Innate Immune Responses to Fungal Allergens.

PURPOSE OF REVIEW: In this review, we describe innate immunity to fungi and the ability of pattern recognition receptors (PRRs) to recognize fungal-associated molecular patterns (FAMPs) and danger-associated molecular patterns (DAMPs). RECENT FINDINGS: Protective responses against fungal antigens can be divided into two parts: innate immunity and adaptive immunity. Detection of foreign substance by the innate immune system is mediated by a variety of genetically encoded receptors known as pattern recognition receptors (PRRs). These PRRs bind to PAMPs (pathogen-associated molecular patterns) and more specifically to fungal-associated molecular patterns or FAMPs on target microorganisms. They also bind to DAMPs (damage-associated molecular patterns) which are substances released due to tissue and cell damage. PRRs can be divided into several families including Toll-like receptors (TLRs), nucleotide-oligomerization domain (NOD)-like receptors (NLRs), and C-type lectin receptors. Fungal PRRs can respond to internal and external components found in fungi. In addition, a number of fungal products, including some fungal allergens, seem to mimic or represent DAMPs. Collectively, activation of these fungal PRRs alerts the innate immune system to the presence of fungal exposure and can promote both innate and adaptive immune responses.

Environmental assessment and exposure reduction of cockroaches: a practice parameter.

This parameter was developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology. The AAAAI and the ACAAI have jointly accepted responsibility for establishing "Environmental assessment and remediation: a practice parameter." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single person, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion. The findings and conclusions in this manuscript are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC).

Human IgE antibody serology: a primer for the practicing North American allergist/immunologist.

The allergist/immunologist judiciously diagnoses allergic disease by using confirmatory IgE antibody data from in vivo and in vitro assays after the collection of a clinical history. After an overview of historical events, clinically available allergen-specific IgE assays from Phadia, Siemens, and Hycor are contrasted by their design and performance characteristics. The assays share comparable working ranges, analytical sensitivities, and excellent precision, reproducibility, and linearity to a performance standard of <15% coefficients of variation. However, multiple interlaboratory studies have confirmed that the 3 IgE antibody assays either detect different populations of IgE antibody or do not measure the same antibodies with comparable efficiencies. The clinical consequence is that IgE antibody results from the 3 assays are not interchangeable or equivalent. Data generated with one assay cannot be directly extrapolated to published predictive outcomes based on IgE antibody levels from a different assay. The transition from allergen extract-based to allergenic components reagents is discussed, emphasizing the chip-based microarray's strength in identifying IgE antibody cross-reactivity. US Food and Drug Administration-cleared point-of-care IgE antibody lateral flow cassettes are overviewed. Finally, IgE antibody concentration, affinity, clonality (epitope specificity), and specific activity (specific/total IgE ratio) are examined as humoral immune response parameters measured by serologic assays that affect effector cell degranulation and ultimately allergic disease expression.

Air filters and air cleaners: rostrum by the American Academy of Allergy, Asthma & Immunology Indoor Allergen Committee.

The allergist is generally recognized as possessing the greatest expertise in relating airborne contaminants to respiratory health, both atopic and nonatopic. Consequently, allergists are most often asked for their professional opinions regarding the appropriate use of air-cleaning equipment. This rostrum serves as a resource for the allergist and other health care professionals seeking a better understanding of air filtration.

Testing for allergic disease: parameters considered and test value.

BACKGROUND: Test results for allergic disease are especially valuable to allergists and family physicians for clinical evaluation, decisions to treat, and to determine needs for referral. METHODS: This study used a repeated measures design (conjoint analysis) to examine trade offs among clinical parameters that influence the decision of family physicians to use specific IgE blood testing as a diagnostic aid for patients suspected of having allergic rhinitis. Data were extracted from a random sample of 50 family physicians in the Southeastern United States. Physicians evaluated 11 patient profiles containing four clinical parameters: symptom severity (low, medium, high), symptom length (5, 10, 20 years), family history (both parents, mother, neither), and medication use (prescribed antihistamines, nasal spray, over-the-counter medications). Decision to recommend specific IgE testing was elicited as a "yes" or "no" response. Perceived value of specific IgE blood testing was evaluated according to usefulness as a diagnostic tool compared to skin testing, and not testing. RESULTS: The highest odds ratios (OR) associated with decisions to test for allergic rhinitis were obtained for symptom severity (OR, 12.11; 95%CI, 7.1-20.7) and length of symptoms (OR, 1.46; 95%CI, 0.96-2.2) with family history having significant influence in the decision. A moderately positive association between testing issues and testing value was revealed (beta = 0.624, t = 5.296, p < or = 0.001) with 39% of the variance explained by the regression model. CONCLUSION: The most important parameters considered when testing for allergic rhinitis relate to symptom severity, length of symptoms, and family history. Family physicians recognize that specific IgE blood testing is valuable to their practice.

