Perennial Rhinitis Research Articles

Nasal responsiveness to allergen and histamine in patients with perennial rhinitis with and without a late phase response.

BACKGROUND: In the lower airways an association has been found between early phase reaction (EPR), late phase reaction (LPR), and bronchial hyperreactivity. However, this association has not been shown for...

A randomized double-blind placebo controlled study of azelastine nasal spray in children with perennial rhinitis

One hundred and twenty five children (median age 8.71 years) suffering from perennial allergic rhinitis were treated in a randomized, double-blind, parallel group study comparing azelastine nasal spray 0.14 mg/nostril twice daily (0.56 mg/day) and placebo nasal spray. Medication was given for a period of 6 weeks which followed a 2 week placebo washout period in all patients. Subjects were aged between 5 and 12 and were skin prick positive to either house dust mites and/or cat or dog dander. Concomitant anti allergic treatment was not permitted during the study. Severity of rhinitis symptoms was scored daily by the child or his/her parents on a diary card using a visual analogue scale (VAS) for each evaluated symptom: 0, absent-100, could not be worse. Mean weekly scores were calculated. Symptoms evaluated were: sneezing, nasal blockage, nasal itch and rhinorrhea. In addition, at each clinic visit the investigator evaluated symptoms using a verbal score of 0, no symptom-3, severe. Compared to the baseline, for each of the six study weeks, the reduction in the VAS scores for all four symptoms was statistically greater for the azelastine group compared to the placebo group. The investigator's assessment at clinic visits bore out these results. Both azelastine nasal spray and placebo were well tolerated, no serious adverse events were reported. During the treatment phase of the study a total of 36 adverse events were reported by 25 patients (azelastine 10, placebo 15). The most frequently occurring events were pharyngitis (azelastine 5, placebo 3), cough (azelastine 3, placebo 1) and bronchitis (azelastine 1, placebo 3). In conclusion, azelastine has been shown to be effective in the treatment of perennial rhinitis in children aged 5–12 years and to be superior to placebo in the relief of all symptoms assessed, namely sneezing, nasal blockage, nasal itch and rhinorrhea.

Once-daily mometasone furoate nasal spray: efficacy and safety of a new intranasal Glucocorticoid for Allergic Rhinitis

Once-daily mometasone furoate nasal spray (MFNS) is a new intranasal glucocorticoid for the treatment of seasonal allergic rhinitis and perennial rhinitis, and for the prophylaxis of seasonal allergic rhinitis. This paper reviews key findings from the clinical development program for MFNS, comprising more than 20 clinical trials with more than 6000 patients worldwide. MFNS exhibits strong anti-inflammatory activity in vitro and in vivo, and has a rapid onset of action, affording clinically significant symptom relief in 28% of patients within 12 hours of the first dose. Once-daily MFNS is at least as effective as other intranasal glucocorticoids, including twice-daily beclomethasone dipropionate and once-daily fluticasone propionate and budesonide. MFNS is well tolerated and has no detectable effect on the hypothalamic-pituitary-adrenal axis, even at up to 20 times the recommended daily dose. MFNS does not cause atrophy of the nasal mucosa; in fact, prolonged treatment tends to restore the nasal mucosa to a more normal phenotype. The once-daily dosing schedule of MFNS may improve patient compliance, while its high margin of systemic safety and rapid onset of action may enhance patient and physician acceptance

Allergic rhinitis and asthma: How important is the link?

