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Objectives: Inflammation is known to be associated with the progression of cancer. The study was designed to characterise the systemic inflammation in patients with oropharyngeal squamous cell carcinoma (OPSCC) and investigate its relation to tumour size, ability to metastasise and HPV status. Materials and Methods: Blood was obtained from 58 patients with OPSCC and 90 healthy controls and analysed with leucocyte differential count. Results: The patients with OPSCC displayed an increased number of neutrophils and monocytes, whereas the lymphocytes were suppressed compared to the healthy controls. The neutrophils‐to‐lymphocyte ratio (NLR) and the monocyte‐to‐lymphocyte ratio (MLR) were calculated, and patients with large tumours exhibited high NLR and MLR. Further, patients with regional lymph node spread displayed a low NLR and MLR. Patients with HPV‐positive tumours (n = 48) had a lower NLR than the patients (n = 8) with HPV‐negative tumours. Conclusion: This study demonstrates that patients with OPSCC have an increased systemic inflammation that is affected by the HPV status, the size of the tumour and lymph node spread. [ABSTRACT FROM AUTHOR]

In this review, we report on relevant current topics in allergen immunotherapy ( AIT) which were broadly discussed during the first Aarhus Immunotherapy Symposium (Aarhus, Denmark) in December 2015 by leading clinicians, scientists and industry representatives in the field. The aim of this symposium was to highlight AIT-related aspects of public health, clinical efficacy evaluation, mechanisms, development of new biomarkers and an overview of novel therapeutic approaches. Allergy is a public health issue of high socioeconomic relevance, and development of evidence-based action plans to address allergy as a public health issue ought to be on national and regional agendas. The underlying mechanisms are in the focus of current research that lays the ground for innovative therapies. Standardization and harmonization of clinical endpoints in AIT trials as well as current knowledge about potential biomarkers have substantiated proof of effectiveness of this disease-modifying therapeutic option. Novel treatments such as peptide immunotherapy, intralymphatic immunotherapy and use of recombinant allergens herald a new age in which AIT may address treatment of allergy as a public health issue by reaching a large fraction of patients. [ABSTRACT FROM AUTHOR]

Background A previous investigation of all 10 TLR genes for associations with allergic rhinitis ( AR) detected a number of significant SNPs in the TLR8 locus. The associations indicated that an accumulation of rare variants could explain the signal. This study therefore searches for rare variants in the TLR8 region and also investigates the reproducibility of previous SNP associations. Methods The TLR8 gene was resequenced in 288 AR patients from Malmö and the data were compared with publically available data. Seven previously AR-associated SNPs from TLR8 were analyzed for AR associations in 422 AR patients and 859 controls from the BAMSE cohort. The associations detected in present and previous studies were compared. Results Sequencing detected 13 polymorphisms (three promotor and 10 coding) among 288 AR patients. Four of the coding polymorphisms were rare ( MAF < 1%) and three of those were novel. Two coding polymorphisms were benign missense mutations and the rest were synonymous. Comparison with 1000Genomes and Exome Aggregation Consortium data revealed no accumulation of rare variants in the AR cases. The AR association tests made using the BAMSE cohort yielded five P-values <0.05. Tests of IgE levels yielded four significant SNP associations to birch pollen. Comparing results between different populations revealed opposing risk alleles, different gender effects, and response to different allergens in the different populations. Conclusions Rare variants in TLR8 are not associated with AR. Comparison of present and previous association studies reveals contradictory results for common variants. Thus, no associations exist between genetic variation in TLR8 and AR. [ABSTRACT FROM AUTHOR]

Background: Three genomewide metastudies have recently reported associations with self-reported allergic rhinitis and allergic sensitization. The three studies together identified a set of 37 loci but showed low concordance. This study inves-tigates the reproducibility of the detected single nucleotide polymorphism (SNP) associations in an extensively characterized longitudinal cohort, BAMSE. Methods: Phenotypic evaluation of allergic rhinitis (AR) and allergic sensitization was performed on 2153 children from BAMSE at 8 and 16 years of age. Allele frequencies of 39 SNPs were investigated for association with the exact allergic phenotypes of the metastudies. Odds ratios and false discovery rates were calcu-lated, and the impact of asthma was evaluated. The cases were also evaluated for age at onset effects (≤ or >8 years of age). Results: Association tests of the 39 SNPs identified 12 SNPs with P-values < 0.05 and 0-values < 0.10. Two of the four loci (TLR6-TLR1 and HLA-DQAl-HLA-DQB1) identified in all three original studies were also identified in this study. Three SNPs located in the TLR6-TLR1 locus had the lowest /"-values and ß-val- ues < 0.1 when using a well-defined AR phenotype. Two loci showed significant age at onset effects, but the effect of asthma on the associations was very limited. Conclusion: The TLR6-TLR1 locus is likely to have a central role in the develop-ment of allergic disease. The association between genetic variation in the SSTR1-MIPOL1 and TSLP-SLC25A46 loci and age at onset is the first report of age at onset effects in allergic rhinitis. [ABSTRACT FROM AUTHOR]

Background and Purpose: The guinea pig trachea (GPT) is commonly used in airway pharmacology. The aim of this study was to define the expression and function of EP receptors for PGE(2) in GPT as there has been ambiguity concerning their role.Experimental Approach: Expression of mRNA for EP receptors and key enzymes in the PGE(2) pathway were assessed by real-time PCR using species-specific primers. Functional studies of GPT were performed in tissue organ baths.Key Results: Expression of mRNA for the four EP receptors was found in airway smooth muscle. PGE(2) displayed a bell-shaped concentration-response curve, where the initial contraction was inhibited by the EP(1) receptor antagonist ONO-8130 and the subsequent relaxation by the EP(2) receptor antagonist PF-04418948. Neither EP(3) (ONO-AE5-599) nor EP(4) (ONO-AE3-208) selective receptor antagonists affected the response to PGE(2). Expression of COX-2 was greater than COX-1 in GPT, and the spontaneous tone was most effectively abolished by selective COX-2 inhibitors. Furthermore, ONO-8130 and a specific PGE(2) antibody eliminated the spontaneous tone, whereas the EP(2) antagonist PF-04418948 increased it. Antagonists of other prostanoid receptors had no effect on basal tension. The relaxant EP(2) response to PGE(2) was maintained after long-term culture, whereas the contractile EP(1) response showed homologous desensitization to PGE(2), which was prevented by COX-inhibitors.Conclusions and Implications: Endogenous PGE(2), synthesized predominantly by COX-2, maintains the spontaneous tone of GPT by a balance between contractile EP(1) receptors and relaxant EP(2) receptors. The model may be used to study interactions between EP receptors. [ABSTRACT FROM AUTHOR]

