Vital capacity and inspiratory capacity as additional parameters to evaluate bronchodilator response in asthmatic patients: a cross sectional study

ABSTRACT: BACKGROUND: Bronchodilator response in patients with asthma is evaluated based on post-bronchodilator increase in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). However, the need for additional parameters, mainly among patients with severe asthma, has already been demonstrated. METHODS: The aim of this study was to evaluate the usefulness of vital capacity (VC) and inspiratory capacity (IC) to evaluate bronchodilator response in asthma patients with persistent airflow obstruction. The 43 asthma patients enrolled in the study were stratified into moderate or severe airflow obstruction groups based on baseline FEV1. All patients performed a 6-minute walk test before and after the bronchodilator (BD). A bipolar visual analogue scale post-BD was performed to assess clinical effect. The correlation between VC and IC and clinical response, determined by visual analogue scale (VAS) and 6-minute walk test (6MWT), was investigated. RESULTS: Patients in the severe group presented: 1) greater bronchodilator response in VC (48% vs 15%, p = 0.02), 2) a significant correlation between VC variation and the reduction in air trapping (Rs = 0.70; p < 0.01), 3) a significant agreement between VC and VAS score (kappa = 0.57; p < 0.01). There was no correlation between IC and the reduction in air trapping or clinical data. CONCLUSIONS: VC may be a useful additional parameter to evaluate bronchodilator response in asthma patients with severe airflow obstruction.     

The distribution of HLA alleles among children with atopic asthma in Croatia

Allergic asthma is a multifactorial disease involving well known environmental factors and less identified genetic components. In several studies the HLA genes have been implicated in the development of asthma and atopy, but the importance of these associations remains unclear. The aim of the present study was to analyse the distribution of specificities at HLA class I loci (-A and -B) and HLA class II locus (-DRB1) in a group of 143 Croatian children with atopic asthma, regarding total serum IgE and specific IgE against common inhalant allergens, as well as their connection with different asthmatic phenotypes and to identify HLA genotype which increases the risk for atopy or asthma or which has a protective effect. As controls we used a group of 163 healthy unrelated individuals. HLA class I antigens were determined by serology, while DRB1 specificities were detected by polymerase-chain reaction amplification and hybridisation with sequence specific oligonucleotide probes method (PCR-SSOP). We found no significant correlation between any of the HLA-A antigens and asthma, atopy or associated atopic phenotypes. At HLA-B locus, HLA-B8 antigen was significantly increased among asthmatic patients (p = 0.002), patients with high total serum IgE (p = 0.002), as well as among patients sensitizated to Dermatophagoides pteronyssinus (Der p) (p = 0.014) and among patients sensitizated to Der p + Dactylis glomerata (Dact g) or Ambrosia elatior (Amb a) (p = 0.004). Among HLA-DRB1 specificities, HLA-DRB1 *01 showed positive correlation with asthma and atopy (p = 0.034), while HLA-DRB1*03 specificity was observed with significantly higher frequency among patients with total serum IgE > or = 400 KU/L (p = 0.048). HLA-DRB1*16 specificity was observed with significantly lower frequency among patients with asthma only in comparison to healthy controls (p = 0.027) and to patients with asthma and allergic rhinitis (p = 0.005). In conclusion, our data suggest that HLA specificities play a relevant role in predisposition to asthma, as well as in different clinical forms of atopic diseases. HLA-B8, HLA-DRB1*01 and HLA-DRB1*03 genotype increases the risk for atopic asthma and high serum IgE.     

Association between toenail zinc concentrations and incidence of asthma among American young adults: The CARDIA study

