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This chapter examines a variety of immunologic-mediated lung diseases. Hypersensitivity pneumonitis is caused by exposure to a variety of antigens that elicit a Th1-mediated hypersensitivity response in the lungs. In contrast eosinophilic lung disease is typically a Th2-mediated response manifested by a prominent eosinophilic inflammatory response in the lungs. Eosinophilic lung diseases in which a causative antigen exposure has been identified include allergic bronchopulmonary aspergillosis, drug induced eosinophilia, and helminth associated eosinophilic lung disease. There are other eosinophilic lung diseases in which a causative exposure has not been identified, such as acute and chronic eosinophilic pneumonia, eosinophilic granuloma, and Churg-Strauss syndrome. Finally, hypereosinophilic syndrome, a systemic eosinophilic disorder in which the lung may be affected, is described.

Allergic fungal rhinosinusitis (AFRS) is a subset of chronic rhinosinusitis with nasal polyps (CRSwNP) characterized by antifungal IgE sensitivity, eosinophil-rich mucus (ie, allergic mucin), and characteristic computed tomographic and magnetic resonance imaging findings in paranasal sinuses. AFRS develops in immunocompetent patients, with occurrence influenced by climate, geography, and several identified host factors. Molecular pathways and immune responses driving AFRS are still being delineated, but prominent adaptive and more recently recognized innate type 2 immune responses are important, many similar to those established in patients with other forms of CRSwNP. It is unclear whether AFRS represents merely a more extreme expression of pathways important in patients with CRSwNP or whether there are other disordered immune responses that would define a distinct endotype or endotypes. Although AFRS and allergic bronchopulmonary aspergillosis share some analogous immune mechanisms, the 2 conditions do not occur commonly in the same patient. Treatment of AFRS almost always requires surgical debridement of the involved sinuses. Oral corticosteroids decrease recurrence after surgery, but other adjunctive pharmacologic agents, including topical and oral antifungal agents, do not have a firm evidence basis for use. There is good rationale for use of biologic agents that target eosinophilic inflammation or other type 2 responses, but studies in patients with AFRS are required.

Fungi cause a wide spectrum of fungal diseases of the upper and lower airways. There are three main phyla involved in allergic fungal disease: (1) Ascomycota (2) Basidiomycota (3) Zygomycota. Allergic fungal rhinosinusitis (AFRS) causes chronic rhinosinusitis symptoms and is caused predominantly by Aspergillus fumigatus in India and Bipolaris in the United States. The recommended treatment approach for AFRS is surgical intervention and systemic steroids. Allergic bronchopulmonary aspergillosis (APBA) is most commonly diagnosed in patients with asthma or cystic fibrosis. Long term systemic steroids are the mainstay treatment option for ABPA with the addition of an antifungal medication. Fungal sensitization or exposure increases a patient's risk of developing severe asthma and has been termed severe asthma associated with fungal sensitivity (SAFS). Investigating for triggers and causes of a patient's asthma should be sought to decrease worsening progression of the disease.

There remains a lack of agreement on diagnostic criteria and approaches to treatment of patients with allergic bronchopulmonary aspergillosis (ABPA). The results of a survey of American Academy of Allergy, Asthma,Immunology members regarding these 2 issues are presented and compared for concordance with published recommendations. The literature was reviewed for pertinent reports, and an electronic survey was conducted of American Academy of Allergy, Asthma,Immunology members and fellows regarding diagnostic criteria, numbers of patients evaluated for ABPA, and treatment approaches. From 508 respondents to the survey sent to 5155 US physicians in the American Academy of Allergy, Asthma,Immunology database of members and fellows, 245 health professionals (48%) had treated at least 1 patient with ABPA in the previous year. For the diagnosis of ABPA, there was a difference in the threshold concentration of total serum IgE because 44.9% used ≥417 kU/L, whereas 42.0% used ≥1000 kU/L. Analysis of these findings suggests that ABPA might be underdiagnosed. With regard to pharmacotherapy, oral steroids were recommended for 97.1% of patients and oral steroids plus inhaled corticosteroids plus antifungal agent were used with 41.2% of patients. The armamentarium for treatment of ABPA includes oral corticosteroids as the initial treatment with inhaled corticosteroids used for management of persistent asthma. Azoles remain adjunctive. Published experience with omalizumab has been limited.

