IgE antibody to Aspergillus fumigatus recombinant allergens in cystic fibrosis patients with allergic bronchopulmonary aspergillosis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) is characterized by a heightened Th2 CD4+ T-cell response to Aspergillus fumigatus (Af) allergens and a hyper-immunoglobulin E (IgE) state compared with cystic fibrosis patients without ABPA. The IgE serologic differentiation of ABPA from atopic CF patients can be difficult. We propose as the reactivity with purified antigens varies qualitatively and quantitatively and that the antibody response is more specific than with crude Af antigen extract, the IgE responses to purified recombinant Af allergens may differentiate ABPA from atopic CF patients. METHODS: Serum IgE reactivity to seven recombinant purified allergens and to a crude extract of Af was measured in 15 ABPA, in 23 Af skin test positive (ST+), and in 19 Af skin test negative (ST-) CF patients. Four of the ABPA CF patients were studied before and after developing ABPA. Nine ABPA patients were studied during flares and remissions of ABPA. RESULTS: Allergic bronchopulmonary aspergillosis patients had significantly increased IgE reactivity to Asp f2, f3, f4, f6, and f16 compared with the Af ST+ and ST- non-ABPA CF patients. In the ABPA patients studied before and after developing ABPA, IgE reactivity also increased to Asp f2, f3, f4, and f6, and to the crude extract. In ABPA CF patients, IgE reactivity to Asp f1, f2, f3, and f6 significantly increased during periods of ABPA flares compared with periods of remission. Analysis of the receiver operating curve demonstrated that IgE reactivity to Asp f3 and f4 gave the best sensitivity and specificity and were better than IgE reactivity to a crude extract of Aspergillus. Furthermore, in ABPA patients studied during periods of remission the IgE reactivity to Asp f3 and f4 remained significantly elevated compared with Af ST+ non-ABPA patients. The IgE responses when considered either to be positive or negative to Asp f3 and f4 significantly differentiated ABPA from Af ST+ and ST- non-ABPA CF patients. In contrast, IgE reactivity was considered positive to the crude extract in 89% of ABPA, 61% of Af ST+, and 0% of Af ST- non-ABPA CF patients. CONCLUSIONS: Immunoglobulin E reactivity to a panel of purified Af allergens, especially to Asp f3 and f4, differentiates ABPA from atopic Af ST+ non-ABPA CF patients. Serial determinations of IgE reactivity to individual purified Aspergillus antigens, especially Asp f3, demonstrates that increases in IgE reactivity may provide improved distinction between stages of flares and remission compared with changes in IgE reactivity to a crude Aspergillus extract.

"Allergic sinusitis" revisited.

BACKGROUND: "Allergic sinusitis" is a frequently used term but there is question about its true existence. OBJECTIVE: To detect the presence of allergic inflammation of the sinuses in five highly symptomatic ragweed sensitive adults. METHOD: Three imaging techniques were utilized: SPECT bone imaging, SPECT Indium111 labeled WBC uptake, and FDG F-18 (PET scanning). RESULTS: We could find no evidence of sinus involvement in association with severe allergic rhinitis. CONCLUSIONS: Employing three different imaging modalities, we were unable to demonstrate inflammation of the sinuses in patients with allergic rhinitis.

Pediatricians' attitudes towards allergy: past and present attitudes of pediatricians towards allergy.

BACKGROUND: In 1971 we published a survey of pediatricians' knowledge, attitudes, and practices relative to the field of allergy. This current survey was conducted to determine how these attitudes and practices have changed over the past 27 years. METHODS: Our survey, consisting of 17 questions, was sent to 250 board certified pediatricians in the St. Louis area. Seven of the questions were similar to those in the 1971 survey, while the other ten were new questions which we thought were pertinent to the field of allergy currently. RESULTS: In 1971, 75% of the pediatricians felt the specialty of allergy had great or moderate importance for the practice of pediatrics compared with 99% in 1998. In 1998, the number of physicians who felt that there was at least some value to skin testing had increased from 1971, although, only 36% felt it had great value. In 1971, 23% of pediatricians performed their own skin tests compared with 3% in 1998. Nine percent indicated that they had never referred a patient to an allergist in 1971, compared with 2% in 1998. Our new questions looked at to whom respondents were more likely to refer patients with: (1) asthma (68% allergy, 27% pulmonary, 4% both), (2) urticaria (53% allergy, 41% dermatology, 2% both), (3) chronic eczema (45% allergy, 50% dermatology, 2% both), and (4) chronic sinusitis (24% allergy, 74% otolaryngology, 2% both). Older physicians placed greater importance on the field of allergy and skin testing and were more likely to refer to an allergist than physicians under the age of 40 years. CONCLUSION: Our results indicate that although there has been significant change in 27 years, allergists must be more aggressive in developing the knowledge, attitudes, and practices of physicians relative to the field of allergy.

