The Impact of Allergic Rhinitis and Asthma on Human Nasal and Bronchial Epithelial Gene Expression

Background

The link between upper and lower airways in patients with both asthma and allergic rhinitis is still poorly understood. As the biological complexity of these disorders can be captured by gene expression profiling we hypothesized that the clinical expression of rhinitis and/or asthma is related to differential gene expression between upper and lower airways epithelium.

Objective

Defining gene expression profiles of primary nasal and bronchial epithelial cells from the same individuals and examining the impact of allergic rhinitis with and without concomitant allergic asthma on expression profiles.

Methods

This cross-sectional study included 18 subjects (6 allergic asthma and allergic rhinitis; 6 allergic rhinitis; 6 healthy controls). The estimated false discovery rate comparing 6 subjects per group was approximately 5%. RNA was extracted from isolated and cultured epithelial cells from bronchial brushings and nasal biopsies, and analyzed by microarray (Affymetrix U133+ PM Genechip Array). Data were analysed using R and Bioconductor Limma package. For gene ontology GeneSpring GX12 was used.

Results

The study was successfully completed by 17 subjects (6 allergic asthma and allergic rhinitis; 5 allergic rhinitis; 6 healthy controls). Using correction for multiple testing, 1988 genes were differentially expressed between healthy lower and upper airway epithelium, whereas in allergic rhinitis with or without asthma this was only 40 and 301 genes, respectively. Genes influenced by allergic rhinitis with or without asthma were linked to lung development, remodeling, regulation of peptidases and normal epithelial barrier functions.

Conclusions

Differences in epithelial gene expression between the upper and lower airway epithelium, as observed in healthy subjects, largely disappear in patients with allergic rhinitis with or without asthma, whilst new differences emerge. The present data identify several pathways and genes that might be potential targets for future drug development.     

Does Pet Ownership in Infancy Lead to Asthma or Allergy at School Age? Pooled Analysis of Individual Participant Data from 11 European Birth Cohorts

Objective

To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6–10 years.

Design

Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s.

Exposure definition

Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life.

Outcome definition

Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6–10 years of age.

Data synthesis

Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models.

Results

We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with “no pets” (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I² = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with “no pets” (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I² = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to “no pets” resulted in an odds ratio of 1.04 (0.59 to 1.84) (I² = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens.

Conclusions

Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6–10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.     

Prevalence of Asthma and Allergic Rhinitis among Adults in Yaounde,Cameroon

Background

Population-based estimates of asthma and allergic rhinitis in sub-Saharan African adults are lacking. We assessed the prevalence and determinants of asthma and allergic rhinitis in urban adult Cameroonians.

Methods

A community-based survey was conducted from December 2013 to April 2014 among adults aged 19 years and above (N = 2,304, 57.3% women), selected through multilevel stratified random sampling across all districts of Yaounde (Capital city). Internationally validated questionnaires were used to investigate the presence of allergic diseases. Logistic regressions were employed to investigate the determinants of allergic conditions.

Results

Prevalence rates were 2.7% (95% CI: 2.1-3.4) for asthma-ever, 6.9% (5.9-7.9) for lifetime wheezing, 2.9% (92.2-3.6) for current wheezing and 11.4% (10.1-12.7) for self-reported lifetime allergic rhinitis; while 240 (10.4%) participants reported current symptoms of allergic rhinitis, and 125 (5.4%) had allergic rhino-conjunctivitis. The prevalence of current asthma medication use and self-reported asthma attack was 0.8 (0.4-1.2) and 1 (0.6-1.4) respectively. Multivariable adjusted determinants of current wheezing were signs of atopic eczema [2.91 (1.09-7.74)] and signs of allergic rhinitis [3.24 (1.83-5.71)]. Age group 31-40 years [0.27(0.09-0.78), p = 0.016] was an independent protective factor for wheezing. Determinants of current rhinitis symptoms were active smoking [2.20 (1.37-3.54), p<0.001], signs of atopic eczema [2.84 (1.48-5.46)] and current wheezing [3.02 (1.70-5.39)].

Conclusion

Prevalence rates for asthma and allergic rhinitis among adults in this population were at the lower tails of those reported in other regions of the world. Beside the classical interrelation between allergic diseases found in this study, active smoking was an independent determinant of allergic rhinitis symptoms. Nationwide surveys are needed to investigate regional variations.     

