Design and baseline characteristics of the epidemiology and natural history of asthma: Outcomes and Treatment Regimens (TENOR) study: a large cohort of patients with severe or difficult-to-treat asthma.

BACKGROUND: Patients with severe and difficult-to-treat asthma represent a small percentage of asthma patients, yet they account for much of the morbidity, mortality, and cost of disease. The goal of The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study is to better understand the natural history of asthma in these patients. OBJECTIVE: To describe the methods and baseline characteristics of the TENOR study cohort. METHODS: The TENOR study is a 3-year, multicenter, observational study of patients with severe or difficult-to-treat asthma. From January through October 2001, more than 400 US pulmonologists and allergists enrolled patients. Patients 6 years or older who were considered to have severe or difficult-to-treat asthma by their physicians were eligible. Patients have been receiving care for 1 year or more, have a smoking history of 30 pack-years or less, and have current high medication or health care utilization in the past year. Data are collected semiannually. RESULTS: A total of 4,756 patients enrolled and completed a baseline visit. Overall, 73% of the TENOR study patients are adults, 10% are adolescents, and 16% are children. According to physician evaluation, 48% of patients have severe asthma, 48% have moderate asthma, 3% have mild asthma, and 96% have difficult-to-treat asthma. Severe asthmatic patients have the highest health care utilization in the past 3 months (P < .001). CONCLUSIONS: The TENOR study is the largest cohort of patients with severe or difficult-to-treat asthma. Although patients are equally divided into moderate or severe asthma categories, most are considered difficult-to-treat. The TENOR study highlights the lack of control in moderate-to-severe asthma and provides a unique opportunity to examine factors related to health outcomes in this understudied population.     

Asthma in older adults: observations from the epidemiology and natural history of asthma: outcomes and treatment regimens (TENOR) study.

BACKGROUND: The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) was a 3-year, multicenter, observational study of 4,756 patients 6 years or older with severe or difficult-to-treat asthma by physician evaluation. More than 280 pulmonologist and allergist sites across the United States participated. OBJECTIVE: To compare health care utilization (HCU), medication use, asthma control, and quality of life (QoL) in older (> or =65 years; n = 566) and younger (18-64 years; n = 2,912) adult patients in TENOR. METHODS: Patients had to be under a physician's care for at least 1 year and have high medication use or HCU in the past year. Heavy smokers (> or =30 pack-years) and patients with cystic fibrosis were excluded. RESULTS: Although older patients in TENOR had worse lung function as measured by decreased percent predicted forced expiratory volume in 1 second (FEV1) (P < .001), they had significantly lower HCU compared with younger patients. They also had higher use of inhaled corticosteroids and better QoL than younger patients. Older patients reported fewer problems controlling their asthma (P < .001) but reported worse communication with their physicians (P = .02). CONCLUSIONS: Older patients in TENOR appeared to do better than younger patients, despite having worse lung function. Older patients in TENOR may have received more aggressive care than older asthmatic patients in other studies, based on a higher use of inhaled and oral corticosteroids. Whether differences in treatment or disease influenced other physiologic or inflammatory outcomes that contribute to the disconnect between HCU and FEV1 awaits further study.     

Key findings and clinical implications from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study

Patients with severe or difficult-to-treat asthma are an understudied population but account for considerable asthma morbidity, mortality, and costs. The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study was a large, 3-year, multicenter, observational cohort study of 4756 patients (n=3489 adults ≥ 18 years of age, n=497 adolescents 13-17 years of age, and n=770 children 6-12 years of age) with severe or difficult-to-treat asthma. TENOR's primary objective was to characterize the natural history of disease in this cohort. Data assessed semiannually and annually included demographics, medical history, comorbidities, asthma control, asthma-related health care use, medication use, lung function, IgE levels, self-reported asthma triggers, and asthma-related quality of life. We highlight the key findings and clinical implications from more than 25 peer-reviewed TENOR publications. Regardless of age, patients with severe or difficult-to-treat asthma demonstrated high rates of health care use and substantial asthma burden despite receiving multiple long-term controller medications. Recent exacerbation history was the strongest predictor of future asthma exacerbations. Uncontrolled asthma, as defined by the 2007 National Heart, Lung, and Blood Institute guidelines' impairment domain, was highly prevalent and predictive of future asthma exacerbations; this assessment can be used to identify high-risk patients. IgE and allergen sensitization played a role in the majority of severe or difficult-to-treat asthmatic patients.     