Innate and Adaptive Immune Response to Fungal Products and Allergens.

Exposure to fungi and their products is practically ubiquitous, yet most of this is of little consequence to most healthy individuals. This is because there are a number of elaborate mechanisms to deal with these exposures. Most of these mechanisms are designed to recognize and neutralize such exposures. However, in understanding these mechanisms it has become clear that many of them overlap with our ability to respond to disruptions in tissue function caused by trauma or deterioration. These responses involve the innate and adaptive immune systems usually through the activation of nuclear factor kappa B and the production of cytokines that are considered inflammatory accompanied by other factors that can moderate these reactivities. Depending on different genetic backgrounds and the extent of activation of these mechanisms, various pathologies with resulting symptoms can ensue. Complicating this is the fact that these mechanisms can bias toward type 2 innate and adaptive immune responses. Thus, to understand what we refer to as allergens from fungal sources, we must first understand how they influence these innate mechanisms. In doing so it has become clear that many of the proteins that are described as fungal allergens are essentially homologues of our own proteins that signal or cause tissue disruptions.

RBL cells expressing human Fc epsilon RI are a sensitive tool for exploring functional IgE-allergen interactions: studies with sera from peanut-sensitive patients.

Rat basophilic leukemia cells (RBL SX-38) express the alpha, beta, and gamma chains of human Fc epsilon RI. Following sensitization with IgE from a subset of allergic human donors, these cells can be triggered by exposure to anti-IgE or to very low concentrations of specific allergens. We examined 18 sera from patients who were highly sensitive to peanuts by history and had anti-peanut IgE by in vitro testing. The ability of these sera to sensitize the RBL SX-38 cells for degranulation with peanut allergens correlates very well with the absolute amount of anti-peanut IgE (r=0.95; p<0.001). The most effective sera contained at least 50 kU/l of total IgE and at least 15 kU/l of peanut-specific IgE. RBL SX-38 cells sensitized with these sera degranulated optimally upon exposure to anti-IgE (net degranulation of 40+/-8%, means+/-S.D.; n=8) and to a 10(5)-10(6) dilution of crude peanut extract (CPE) (37+/-7% net degranulation; 93+/-13% of that seen with anti-IgE). This assay is quite sensitive. Cells sensitized with selected sera are activated by exposure to a 1:10(7) dilution of the CPE containing picogram amounts of peanut allergens. This assay is also quite specific. Cells sensitized with sera from patients with anti-peanut IgE and no detectable IgE against soybean, walnut or grass pollen did not degranulate following exposure to these latter antigens. The converse was also true; cells sensitized with sera from patients without anti-peanut IgE did not react to peanut. These data demonstrate that RBL cells expressing human Fc epsilon RI form the basis of a useful model system for the detection of allergens and for the study of IgE-allergen interactions.

Accuracy of IgE antibody laboratory results.

BACKGROUND: Studies have demonstrated that the magnitude of sensitization as evidenced by specific IgE (sIgE) levels provides significant information as to whether a sensitized individual is likely to be truly reactive. However, it is not clear that quantitative sIgE results provided by different laboratories using different technologies are comparable. OBJECTIVE: To investigate whether similar results were obtained from Clinical Laboratory Improvement Act-certified laboratories that used 3 common systems for sIgE antibody determination with serum samples and mouse-human IgE chimeric antibodies with known specificity and quantity. METHODS: Sixty samples for peanut and 20 for soy were submitted for sIgE determination on 3 different systems: ImmunoCAP, Immulite, and Turbo radioallergosorbent test (RAST). Mouse-human chimeric IgE antibodies specific for the major birch allergen Bet v 1 and for the dust mite allergen Der p 2 were also included. RESULTS: A qualitative evaluation using a cutoff of 0.35 kUA/L showed some differences in the ability to detect sIgE sensitization, with the Turbo RAST being most variable. However, considerable differences were found with quantitative evaluation, with Immulite overestimating and Turbo RAST underestimating sIgE compared with ImmunoCAP. Similar discrepancies were seen with the mouse-human chimeric IgE antibody samples. CONCLUSION: These findings have potentially serious clinical implications, since each of these systems is widely used. It is therefore important that all laboratories clarify which system they are using. Just because 2 systems present their results in the same units does not mean that the results are necessarily correct or interchangeable.

