Low-dose local nasal immunotherapy in children with perennial allergic rhinitis due to Dermatophagoides

BACKGROUND: Allergen specific immunotherapy was known to be useful in the treatment of respiratory allergic disease. Local nasal immunotherapy (LNIT) offers advantages such as a good efficacy/safety ratio and a more convenient allergen delivery. The aim of this study was to assess the safety and clinical efficacy of a modified scheduling of LNIT in 32 children with allergic rhinitis due to Dermatophagoides. METHODS: A multicentre, randomized, double-blind placebo controlled study carried out for two years, with a modified schedule of LNIT treatment: a build-up phase at increasing dosages from 2.5 AU to 80 AU and a maintenance period at low dosage (80 AU) once a week. Symptom and medication scores. threshold dose with specific nasal provocation test (NPT) and immunological parameters (IgE and IgG4) were evaluated. RESULTS: No important local or systemic side-effects were observed in children who completed the study. Compared to placebo, the active treatment group showed significant improvement in rhinitis symptoms and a reduction of drug consumption after 18 months of LNIT. These results were confirmed by a significant reduction of allergen specific nasal reactivity. Serum and nasal specific IgE and IgG4 did not show any difference in the two groups. CONCLUSIONS: The safety and clinical efficacy of low-dose LNIT suggests that this therapy may be useful in the treatment of allergic rhinitis disease in children.     

Nasal conditioning in perennial allergic rhinitis after nasal allergen challenge

BACKGROUND: Antigen challenge in seasonal allergic rhinitis is considered to be associated with an increased ability of the nose to condition inspired air. In contrast, little is known about air conditioning after antigen challenge in perennial allergic rhinitis (PAR). OBJECTIVE: The aims of this study were to investigate whether antigen challenge in PAR changes nasal air conditioning and to assess the relationship between nasal conditioning and nasal patency and geometry. METHODS: Nineteen subjects with PAR were enrolled into this study. Measurement of nasal conditioning, active anterior rhinomanometry (AAR), acoustic rhinometry (AR), and clinical symptom evaluation were performed before and after nasal allergen challenge with allergen extracts from house dust mites. RESULTS: Ten and 20 min after nasal allergen challenge, the total water content of the air measured in the nasopharynx and the water gradient across the nose were significantly higher in the nasal cavity in which the allergen extract was sprayed. The temperature on both sides of the nose increased non-significantly after nasal allergen challenge. No correlation to data obtained by AAR, AR, and clinical symptom evaluation after nasal allergen challenge was found. CONCLUSION: We suggest that an increase in mucosal humidity due to the allergic provocation might be responsible for the increase in nasal conditioning capacity because no correlation to changes in nasal perimeter and patency was found.     

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.     

Diagnostic value of nasal provocation challenge with allergens in children

A total of 106 children suffering from perennial rhinitis and/or asthma, and all allergic to Dermatophagoides pteronyssinus (DP), underwent nasal provocation challenge (NPC) with DP to determine the best method of diagnosis. Posterior rhinomanometry was uninterpretable in 17 patients and gave negative results in 31. Clinical scores for sneezing and rhinorrhea were more effective but did not diagnose the disorder in 11 children. However, nine of the 11 had significant increases in eosinophil count in the late phase. Clinical scores and cytology were also useful for assessing whether NPC with allergens was positive in children. The feasibility and safety of NPC with DP are high for rhinitic and stable asthmatic patients, but mild reactions may occur during the late phase.     

Nasal hyperreactivity in rhinitis: A diagnostic and therapeutic challenge

Although nasal hyperreactivity (NHR) is a common feature in patients suffering from allergic and nonallergic rhinitis, it is widely neglected during history taking, underdiagnosed in the majority of patients with rhinitis and rhinosinusitis, not considered as an outcome parameter in clinical trials on novel treatments for rhinitis and rhinosinusitis, and no target for routine treatment. In contrast to the simple nature of diagnosing NHR by a history of nasal symptoms induced by nonspecific exogenous and/or endogenous triggers, quantification is hardly performed in routine clinic given the lack of a simple tool for its diagnosis. So far, limited efforts have been invested into gaining better insight in the underlying pathophysiology of NHR, helping us to explain why some patients with inflammation develop NHR and others not. Of note, environmental and microbial factors have been reported to influence NHR, contributing to the complex nature of understanding the development of NHR. As a consequence of the neglect of NHR as a key clinical feature of rhinitis and chronic rhinosinusitis (CRS), patients with NHR might be suboptimally controlled and/or dissatisfied with current treatment. We here aim to provide a comprehensive overview of current knowledge on the pathophysiology, and the available tools to diagnose and treat NHR.     