Association between IgE levels and asthma severity among African American, Mexican, and Puerto Rican patients with asthma

BACKGROUND: High levels of IgE are associated with asthma. Whether higher levels of IgE are associated with more severe asthma is still unclear. OBJECTIVE: To determine whether IgE is associated with asthma severity among Latino and African American subjects with asthma. METHODS: We assessed lung function and asthma severity among African American, Mexican, and Puerto Rican patients with asthma with high IgE levels (> or =100 IU/mL; n = 492) and compared these values to those of patients with asthma with low IgE levels (<100 IU/mL; n = 247). We also examined IgE as a continuous variable among these groups. RESULTS: Patients with asthma with high IgE had a lower mean FEV(1) (87.6 +/- 17.1, percent of predicted) than patients with asthma with low IgE (91.5 +/- 17.0; P = .031). Regardless of race and ethnicity, baseline FEV(1), forced expiratory flow, and FEV(1)/forced vital capacity were lower among subjects with high IgE than among subjects with low IgE (P = .031, P < .0001, P = .0001, respectively). In addition, 54.7% of patients with asthma with high IgE had been previously hospitalized, compared with 44.1% of patients with asthma with low IgE (odds ratio, 1.33; 95% CI, 1.04-1.71). CONCLUSION: Higher IgE is associated with lower baseline lung function and more severe asthma among these populations. CLINICAL IMPLICATIONS: Among patients with asthma from 3 ethnically distinct groups, total IgE levels are inversely correlated with baseline lung function and asthma severity.     

Contribution of dust mite and cat specific IgE to total IgE: relevance to asthma prevalence

BACKGROUND: The prevalence of asthma is strikingly different in some Westernized countries: approximately 20% in New Zealand and approximately 8% in northern Sweden. OBJECTIVE: We investigated differences in total IgE and in the prevalence of wheezing related to the observation that high exposure to dust mite allergens induces high titers of IgE antibodies. METHODS: Two age-matched, population-based cohorts-1155 children in New Zealand (224 sera) and 3431 children (797 sera) in the Norrbotten area of Sweden-were studied. Sera were assayed for total IgE and specific IgE antibodies to relevant allergens. RESULTS: The mean total IgE among wheezing children was higher in New Zealand than Sweden (218 IU/mL vs 65.2 IU/mL; P < .001). In addition, the prevalence of high titer specific IgE antibody (> or =50 IU/mL) was greater among the wheezing children in New Zealand compared with Sweden (35.7% vs 13.0%; P < .001). Specific IgE antibody to mite in New Zealand was significantly related to high total IgE (> or =200 IU/mL; r = 0.47; P < .001), whereas the IgE antibody response to cat allergens did not make a significant contribution to high total IgE in either country. CONCLUSION: The quantity of IgE antibody produced to dust mite provides a possible explanation for the higher total IgE levels found in children in New Zealand and may help to explain the differences in prevalence and severity of asthma between these 2 countries. CLINICAL IMPLICATIONS: Specific IgE antibody responses to dust mite and cat allergens may contribute differently to total serum IgE and to the prevalence of allergic disease.     

Relationship between extremely low total serum IgE levels and rhinosinusitis.