Increased prevalence of symptoms of rhinitis but not of asthma between 1990 and 2008 in Swedish adults: comparisons of the ECRHS and GA²LEN surveys

Background

The increase in asthma prevalence until 1990 has been well described. Thereafter, time trends are poorly known, due to the low number of high quality studies. The preferred method for studying time trends in prevalence is repeated surveys of similar populations. This study aimed to compare the prevalence of asthma symptoms and their major determinants, rhinitis and smoking, in Swedish young adults in 1990 and 2008.

Methods

In 1990 the European Community Respiratory Health Survey (ECRHS) studied respiratory symptoms, asthma, rhinitis and smoking in a population-based sample (86% participation) in Sweden. In 2008 the same symptom questions were included in the Global Allergy and Asthma European Network (GA²LEN) survey (60% participation). Smoking questions were however differently worded. The regions (Gothenburg, Uppsala, Umeå) and age interval (20–44 years) surveyed both in 1990 (n = 8,982) and 2008 (n = 9,156) were analysed.

Results

The prevalence of any wheeze last 12 months decreased from 20% to 16% (p<0.001), and the prevalence of “asthma-related symptoms” was unchanged at 7%. However, either having asthma attacks or using asthma medications increased from 6% to 8% (p<0.001), and their major risk factor, rhinitis, increased from 22% to 31%. Past and present smoking decreased.

Conclusion

From 1990 to 2008 the prevalence of obstructive airway symptoms common in asthma did not increase in Swedish young adults. This supports the few available international findings suggesting the previous upward trend in asthma has recently reached a plateau. The fact that wheeze did not increase despite the significant increment in rhinitis, may at least in part be due to the decrease in smoking.     

Differences in allergen-induced T cell activation between allergic asthma and rhinitis: Role of CD28, ICOS and CTLA-4

Background

Th2 cell activation and T regulatory cell (Treg) deficiency are key features of allergy. This applies for asthma and rhinitis. However with a same atopic background, some patients will develop rhinitis and asthma, whereas others will display rhinitis only. Co-receptors are pivotal in determining the type of T cell activation, but their role in allergic asthma and rhinitis has not been explored. Our objective was to assess whether allergen-induced T cell activation differs from allergic rhinitis to allergic rhinitis with asthma, and explore the role of ICOS, CD28 and CTLA-4.

Methods

T cell co-receptor and cytokine expressions were assessed by flow cytometry in PBMC from 18 house dust mite (HDM) allergic rhinitics (R), 18 HDM allergic rhinitics and asthmatics (AR), 13 non allergic asthmatics (A) and 20 controls, with or without anti-co-receptors antibodies.

Results

In asthmatics (A+AR), a constitutive decrease of CTLA-4+ and of CD4+CD25+Foxp3+ cells was found, with an increase of IFN-γ+ cells. In allergic subjects (R + AR), allergen stimulation induced CD28 together with IL-4 and IL-13, and decreased the proportion of CTLA-4+, IL-10+ and CD4+CD25+Foxp3+ cells. Anti-ICOS and anti-CD28 antibodies blocked allergen-induced IL-4 and IL-13. IL-13 production also involved CTLA-4.

Conclusions

T cell activation differs between allergic rhinitis and asthma. In asthma, a constitutive, co-receptor independent, Th1 activation and Treg deficiency is found. In allergic rhinitis, an allergen-induced Treg cell deficiency is seen, as well as an ICOS-, CD28- and CTLA-4-dependent Th2 activation. Allergic asthmatics display both characteristics.     

Consumption of Artificially-Sweetened Soft Drinks in Pregnancy and Risk of Child Asthma and Allergic Rhinitis

Background

Past evidence has suggested a role of artificial sweeteners in allergic disease; yet, the evidence has been inconsistent and unclear.

Objective

To examine relation of intake of artificially-sweetened beverages during pregnancy with child asthma and allergic rhinitis at 18 months and 7 years.

Methods

We analyzed data from 60,466 women enrolled during pregnancy in the prospective longitudinal Danish National Birth Cohort between 1996 and 2003. At the 25th week of gestation we administered a validated Food Frequency Questionnaire which asked in detail about intake of artificially-sweetened soft drinks. At 18 months, we evaluated child asthma using interview data. We also assessed asthma and allergic rhinitis through a questionnaire at age 7 and by using national registries. Current asthma was defined as self-reported asthma diagnosis and wheeze in the past 12 months. We examined the relation between intake of artificially-sweetened soft drinks and child allergic disease outcomes and present here odds ratios with 95% CI comparing daily vs. no intake.