Background and Purpose The guinea pig trachea ( GPT) is commonly used in airway pharmacology. The aim of this study was to define the expression and function of EP receptors for PGE2 in GPT as there has been ambiguity concerning their role. Experimental Approach Expression of mRNA for EP receptors and key enzymes in the PGE2 pathway were assessed by real-time PCR using species-specific primers. Functional studies of GPT were performed in tissue organ baths. Key Results Expression of mRNA for the four EP receptors was found in airway smooth muscle. PGE2 displayed a bell-shaped concentration-response curve, where the initial contraction was inhibited by the EP1 receptor antagonist ONO-8130 and the subsequent relaxation by the EP2 receptor antagonist PF-04418948. Neither EP3 ( ONO- AE5-599) nor EP4 ( ONO- AE3-208) selective receptor antagonists affected the response to PGE2. Expression of COX-2 was greater than COX-1 in GPT, and the spontaneous tone was most effectively abolished by selective COX-2 inhibitors. Furthermore, ONO-8130 and a specific PGE2 antibody eliminated the spontaneous tone, whereas the EP2 antagonist PF-04418948 increased it. Antagonists of other prostanoid receptors had no effect on basal tension. The relaxant EP2 response to PGE2 was maintained after long-term culture, whereas the contractile EP1 response showed homologous desensitization to PGE2, which was prevented by COX-inhibitors. Conclusions and Implications Endogenous PGE2, synthesized predominantly by COX-2, maintains the spontaneous tone of GPT by a balance between contractile EP1 receptors and relaxant EP2 receptors. The model may be used to study interactions between EP receptors. [ABSTRACT FROM AUTHOR]

Summary Background The existence of a link between inflammation in upper and lower airways is well established. It may therefore be assumed that the nose could be used to study inflammatory events in the lower airways. Objective This study aimed to evaluate a lipopolysaccharide ( LPS) nasal challenge model by investigating the effect of the CXCR2 inhibitor AZD8309 on neutrophilic inflammation. Methods A total of 18 healthy volunteers were randomized in a placebo-controlled, double-blind, cross-over study. AZD8309 or placebo was dosed for 3 days. Subjects were challenged nasally with LPS (50 μg/nostril), and nasal lavage was performed 6 and 24 h later. Leucocytes, neutrophils and inflammatory mediators were assessed in the lavage fluid. The outcome was compared with data from analogous experiments performed in a model of inhaled LPS followed by induced sputum. This trial was registered in the Current Controlled Trials register ( ISRCTN trial number: ISRCTN46666382). Results The leucocytes in nasal lavage consisted to 99% of neutrophils on average. Treatment with AZD8309 reduced the leucocyte count to 48% of placebo 6 h after the LPS challenge. There was also a reduction in LTB4 levels to 45% of placebo after 6 h and in the neutrophil elastase activity after 24 h. No major adverse events were seen with either AZD8309 or placebo. The nasal LPS model induced only minimal local irritation and no signs of systemic inflammation. Conclusions and Clinical Relevance LPS-induced neutrophil recruitment was reduced by inhibition of CXCR2. This outcome mimicked the response previously seen in a lower airway LPS model. Hence, the nasal model offers a convenient and well-tolerated alternative for pharmacological evaluation of anti-inflammatory drugs affecting neutrophilic migration and activity. [ABSTRACT FROM AUTHOR]

Background: Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are newly discovered cytosolic receptors belonging to the pattern-recognition receptor family. They detect various pathogen-associated molecular patterns, triggering an immune response. The knowledge about these receptors, and their role in health and disease, is limited. The aim of the present study was to characterize the expression of NOD1, NOD2, and NALP3 in the human upper airways. Methods: Surgical samples were obtained from patients with tonsillar disease (n = 151), hypertrophic adenoids (n = 9), and nasal polyposis (n = 24). Nasal biopsies were obtained from healthy volunteers (n = 10). The expression of NOD1, NOD2, and NALP3 was analyzed using real-time PCR and immunohistochemistry.Results: Expression of NOD1, NOD2, and NALP3 mRNA and protein were seen in all tissue specimens. The NLR mRNA was found to be higher in nasal polyps than in normal nasal mucosa, and local steroid treatment reduced the NLR expression in polyps. In contrast, tonsillar infection with Streptococcus pyogenes or Haemophilus influenzae did not affect the NLR expression. Conclusions: The present study demonstrates the presence of NLRs in several upper airway tissues and highlights a potential role of NLRs in chronic rhinosinusitis with polyps. [ABSTRACT FROM AUTHOR]

Background: The European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS) incorporates symptomatic, endoscopic, and radiologic criteria in the clinical diagnosis of chronic rhinosinusitis (CRS), while in epidemiological studies, the definition is based on symptoms only. We aimed to assess the reliability and validity of a symptom-based definition of CRS using data from the GA2LEN European survey. Methods: On two separate occasions, 1700 subjects from 11 centers provided information on symptoms of CRS, allergic rhinitis, and asthma. CRS was defined by the epidemiological EP3OS symptom criteria. The difference in prevalence of CRS between two study points, the standardized absolute repeatability, and the chancecorrected repeatability (kappa) were determined. In two centers, 342 participants underwent nasal endoscopy. The association of symptom-based CRS with endoscopy and self-reported doctor-diagnosed CRS was assessed. Results: There was a decrease in prevalence of CRS between the two study phases, and this was consistent across all centers ()3.0%, 95% CI: )5.0 to )1.0%, I2 = 0). There was fair to moderate agreement between the two occasions (kappa = 39.6). Symptom-based CRS was significantly associated with positive endoscopy in nonallergic subjects, and with self-reported doctor-diagnosed CRS in all subjects, irrespective of the presence of allergic rhinitis. Conclusion: Our findings suggest that a symptom-based definition of CRS, according to the epidemiological part of the EP3OS criteria, has a moderate reliability over time, is stable between study centers, is not influenced by the presence of allergic rhinitis, and is suitable for the assessment of geographic variation in prevalence of CRS. [ABSTRACT FROM AUTHOR]