BACKGROUND: The few studies examining clinical manifestations in adults with serum IgE levels less than 2.0 IU/mL provide conflicting information. OBJECTIVE: To examine self-reported respiratory disease in women with total serum IgE levels less than 2.0 IU/mL to further elucidate previous reports of an association between IgE deficiency and chronic rhinosinusitis. METHODS: In a geographically based cohort of 626 pregnant women, total serum IgE levels were measured using a standard assay with a lower limit of detection of 2.0 IU/mL. Sera with IgE levels less than 2.0 IU/mL were assayed again using a low IgE protocol with a detection limit of 0.02 IU/mL. RESULTS: Twenty-one individuals (3.4%) were found to have IgE levels less than 2.0 IU/mL. On repeated assay, 20 of these individuals with available clinical data were found to have detectable IgE levels ranging from 0.5 to 2.1 IU/mL (geometric mean, 1.2 IU/mL). None of these individuals with low IgE levels had physician-diagnosed sinusitis compared with 19.3% (113/585) of those with IgE levels of 2.0 IU/mL or greater (P = .03). Physician-diagnosed asthma was also less prevalent (1/19, 5.3%) in the low IgE group compared with 20.6% in those with higher IgE levels, but this was not significant (P = .14). The low IgE group reported a higher prevalence of hay fever symptoms than the remaining cohort (31.6% vs 24.4%; P = .43) but had less physician-diagnosed hay fever (5.3% vs 15.8%; P = .34). CONCLUSIONS: Low serum IgE levels were relatively common in these pregnant women. In contrast to previous studies, a low IgE level was not associated with chronic rhinosinusitis.     

Efficacy of omalizumab in asthmatic patients with IgE levels above 700 IU/mL: a retrospective study

BackgroundOmalizumab is approved for patients with poorly controlled asthma with serum IgE levels between 30 and 700 IU/mL and positive test results for perennial allergens. Its efficacy in patients with IgE levels greater than 700 IU/mL is unclear.ObjectiveTo evaluate the response of asthmatic patients treated with omalizumab with IgE levels greater than 700 IU/mL.MethodsAsthmatic patients treated with omalizumab for 6 months or longer with elevated IgE levels were evaluated retrospectively. Emergency department (ED) visits, hospitalizations, change in forced expiratory volume in 1 second, corticosteroid bursts, and Asthma Control Test (ACT) scores were recorded for a period of 6 months before and after treatment.ResultsTwenty-six patients with an IgE level greater than 700 IU/mL (group 1) were matched by age, sex, and severity of asthma to patients with an IgE of 30 to 700 IU/mL (group 2). The mean numbers of ED visits before and after treatment were 0.96 vs 0.23 (P = .008) in group 1 and 0.65 vs 015 (P = .02) in group 2. Both group 1 and group 2 had an improvement in asthma control based on the mean ACT score before and after treatment (15.6 vs 18.9 [P = .02] and 15.4 vs 19 [P = .006], respectively). There was also a significant reduction in the frequency of systemic corticosteroid use during the 6 months before and after treatment (2.58 vs 0.96 [P < .001] and 2.62 vs 1.23 [P < .001] systemic steroid treatments, respectively).ConclusionOmalizumab was as effective in reducing ED visits, controlling asthma symptoms, and reducing the need for systemic corticosteroids in patients with IgE levels greater than 700 IU/mL compared with patients with levels of 30 to 700 IU/mL.     

Characteristics and diagnoses of cockroach-sensitive bronchial asthma.

Bronchial asthma with cockroach hypersensitivity is prevalent among urban asthmatic populations. To elucidate characteristics of cockroach asthma, we analyzed 592 consecutive urban Chicago asthmatic patients retrospectively. Allergy skin testing (AST) with common inhalants, serum total IgE, and cockroach-specific IgE (IgE-CR) antibodies were measured. Some cockroach asthmatics were studied further for bronchial reactivity in vivo and histamine releasability (HR) in vitro against cockroach allergen (CRa), and diagnostic accuracy for asthma was analyzed. Clinical characteristics were evaluated and compared with those of ragweed asthmatics and asthmatics in general. Two hundred eighty-three (196 women, 87 men) were reactive to CRa by AST. The average age and duration of cockroach asthma were 30.4 and 15.1 years, respectively. Steroid dependency of the cockroach asthma was higher (32%) than those of general asthmatics (P less than .05) and ragweed asthma (P less than .05). IgE level was elevated (geometric mean 413.2 IU/mL), higher than that of general asthmatics (P less than .001), and 87% showed IgE level higher than 100 IU/mL. IgE-CR and BPT-CR were positive in 61% (175 tested) and in 87% (166 tested), respectively. Sensitivity and specificity of skin test were 99% and 40%, while those of IgE-CR were 91% and 58%, respectively. IgE-CR increased probability of cockroach asthma from 87% to 91%. BPT with CRa was correlated well with the HR of leukocytes (P less than .0001). Thus, cockroach asthma is a severe allergic asthma and can be diagnosed accurately by skin test plus BPT or skin test plus HR.     

