Elevated levels of mannan-binding lectin [corrected] (MBL) and eosinophilia in patients of bronchial asthma with allergic rhinitis and allergic bronchopulmonary aspergillosis associate with a novel intronic polymorphism in MBL

Mannan-binding lectin (MBL), an important component of innate immunity, binds to a range of foreign antigens and initiates the lectin complement pathway. Earlier studies have reported high plasma MBL levels in allergic patients in comparison to healthy controls. In view of varied plasma MBL levels being determined by genetic polymorphisms in its collagen region, we investigated the association of single nucleotide polymorphisms (SNPs) in the collagen region of human MBL with respiratory allergic diseases. The study groups comprised patients of bronchial asthma with allergic rhinitis (n = 49) and allergic bronchopulmonary aspergillosis (APBA) (n = 11) and unrelated age-matched healthy controls of Indian origin (n = 84). A novel intronic SNP, G1011A of MBL, showed a significant association with both the patient groups in comparison to the controls (P < 0.01). Patients homozygous for the 1011A allele showed significantly higher plasma MBL levels and activity than those homozygous for the 1011G allele (P < 0.05). The 1011A allele also showed a significant correlation with high peripheral blood eosinophilia (P < 0.05) and low forced expiratory volume in 1 s (FEV(1)) (P < 0.05) of the patients. We conclude that the 1011A allele of MBL may contribute to elevated plasma MBL levels and activity and to increased severity of the disease markers in patients of bronchial asthma with allergic rhinitis and ABPA.     

Lack of association between ADAM33 gene and asthma in a Chinese population

Asthma is a complex polygenic disease with gene-environment interactions being important. It has been previously suggested that ADAM33, which is a member of a gene family that encodes membrane-anchored proteins with a disintegrin and a metalloprotease domain, is primarily expressed in lung fibroblasts and bronchial smooth muscle cells and has been associated with airway remodelling and bronchial hyperresponsiveness. A significant association has previously been demonstrated between single nucleotide polymorphisms (SNPs) and haplotypes of the ADAM33 and asthma in ethnically diverse populations. To assess whether SNPs or haplotypes of ADAM33 are related to asthma in a Chinese Han population, we genotyped three SNPs of ADAM33 (7575G/A in intron 6, 11188A/T in intron 19, and 12433T/C in exon 20) in a case-control study involving 296 patients with asthma and 270 healthy controls. No significant association was detected between these three SNPs and asthma susceptibility in the Chinese population.     

Mannose‐binding lectin exon 1 and promoter polymorphisms in tuberculosis disease in a mediterranean area

Mannose‐binding lectin (MBL) is a serum protein that activates the complement and mediates phagocytosis. MBL levels and MBL2 genotype may impact upon host susceptibility to tuberculosis (TB) disease but evidence to date has been conflicting. MBL2 exon 1 and promoter genotyping and serum MBL concentrations were determined in 79 patients with active tuberculosis (58 pulmonary TB and 21 extrapulmonary or miliary TB) and 120 household healthy contacts (HHC) from a Mediterranean area (Majorca Island, Spain). Significantly higher serum MBL levels were found in patients with active tuberculosis than in HHC [median MBL concentrations 3430 ng mL^?1 (10–28 415) and 2600 ng mL^?1 (5–20 000) respectively, P = 0.002]. These higher MBL levels were mainly related to the most prevalent YA/YA wild‐type diplotype. There was a strong correlation between MBL2 exon 1 and promoter genotype and MBL levels. The diplotype LYQA/HYPA was present in 12 out of 57 of the pulmonary TB cases but in none of the extrapulmonary TB patients. Diplotype LXPA/HYPA, producer of high levels of MBL, was significantly more frequent in HHC than in patients (16.8% vs. 6.4%, P = 0.031) suggesting a protective role against the development of TB disease that has not been previously found.     

