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PubMed2005

Inner City Asthma Study: relationships among sensitivity, allergen exposure, and asthma morbidity.

BACKGROUND: Asthma-associated morbidity is rising, especially in inner city children. OBJECTIVE: We evaluated the allergen sensitivities, allergen exposures, and associated morbidity for participants in the Inner City Asthma Study. We also determined geographic variations of indoor allergen levels. METHODS: Nine hundred thirty-seven inner city children 5 to 11 years old with moderate to severe asthma underwent allergen skin testing. Bedroom dust samples were evaluated for Der p 1, Der f 1, Bla g 1, Fel d 1, and Can f 1. RESULTS: Skin test sensitivities to cockroach (69%), dust mites (62%), and molds (50%) predominated, with marked study site-specific differences. Cockroach sensitivity was highest in the Bronx, New York, and Dallas (81.2%, 78.7%, and 78.5%, respectively), and dust mite sensitivity was highest in Dallas and Seattle (83.7% and 78.0%, respectively). A majority of homes in Chicago, New York, and the Bronx had cockroach allergen levels greater than 2 U/g, and a majority of those in Dallas and Seattle had dust mite allergen levels greater than 2 microg/g. Levels of both of these allergens were influenced by housing type. Cockroach allergen levels were highest in high-rise apartments, whereas dust mite allergen levels were highest in detached homes. Children who were both sensitive and exposed to cockroach allergen had significantly more asthma symptom days, more caretaker interrupted sleep, and more school days missed than children who were not sensitive or exposed. CONCLUSION: Geographic differences in allergen exposure and sensitivity exist among inner city children. Cockroach exposure and sensitivity predominate in the Northeast, whereas dust mite exposure and sensitivity are highest in the South and Northwest. Cockroach allergen appears to have a greater effect on asthma morbidity than dust mite or pet allergen in these children.

Air Pollution, Indoor↗
PubMed2005

Allergen avoidance in asthma: what do we do now?

Although allergen exposure can clearly aggravate the condition of sensitized patients with asthma, there is uncertainty and controversy about exactly which allergen avoidance interventions should be recommended to patients with asthma. Interventions that appear logical may fail to be clinically efficacious for several reasons. Although narrow interventions, such as allergen-impermeable mattress covers to reduce exposure to dust mite allergens, may offer little benefit if used alone, recent evidence suggests that a multifaceted, home-based environmental intervention focusing on multiple exposures may provide clinical benefits to patients with asthma. The role of allergen avoidance in infancy in the primary prevention of asthma is a subject of active investigation, but data remain too preliminary to make public health recommendations in this regard.

Allergens↗
PubMed2005

Cystatin A inhibits IL-8 production by keratinocytes stimulated with Der p 1 and Der f 1: biochemical skin barrier against mite cysteine proteases.

BACKGROUND: Der p 1 and Der f 1 are the most immunodominant allergens produced by house dust mites and are suspected to be involved in the pathogenesis of allergy through their cysteine protease activity. However, stimulation of keratinocytes by these protease allergens and protective systems in the skin against them have not been well investigated. OBJECTIVE: We purified and identified the dominant skin-derived inhibitor against the proteolytic activities of these allergens and analyzed its effect on keratinocyte activation. METHODS: Recombinant allergens were used for the experiments. We analyzed whether human sweat inhibits the enzymatic activities of Der p 1 and Der f 1 and used sweat as the skin-derived material to isolate the inhibitor. The inhibitor was purified by means of column chromatography and subsequently identified by means of protein sequencing and immunoblotting. Keratinocytes were stimulated with the allergens in the absence or presence of the inhibitor, and the concentration of secreted IL-8 was measured. RESULTS: Sweat inhibited the proteolytic activities of Der p 1 and Der f 1. The sweat inhibitor was identified as cystatin A. The stimulation of normal human keratinocytes and the human keratinocyte cell line HaCaT with these protease allergens upregulated IL-8 secretion, and addition of cystatin A blocked this upregulation. Normal human keratinocytes secreted cystatin A into the medium. CONCLUSIONS: The proteolytic activity of Der p 1 and Der f 1 stimulates human keratinocytes in vitro. Cystatin A produced by keratinocytes is the dominant biochemical skin barrier that eliminates the enzymatic activity of these mite cysteine proteases and prevents them from stimulating keratinocytes.