BackgroundAs an essential micronutrient, zinc plays an important role in modulating the immune system. However, data on the association between zinc concentrations and asthma incidence are sparse, especially in adults.MethodsWe prospectively followed up 3682 individuals aged 20–32 years without history of asthma or current asthma at baseline from 1987–1988 to 2015–2016. Zinc concentrations were measured in toenail clippings collected at Exam Year 2 using inductively-coupled-plasma mass spectroscopy. Asthma was diagnosed by a physician and/or reported medication use for asthma control with verification. Cox regression was used to model the association between toenail zinc concentrations and asthma incidence.ResultsOver an average of 22.5 years of follow-up, 508 incident cases of asthma were identified. After adjustment for potential confounders, no statistically significant association was found between zinc concentration and asthma incidence (HR = 0.81; 95% CI: 0.62, 1.07; P_{linear trend} = 0.26). The observed association was not materially modified by sex, body mass index, smoking or atopic status. When stratifying data by race, a significant inverse linear association was found among African Americans (per 1 standard deviation increment in toenail zinc concentrations: HR = 0.86; 95% CI: 0.75, 0.99; P_{linear trend} = 0.03), but not in Caucasians (HR = 1.07; 95% CI: 0.91, 1.25; P_{linear trend} = 0.42), though the test for interaction was not statistically significant (P_interaction = 0.099).ConclusionsFindings from this prospective cohort study do not support a significant longitudinal association between toenail zinc concentrations and incidence of asthma among American young adults. Future studies are needed to confirm our findings.     

不同严重程度支气管哮喘患者血清LXA4水平的表达及临床意义

目的:探讨不同严重程度支气管哮喘患者血清脂氧素A4(LXA4)水平的表达及临床意义。方法:选取我院2015年10月到2016年11月收治的支气管哮喘患者86例作为研究组,另选同期我院体检结果为健康的40例志愿者纳入正常对照组,根据病情的不同严重程度将研究组分为轻度持续组(26例)、中度持续组(36例)、重度持续组(24例)。比较正常对照组和研究组患者的血清LXA4水平,比较研究组不同严重程度的第1s用力呼气量占预计值的百分比(FEV1%),并分析支气管哮喘患者的LXA4水平与FEV1%的相关性。结果:轻度持续组、中度持续组、重度持续组和正常对照组血清中LXA4水平整体比较差异有统计学意义(P0.05);中度持续组血清中LXA4水平显著高于轻度持续组、重度持续组和正常对照组,重度持续组血清中LXA4水平显著高于轻度持续组和正常对照组,轻度持续组血清中LXA4水平显著高于正常对照组,差异有统计学意义(P0.05);轻度持续组、中度持续组、重度持续组的FEV1%整体比较差异有统计学意义(P0.05);重度持续组的FEV1%显著低于轻度持续组和中度持续组,中度持续组的FEV1%显著低于轻度持续组,差异有统计学意义(P0.05);经Spearman统计分析,支气管哮喘患者的LXA4水平与FEV1%呈明显的负相关(r=-0.486,P=0.041)。结论:LXA4在支气管哮喘中度持续患者血清中表达最高,在轻度持续患者血清中表达最低,支气管哮喘越严重FEV1%水平越低,同时LXA4水平与FEV1%呈明显的负相关。     

Leukotrienes and 8-isoprostane in exhaled breath condensate in bronchoprovocation tests with occupational allergens

Exhaled breath condensate (EBC) contains many substances, which could help in diagnosis of occupational asthma. The aim of the study is to monitor leukotrienes (LT) and 8-isoprostane from EBC in bronchoprovocation tests with allergens in 47 patients with suspected occupational asthma. Forty-one patients were tested negative. In negative bronchoprovocation tests, no significant differences (P<0.05) were seen between the five measurements during and after the test. In control measurements (without provocation), significant differences were found among four measurements done within 24h for 8-isoprostane (P=0.0138). The relationship between the log transformed ratios of the EBC parameters and FEV(1) was never significant at the 5% level in control measurements, while in negative tests, statistical significance was recorded for LTB(4) (P=0.0299) before and 5h after the test. Six of 47 patients were tested positive. Such a small number of patients did not allow proper statistical analysis and therefore, the results are described separately for each patient.     