Association of cigarette smoking with elevated serum IgE levels in Hispanic Puerto Rican men.

Unexplained elevation of serum IgE concentrations occurs in cigarette-smoking Caucasian males from temperate zones. To determine whether race or geography might be factors, we measured serum IgE concentrations in 94 Puerto Rican Hispanic patients, including smokers and nonsmokers. Mean serum IgE levels were elevated in our total patient population compared with Caucasian Americans. Geometric mean IgE was significantly increased in total smokers (157 IU/mL) compared with nonsmokers (78 IU/mL) and in male smokers greater than age 55 years (335 IU/mL) compared with male nonsmokers (41 IU/mL). Serum IgE was not significantly increased in female smokers. Among patients older than 55 years, persistent elevation of serum IgE occurred in male smokers. Our findings in a Puerto Rican Hispanic population are similar to those in studies of Caucasian smokers in temperate zones.     

Relationship between IgE and specific aeroallergen sensitivity in Alaskan native children.

BACKGROUND: The relationship between atopic disease and serum IgE levels varies among populations and geographic regions. The close association of atopy with IgE may not occur in subarctic populations as it does in developed countries in temperate climates. OBJECTIVE: To evaluate the relationship between total and specific IgE concentrations and clinical atopy in 5- to 8-year-old Alaskan native children. METHODS: Medical record reviews, interviews, physical examinations, serum IgE measurements, and radioallergosorbent testing (RAST) were performed. RESULTS: The IgE geometric mean was 122.1 IU/mL. Fifty-eight percent of patients had IgE levels greater than 70 IU/mL, and 17% had levels greater than 1,000 IU/mL; 14% had RAST values greater than 0.35 kU/L. Both IgE levels greater than 70 IU/mL and greater than 1,000 IU/mL were associated with RAST values greater than 0.35 IU/L (P = .004) and early wheezing (P = .005) but not with current wheezing, asthma, eczema, or a history of allergies. A RAST value greater than 3.51 kU/L was associated with eczema (P = .04) but not with allergies or wheezing. Children with current wheezing were more likely to have allergies (P = .03) but not eczema, an IgE level greater than 70 IU/mL, or a positive RAST value. Children hospitalized with respiratory syncytial virus (RSV) were not more likely than controls to have current wheezing. CONCLUSIONS: Elevated serum IgE concentrations, including levels greater than 1,000 IU/mL, are common among Alaskan native children; positive RAST reactions to aeroallergens are not. The IgE levels do not relate to wheezing, eczema, a history of allergies, or past hospitalization for RSV infection but likely reflect infections other than RSV and environmental factors in subarctic indigenous populations.     

Aspirin sensitivity and severity of asthma: evidence for irreversible airway obstruction in patients with severe or difficult-to-treat asthma

BACKGROUND: Patients with aspirin sensitivity experience hyperplastic sinusitis and nasal polyposis. We speculated that similar mechanisms could be acting in the lower airway and that these individuals would demonstrate more severe asthma and irreversible loss of lung function. OBJECTIVE: We sought to investigate the role of aspirin-exacerbated respiratory disease (AERD) as a risk factor for the development of irreversible airway obstruction. METHODS: The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study is a multicenter observational study of subjects with severe or difficult-to-treat asthma. Data were compared between subjects who reported asthma exacerbation after aspirin ingestion and those who did not. The primary measure of bronchodilator-resistant obstruction (possible remodeling) was the maximally achieved postbronchodilator spirometry averaged over the 3-year duration of the study. RESULTS: Adult subjects (>/=18 years) with AERD (n = 459) were compared with subjects with non-aspirin-sensitive asthma (n = 2848). Subjects with AERD had significantly lower mean postbronchodilator percent predicted FEV(1) compared with subjects with non-aspirin-sensitive asthma (75.3% vs 79.9%, P < .001). Differences in spirometry between the 2 cohorts persisted after controlling for potential confounding variables. In addition, subjects with AERD were more likely to have severe asthma by means of physician assessment (66% vs 49%, P < .001), to have been intubated (20% vs 11%, P < .001), to have a steroid burst in the previous 3 months (56% vs 46%, P < .001), and to have required high-dose inhaled corticosteroids (34% vs 26%, P < .001). CONCLUSIONS: These data suggest that aspirin sensitivity is associated with increased asthma severity and possible remodeling of both the upper and lower airways.     

