Nasal ocular reflexes and eye symptoms in patients with allergic rhinitis.

BACKGROUND: Allergic patients often complain of eye symptoms during the allergy season. A possible mechanism for these eye symptoms is a nasal ocular reflex. OBJECTIVE: To demonstrate eye symptoms after nasal allergen challenge. METHODS: In a double-blind, placebo-controlled, crossover, clinical trial, 20 patients with seasonal allergic rhinitis were challenged in 1 nostril with antigen, and the response was monitored in both nostrils and in both eyes. Symptoms were recorded. Filter paper disks (intranasally) and Schirmer strips (intraocularly) were used for collecting secretions, which were subsequently eluted for the measurement of histamine and albumin levels. Patients were treated once topically at the site of challenge with azelastine or placebo. RESULTS: After placebo treatment, ipsilateral nasal challenge caused nasal symptoms and an increase in secretion weights; both were blocked by treatment with azelastine. Histamine and albumin levels increased only at the site of nasal challenge. Azelastine pretreatment inhibited the increase in albumin but not histamine levels. Symptoms of itchy and watery eyes increased significantly compared with symptoms with sham challenge after nasal allergen and were blocked by azelastine use. Ocular secretion weights increased bilaterally after placebo use and were not inhibited by azelastine use. CONCLUSIONS: Nasal allergen challenge releases histamine at the site of the challenge, which probably initiates a nasonasal and a nasal ocular reflex. This reflex is reduced by an H1-receptor antagonist applied at the site of the challenge. The eye symptoms associated with allergic rhinitis probably arise, in part, from a naso-ocular reflex.     

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.     

Nasal obstruction in patients with seasonal allergic rhinitis: relationships between allergic inflammation and nasal airflow

BACKGROUND: Nasal obstruction is a typical symptom of allergic rhinitis. Allergic rhinitis is characterized by a Th2-dependent inflammation. The aim of this study was to evaluate the possible relationships between allergic inflammation, including inflammatory cells and cytokine pattern, and nasal airflow in patients with nasal obstruction due to seasonal allergic rhinitis. METHODS: Fifty patients (31 males and 19 females, mean age 31.9 +/- 4.8 years) with seasonal allergic rhinitis were evaluated during the pollen season. All of them had moderate to severe nasal obstruction. Total symptom score, rhinomanometry, nasal lavage, and nasal scraping were assessed in all subjects. Inflammatory cells were counted by conventional staining; IL-4, IL-5, IL-8, and IFNgamma were measured by immunoassay on fluids recovered from nasal lavage. RESULTS: Significant positive relationships were demonstrated between eosinophil infiltration and IL-4 levels (p < 0.0001), eosinophils and IL-5 levels (p < 0.0001), and eosinophils and IL-8 levels (p < 0.0001). Significant negative relationships were demonstrated between eosinophil infiltration and IFNgamma levels (p < 0.0001) and eosinophil infiltration and nasal airflow (p < 0.001). CONCLUSIONS: This study demonstrates the close connection between Th2 cytokines and eosinophil infiltration. In addition, there is clear evidence concerning the relationship between eosinophil infiltration and nasal airflow. These findings constitute first evidence of the relationship between nasal airflow impairment and Th2-related inflammation in seasonal allergic rhinitis.     

Airway function and nasal inflammation in seasonal allergic rhinitis and asthma

BACKGROUND: Allergic rhinitis (AR) and asthma are frequently associated and characterized by a Th2-dependent inflammation. Nasal and bronchial obstruction may be objectively measured. OBJECTIVE: The aim of this study was to evaluate the relationships among upper and lower airway function and nasal inflammation in subjects with seasonal allergic rhinitis (SAR) and asthma. METHODS: Twenty out-patients (12 males and eight females, mean age: 23.4+3.6 years) with SAR and asthma were evaluated during the pollen season. All of them showed a moderate-severe grade of nasal obstruction. Total symptom score, rhinomanometry, spirometry, nasal lavage, and nasal scraping were obtained in all subjects. Eosinophils were counted by conventional staining; IL-4 and IFN-gamma were measured by immunoassay on fluids recovered from nasal lavage. RESULTS: Functional parameters, i.e. nasal airflow and forced expiratory volume in 1 s (FEV(1)), were correlated with nasal eosinophils (R(2)>0.83, P<0.001). Inflammatory parameters, i.e. eosinophils were correlated with immunological parameters, i.e. IL-4 and IFN-gamma levels (R(2)=0.93, P<0.001). Nasal symptoms were correlated with nasal airflow (rho=-0.71, P< or =0.01) and eosinophils (rho=0.72, P<0.01). Nasal airflow was correlated with FEV(1) (r=0.89, P<0.0001). CONCLUSIONS: This study demonstrates the close connection between Th2 cytokines and eosinophil infiltration in the nose. There is also clear evidence concerning the relationships between eosinophils infiltration and cytokines levels. Nasal eosinophils can be regarded as the most important predictors of upper and lower airway functions. These findings constitute first evidence of a relationship among nasal Th2-related inflammation and nasal and bronchial airflow in patients with SAR and asthma.     