To cite this article: Bogefors J, Rydberg C, Uddman R, Fransson M, Månsson A, Benson M, Adner M, Cardell LO. Nod1, Nod2 and Nalp3 receptors, new potential targets in treatment of allergic rhinitis? Allergy 2010; 65: 1222–1226. Background: Recently, a new set of pattern-recognition receptors, the nucleotide-binding oligomerization domain (Nod)-like receptors (NLRs), have emerged. Their activation, either by allergens or microbes, triggers an inflammatory response. The knowledge about NLRs in human airways is limited. Aim of the study: To investigate presence of NLRs in the human nose of healthy individuals and patients with intermittent allergic rhinitis outside and during pollen season. Methods: The expression of Nod1, Nod2, and Nalp3 in nasal biopsies was determined with real-time RT-PCR and immunohistochemistry. Cultured primary human nasal epithelial cells (HNECs) were analyzed using real-time RT-PCR and flow cytometry to further verify the presence of NLRs in the epithelium. Results: Immunohistochemical analysis revealed presence of Nod1, Nod2, and Nalp3 in the nasal epithelium. This was corroborated in cultured HNECs. Patients suffering from symptomatic allergic rhinitis exhibited lower Nod1 and Nalp3 mRNA levels than both controls and patients during pollen season. Nod2 expression was found in all specimens tested, but no differences were seen between the three groups. Conclusion: Nod1, Nod2, and Nalp3 receptors were found to be present in the human nose. The expression of Nod1 and Nalp3 were down-regulated during pollen season among patients with allergic rhinitis. This opens up for new insights and novel therapeutic strategies in inflammatory airway disease. [ABSTRACT FROM AUTHOR]

To cite this article: Hellgren J, Cervin A, Nordling S, Bergman A, Cardell LO. Allergic rhinitis and the common cold – high cost to society. Allergy 2010; 65: 776–783. Background: The common cold and allergic rhinitis constitute a global health problem that affects social life, sleep, school and work performance and is likely to impose a substantial economic burden on society because of absence from work and reduced working capacity. This study assesses the loss of productivity as a result of both allergic rhinitis and the common cold in the Swedish working population. Methods: Four thousand questionnaires were sent to a randomized adult population, aged 18–65 years, in Sweden, stratified by gender and area of residence (metropolitan area vs rest of the country). The human capital approach was used to assign monetary value to lost productivity in terms of absenteeism (absence from work), presenteeism (reduced working capacity while at work) and caregiver absenteeism (absence from work to take care of a sick child). Results: Thousand two hundred and thirteen individuals responded, response rate 32%. The mean productivity loss was estimated at 5.1 days or € 653 per worker and year, yielding a total productivity loss in Sweden of € 2.7 billion a year. Of the total costs, absenteeism (44%) was the dominant factor, followed by presenteeism (37%) and caregiver absenteeism (19%). Poisson regression analyses revealed that women, people in the 18–29 year age group, and respondents with ‘ doctor-diagnosed asthma’ reported more lost days than the rest of the group. Conclusion: In Sweden, the cost of rhinitis is € 2.7 billion a year in terms of lost productivity. A reduction in lost productivity of 1 day per individual and year would potentially save € 528 million. [ABSTRACT FROM AUTHOR]

To cite this article: Bryborn M, Halldén C, Säll T, Cardell LO. CLC– a novel susceptibility gene for allergic rhinitis?. Allergy 2010; 65: 220–228. Background: Studies of the nasal lavage fluid proteome have previously identified proteins differently expressed in patients with symptomatic allergic rhinitis, e.g. S100A7, prolactin-inducible protein (PIP), wingless-type MMTV integration site family, member 2B (WNT2B), Charcot-Leyden crystal protein (CLC) and palate lung nasal epithelial clone (PLUNC). The aim of the present study was to investigate if genetic variation associated with allergic rhinitis can be found in these genes. Methods: Peripheral blood was collected from 251 patients with birch and/or grass pollen-induced allergic rhinitis and 386 nonatopic healthy controls. A total of 39 single nucleotide polymorphisms (SNPs) distributed over the genes PIP, WNT2B, CLC and PLUNC were selected from dbSNP, genotyped and investigated for associations with allergic rhinitis. Twelve additional SNPs were subsequently analysed for CLC. Results: All 22 investigated SNPs in CLC were polymorphic. Ten SNPs yielded significant differences between cases and controls with respect to genotype frequencies. Homozygotes for the minor allele were more common in allergic individuals compared to healthy controls. The minor alleles of these SNPs were all located on the same haplotype. Furthermore, homozygotes for the minor allele of two of the promoter SNPs had higher average scores for birch in skin prick test. In contrast, for seven SNPs within the gene, heterozygotes and homozygotes for the major allele had higher average scores for grass. None of the other three genes showed association. Conclusion: Genetic variation in CLC was found to be associated with allergic rhinitis. The pattern of variation is compatible with a recessive inheritance model and the previously observed altered protein levels detected in patients with allergic rhinitis. [ABSTRACT FROM AUTHOR]

Background: Some patients with allergic asthma treated with anti-IgE (Xolair®) do not become symptom free. Better criteria for response assessment than allergy skin tests or IgE determination are needed. The impact of the size of the disease relevant allergen-specific IgE antibody fraction, i.e. the percentage of IgE antibody of total IgE, was evaluated in cat allergic patients treated with the recommended doses of Xolair®. Results were measured as changes in basophil allergen threshold sensitivity (CD-sens). Methods: In a double-blind placebo controlled trial 20 patients with a high (>3.8%) and 18 with a low (<1%) percentage of IgE antibodies to cat were given Xolair® for 16 weeks and the change in CD-sens was compared to 11 and 10 patients, respectively, in each group receiving placebo. Results: The CD-sens dropped significantly in both the high ( P < 0.001) and low ( P < 0.001) group on Xolair® but did not change significantly after placebo. For Xolair®-treated patients, at the end of the trial there was a highly significant ( P < 0.001) difference in CD-sens between the high group, where no patients, and the low group, where 13/18 patients, had become negative. Conclusions: The currently recommended doses of Xolair® very efficiently eliminate IgE antibodies if the IgE antibody fraction is <1% of total IgE but has not enough effect on allergen sensitivity if the fraction is >3–4%. Further studies will show if increased doses of Xolair® would help also these patients, who seem to represent about 1/3 of the patient population. [ABSTRACT FROM AUTHOR]