Results

At 18 months, we found that mothers who consumed more artificially-sweetened non-carbonated soft drinks were 1.23 (95% CI: 1.13, 1.33) times more likely to report a child asthma diagnosis compared to non-consumers. Similar results were found for child wheeze. Consumers of artificially-sweetened carbonated drinks were more likely to have a child asthma diagnosis in the patient (1.30, 95% CI: 1.01, 1.66) and medication (1.13, 95% CI: 0.98, 1.29) registry, as well as self-reported allergic rhinitis (1.31, 95% CI: 0.98, 1.74) during the first 7 years of follow-up. We found no associations for sugar-sweetened soft drinks.

Conclusion

Carbonated artificially-sweetened soft drinks were associated with registry-based asthma and self-reported allergic rhinitis, while early childhood outcomes were related to non-carbonated soft drinks. These results suggest that consumption of artificially-sweetened soft drinks during pregnancy may play a role in offspring allergic disease development.     

Effects of a dual CCR3 and H1-antagonist on symptoms and eosinophilic inflammation in allergic rhinitis

Background

The CC-chemokine receptor-3 (CCR3) has emerged as a target molecule for pharmacological intervention in allergic inflammation.

Objective

To examine whether a dual CCR3 and H₁-receptor antagonist (AZD3778) affects allergic inflammation and symptoms in allergic rhinitis.

Methods

Patients with seasonal allergic rhinitis were subjected to three seven days'' allergen challenge series. Treatment with AZD3778 was given in a placebo and antihistamine-controlled design. Symptoms and nasal peak inspiratory flow (PIF) were monitored in the morning, ten minutes post challenge, and in the evening. Nasal lavages were carried out at the end of each challenge series and α₂-macroglobulin, ECP, and tryptase were monitored as indices of allergic inflammation.

Results

Plasma levels of AZD3778 were stable throughout the treatment series. AZD3778 and the antihistamine (loratadine) reduced rhinitis symptoms recorded ten minutes post challenge during this period. AZD3778, but not the anti-histamine, also improved nasal PIF ten minutes post challenge. Furthermore, scores for morning and evening nasal symptoms from the last five days of the allergen challenge series showed statistically significant reductions for AZD3778, but not for loratadine. ECP was reduced by AZD3778, but not by loratadine.

Conclusions

AZD3778 exerts anti-eosinophil and symptom-reducing effects in allergic rhinitis and part of this effect can likely be attributed to CCR3-antagonism. The present data are of interest with regard to the potential use of AZD3778 in allergic rhinitis and to the relative importance of eosinophil actions to the symptomatology of allergic rhinitis.

Trial registration

EudraCT No: 2005-002805-21.     

Common household chemicals and the allergy risks in pre-school age children

Background

The risk of indoor exposure to volatile organic compounds (VOCs) on allergic airway diseases in children remains unknown.

Objective

We examined the residential concentrations of VOCs, emitted from building materials, paints, furniture, and other lifestyle practices and the risks of multiple allergic diseases as well as the IgE-sensitization in pre-school age children in Sweden.

Methods

In a case-control investigation (198 case children with asthma and allergy and 202 healthy controls), air samples were collected in the room where the child slept. The air samples were analyzed for the levels of eight classes of VOCs.

Results

A natural-log unit of summed propylene glycol and glycol ethers (PGEs) in bedroom air (equal to interquartile range, or 3.43 – 15.65 µg/m³) was associated with 1.5-fold greater likelihood of being a case (95% CI, 1.1 – 2.1), 1.5-fold greater likelihood of asthma (95% CI, 1.0 – 2.3), 2.8-fold greater likelihood of rhinitis (95% CI, 1.6 – 4.7), and 1.6-fold greater likelihood of eczema (95% CI, 1.1 – 2.3), accounting for gender, secondhand smoke, allergies in both parents, wet cleaning with chemical agents, construction period of the building, limonene, cat and dog allergens, butyl benzyl phthalate (BBzP), and di(2-ethylhexyl)phthalate (DEHP). When the analysis was restricted to the cases, the same unit concentration was associated with 1.8-fold greater likelihood of IgE-sensitization (95% CI, 1.1 – 2.8) compared to the non-IgE sensitized cases. No similar associations were found for the other classes of VOCs.

Conclusion

We propose a novel hypothesis that PGEs in indoor air exacerbate and/or induce the multiple allergic symptoms, asthma, rhinitis and eczema, as well as IgE sensitization respectively.     