Assessment of the correlation of rhinometry with the symptoms and signs of allergic rhinitis in children

The measurement of nasal patency by anterior rhinometry is a potentially useful tool in evaluating patients with various forms of rhinitis. This study measured both nasal air flow by anterior rhinometry and symptom/sign scores in 49 children with perennial allergic rhinitis. We found that anterior rhinometry in children is (1) a simple, rapid procedure, (2) well accepted by the pediatric patient, and (3) a valid technique for objectively assessing and quantifying the somewhat subjective parameters that physicians traditionally follow for allergic rhinitis.     

Nasal endoscopic findings in patients with perennial allergic rhinitis

Nasal endoscopy was carried out in 83 patients with perennial allergic rhinitis to evaluate endonasal anatomic variation and to find the correlation between the symptoms of patients and the endoscopic findings. All of the patients had nasal symptoms, 7.2% of the patients were runner, 7.2% were blocker and 85.6% were both. 86.75% of the patients had allergy-related symptoms, i.e. throat symptoms (73.5%), sinus headache (50.6%), and smell disturbance (10.8%). 95.2% of patients had abnormal endoscopic findings, i.e. deviated nasal septum (72.3%), abnormal middle turbinate (49.4%), narrowing of the entrance into the frontal recess (30.1%), septal spur (25.3%), obstruction of the entrance into the frontal recess (19.3%), nasal polyps (15.7%), mucopurulent discharge (14.5%), inferior turbinate hypertrophy (10.8%), abnormal uncinate process (9.6%), abnormal ethmoid bullae (7.2%), and enlargement of aggar nasi cells (2.4%). There was no significant correlation between each symptom and each endoscopic finding. However, there was a significant correlation between sinus headache and all of the combined abnormal endoscopic findings (P<0.05). These findings suggested that variations in endonasal anatomy was not by itself a pathology or a cause of symptoms. However, a combination of these variations may narrow the cleft of the ostiomeatal unit and cause contact area or stenosis, which predisposed patients to persistent symptoms, recurrent infection or resistance to therapy in patients with perennial allergic rhinitis. The endoscope might be a very useful tool for allergists, immunologists, and rhinologists, who work in the nose to deal with these cases.     

Nasal histamine challenges in symptomatic allergic rhinitis

Twenty subjects (seven with perennial allergic rhinitis, seven with symptomatic seasonal allergic rhinitis, and six normal control subjects) underwent assessment of nasal sensitivity to histamine. Nasal resistance was measured by posterior rhinometry under control conditions and after log incremental doses of histamine solution pipetted into the nose (0.5 to 5000 micrograms). Allergic subjects exhibited a twofold rise of nasal resistance with doses of 0.5, 5, or 50 micrograms of histamine, whereas the nasal resistance in normal subjects remained unchanged until 500 or 5000 micrograms of histamine had been administered. Nasal reactivity to histamine was not correlated with symptoms on the day of testing but was correlated with the number of positive wheals to skin prick testing. It was concluded that nasal resistance is more sensitive to histamine in subjects with allergic rhinitis than in normal control subjects and that this difference may be used as the basis of a diagnostic test.     