Animals↗
PubMed2005

Improving indoor environments: reducing allergen exposures.

Homes cannot be made allergen free, but exposure to the major indoor allergens can be reduced. All reduction recommendations are based on the principle of reducing or isolating the source, and certain recommendations can be made on the basis of published evidence. House dust mite avoidance measures include fitting allergen-proof mattress and pillow encasings, washing bedding regularly, and reducing humidity. Furred pet avoidance requires removal of the pet form the home, followed by thorough and repeated cleaning; room air cleaners, washing the pet, and isolating the pet from a bedroom are ineffective alternatives. Cockroach allergen avoidance begins with effective pest control, followed by thorough and repeated cleaning; 1 to 2 months are required to eliminate roaches, and an additional 4 to 6 months are required to remove residual allergen. Once allergen levels have been reduced, continued efforts are necessary to maintain the home free of allergen sources.

Air Pollutants↗
PubMed2005

Exposure to indoor allergens in day-care facilities: results from 2 North Carolina counties.

BACKGROUND: With 63% of US children under 5 years of age in regular child care, day-care facilities could be an important source of exposure to indoor allergens. OBJECTIVE: This study examined levels of 7 indoor allergens in 89 day-care facilities in 2 North Carolina counties. METHODS: At each facility, a questionnaire was administered, observations were made, and vacuumed dust samples were collected from carpeted and noncarpeted areas of one room. Allergen concentrations were measured with antibody-based ELISAs. RESULTS: Each allergen was detected in a majority of facilities (52% to 100%). Geometric mean concentrations were 5.19 mug/g for Alternaria alternata , 2.06 mug/g for Can f 1, 1.43 microg/g for Fel d 1, 0.21 U/g for Bla g 1, 0.20 microg/g for Der p 1, 0.10 microg/g for Der f 1, and 0.01 microg/g for Mus m 1. Concentrations for 5 of the 7 allergens were not statistically different from concentrations found in southern US homes sampled in the National Survey of Lead and Allergens in Housing. In rooms with carpet and hard-surfaced flooring, levels of A alternata , Can f 1, Der f 1, Der p 1, and Fel d 1 were statistically higher on carpet. CONCLUSIONS: In this survey of day-care facilities in North Carolina, detectable levels of indoor allergens were commonly found. For many young children and day-care staff, day-care facilities might be a source of clinically relevant exposures to indoor allergens.

Air Pollution, Indoor↗
PubMed2005

Effect of body mass on exercise-induced bronchospasm and atopy in African children.

BACKGROUND: Sensitization to allergen is common in rural populations in less affluent countries, but atopic disease is less frequent than in richer countries. Variables explaining this dichotomy may provide insight into underlying mechanisms of atopic diseases like asthma. OBJECTIVE: To test whether risk of exercise-induced bronchospasm (EIB) in urbanized African populations is increased in association with greater skin sensitivity or increased body mass. METHODS: A total of 3322 children were enrolled in a prevalence survey of EIB in urban and rural South Africa. Children responding positively to an exercise challenge and a random sample of children responding negatively were recruited into a case-control study (393 controls, 380 cases). Subjects were investigated by using allergen skin prick testing, anthropometry, and assay of IgE. Stools were analyzed for parasite infestation. RESULTS: The prevalence of EIB was higher in urban (14.9%) than rural (8.9%) areas (P < .0001). The difference in risk of EIB between urban and rural subjects was associated with atopy (odds ratio [OR] for upper tertile of skin wheal diameter, 2.65; 95% CI, 1.43-4.89; P < .0001), increasing weight (OR for upper tertile of body mass index [BMI], 2.17; 95% CI, 1.45-3.26; P = .001), and affluence. Increasing BMI was also associated with a greater strength of association between specific IgE and the corresponding skin test (Dermatophagoides pteronyssinus, OR for a positive skin test result in presence of specific IgE: heavier subjects, OR, 34.6; 95% CI, 0.9-109.3; P < .0001; lighter subjects, OR, 8.05; 95% CI, 2.74-23.6; P < .001). CONCLUSION: Increases in BMI of rural children in subsistence economies may lead to an increased prevalence of atopic disease. This observation merits further investigation in prospective studies.