Effects of MASP2 haplotypes and MASP‐2 levels in hepatitis C‐infected patients

Mannan‐binding lectin (MBL) and MBL‐associated serine protease 2 (MASP‐2) are components of the lectin pathway, which activate the complement system after binding to the HCV structural proteins E1 and E2. We haplotyped 11 MASP2 polymorphisms in 103 HCV patients and 205 controls and measured MASP‐2 levels in 67 HCV patients and 77 controls to better understand the role of MASP‐2 in hepatitis C susceptibility and disease severity according to viral genotype and fibrosis levels. The haplotype block MASP2*ARDP was associated with protection against HCV infection (OR = 0.49, p = .044) and lower MASP‐2 levels in controls (p = .021), while haplotype block AGTDVRC was significantly increased in patients (OR = 7.58, p = .003). MASP‐2 levels were lower in patients than in controls (p < .001) and in patients with viral genotype 1 or 4 (poor responders to treatment) than genotype 3 (p = .022) and correlated inversely with the levels of alkaline phosphatase, especially in individuals with fibrosis 3 or 4 (R = ?.7, p = .005). MASP2 gene polymorphisms modulate basal gene expression, which may influence the quality of complement response against HCV. MASP‐2 levels decrease during chronic disease, independently of MASP2 genotypes, most probably due to consumption and attenuation mechanisms of viral origin and by the reduced liver function, the site of MASP‐2 production.     

Sinonasal pathology in nonallergic asthma and COPD: 'united airway disease' beyond the scope of allergy

Background:  In contrast to the epidemiological and clinical association between allergic rhinitis and asthma, upper airway inflammation is less characterized in patients with nonatopic asthma and virtually unexplored in chronic obstructive pulmonary disease (COPD). Here, sinonasal pathology is studied in patients with allergic asthma, nonallergic asthma and COPD.
Methods:  Ninety patients with stable bronchial disease were included in the study, of which 35 were diagnosed with allergic asthma, 24 with nonallergic asthma and 31 with COPD. Concurrently, 61 control subjects without pulmonary disease were included and matched for age and smoking habits respectively with the asthma and the COPD group. Sinonasal symptoms were evaluated on a visual analogue scale and rhinosinusitis-related impairment of quality of life was assessed with the sino-nasal outcome test-22 (SNOT-22) questionnaire. Nasal mucosal abnormalities were quantified with nasal endoscopy and nasal secretions collected for measuring inflammatory mediators.
Results:  Allergic asthmatics, nonallergic asthmatics and COPD patients reported more nasal symptoms than their respective control subjects, had a higher SNOT-22 score and presented more mucosal abnormalities in the nose. Nasal secretions of both allergic and nonallergic asthmatics contained higher levels of eotaxin, G-CSF, IFN-γ and MCP-1 than controls. Allergic asthmatics had higher nasal IP-10 levels as well. COPD-patients had higher nasal levels of eotaxin, G-CSF and IFN-γ than controls.
Conclusion:  Patients with allergic and nonallergic asthma and COPD show increased nasal symptoms and more nasal inflammation. Hence, our data confirm the 'united airways' concept to be beyond the scope of allergic asthma.     

Acute-phase responsiveness of mannose-binding lectin in community-acquired pneumonia is highly dependent upon MBL2 genotypes

Mannose-binding lectin (MBL) is a pattern recognition receptor of the complement system and plays an important role in innate immunity. Whether or not MBL acts as an acute-phase response protein in infection has been an issue of extensive debate, because MBL responses have shown a high degree of heterogeneity. Single nucleotide polymorphisms (SNPs) in the promoter (wild-type Y versus X) and exon 1 (A versus 0) of the MBL2 gene can lead to MBL deficiency. This study investigated the influence of SNPs in the promoter and exon 1 of the MBL2 gene on the acute-phase responsiveness of MBL in 143 patients with community-acquired pneumonia. Acute-phase reactivity was observed only in MBL-sufficient genotypes (YA/YA, XA/YA, XA/XA and YA/0). In patients with wild-type exon 1 genotype A/A, positive acute-phase responses were associated with the presence of the YA haplotype and negative responses with its absence. Genotypes YA/0 and XA/XA produced equal levels of MBL in convalescence. In the acute phase, however, patients with genotype XA/XA displayed negative acute-phase responses more often than those with genotype YA/0. Correlation of MBL and C-reactive protein levels in the acute phase of pneumonia also depended upon the MBL2 genotype. In conclusion, acute-phase responsiveness of MBL was highly dependent upon the MBL2 genotype. These data suggest that heterogeneity in protein responses in the acute phase of disease should always be viewed in the light of possible influences of genetic differences in both structural and regulatory parts of the gene.     