A 61-year-old woman presented to our Allergy/Immunology clinic for pruritic dermatitis of both arms since 2006. Initial symptoms included pruritus and burning dysesthesias of the upper extremities without a rash. Months later an excoriated, papular rash developed along the upper extremities. Cold compresses provided some relief, whereas sun exposure worsened symptoms. Over the years consultations with multiple dermatologists did not elicit a diagnosis, and symptoms did not improve after numerous trials of topical corticosteroids and systemic antihistamines. The differential diagnosis of pruritic rash is extensive; however, in the case of chronic pruritus without a primary rash other diagnoses should come to mind. Although pruritus is a hallmark of many atopic conditions, as allergists-immunologists it is important to remember that not all pruritus is atopic in nature. Prompt recognition and treatment of an occult process presenting primarily with pruritus will likely result in improved outcomes for the patient.

Asthma is a common disorder that in 2009 afflicted 8.2% of adults and children, 24.6 million persons, in the United States. In patients with moderate and severe persistent asthma, there is significantly increased morbidity, use of health care support, and health care costs. Epidemiologic studies in the United States and Europe have associated mold sensitivity, particularly to Alternaria alternata and Cladosporium herbarum, with the development, persistence, and severity of asthma. In addition, sensitivity to Aspergillus fumigatus has been associated with severe persistent asthma in adults. Allergic bronchopulmonary aspergillosis (ABPA) is caused by A fumigatus and is characterized by exacerbations of asthma, recurrent transient chest radiographic infiltrates, coughing up thick mucus plugs, peripheral and pulmonary eosinophilia, and increased total serum IgE and fungus-specific IgE levels, especially during exacerbation. The airways appear to be chronically or intermittently colonized by A fumigatus in patients with ABPA. ABPA is the most common form of allergic bronchopulmonary mycosis (ABPM); other fungi, including Candida, Penicillium, and Curvularia species, are implicated. The characteristics of ABPM include severe asthma, eosinophilia, markedly increased total IgE and specific IgE levels, bronchiectasis, and mold colonization of the airways. The term severe asthma associated with fungal sensitization (SAFS) has been coined to illustrate the high rate of fungal sensitivity in patients with persistent severe asthma and improvement with antifungal treatment. The immunopathology of ABPA, ABPM, and SAFS is incompletely understood. Genetic risks identified in patients with ABPA include HLA association and certain T(H)2-prominent and cystic fibrosis variants, but these have not been studied in patients with ABPM and SAFS. Oral corticosteroid and antifungal therapies appear to be partially successful in patients with ABPA. However, the role of antifungal and immunomodulating therapies in patients with ABPA, ABPM, and SAFS requires additional larger studies.

The author surveys and assesses economic indicators and trends for the period January-November 2009.

Background Recent reports have attempted to redefine the accepted diagnostic criteria for allergic fungal rhinosinusitis (AFRS), a form of chronic rhinosinusitis (CRS) with nasal polyps. As a result, the existence of AFRS as a distinct entity has been questioned, suggesting that allergy has no role in CRS with sinonasal eosinophilia, and the condition should be referred to as eosinophilic fungal rhinosinusitis. The purpose of the study was to differentiate between AFRS and CRS by studying antibody responses in these two clearly defined patient groups. Methods Ninety-nine patients were enrolled and classified as AFRS or CRS (without AFRS). Serum total IgE, IgG anti–Alternaria-specific antibodies (UniCAP 100), and IgE antifungal antibodies (immunoblotting) were compared between the groups. Results Sixty-four patients fit the traditional criteria for AFRS, with 35 as CRS. Mean serum total IgE and mean IgG anti–Alternaria-specific antibodies were statistically significantly increased in AFRS over CRS patients. There was also a statistically significant increase in the mean number of IgE antifungal bands from AFRS compared with CRS patients. Conclusion We have shown a clear immunologic difference between AFRS and CRS patients. The overwhelming evidence of increased total IgE and fungal-specific IgE in AFRS supports an allergic component in AFRS. IgG anti–Alternaria-specific antibodies also point to an exaggerated fungal immune response in these patients. These results support the existence of AFRS as a separate, distinct entity of CRS. It is important to recognize AFRS to ensure proper treatment in these patients.

