.2-18.6) for placebo vs. budesonide, 2.9 (1.0-8.4) for placebo vs. montelukast, and 2.1 (1.1-4.5) for budesonide vs. montelukast. For exhaled nitric oxide (p.p.b.) there was significant (P < 0.05) suppression with both montelukast (10.9) and budesonide (10.1) compared with placebo (18.8). For nasal nitric oxide and nasal peak flow there were only significant differences with budesonide compared with placebo. Both treatments reduced total seasonal allergic rhinitis symptoms but only budesonide had a significant effect on nasal symptoms. CONCLUSION: Once-daily inhaled plus intranasal budesonide and once daily montelukast showed comparable efficacy on lower airway, but only the budesonide had significant efficacy on upper airway inflammatory markers. Both treatments significantly reduced allergic rhinitis symptoms.     

Protective effect of montelukast on lower and upper respiratory tract responses to short-term cat allergen exposure.

BACKGROUND: Challenge with short-term exposure to airborne cat allergen in sensitized patients produces pulmonary function changes and rhinitis symptoms. OBJECTIVE: To determine the benefit of montelukast, 10 mg, for patients with concomitant asthma and allergic rhinitis as demonstrated by protection against both lower and upper airway responses to cat allergen challenge. METHODS: This randomized, crossover study treated patients with montelukast vs placebo during two 2-week, double-blind treatment periods, separated by a 1-week washout period. After each treatment period, patients underwent a 60-minute or less exposure to high levels of airborne cat allergen. Lower and upper airway responses were measured by spirometry and symptom scores. RESULTS: Of 52 patients with data from both treatment arms, 79% of patients taking montelukast and 67% taking placebo were exposed to the full 60-minute allergen challenge. Montelukast provided significant (P < or = .001) protection against allergen challenge in the lower airway coprimary end point of area under the curve during challenge (AUC0-60min) for percentage decrease in forced expiratory volume in 1 second: mean of 10.5% per hour and 14.7% per hour for montelukast and placebo, respectively. Although the effect on the overall nasal symptoms score (NSS) coprimary end point of AUC0-60min was not statistically significance (P = .12), nasal congestion during the challenge and NSS during recovery showed statistically significant (P = .048) protection by montelukast. Additional analyses of simultaneous lower and upper airway responses showed that more patients taking montelukast (22, 43%) vs placebo (13, 26%) were protected from both asthma and rhinitis (P = .02), with an odds ratio of 2.24 (95% CI, 1.16-4.32) in favor of montelukast. CONCLUSIONS: Montelukast has a protective effect against both lower and upper airway responses during exposure to high levels of cat allergen.     

Combined mediator blockade or topical steroid for treating the unified allergic airway

BACKGROUND: Asthma and allergic rhinitis are manifestations of a single unified allergic airway, for which the best treatment is uncertain. OBJECTIVE: To compare the anti-inflammatory efficacy in the unified allergic airway of combined oral mediator antagonism and combined topical steroid. METHODS: Subjects with asthma and perennial allergic rhinitis entered a randomized double blind crossover study comparing montelukast 10 mg and cetirizine 10 mg to extra-fine inhaled beclomethasone 400 mcg/day and intranasal beclomethasone 200 mcg/day, each taken once daily for 2 months, after 2-week placebo washouts. Measurements were made after each washout and randomized treatment, comprising: methacholine PC20, exhaled and nasal nitric oxide, blood eosinophils and eosinophilic cationic protein, symptoms, lung and nasal function tests. RESULTS: Seventeen patients completed per protocol. For PC20 and exhaled nitric oxide, only combined topical steroid produced improvements (P < 0.005) from placebo baseline. Combined steroid was superior by a 0.93 (95% CI 0.14-0.93, P < 0.05) doubling dilution difference for PC20 and a 0.99 (95% CI 0.9-15.1, P < 0.01) doubling difference for exhaled nitric oxide. Both treatments attenuated eosinophils and eosinophilic cationic protein, and reduced nasal symptoms (P < 0.05). Only steroid improved nasal nitric oxide (P=0.05) and asthma symptoms (P < 0.05). Neither treatment affected lung or nasal function tests. CONCLUSION: Combined topical steroid and combined mediator antagonism both attenuated systemic inflammation in the unified allergic airway, but only the former reduced bronchial and nasal inflammatory markers. The relevance of this to exacerbations and airway remodelling needs to be defined.     