Symptoms of Chronic and Allergic Rhinitis and Occurrence of Nasal Secretion Granulocytes in University Students, School Children and Infants

The prevalence of chronic and allergic rhinitis was studied in an unselected population sample consisting of 315 university students and 319 school children. History was taken by questionnaire, nasal appearance was examined by rhinoscopy, and a nasal smear was studied in all subjects. For comparison, nasal smears were also collected from 60 normal infants. Allergic rhinitis complaints were reported by 28% of the students and by 13% of the school children, with no significant difference in sex distribution. The cytological examination revealed secretion eosinophilia in 20% of the students, 28% of the school children, and 22% of the infants. Secretion eosinophilia correlated significantly with allergic rhinitis history, and with nasal mucosal swelling and nasal secretion seen on rhinoscopy. Nasal secretion neutrophilia, which occurred in 47% of the students, 79% of the school children and 97% of the infants, seemed to have an adverse effect on the reliability of secretion eosinophilia as an indicator of active nasal allergy. Possible reasons for the rising prevalence rates of allergic rhinitis are discussed.     

Intranasal capsaicin reduces nasal hyperreactivity in idiopathic rhinitis: a double-blind randomized application regimen study

BACKGROUND: In a recent study, we showed that intranasal capsaicin spray gives a significant and long-term reduction of symptoms in nonallergic noninfectious perennial rhinitis patients. However, in daily practice, the studied application regimen proved to be impractical because of the large number of visits required in a short period of time. In the present study, we conducted a double-blind double-dummy parallel groups trial to determine whether a more practical capsaicin application schedule is equally effective. METHODS: Thirty patients were randomized into two different treatment regimens: one group received capsaicin five times on the first day at 1-h intervals. This was followed by a placebo dummy once every second or third day for a total of five treatments 2 weeks after the capsaicin application (group A). The other group (B) received the placebo dummy five times on the first day followed by capsaicin once every second or third day for a total of five treatments 2 weeks after the placebo application. RESULTS: The visual analogue scale scores for overall nasal symptoms, rhinorrhea and nasal blockage showed significant decrease after the start of treatment in both groups, with a significantly steeper decrease in group A. A significant reduction in cold dry air dose responsiveness was also found up to 9 months after therapy in both groups, reflecting a decrease in nasal hyperreactivity. No significant changes in safety data (smell, blood pressure, heart rate) were found. CONCLUSIONS: We conclude that intranasal capsaicin seems safe to use and that five treatments of capsaicin on a single day is at least as effective as five treatments of capsaicin in 2 weeks.     

Nasal endoscopy in asthmatic children: assessment of rhinosinusitis and adenoiditis incidence, correlations with cytology and microbiology

BACKGROUND: Upper respiratory airway diseases may induce a worsening of asthma. Sinusitis represents one of the most common chronic diseases. The association of asthma and sinusitis varies greatly in different studies, depending on diagnostic procedures. OBJECTIVE: The aims were: (i) to demonstrate that nasal endoscopy may be easily feasible in asthma at paediatric age; (ii) to evaluate the incidence of rhinosinusitis and adenoiditis in children with asthma by nasal endoscopy; (iii) to correlate inflammatory parameters such as cytology and microbiological cultures with nasal endoscopy findings. SUBJECTS AND METHODS: One hundred and forty-five asthmatic children were evaluated, 48 males and 97 females, with an average age of 7.27 years. Evaluated parameters were the incidence of rhinosinusal infections in asthmatic children, and the role of: (i) nasal endoscopy, (ii) nasal cytology, and (iii) nasal microbiology in their diagnoses. RESULTS: Nasal endoscopy was successfully performed on 128 patients. Twenty-six children had endoscopic rhinosinusitis alone, 10 had adenoiditis alone, and 35 showed endoscopic rhinosinusitis associated with adenoiditis. There were significant correlations between endoscopic rhinosinusitis and adenoiditis (P < 0.001), between clinical and endoscopic rhinosinusitis (P < 0.001), between endoscopic rhinosinusitis and adenoiditis and microbiology (P < 0.05 and P < 0.0001, respectively), and between microbiology and cytology (P < 0.05). CONCLUSION: This study shows that rhinosinusal infections are common in asthmatic children. Moreover, nasal endoscopy might represent a fruitful tool in the management of asthmatic children.     

Nasal cytology in allergic processes and other syndromes caused by hyperreactivity

The spontaneous nasal secretions from about 128 patients with the symptomatic triad of rhinorrhea, sneezing, and nasal obstruction were studied. The cytological examination consisted of a morphological evaluation and a semiquantitative evaluation. Noncellular and nonliving presences in the smears have been considered, including mucus, Charcot-Layden crystals, and pollen grains, as well as fungi and bacilli. We found a net increase in eosinophils, goblet cells, and cellular debris in secretions of atopic patients. Pollen grains and vegetative fragments were present in the nasal smears of pollinosis. The presence of fungi was observed in five cases of allergic rhinopathy. The exfoliative cytology represents a valuable means for the differential diagnosis of rhinitis. In particular, the presence of noncellular elements has value regarding rhinocytology.     