Once viewed as a "young person's disease," allergic rhinitis (AR) is becoming increasingly common in the elderly. Effective treatment is necessary not only to minimize the impact of AR in the older population, but to prevent the onset or exacerbation of asthma. This review was conducted to examine the clinical evidence regarding the efficacy and safety of therapies for AR in the elderly. MEDLINE searches of the literature were performed to identify key consensus statements, expert opinions, and clinical trials related to the management of AR in older individuals. The selection of treatment for elderly patients with AR must consider age-dependent physiologic factors (such as metabolic alterations, changes in the nasal mucosa, difficulty swallowing, and visual or motor problems) that may affect responses to therapy. Both first- and second-generation antihistamines are associated with a higher incidence of adverse events and drug:drug interactions in older than younger individuals, and oral decongestants pose risks in the presence of a variety of comorbidities known to be more common in the elderly. Leukotriene receptor antagonists are as effective as antihistamines, but are inferior to intranasal corticosteroids and have the potential for interactions with a wide range of drugs. Intranasal corticosteroids have the most favorable safety and efficacy profiles in older individuals with AR. The diagnosis and management of AR in the elderly require approaches tailored to specific age-related factors. Based on the available evidence, intranasal corticosteroids offer the best option for the treatment of older patients with AR.

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a bronchial allergic inflammatory reaction to Aspergillus fumigatus that occurs in a minority of susceptible asthmatic and cystic fibrosis (CF) patients. Previous studies identified that HLA-DR2/DR5 was associated with susceptibility to develop ABPA; however, HLA-DR2/DR5 occurs frequently in non-ABPA patients as well.Objective: We hypothesize that in addition to HLA-DR restriction, other genetic risk factors predispose asthmatic and CF patients to develop ABPA. Methods: HLA-DR and interleukin-4 (IL-4) receptor α-chain (IL-4RA), IL-13, and IL-10 -1082 polymorphisms were examined in 41 asthmatic and CF patients with ABPA and in 84 asthmatic and CF non-ABPA patients.Results: HLA-DR2 and/or DR5 were identified in 70.7% of ABPA patients and in 35.7% of non-ABPA patients. IL-4RA single-nucleotide polymorphisms (SNPs) were present in 95% of ABPA patients, with the ile75val SNP in 80.5% of ABPA patients. Both HLA-DR2/DR5 and IL-4RA SNPs individually we...

Background Hypersensitivity pneumonitis (HP) is an immune-mediated hypersensitivity reaction to a variety of inhaled particles that may lead to acute, subacute, or chronic interstitial pneumonitis and possibly end-stage lung disease. Avian antigens most commonly cause HP in children, but fungi have also been implicated. Objective To describe a 15-year-old girl and her 6-year-old brother who developed HP from residential exposure to Aureobasidium pullulans . Methods Allergy skin testing, serum precipitating antibodies, pulmonary function testing, chest radiography, chest computed tomography, bronchoalveolar lavage, and a home survey for possible causative antigens were performed. Results Both patients lived on a horse farm and had fatigue, weight loss, cough, and dyspnea. The siblings had restrictive patterns on pulmonary function tests, with decreased diffusion capacity of carbon monoxide, ground-glass opacities on high-resolution chest computed tomography, and serum precipitins to A pullulans . Bronchoalveolar lavage in the girl demonstrated lymphocytosis, with a preponderance of CD8 + T cells and natural killer cells. Symptoms improved after the children vacated the home and recurred on repeated exposure in both patients. Home evaluation revealed extensive mold contamination, with A pullulans counts of 659, 329, and 71 CFU/m 3 in the boy's bedroom, the girl's bedroom, and outdoors, respectively. Conclusions The diagnosis of HP in these siblings is supported by the clinical history, the diagnostic findings, and the recurrence of symptoms on repeated exposure. These cases represent the second report of HP resulting from nonoccupational exposure to A pullulans in North America and the first report in children.

The etiology of allergic bronchopulmonary aspergillosis (ABPA) is not well understood. A clinical phenotype resembling the pulmonary disease seen in cystic fibrosis (CF) patients can occur in some individuals with ABPA. Reports of familial occurrence of ABPA and increased incidence in CF patients suggest a possible genetic basis for the disease. To test this possibility, the entire coding region of the cystic fibrosis transmembrane regulator (CFTR) gene was analyzed in 11 individuals who met strict criteria for the diagnosis of ABPA and had normal sweat electrolytes (< or = 40 mmol/liter). One patient carried two CF mutations (deltaF508/R347H), and five were found to carry one CF mutation (four deltaF508; one R117H). The frequency of the deltaF508 mutation in patients with ABPA was significantly higher than in 53 Caucasian patients with chronic bronchitis (P < .0003) and the general population (P < .003). These results suggest that CFTR plays an etiologic role in a subset of ABPA patients.