Characterization of Rhinitis According to the Asthma Status in Adults Using an Unsupervised Approach in the EGEA Study

Background

The classification of rhinitis in adults is missing in epidemiological studies.

Objective

To identify phenotypes of adult rhinitis using an unsupervised approach (data-driven) compared with a classical hypothesis-driven approach.

Methods

983 adults of the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA) were studied. Self-reported symptoms related to rhinitis such as nasal symptoms, hay fever, sinusitis, conjunctivitis, and sensitivities to different triggers (dust, animals, hay/flowers, cold air…) were used. Allergic sensitization was defined by at least one positive skin prick test to 12 aeroallergens. Mixture model was used to cluster participants, independently in those without (Asthma-, n = 582) and with asthma (Asthma+, n = 401).

Results

Three clusters were identified in both groups: 1) Cluster A (55% in Asthma-, and 22% in Asthma+) mainly characterized by the absence of nasal symptoms, 2) Cluster B (23% in Asthma-, 36% in Asthma+) mainly characterized by nasal symptoms all over the year, sinusitis and a low prevalence of positive skin prick tests, and 3) Cluster C (22% in Asthma-, 42% in Asthma+) mainly characterized by a peak of nasal symptoms during spring, a high prevalence of positive skin prick tests and a high report of hay fever, allergic rhinitis and conjunctivitis. The highest rate of polysensitization (80%) was found in participants with comorbid asthma and allergic rhinitis.

Conclusion

This cluster analysis highlighted three clusters of rhinitis with similar characteristics than those known by clinicians but differing according to allergic sensitization, and this whatever the asthma status. These clusters could be easily rebuilt using a small number of variables.     

Smoking in Asthma Is Associated with Elevated Levels of Corticosteroid Resistant Sputum Cytokines—An Exploratory Study

Background

Current cigarette smoking is associated with reduced acute responses to corticosteroids and worse clinical outcomes in stable chronic asthma. The mechanism by which current smoking promotes this altered behavior is currently unclear. Whilst cytokines can induce corticosteroid insensitivity in-vitro, how current and former smoking affects airway cytokine concentrations and their responses to oral corticosteroids in stable chronic asthma is unclear.

Objectives

To examine blood and sputum cytokine concentrations in never, ex and current smokers with asthma before and after oral corticosteroids.

Methods

Exploratory study utilizing two weeks of oral dexamethasone (equivalent to 40 mg/day prednisolone) in 22 current, 21 never and 10 ex-smokers with asthma. Induced sputum supernatant and plasma was obtained before and after oral dexamethasone. 25 cytokines were measured by multiplex microbead system (Invitrogen, UK) on a Luminex platform.

Results

Smokers with asthma had elevated sputum cytokine interleukin (IL) -6, -7, and -12 concentrations compared to never smokers with asthma. Few sputum cytokine concentrations changed in response to dexamethasone IL-17 and IFNα increased in smokers, CCL4 increased in never smokers and CCL5 and CXCL10 reduced in ex-smokers with asthma. Ex-smokers with asthma appeared to have evidence of an ongoing corticosteroid resistant elevation of cytokines despite smoking cessation. Several plasma cytokines were lower in smokers with asthma compared to never smokers with asthma.

Conclusion

Cigarette smoking in asthma is associated with a corticosteroid insensitive increase in multiple airway cytokines. Distinct airway cytokine profiles are present in current smokers and never smokers with asthma and could provide an explanatory mechanism for the altered clinical behavior observed in smokers with asthma.     

Association of serum Clara cell protein CC16 with respiratory infections and immune response to respiratory pathogens in elite athletes

Background

Respiratory epithelium integrity impairment caused by intensive exercise may lead to exercise-induced bronchoconstriction. Clara cell protein (CC16) has anti-inflammatory properties and its serum level reflects changes in epithelium integrity and airway inflammation. This study aimed to investigate serum CC16 in elite athletes and to seek associations of CC16 with asthma or allergy, respiratory tract infections (RTIs) and immune response to respiratory pathogens.

Methods

The study was performed in 203 Olympic athletes. Control groups comprised 53 healthy subjects and 49 mild allergic asthmatics. Serum levels of CC16 and IgG against respiratory viruses and Mycoplasma pneumoniae were assessed. Allergy questionnaire for athletes was used to determine symptoms and exercise pattern. Current versions of ARIA and GINA guidelines were used when diagnosing allergic rhinitis and asthma, respectively.