Background: Chronic noninfectious, nonallergic rhinitis (NINAR) is a complex syndrome with a principally unknown pathophysiology. New technology has made it possible to examine differentially expressed genes and according to network theory, genes connected by their function that might have key roles in the disease. Methods: Connectivity analysis was used to identify NINAR key genes. mRNA was extracted from nasal biopsies from 12 NINAR patients and 12 healthy volunteers. Microarrays were performed using Affymetrix chips with 54 613 genes. Data were analysed with the Ingenuity Pathway System for organization of genes into annotated biological functions and, thereafter, linking genes into networks due to their connectivity. The regulation of key genes was confirmed with reverse transcription-polymerase chain reaction (RT-PCR). Results: In all, 43 genes were differentially expressed. The functional analysis showed that these genes were primarily involved in cellular movement, haematological system development and immune response. Merging these functions, 10 genes were found to be shared. Network analysis generated three networks and two of these ‘shared genes’ in key positions, c-fos and cell division cycle 42 (Cdc42). These genes were upregulated in both the array and the RT-PCR analysis. Conclusion: Ten genes were found to be of pathophysiological interest for NINAR and of these, c-fos and Cdc42 seemed to be of specific interest due to their ability to interact with other genes of interest within this context. Although the role of c-fos and Cdc42 in upper airway inflammation remains unknown, they might be used as potential disease markers. [ABSTRACT FROM AUTHOR]

Background: Identification of disease-associated single nucleotide polymorphisms (SNPs) in seasonal allergic rhinitis (SAR) may be facilitated by focusing on genes in a disease-associated pathway. Objective: To search for SNPs in genes that belong to the T-cell receptor (TCR) pathway and that change in expression in allergen-challenged CD4+ cells from patients with SAR. Methods: CD4+ cells from patients with SAR were analysed with gene expression microarrays. Allele, genotype and haplotype frequencies were compared in 251 patients and 386 healthy controls. Results: Gene expression microarray analysis of allergen-challenged CD4+ cells from patients with SAR showed that 25 of 38 TCR pathway genes were differentially expressed. A total of 62 SNPs were analysed in eight of the 25 genes; ICOS, IL4, IL5, IL13, CSF2, CTLA4, the inducible T-cell tyrosine kinase ( ITK) and CD3D. Significant chi-squared values were identified for several markers in the ITK kinase gene region. A total of five SNPs were nominally significant at the 5% level. Haplotype analysis of the five significant SNPs showed increased frequency of a haplotype that covered most of the coding part of ITK. The functional relevance of ITK was supported by analysis of an independent material, which showed increased expression of ITK in allergen-challenged CD4+ cells from patients, but not from controls. Conclusion: Analysis of SNPs in TCR pathway genes revealed that a haplotype that covers a major part of the coding sequence of ITK is a risk factor for SAR. [ABSTRACT FROM AUTHOR]

Background: We have previously demonstrated the presence of toll-like receptor 9 in the nasal mucosa of both healthy and allergic individuals. CpG motifs, found in bacterial and viral DNA, elicit strong immunostimulatory effects via this receptor. CpG is known to skew the immune system towards a T helper 1 (Th1) profile, thereby suppressing Th2-driven allergic responses. This study was designed to examine the effects of CpG administration in the human nose. Methods: Twenty subjects, of whom 10 suffered from seasonal allergic rhinitis (AR), were challenged intranasally with CpG outside pollen season. Symptom scores, nasal airway resistance (NAR), and nasal and pulmonary nitric oxide (NO) levels were assayed prior to challenge and 30 min, 6, 24 and 48 h post challenge. The presence of leukocytes and various cytokines were analyzed in nasal lavage (NAL) fluids before and after CpG exposure. Results: Increased NAR, nasal NO production and secretion of interleukin (IL)-1β, IL-6, and IL-8 were seen after CpG exposure. Further analysis revealed that this inflammatory response was more marked in healthy subjects than among patients with AR, although a higher basal inflammatory response was recorded in the allergic group. In vitro experiments suggest that the effects induced by CpG are mediated by epithelial cells and neutrophils. Conclusion: Nasal administration of CpG induces a local airway inflammation, more distinct among healthy than allergic individuals. The reduced responsiveness to CpG in allergic patients might be related to the ongoing minimal persistent inflammation. Results from cytokine analyses reflect the ability of CpG to induce a pro-inflammatory Th1-like immune response. [ABSTRACT FROM AUTHOR]

Background: Allergen-specific immunotherapy (ASIT) in allergic rhinitis and asthma is the only treatment that effects the long-term development of these diseases. Basophil allergen threshold sensitivity, CD-sens, which is a valuable complement to resource-demanding clinical challenge tests, was used to monitor the initiation of ASIT induced allergen ‘blocking activity’. Methods: Patients IgE-sensitized to timothy ( n = 14) or birch ( n = 19) pollen were started on conventional (8–16 weeks) or ultra rush ASIT, respectively, and followed by measurements of CD-sens, allergen binding activity (ABA) and serum IgG4- and IgE-antibody concentrations. Results: CD-sens decreased during the early phase of ASIT-treatment. In parallel, ABA increased and correlated significantly with the increasing levels of IgG4 antibody concentrations. High dosages of allergen were more effective while mode of dosing up did not seem to matter. No change was seen in basophil reactivity. Conclusion: CD-sens and ABA, in contrast to basophil reactivity, seem to be promising tools to monitor protective immune responses initiated by ASIT. [ABSTRACT FROM AUTHOR]

Nonallergic rhinitis (NAR) can be defined as a chronic nasal inflammation which is not caused by systemic IgE-dependent mechanisms. It is common and probably affects far more than 200 million people worldwide. Both children and adults are affected. However, its exact prevalence is unknown and its phenotypes need to be evaluated using appropriate methods to better understand its pathophysiology, diagnosis and management. It is important to differentiate between infectious rhinitis, allergic/NAR and chronic rhinosinusitis, as management differs for each of these cases. Characterization of the phenotype, mechanisms and management of NAR represents one of the major unmet needs in allergic and nonallergic diseases. Studies on children and adults are required in order to appreciate the prevalence, phenotype, severity and co-morbidities of NAR. These studies should compare allergic and NAR and consider different age group populations including elderly subjects. Mechanistic studies should be carried out to better understand the disease(s) and risk factors and to guide towards an improved diagnosis and therapy. These studies need to take the heterogeneity of NAR into account. It is likely that neuronal mechanisms, T cells, innate immunity and possibly auto-immune responses all play a role in NAR and may also contribute to the symptoms of allergic rhinitis. [ABSTRACT FROM AUTHOR]