Animals↗
PubMed2005

IgE antibody quantification and the probability of wheeze in preschool children.

BACKGROUND: IgE-mediated sensitization is usually considered a dichotomous variable (either sensitized or not). Quantitative IgE antibody analysis may better predict the expression of wheeze. OBJECTIVE: Within the context of a population-based birth cohort, we investigated the association among wheeze, lung function, and specific IgE antibody levels. METHODS: Children (n = 521) were followed to age 5 years with repeated questionnaires, skin testing, and measurement of lung function (specific airway resistance) and specific serum IgE (ImmunoCAP). RESULTS: Using specific IgE as a continuous variable, the risk of current wheeze increased significantly with increasing IgE to mite, cat, and dog (P < .0001). When IgE levels to these 3 allergens were summed, the probability of current wheeze increased 1.33-fold (95% CI, 1.21-1.47; P < .0001) per logarithmic unit increase, corresponding to an odds ratio of 3.1 at 10 and 4.25 at 30 kU(A)/L (kilo units of Allergen per liter). Similarly, increasing sum of mite-specific, cat-specific, and dog-specific IgE was associated with reduced lung function (P = .004). Among sensitized children (n = 184), the sum of mite, cat, and dog IgE was the strongest associate of current wheeze (odds ratio, 1.28; 95% CI, 1.13-1.46; P < .001), corresponding to an odds ratio of 2.56 at 10 and 3.32 at 30 kU(A)/L. There was no association between current wheeze and the size of skin test wheal. Furthermore, the sum of IgE to mite, cat, and dog at age 3 years increased the risk of persistent wheeze by age 5 years (2.15-fold/logarithmic unit increase in the specific IgE). CONCLUSION: IgE-mediated sensitization is not an all or nothing phenomenon. The probability of wheeze and reduced lung function increases with increasing specific IgE antibody levels.

Airway Resistance↗
PubMed2006

Three-dimensional structure and IgE-binding properties of mature fully active Der p 1, a clinically relevant major allergen.

BACKGROUND: Der p 1 is a 25-kd allergen with cysteine protease activity. Sensitization to Der p 1 affects a large proportion of individuals with allergy, resulting in rhinitis, asthma, and/or atopic dermatitis. OBJECTIVE: We determined the Der p 1 crystallographic structure to understand the relationships among structure, function, and allergenicity. METHODS: Recombinant pro-Der p 1 was produced in Pichia pastoris and allowed to mature spontaneously before purification by a 2-step procedure. Protease activity was checked by using a fluorogenic peptide substrate. Allergenicity was analysed by IgE binding assays and basophil activation test. The determination of the 3-dimensional structure was obtained by X-ray crystallography at 1.9 A resolution. RESULTS: The recombinant protein is fully active and expresses an allergenicity equivalent to its natural counterpart. Der p 1 exhibits a cysteine protease fold typical of the papain family, has a magnesium binding site, and forms dimers with a large interface. The crystal lattice shows that the dimers are tightly packed in a compact double layer of proteins. Such an assembly likely exists in dry fecal pellets, the natural form of allergen exposure, and appears ideal to interact with cell surface and trigger allergic inflammation. CONCLUSION: We present here the 3-dimensional structural features of mature fully active Der p 1, one of the main allergens involved in human allergic diseases. This opens the possibility to evaluate the importance of enzymatic activity in pathology and possible new therapeutic interventions.

Allergens↗
PubMed2006

Intranasal air sampling in homes: relationships among reservoir allergen concentrations and asthma severity.