Eosinophilic inflammation, remodeling of lower airway, bronchial responsiveness and cough reflex sensitivity in non-asthmatic subjects with nasal allergy

BACKGROUND: It has been reported that nasal allergy influences the lower airway inflammation and functions. We elucidated whether nasal allergy would contribute to lower airway inflammation and functions. METHODS: 266 subjects aged 21-39 years were interviewed with special emphasis on history of asthma and nasal allergies (perennial allergic rhinitis (PAR) and seasonal allergic rhinitis (Japanese cedar pollinosis; PO)). Symptomatic subject was defined when nasal symptoms were present during a 3-week study period. Pulmonary function, provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 s (PC20), capsaicin cough threshold defined as capsaicin concentration eliciting 5 or more coughs (C5) and eosinophil percentage in hypertonic saline-induced sputum were measured. RESULTS: Based on the interview, 232 subjects without asthma were divided into symptomatic (n = 25) and asymptomatic (n = 22) PAR, PO on-season (n = 15) and off-season (n = 36), and non-nasal allergy subjects (control) (n = 134). Sputum eosinophils were significantly greater in symptomatic PAR than another four groups (p < 0.01). FEV1/FVC ratio was significantly lower in PAR than control (p < 0.05). Maximum mean expiratory flow was lower in PAR than control (asymptomatic: p < 0.05, symptomatic: p = 0.06). C5 was not different among groups. PAR tended to have a lower PC20 compared to control (symptomatic: p = 0.078; asymptomatic: p = 0.086). CONCLUSIONS: These results suggest that eosinophilic inflammation occurred in symptomatic period of PAR may contribute to development of lower airway remodeling and bronchial hyperresponsiveness. Reversely, PO may not be associated with lower airway eosinophilic inflammation or abnormal bronchial functions. Nasal allergy dose not influence the cough reflex sensitivity.     

Association between sensitized to food allergens and childhood allergic respiratory diseases in Taiwan

BackgroundSensitization to allergen has long been known to be relate to childhood allergic diseases. Polysensitised children have more severe atopic diseases, whereas allergic rhinitis or asthma children with cosensitized to food and inhalant allergens were under-researched.ObjectiveTo realize the association between sensitization to food allergens and pediatric allergic rhinitis and asthma in Taiwan.MethodsWe included 138 participants with sensitized to allergen as assessed by serum-specific IgE. 87 of 138 participants had allergic rhinitis and 51 participants had asthma. All participants underwent a physical examination and measurement of serum total and specific IgE values. Besides, nasal peak expiratory flow rate (nPEFR) that was performed by the participants with allergic rhinitis and were requested to complete the Pediatric Rhinoconjunctivitis Quality of Life Questionnaires (PRQLQ). Lung function test and asthma control test (ACT)/child asthma control test (C-ACT) were performed by the participants with asthma.Results39 of 87 allergic rhinitis participants with sensitized to food and inhalant allergens (AR food group), 48 of 87 allergic rhinitis participants with sensitized to inhalant allergen alone (AR inhalant group). The AR food group had significantly lower nPEFR values and higher total IgE values (p < 0.05) compared with the AR inhalant group. The AR food group had higher PRQLQ scores than the AR inhalant group. 24 of 51 asthma participants with sensitized to food and inhalant allergens (Asthma food group), 27 of 51 asthma participants with sensitized to inhalant allergen alone (Asthma inhalant group). The Asthma food group had significantly higher total IgE values (p < 0.05) compared with the Asthma inhalant group. The Asthma food group had lower lung function test values and asthma control test (ACT) scores than the other group.ConclusionsChildren with cosensitized to food and inhalant allergens have more severe clinical symptoms and abnormal laboratory findings. Sensitization to food allergen was more related to pediatric allergic rhinitis than asthma. We may need larger, longer and extended studies to confirm these findings.     