Increased serum IgE in alcohol abusers

Background: It has been reported that total serum IgE is increased in patients with alcoholic cirrhosis, but it is not clear if this fact is related to alcoholic liver disease or to alcohol intake. Objective: To measure serum IgE in a group of chronic alcoholics with different stages of liver injury in order to elucidate if IgE increase is related to alcoholic liver damage. Patients and methods: Total serum IgE was determined by enzyme immunoassay in 186 chronic alcoholic patients (137 male/49 female) and 101 healthy controls. Patients and controls with known reasons for IgE elevation were excluded. Among alcoholic patients, 24 had fatty liver, 28 hepatic fibrosis, 29 alcoholic hepatitis, and 67 liver cirrhosis (38 patients were not evaluable concerning liver injury). Results: Total serum IgE was found to be increased in alcoholics (median 154.5IU/mL, range 1–7329IU/mL) with respect to healthy controls (median 20IU/mL, range < 1–1417 IU/mL) (P < 0.001). IgE increase was moderate (180–1000 IU/mL) in 60 alcoholics (32.3%) and marked (> 1000 IU/mL) in 27 (14.5%). Male alcoholics had higher IgE levels than females (median 191 IU/mL and range 1–7329 IU/mL vs 105IU/mL and range 2–2189IU/mL) (P= 0.009). On logistic regression analysis, alcoholism, male sex and younger age (but not smoking) were independently associated with higher IgE levels. No clear relationship was noted between serum IgE and severity of alcoholic liver disease. Thus, no correlation was observed between IgE and parameters of liver function (serum bilirubin, albumin or prothrombin index). Likewise, IgE concentrations were not significantly different in patients with liver cirrhosis with respect to patients with less severe liver disease. Serum IgE was increased (> 180 IU/mL) in 47.8 % of cirrhotics and in 44% of patients without liver cirrhosis. In contrast, other immunoglobulins (IgG, IgA and IgM) were significantly correlated with liver dysfunction. Conclusion: Chronic alcoholism should be considered as a cause of increased total serum IgE, regardless of the severity of the underlying liver disease.     

Leukotrienes and 8-isoprostane in exhaled breath condensate of children with stable and unstable asthma

BACKGROUND: Cysteinyl-leukotrienes (cys-LTs) and 8-isoprostane are biomarkers of airway inflammation and oxidative stress. OBJECTIVE: The aim of this study was to evaluate cys-LT and 8-isoprostane levels in exhaled breath condensate (EBC) of children with different degrees of asthma severity. METHODS: EBC was collected from 14 steroid-naive children with mild persistent asthma, 13 children with stable mild- to-moderate persistent asthma treated with inhaled corticosteroids (ICS), 9 ICS-treated children with unstable asthma, and 19 healthy children. RESULTS: In the three groups of asthmatic children, EBC concentrations of cys-LTs and 8-isoprostane were significantly higher than in control children (steroid-naive asthmatic children: cys-LTs median, 10.8 pg/mL, P <.001, 8-isoprostane, 16.2 pg/mL, P <.001; ICS-treated stable asthmatic children: cys-LTs, 12.7 pg/mL, P <.001, 8-isoprostane, 18.1 pg/mL, P <.001; children with unstable asthma: cys-LTs, 106.0 pg/mL, P <.01, 8-isoprostane, 29.7 pg/mL, P <.01; control children: cys-LTs, 4.3 pg/mL, 8-isoprostane, 3.5 pg/mL). Cys-LT levels were higher in children with unstable asthma than in the other two asthmatic groups (P <.05). FE(NO) levels were significantly higher in steroid-naive and in children with unstable asthma compared with ICS-treated children with stable asthma (P <.01). CONCLUSIONS: Our study shows that EBC cys-LTs and 8-isoprostane concentrations are higher in asthmatic children than in healthy control children, with scattered values in patients with unstable asthma. These findings suggest that EBC eicosanoid measurement may have useful clinical implications for investigating phenotype differences among asthmatic patients.     