BACKGROUND: The relationship among inhaled allergen exposure, sensitization, and asthma severity is unknown. OBJECTIVES: To investigate the relationship among personal allergen exposure, reservoir dust allergen concentrations, and physiological measures of asthma severity; to examine the numbers of particles inspired that react with autologous IgE and IgG4. METHODS: A total of 117 patients with asthma wore 5 nasal air samplers (NASs) at home: 1 each for exposure to mite, cat and dog allergens, NAS-IgE, and NAS-IgG4. NASs were processed by HALOgen assay for allergen measurement and incubated with autologous serum for detection of NAS-IgE and NAS-IgG4. Reservoir allergen concentrations were measured by ELISA. Subjects' asthma severity was ascertained by measurement of lung function, exhaled nitric oxide, and nonspecific bronchial reactivity to histamine. RESULTS: Nasal air sampler counts correlated with reservoir concentrations for cat (r=0.31; P=.001) and dog (r=0.20; P=.03) but not mite allergen (r=0.001; P=1.0). There was no significant relationship between sensitization with exposure measured by NAS to any allergen and PD20FEV1 (F[3,60]=1.60; P=.20); however, sensitization with exposure in dust reservoirs had significant effects on PD20FEV1 for any allergen (F[3,59]=3.12; P=.03), cat (F[3,59]=3.77; P=.01), and mite (F[3,59]=2.78; P=.05), but not dog (F[3,59]=1.06; P=.37). We repeated the analysis with separate variables for sensitization and exposure, controlling for the confounders; sensitization but not exposure conferred lower PD20FEV1 values. However, increasing cat allergen exposure was associated with improving bronchial reactivity in not cat-sensitized patients. NAS-IgE and NAS-IgG4 counts bore no relationship to any measure of asthma severity. CONCLUSION: Nasal air samplers confer no advantage over reservoir dust analysis for studies of asthma severity. CLINICAL IMPLICATIONS: In common with other measures of exposure, single nasal air samples do not provide a useful measure of home allergen exposure for the individual patient with allergic asthma.

Adolescent↗
PubMed2006

Der p 1 peptide on virus-like particles is safe and highly immunogenic in healthy adults.

BACKGROUND: In mice, highly repetitive antigens, such as those present on bacterial or viral surfaces, efficiently cross-link B-cell receptors and therefore induce strong IgG responses. In this study we covalently coupled a synthetic 16-amino-acid sequence of the allergen Der p 1 to a virus-like particle derived from the bacteriophage Qbeta (Qbeta-Der p 1). OBJECTIVE: We evaluated the safety and immunogenicity of Qbeta-Der p 1 in human subjects and compared different doses and routes of immunization. METHODS: In a phase I trial 24 healthy volunteers were randomly assigned to one of 4 treatment groups. Group 1 received 50 microg of Qbeta-Der p 1 intramuscularly, group 2 received 50 microg of Qbeta-Der p 1 subcutaneously, group 3 received 10 microg of Qbeta-Der p 1 intramuscularly, and group 4 received 10 microg of Qbeta-Der p 1 subcutaneously. Boosting immunizations with 10 microg were given after 1 and 3 months. Antibody titers were measured after 1, 3, 4, 6, 12, and 18 months. RESULTS: The vaccine Qbeta-Der p 1 was well tolerated. Significant IgG responses were observed 4 weeks after a single injection. Individuals receiving 50 microg of the vaccine had significantly higher IgG titers than those vaccinated with 10 microg. However, the route of immunization (subcutaneous vs intramuscular) had no effect. In the 50-microg dose group, strong antibody responses against Der p 1 with average titers of 1:2000 were obtained. CONCLUSION: Vaccination with a peptide antigen covalently coupled to highly repetitive virus-like particles represents an adjuvant-free means of rapidly inducing high antibody titers in human subjects. CLINICAL IMPLICATIONS: Allergens coupled to virus-like particles can be used to enhance the efficiency of allergen-specific immunotherapy.

Adolescent↗
PubMed2006

Early-life domestic aeroallergen exposure and IgE sensitization at age 4 years.