Background Allergic rhinitis (AR) is an inflammatory reaction not confined to a single local compartment, but rather involving the whole airway system. Allergens known to induce AR are not always the sole trigger of the inflammatory reaction as infections and organic dust might also cause exacerbations of rhinitis and associated conditions. Objective To examine the effects of intranasal lipopolysaccharide (LPS) exposure, as a surrogate for upper airway bacterial infections, in patients with symptomatic AR. Methods Fourteen patients with a history of moderate to severe pollen-induced AR were challenged intranasally with LPS. After 3–6 weeks, the same patients were challenged again, first with allergen and 24 h later with LPS. Nasal symptom scores, nasal lavage leucocyte counts and nasal airway resistance were assessed at 6–24 h after each provocation along with measurements of nitric oxide (NO) levels in the nose and lung. Results Six hours after the LPS challenge, an increased level of leucocytes could be obtained in the lavage fluid, but no symptoms were experienced and no increase in nasal resistance could be recorded. The NO production in the upper and lower airways was similar before and 6 h after the provocation. In contrast, in patients exposed to pollen before the LPS challenge, both the nasal and the pulmonary NO levels were enhanced. This was accompanied by an increase in leucocytes. Conclusion The present study demonstrates a priming effect of allergen on the nasal response to LPS as well as the presence of a systemic link between airway mucosal sites in the upper and lower airways. This suggests that exogenously derived signals, like upper airway infections, can interfere with the initiation, maintenance and progression of asthma. [ABSTRACT FROM AUTHOR]

Background: Decreased levels of the anti-inflammatory Clara Cell Protein 16 (CC16) are found in intermittent allergic rhinitis (IAR) and asthma. In asthma this decrease has been associated with hyperreactivity and the A38G single nucleotide polymorphism (SNP). The aim of this study was to examine if IAR is associated with signs and symptoms of rhinitis and the A38G SNP. Methods: Nasal fluid CC16 was analyzed in 20 patients with IAR before allergen challenge and 1 and 6 h after challenge, and from 28 healthy controls. The A38G SNP was analyzed in 80 patients with IAR and 106 controls. Nasal biopsies were obtained from three subjects in each group for immunohistochemical analysis of CC16. Results: In the allergen-challenged patients symptoms and rhinoscopic signs of rhinitis increased after 1 h and normalized after 6 h. In contrast, nasal fluid CC16 decreased 1 h after allergen challenge and returned to baseline after 6 h. Nasal fluid CC16 levels did not differ from controls before and 6 h after challenge. Immunohistochemical investigation showed intense CC16 staining in the nasal epithelium of both patients before season and healthy controls, but weak staining in symptomatic patients during season. No significant association between the A38G SNP and IAR was found. Conclusion: There was an inverse relation between nasal fluid CC16 levels and symptoms and signs of rhinitis in allergen-challenged patients with IAR. However, there was no association between IAR and the A38G SNP. [ABSTRACT FROM AUTHOR]

Background: Monitoring of the allergen sensitivity of a patient is most important for optimal patient care and a basic prerequisite for immunomodulating treatment. The objective of this study was to investigate how basophil allergen sensitivity can be applied in the monitoring of anti-immunoglobulin E (IgE) treatment. Methods: Basophils from timothy grass pollen allergic patients were, by flow cytometry, analysed for allergen threshold sensitivity (CD-sens) by measuring CD63 up-regulation on CD203c-identified basophils. The results were compared with maximal percentage CD63 up-regulation at one allergen dose (CD-max), skin prick test end-point allergen titration, (SPT-sens), nasal provocation titration tests (nasal provocation titre) and serum IgE and IgE antibody concentrations. Results: There was a significant correlation ( r = 0.50, P = 0.01) between CD-sens and SPT-sens, CD-sens and the IgE antibody concentration in percentage of ‘total IgE’ (relative IgE antibody concentration) ( r = 0.72, P < 0.001) as well as between CD-sens and nasal provocation titre ( r = 0.54, P < 0.05) but, in contrast, CD-max did not correlate with any of the sensitization parameters, i.e. SPT-sens, nasal provocation titre, absolute and relative IgE antibody concentration or CD-sens. CD-sens could be used to monitor omalizumab treatment efficacy while, based on CD-max, four of seven symptom-free patients on omalizumab would have been classified as having ongoing allergy. Conclusions: CD-sens seems to be very useful for the determination of a patient's allergen sensitivity and should be evaluated for the measurement and monitoring of anti-IgE treatment efficacy. CD-max, the conventional approach to basophil allergen challenge, which mirrors cell reactivity, gives incorrect information. [ABSTRACT FROM AUTHOR]

Background In allergic diseases, eosinophils in affected tissues release granule proteins with cytotoxic, immunoregulatory, and remodelling-promoting properties. From recent observations, it may be assumed that eosinophils degranulate already in circulating blood. If degranulation occurs in the circulation, this could contribute to widespread systemic effects and provide an important marker of disease. Objective To determine the degranulation status of circulating eosinophils in common allergic diseases. Methods Using a novel approach of whole blood fixation and leucocyte preparation, the granule morphology of blood eosinophils from healthy subjects, non-symptomatic patients, symptomatic patients with asthma, asthma and Churg–Strauss syndrome, allergic rhinitis, and atopic dermatitis was evaluated by transmission electron microscopy (TEM) and eosinophil peroxidase (TEM) histochemistry. Plasma and serum levels of eosinophil cationic protein were measured by fluoroenzymeimmunoassay. Selected tissue biopsies were examined by TEM. Results Regardless of symptoms, circulating eosinophils from allergic patients showed the same granule morphology as cells from healthy subjects. The majority of eosinophil-specific granules had preserved intact electron-density (96%; range: 89–98%), while the remaining granules typically exhibited marginal coarsening or mild lucency of the matrix structure. Abnormalities of the crystalline granule core were rarely detected. Furthermore, granule matrix alterations were not associated with any re-localization of intracellular EPO or increase in plasma eosinophil cationic protein. By contrast, eosinophils in diseased tissues exhibited cytolysis (granule release through membrane rupture) and piecemeal degranulation (loss of granule matrix and core structures). Conclusion In symptomatic eosinophilic diseases, circulating blood eosinophils retain their granule contents until they have reached their target organ. [ABSTRACT FROM AUTHOR]

Intermittent allergic rhinitis (IAR) results from interactions between a large number of pro- and anti-inflammatory mediators. Little is known about anti-inflammatory mediators in IAR. DNA microarrays allow simultaneous analysis of the whole transcriptome in a sample.To identify anti-inflammatory transcripts in nasal fluid cells from patients with IAR during season and from healthy controls.Nasal lavage fluids were obtained from 15 patients with symptomatic birch/and or grass pollen-induced IAR and 28 healthy controls. RNA was extracted from the nasal fluid cells and pooled into one patient- and one control pool. These were analysed with DNA microarrays containing more than 44 927 genes and variants.Seventeen thousand three hundred and fifty three genes were expressed in the controls and 17 928 in the patients. One thousand five hundred and seventy nine of the genes had higher expression in patients than in controls, and 1570 had lower expression in patients. Out of 189 up-regulated inflammatory genes, 187 were pro-inflammatory and two were anti-inflammatory. These genes regulated key steps of inflammation, ranging from influx of leukocytes to immunoglobulin production. By comparison, out of 49 down-regulated inflammatory genes, 36 were pro-inflammatory and 13 were anti-inflammatory. The anti-inflammatory gene that decreased most in expression in the patients was uteroglobin (also known as Clara Cell protein 16, CC16). The nasal fluid concentrations of uteroglobin protein were significantly lower in patients than in controls, 5.43±1.53 and 12.93±2.53 ng/mL, respectively (P<0.05).IAR is associated with decreased expression of uteroglobin and other anti-inflammatory genes. [ABSTRACT FROM AUTHOR]