Dysfunction of the upper and lower airways frequently coexist, and they appear to share key elements of pathogenesis. Data from epidemiologic studies indicate that nasal symptoms are experienced by as many as 78% of patients with asthma and that asthma is experienced by as many as 38% of patients with allergic rhinitis. Studies also have identified a temporal relation between the onset of rhinitis and asthma, with rhinitis frequently preceding the development of asthma. Patients with allergic rhinitis and no clinical evidence of asthma commonly exhibit nonspecific bronchial hyperresponsiveness. The observation that management of allergic rhinitis also relieves symptoms of asthma has heightened interest in the link between these diseases. Intranasal corticosteroids can prevent increases in nonspecific bronchial reactivity and asthma symptoms associated with seasonal pollen exposure. Similarly, among patients with perennial rhinitis, daily asthma symptoms, exercise-induced bronchospasm, and bronchial responsiveness to methacholine are reduced after administration of intranasal corticosteroids. Antihistamines, with or without decongestants, reduce seasonal rhinitis symptoms, asthma symptoms, and objective measurements of pulmonary function among patients with rhinitis and asthma. The mechanisms that connect upper and lower airway dysfunction are under investigation. They include a nasal-bronchial reflex, mouth breathing caused by nasal obstruction, and pulmonary aspiration of nasal contents. Nasal allergen challenge results in increases in lower airway reactivity within 30 minutes, suggesting a neural reflex. Improvements in asthma associated with increased nasal breathing may be the result of superior humidification, warming of inspired air, and decreased inhalation of airborne allergens. Postnasal drainage of inflammatory cells during sleep also may affect lower airway responsiveness. A link between allergic rhinitis and asthma is evident from epidemiologic, pathophysiologic, and clinical studies. Future research, however, is needed to determine whether nasal therapy can alter the natural history of asthma. (J Allergy Clin Immunol 1997; 99:S781-6.)

Nasal Pathophysiology Impacts Bronchial Reactivity in Asthmatic Patients with Allergic Rhinitis

Galen was the first to notice a relationship between nasal pathology and asthma (1). Numerous studies have been done throughout the years which point to this rela tionship, but it is not routine for physicians to treat nasal inflammation with maintenance medications in patients with asthma. A recent article (2) in the New England Journal of Medicine reviewing the pathophysiology of asthma failed to mention the contributory role of inflammation in the nose and sinuses to hyperreactivity of the bronchi. Another review (3) of the relationship between asthma and sinusitis in the pediatric literature failed to mention the possibility that allergic rhinitis also might contribute to lung hyperreactivity. This review is undertaken to alert primary care physicians to the significance with which both allergic and perennial rhinitis and sinusitis contribute to the success or failure of a management program for certain patients with asthma.

3. Nasal mast cells in perennial allergic rhinitics exhibit increased expression of the FcεRI, CD40L, IL-4, and IL-13, and can induce IgE synthesis in B cells.

3. Nasal mast cells in perennial allergic rhinitics exhibit increased expression of the FcεRI, CD40L, IL-4, and IL-13, and can induce IgE synthesis in B cells.

107 Nasal mast cells from perennial allergic rhinitics can induce IgE synthesis in B cells.

107 Nasal mast cells from perennial allergic rhinitics can induce IgE synthesis in B cells.

Relationship between nasal hyperreactivity, mediators and eosinophils in patients with perennial allergic rhinitis and controls

In perennial allergic rhinitis, patients are almost daily exposed to aeroallergens. This ongoing allergic reaction results in increased sensitivity to allergens and non-specific stimuli. It is generally known that inflammatory cells and mediators are involved in the pathogenesis of the allergic reaction. To study the relationship between nasal hyperreactivity and nasal inflammation during natural allergen exposure. In 48 patients with perennial allergic rhinitis and in 11 volunteers a nasal brush, a nasal lavage and a histamine challenge were performed. Nasal inflammation was estimated by the number of eosinophils, levels of albumin, tryptase, prostaglandin D2 (PGD2), eosinophil cationic protein (ECP) and leukotriene C4/D4/E4 (LTC4/D4/E4). In contrast to PGD2 and tryptase, eosinophils (1.9 vs 0%, P = 0.0023), LTC4/ D4/E4 (17.51 vs 1.43 pg/mL, P < 0.0001) and albumin (8.61 vs 2.37 mg/mL, P = 0.0008) were significantly increased in rhinitis patients as compared with controls. Patients also showed increased responses to nasal histamine challenge assessed using a composite symptom score (21.5 vs 4 points, P < 0.0001). The nasal response to histamine was weakly correlated with the total number of eosinophils in the cytospin (correlation coefficient r = 0.38, P = 0.009). Nasal hyperreactivity is correlated with the percentage of eosinophils in patients with perennial rhinitis. The patients' mediator profiles suggest that eosinophils are important in the ongoing allergic reaction and nasal hyperreactivity.

Allergy to cockroaches in patients with asthma and rhinitis in an urban area (Madrid).