Importance Soy isoflavone supplements are used to treat several chronic diseases, although the data supporting their use are limited. Some data suggest that supplementation with soy isoflavone may be an effective treatment for patients with poor asthma control. Objective To determine whether a soy isoflavone supplement improves asthma control in adolescent and adult patients with poorly controlled disease. Design, Setting, and Participants Multicenter, randomized, double-blind, placebo-controlled trial conducted between May 2010 and August 2012 at 19 adult and pediatric pulmonary and allergy centers in the American Lung Association Asthma Clinical Research Centers network. Three hundred eighty-six adults and children aged 12 years or older with symptomatic asthma while taking a controller medicine and low dietary soy intake were randomized, and 345 (89%) completed spirometry at week 24. Interventions Participants were randomly assigned to receive soy isoflavone supplement containing 100 mg of total isoflavones (n=193) or matching placebo (n=193) in 2 divided doses administered daily for 24 weeks. Main Outcomes and Measures The primary outcome measure was change in forced expiratory volume in the first second (FEV 1 ) at 24 weeks. Secondary outcome measures were symptoms, episodes of poor asthma control, Asthma Control Test score (range, 5-25; higher scores indicate better control), and systemic and airway biomarkers of inflammation. Results Mean changes in prebronchodilator FEV 1 over 24 weeks were 0.03 L (95% CI, −0.01 to 0.08 L) in the placebo group and 0.01 L (95% CI, −0.07 to 0.07 L) in the soy isoflavone group, which were not significantly different ( P = .36). Mean changes in symptom scores on the Asthma Control Test (placebo, 1.98 [95% CI, 1.42-2.54] vs soy isoflavones, 2.20 [95% CI, 1.53-2.87]; positive values indicate a reduction in symptoms), number of episodes of poor asthma control (placebo, 3.3 [95% CI, 2.7-4.1] vs soy isoflavones, 3.0 [95% CI, 2.4-3.7]), and changes in exhaled nitric oxide (placebo, −3.48 ppb [95% CI, −5.99 to −0.97 ppb] vs soy isoflavones, 1.39 ppb [95% CI, −1.73 to 4.51 ppb]) did not significantly improve more with the soy isoflavone supplement than with placebo. Mean plasma genistein level increased from 4.87 ng/mL to 37.67 ng/mL ( P Conclusions and Relevance Among adults and children aged 12 years or older with poorly controlled asthma while taking a controller medication, use of a soy isoflavone supplement, compared with placebo, did not result in improved lung function or clinical outcomes. These findings suggest that this supplement should not be used for patients with poorly controlled asthma. Trial Registration clinicaltrials.gov Identifier:NCT01052116

Recently, it has been recognized that inflammation is the major cause of chronic rhinosinusitis (CRS) rather than bacterial infection. Fungi have emerged as a possible pathogenic agent that drives CRS. One clear-cut group of fungal sinusitis can be divided into invasive and noninvasive. The condition that the allergist is most likely to see is allergic fungal sinusitis. Generally, it appears in atopic, immunocompetent, adolescents and young adults and is marked by the presence of nasal polyps and allergic mucin, which includes eosinophils, Charcot-Leyden crystals, and fungal hyphae. Computer tomographic imaging shows sinus opacification with hyperdense areas. Treatment has been successful with definitive nasosinus surgery and long-term oral prednisone. There is some evidence that fungi also may account for a large percentage of the remaining CRS patients. In this instance, the immune response to common airborne fungi appears to be IgG mediated rather than IgE mediated. Promising therapeutic results have been seen with intranasal antifungal agents but larger multicenter double-blinded placebo-controlled studies are needed. Another unanswered question includes the possible role of staphylococcus-derived enterotoxins in the pathogenesis of CRS.

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.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.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.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).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.

Asthma is an important problem in the elderly, our fastest growing age group. Asthma in the elderly is sometimes underdiagnosed and undertreated. The elderly asthmatic has a poorer quality of life, is hospitalized more often and is more likely to die. Comorbid conditions are much more common in the elderly and impact greatly on the diagnosis and management of asthma in this age group. While allergy is less common in the elderly than in younger age groups, it should still be considered in any patient with asthma. The management of asthma in the elderly must take into consideration comorbid conditions, polypharmacy and the increased probability of adverse reactions from medications.