Changes in airway inflammation following nasal allergic challenge in patients with seasonal rhinitis

BACKGROUND: Seasonal allergic rhinitis could predispose to the development of chronic bronchial inflammation as observed in asthma. However, direct links between nasal inflammation, bronchial inflammation and airway responsiveness in patients with seasonal allergic rhinitis and without asthma are not fully understood. The aim of this study was to analyse the changes induced by allergic nasal challenge outside the pollen season in airway responsiveness and bronchial inflammation of patients with seasonal allergic rhinitis. METHODS: Nine patients were evaluated after either grass pollens or placebo nasal challenge in a randomized cross-over double-blinded trial. Nasal parameters were recorded hourly and airway responsiveness was assessed by methacholine challenge. Cytological examinations and cytokine measurements were performed in nasal lavage and induced sputum. Eosinophil activation was investigated by eosinophil-cationic protein expression and secretion. RESULTS: Airway responsiveness was increased after allergic nasal challenge. Total eosinophils and eosinophils expressing eosinophil-cationic protein were increased in induced sputum after allergic nasal challenge. Both eosinophil number and eosinophil-cationic protein concentration in induced sputum were correlated to methacholine responsiveness. CONCLUSIONS: These results suggest that eosinophils participate to the bronchial inflammation in patients with seasonal allergic rhinitis following allergic nasal challenge outside the pollen season and might explain changes in airway responsiveness.     

Lectin complement pathway gene profile of the donor and recipient does not influence graft outcome after kidney transplantation

In kidney transplantation, complement activation was found to be induced by donor brain death, renal ischemia-reperfusion injury and allograft rejection. There are three known pathways of complement activation: the classical, lectin and the alternative pathway. The lectin complement pathway can be activated upon pattern recognition by mannan binding lectin (MBL) or ficolins (FCN). Single nucleotide polymorphisms (SNPs) in the genes encoding the lectin pathway proteins determine their functional activity and serum levels. The aim of this study was to investigate the role of the lectin gene profile of the donor and recipient on post-transplant outcome. A total of 12 functional SNPs in the MBL2, FCN2 and MBL-associated serine proteases 2 (MASP2) genes of 1271 donor-recipient pairs were determined. Lectin genotypic variants were analyzed for association with primary non-function (PNF), delayed graft function (DGF), biopsy proven acute rejection, death-censored graft survival and patient survival. Multivariate analyses found no association of donor and recipient MBL2 and MASP2 genotype with allograft outcome. Analysis of separate functional SNPs and haplotypes in the FCN2 gene of the donor and recipient did not reveal an association with transplant outcome. Also, the joint effect of the MBL2 and FCN2 genotype was not associated with allograft outcome.This study shows that the genetic profile of the lectin pathway of complement activation of the donor and recipient is not associated with allograft outcome after kidney transplantation.     

Airway inflammation in asthma and perennial allergic rhinitis. Relationship with nonspecific bronchial responsiveness and maximal airway narrowing

BACKGROUND: Eosinophilic airway inflammation is the hallmark of asthma, but it has also been reported in other conditions such as allergic rhinitis. We have tested whether the analysis of cells and chemicals in sputum can distinguish between patients with mild allergic asthma, those with allergic rhinitis, and healthy controls. The relationship between inflammation markers in sputum and nonspecific bronchial hyperresponsiveness to methacholine (BHR) (PD20 and maximal response plateau [MRP] values) was also evaluated. METHODS: We selected 31 mild asthmatics and 15 rhinitis patients sensitized to house-dust mite. As a control group, we studied 10 healthy subjects. Every subject underwent the methacholine bronchial provocation test (M-BPT) and sputum induction. Blood eosinophils and serum ECP levels were measured. Sputum cell differentials were assessed, and eosinophil cationic protein (ECP), tryptase, albumin, and interleukin (IL)-5 levels were measured in the entire sputum supernatant. RESULTS: Blood eosinophils and serum ECP levels were higher in asthma patients and rhinitis than in healthy controls, but no difference between asthma patients and rhinitis patients was found. Asthmatics had higher eosinophil counts and higher ECP and tryptase levels in sputum than rhinitis patients or control subjects. Sputum albumin levels were higher in asthmatics than in controls. Rhinitis patients exhibited higher sputum eosinophils than healthy controls. An association between sputum eosinophil numbers and MPR values (r= -0.57) was detected, and a trend toward correlation between sputum ECP levels and PD20 values (r= -0.47) was found in the rhinitis group, but not in asthmatics. No correlation between blood eosinophilic inflammation and lung functional indices was found. CONCLUSIONS: Induced sputum is an accurate method to study bronchial inflammation, allowing one to distinguish between rhinitis patients and mildly asthmatic patients. The fact that no relationship was detected between sputum inflammation and BHR suggests that other factors, such as airway remodeling, may be at least partly responsible for BHR in asthma.     