Results

Asthma was diagnosed in 13.3% athletes, of whom 55.6% had concomitant allergic rhinitis. Allergic rhinitis without asthma was diagnosed in 14.8% of athletes. Mean CC16 concentration was significantly lower in athletes versus healthy controls and mild asthmatics. Athletes reporting frequent RTIs had significantly lower serum CC16 and the risk of frequent RTIs was more than 2-fold higher in athletes with low serum CC16 (defined as equal to or less than 4.99 ng/ml). Athletes had significantly higher anti-adenovirus IgG than healthy controls while only non-atopic athletes had anti-parainfluenza virus IgG significantly lower than controls. In all athletes weak correlation of serum CC16 and anti-parainfluenza virus IgG was present (R = 0.20, p < 0.01). In atopic athletes a weak positive correlations of CC16 with IgG specific for respiratory syncytial virus (R = 0.29, p = 0.009), parainfluenza virus (R = 0.31, p = 0.01) and adenovirus (R = 0.27, p = 0.02) were seen as well.

Conclusions

Regular high-load exercise is associated with decrease in serum CC16 levels. Athletes with decreased CC16 are more susceptible to respiratory infections. Atopy may be an additional factor modifying susceptibility to infections in subjects performing regular high-load exercise.     

Control of allergic rhinitis and asthma test – a formal approach to the development of a measuring tool

Background

The concurrent management of allergic rhinitis and asthma (ARA) has been recommended by Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines. However, a tool capable of assessing simultaneously the control of upper and lower airways diseases is lacking.

Aim

To describe the studies conducted to design the control of ARA test (CARAT) questionnaire.

Methods

We performed a literature review to generate a list of potentially important items for the assessment of control of ARA. A formal consensus development process, that used an innovative web-based application, was designed – 111 experts in ARA and 60 patients participated. At the final consensus meeting, 25 primary and secondary care physicians formulated the questions and response options. A qualitative feasibility study (n = 31 patients) was conducted to evaluate the comprehensibility of the questionnaire while testing two different designs.

Results

Thirty-four potentially important items were identified. All the steps of the consensus process were completed in 2.5 months. The opinions of experts and patients lead to the formulation of 17 questions. At the feasibility study the instructions and wording problems were corrected and a semi-tabular format was chosen.

Conclusion

A tool to measure the control of allergic rhinitis and asthma was developed using a comprehensive set of methodological steps ensuring the design quality and the face and content validity. Additional validation studies to assess the psychometric properties of the questionnaire have started.     

Serum IgE reactivity profiling in an asthma affected cohort

Background

Epidemiological evidence indicates that atopic asthma correlates with high serum IgE levels though the contribution of allergen specific IgE to the pathogenesis and the severity of the disease is still unclear.

Methods

We developed a microarray immunoassay containing 103 allergens to study the IgE reactivity profiles of 485 asthmatic and 342 non-asthmatic individuals belonging to families whose members have a documented history of asthma and atopy. We employed k-means clustering, to investigate whether a particular IgE reactivity profile correlated with asthma and other atopic conditions such as rhinitis, conjunctivitis and eczema.

Results

Both case-control and parent-to-siblings analyses demonstrated that while the presence of specific IgE against individual allergens correlated poorly with pathological conditions, particular reactivity profiles were significantly associated with asthma (p<10E-09). An artificial neural network (ANN)-based algorithm, calibrated with the profile reactivity data, correctly classified as asthmatic or non-asthmatic 78% of the individual examined. Multivariate statistical analysis demonstrated that the familiar relationships of the study population did not affect the observed correlations.

Conclusions

These findings indicate that asthma is a higher-order phenomenon related to patterns of IgE reactivity rather than to single antibody reactions. This notion sheds new light on the pathogenesis of the disease and can be readily employed to distinguish asthmatic and non-asthmatic individuals on the basis of their serum reactivity profile.     

A non-human primate model for gluten sensitivity

Background and Aims

Gluten sensitivity is widespread among humans. For example, in celiac disease patients, an inflammatory response to dietary gluten leads to enteropathy, malabsorption, circulating antibodies against gluten and transglutaminase 2, and clinical symptoms such as diarrhea. There is a growing need in fundamental and translational research for animal models that exhibit aspects of human gluten sensitivity.

