Non-atopic Rhinitis Research Articles

Local allergic rhinitis - a big challenge in clinical practice

Local allergic rhinitis is a new rhinitis phenotype characterized by symptoms similar to allergic rhinitis, in non-atopic patients with a positive nasal allergen provocation test (NAPT). The disease is diagnosed in over 25% of non-atopic patients with rhinitis, marked as non-atopic rhinitis. It most often has perennial and severe symptoms and a progressive course. It is often associated with conjunctivitis and/or asthma. It is necessary to consider local allergic rhinitis in patients with non-atopic rhinitis. The gold standard for diagnosis is a positive NAPT. Pharmacological therapy fails to stop the natural progression and development of comorbidities. Allergen immunotherapy reduces the symptoms, consumption of medicines and increases the tolerance to allergens responsible for local allergic rhinitis. New studies are needed to confirm the curative effects and evaluate the preventive effects of allergen immunotherapy.

Non-Atopic Rhinitis at Age 6 Is Associated With Subsequent Development of Asthma

The role of nonatopic rhinitis, aka nonallergic rhinitis (NAR), in relation to the development of asthma has not been extensively studied. The purpose of this study was to assess the role of NAR in the long-term development of asthma among participants in the Tucson Children’s Respiratory Study (TCRS).The TCRS is a nonselected birth cohort enrolled from 1980 to 1984. Participants were evaluated regularly through the age of 32 years.At the visit at age 6 years, rhinitis was determined by an affirmative response to a question about runny, stuffy, and itchy nose, apart from colds. “Active” rhinitis, asthma, or wheeze was defined as symptoms reported within the previous year at the 6-year visit. Skin prick testing to a range of local aeroallergens was performed at the 6-year visit. Atopy was defined as having a positive skin test result. Researchers in this study assessed the frequency of affirmative answers to questions about asthma at age 32 years among TCRS subjects, who did not have active wheeze or asthma at age 6 years.Overall, 521 subjects were analyzed. At age 6 years, 38% had active rhinitis, and 33% were atopic. Among nonatopic children, those with active rhinitis were significantly more likely to develop asthma through age 32 years than those without rhinitis (P = .005). Among those with atopy at age 6 years, those with and without active rhinitis also had increased risk of asthma development, compared with the nonatopic population (active rhinitis, P < .001 and nonactive rhinitis, P = .035). Sex, ethnicity, and maternal asthma did not influence these findings.This is the first study to show that NAR can increase the risk of developing asthma. Rhinitis (atopic or nonatopic) and atopy (with or without rhinitis) are both associated with the development of subsequent asthma.Strengths of this study include the use of a large cohort population with longitudinal data. Weaknesses involve the challenges in capturing and analyzing environmental factors (eg, smoke and particulate exposures) that may also contribute to the risk of asthma. Future studies should assess whether treating NAR helps with asthma control or prevents the development of asthma altogether.

How to Diagnose and Treat Local Allergic Rhinitis: A Challenge for Clinicians.

Chronic rhinitis is a very common disease that can be divided in various phenotypes. Historically, the condition has been classified into the allergic rhinitis (AR) and non-allergic non-infectious rhinitis (NAR) forms, based on the results of the classical biomarkers of atopy: skin prick test and serum allergen-specific IgE However, this classification does not reflect the complexity of the rhinitis syndrome, as illustrated by the existence of non-atopic rhinitis patients who display a nasal reactivity to environmental allergens. This new phenotype has been termed local allergic rhinitis (LAR) and can be only recognized if an additional test such as the nasal allergen challenge (NAC) is integrated in the diagnostic algorithm for chronic rhinitis. Recent data shows that the NAC is a very safe and reliable technique ready for the clinical practice. LAR is a differentiated rhinitis phenotype which often commences during childhood and quickly progresses towards a clinical worsening and the association of comorbidities in other mucosal organs. Recent evidence supports the existence of a bronchial counterpart of LAR (local allergic asthma), which highlights the pathophysiological links between the upper and lower airways and reinforces the united airways concept. Importantly, several controlled studies have demonstrated the ability of allergen immunotherapy to control LAR symptoms while the therapy is being administered. This review emphasizes the need to implement the NAC in the clinical practice in order to facilitate the recognition of LAR patients, allowing for an early prescription of specific therapies with disease-modifying potential.

Is the evidence of local allergic rhinitis growing?