Previous studies have established that cockroach allergens are important sensitizing agents in the induction of rhinitis and asthma principally in urban areas. This study was undertaken to assess skin test reactivity and specific IgE antibody reactivity to extracts of Periplaneta americana (P.a.), Blattella germanica (B.g.), B. orientalis (B.o.), and a fecal extract of B. germanica (FEB.g.) in a group of patients with rhinitis and asthma living in an urban area in Europe. We examined clinical characteristics and aerollergen sensitivities of 171 consecutive Madrid urban patients with rhinitis and asthma who met the criteria for the study. A comprehensive clinical evaluation was followed by skin prick test with common allergens and saline extracts of P.a., B.g., B.o., and FEB.g. and measurement of serum specific IgE antibody to cockroach extracts. The age of patients ranged from 7 to 68 years (mean 20.4 +/- 16). A total of 153 (90.5%) subjects were atopic and 19 (10%) were considered nonallergic. Pollen sensitivity (66.5%) was most prevalent, distantly followed by sensitivity to cockroach (25.7%), mite (20%), cat (15.5%), Alternaria alternata (14.5%), dog (14%), and food (2%). Skin test reactivity to cockroach extracts was 37 (21.6%) to B.o., 20 (11.6%) to P.a., 19 (11.1%) to B.g. and five (2.9%) to FEB.g. Twenty-one of these patients had rhinitis, 19 rhinitis and asthma, and one only asthma; 26 had perennial symptoms, while 16 had seasonal (spring) symptoms; three (1.7%) patients had only positive prick test to cockroach; all had perennial rhinitis and/or asthma. Eighteen (10.5%) patients had specific serum IgE (RAST 1 or 2) to B.o., 13 (7.6%) to P.a., and six (3.5%) to B.g. Eighty (46.7%) patients had visual evidence of cockroach infestation in their home, mostly B.o.; 31 had positive prick test to cockroach (P < 0.0003). The results indicate that sensitivity to outdoor allergens (pollen) is more prevalent than to indoor allergens. Cockroach sensitization is the most important indoor allergen in our area, and B.o. accounts for most cockroach sensitization.

Learning impairment and allergic rhinitis.

Allergic rhinitis is underestimated as a cause of suffering and diminished quality of life in children and adolescents. If nasal symptoms such as itching, sneezing, rhinorrhea, and congestion are not well controlled during the day, they may contribute to learning problems during school hours. If these symptoms are not well controlled during the night, they may contribute to nocturnal sleep loss, secondary daytime fatigue and learning impairment. Even uncomplicated seasonal allergic rhinitis may be associated with reduced ability to learn, and the likelihood of learning problems may increase in severe perennial rhinitis or in rhinitis associated with complications such as sinusitis or eustachian tube dysfunction and conductive hearing loss. Also, many of the medications used to treat allergic rhinitis may cause central nervous system adverse effects and contribute to learning impairment. For some medications, such as inhaled glucocorticoids and decongestants, the potential effect on central nervous system function and learning has not been tested. For others such as H1-receptor antagonists (antihistamines), well-designed, prospective studies have been performed. The newer relatively nonsedating medications such as terfenadine, astemizole, loratadine, cetirizine, and fexofenadine have less potential to impair central nervous system function and learning than their predecessors.

A comparison of morphological effects on the rabbit nasal and sinus mucosa after surgical denervation and topical capsaicin application.

In order to study morphological effects on the nasal and sinus mucosa, New Zealand White rabbits underwent either unselective, regional sectioning of sensory and parasympathetic nerve branches or topical treatment of the mucosa with capsaicin. Ten days after treatment, mucosal specimens were analyzed by light and electron microscopy. Immunohistochemistry was used to evaluate neuropeptides present, in particular substance P, calcitonin gene-related peptide, vasoactive intestinal peptide and neuropeptide Y. In surgically denervated rabbits, mucosal glands were found to be enlarged and contained an increased number of zymogen granules having a bipartite substructure. Topical capsaicin application caused localized epithelial changes in the sinus mucosa and maxilloturbinal region of the nose, including clotting of cilia and an increased number of goblet cells. Reduced amounts of all neuropeptides investigated were found in the surgically denervated animals, while topical capsaicin treatment had only marginal effects on the mucosal neuropeptide content. The morphological changes observed after surgical denervation suggest an imbalance between neural stimulation and secretory capacity of the mucosal glands. These findings could explain the difference in clinical effect noted between sectioning of the vidian nerve and topical treatment with capsaicin in patients with perennial rhinitis.