Introduction to nasal and pulmonary allergy cascade

The early phase of an IgE-dependent allergic reaction is followed by the activation of a complex network of inflammatory phenomena – T lymphocytes, cytokines, mediators, and adhesion molecules – that mediate late and ongoing allergic symptoms. The kinetics of respiratory inflammation following allergen exposure involve the migration of inflammatory cells to the mucosa within about 30 min, increased inflammatory infiltration over the following hours, and then slow subsidence. A relationship between asthma and allergic rhinitis is supported by epidemiological, histological, physiological, and immunopathological data, and by the response of asthma symptoms in rhinitic patients to intranasal corticosteroids and antihistamines. For example, there is no morphological difference between the bronchial inflammatory response following allergen-specific challenge in patients suffering from asthma alone or rhinitis alone. It is the allergen dose that makes the difference in the airway response to allergen in allergic rhinitis and asthma. Recognition of the relationship between asthma and allergic rhinitis has led to the introduction of new diagnostic terminology and treatment recommendations: 1) patients with persistent rhinitis should be evaluated for asthma; 2) patients with persistent asthma should be evaluated for rhinitis; and 3) a strategy should combine the treatment of upper and lower airways in terms of efficacy and safety.     

Different serum soluble Fas levels in patients with allergic rhinitis and bronchial asthma

BACKGROUND: The pathogeneses of allergic rhinitis and bronchial asthma are believed to be closely mutually related because of the similar dynamics of allergy-inducing cells and molecules and clinical overlap. In this study, we compared these diseases in the dynamics of cell apoptosis-regulating molecules. METHODS: Allergic rhinitis patients (n=36), bronchial asthma patients (n=22), and healthy subjects (n=32) were subjected to measurement of serum (soluble Fas) (sFas) levels during the stable and attack disease phases by a sandwich enzyme-linked immunosorbent assay. RESULTS: Serum sFas levels in patients with allergic rhinitis during the attack phase were significantly lower (P<0.0001) than those in healthy individuals. There were no differences between them during the attack and stable disease phases. In contrast, serum sFas levels in patients with bronchial asthma during the attack phase were higher (P<0.0005) than those in healthy individuals. Interestingly, the levels during the attack phase were lower (P<0.002) than those during the stable phase. CONCLUSIONS: Our results suggest a different pathogenesis for allergic rhinitis and bronchial asthma at the cell apoptosis-linked step.     

Mannose-binding lectin genotype and serum levels in patients with chronic and allergic pulmonary aspergillosis

Several studies suggest mannose-binding lectin (MBL) deficiency is associated with various manifestations of aspergillosis. MBL serum levels and function are genetically determined, but levels rise during inflammation. We address the relative frequency of deficient genotypes, the relationship between serum level and genotype and both age and disease manifestations in patients with chronic pulmonary (CPA) and allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS). DNA was extracted from blood samples, and MBL2 genotyping was performed using the INNO-LiPA MBL2 kit. Serum MBL concentrations were determined using ELISA. One hundred and eight patients were evaluated, 70 (65%) with CPA, 38 (35%) with allergic disease (ABPA, SAFS or undefined) and 13 (12%) had both CPA and ABPA. The mean MBL serum level was 1849 μg L(-1) and did not differ between groups. Forty subjects (37%) had exon 1 genotypes producing nonfunctional MBL (A/B, A/C, A/D and O/O), a frequency not different from published normal controls. A/A subjects with CPA had higher levels (2981 μg L(-1)) compared with allergic A/A subjects (2202 μg L(-1)) (pc0.012). No single haplotype, genotype or allele was significantly related to any aspergillosis phenotype. Worse breathlessness was associated with higher MBL levels among A/A subjects (P = 0.009) and conversely nonfunctional genotypes. Mean MBL values were higher in those with an Medical Research Council (MRC) breathlessness score of 5 compared with those with and MRC score of 1 (P = 0.023). A/A allergic subjects (n = 27) in this study were ≈ 11 years younger than allergic A/O subjects (n = 11, P = 0.02). Subjects with worse respiratory status or more severe CPA had higher MBL serum levels (P = 0.023; P = 0.034). Bronchiectasis was not associated with MBL levels in CPA or allergic aspergillosis. MBL genotype and serum level modulate progression of aspergillosis.     