Experimental rhinovirus challenges in adults with mild asthma: response to infection in relation to IgE

BACKGROUND: Although most children and young adults with asthma are atopic, exacerbations of asthma are frequently associated with viral respiratory tract infections, especially those caused by rhinovirus (HRV). OBJECTIVE: Young atopic adults with mild asthma were evaluated before and during an experimental HRV infection to test the hypothesis that airway inflammation before virus inoculation may be a risk factor for an adverse response to HRV. METHODS: Experimental HRV infections were evaluated in 16 allergic volunteers with mild asthma and 9 nonatopic control patients (age, 18 to 30 years). Before virus inoculation, each participant was screened with tests for lung function, prick skin tests for sensitization to common aeroallergens, measurements of total serum IgE, and serum neutralizing antibody to rhinovirus-16 (the serotype used for inoculation). The response to infection was monitored for 21 days by using symptom diary cards, tests for lung function, and markers of airway inflammation in nasal washes, blood, and expired air. RESULTS: During the infection, asthmatic patients had cumulative upper and lower respiratory tract symptom scores that were significantly greater over the course of 21 days than scores from the control patients. At baseline, the asthmatic patients also had increased sensitivity to methacholine and significantly lower values for FEV(1) (percent predicted) than the control patients (geometric mean and intraquartile values: 87% [79% to 91%] for the asthmatic patients and 101% [90% to 104%] for the control patients, P <.03). Among the patients with mild asthma, 6 had levels of total serum IgE that were substantially elevated (range, 371 to 820 IU/mL) compared with 10 who had lower levels (range, 29 to 124 IU/mL). Those with high levels of IgE had significantly greater lower respiratory tract symptom scores during the initial 4 days of the infection than the low IgE group. They also had higher total blood eosinophil counts at baseline, increased eosinophil cationic protein in their nasal washes (>200 ng/mL), and augmented levels of expired nitric oxide at baseline and during peak cold symptoms. In contrast, levels of soluble intracellular adhesion molecule-1 in nasal wash supernatants from the asthmatic patients with high IgE were diminished, both at baseline and during the infection. CONCLUSIONS: The reduced lung function and increased markers of inflammation observed before virus inoculation in the asthmatic patients who had high levels of total serum IgE may be risk factors for an adverse response to infections with HRV.     

Immunoglobulin E pattern in cigarette smokers

Serum IgE levels in healthy blood donors who had no history of atopy were measured by a paper-disc RIA and analyzed according to the donors' smoking habits. The IgE geometric mean for regular smokers was 41.7 IU/ml, which was significantly higher than that for nonsmokers (19.3 IU/ml) or rare smokers (22.7 IU/ml). Whereas 28% of smokers had IgE levels greater than 200 IU/ml, none of the rare smokers or nonsmokers did. IgE levels in smokers showed a moderate inverse correlation with the degree of smoking. The mean IgE level was 189.8 IU/ml in those who smoked 1–9 cigarettes/day but only 32.8 IU/ml in those who smoked 10–19 cigarettes per day and 11.1 IU/ml in those who smoked 20 or more cigarettes/day. The number of years a person smoked did not seem to significantly influence the IgE level. The mean IgE level in ex-smokers (50.5 IU/ml) was much lower than in current light smokers but was still higher than in nonsmokers. There was a moderate inverse correlation between IgE levels and duration of cessation of smoking. Our data suggest a characteristic pattern for the influence of cigarette smoking on serum IgE level, namely, a striking rise associated with light smoking and a remarkable drop in heavy smokers, and such changes seemed reversible after the habit was stopped. Smoking status, therefore, appears to be an important consideration in interpreting serum IgE levels and in revising the "norms" of IgE levels.     