BACKGROUND: Although it is widely assumed that childhood sensitization to common aeroallergens is directly related to allergen exposure in early life, few longitudinal studies have investigated this issue, and available data are scarce and mainly limited to high-risk groups. OBJECTIVE: We sought to assess the role of early exposure to 2 major household aeroallergens (Der p 1 and Fel d 1) in sensitization at the age of 4 years. METHODS: Pregnant women and their children were recruited for the Asthma Multicenter Infant Cohort Study. Three cohorts (Ashford in the United Kingdom and Menorca and Barcelona in Spain) followed the same research protocol. A total of 1611 newborn children were initially included in the cohort, from whose homes we collected dust samples at 3 months of age for 1474; Der p 1 and Fel d 1 levels were measured. Of these children, we obtained blood for specific IgE determination in 1019. RESULTS: The risk of Fel d 1 sensitization increased with exposure in a nonlinear manner. No association was found between specific IgE to Der p 1 and aeroallergen levels of exposure at early life in 2 centers, but a positive association was observed in the third. CONCLUSIONS: The dose-response relationships between allergen exposure and sensitization differ between allergens and might vary between different locales. The hypothesis that sensitization to house dust mite is directly related to levels of allergen exposure might not apply to the general population or to different ranges of exposure. CLINICAL IMPLICATIONS: Aeroallergen avoidance might not have any important effect on the incidence of sensitization.

Air Pollution, Indoor↗
PubMed2006

An essential role for dendritic cells in human and experimental allergic rhinitis.

BACKGROUND: In allergic rhinitis (AR) CD4(+) T(H)2 lymphocytes control inflammation by secreting T(H)2 cytokines, but little is known about how these cells are activated to cause disease. OBJECTIVE: We sought to study the contribution of antigen-presenting dendritic cells (DCs) in activating T(H)2 cells and controlling allergic inflammation. METHODS: Nasal mucosal biopsy specimens were taken from patients with house dust mite allergy and perennial AR and healthy control subjects. DC numbers were evaluated by using immunohistochemistry. The functional role of DCs was studied in a novel mouse model for AR using BALB/c mice and CD11c-diphtheria toxin (DT) receptor transgenic mice. RESULTS: In symptomatic patients with perennial AR, the number of CD1a(+) and CD11c(+) MHCII(+) DCs was higher in the epithelium and lamina propria of the nasal mucosa compared with that seen in healthy control subjects. In patients with AR, DCs had a more mature (CD86(+)) phenotype and were found in close approximation with T lymphocytes. Similarly, in a mouse model of ovalbumin (OVA)-induced AR, CD11c(+) DCs accumulated in areas of nasal eosinophilic inflammation and clustered with CD4(+) T lymphocytes. CD11c(+) DCs were conditionally depleted during allergen challenge by means of systemic administration of DT to CD11c-diphtheria toxin receptor transgenic mice to address the functional role of DCs in maintaining inflammation. In the absence of CD11c(+) DCs, nasal OVA challenge in OVA-sensitized mice did not induce nasal eosinophilia and did not boost OVA-specific IgE levels or T(H)2 cytokine production in the cervical lymph nodes. Conversely, when OVA-pulsed DCs were administered intranasally to sensitized mice, they strongly enhanced OVA-induced nasal eosinophilia and T(H)2 cytokine production. CONCLUSIONS: These data in human subjects and mice suggest an essential role for nasal DCs in activation of effector T(H)2 function leading to AR. CLINICAL IMPLICATIONS: Nasal DCs play an essential role in AR and therefore constitute a novel target for therapeutic intervention.

Animals↗
PubMed2006

Allergen-dependent solubilization of IL-13 receptor alpha2 reveals a novel mechanism to regulate allergy.

BACKGROUND: Allergic sensitization affects half of western populations and often precedes the development of allergic disorders including asthma. Despite the critical role of allergens in the pathogenesis of these disorders, little is known about how allergens modulate the immune response. IL-13 receptor alpha2 (IL-13Ralpha2) is a decoy receptor for IL-13. OBJECTIVE: Although the existence of soluble IL-13Ralpha2 has been documented, the mechanisms underlying its generation are unknown. Many allergens possess protease activity; we investigated whether IL-13Ralpha2 is solubilized in response to allergen treatment. METHODS: We evaluated the ability of allergens to solubilize IL-13Ralpha2 in vitro and in vivo and examined the effect on IL-13 signaling and responses. RESULTS: We determined that treatment of cells with house dust mite (HDM) allergen or purified Dermatophagoides pteronyssinus or Dermatophagoides farinae, but not other allergens, resulted in release of soluble IL-13Ralpha2 that was biologically active and inhibited IL-13 signaling. Prolonged exposure to HDM or treatment with mold allergens resulted in IL-13Ralpha2 degradation. This was associated with increased IL-13 signaling. A single treatment of HDM in vivo resulted in release of IL-13Ralpha2 into the bronchoalveolar lavage (BAL) fluid. BAL fluid from humans also contained IL-13Ralpha2; BAL fluid from individuals with asthma contained less IL-13Ralpha2 than that from controls. CONCLUSION: Allergen exposure can directly affect the level of soluble IL-13Ralpha2 in a way that affects IL-13 signaling and responses. CLINICAL IMPLICATIONS: Soluble IL-13Ralpha2 may be an important biomarker of environmental allergen exposure and asthma.