To examine the recent advances on epidemiological studies, diagnostic approach and clinical management of local allergic rhinitis (LAR) in adults and children. Evidence about LAR is growing especially in pediatric and Asian populations. The prevalence of LAR is lower in Asian countries compared with western countries in both children and adults. LAR is considered a chronic condition and an independent rhinitis phenotype that affects up to 26.5% of nonatopic rhinitis patients. The disease rapidly progress toward the clinical worsening with associated onset of asthma and conjunctivitis, which further impairs patient's quality of life. Nasal Allergen Provocation Test is the diagnostic gold standard that can be complemented by basophil activation test and the detection of specific IgE in nasal secretions. Allergen immunotherapy induces a significant and early improvement in both clinical symptoms and quality of life in LAR patients. LAR is a common entity, with different prevalence depending on geographical locations. LAR has to be considered in the process of differential diagnosis in children and adults with rhinitis. Diagnosis of LAR is crucial in order to start an etiologic treatment such as allergen immunotherapy, which has proven to be very effective in these patients.

Allergic Rhinitis in Preschool Children and the Clinical Utility of FeNO.

PurposeThe nature of allergic rhinitis (AR) in preschool aged children remains incompletely characterized. This study aimed to investigate the prevalence of AR and its associated risk factors in preschool-aged children and to assess the clinical utility of fractional exhaled nitric oxide (FeNO).MethodsThis general population-based, cross-sectional survey included 933 preschool-aged (3- to 7-year-old) children from Korea. Current AR was defined as having nasal symptoms within the last 12 months and physician-diagnosed AR.ResultsThe prevalence of current AR in preschool children was 17.0% (156/919). Mold exposure (adjusted odds ratio [aOR], 1.67; 95% confidence interval [CI], 1.15-2.43) and the use of antibiotics (aOR, 1.97; 95% CI, 1.33-2.90) during infancy were associated with an increased risk of current AR, whereas having an older sibling (aOR, 0.52; 95% CI, 0.35-0.75) reduced the risk. Children with current atopic AR had significantly higher geometric mean levels of FeNO compared to those with non-atopic rhinitis (12.43; range of 1standard deviation [SD], 7.31-21.14 vs 8.25; range of 1SD, 5.62-12.10, P=0.001) or non-atopic healthy children (8.58; range of 1SD, 5.51-13.38, P<0.001). The FeNO levels were higher in children with current atopic AR compared with atopic healthy children (9.78; range of 1SD, 5.97-16.02, P=0.083).ConclusionsMold exposure and use of antibiotics during infancy increases the risk of current AR, whereas having an older sibling reduces it. Children with current atopic AR exhibit higher levels of FeNO compared with non-atopic rhinitis cases, suggesting that FeNO levels may be a useful discriminatory marker for subtypes of AR in preschool children.

A Case of Codeine Induced Anaphylaxis via Oral Route

Codeine is widely prescribed in clinical settings for the relief of pain and non-productive coughs. Common adverse drug reactions to codeine include constipation, euphoria, nausea, and drowsiness. However, there have been few reports of serious adverse reactions after codeine ingestion in adults. Here, we present a case of severe anaphylaxis after oral ingestion of a therapeutic dose of codeine. A 30-year-old Korean woman complained of the sudden onset of dyspnea, urticaria, chest tightness, and dizziness 10 minutes after taking a 10-mg dose of codeine to treat a chronic cough following a viral infection. She had previously experienced episodes of asthma exacerbation following upper respiratory infections, and had non-atopic rhinitis and a food allergy to seafood. A skin prick test showed a positive response to 1-10 mg/mL of codeine extract, with a mean wheal size of 3.5 mm, while negative results were obtained in 3 healthy adult controls. A basophil histamine release test showed a notable dose-dependent increase in histamine following serial incubations with codeine phosphate, while there were minimal changes in the healthy controls. Following a CYP2D6 genotype analysis, the patient was found to have the CYP2D6*1/*10 allele, indicating she was an intermediate metabolizer. An open label oral challenge test was positive. To the best of our knowledge, this is the first report of a patient presenting with severe anaphylaxis after the ingestion of a therapeutic dose of codeine, which may be mediated by the direct release of histamine by basophils following exposure to codeine.