Cat and dust mite sensitivity and tolerance in relation to wheezing among children raised with high exposure to both allergens

BACKGROUND: Recent evidence has suggested that high exposure to cat allergens is associated with decreased prevalence of sensitization to cat and, in some studies, decreased asthma. OBJECTIVE: Our objective was to study antibodies to cat and mite allergens and their relationship to wheezing in a country with high exposure to both allergens. METHODS: Sera from 112 wheezing and 112 control children aged 10 to 11 years in a nested case-control study in New Zealand were assayed for specific IgE antibody, as well as IgG antibody and IgG4 antibody, to Der p 1 and Fel d 1. RESULTS: IgE antibody to both mite (99/224) and cat (41/224) were strongly associated with wheezing (odds ratios, 5.2 and 6.5, respectively). Children who had ever lived with a cat were less likely to have IgE antibody to cat (20/141 vs 21/83, P < .04); however, cat ownership had no effect on IgE antibody to mite (67/141 vs 32/83, P = .23). Among sensitized children, cat ownership was associated with a lower prevalence of IgE antibody to cat (28% vs 66%, P < .001), and this analysis remained significant after exclusion of children whose families had chosen not to own a cat. Among sensitized subjects, the mean titer of IgE antibody to cat (1.7 IU/mL) was 10-fold lower than for mite (22.1 IU/mL). A cat in the home had no significant effect on endotoxin or mite allergen in house dust, whereas cat allergen was much higher (40.8 vs 3.3 microg/g). CONCLUSION: The response to these 2 allergens was distinct on the basis of the prevalence of sensitization, the titer of IgE antibody, and the effect of cat ownership. The results suggest that induction of tolerance to cat allergen is an allergen-specific phenomenon that cannot be attributed to endotoxin or family choice. The strength of the IgE antibody response to dust mite in humid climates could contribute to the increased prevalence and severity of asthma.     

Comparison of total IgE and anti-mite IgE antibody levels in the sera of patients with atopic dermatitis and/or atopic bronchial asthma

In the present study characterization of serological features of AD and/or BA patients were attempted. Nearly all of the patients (23 out of 24) with AD with or without episodes of BA had total IgE levels higher than 1,000 IU/ml. Conversely, 14 out of the 15 BA patients showed total IgE levels less than 1,000IU/ml.9 out of the 14 AD patients with BA(AD + BA) had histories of childhood asthma but required no current treatment for BA. The rest of the AD + BA patients required medication for BA but they were easily controllable with conventional bronchodilators such as beta 2 stimulators and/or xanthine derivatives. It was shown that AD patients (n = 6) with extremely high titers of anti-mite IgE antibodies (more than 110 PRU/ml up to 820 PRU/ml) remained free from BA episodes in the presence of hyper IgE immunoglobulinemia (1,818 IU/ml to 47,300 IU/ml). The results indicated that hyper IgE immunoglobulinemia in atopic patients might prevent the development of severe BA, but on the other hand, increase the possibility of developing AD.     

Analysis of vascular endothelial growth factor levels in induced sputum samples from patients with cough variant asthma.

BACKGROUND: We previously found that vascular endothelial growth factor (VEGF) levels in induced sputum samples are increased in patients with classic asthma and are associated with the degree of airflow obstruction and airway microvascular permeability. OBJECTIVE: To examine VEGF levels and the degree of airway microvascular permeability in patients with cough variant asthma (CVA). METHODS: Levels of VEGF in induced sputum samples and airway microvascular permeability were examined in 12 controls, 16 patients with CVA, and 16 patients with classic asthma. We also evaluated the relationship between VEGF level and the clinical features of these 2 disorders. RESULTS: Mean (SD) VEGF levels and airway vascular permeability index values were significantly higher in patients with CVA (VEGF: 2,520 [1,050] pg/mL; P < .001; vascular permeability index: 0.017 [0.006]; P = .003) and classic asthma (4,750 [1,260] pg/mL; P < .001; 0.028 [0.009]; P < .001) than in controls (1,420 [1,230] pg/mL; 0.009 [0.003]). Furthermore, these values were significantly higher in patients with classic asthma vs CVA. We also found significant correlations between VEGF level and airway vascular permeability index in patients with CVA (r = 0.60; P = .02) vs classic asthma (r = 0.83; P = .001). Furthermore, VEGF levels were inversely correlated with the degree of airflow obstruction and airway hyperresponsiveness to methacholine in patients with CVA and classic asthma. CONCLUSIONS: Airway microvascular hyperpermeability induced by elevated VEGF levels contributes to abnormal airway function in CVA and classic asthma, and differences in the clinical features of these 2 disorders may depend on airway VEGF levels.     