The impact of allergic rhinitis on work productivity.

AIM: Patients with allergic rhinitis experience a multitude of symptoms that usually compromise some aspect of lifestyle. However, few data are available that specifically address the impact of allergic rhinitis on work productivity. METHODS: A questionnaire was developed and mailed to 2,065 patients enrolled in a 500,000-member managed care organisation. Patients were identified by diagnostic codes for allergic rhinitis as determined by a retrospective examination of medical and prescription claims records from January 1 2000 to December 31 2000. Patients were divided into three different care groups according to whether they were managed by family physicians, by allergists, or were self-managed. RESULTS: Chi-square and analysis of variance tests revealed significant differences among the three care groups (p<0.05) for years with allergies, symptoms, family history, testing, immunotherapy, test value, and prescribed antihistamine use. Multiple linear regression analysis revealed that sleep, health, certain allergy symptoms and prescribed antihistamines were significantly related to work productivity. CONCLUSIONS: The results of this study revealed that the ability of individuals with allergic rhinitis to engage in productive work is influenced by sleep, health-related quality of life (HRQoL), specific symptoms, and prescribed antihistamine use.

Critical analysis of studies concerning reports of respiratory sensitization to certain wood dusts.

Studies have been published reporting that exposures to certain wood dusts are sensitizing, resulting in respiratory symptoms in susceptible individuals. Many of the publications in this field are case reports that collectively have a number of important shortcomings. Illuminating these should further our understanding of whether respiratory sensitization results from occupational exposure to particular wood dusts. The aim of this study was to critically review and understand the evidence to date regarding reported respiratory sensitization in connection with wood dusts from oak, beech, pine, ash, and western red cedar. Publications dealing with these commercially important woods in North America have been selected from the Pubmed/Medline database (1966 to the present) using the key word, wood dust. These articles, along with supporting references on procedures and techniques, are reviewed according to the strengths and weaknesses of evidence and conclusions presented. Evidence from skin testing, specific immunoglobulin E measurements, and basophil histamine release tests suggests that reported symptoms are not likely to be immunologically derived. Because of methodological problems, challenge tests with specific wood dusts do not support the conclusion that reactions to certain wood dusts are specific. Experiments with nonspecific bronchoconstrictive agents indicate that a number of study subjects possess hyperresponsive airways. Thus, select individuals can demonstrate various respiratory symptoms in the woodworking industry, but any specificity or direct cause is currently unproved. Current studies do not support that exposure to wood dusts from a number of common North American wood species causes immunologic sensitization in woodworkers. Rather, symptoms reported in some studies of exposed workers seem to follow the paradigm for nonspecific respiratory responses in individuals with hyperresponsive airways.

Influence of patient care provider on patient health outcomes in allergic rhinitis.

BACKGROUND: Diagnosing and managing the symptoms of allergic rhinitis are largely the responsibility of family physicians and allergists, but some patients choose self-management. However, few data are available to determine how the choice of care relates to measures of patient outcomes, such as the ability to perform activities, quality of life, and productivity. OBJECTIVE: To examine and compare patients' ability to perform activities, quality of life, productivity, and symptoms according to care provider: family physician, allergist, or self-management. METHODS: A questionnaire was developed and mailed to 2,065 patients enrolled in a 500,000-member managed care organization. Patients were identified by diagnostic codes for allergic rhinitis as determined from a retrospective examination of medical and prescription claims records between January 1, 2000, and December 31, 2000. RESULTS: Chi-squared Tests revealed statistically significant differences for symptoms, family history, testing, immunotherapy, and test value among patient care providers. Multivariate analysis of variance revealed statistically significant differences for activities, symptoms, and quality of life among patient care providers. Findings support the use of diagnostic testing to improve patient outcomes. Symptoms were statistically significantly associated with measures of productivity. CONCLUSIONS: Patient outcomes vary with respect to patient care group. It is imperative that patients suspected of having allergic rhinitis undergo appropriate evaluation and testing. Outcomes can be optimized if allergists and family physicians have access to appropriate diagnostic tools, such as skin testing and serologic tests for specific IgE antibodies.

Usefulness of specific IgE antibody tests: a progress report.