Natural Evolution of Local Allergic Rhinitis

Local allergic rhinitis (LAR) affects an important group of non-atopic rhinitis patients. However, whether LAR is a first step in the development of classical allergic rhinitis (AR) with systemic atopy or not, it is still unknown. In this study we have evaluated the natural evolution of LAR and possible conversion to AR. A prospective follow-up study has been carried out in 346 LAR patients with up to 18 months of evolution and positive response to nasal provocation test with at least one aeroallergen. Clinical questionnaire, spirometry, skin prick testing, and serum specific IgE antibodies to common aeroallergens were evaluated yearly. The clinical profile of patients was a non-smoker woman with moderate/severe persistent perennial rhinitis, without family history of atopy and city dwelling. At initial evaluation conjunctivitis (52,43%) and asthma (18,45%) were the most frequent comorbidities, and D. pteronyssinus (54,4%) the main involved aeroallergen detected by nasal allergen provocation test. Data from 176 LAR patients who have completed 4 years of evaluation showed worsening of rhinitis in 26,2%, new association to conjunctivitis and asthma in 7.8% and 5.8% respectively. New systemic sensitization to aeroallergens was detected by SPT and/or serum specific IgE in 6.81% of patients. These sensitisations appeared during first 2-3 years of evolution. These data support that LAR and classical AR can be two independent entities, because only a small proportion of LAR patients converted to AR over time. However in order to better support these differences a longer follow-up study is actually in progress.

Correlation between nasal nitric oxide, nasal airway resistance and atopy in patients of allergic rhinitis

Background: Nasal airway resistance (NAR) is dependent upon the tone of the nasal vasculature, which is regulated by endothelially derived nitric oxide (NO). Aim: The aim of this study was to investigate the relationship between nasal nitric oxide (nNO) levels, NAR and atopy in patients of allergic rhinitis (AR). Materials and Methods: The subjects were assessed for nNO levels by NIOX chemiluminescence analyzer. NAR was measured by 4-Phase-Rhinomanometry using RHINOTEST 1000. Atopy was assessed by skin prick testing against 58 common aeroallergens. Statistical Analysis: SPSS, Chicago, IL, USA, statistical package version 14 using independent sample t-test and Pearson correlation Results: In the study, 15 diagnosed cases of AR and five healthy volunteers as control were included. In the control group, the mean total NAR was 0.16 ± 0.08 kPa/l/s while in AR group mean total NAR was 0.22 ± 0.1 kPa/ l/s (P = 0.4). In AR group mean left and right NAR were 0.50 ± 0.28 kPa/l/s and 0.52 ± 0.4 kPa/l/s respectively and mean nNO levels of right and left nostrils were 291.2 ± 122.90 ppb and 251 ± 171.16 ppb (P = 0.7). No correlation was found between the left or right unilateral NAR and nNO levels, respectively. Similarly, no significant correlation of unilateral NAR and NO levels were found in the control group. Atopic AR patients had higher NAR (P = 0.001) and nNO (P = 0.06) compared with non-atopic rhinitis patients. Conclusion: In our study, AR group had higher NAR, but no correlation was found between nNO and NAR in either groups. The atopic AR patients had significantly higher NAR in comparison with non-atopic patients.

Sex and atopy influences on the natural history of rhinitis

Rhinitis is a common condition associated with significant under-recognized morbidity and impaired quality of life. The natural history of rhinitis is poorly characterized. Better understanding of its natural history and associated risk factors would improve the ability to effectively manage rhinitis in clinical practice. This review focuses on the current research findings on the natural history of rhinitis and how that is influenced by atopy and sex. Recent work from the Isle of Wight Birth Cohort Study has demonstrated that the prevalence of atopic rhinitis increases steadily in the first 18 years of life in both sexes. However, nonatopic rhinitis behaves differently during adolescence. Its prevalence decreases in boys but continues to increase in girls resulting in a female predominance after puberty. Numerous recent studies have proposed potential roles for sex-related and adipose-related hormonal changes in influencing the course of allergic disease. Further research is needed to establish mechanisms that could underlie such findings. Rhinitis becomes increasingly common through childhood, with prevalence during adolescence being mediated by differential effects of sex and atopy. Mechanisms to explain these findings await elucidation.