Use of a chimeric ELISA to investigate immunoglobulin E antibody responses to Der p 1 and Der p 2 in mite-allergic patients with asthma, wheezing and/or rhinitis

BACKGROUND: Sensitization to indoor allergens, particularly to dust mites, is a strong risk factor for asthma in children and adults. Assessment of sensitization is carried out using in vivo and in vitro tests to detect specific IgE antibodies. OBJECTIVE: To investigate IgE antibody responses to mites in patients with asthma, wheezing and/or rhinitis, using chimeric ELISA to measure specific IgE antibodies to mite allergens Der p 1 and Der p 2. METHODS: Specific IgE antibodies to Der p 1 and Der p 2 were quantified by chimeric ELISA, and compared with IgE to Dermatophagoides pteronyssinus (Dpt) measured using the CAP system (Pharmacia). A panel of sera from 212 patients with asthma, wheezing and/or rhinitis and 11 controls was analysed. RESULTS: There was a significant correlation between IgE to Dpt measured by CAP and IgE to Der p 1 (r = 0.81, P < 0.001), Der p 2 (r = 0.79, P < 0.001) and combined Der p 1 and Der p 2 (r = 0.86, P < 0.001). Seventy per cent of all patients had IgE to Dpt, and of those, 76.5% had IgE to Der p 1, 79.2% had IgE to Der p 2 and 83.1% had IgE to Der p 1 and Der p 2 combined. Considering the cut-off level of 2 IU/mL of IgE to either Der p 1 or Der p 2, the predictive value for a positive IgE to Dpt by CAP was greater than 95%. CONCLUSIONS: The chimeric ELISA allowed accurate quantification of IgE antibodies to Dpt allergens Der p 1 and Der p 2, and it could be useful for studying immune responses to mites in patients with asthma and/or rhinitis.     

Leptin: does it have any role in childhood asthma?

BACKGROUND: Although there is evidence of a positive association between asthma and obesity in adults and children, very little is known about the role of leptin in asthmatic children. OBJECTIVES: The aims of this study were to evaluate the relation between leptin and parameters of atopy and asthma in children. METHODS: Body mass index (BMI) and serum leptin levels were measured in 102 (37 female, 65 male; mean age, 5.9 +/- 3.4 years) asthmatic and 33 (14 female, 19 male; mean age, 6.1 +/- 3.4 years) healthy children. Skin prick tests, total serum IgE, and pulmonary function tests were performed and were completed. RESULTS: A significant difference was observed in serum leptin levels between asthmatic and healthy children. Median (interquartile range) levels were 3.53 (2.06-7.24) ng/mL and 2.26 (1.26-4.71) ng/mL, respectively (P=.008). Subgroup analysis revealed that this difference in leptin levels was confined entirely to boys: 3.09 (1.99-7.51) ng/mL in boys with asthma versus 1.52 (1.06-3.17) ng/mL in boys without asthma (P=.003). By logistic regression analysis, we found that leptin was a predictive factor for having asthma (odds ratio, 1.98; CI, 1.10-3.55; P=.021), whereas sex, age, or BMI were not. In a stepwise multiple regression analysis including sex (P=.001), age (P=.016), BMI (P <.001), and asthma (P=.022), all of these variables were found to affect log leptin levels (R2=0.404). There was no significant sex difference in serum leptin levels among asthmatic children, whereas healthy boys had significantly lower leptin levels than healthy girls (P=.019). Atopic asthmatic subjects had significantly higher leptin levels than nonatopic asthmatic subjects (P=.038) with similar BMI. A significant, but weak, correlation was observed between leptin levels and IgE in the overall group of asthmatic children (r=0.231; P=.019). Again, this correlation was confined entirely to boys (r=0.319; P=.010). There was no relation between leptin levels and skin prick tests, pulmonary function tests, passive smoking, birth weight, and duration of breast-feeding. CONCLUSION: Our findings suggest that leptin may play a role in atopic asthma. High serum leptin levels in asthmatic boys may partly explain the higher prevalence of childhood asthma in male sex.