LEARNING OBJECTIVES: To enable the readers to recognize some of the history, problems, progress, interpretation, and present status of assays for specific IgE (s-IgE) antibodies. DATA SOURCES: Peer-reviewed literature in the field. STUDY SELECTION: Key articles were selected by the author. RESULTS: Clinical and analytical studies have differed widely in their conclusions as to the performance of tests for s-IgE. Study conclusions depend on the testing method used, the allergen(s) studied, patient selection, and, most importantly, the standards used for comparison. Today, only a handful of the once commercially developed assays still exist, and some of these still do not compare well to an analytical ideal standard. However, with the extent of regulation and economic pressures, most of the surviving s-IgE tests are considerably improved over what had existed before them. CONCLUSIONS: Allergic diseases with multiple symptom patterns seem to be increasing in modern societies. Objective methods are needed to differentiate allergic origins from other mechanisms that cause similar symptoms. Accurate, quantitative, and objective methods for s-IgE measurement are now available and can be used effectively in clarifying allergic diagnoses when interpreted in conjunction with the clinical history.

Evidence-based strategies for treatment of allergic rhinitis.

In this review, an evidence-based medicine approach to diagnosis and treatment for allergic rhinitis is reviewed. We performed a search of the medical literature for randomized, placebo-controlled trials of nonsedating antihistamines, intranasal corticosteroids, montelukast, azelastine, allergen immunotherapy, and anti-IgE. The mean numbers needed to treat were: nonsedating antihistamines--15.2; nasal corticosteroids--4.4; montelukast--14.3; azelastine--5.0; allergen immunotherapy--4.6; and anti-IgE--12.4. Treatment thresholds for use were: antihistamines--23%; nasal corticosteroids--8%; azelastine--16%; montelukast--8%; anti-IgE--50%; and immunotherapy--25%. When used appropriately, this information could become very useful for clinicians, particularly if cost, convenience, and other indirect factors can be included.

Are our impressions of allergy test performances correct?

BACKGROUND: The clinical diagnosis is often subjective and susceptible to bias, yet it is the primary standard by which diagnostic tests are judged. Consequently, our opinions regarding various diagnostic tests may not be entirely accurate. OBJECTIVE: To investigate the accuracy of the clinical history compared with concordant skin and quantitative specific IgE (s-IgE) measurements. METHODS: Consecutive, consenting patients (N = 152) at 2 different allergy centers were examined by history and physical examination (HPE) alone to determine their sensitivity to 7 common allergens. Results were classified as positive, negative, or indeterminate. The HPE results were then compared to concordant skin prick testing (SPT) and s-IgE measurements and to quantitative IgE antibody measurements with and without knowledge of the SPT results. RESULTS: Diagnosis by HPE deviated considerably from concordant SPT and s-IgE results. This deviation differed between allergists and allergens, reflecting a positive HPE bias that averaged 22%. Seventy-six percent of the HPE results judged indeterminate were resolved as negative. Using additional information from the quantification of s-IgE antibodies, considerable differences between the sites in the level of s-IgE associated with a positive HPE result with and without SPT results were observed. CONCLUSIONS: Relative to the SPT and quantification of s-IgE antibodies, the diagnosis by HPE alone to common allergens is not consistent. Discrepancies were dependent on both allergen and allergist. The quantitative s-IgE data revealed that allergists use available information from the HPE and SPT differently. Since the HPE is the primary standard used in judging test efficacy (sensitivity and specificity), our current impressions of test performances are not likely to be accurate.

Health effects of air pollution.

The general public, especially patients with upper or lower respiratory symptoms, is aware from media reports that adverse respiratory effects can occur from air pollution. It is important for the allergist to have a current knowledge of the potential health effects of air pollution and how they might affect their patients to advise them accordingly. Specifically, the allergist-clinical immunologist should be keenly aware that both gaseous and particulate outdoor pollutants might aggravate or enhance the underlying pathophysiology of both the upper and lower airways. Epidemiologic and laboratory exposure research studies investigating the health effects of outdoor air pollution each have advantages and disadvantages. Epidemiologic studies can show statistical associations between levels of individual or combined air pollutants and outcomes, such as rates of asthma, emergency visits for asthma, or hospital admissions, but cannot prove a causative role. Human exposure studies, animal models, and tissue or cellular studies provide further information on mechanisms of response but also have inherent limitations. The aim of this rostrum is to review the relevant publications that provide the appropriate context for assessing the risks of air pollution relative to other more modifiable environmental factors in patients with allergic airways disease.