Dissecting the role of eosinophil cationic protein in upper airway disease

Eosinophil granulocyte myeloid cells are increased in atopic and nonatopic rhinitis, chronic rhinosinusitis (CRS) and atopic keratoconjunctivitis, diseases of the upper respiratory tract. Eosinophils contain several basic granule proteins, the best known being the eosinophil cationic protein (ECP). ECP is a cytotoxic, pro-fibrotic ribonuclease, which is found deposited in these eosinophil-related diseases and is often used in parallel with blood eosinophilia to monitor those diseases. The contribution of eosinophils and their granule proteins to disease pathogenesis have been debated; recent findings might bring these cells to the center of attention. Novel mediators of atopic disease, interleukin-17 (IL-17) and IL-33 have been found in the upper respiratory tract. These cytokines stimulate eosinophils to survival and degranulation, IL-17 via granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-33 directly. Transforming growth factor (TGF)-β has been found in CRS and atopic keratoconjunctivitis mucosa, its production possibly stimulated by ECP. ECP is detected in nasal mucosa of local allergic reactions, entopy, in rhinitis and CRS. ECP might be released from freely circulating eosinophil granules or in association with eosinophil mitochondrial DNA, both means of release for pathogen defence. Novel evidence suggests that eosinophils and ECP might have new prominent roles in development of diseases of the upper respiratory tract.

Pilot Study of Personality Traits Assessed by the Karolinska Scales of Personality (KSP) in Asthma, Atopy, and Rhinitis

Asthma and atopy are common diseases. To study associations between personality and asthma, atopy, rhinitis, and personality traits were measured on the Karolinska Scales of Personality for 193 persons working in 19 buildings with suspected indoor air problems. In addition, information on history of atopy, asthma, and rhinitis was collected by postal questionnaire. In analyses, asthma was associated with higher impulsiveness scores, and atopy in non-asthmatics was associated with higher social desirability scores and lower irritability, guilt, and impulsiveness scores. Non-atopic rhinitis was associated with scores on several anxiety-related scales, while atopic rhinitis was not associated with scores on the Karolinska Scales of Personality. This exploration implies that asthma, atopy, and rhinitis may be associated with various but different personality trait scores. The finding of such personality trait associations in persons with non-asthmatic atopy raises the question of a potential role of an emotional conflict in atopy and the role of personality in asthma, atopy, and rhinitis.

SICAM-1 and TNF-α in Asthma and Rhinitis: Relationship with the Presence of Atopy

Background. A genetically determined overproduction of specific immunoglobulin E (IgE) underlies many diseases like asthma or allergic rhinitis. IgE as well as tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) play a critical role in the induction and maintenance of inflammation. While the correlation between IgE and atopy is inseparable, little is known about the correlation of atopy with markers of inflammation. Objective. We investigated the relationship between the serum concentrations of TNF-α, soluble ICAM-1 (sICAM-1), and the presence of atopy in patients with persistent rhinitis or asthma. Methods. Serum concentrations of sICAM-1, TNF-α, and total IgE were investigated in 64 adults with persistent allergic rhinitis, 17 subjects with nonatopic rhinitis, 90 patients with asthma, and 21 healthy individuals. Atopy was diagnosed on the basis of positive family history, skin prick tests, and serum IgE concentration. Results. Total IgE concentration was significantly higher in patients with atopic rhinitis or asthma when compared with nonatopic patients and healthy individuals and was the highest in patients suffering from severe atopic asthma who were not treated with systemic glucocorticosteroids. Although there were marked alterations in IgE in atopic and nonatopic patients, there were no significant differences between atopic and corresponding groups of nonatopic rhinitic and asthmatic patients in sICAM-1 and TNF-α concentrations. (sICAM-1 in rhinitis: atopic vs. nonatopic patients: 224.02 and 221.08 ng/ml, respectively, p > .05; in mild/moderate asthma: atopic vs. nonatopic: 306.22 and 326.39 ng/ml, respectively, p > .05; severe asthma without oral corticosteroids therapy: atopic vs. nonatopic: 418.03 and 468.09 ng/ml, respectively, p > .05; and severe asthma with oral corticosteroids therapy: atopic vs. nonatopic: 320.66 and 308.09 ng/ml, respectively, p > .05). Conclusions. Concentrations of sICAM-1 and TNF-α are significantly higher in patients with asthma compared with those observed in patients with rhinitis, but they are independent of the presence of atopy.