Allergens↗
PubMed2004

Effect of an antiallergic drug (Olopatadine hydrochloride) on TARC/CCL17 and MDC/CCL22 production by PBMCs from patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the predominant infiltration of Th2-type cells in lesional skin. Thymus and activation-regulated chemokine (TARC/CCL17) and monocyte-derived chemokine (MDC/CCL22) are Th2-type cytokines, and it has been reported that serum CCL17 and CCL22 levels are associated with AD disease activity. Olopatadine hydrochloride (Olopatadine) is an antiallergic drug with selective histamine H(1) receptor antagonist activity. The effect of Olopatadine on chemokine production by peripheral blood mononuclear cells (PBMCs) in AD patients has not been completely elucidated. OBJECTIVES: This study was undertaken to clarify the effects of Olopatadine on CCL17 and CCL22 production by PBMCs from patients with AD during the treatment. METHODS: We measured plasma levels of CCL17, CCL22, IFNgamma, IL-12 and IL-18 in 15 patients with AD before and after treatment with oral Olopatadine (10 mg/day) for 4 weeks. We also examined disease activity using SCORAD index, eosinophil numbers in peripheral blood and serum levels of LDH. PBMCs from the patients were taken before and after the treatment and cultured with or without dust mite allergen extract (DME) for 3 or 5 days. CCL17, CCL22, IFNgamma, IL-12 and IL-18 levels in the supernatants of cultured PBMCs were measured. RESULTS: SCORAD index and eosinophil numbers in peripheral blood significantly decreased during treatment of AD patients with oral Olopatadine and topical corticosteroids for 4 weeks. The plasma levels of CCL17 and CCL22 significantly decreased after the treatment compared with before the treatment (p<0.05) and were significantly correlated with SCORAD index. PBMCs from AD patients taken after the treatment and cultured with DME for 5 days, showed significantly lower levels of CCL17 production than those taken before the treatment (p=0.018). PBMCs from AD patients taken after the treatment and cultured with DME for 5 days, also showed significantly lower levels of IFNgamma production than those taken before the treatment (p=0.012). CONCLUSION: Our data demonstrate that Olopatadine inhibits CCL17 and CCL22 production by PBMCs from AD patients, which are important regulators of Th2 recruitment in the skin.

Adult↗
PubMed2004

Dust mites living in human lungs--the cause of asthma?

Asthma does not have a clear cause and may represent a cluster of diseases. We propose that asthma in house dust mite sensitive patients may be caused by recurrent inhalation of live dust mites which are able to live for some time in the bronchioles of the lung. To provide themselves with a food source, the mites may purposefully excrete proteolytic enzymes, including Der p1, which increase epithelial shedding by freeing cells from the basement membrane. The mites then feed on the shed respiratory epithelial cells. Consequent loss of an intact respiratory epithelium exposes underlying tissues to dust mite protein and other allergens triggering sensitisation to these proteins. Later, repeated infestation provokes an allergic response which manifests itself as asthma attacks. The evidence for this hypothesis was tested against the Bradford-Hill criteria for causation; consistency, strength, temporal association and dose response. Potential areas for further research were also identified. The association between asthmatic symptoms and pulmonary acariasis was consistent across a number of studies. Determining the strength of the association and any dose response requires more work which is dependent on the development of better tests for the detection of mites in sputum. There was tentative evidence of a temporal association in the published studies identified. Biological plausibility and experimental evidence was available for pulmonary acariasis in primates and arsenic treatment was effective in humans. Better tests for mites in sputum are needed, as is work to assess more modern anti-acaricidal drugs in dust mite sensitive asthmatics.