Heart Rate Variability During 24 Hours in Asthmatic Children

The autonomic circadian rhythm plays an important role in asthma. In recent years it has become possible to evaluate autonomic nervous function (ANF) using analysis of heart rate variability (HRV). We analyzed the HRV in the 24h period following the state without an asthma attack in order to study the relationship between asthma and ANF. The HRV was analyzed in 94 asthmatic children (ages 5–15 years). These subjects were divided into groups according to the severity of their asthma. After recording a 24h ambulatory electrocardiograph (AECG), the HRV was analyzed by a computer. Evaluation of the HRV was carried out using time-domain and frequency-domain analyses. The ANF of asthma subjects was decreased in comparison to the normal group. The severity of asthma had a significant effect on the %RR50 (the proportion of cycles during which the difference is > 50 ms), the SD (standard deviation; mean of standard deviation of all normal RR intervals for all 5-minute periods), the low-frequency (LF) band (0.04 to 0.15 Hz), and the high-frequency (HF) band (0.15 to 0.4 Hz) (%RR50: F = 4.31, p = 0.01; SD: F=3.48, p = 0.03; LF: F=3.67, p = 0.02; HF: F=3.41, p = 0.03). These values were lowest in the severe asthma group. With regard to the therapy grouping, the index that exhibited a significant difference was the NNA (mean of normal-to-normal RR intervals over 24h) (F = 4.43, p = 0.01) In conclusion, even in the normal condition in which the patient is free of an asthma attack, the ANF of asthma sufferers differs from that of normal children. It is possible that the different ANF of asthma sufferers is related to the severity of the asthma. (Chronobiology International, 14(6), 597–606, 1997)     

The influence of the bronchodilatation test on the duration of forced expiratory tracheal noises in young men

The diagnostic efficiency of estimating the duration of forced expiratory noises under the conditions of bronchial obstruction has been shown. The objective of this study was to analyze the response of the forced expiratory noise duration to the bronchodilatation test with the β₂-agonist in the age- and genderhomogenous group of healthy volunteers and bronchial asthma patients selected as a model of variable bronchial obstruction. Two hundred and sixty young men (16–25 years old) were examined. It was shown that the prevailing type of response in bronchial asthma patients with spirometry confirmed bronchial obstruction was shortened forced expiratory noises. Furthermore, the degree of the shortening considerably depended on the severity of the background bronchial obstruction. The absence of a statistically significant response of the forced expiratory noise duration dominated among healthy volunteers (nonsmokers as well as smokers) and bronchial asthma patients without a spirometry confirmed bronchial obstruction. However, the shortened response occurred much more frequently in bronchial asthma patients than in healthy volunteers. The high specificity (86%) of the response as shortened forced expiratory noises to the β₂-agonist may be useful for diagnostics.     

High-performance liquid chromatographic analysis of cyclosporin A in rat blood and liver using a commercially available internal standard

An automated and rapid method for quantifying malondialdehyde (MDA) in breath condensate was developed and validated. The method is based on derivatisation with thiobarbituric acid, HPLC separation and fluorescence detection and is optimised for determination of MDA in breath condensate. Sample collection is non-invasive and simple. The detection limit (4.1 nM) is low, precision is good and the analysis time is short. The response is linear in the concentration range of 0.020 to 1.0 microM. Samples could be stored for 1 month at -20 degrees C and for 3 months at -80 degrees C without losses. Using this method, there was no statistically significant difference between patients with asthma and patients without asthma. However, among females, subjects with asthma had higher MDA levels as compared to females without asthma (0.17 vs. 0.12 pmol/s, p=0.04). The use of the method when studying airway inflammation has to be further evaluated.     

Serum Myeloperoxidase as a Biomarker of Asthma Severity Among Adults: A Case Control Study

Background:The contribution of neutrophils is still indistinct in the inflammatory response of bronchial asthma (BAs). Myeloperoxidase (MPO) is an enzyme released from the primary azurophilic granules of the neutrophils. The study aimed to evaluate the levels of serum MPO as a biomarker for the assessment of the level of asthma control. Methods:The study participants included 94 asthmatic patients and 86 healthy controls. The identification of asthma severity had assessed using the ''''Global Initiative for Asthma guidelines''''. Asthmatic adults had divided into three groups: Good (n= 22), partial (n= 30), and poor control (n= 44). Also, patients have been divided again into two groups (treated and untreated) for BAs.Results:The predicted FEV1% and the peak expiratory flow (PEF/L) of all participants had verified by spirometry. The mean patients’ age was 31.9±15.1 year, with a predominance of females. The mean asthma duration was 10.5±8.6 years. Mean spirometric parameters (FEV1 and PEF) were significantly lower among the patients (0.00). Significant higher MPO levels had observed among BAs patients (p-0.00). The MPO levels have not differed significantly with asthma levels and had significant differences with the history of treatment. There was a nonsignificant negative correlation between the mean MPO levels and the spirometry variables among the patients. ROC curves revealed a sensitivity, specificity, accuracy for MPO (80.9%, 72.1%, and 84.3%), respectively to predict asthmatic severity.Conclusion:There were significantly higher MPO levels compared to healthy controls. Levels of serum MPO had a non-significant positive correlation with levels of asthma control, but a negative non-significant correlation with spirometric results. Key Words: Asthma, And Neutrophils, FEV1, MPO, PEF     

Systemic and local eosinophil inflammation during the birch pollen season in allergic patients with predominant rhinitis or asthma

Background

The aim of the study was to investigate inflammation during the birch pollen season in patients with rhinitis or asthma.