Many common chronic inflammatory disorders have strong HLA gene associations, particularly with MHC class II. Allergic fungal rhinosinusitis (AFS) and hypertrophic sinus disease (HSD) are chronic sinonasal mucosal inflammatory disorders. Allergic bronchopulmonary aspergillosis, a disorder analogous to AFS, was recently reported to have HLA-MHC class II associations.We sought to determine whether MHC class II is also associated with AFS and HSD.HLA DNA genotyping was obtained on 44 patients with AFS and 30 patients with HSD (of which 21 were atopic).Sixty-six percent of patients with AFS carried at least one HLA-DQB1 *03 allele; DQB1 *0301 and DQB1 *0302 were the most frequent allelic variants (odds ratio [OR] vs healthy subjects = 8.22; 95% CI, 4.30-15.73; P.001; OR vs all patients with HSD = 1.93; 95% CI, 1.09-3.41; P.01; OR vs atopic patients with HSD = 2.57; 95% CI, 1.46-4.53; P.001). Of the 31 patients with AFS and positive Bipolaris spicifera cultures, 68% had DQB1 *03, with DQB1 *0301 and DQB1 *0302 being most frequent (OR vs healthy subjects = 8.93; 95% CI, 4.65-17.15; P.001; OR vs patients with HSD = 2.10; 95% CI, 1.18-3.73; P.001). Of the 30 patients with HSD, 50% carried DQB1 *03 (OR vs healthy subjects = 4.25; 95% CI, 2.25-8.02; P.001) but differed in frequencies of DQB1 *03 allelic variants compared with patients with AFS ( P = .0004). For HSD, nonatopic subjects had the highest DQB1 *03 association (OR vs healthy subjects = 8.63; 95% CI, 4.50-16.54; P.001). DQB1 *03 allelic variants did not correlate with allergy skin test results, atopic status, total serum IgE levels, culture results, asthma, or aspirin-nonsteroidal anti-inflammatory drug hypersensitivity.Patients with AFS and HSD have HLA-DQB1 *03 alleles as a risk factor for disease, with AFS having the highest association. However, they differ in DQB1 *03 allelic variant frequencies, suggesting several potential roles for MHC class II in their immunopathogenesis.

Objectives: to develop consensus definitions for rhinosinusitis and outline strategies useful in clinical trials

Allergic bronchopulmonary aspergillosis (ABPA) is a rare complication in patients with asthma but more common in patients with cystic fibrosis. In the presence of the fungus Aspergillus fumigatus (Af) in the lower respiratory tract, patients mount a heightened IgG and IgE humoral response specific for Af antigens. Studies on ABPA have suggested a pathogenic role for antigen specific CD4+ Th2 like T lymphocytes producing increased levels of IL-4 and IL-5. MHC class II genes coding for highly polymorphic HLA molecules have been shown to be the likely candidates for controlling immune responses to common allergens. However there has been a lack of information on the pathophysiological role of HLA genes in the development of ABPA. This review describes an association between HLA- class II alleles and the specific responses to Af antigen (Asp f 1) in ABPA. These studies focused on MHC restriction and distribution of HLA- class II alleles in two groups of unrelated North American Caucasian patients with cystic fibrosis and/or asthma. One group consisted of patients with a confirmed diagnosis of ABPA and a second group of patients with Af sensitivity but no ABPA. HLA association studies revealed that the predisposition to develop ABPA is associated with HLA-DR2 and DR5, and possibly DR4 or DR7. A strong association of HLA-DR antigens with ABPA reflects that HLA-DR molecules may present disease-causing peptides. On the other hand a significant association of HLA-DQ2 with Af sensitive nonABPA indicates the involvement of HLA-DQ molecules in protection. A combination of these genetic factors determines the outcome of ABPA in patients with cystic fibrosis and asthma.

Background Primary paranasal aspergillus granuloma (PPAG) is a slowly progressive chronic infection of the sinus extending beyond the confines of the sinus. It has been reported only in patients from the Sudan and India. Microscopically, it differs from chronic invasive fungal sinusitis in that there are pseudotubercles containing giant cells, histiocytes, lymphocytes, plasma cells, newly formed capillaries, eosinophils, and Aspergillus fungal elements. Conclusion We describe the first case of PPAG in the United States in an immunocompetent nonatopic woman who had never left Missouri.