Nasal cytokines in common cold and allergic rhinitis

Coronavirus-induced common cold and allergen-induced rhinitis are characterized by nasal mucosal exudation of bulk blood plasma. The mucosal exudation process involves ‘flooding’ of the lamina propria with plasma-derived binding proteins and it is possible that subepithelial inflammatory cytokines and mediators may be moved by the exudate to the mucosal surface. In this study, we have analysed cytokine levels in nasal lavage (NAL) fluids from non-allergic subjects inoculated with coronavirus (n= 20) and from subjects with allergic (birch pollen) rhinitis subjected to additional allergen challenge (samples were obtained 35min post challenge) in the laboratory (n= 10). Ten of the 20 inoculated subjects developed common cold and 10 remained healthy. Interferon-γ (IFN-γ), interleukin-1β (IL-1β), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, and IL-6 were analysed in unprocessed NAL fluids using immunoassays. The subjects who developed common cold had increased NAL fluid levels of IFNγ (P < 0.05) that correlated well with the symptoms (P < 0.001). IFNγ did not increase in subjects with allergic rhinitis. IL-1β levels were similar in NAL fluids obtained from all inoculated subjects. In the subjects with allergic rhinitis NAL fluid levels of both IL-1β and GM-CSF were increased (P < 0.05). GM-CSF was not detected in common cold. IL-4 and IL-6 were not detectable in any of the NAL fluids. The present cytokines may not only emanate from superficial mucosal cells. By aiding plasma exudation subepithelial cytokines may potentially also be retrieved on the mucosal surface. Our study provides original in vivo data supporting the notion that a TH-1 profile of cytokines, notably IFNγ, is present in viral infection and further supporting the view that GM-CSF is an important cytokine in allergic airways disease.     

Validating childhood symptoms with physician-diagnosed allergic rhinitis

BackgroundMultiple population-based and high-risk cohort studies use parental questionnaire responses to define allergic rhinitis (AR) in children. Individual questionnaire items have not been validated by comparison with physician-diagnosed AR (PDAR).ObjectiveTo identify routine clinical questions that best agree with a physician diagnosis of AR and can be used for early case identification.MethodsChildren participating in a longitudinal birth cohort study were evaluated at ages 1 through 4 and at age 7 (n = 531) using questionnaires, physical examinations, and skin prick tests (SPT) with 15 aeroallergens (AG). Parents answered 3 stem questions pertaining to their child, including presence of nasal symptoms absent a cold/flu (ISAAC-validated question), presence of hayfever, and ocular itch. Substem questions were answered with details regarding seasonality, nasal triggers, and ocular seasonality. A global assessment of allergic diseases, including AR, was performed by a specialty-trained clinician. Percent agreement, sensitivity, specificity, and positive predictive values were assessed for individual stem and substem questions.ResultsPositive response to having hayfever and presence of ocular symptoms had the highest specificity (84% and 69%, respectively) and the highest percent agreement (74% and 68%) with PDAR. Identification of triggers for nasal and ocular symptoms had the highest sensitivity (89%). Positive predictive values ranged from 31 to 39%. Combining 2 responses with highest agreement increased specificity for PDAR to 91%.ConclusionResponses to hayfever and ocular symptoms had better specificity and percent agreement with PDAR than the ISAAC-validated questionnaire item. Combining 2 rhinitis questions sharply increases specificity and may improve diagnostic accuracy of clinical questions.     

Nasal nitric oxide is increased in allergic rhinitis

Background Nitric oxide (NO) plays a major role in the regulation of vascular tone and in non-specific host defence. The epithelium in the paranasal sinuses was recently identified as the major site of NO production in the upper airways. Objective To investigate NO status in allergic rhinitis, we compared the NO concentration in the nasal cavities of control subjects (n= 19) and in patients with allergic rhinitis (n= 36) with symptoms (WS, n= 17) or without symptoms (WOS, n= 19) on the day of the test. Methods NO concentration was measured using a chemiluminescent analyser aspiring from each nasal cavity at a sampling flow rate of 0.7L/min, before and 10min after administration of a nasal vasoconstrictor. Results The mean NO concentration (± se) in the control was 235 ± 11 ppb and 225 ± 9 ppb in the right and left nostrils respectively, and was decreased by 14% and 12% by the nasal vasoconstrictor (P < 0.001). The NO concentration in patients with allergic rhinitis was significantly higher in the right and left nostrils (382 × 20 ppb and 396 ± 28 respectively, P < 0.0001 versus control). All WOS patients demonstrated normal or increased NO concentrations in both nostrils, whereas two WS patients showed decreased NO concentrations in the left nostril. Inhalation of a nasal vasoconstrictor increased NO concentration by 6% and 27% in the right and left nostrils respectively in WS patients. Conclusion Nasal NO concentration is increased in patients with allergic rhinitis. Interestingly, patients without symptoms on the day of the test also showed a clear-cut increase in nasal NO production, which could reflect a permanent inflammation of the sinus mucosa.     

Nasal inflammatory mediator release in ragweed allergic rhinitis: correlation with cellular influx into nasal secretions.