Motivation for participation in clinical trials of drugs for the treatment of asthma, seasonal allergic rhinitis, and perennial nonallergic rhinitis

While previous studies of enrollment motivation have been conducted with either healthy subjects or subjects with certain other diseases, little is known about the motives of subjects with asthma or rhinitis symptoms who seek to enter clinical trials. This study was conducted to assess the self-reported role that altruism, healthcare receipt, and financial gain play in the motivation of subjects with symptoms of bronchial asthma, seasonal allergic rhinitis, and perennial nonallergic rhinitis who attempted to enroll in clinical trials. Subjects with symptoms of asthma, allergic rhinitis, and perennial nonallergic rhinitis who sought to enroll in phase III clinical trials completed surveys from December 1991 to August 1992 (n = 295). The importance of altruistic and nonaltruistic motives was rated on numerical scales. Improved control of symptoms and learning more about the illness and medications for treatment were the most important nonaltruistic motives (P less than .05). Financial motives and second opinion were moderately important but less important than healthcare motives (P less than .05). This population as a whole agreed that the altruistic motives listed in the survey were reasons to enroll. Subjects with symptoms of asthma, allergic rhinitis, and perennial nonallergic rhinitis entered clinical trials for altruistic reasons and to receive healthcare treatment for their chronic illness including related health education. For the entire group, self-reported financial motives were less important than illness-related healthcare.

The treatment of hyposmia with intranasal steroids

Hyposmia is a neglected symptom in patients with rhinitis. We studied 25 patients presenting with perennial rhinitis. Fifteen patients expressed hyposmia as a significant symptom. University of Pennsylvania smell identification test (UPSIT) and visual analogue scales (VAS) were used to score the symptoms of hyposmia, nasal obstruction and nasal discharge before and after six weeks treatment with betamethasone sodium phosphate drops. Those patients with initial symptoms of hyposmia significantly improved their UPSIT scores (p = 0.00009) and their VAS scores for hyposmia (p = 0.00133). Despite a significant decrease in the sensation of nasal obstruction, the non-hyposmics showed no increase in UPSIT scores after betamethasone therapy. There was no clear correlation between UPSIT results and other symptom scores. The judicious use of betamethasone drops in the treatment of rhinogenic hyposmia can be recommended.

Topical Corticosteroid Therapy of Rhinitis

The introduction of nasal corticosteroids 20 years ago has been the most important therapeutic progress in rhinitis management since the introduction of the first generation of antihistamines. Our knowledge of the mode of action of corticosteroids is still incomplete, although a series of intranasal studies has now clarified this problem as the airway mucous membrane of the nose is easily accessible for investigation. Nasal corticosteroids are a highly effective therapeutic modality that can be used for long term therapy of allergic rhinitis, perennial nonallergic rhinitis and nasal polyposis. Experience for 20 years has shown that the adverse effects from this type of treatment are negligible, and far less serious than those occurring in the skin following long term use of corticosteroid ointment. Intranasal corticosteroids can therefore be considered as first-line treatment for allergic and nonallergic rhinitis. The major disadvantage of this type of treatment is the slow onset of action and the lack of effect on itchy eyes. For that reason, the second generation antihistamines are the drugs of choice in patients having occasional symptoms. However, in our opinion, intranasal corticosteroids are preferable in patients who have symptoms on a regular basis, either in the pollen season or all year.

アレルギー性鼻炎とその類似疾患の下気道過敏性

Perennial rhinitis was classified as allergic rhinitis, probable allergic rhinitis, vasomotor rhinitis or eosinophilic nonallergic rhinitis. Then these various types were classified according to whether there was any difference with respect to lower respiratory tract hypersensitivity for methacholine.The various types of perennial rhinitis were identified through eosinophilic cell number in nasal smears, allergen skin testing, and IgE RIST and IgE RAST determination. In addition, we carried out a methacholine nasal provocation test using an Astograph and an allergen nasal provocative test.Lower respiratory tract hypersensitivity was determined based on respiratory resistance, spirometry and a flow-volume curve before and after methacholine inhalation through the nose.The lower respiratory tract of the subjects with perennial rhinitis showed differences in terms of methacholine hypersensitivity. Allergic rhinitis showed methacholine hypersensitivity in the entire lower respiratory tract. Probable allergic rhinitis showed hypersensitivity in the large airway. Vasomotor rhinitis showed hypersensitivity in the relative large airway. Eosinophilic nonallergic rhinitis did not show hypersensitivity in the lower respiratory tract.