Methods

Using ELISA-based antibody assays, we screened a population of captive rhesus macaques with chronic diarrhea of non-infectious origin to estimate the incidence of gluten sensitivity. A selected animal with elevated anti-gliadin antibodies and a matched control were extensively studied through alternating periods of gluten-free diet and gluten challenge. Blinded clinical and histological evaluations were conducted to seek evidence for gluten sensitivity.

Results

When fed with a gluten-containing diet, gluten-sensitive macaques showed signs and symptoms of celiac disease including chronic diarrhea, malabsorptive steatorrhea, intestinal lesions and anti-gliadin antibodies. A gluten-free diet reversed these clinical, histological and serological features, while reintroduction of dietary gluten caused rapid relapse.

Conclusions

Gluten-sensitive rhesus macaques may be an attractive resource for investigating both the pathogenesis and the treatment of celiac disease.     

Patients with Asthma and Comorbid Allergic Rhinitis: Is Optimal Quality of Life Achievable in Real Life?

Objectives

Asthma trials suggest that patients reaching total disease control have an optimal Health Related Quality of Life (HRQoL). Moreover, rhinitis is present in almost 80% of asthmatics and impacts asthma control and patient HRQoL. We explored whether optimal HRQoL was reachable in a real-life setting, and evaluated the disease and patient related patterns associated to optimal HRQoL achievement.

Methods and Findings

Asthma and rhinitis HRQoL, illness perception, mood profiles, rhinitis symptoms and asthma control were assessed by means of validated tools in patients classified according to GINA and ARIA guidelines. Optimal HRQoL, identified by a Rhinasthma Global Summary (GS) score ≤20 (score ranging from 0 to 100, where 100 represents the worst possible HRQoL), was reached by 78/209 (37.32%). With the exception of age, no associations were found between clinical and demographic characteristics and optimal HRQoL achievement. Patients reaching an optimal HRQoL differed in disease perception and mood compared to those not reaching an optimal HRQoL. Asthma control was significantly associated with optimal HRQoL (χ² = 49.599; p<0.001) and well-controlled and totally controlled patients significantly differed in achieving optimal HRQoL (χ² = 7.617; p<0.006).

Conclusion

Approximately one third of the patients in our survey were found to have an optimal HRQoL. While unsatisfactory disease control was the primary reason why the remainder failed to attain optimal HRQoL, it is clear that illness perception and mood also played parts. Therefore, therapeutic plans should be directed not only toward achieving the best possible clinical control of asthma and comorbid rhinitis, but also to incorporating individualized elements according to patient-related characteristics.     

Spontaneous eosinophilic nasal inflammation in a genetically-mutant mouse: comparative study with an allergic inflammation model

Background

Eosinophilic inflammation is a hallmark of chronic rhinosinusitis with nasal polyps. To model this disease process experimentally, nasal sensitization of mice with ovalbumin or aspergillus has been described. Here, we describe a genetically mutant mouse that develops robust spontaneous nasal eosinophilic inflammation. These mice lack the enzyme SHP-1 that down-regulates the IL-4Rα/stat6 signaling pathway. We compared nasal inflammation and inflammatory mediators in SHP-1 deficient mice (mev) and an ovalbumin-induced nasal allergy model.

Methods

A novel technique of trans-pharyngeal nasal lavage was developed to obtain samples of inflammatory cells from the nasal passages of allergic and mev mice. Total and differential cell counts were performed on cytospin preparations. Expression of tissue mRNA for IL-4, IL-13, and mouse beta-defensin-1 (MBD-1) was determined by quantitative PCR. Eotaxin in the lavage fluid was assessed by ELISA.

Results

Allergic and mev mice had increased total cells and eosinophils compared with controls. Expression of IL-4 was similarly increased in both allergic and mev mice, but expression of IL-13 and eotaxin was significantly greater in the allergic mice than mev mice. Eotaxin was significantly up-regulated in both allergic rhinitis and mev mice. In both models of eosinophilic inflammation, down-regulation of the innate immune marker MBD-1 was observed.

Conclusions

The mev mice display spontaneous chronic nasal eosinophilic inflammation with potential utility for chronic rhinosinusitis with nasal polyps research. The eosinophilic infiltrate is more robust in the mev mice than allergic mice, but Th2 cytokine expression is not as pronounced. Decreased MBD-1 expression in both models supports the concept that Th2-cytokines down-regulate sinonasal innate immunity in humans, and suggests a role for mouse models in investigating the interaction between adaptive and innate immunity in the sinonasal mucosa.