Background In 1971, we published a survey regarding pediatricians' attitudes toward the field of allergy/immunology (A/I). Results indicated general attitudes and practices fell short of what most allergist-immunologists would hope. We revisited this in 1998 to determine how pediatricians' attitudes toward A/I had changed nearly 3 decades later. Despite some advances, results from 1998 revealed that A/I remained a misunderstood specialty. With the increasing incidence of atopic disorders and improving awareness of primary immunodeficiency, it is more important today than ever before that pediatricians and general practitioners have a strong appreciation for the scope of disorders the subspecialty of A/I encompasses. Objective To reevaluate attitudes and practices of pediatricians toward A/I 40 years after the initial study and 13 years after this topic was last addressed. Methods A 25-question survey was mailed to 293 pediatricians in the St Louis area. Surveys were completed confidentially. Pearson correlation and χ 2 analyses were performed. Results Of 293 pediatricians polled, 135 (46%) responded. Referrals to allergist-immunologists for urticaria have increased. Fewer pediatricians are referring asthma and atopic dermatitis patients to allergist-immunologists. Personal experience referring to an allergist-immunologist remains the greatest influence on current attitudes toward A/I. Prior exposure to A/I during medical education continues to have the least influence on pediatricians' attitudes toward A/I. Conclusion Increased appropriate referrals and improved patient outcomes could result from efforts to enhance A/I education during medical school and residency, maintain effective communication with referring physicians, and break down referral barriers to improve physicians' attitudes toward A/I.

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 Indium 111 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.

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.

The fatty liver dystrophy ( fld ) mutant mouse is characterized by neonatal fatty liver and hypertriglyceri- demia that resolve at weaning, and neuropathy affecting pe- ripheral nerve in adulthood. We now report additional sig- nificant manifestations of this single gene mutation, which include adipose tissue deficiency, glucose intolerance, and increased susceptibility to atherosclerosis. In adult fld/fld mice, both white and brown fat pads exhibit an 80% reduc- tion in mass compared with wild-type controls, and consist of immature adipocytes as assessed by morphological and molecular criteria. The lack of lipid accumulation in fld/fld adipose tissue could be attributed, in part, to a failure to in- duce expression of lipoprotein lipase and enzymes involved in fatty acid synthesis, such as fatty acid synthase and acetyl- CoA carboxylase. Related to the deficiency of adipose tissue, fld/fld mice were also found to exhibit profound glucose in- tolerance, modest hyperinsulinemia, and reduced tissue re- sponse to insulin. As insulin resistance is a important risk factor in vascular disease, we examined susceptibility of fld/fld mice to diet-induced atherosclerosis. Mutant mice fed an atherogenic diet developed 2-fold greater aortic lesions than their wild-type counterparts, despite having a less atherogenic lipoprotein cholesterol profile. The fld adipose-deficient phe- notype has both similarities to and distinctions from the group of rare human diseases known as lipodystrophies. — Reue, K., P. Xu, X-P. Wang, and B. G. Slavin. Adipose tissue deficiency, glucose intolerance, and increased atherosclero- sis result from mutation in the mouse fatty liver dystrophy ( fld ) gene. J. Lipid Res. 2000. 41: 1067-1076.

Cockroach allergen is important in asthma. Practical methods to reduce exposure are needed.We sought to evaluate the effectiveness of house cleaning and professional extermination on lowering cockroach antigen levels in inner-city dwellings.As part of the National Cooperative Inner-City Asthma Study intervention, 265 of 331 families with asthmatic children who had positive skin test responses to cockroach allergen consented to a professional home extermination with 2 applications of a cockroach insecticide (Abamectin, Avert) combined with directed education on cockroach allergen removal. On a random subset of 48 homes undergoing cockroach extermination in the intervention group, Bla g 1 was measured in settled dust from the kitchen, bedroom, and TV/living room. The first sample was collected 1 week before extermination, with additional samples after the exterminations at approximately 2, 6, and 12 months after the first sample. Self-reported problems with cockroaches were collected at baseline and after 12 months of follow-up in both the intervention and control group.The geometric mean kitchen level of Bla g 1 decreased at 2 months (33.6 U/g) relative to preextermination levels (68.7 U/g, P.05). The percent of kitchens with over 8 U/g of Bla g 1 followed a similar pattern, but only the decrease from preextermination to 6-month levels was significant (86.8% vs 64.3%, P.05). By the 12-month visit, the allergen burden had returned to or exceeded baseline levels. Except for an increase in the bedroom at 2 months (8.9 U/g vs 11.1 U/g, P.05), no other significant change was seen. Only about 50% of the families followed the cleaning instructions; no greater effect was found in these homes. Self-reported problems with cockroaches showed no difference between the intervention and control group after 1 year of follow-up.Despite a significant, but short-lived, decrease the cockroach allergen burden remained well above levels previously found to be clinically significant.