Glucocorticoids are effective drugs for controlling symptoms and airway inflammation in respiratory diseases such as asthma and chronic obstructive pulmonary disease. However, the mechanisms behind their effects are not fully understood. We have recently demonstrated that prolonged exposure to the pro-inflammatory mediator tumour necrosis factor-α (TNF-α) markedly enhanced contractile responses to des-Arg9-bradykinin (selective bradykinin B1 receptor agonist) and bradykinin (selective bradykinin B2 receptor agonist) in murine airways. This increase was paralleled with elevated mRNA levels for bradykinin B1 and B2 receptors, a process involving intracellular mitogen-activated protein kinase pathways.To investigate the effects of glucocorticoids on the TNF-α up-regulated bradykinin B1 and B2 receptor response.Tracheal segments from BALB/c J mice were cultured with and without TNF-α, in the absence and presence of the transcriptional inhibitor actinomycin D or the glucocorticoid, dexamethasone. The contractile response induced by des-Arg9-bradykinin and bradykinin was subsequently assessed in a myograph system and mRNA for bradykinin B1 and B2 receptors was quantified using real-time polymerase chain reaction.Actinomycin D abolished and dexamethasone concentration-dependently suppressed the TNF-α-induced enhancement of the des-Arg9-bradykinin and bradykinin responses. This was paralleled by a reduction of the mRNA expression for the bradykinin B1 and B2 receptors.The presented data suggests the involvement of transcriptional mechanisms in the up-regulation of bradykinin B1 and B2 receptors during asthmatic airway inflammation, as well as in their down-regulation following glucocorticoid treatment. [ABSTRACT FROM AUTHOR]

TheMoraxellaimmunoglobulin (Ig) D-binding protein (MID) induces a strong proliferative response in human peripheral blood IgD+ B cells from adults isolated by positive selection using anti-CD19-conjugated microbeads. Here, we show that tonsillar B cells from children isolated with positive selection are unable to respond to MID stimulation. The proliferative response was very low or absent at various concentrations of MID tested and at different time points analysed, whereas the MID response of tonsillar B cells from adults isolated with positive selection was considerably higher. Tonsillar B cells from children isolated with positive selection responded to formalin-fixed preparations ofMoraxella catarrhalisandStaphylococcus aureusCowan strain I. In comparison to cells isolated with positive selection, a much higher proliferative response was recorded in tonsillar B cells from children isolated with negative selection, indicating that occupation of the CD19 molecule (i.e. positive selection) inhibited the response. Indeed, the addition of anti-CD19 monoclonal antibodies (MoAb) to MID-activated tonsillar B cells from children isolated with negative selection strongly inhibited the proliferative response. In contrast, anti-CD21 MoAb at the same concentration did only show a minor inhibition on the MID-induced response. Pre-incubation of tonsillar B cells isolated from children with anti-CD19 or anti-CD21 MoAb did not affect the binding of biotin-conjugated MID as analysed by flow cytometry. These results suggest that MID-activated tonsillar B cells from children have a strong requirement for signalling through the CD19 molecule. Future experiments will further reveal the importance of CD19 and possibly other molecules for optimal activation of tonsillar B cells isolated from both children and adults. [ABSTRACT FROM AUTHOR]

Asthma is a chronic airway disease, known to involve several inflammatory mediators. Little is known about how these mediators interact in order to produce or attenuate even basic features of the disease, like airway hyper-reactivity and remodelling. Endothelin-1 (ET-1) and IL-1β are two mediators suggested to play important roles in the induction of airway inflammation. To investigate the interactions between ET-1 and IL-1β, using a novel in vitro model of asthma, focusing on airway smooth muscle contractility. Isolated murine tracheal segments were cultured from 1 to 8 days in the absence and presence of IL-1β. The subsequent contractile responses to sarafotoxin 6c (S6c) (selective agonist for ETB receptor) and sarafotoxin 6b (S6b) (ETA and ETB receptor agonist) were recorded by a myographs system. In all experiments, ETB receptors were desensitized before the contractile response to S6b was recorded. Thus, the response to S6b is only mediated by ETA receptors in the present study. The mRNA expressions for ET-1 and endothelin (ET) receptors were quantified by real-time PCR. Organ culture in the presence of IL-1β attenuated the maximal contraction induced by S6c, but not S6b. This reduction was concentration-dependent and was significant after 2, 4 and 8 days of culture. To investigate the mechanisms behind this, inhibitors for endothelin converting enzyme (ECE) phosphoramidon, c-JUN N-terminal kinase (JNK) SP600125, extracellular-signal-regulated kinase 1/2(ERK 1/2) PD98059 and p38 pathway SB203580 were used. Individually, SP600125 and PD98059, but not SB203580, could partly reverse the reduction induced by IL-1β. An additional effect was obtained when SP600125 and PD98059 were combined. The mRNA expressions for ET-1 and ETB receptor were up- and down-regulated, respectively, by IL-1β. Presence of IL-1β in the airways attenuate the contractile response mediated via ETB receptors, an effect dependent on ECE, JNK and ERK 1/2 pathways. [ABSTRACT FROM AUTHOR]

IL-4 is believed to play a role in asthma and chronic obstructive pulmonary disease through promotion of eosinophilic inflammation and mucus hypersecretion. Whether IL-4 can induce a direct effect on airway smooth muscle remains unknown. To investigate the effect of IL-4 on airway smooth muscle, focusing on the contractile response to des-Arg9-bradykinin and bradykinin. Tracheal segments from murine airways were cultured for 1–8 days in the absence and presence of IL-4. The smooth muscle response induced by des-Arg9-bradykinin and bradykinin was investigated in myographs. Expression levels for the IL-4-, bradykinin B1- and B2-receptors were characterized using RT-PCR. Specific inhibitors were used to study signal changes along the IL-4 receptor- (IL-4R-) coupled mitogen-activated protein (MAP) kinase (MAPK) pathways. IL-4 treatment increased the contractile response to des-Arg9-bradykinin and bradykinin in a concentration- and time-dependent manner. Dexamethasone and the transcriptional inhibitor actinomycin D blocked this effect. c-Jun N-terminal kinase inhibitor SP600125 also blocked the effect of both des-Arg9-bradykinin and bradykinin, whereas p38 inhibitor SB203580 blocked only the former and the MAPKK inhibitor PD098059, only the latter agonist responses. IL-4 treatment increased the mRNA levels representing bradykinin B1- but not B2-receptors. Levels of IL-4R were not altered during culture. Long-term exposure to IL-4 increases the contractile response induced by des-Arg9-bradykinin and bradykinin in cultured murine airways. This effect appears to be mediated via an up-regulation of B1-receptors and altered signalling along the MAPK pathways. [ABSTRACT FROM AUTHOR]