Methods

Subjects with birch pollen asthma (n = 7) or rhinitis (n = 9) and controls (n = 5) were studied before and during pollen seasons. Eosinophils (Eos), eosinophil cationic protein (ECP) and human neutrophil lipocalin were analysed.

Results

Allergic asthmatics had a larger decline in FEV1 after inhaling hypertonic saline than patients with rhinitis (median) (-7.0 vs.-0.4%, p = 0.02). The asthmatics had a lower sesonal PEFR than the rhinitis group. The seasonal increase in B-Eos was higher among patients with asthma (+0.17 × 109/L) and rhinitis (+0.27 × 109/L) than among controls (+0.01 × 109/L, p = 0.01). Allergic asthmatics and patients with rhinitis had a larger increase in sputum ECP (+2180 and +310 μg/L) than the controls (-146 μg/L, p = 0.02). No significant differences in inflammatory parameters were found between the two groups of allergic patients.

Conclusion

Patients with allergic asthma and rhinitis have the same degree of eosinophil inflammation. Despite this, only the asthmatic group experienced an impairment in lung function during the pollen season.     

The prevalence and pulmonary consequences of anxiety and depressive disorders in patients with asthma

The aim of this study was to determine the prevalence of anxiety and depression symptoms in outpatients with treated asthma and to determine the influence of anxiety and depression symptoms on lung function and asthma symptoms. The study was conducted in the pulmonary clinic of the Department of Pulmonary Diseases, Osijek University Hospital Centre, on 200 outpatients with asthma, aged 18-50 years, of which there were 65.5% women and 35.5% men. Each patient underwent a clinical examination with an extensive anamnesis and lung auscultation. The lung function was tested by spirometry. Demographic data and data on general and socioeconomic characteristics were evaluated using a questionnaire created internally for the purposes of this research, psychological status was assessed by HAD questionnaire, and Q test was used as a measure of asthma control. Based on the HAD questionnaire, 44.5% of asthma patients met the criteria for anxiety, and 24.5% of asthma patients met the criteria for depression. There was no significant correlation between asthma symptoms and the degree of anxiety or depression, while the pulmonary function of asthma patients negatively correlated with the degree of anxiety and depression. Pulmonary function in asthma patients with symptoms of anxiety and depression was significantly poorer than in asthma patients without anxiety and/or depression symptoms. The results show that among asthma patients there are large number of those who have symptoms of anxiety and depression. Asthma patients with symptoms of anxiety and depression have poorer lung function than patients with only asthma symptoms, however there is no significant correlation between the lung function and symptoms of asthma. We have confirmed that patients with anxiety symptoms visit general practitioners or EMS significantly more when compared to patients with depression symptoms.     

Bcl1 polymorphism of glucocorticoid receptor gene in patients with bronchial asthma with obesity

The objective of this investigation was to analyze possible association between Bcl1 polymorphism of glucocorticoid receptor gene and obesity in patients with bronchial asthma (BA). The study involved 188 patients with bronchial asthma and 95 apparently healthy adult individuals. Generally accepted assessments and examinations for BA diagnosis, and anthropometric, molecular-genetic and statistic methods of investigation were used in the research. It was found out that the patients with BA demonstrated higher body mass index (BMI) and higher ratio of fat centralization much more often, than the control group. Genotypes distribution for Bcl1 polymorphism in patients with BA showed a statistically significant difference between patients with different BMI unlike the control group. Comparison of genotype frequency for Bcl1 polymorphism in glucocorticoid receptor gene in individuals with different ratio of fat centralization in the control group and in the patients with BA separately showed statistically significant differences in the distribution of gene allelic variations only among the patients with BA. It was demonstrated that G/G genotype in the patients with visceral obesity was associated with BA.     