Fatty liver dystrophy (fld) is an autosomal recessive mutation in mice characterized by hypertriglyceridemia and fatty liver during neonatal development. The fatty liver in fld/fld mice spontaneously resolves between the age of 14–18 days, at which point the animals develop a neuropathy associated with abnormal myelin formation in peripheral nerve. We have investigated the morphological and biochemical alterations that occur in the fatty liver of neonatal fld/fld mice. Studies at the light and electron microscopic level demonstrated the accumulation of lipid droplets and hypertrophic parenchymal cells in fld neonates, with no apparent liver pathology after resolution of the fatty liver. To better characterize the biochemical basis for the development of fatty liver in fld mice, we compared protein expression patterns in the fatty liver of fld mice and in the liver of phenotypically normal (wild-type) littermates using quantitative two-dimensional gel electrophoresis. We detected 24 proteins with significantly altered expression levels (P < 0.001) in the fld fatty liver, 15 of which are proteins that are altered in abundance by peroxisome proliferating chemicals. As these compounds characteristically elicit changes in the expression of mitochondrial and peroxisomal enzymes involved in fatty acid oxidation, we quantitated rates of fatty acid oxidation in hepatocytes isolated from fld and wild-type mice. These studies revealed that hepatic fatty acid oxidation in fld neonates is reduced by 60“% compared to wild-type littermates. In hepatocytes from adult fld mice that no longer exhibit a fatty liver, oxidation rates were similar to those in hepatocytes from age-matched wild-type mice. These findings indicate that altered expression of proteins involved in fatty acid oxidation is associated with triglyceride accumulation in the fld fatty liver. —Rehnmark, S., C. S. Giometti, B. G. Slavin, M. H. Doolittle, and K. Reue. The fatty liver dystrophy mutant mouse: microvesicular steatosis associated with altered expression levels of peroxisome proliferator-regulated proteins. J. Lipid Res. 1998. 39: 2209–2217.

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 microcuries 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.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease mediated by an allergic late-phase inflammatory response to Aspergillus fumigatus antigens characterized by markedly elevated allergen specific and total immunoglobulin E (IgE) levels and eosinophilia, and manifested by wheezing, pulmonary infiltrates, and pulmonary bronchiectasis and fibrosis. ABPA afflicts only a small percentage of susceptible atopic individuals with either asthma or cystic fibrosis (CF). ABPA is unique in that it is caused by A. fumigatus, a living fungus growing within the mucosal lumen of the bronchi that releases a multitude of proteins whose biologic function alters the host immune responses in addition to being immunogenic. Elucidation of the immunopathogenesis of ABPA has provided valuable information related to allergen-induced chronic asthma. More recently, immunogenetic studies have further contributed to the understanding of the immunopathogenesis of why certain individuals are susceptible to develop ABPA. Immunologic responses to Aspergillus, as well as to other microorganisms, may be categorized as either T helper (Th)1 or Th2 CD4+ T-cell responses. 61,110,128 Th1 CD4+ T-cell cytokines, such as interferon gamma (IFN-γ), interleukin 2 (IL-2), and tumor necrosis factor (TNF)-β, enhance cytotoxic and macrophage activity (e.g., cellular immunity), whereas Th2 CD4+ T-cell cytokines, such as IL-4, IL-5, IL-10, and IL-13, promote antibody synthesis (e.g., humoral antibody immunity) (Table 1). It is hypothesized that protective host immunity to A. fumigatus is a Th1 CD4+ T-cell response, whereas a Th2 CD4+ T-cell humoral response found in ABPA is nonprotective and leads to a hypersensitivity pulmonary lung disease.

The relationship between infectious rhinitis and sinusitis is so clear that the suggestion has been made that the term “rhinosinusitis” might more precisely define the disease state.1 Several considerations support this contention. Rhinitis typically precedes sinusitis, and sinusitis without rhinitis is rare. The mucosae of the nasal and sinus tissues are contiguous, and the symptoms of nasal obstruction and nasal discharge are prominent in sinusitis. In certain clinical situations, either rhinitis (i.e., allergic rhinitis) or sinusitis (i.e., acute frontal sinusitis) may occur alone, but in most instances there is some involvement of the contiguous secondary site. A recent study, using computerized tomography (CT), documented that radiographic changes do occur in the sinuses of otherwise healthy patients with uncomplicated viral upper respiratory infections of brief duration.2 It is therefore clear that infectious rhinitis will predispose to the development of sinusitis. Before discussing the possibility that allergic rhinitis is associated with or is a cause of sinusitis, we will review some basic aspects of sinus anatomy and physiology.