Association between interleukin-1 receptor antagonist gene and asthma-related traits in a German adult population

Background:  A recent study in German and Italian families associated variants in the interleukin-1 receptor antagonist (IL1RA) gene with asthma. The aim of the present study was to further investigate the role of single nucleotide polymorphisms (SNPs) in the IL1RA gene in the development of atopy and lifelong asthma in a population-based study.
Methods:  DNA samples from the German centres of the European Community Respiratory Health Survey were analysed for genetic variants in the IL1RA gene and the development of asthma, atopy and bronchial hyperreactivity.
Results:  Carriers of the rare G allele of SNP rs447713 had a significantly increased risk of developing asthma ( P  = 0.0013) and allergic sensitization ( P  = 0.0119). Carriers of the rare C allele of SNP rs3087271 had an increased risk of asthma ( P  = 0.0227) and high immunoglobulin E (IgE) levels ( P  = 0.0232). A haplotype built from eight SNPs in the IL1RA gene (A-C-A-G-A-C-G-A) was associated with a higher prevalence of asthma ( P  = 0.007) and high total IgE ( P  = 0.02). Bronchial hyperreactivity was positively associated with the haplotype A-C-G-G-A-C-G-C ( P  = 0.02) and negatively with the A-C-G-G-A-C-T-C ( P  = 0.03).
Conclusion:  A previously described association between IL1RA and asthma in families could be reproduced in a population-based sample. The genetic variants of IL1RA gene do not to seem to affect asthma alone, but to act as modulators of asthma-related traits as well, where different haplotypes drive the development of different phenotypes.     

Coding and non-coding polymorphisms in the lectin pathway activator L-ficolin gene in 188 Dutch blood bank donors

Human L-ficolin (FCN) is a serum lectin characterized by a collagen-like and a fibrinogen-like domain that can activate the lectin pathway of complement. Structural and functional similarities to mannose-binding lectin (MBL) suggest a role for L-ficolin in innate immunity. Structural polymorphisms in the MBL2 gene lead to functional deficiency of MBL. Polymorphisms in the FCN2 gene have not been studied previously. We developed 10 denaturing gradient gel electrophoresis (DGGE) assays to screen a total of 188 Dutch Caucasians for polymorphisms in FCN2. Total gene screening in this large cohort revealed 10 single nucleotide polymorphisms (SNPs). Interestingly, two conserved coding SNPs were found in exon 8, leading to amino acid substitutions within the fibrinogen-like domain. Fibrinogen-like domains are highly conserved among several proteins in many species. As this domain is responsible for binding of L-ficolin, these newly found coding polymorphisms could alter the affinity of the protein for its substrates and possibly alter the ability of L-ficolin to recognize invading microorganisms.     

Impact of allergic rhinitis on asthma: effects on spirometric parameters

Background:  Close association exists between allergic rhinitis and asthma. Moreover, allergic rhinitis is a strong risk factor for the onset of asthma in adults. This study was aimed at evaluating a large group of patients with moderate-to-severe and persistent allergic rhinitis alone for investigating the presence of spirometric abnormalities and possible risk factors related to it.
Methods:  A total of 392 patients with persistent allergic rhinitis were prospectively and consecutively evaluated. Clinical examination, skin prick test and spirometry were performed in all patients.
Results:  There were 24 (6.1%) patients with forced vital capacity (FVC < 80%) of predicted, 50 (12.8%) with forced expiratory volume in the first second (FEV₁ < 80%) of predicted and 341 (87.0%) with forced expiratory flow at 25% and 75% of the pulmonary volume (FEF_25–75) < 80% of predicted. The logistic regression analysis evidenced that rhinitis duration (OR_Adj: 1.9/year) and sensitization to house dust mites (OR_Adj: 8.2) were significantly associated with impaired values of 2 or 3 spirometric parameters.
Conclusion:  This study highlights the close link between upper and lower airways and the role of some risk factors, such as duration and mites sensitization, as early prognostic markers of bronchial involvement in patients with moderate-to-severe and persistent allergic rhinitis alone.     