The influence of gender and atopy on the natural history of rhinitis in the first 18 years of life

Longitudinal studies of the natural history of childhood and adolescent rhinitis are lacking. To investigate the natural history of rhinitis up to 18 years of age, and how that is influenced by gender and atopy. The Isle of Wight birth cohort was recruited in 1989 (n=1456). Questionnaire data on nasal symptoms (rhinitis) were collected at 1, 2, 4, 10 and 18 years of age. To define atopy, skin prick tests were conducted at 4, 10 and 18 years. The 12-month period prevalence plus positive and negative transitions (defined as change in disease status in two consecutive study assessments) were stratified by gender and atopic status. Overall rhinitis prevalence increased from 5.4% at 4 years to 35.8% at 18 years (P<0.001), without gender difference. Atopic rhinitis prevalence increased steadily from 3.4% at 4 years to 27.3% at 18 years (P<0.001), was commoner in boys at 18 years (P=0.02) and associated with greater positive transition in boys from 10 to 18 years (P=0.01). Prevalence of non-atopic rhinitis also increased from 4 to 18 years (P=0.003) and was greater in girls at 18 years (P<0.001) reflecting higher female positive transition from 10 to 18 years (P<0.001). Non-atopic rhinitis negative transition (remission) was highest in early life and reduced in later childhood/adolescence. Atopic rhinitis becomes increasingly common as children grow into adolescents, with stronger associations to male gender. Non-atopic rhinitis shows a female predominance at 18 years as girls 'grow into' it more during adolescence. Our findings suggest differential gender effects on the increasing prevalence of both atopic and non-atopic rhinitis in adolescence. A better understanding of how gender and atopic status influence rhinitis during adolescence emerges from this study. Application of such knowledge could help to improve clinical recognition, judge prognosis and ultimately improve management of this common condition.

Added value with extended NO analysis in atopy and asthma

Assessments of the usefulness of exhaled nitric oxide (NO) in the treatment of asthma have given conflicting results. It is not always obvious if atopic status has been tested in these evaluations. The aim of the study is to use extended NO analysis to characterize subjects from a random sample populations with focus on rhinitis and asthma. Data were extracted from the European Community Respiratory Health Survey II. A subgroup from the Uppsala site that had had their NO measured at multiple flow rates was included (n = 284). The nonlinear model for NO parameters was used. Atopy was defined as having a titre against at least one of the tested allergens ≥0·35 kU l(-1) . Bronchial responsiveness was assessed by methacholine challenge. Subjects with non-atopic rhinitis or non-atopic asthma could not be separated from healthy subjects regarding NO parameters. There was a gradual increase with atopy in airway diffusion rate (D(aw) NO); healthy subject 8·0 (7·3, 8·8), healthy atopic 8·8 (6·7, 11·5), atopic rhinitis 10·6 (9·0, 12·4) and atopic asthma 11·2 (9·9, 28·3) ml s(-1) [geometrical mean (CI(95%) )]. There was a correlation between bronchial responsiveness and D(aw) NO in atopic rhinitis (r = -0·41, P<0·01), and bronchial responsiveness and airway wall content of NO (C(aw) NO) in atopic asthma (r = -0·56, P<0·001). It is of importance to characterize atopic status when evaluating the association between NO and asthma. Our results indicate that the use of extended NO analysis, with particular attention to D(aw) NO and C(aw) NO, may be useful in monitoring treatment for rhinitis and asthma.

Evidence for the involvement of free light chain immunoglobulins in allergic and nonallergic rhinitis

Allergic rhinitis is characterized by mast cell degranulation induced by antigen cross-linking of IgE. It has been proposed that some patients with rhinitis show nasal allergy in the absence of systemic markers of atopy, termed entopy. Recent murine studies suggest the existence of an IgE-independent hypersensitivity response involving antigen-induced mast cell activation, mediated by immunoglobulin free light chains (FLCs). To determine whether FLC is associated with mast cell-mediated nasal hypersensitivity and its relationship with eosinophilic activity in allergic and nonatopic rhinitis. Patients with allergy and nonallergic rhinitis with eosinophilia syndrome (NARES) had levels of soluble FLC measured in nasal secretions and serum. In addition, levels of the nasal inflammatory mediators mast cell tryptase and eosinophil cationic protein were quantified. Cellular expression of kappa and lambda FLC was characterized in the nasal mucosa of allergic and nonatopic idiopathic rhinitis and control subjects by using immunohistochemistry. Immunopositive cells were phenotyped by using laser microdissection and PCR. Free light chain was significantly increased in nasal secretions of subjects with allergy and NARES, and in serum of patients with NARES. Nonatopic patients with allergy showed significantly increased nasal mast cell tryptase and eosinophil cationic protein. FLC-positive cells were significantly increased in allergic and nonatopic mucosa, and were shown to be mast cells and plasma cells. Nasal FLC is significantly increased in allergic and nonatopic rhinitis nasal mucosa, suggesting a role in nasal hypersensitivity. Further studies are needed to identify which allergens trigger FLC-mediated responses in nonatopic rhinitis.