Growth during early childhood in asthmatic children: relation to inhalation steroid dose and clinical severity score

BACKGROUND/AIM: While short-term studies reported a growth retardation in children with asthma treated with inhaled steroids, long-term studies described attainment of adult heights within the target height range. In the present work, we describe the growth pattern of children with asthma. METHODS: In 58 children with asthma, we compared the height at age 3 years with the height at a mean age of 7.5 years during a 12-month study period. RESULTS: No differences in growth could be detected within the study year. Children in the lowest tertile but not in other tertiles for asthma severity score and inhaled steroid dose showed a significant decrease in height standard deviation scores from age 3 to age 7.5 years. CONCLUSION: The decrease in height standard deviation scores might be explained by undertreatment or an individual sensitivity to inhaled steroids.     

Serum levels of interleukin-13 and interferon-gamma from adult patients with asthma in Mysore

Serum protein analysis for noninvasive quantification of airway inflammation in asthma is a promising research tool in the field of lung diseases. Cytokines are believed to have major role in inflammatory process of the airways of the lung. There is an imbalance between T-helper (Th)-2 cells, which secrete interleukin (IL)-4 and interleukin (IL)-13, and Th1 cells, which secrete interferon (IFN)-gamma in asthma. To test the hypothesis that serum IL-13 and IL-4 levels may be elevated whereas IFN-gamma would be decreased in this cohort of patients, a property that could make them possible candidate biomarkers in determining asthma occurrence and severity, we measured concentrations of IL-4, IL-13 and IFN-gamma in serum samples of 88 subjects (44 normal, 12 with mild asthma, 16 with moderate asthma, and 16 with severe asthma). Serum Levels of IL-4, IL-13, and IFN-gamma were determined by an enzyme-linked immune-sorbent assay (ELISA). Median serum level of IFN-gamma in asthmatic patients was 8.0pg/ml, while it was 11.4pg/ml in healthy controls. However, the difference was not significant. Among the different age groups in whom IFN-gamma was assessed, the highest median value in both cases and controls was observed in the age group of 31-40years. The median serum level of IL-13 was 40.0pg/ml in asthmatic patients and 58.25pg/ml in healthy controls. The difference was not significant. On subgroup analysis, no significant difference of IFN-gamma and IL-13 between asthma of different severities was observed. The study also revealed nonsignificant difference of serum cytokines with the duration of asthma, number of allergens, and severity of sensitization. Normal serum levels of IFN-gamma and IL-13 in asthmatic patients suggest their neutral role in the inflammatory process; however, more studies are required to establish the effect of these cytokines in adulthood asthma in different ethnic populations.     

儿童哮喘与肺炎支原体感染关系的探讨

目的:探讨儿童哮喘发作与肺炎支原体(MP)感染之间的关系,并分析合并MP感染的患儿的临床表现。方法:将79例2-14岁急性哮喘发作的患儿依据病史分做两组:第一次哮喘发作的35人(始发哮喘组),已经有哮喘病史的44人(复发哮喘组)。采用被动冷凝集法检测两组患儿肺炎支原体抗体(MP-IgM)。结果:始发哮喘组和复发哮喘组分别有16例(45.7%)和10例(22.7%)患儿MP-IgM阳性(P0.05)。始发哮喘组与复发哮喘组MP-IgM阳性的患儿发热和肺部啰音发生率明显高于MP-IgM阴性的患儿(P0.05),血清IgE水平也明显高于MP-IgM阴性的患儿(P0.05)。结论:MP感染与儿童哮喘发作关系密切,合并MP感染的哮喘患儿发热或肺部啰音发生率明显高于未合并MP感染的哮喘患儿。     

A comparison of glycan expression and adhesion of mouse-adapted strains and clinical isolates of Helicobacter pylori

The role of Mycoplasma pneumoniae infection as a trigger for asthma exacerbations is well supported in previous studies. This study was designed to investigate the role of M. pneumoniae infection in acute exacerbation of asthma in children. A total of 150 patients (110 males, 40 females) were studied and immunoglobulin M (IgM) antibodies to M. pneumoniae were detected by enzyme-linked immunosorbent assay (ELISA), and PCR amplification was performed for the P1 gene to associate M. pneumoniae infection with asthma. As compared with 33 children with asthma, only two of the control subjects had positive IgM titers for M. pneumoniae , which was statistically significant ( P =0.002). A total of 15 children with asthma were positive by PCR for the P1 gene while none of the controls had a positive PCR. Of these positive cases, 24 cases were positive only by ELISA, six were positive only by PCR and nine patients were found to be positive by both ELISA and PCR. All the clinical characteristics of the patients at baseline were comparable between the moderate and the severe group of patients statistically, except for the peak expiratory flow rate. Mycoplasma pneumoniae infection was found to have a significant association with acute exacerbation in the moderate group of asthma patients by PCR ( P =0.01). These data suggest that M. pneumoniae infection may contribute to asthma exacerbation.     