Functional polymorphisms in the mannan-binding lectin 2 gene: effect on MBL levels and otitis media

BACKGROUND: Mannan-binding lectin (MBL) can bind to microorganisms, initiating the lectin pathway of complement activation. Aberrant MBL serum levels, caused by MBL2 gene polymorphisms, are a possible risk factor for recurrent infections. Within the 7 common MBL haplotypes, still considerable variation in MBL serum levels exists. OBJECTIVE: To investigate functional MBL levels and MBL2 polymorphisms in a large cohort of children with recurrent acute otitis media. METHODS: Twelve genetic variants in the MBL2 gene and functional MBL serum levels were determined in a cohort of children with recurrent acute otitis media. Haplotypes were constructed and associated with functional MBL serum levels and the number of otitis episodes in the previous year. RESULTS: The 7 common MBL2 haplotypes mainly determine the level of functional MBL in serum. In addition, the 3130G>C single nucleotide polymorphism, located in exon 4, further significantly influenced functional MBL levels within the LXPA haplotype. LXPA carriers with 3130G showed a significantly lower geometric mean functional MBL serum level of 0.19 mug/mL compared with 0.70 mug/mL in 3130C carriers (P = .026). Nonwild-type MBL2 carriers between 12 and 24 months had a significantly increased number of otitis episodes (5.1/y) compared with wild-type MBL2 carriers (4.1/y; P = .027). In older children, this association was not found anymore. CONCLUSION: Additional single nucleotide polymorphisms within the 7 common haplotypes can further explain the observed variation in functional MBL serum levels. MBL seems to be of particular clinical importance during early childhood, when maternally derived antibodies have waned, and protective adaptive immunity is not well developed yet. CLINICAL IMPLICATIONS: Single nucleotide polymorphisms in the promoter region, in exon 1, and in exon 4 of MBL2 contribute to increased risk for otitis media in children younger than 2 years.     

Mucosal and systemic inflammatory changes in allergic rhinitis and asthma: a comparison between upper and lower airways

BACKGROUND: Local airway inflammation and airway remodelling are considered important in the clinical expression of allergic asthma. OBJECTIVE: The aim of this study was to compare airway inflammation and remodelling in nasal and bronchial mucosa of subjects with allergic rhinitis with or without asthma. METHODS: Four experimental groups were formed: allergic asthma and rhinitis (n = 19); allergic rhinitis, no asthma (n = 18); atopic subjects, no asthma, no rhinitis (n = 8) and non-allergic healthy control subjects (n = 16). Blood samples, nasal and bronchial biopsy specimens were collected during stable disease. Immunohistochemistry was performed for eosinophils (MBP), mast cells (CD117) and vascular endothelium (CD31). Epithelial loss, reticular basement membrane (RBM) thickness and subepithelial vascularity was assessed with a computer-assisted image analysis system. RESULTS: In nasal and bronchial mucosa, numbers of eosinophils were significantly higher in rhinitis patients with and without asthma than in asymptomatic atopics (P < 0.05) and controls (P < or = 0.01). In bronchial mucosa, the RBM was significantly thickened in rhinitis patients with and without asthma compared to asymptomatic atopics (P < 0.05) and controls (P < 0.01), while in nasal mucosa no differences were seen. Patients with asthma and rhinitis had increased numbers of blood eosinophils (P = 0.05) and skin test reactivity (P = 0.01) compared to patients with rhinitis only. No significant differences could be found between the investigated groups with respect to serum IL-5 and eotaxin levels, the number of mucosal mast cells and the degree of epithelial loss and subepithelial vascularity. Epithelial desquamation was significantly increased in the bronchial mucosa compared to nasal mucosa, not only in asthmatics (P < 0.001), but also in atopics without asthma and rhinitis (P = 0.02). CONCLUSIONS: This study shows that allergic inflammation, increased basement membrane thickness and epithelial desquamation are present in the lower airways of atopic subjects, even before the onset of clinical symptoms. Despite the presence of inflammatory cells, no structural changes could be assessed in nasal mucosa of allergic patients.     