Allergens↗
PubMed2005

Evidence that negative feedback between antibody concentration and affinity regulates humoral response consolidation to a non-infectious antigen in infants.

The dynamics of human antigen-specific immunoglobulin (Ig) responses in early life are not well characterized. We have previously observed an inverse relationship between allergen-specific Ig concentration and allergen-Ig-binding affinity in allergen-sensitive atopic adults, suggesting a possible feedback relationship between these variables. We prospectively studied children (6 months to 6 years) with and without atopic sensitization to the Der p 1 major allergen. Experimental results showed the following trends. (1) In both study groups, there was little change with age in average Der p 1-specific Ig (IgG1 or IgE) concentrations or allergen-Ig-binding affinities, and concentrations and affinities were independent. (2) Among individuals, however, there was a negative correlation between Ig concentration changes and affinity changes with age. (3) The rate of increase with age of the non-atopic Der p 1-IgG1 total binding capacity (Ig concentration x Ig affinity) paralleled that for the atopic Der p 1-IgE total binding capacity, and there was a comparable 'consolidation' of responses with age reflected by a narrowing of the variance of total binding capacity values. Except for the Ig classes involved, development of a humoral response to a non-infectious allergen is similarly regulated in atopic and non-atopic children, with Ig total binding capacity as the key regulatory variable. These results also suggest that there is a time-dependent feedback relationship between Ig concentrations and affinities that establishes an optimal Ig total binding capacity for a given environmental 'antigen load'. A theoretical model is proposed to account for this relationship.

Allergens↗
PubMed2005

Nasal obstruction is the key symptom in hay fever patients.

BACKGROUND: Allergic rhinitis is characterized by a Th2-dependent inflammation. Nasal obstruction largely depends on allergic inflammation. OBJECTIVE: The aim of this study was to evaluate the possible role of the symptom nasal obstruction in assessing patients with hay fever. METHODS: Fifty patients (mean age, 23.7 +/- 4.9 years) with hay fever were evaluated both during and outside pollen season. All of them had moderate-severe grade of nasal obstruction. Total symptom score (TSS), rhinomanometry, nasal lavage, nasal scraping, spirometry, and methacholine bronchial challenge were performed in all subjects. RESULTS: During the pollen season, patients with severe nasal obstruction showed significantly higher values of TSS, IL-4, IL-5, IL-8, nasal eosinophils and neutrophils, and significantly lower values of nasal airflow, IFNgamma, FEV1, FVC, and FEF 25-75 in comparison with patients with moderate nasal obstruction. Twenty (83%) patients with severe nasal obstruction showed bronchial hyperreactivity (BHR), whereas only 6 (25%) patients with moderate nasal obstruction had BHR. Outside the pollen season overlapping results were observed. CONCLUSIONS: This study provides evidence about the key role played by nasal obstruction in assessing patients with allergic rhinitis.

Adult↗
PubMed2006

Relationship between house dust mite (HDM) allergen exposure level and inhaled corticosteroid dosage in HDM-sensitive asthma patients on a self management program.

AIM: To assess whether exposure to house dust mite (HDM) allergens hampers a tapering off of inhaled corticosteroid (ICS) dosage in HDM-sensitive asthma patients. METHODS: Asthma patients sensitised to HDM allergens and using ICS were selected from general practices for this observational study. Dust samples from bed mattresses were taken to assess exposure ('no', 'low', 'intermediate' or 'high') to HDM allergens with a semi-quantitative test (Acarex). Patients were trained to use a self management plan to adjust the dose of ICS according to symptoms and peak flow. The observation period was three months. RESULTS: Outcomes from 123 patients were analysed. Within the 'no' and 'low' HDM exposure groups the proportion of patients who increased the dosage of their ICS medication was significantly lower than the proportion who tapered off or remained on the same dose of ICS. The group with high exposure to HDM allergens had the highest proportion of patients who increased their dose of ICS (p = 0.055). CONCLUSIONS: High exposure to HDM allergens seems to coincide with the use of higher dose ICS treatment in asthma patients sensitised to HDM allergens.

Administration, Inhalation↗