International variation in prevalence of rhinitis and its relationship with sensitisation to perennial and seasonal allergens

The relative importance of atopy in the aetiology of rhinitis is largely unknown. The present study investigated the geographical variations in rhinitis in relation to atopy. The cross-sectional study involved 54,178 children (aged 8-12 yrs) from 30 study centres in 22 countries worldwide. Symptoms of rhinoconjunctivitis and rhinitis without conjunctivitis in the last 12 months were reported in parental questionnaires and children were skin-prick tested. The prevalence of rhinoconjunctivitis and rhinitis without conjunctivitis varied widely (1.5-24.5% and 1.4-45.2%, respectively). For rhinoconjunctivitis, the population attributable fraction (PAF) varied 0-71% for a positive skin-prick test to one or more seasonal allergens and 0-41% for perennial allergens. The PAF for sensitisation to seasonal and perennial allergens was higher in affluent countries (36 and 25%, respectively) than nonaffluent countries (1.3 and 12.6%, respectively). For rhinitis without conjunctivitis, the PAF for perennial allergens was 8 and 4% for affluent and nonaffluent countries, respectively. No significant PAF was found for seasonal allergens. Overall, atopy explained only a limited proportion of rhinitis symptoms, suggesting that the importance of other environmental factors has been under emphasised, particularly in less affluent countries. Atopy seems to be only marginally relevant for rhinitis without conjunctivitis, which seems mainly to reflect nonatopic rhinitis.

Local mucosal immunoglobulin E production: does allergy exist in non‐allergic rhinitis?

In this review, we critically evaluate the evidence for local IgE production in allergic rhinitis mucosa and the concept of local allergy in non-atopic idiopathic rhinitis. Significantly, fewer studies have focused on the disease pathways associated with non-allergic rhinitis compared with their allergic counterparts. Recently, there's been a revival of the hypothesis concerning the existence of local tissue-specific allergic disease confined to the nasal mucosa of some systemically non-atopic rhinitis subjects. Providing the evidence for local mucosal IgE production in allergic rhinitis is a pre-requisite to reviewing its existence in non-allergic rhinitis. In addition, practical and theoretical approaches useful in the detection of allergy in non-allergic rhinitis will be discussed. Furthermore, successful therapeutic regimens used in the treatment of non-allergic rhinitis will be examined as these could provide an insight into the underlying pathophysiology of this common but poorly understood disease.

Functional plasticity of human respiratory tract dendritic cells: GM-CSF enhances T H2 development

Dendritic cells within the human respiratory mucosa (RTDCs) are proposed to initiate immune responses to foreign antigens. Their capacity to polarize T-cell responses, however, has not been investigated. To compare RTDCs with peripheral blood dendritic cells (PBDCs) with regard to phenotype, cytokine production, capacity to polarize T-cell responses, and effects of exposure to the pleiotropic cytokine, GM-CSF. CD1a(+) RTDCs and CD1c(+) PBDCs were purified from nasal turbinates of patients with nonatopic rhinitis and peripheral blood of healthy individuals, respectively. In some experiments, matched CD1c(+) RTDCs and PBDCs from patients with rhinitis were compared. The phenotype of DC was examined by flow cytometry and cytokine production by cytometric bead array. DCs were cocultured with allogeneic naive CD4(+) T cells, and cytokine production was determined by immunophenotyping, cytometric bead array, and ELISA. Both RTDCs and PBDCs exhibited an immature phenotype, but RTDCs expressed lower levels of MHC class II antigen. Cross-linking of CD40 on PBDCs, but not RTDCs, induced production of IL-12p70. In mixed lymphocyte cultures, RTDCs induced a T(H)1/T(H)2 profile, whereas PBDCs induced a T(H)1 profile. Exposure of RTDCs to GM-CSF induced a T(H)2 pattern of response in the mixed lymphocyte cultures. In contrast, exposure of PBDCs to GM-CSF promoted a T(H)1 response. This report emphasizes the importance of studying tissue-derived primary DCs, demonstrates functional plasticity of RTDCs, and implicates GM-CSF in amplifying the potential of RTDCs to initiate T(H)2 responses in the airways.