Exhaled nitric oxide in seasonal allergic rhinitis: influence of pollen season and therapy

Exhaled nitric oxide (eNO) has been proposed as a potential indirect marker of lower airway inflammation in asthma. To investigate the existence of lower airways inflammation in allergic rhinitis eNO measurements were performed in 32 patients with symptomatic and asymptomatic seasonal allergic rhinitis early in and out of pollen seasons and in 80 healthy volunteers. To further define how exhaled NO is modified by therapy, NO levels were detected following 1-month treatment with either inhaled steroids or non-steroids therapy with nedocromil. Exhaled NO (mean +/- SE) was significantly elevated in patients with seasonal allergic rhinitis with and without symptoms (24.2 + 2.5 and 13.9 + 2.9 ppb, respectively) as compared to healthy volunteers (4.5 + 0.3 ppb) both in and out of pollen season (21.2 + 2.1 and 9.0 + 1.4 p.p.b., respectively) with a higher increase during the allergen exposure in season. Higher levels of exhaled NO were detected in patients with symptoms, either from the upper or lower airways, and with bronchial hyperreactivity. The increased exhaled NO in symptomatic patients was reduced only by inhaled steroids and not by nedocromil. These findings possibly suggest the existence of lower airway inflammation in both symptomatic and asymptomatic patients with seasonal allergic rhinitis in and out of pollen season. Thus, exhaled NO may be used as a non-invasive index for early detection of lower airway inflammation and for monitoring the optional treatment in patients with seasonal allergic rhinitis.     

Differences in mediator release between allergic rhinitis and asthma

To determine why patients with allergic rhinitis alone differ in their airway response to inhaled allergen compared to patients with allergic asthma, bronchial lavage was performed in 10 subjects with allergic asthma and in five subjects with allergic rhinitis, before and after inhalation challenge with antigen to produce an immediate asthmatic reaction. Before antigen challenge, the subjects with asthma had higher absolute neutrophil counts in the lavage fluid. After antigen challenge, the subjects with asthma released significant amounts of bronchoconstrictive mediators, such as histamine and thromboxane B2 into the lavage fluid, whereas subjects with rhinitis alone did not. There was also a significant increase in prostaglandin E2 in the subjects with asthma after antigen challenge. Nonimmunologic bronchoconstriction with methacholine inhalation challenge in six other subjects with asthma did not demonstrate an increase in any of the lavage fluid mediator levels that were measured. A positive correlation was found between methacholine provocative concentration causing a 20% drop in FEV1 and the concentration of prostaglandin E2 in the lavage fluid before challenge. The significance of this observation has yet to be determined. The results suggest that subjects with allergic asthma differ from subjects with rhinitis alone in their capacity to release more mediators into the airways on antigen challenge. It is not known whether this increase in mediators is due to increase in the number of mast cells in the airways or due to increase in mediator releasability from the mast cells of subjects with asthma.     

Mannose binding lectin gene polymorphisms and asthma

BACKGROUND: Bronchial asthma is a chronic inflammatory disorder of the airways. Recently, it has been suggested that complement plays significant roles in asthma. Mannose-binding lectin (MBL) is one of the key molecules in complement activation pathways that are associated with several infectious and immune disorders. SUBJECTS AND METHOD: To investigate whether MBL plays roles in asthma, we analysed MBL2 polymorphisms (allele B, H/L and Y/X) and plasma MBL levels in a Japanese adult population including 232 healthy controls and 579 asthmatics. RESULTS: Although there was linkage disequilibrium among the three polymorphisms, each polymorphism significantly affects serum MBL levels independently. However, there were no significant differences between asthmatics and controls in MBL2 genotype distribution and in MBL concentrations [1.47+/-0.07(SE) mg/L for asthmatics and 1.66+/-0.14 mg/L for controls, P=0.2]. MBL levels and genotype have no significant relationship with serum IgE, pulmonary functions, and the severity of asthma. CONCLUSION: Although plasma MBL levels depend on the MBL2 polymorphisms, these polymorphisms and plasma MBL levels are not associated with the asthma phenotype.