Background Only 9 adult cases of immediate-hypersensitivity reaction to ladybugs, also known as Asian lady beetles ( Harmonia axyridis ), have been documented in the literature. These patients have all shown symptoms of allergic rhinoconjunctivitis or asthma from exposure to ladybugs. Objective To describe the first pediatric patients with severe allergic facial angioedema requiring emergency department management after exposure to ladybugs. Methods Evidence of IgE-mediated hypersensitivity to ladybugs was documented by positive skin prick test reactions, correlating with exposure history. Results Two cases in preschool boys had similar features, although they were evaluated and tested by 2 different allergists. Both patients developed severe facial or periocular angioedema with no significant respiratory involvement after exposure to ladybugs outside their infested homes. Both patients required an emergency department visit for treatment. Allergy evaluation using ladybug extract for skin prick testing showed markedly positive reactions in both patients. There were no further episodes after environmental control measures were instituted. Conclusions Although allergic respiratory or cutaneous reactions to ladybugs are uncommon, a high index of suspicion from exposure history and confirmatory skin testing can be conclusive for the diagnosis.

A finite-volume numerical method for studying shallow water flows over an arbitrary bed profile in the presence of external force has been proposed in [33]. This method uses the quasi-two-layer model of hydrodynamic flows over a stepwise boundary with advanced consideration of the flow features near the step. A distinctive feature of the suggested model is a separation of the studied flow into two layers in calculating the flow quantities near each step, and improving by this means the approximation of depth-averaged solutions of the initial three-dimensional Euler equations. We are solving the shallow-water equations for one layer, introducing the fictitious lower layer only as an auxiliary structure in setting up the appropriate Riemann problems for the upper layer. Besides, the quasi-two-layer approach leads to the appearance of additional terms in the one-layer finite-difference representation of balance equations. Numerical simulations are performed based on the proposed in [33] algorithm of various physical phenomena, such as breakdown of the rectangular fluid column over an inclined plane, large-scale motion of fluid in the gravity field in the presence of Coriolis force over amounted obstacle on the underlying surface. Computations are made for the two-dimensional dam-break problem on a slope precisely conform to laboratory experiments. The interaction of the Tsunami wave with the shore line including an obstacle has been simulated to demonstrate the efficiency of the developed algorithm in domains, including partly flooded and dry regions.

Rhinitis and sinusitis are common bothersome conditions in the elderly. Despite the importance of these diseases to the clinician, little information exists in the medical literature. A review of four recently published geriatric medicine textbooks reveals that not one includes rhinitis or sinusitis in the index. 6,7,13,14 It is interesting to note that, on the other hand, all four indexes include sinoatrial disease.

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.

Hormone-sensitive lipase (HSL) mediates the lipolysis of triacylglycerol from mammalian adipocytes, resulting in the release of non-esterified fatty acids and glycerol. Although numerous studies have examined the hormonal regulation of HSL, the measurement of HSL mRNA levels in response to hormonal regulators has not been studied. This study was designed to determine the effects of epinephrine, growth hormone, glucagon, and dexamethasone on HSL expression by measuring HSL mRNA levels and glycerol release in primary cultures of rat adipocytes. Exposure of adipocytes to epinephrine at 10(-7) M and 10(-5) M for 4 h resulted in an increase in medium glycerol (209 +/- 46%, and 284 +/- 58% of control, P < 0.001, respectively). However, no change in HSL mRNA levels occurred due to the epinephrine treatment. Similarly, the peptides glucagon (10(-7) M and 10(-5) M for 4 h) and growth hormone (100 ng/ml for 24 h) resulted in increased medium glycerol and had no effect on HSL mRNA levels in adipocytes. Dexamethasone was added to adipocyte cultures for 4 and 24 h, and resulted in a dose-dependent increase of medium glycerol (102 +/- 8%, 138 +/- 8% (P < 0.001), and 168 +/- 24% (P < 0.001) for 10(-8) M, 10(-7) M, and 10(-6) M, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)