Objective assessments of allergic and nonallergic rhinitis in young children

Background:  Allergic and nonallergic rhinitis are common childhood disorders.
Objective:  To study nasal eosinophilia and nasal airway patency in young children with allergic and nonallergic rhinitis to assess the pathology behind such diagnoses.
Methods:  We investigated 255 children at six years of age from the Copenhagen Prospective Study on Asthma in Childhood birth cohort assessing rhinitis history, specific immunoglobulin E relevant to rhinitis symptoms, nasal eosinophilia and nasal airway patency by acoustic rhinometry before and after decongestion. Associations were studied in a multivariate graphical model corrected for gender, height and nasal steroid usage.
Results:  Allergic rhinitis was significantly and directly associated with irreversible nasal airway obstruction (reduced decongested nasal airway patency) ( P  =   0.004), whereas nonallergic rhinitis was not. Both allergic rhinitis ( P  =   0.000) and nonallergic rhinitis ( P  =   0.014) were directly and significantly associated with nasal eosinophilia, but this association was stronger for allergic rhinitis.
Conclusion:  Allergic rhinitis and nonallergic rhinitis are of different pathologies as suggested from their different associations not only to allergy but importantly also to irreversible nasal airway obstruction and eosinophilic inflammation. 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 at the age of 6 years. Nonallergic rhinitis exhibited no change in the nasal airway patency, but some nasal mucosal eosinophilia albeit less than children with allergic rhinitis.     

Changes in bronchial responsiveness following nasal provocation with allergen.

The relationship between upper airway inflammation and asthma is controversial. In the current study, we sought to investigate the relationship between allergic rhinitis and lower airway dysfunction by performing double-blind, randomized nasal challenges with allergen or placebo. Subjects were selected for a prior history of asthma exacerbations after the onset of seasonal allergic rhinitis symptoms. After the induction of a marked nasal-allergic reaction (with a technique of nasal provocation that limited allergen delivery to the nose), there were no changes in FEV1, specific conductance, or lung volumes either 30 minutes or 4 1/2 hours after nasal allergen challenge, nor any changes in peak flow rates followed hourly until the next day. However, nasal provocation with allergen resulted in a relative increase in bronchial responsiveness to methacholine compared with that to placebo (p = 0.011 at 30 minutes and p = 0.0009 at 4 1/2 hours after challenge). Our study suggests that, although a nasal-allergic response does not induce airflow limitation of the lower airways, it can alter bronchial responsiveness.     

Role of IL-25, IL-33, and TSLP in triggering united airway diseases toward type 2 inflammation

Under the concept of "united airway diseases," the airway is a single organ wherein upper and lower airway diseases are commonly comorbid. The upper and lower airways are lined with respiratory epithelium that plays a vital role in immune surveillance and modulation as the first line of defense to various infective pathogens, allergens, and physical insults. Recently, there is a common hypothesis emphasizing epithelium-derived cytokines, namely IL-25, IL-33, and TSLP, as key regulatory factors that link in immune-pathogenic mechanisms of allergic rhinitis (AR), chronic rhinosinusitis (CRS), and asthma, mainly involving in type 2 inflammatory responses and linking innate and adaptive immunities. Herein, we review studies that elucidated the role of epithelium-derived triple cytokines in both upper and lower airways with the purpose of expediting better clinical treatments and managements of AR, CRS, asthma, and other associated allergic diseases via applications of the modulators of these cytokines.