Lipid-derived mediators are found in nasal secretions during the early and late phase of allergic responses. To explore this early response further, concentrations of inflammatory mediators were measured along with characterization of specific cell influx during dose-dependent ragweed challenges. Ten allergic rhinitis subjects underwent two unilateral nasal lavages using 3-fold concentrations of short ragweed antigen. Low doses of ragweed (0.016-0.114 units Amb a I) did not provoke cell influx (1 of 18 challenges), whereas moderate doses (0.432-1.3 units Amb a I) induced cell influxes in 7 of 18 and at high doses in 8 of 17 challenges (3.39-11.7 units Amb a I). The differential of the cellular influx was greater than 50% neutrophils in 7 challenges; greater than 50% eosinophils in 3, and a mixed pattern in 6. There was a significant association between the dose of antigen and the level of prostaglandin D2 (PGD2), leukotrienes (LTs) C4, D4 and E4. Challenges with an eosinophilic influx tended to be associated with higher concentrations of mediators than neutrophilic influxes. Similar to the immediate skin response, the early allergic response in the nose demonstrated a cell influx with release of PGD2, LTsC4, D4 and E4. Nasal cellular inflammation therefore can occur within minutes of allergen exposure.     

The origins of basophils and eosinophils in allergic inflammation

The bone marrow actively participates in the production of IgE-positive inflammatory cells (eosinophils, basophils, and mast cells), which are typically recruited to tissues in atopic individuals. Understanding the signaling between the tissue and the bone marrow at the molecular level may well open up new avenues of therapy for allergic inflammation. (J Allergy Clin Immunol 1998;102:S74-6.)     

Apoptosis of eosinophils and lymphocytes in allergic inflammation.

A characteristic feature of apoptosis is that the cellular contents that are biologically active are always surrounded by the cell membrane throughout the entire process. Thus the apoptotic cells are eliminated calmly and quickly without evoking inflammation. In allergic inflammation activated eosinophils and lymphocytes have been known to accumulate at the site of inflammation at least in part because of their prolonged survival. Corticosteroids are the most potent anti-inflammatory agent used for treating asthma. They inhibit the prolonged survival of eosinophils and lymphocytes directly by inducing apoptosis and indirectly by suppressing the release of cytokines supporting their survival. Theophylline, a classical bronchodilator, has been reported to have anti-inflammatory effects. Surprisingly, theophylline inhibited the prolonged survival of eosinophils in the presence of IL-5 in vitro by means of induction of apoptosis. Lymphocytes also undergo apoptosis in the presence of theophylline. One of the mechanisms for theophylline to induce apoptosis in eosinophils and lymphocytes is to elevate intracellular cyclic adenosine monophosphate because phosphodiesterase inhibitors and adenylate cyclase activators, which increase intracellular cyclic adenosine monophosphate, can cause apoptosis in those cells. Induction of apoptosis is beneficial in allergic inflammation, and the use of corticosteroids and theophylline in combination may be appropriate to induce apoptosis in eosinophils and lymphocytes.     

Nasal provocation of patients with allergic rhinitis and the hypothalamic-pituitary-adrenal axis.

BACKGROUND: Allergic rhinitis is a common problem involving activation of nasal mast cells and irritability. The hypothalamic-pituitary-adrenal (HPA) axis is stimulated in cases of emotional or environmental stress, and mast cells have been implicated in stress-induced immune responses. OBJECTIVE: To investigate whether intranasal challenge of patients allergic to a single antigen would stimulate the HPA axis. METHODS: Plasma corticotropin and cortisol levels were measured 20, 40, 60, 80, 100, and 120 minutes after intranasal antigen administration in healthy volunteers (n=3) and in patients with rhinitis who are allergic to Parietaria (n=10). RESULTS: Mean +/- SD corticotropin levels were 24.43 +/- 14.38 pg/mL in patients compared with 8.83 + 5.02 pg/mL in controls, and this increase was statistically significant (P = .049). Patient cortisol levels also increased to a mean +/- SD of 8.87 +/- 4.90 pg/mL (at 40 minutes) compared with 4.36 +/- 1.72 pg/mL in controls (P = .11 due to 1 outlier). Compared with individual patient prechallenge levels, corticotropin levels increased in 7 patients and cortisol levels increased in 5 at 40 minutes. CONCLUSION: These results suggest that allergic rhinitis may activate the HPA axis. A larger study with additional controls is required for definitive conclusions.