Asthma is a chronic inflammatory disease characterized by airway hyper-responsiveness. Alterations in the neurogenic control are believed to contribute to the pathogenesis. Yet, the long-term interaction between nerves and inflammatory mediators, such as the neurotrophin nerve growth factor (NGF), are not fully understood much due to the absence of appropriate experimental assays. To develop an ex vivo mouse organ culture assay and to investigate the effects of NGF on nerve-mediated airway contractions. Mouse tracheal segments were cultured in periods of up to 16 days. Their contractile responses to electric field stimulation (EFS) were investigated. In addition, the effect of 4 days of NGF treatment was analysed using EFS and immunohistochemistry. EFS (0.2–25.6 Hz) induced reproducible and frequency-dependent cholinergic contractions of both fresh and cultured tracheal segments. The main part of the EFS response was blocked by tetrodotoxin or atropine. After 4 days in culture, regional differences appeared, with stronger EFS responses in distal than in proximal segments. More nerve fibres were seen in distal segments than in proximal segments. Treatment with NGF during 4 days of culture increased the innervation of the proximal segments, at the same time as the cholinergic contractile responses to EFS were enhanced dose-dependently. Culture of tracheal segments appears to be a suitable assay for the examination of long-term effects induced by inflammatory mediators on neurally mediated airway contractions. NGF treatment enhanced the cholinergic, nerve-dependent contractions and increased the amount of nerve fibres seen in the murine tracheal segments, suggesting a role for NGF in the development of airway hyper-responsiveness. [ABSTRACT FROM AUTHOR]

Presents an overview of the DNA microarray technology and applications in allergy research. Basic principle of microarrays; Identification of new genes and disease mechanisms; Use to search for DNA polymorphism.

Background: Increased levels of allergen-reactive immunoglobulins (Igs) have been reported in nasal fluids from patients with intermittent allergic rhinitis (IAR) sensitive to ragweed and grass. The aims of this study were to make a detailed characterization of nasal fluid Igs in birch pollen-induced IAR. Methods: Nasal fluids were obtained from 23 patients with birch pollen-induced IAR during and after the birch pollen season, and from 20 healthy controls. Nasal fluid total and Bet v 1-reactive (IgA), IgE and IgG as well as albumin were analyzed by immunoassays. The integrity of IgA and IgG, and the molecular form of IgA were assessed by Western blotting and column fractionation, respectively. Results: Nasal fluid total IgE and IgG, but not IgA, were higher in patients compared with controls. Western blotting indicated no significant degradation of IgA (including S-IgA) and IgG. Most of the IgA, including Bet v 1-reactive antibodies, was of the secretory form and of the IgA1 subclass. Bet v 1-reactive IgA and IgG were present in all patients, but was mostly nondetectable in controls. No significant differences in the levels of Bet v 1-reactive IgA and IgG were found in patients during the birch pollen season compared with off season. Both Bet v 1 and Bet v 2-reactive IgE were nondetectable in most samples. Conclusions: Nasal fluid Bet v 1-reactive IgA and IgG were found in all patients with birch pollen-induced IAR, but not in controls. However, no significant differences were found between patients during and after the birch pollen season. [ABSTRACT FROM AUTHOR]

Background: Carbon monoxide (CO), is an endogenously produced gas, generated by the rate-limiting enzyme heme oxygenase (HO), present in man throughout the respiratory tract. CO can elicit important physiological responses like bronchial relaxation and vasodilation. Both HO expression and CO levels in the airways increase in response to hypoxic challenge and to a wide variety of inflammatory stimuli, such as intermittent allergic rhinitis, asthma and upper respiratory tract infections. A role for CO in airway regulation and inflammation has therefore been suggested. However, information about CO-induced effects on cells involved in airway inflammation is scarce. The present study was designed to investigate if the HO substrate analog hemin could affect neutrophil random migration, and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) induced chemotaxis. Methods: Hemin was added to and incubated with whole blood and the effects of the anticipated CO production were then evaluated on isolated neutrophils using a chemotaxis chamber. Results: A biphasic dose–response curve emerged for both the neutrophil spontaneous random migration and the fMLP-induced chemotaxis. Low concentrations of hemin (10-11 m to 10 -9 m) enhanced the migratory response, whereas higher concentrations (10 -7 m and 10 -5 m) inhibited migration. The inhibition induced by hemin on fMLP-induced migration was abolished after pre-treatment with Rp-8Br-cyclicGMPS, an inhibitor of cyclicGMP. Conclusions: The present data indicate that endogenously produced CO can affect both spontaneous and stimulated neutrophil migration, partly via a cyclicGMP-related process, hence strengthening the idea of a role for CO in airway inflammation. [ABSTRACT FROM AUTHOR]

Background: Neutrophils are signaled to sites of infection and inflammation by different chemotactic stimuli. In order to reach the airways they have to adhere to, and then migrate through, the endothelium of pulmonary vessels. Carbon monoxide (CO) is a gaseous mediator, endogenously produced in the human airways. Increased CO production has been demonstrated during airway inflammation and CO as well as hemin, a substrate for CO producing enzymes, has been shown to affect neutrophil migration. Our objective was to investigate if the neutrophil cell surface expression of CD11b, CD66b and CD63 was changed during intermittent allergic rhinitis and to establish whether CO could affect the expression of these markers of cellular activation. Methods: Blood from 10 healthy volunteers was drawn and incubated with different concentrations of hemin. Blood from 12 other healthy volunteers and from 12 patients with intermittent allergic rhinitis was also drawn during grass pollen season. Neutrophils were then isolated from all these three sets, and their expression of CD antigens measured using flow cytometry. Results: Patients with symptomatic intermittent allergic rhinitis exhibited lower levels of CD11b and CD66b on the neutrophil cell surface. Incubation with hemin decreased the expression of CD11b and CD66b. CD63 was generally weakly expressed and not significantly affected by hemin incubation. Conclusion: Our results demonstrate that expressions of neutrophil cell surface glycoproteins are changed during the season in patents with intermittent allergic rhinitis and that hemin, a substrate for CO production, may act as an inhibitor of neutrophil activation. This indicates a possible role for CO in the immune defense system. Background: Neutrophils are signaled to sites of infection and inflammation by different chemotactic stimuli. In order to reach the airways they have to adhere to, and then migrate through, the endothelium of pulmonary vessels. Carbon monoxide (CO)... [ABSTRACT FROM AUTHOR]

Studies cytokines and their receptors in allergic rhinitis, with special reference to the Th2 hypothesis. Effect of antigen-presenting cells on proliferation of Th2 cells; Pathogenetic mechanisms in allergic rhinitis; Causal roles of cytokines in allergic rhinitis.