Comparison of five new antihistamines (H1-receptor antagonists) in patients with allergic rhinitis using nasal provocation studies and skin tests

BACKGROUND: It was the aim of the authors to compare all of the latest second-generation antihistamines and to see if there were significant differences in their efficacy. It is important for ENT specialists to know if these differences exist, as it is for general practitioners trying to choose between these drugs. METHODS: In 12 confirmed grass pollen allergic patients the authors performed nasal smears to asses eosinophilia, histamine/grass pollen skin tests, and grass pollen nasal provocation tests. All tests were performed before and after administration of one of five different antihistamines (cetirizine, loratadine, ebastine, fexofenadine, mizolastine) or placebo. The order of administration of antihistamines and placebo was randomised, and patients were not aware of which drug they were given. A decrease in nasal eosinophilia (nasal smear), or nasal or skin reactivity (provocation tests) was looked for. RESULTS: A significant decrease in nasal eosinophilia was observed for all antihistamines but not for placebo. For the grass pollen nasal provocation tests, the decrease was significant for nasal blockage and sneezing; for rhinorrhea there was an insignificant decrease that was true for all antihistamines. A significant reduction in histamine/grass pollen skin test reactivity was also observed for all antihistamines, during an 8 h observation period. A significant difference in efficacy between the different antihistamines could not be found with any of the tests performed. CONCLUSIONS: For the newer nonsedating H1-antagonists there appears to be no clinically relevant differences in activities--at least not in our study. Preference of the patient may be the most important factor in making a choice between these drugs.     

Immediate and dual response to nasal challenge with Dermatophagoides pteronyssinus in local allergic rhinitis

Background Local allergic rhinitis (LAR) is characterized by in situ production of specific IgE (sIgE) antibodies and a positive response to a nasal allergen provocation test (NAPT) in the absence of atopy. Objective The aim of this study was to investigate the immunological mechanisms involved in the immediate and late responses after nasal exposure to Dermatophagoides pteronyssinus (DP) in patients with LAR. Methods A total of 40 subjects with LAR to DP were studied and compared with 50 healthy controls. Immediate and late responses to NAPT‐DP were assessed using a visual analogue scale of nasal symptoms and acoustic rhinometry. Tryptase, ECP, total and sIgE‐DP were measured in the nasal lavage by immunoassay at baseline, 15 min, 1, 6 and 24 h after nasal challenge. Results NAPT‐DP was positive in all patients, with significant increases in tryptase (45%), ECP (65%) and sIgE‐DP (25%) (P<0.05). Sixty percent of the LAR patients presented an immediate response to NAPT‐DP and 40% a dual response. Immediate responders showed a fast release of tryptase with a peak at 15 min after NAPT‐DP, and a progressive increase in nasal ECP and sIgE‐DP from 1 to 24 h after challenge, with a peak at 24 h. Dual responders presented persistently higher levels of tryptase from 15 min to 6 h after challenge, and a similar pattern of nasal release of ECP and sIgE‐DP to immediate responders. There were no isolated late responders. NAPT‐DP was negative in all healthy controls, with no increases in tryptase, ECP, or total and sIgE‐DP in nasal secretions. Conclusions The results demonstrated the existence of immediate and dual responses to a NAPT with DP in LAR patients, with the local presence of sIgE and mast cell/eosinophil activation. Cite this as: S. López, C. Rondón, M. J. Torres, P. Campo, G. Canto, R. Fernandez, R. Garcia, A. Martínez‐Cañavate and M. Blanca, Clinical & Experimental Allergy, 2010 (40) 1007–1014.     

Local allergic rhinitis: concept, pathophysiology, and management

Local allergic rhinitis (LAR) is a localized nasal allergic response in the absence of systemic atopy characterized by local production of specific IgE (sIgE) antibodies, a T(H)2 pattern of mucosal cell infiltration during natural exposure to aeroallergens, and a positive nasal allergen provocation test response with release of inflammatory mediators (tryptase and eosinophil cationic protein). Although the prevalence remains to be established, a number of patients previously given a diagnosis of nonallergic rhinitis or idiopathic rhinitis are now being classified as having LAR. Culprit allergens responsible include house dust mite, grass and olive pollens, and many others. For the diagnosis of LAR, neither skin prick testing nor determination of the presence of serum sIgE antibodies is useful, and a nasal allergen provocation test is needed to identify the culprit allergen or allergens. In a certain proportion of cases, local sIgE can be detected, and conjunctivitis, asthma, or both can be associated. Whether patients with LAR will have systemic atopy in the future is a matter of debate. Further studies are needed for examine the prevalence of this phenomenon in different areas, to improve the diagnostic methods to better identify these patients, and to develop therapeutic approaches, including the use of immunotherapy.