Mast cell TNF mRNA expression in nasal mucosa demonstrated by in situ hybridization: a comparison of mast cell detection methods

We have used 35S-labelled RNA probes to detect TNF cytokine gene expression in nasal mucosa derived from patients with perennial rhinitis. As mast cells comprise a minor component of the total cell population in nasal mucosa, additional methods are needed to determine whether mast cells contribute to the cytokine mRNA detected by in situ hybridization. We have combined in situ hybridization with alternate methods to detect mast cells (tryptase immunostaining or toluidine blue staining) and determined that in situ hybridization coupled with tryptase immunostaining provides optimal methods to detect mast cell cytokine gene expression in tissue sections. Using in situ hybridization and tryptase immunostaining, we demonstrate that mast cells in nasal mucosa can express TNF mRNA. However, the number of tryptase −, TNF + cells (1.99 ± 1.59 cells/mm 2) exceeded the number of tryptase +, TNF + mast cells (0.09 ± 0.21 cells/mm 2). Mast cells thus comprised a subpopulation of the total number of TNF mRNA positive cells in nasal mucosa.

Concentrations of myeloperoxidase in nasal secretions of atopic patients after nasal allergen challenge and during natural allergen exposure.

A quantitative determination of myeloperoxidase (MPO) concentration was performed in the nasal secretions of atopic patients (challenged group, n = 17) after nasal allergen challenge outside the pollen season, and of patients with ongoing seasonal (seasonal group, n = 40) and with perennial (perennial group, n = 30) allergic rhinitis. The concentrations of MPO obtained from 10 nonallergic healthy volunteers (control group) were used as a normal control. Results showed that there was no statistical difference between the normal controls (median: 2.0 micrograms/g) and the atopic patients (median: 1.7 micrograms/g) outside the pollen season. After nasal allergen challenge (challenged group), there was no significant difference of MPO at 5 min (median: 1.0 microgram/G), 8 h (median: 1.7 micrograms/g), and 24 h (median: 3.1 micrograms/g) after challenge as compared to the baseline values. Also, there was no significant difference between patients with ongoing seasonal (median: 1.3 micrograms/g) or perennial (median: 1.8 micrograms/g) rhinitis, and atopic patients outside the pollen season. In conclusion, this study showed that MPO is not locally elaborated in measurable quantities in nasal secretions after nasal allergen challenge and during natural allergen exposure. Further studies will be needed to elucidate the role of neutrophils in the pathophysiological processes of allergic rhinitis.

3. Cytokine profile in the nasal mucosa of perennial allergic rhinitics and chronic infectiverhinities, especially with respect to mast cells.

3. Cytokine profile in the nasal mucosa of perennial allergic rhinitics and chronic infectiverhinities, especially with respect to mast cells.

472 Nasal γδ- T cells in perennial allergic rhinitics express the CD40L and induce IgE synthesis

472 Nasal γδ- T cells in perennial allergic rhinitics express the CD40L and induce IgE synthesis

Cutaneous‐mucosal allergic contact reaction due to topical corticosteroids

We report the case of a 41-year-old nonatopic women with a previous history of eczematous reaction due to hydrocortisone who suffered worsening of her perennial rhinitis in association with perinasal dermatitis from the use of budesonide in nasal spray form, and stomatitis and pharyngitis due to budesonide in a bronchial inhaler. Patch tests with a series of 25 corticosteroids, some of them at different concentrations and in different vehicles, were positive to tixocortol pivalate, hydrocortisone, budesonide, prednisolone, hydrocortisone butyrate propionate, triamcinolone acetonide, and fluocinolone acetonide. For some of them, a 1% solution in ethanol gave a positive reaction when a 20% mixture in petrolatum did not. Like other authors, we suggest that some multiple positives may represent sensitization to several steroids independently, true cross-reactions, or both, and that ethanol is a better vehicle than petrolatum.