Evidence for the involvement of two different MHC class II regions in susceptibility or protection in allergic bronchopulmonary aspergillosis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is a disease with uncertain pathology. Studies have suggested a pathogenic role for T(H)2 cells. Previously, we demonstrated, in a small group of patients, that T(H)2 reactivity to a major Aspergillus fumigatus antigen was restricted by HLA-DR2 or HLA-DR5 alleles. OBJECTIVES: We sought to confirm whether susceptibility to ABPA is exclusively associated with HLA-DR locus and to investigate the involvement of HLA-DQ genes in the development of ABPA. METHODS: Genomic DNA was extracted from patients with ABPA, patients without ABPA but with positive A fumigatus skin test responses and asthma or cystic fibrosis, and healthy control subjects. HLA-DR and HLA-DQ genes were detected by using low-resolution typing; high-resolution typing was done only on HLA-DR2- and HLA-DR5-positive individuals by using sequence-specific primers (PCR-SSP). RESULTS: A significantly higher frequency of HLA-DR2 was observed in patients with ABPA versus those without ABPA (corrected P <.01) or healthy control subjects (corrected P <.01). Genotype analysis revealed that susceptibility to ABPA is associated with HLA-DR2 alleles DRB1*1503 and DRB1*1501 and, to a lesser extent, with the HLA-DR5 allele DRB1*1104. The presence of DR4 or DR7 alleles in non-DR2/5 patients with ABPA suggests that these alleles may also be contributing factors in this disease. Another striking observation was the significantly high frequency of HLA-DQ2 in patients without ABPA (67. 4%) compared with patients with ABPA (20.5%) and normal control subjects (37.7%), suggesting that these alleles may confer protection in the population without ABPA. CONCLUSION: These genetic studies suggest that HLA-DR molecules DR2, DR5, and possibly DR4 or DR7 contribute to susceptibility while HLA-DQ2 contributes to resistance and that a combination of these genetic elements determines the outcome of ABPA in patients with cystic fibrosis and asthma.

Occupational rhinitis.

BACKGROUND: Occupational rhinitis is a common but generally unappreciated entity. It frequently exists with asthma but may present alone. While not as dramatic a presentation as bronchial asthma, it nevertheless results in significant discomfort and work inefficiency. The history and physical examination are the most important components to the workup of the patient. The frequent occurrence of an isolated late phase nasal response may make the correct diagnosis confusing. A site visit to the specific work area may give helpful insights to the patient's exposure. Greater objectivity to the diagnosis can be obtained through the rapidly developing technique of rhinomanometry. CONCLUSION: The management of occupational rhinitis should include not simply pharmacotherapy but also environmental control measures. Through these means, patients may be spared the distress and discomfort of occupational rhinitis.

Does inhaled pollen enter the sinus cavities?

BACKGROUND: While there is evidence of an increased incidence of sinusitis in patients with allergic rhinitis, it is unclear whether an allergic process occurs in the sinus tissues per se. OBJECTIVE: The purpose of this study was to determine whether inhaled pollen reaches the sinus mucosa. METHODS: Tc99m labeled ragweed pollen was inhaled by five non-atopic adults. Imaging studies of the sinuses were performed with a tomographic rotating gamma camera. To determine the sensitivity of the technique, the nose and the maxillary sinuses of cadaver heads were painted with varying amounts of Tc99m and then similarly scanned. RESULTS: Scans of the cadaver heads showed clear resolution between the nasal cavity and the maxillary sinus. It was determined that 20 microci was the smallest amount of Tc99m that could be resolved to be in the sinuses. Scans of subjects showed intense activity in the nasal cavity but none in the paranasal sinuses despite the delivery of a supraphysiologic dose of Tc99m ragweed pollen. CONCLUSION: Inhaled ragweed pollen does not appear to enter the paranasal sinuses. It is unlikely that an inhaled antigen-IgE antibody reaction occurs in the sinus mucosa.

Adrenal insufficiency in an adult on inhaled corticosteroids; recovery of adrenal function with inhaled nedocromil sodium.

BACKGROUND: Whereas oral corticosteroids and high-dose inhaled corticosteroids may be associated with suppression of the hypothalamic-pituitary-adrenal axis, medium-dose inhaled corticosteroids have not been reported to be associated with clinically significant adrenal insufficiency in the adult. OBJECTIVE: A case study of adrenal responsiveness after prolonged medium-dose inhaled corticosteroids and after replacement of steroid therapy by inhaled nedocromil sodium is described. METHODS: Standard 250-microg dose ACTH (cosyntropin) stimulation tests were followed after replacement of inhaled triamcinolone acetonide therapy by nedocromil sodium. RESULTS: A 55-year-old woman who had been on inhaled triamcinolone acetonide, 1600 microg/day for 12 years, presented with symptoms of adrenal hypofunction upon inhaled corticosteroid taper. An ACTH stimulation test confirmed adrenal insufficiency. She was switched to inhaled nedocromil sodium with improvement in her clinical syndrome and normalization of her ACTH stimulation test. CONCLUSION: Withdrawal from prolonged use of inhaled medium-dose corticosteroids may be associated with clinically significant adrenal insufficiency in adults. Steroid sparing agents may be considered for those on long-term inhaled corticosteroid therapy.