Selenium status is decreased in patients with intrinsic asthma

Lowered selenium (Se) status has been observed in asthma patients. An increased production of reactive oxygen species (ROS) owing to inflammatory condition has also been found in these patients and thus antioxidant properties of Se via glutathione peroxidase (GPx) activity are of great importance. Concentrations of Se in plasma and erythrocytes as well as eryth-rocyte GPx activity in 22 intrinsic asthma patients (five patients; all women were aspirin-sensitive) were compared with those of 33 control subjects. Se concentrations in both plasma and erythrocytes and GPx activity were decreased in intrinsic asthma patients. There were no significant differences in investigated parameters of Se status between aspirin-tolerant and aspirin-intolerant patients within intrinsic asthma group. Significantly high positive correlation between plasma and erythrocyte Se concentrations was found when regarding all subjects as a whole. Se supplementation might be beneficial to patients with intrinsic asthma, which may be at risk of Se deficiency.     

Montelukast in asthma treatment in Croatia

The aim of this study was to determine the efficacy and safety of montelukast added to previous medication in the treatment of a mild and moderate asthma. Data were obtained via questionnaires given to the physicians and given further to their patients. Patients were divided in two groups, first followed 4 weeks (612 patients) and second followed 8 weeks (91 patients). We found out that there was a significant improvement in FEV1 (forced expiratory volume in first second) and general condition of patients and decreased number of salbutamol inhalations after using montelukast. In the second group of patients we find out the same significant improvement in FEV1, general condition and decrease in salbutamol inhalations after 4 weeks of using montelukast and further improvement after the next month of therapy. We conclude that montelukast is an efficient drug with little side effects and with a good compliance. Montelukast managed to achieve a good asthma control; therefore it has a significant place in asthma therapy.     

HLA-DR2, [HLA-B7, SC31, DR2], and [HLA-B8, SC01, DR3] haplotypes distinguish subjects with asthma from those with rhinitis only in ragweed pollen allergy.

MHC haplotypes were determined for 52 patients with ragweed pollen allergy, with and without asthma, and 27 non-atopic controls. Total IgE levels were unimodally distributed in all study groups and were higher in atopic patients in general compared with non-atopics. There was no difference in total IgE levels in patients with rhinitis only compared with those with rhinitis and asthma. IgE anti-Amb a V was detected (after subtraction of values representing the means + 2 SD of the non-atopics) in 9 of 20 asthmatics but only 3 of 32 patients with only rhinitis and was thus associated with asthma. Mean anti-Amb a V was much higher in the antibody-positive asthmatics (1710 U/ml) than in the positive patients with rhinitis only (469 U/ml). The extended MHC haplotype [HLA-B7, SC31, DR2] and its possible DR-containing fragment (SC31, DR2), were found almost exclusively among the patients with IgE anti-Amb a V and were significantly elevated in patients with asthma. DR2 in general, but not DR2 without SC31, was significantly increased in frequency in patients with anti-Amb a V. In contrast, the extended haplotype [HLA-B8, SC01, DR3] and DR3 in general were increased among patients with rhinitis only and patients without IgE anti-Amb a V compared with general controls. Thus, [HLA-B8, SC01, DR3] and DR3 appear to be "protective" for the production of this antibody and the occurrence of asthma. The findings are consistent with an MHC-linked gene or genes on [HLA-B7, SC31, DR2] (but not necessarily DR2, Dw2, or DQw6 in general) controlling the IgE immune response to Amb a V and associated with asthma in ragweed pollen-sensitive subjects. In patients with rhinitis alone and generally undetectable levels of IgE anti-Amb a V, the increase in [HLA-B8, SC01, DR3] and DR3 may mark a response to an as yet unidentified Ag associated with ragweed allergy and rhinitis only.