Examines the role of nitric oxide (NO) in leukotriene B4- (LTB4) stimulated nasal secretion. Instillation of LTB4; Inhibition of NO synthase; Prevention of LTB4-induced neutrophil recruitment.

Background Allergic rhinitis is a common disease characterized by infiltration of eosinophils into the nasal mucosa during the periods of symptoms. Among chemokines, which attract cells to the site of inflammation, eotaxin is relatively specific for eosinophils. Objective We examined the influence of grass pollen season on nasal eotaxin expression in patients with seasonal allergic rhinitis, as well as the effect of a nasal glucocorticoid on this eotaxin expression. Methods Nineteen patients with allergic rhinitis received treatment with either nasal beclomethasone (400 μg/day) or placebo over a grass pollen season. In these patients, nasal biopsies were taken prior to and during the peak of the pollen season and stained immunohistochemically for eotaxin and EG2 + eosinophils. Five healthy subjects served as controls and gave nasal biopsies once prior to the pollen season. Results Prior to pollen season, there was no significant difference in nasal eotaxin expression between patients with allergic rhinitis and healthy subjects. Grass pollen season induced significant increase in eotaxin expression in placebo-treated (P = 0.04; n = 9) but not in beclomethasone-treated rhinitis patients (P = 0.8; n = 10). During peak grass pollen season, the eotaxin expression in placebo-treated patients was significantly higher compared with healthy subjects outside season (P = 0.03). There was no significant correlation between the expression of eotaxin and the number of EG2 + eosinophils in nasal mucosa. The serum levels of eotaxin in rhinitis patients remained stable over the pollen season. Conclusion Expression of eotaxin in nasal mucosa of grass-pollen allergic rhinitis patients is upregulated during pollen season and treatment with a nasal glucocorticoid protects against this upregulation. [ABSTRACT FROM AUTHOR]

Methods and Results A method for isolating and superfusing a segment of the nasal cavity in the anesthetized dog was developed. Introduction of Pseudmnonas aeruginosa supernatant (PA), which is known to induce IL-8 release, resulted in a marked time-dependent exponential increase in neutrophil recruitment to the nasal chamber. When oxymetazoline (final concentration, 10-5 M), was added to the superfusate, the PA induced-neutrophil migration was inhibited: the addition of benzalchonial chloride to the superfusate had no effect on the PA induced-neutrophil migration. Conclusion We conclude that a α2 adrenoceptor agonist profoundly inhibits neutrophil migration in response to bacterial products. Our novel method allows continuous introduction of stimuli and monitoring of responses in the nasal mucosa. [ABSTRACT FROM AUTHOR]

Presents several abstracts on nasal inflammation presented during the 20th Nordic Congress of Allergology in Oslo, Norway. 'Sildenafil (Viagra) Increases Exhaled Nitric Oxide,' by J.S. Haight, W. Qian, A. Graciano, H. Furlott, P. McClean, N. Zamel, P. Cole; 'Carbon Monoxide, A Role in Rhinitis,' by L.O. Cardell.

Background Carbon monoxide (CO) has emerged as an endogenously produced gaseous mediator known to be involved in bronchial smooth muscle regulation. Increased amounts of CO have been found in exhaled air during asthma and lower airway inflammation. Recently CO has been shown to be produced in the nasal airways, but there are no reports of altered CO levels in nasal airways during inflammation. Objective This study was designed to investigate if CO levels increase in the human nasal airways during inflammatory conditions, such as allergy and upper airway respiratory tract infection (URTI). Methods CO was sampled separately from the upper and lower airways of 13 healthy control subjects, six patients with a history of allergic rhinitis and six patients with URTI. Results Nasal CO levels were increased in subjects with allergic rhinitis, compared to healthy controls (2.07 ± 0.15 ppm, n = 6 and 1.62 ± 0.08 ppm, n = 13, respectively, P < 0.01). CO levels were also increased in patients with URTI, compared to the same controls (1.92 ± 0.09 ppm, n = 6, P < 0.05). Normal levels of CO were found in air from the lower airways among subjects with allergic rhinitis, whereas corresponding levels in the URTI patients were increased. Conclusion The present data demonstrates that upper airway CO levels increase in parallel with different inflammatory stimuli, such as allergy and infection, suggesting a role for CO as marker or mediator of nasal inflammation. [ABSTRACT FROM AUTHOR]

Background Allergic rhinitis results from interactions between a large number of cells and mediators in different compartments of the body. DNA microarrays allow simultaneous measurement of expression of thousands of genes in the same tissue sample. Objective To study gene expression in nasal mucosal biopsies from patients with allergic rhinitis using DNA micro-arrays. Methods Nasal biopsies were obtained from 14 patients with symptomatic birch pollen-induced allergic rhinitis and five healthy controls. RNA was extracted from the biopsies and pooled into one patient pool and one control pool. These were analysed in duplicate with DNA micro-arrays containing more than 12 000 known genes. Results Approximately half of the genes were expressed in the patient and control samples. Guided by the current literature we chose 32 genes of possible relevance to allergic airway inflammation and investigated their relative expression. Among these, transcripts encoding immunoglobulins and their receptors were most abundant. The expression of cytokines and growth factors was low, whereas their corresponding receptors and cell surface markers displayed higher expression levels. IgA had the highest expression of all 12 626 genes. RT-PCR showed that IgA1 was the predominant subclass. This was confirmed by the protein level in nasal fluids. Allergen-specific IgA was significantly higher in patients than in controls and correlated significantly with eosinophil granulae proteins. Conclusion DNA micro-array analysis can be used to identify genes of possible relevance to allergic airway inflammation. In this study, the expression profile in the nasal mucosa was quantitatively dominated by immunoglobulins, particularly IgA. Protein analyses in nasal fluids indicated a role for allergen-specific IgA in eosinophil degranulation. [ABSTRACT FROM AUTHOR]