Nasal polyps and sinusitis.

Despite the prevalence and long history of nasal polyps, many questions still exist with respect to incidence and pathogenesis. Although allergy has been commonly thought to be a major cause, much compelling evidence argues against this. Medical therapy consists of a short course of systemic steroids followed by intranasal steroids. Sinusitis is the most commonly reported chronic disease in the United States. Decrease in ostial size, retention of secretions, and decrease in mucociliary action all contribute to the pathogenesis of sinusitis. The clinical presentation of chronic sinusitis is generally subtle and the clinical index of suspicion must be high. Limited coronal computed tomography is regarded as the most definitive and cost-effective imaging technique for the diagnosis of sinusitis. Appropriate antibiotics must be administered for a sufficient period. In medically resistant sinusitis, functional endoscopic sinus surgery has emerged as the procedure of choice.

The association of HLA-DR alleles and T cell activation with allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease caused by the mold Aspergillus fumigatus. We previously reported that the majority of T cell clones (TCC) isolated from three ABPA patients, and specific for a dominant Ag of A. fumigatus, Asp f 1, were IL-4-producing CD4+ Th2 cells capable of responding to Ag in association with the HLA-DR subtypes DRB1*1501, *1503, and *1601 for HLA-DR2, and DRB1*1101, *1104, and *1202 for HLA-DR5. In the present study we extended the previous findings to determine whether the observed restriction with the HLA-DR2/5 subtypes held importance in a larger patient population. Serotyping revealed that 16 of 18 ABPA patients were either HLA-DR2, HLA-DR5, or both. Compared with a normal control population, the frequencies of HLA-DR2 (50 vs 22.3%) and HLA-DR5 (44.4 vs 19.8%) were significantly increased in these ABPA patients. Genotype analyses of an additional 15 patients identified the same HLA-DR subtypes previously shown functional for Asp f 1 Ag presentation. The relative avidities of Asp f 1 peptides for the purified HLA-DR subtypes, DRB1*1501 (functional) and DRB1*1502 (nonfunctional), were examined to determine whether differential binding to the HLA-DR subtypes explains successful Ag presentation. Similar low binding avidities were detected for both HLA-DR subtypes, indicating that the functionality cannot be simply explained by differences in binding affinities. Thus, the limited number and their role in Ag presentation emphasizes the possibility that the six identified HLA-DR subtypes are important in the pathophysiology of ABPA.

The role of cockroach allergy and exposure to cockroach allergen in causing morbidity among inner-city children with asthma.

BACKGROUND: It has been hypothesized that asthma-related health problems are most severe among children in inner-city areas who are allergic to a specific allergen and also exposed to high levels of that allergen in bedroom dust. METHODS: From November 1992 through October 1993, we recruited 476 children with asthma (age, four to nine years) from eight inner-city areas in the United States. Immediate hypersensitivity to cockroach, house-dust-mite, and cat allergens was measured by skin testing. We then measured major allergens of cockroach (Bla g 1), dust mites (Der p 1 and Der f 1), and cat dander (Fel d 1) in household dust using monoclonal-antibody-based enzyme-linked immunosorbent assays. High levels of exposure were defined according to proposed thresholds for causing disease. Data on morbidity due to asthma were collected at base line and over a one-year period. RESULTS: Of the children, 36.8 percent were allergic to cockroach allergen, 34.9 percent to dust-mite allergen, and 22.7 percent to cat allergen. Among the children's bedrooms, 50.2 percent had high levels of cockroach allergen in dust, 9.7 percent had high levels of dust-mite allergen, and 12.6 percent had high levels of cat allergen. After we adjusted for sex, score on the Child Behavior Checklist, and family history of asthma, we found that children who were both allergic to cockroach allergen and exposed to high levels of this allergen had 0.37 hospitalization a year, as compared with 0.11 for the other children (P=0.001), and 2.56 unscheduled medical visits for asthma per year, as compared with 1.43 (P<0.001). They also had significantly more days of wheezing, missed school days, and nights with lost sleep, and their parents or other care givers were awakened during the night and changed their daytime plans because of the child's asthma significantly more frequently. Similar patterns were not found for the combination of allergy to dust mites or cat dander and high levels of the allergen. CONCLUSIONS: The combination of cockroach allergy and exposure to high levels of this allergen may help explain the frequency of asthma-related health problems in inner-city children.