Mucosal T-cell phenotypes in persistent atopic and nonatopic rhinitis show an association with mast cells.

Allergic rhinitis is characterized by selective expansion of T cell subsets with a CD4+ phenotype. Recently, we identified a subpopulation of nonallergic rhinitis subjects with increased epithelial mast cell and eosinophil populations, suggestive of local mucosal allergy. Previously, T cell subsets have not been characterized in this subselection of nonallergic subjects and furthermore, their relationship to mast cell and basophil effector cells remain unidentified. To determine if a subpopulation of nonallergic subjects with idiopathic rhinitis (IR) have localized allergy confined to their nasal mucosa by comparing the T cell subsets and major histocompatibility complex (MHC) II expressing cells to persistent allergic rhinitis (PAR). Furthermore, the relationship between T cell subsets and mast cells/basophils was investigated. None of the symptomatic patients in this study were clinically allergen-challenged. Nasal turbinate mucosa was removed from patients with PAR, IR and normal controls. Morphometry was performed on immunostained sections for T cell subset populations including CD3+, CD4+, CD8+, CD25+, CD45RA+, CD45RO+, human leucocyte antigen (HLA)-DRalpha (MHC class II), mast cell tryptase and for basophils. Subjects with persistent allergic rhinitis differed to normal controls in showing significantly increased numbers of total (CD3+), activated (CD25+) and allergen-naïve (CD45RA+) T lymphocytes in their nasal mucosa (P < 0.025). The naïve CD45RA+ memory T cells correlated to mucosal mast cells in PAR (P = 0.03). IR patients differ to allergic subjects in showing significantly reduced numbers of epithelial HLA-DRalpha+ cells (P = 0.007), but increased numbers of CD8+ lymphocytes (P = 0.02). The CD8+ T cells correlated with mucosal mast cell numbers (P = 0.02). In both rhinitis groups, basophils were present in very low numbers obviating the need for statistical analysis. PAR is characterized by increased numbers of CD3+, CD25+ and CD45RA+ T lymphocytes compared with normal mucosa. Allergic and nonallergic rhinitis groups can be separated by significant differences in the number of epithelial antigen presenting cells (APCs) (HLA-DRalpha+) and sub-epithelial activated (CD25+) T cells. Moreover, IR patients do not significantly differ to their allergic counterparts with respect to total (CD3+) and naïve (CD45RA+) T cell numbers, or numbers of epithelial activated (CD25+) lymphocytes. IR subjects show significantly increased numbers of CD8+ lymphocytes compared with control mucosa and although our findings suggest that the initiating inflammatory events may differ, both rhinitis groups show a similarity in pathology involving mucosal mast cells with an association to infiltrating T cells.

Hypo-osmolar aerosol induces hyperventilation in chronic non-asthmatic rhinitics

The effect of a hypo-osmolar aerosol on transcutaneous O 2 and CO 2 time course ( PtcO 2, PtcCO 2) was investigated in subjects affected by chronic non-atopic rhinitis, without any history of asthmatic symptoms and no airways hyper-responsiveness. Twelve normal subjects and 12 subjects affected by chronic idiopathic rhinitis, who had normal responsiveness to both hypo-osmolar aerosol and methacholine challenge as measured by the decrease in FEV 1 (mean FEV 1 decrease=5% and PC 20 > 16 mg, respectively) were studied. By means of a transcutaneous mono-electrode, it was possible to study the time course of PtcO 2 and PtcCO 2 during and after a 5-min inhalation of ultrasonically nebulized distilled water (output 2 ml/min −1). A significant decrease in PtcCO 2 and increase in PtcO 2 were observed during the challenge in rhinitics as compared with normal subjects [maximum decrease and maximum increase expressed as mean value (± sd) were −22% (± 6·9) and +12·6% (± 7·2), respectively]. No significant changes in either PtcCO 2 and PtcO 2 were observed after the test. The results of this study suggest that patients affected by idiopathic chronic rhinitis with absence of bronchial hyper-responsiveness may present a hyperventilatory response to the inhalation of hypo-osmolar aerosol; the mechanism of such a response might be due to an upregulation of the irritant receptors of the upper airways.