Fungal Allergy Research Articles

CD8(+) T cells implicated in the pathogenesis of allergic fungal rhinosinusitis.

Fungi in paranasal sinuses are characteristic and considered a major pathogenic factor in a subset of chronic rhinosinusitis (CRS) patients, known as allergic fungal rhinosinusitis (AFRS). CD8+ T cells are enriched in AFRS sinuses but their role in fungal-specific responses is unknown. Alternaria alternata– and Aspergillus fumigatus–specific T lymphocyte responses were investigated in 6 AFRS patients, 10 eosinophilic mucus CRS (EMCRS) patients, 10 CRS with nasal polyps (CRSwNPs) patients, 6 allergic rhinitis with fungal allergy (ARFA) patients, and five controls. Fungal-specific proliferation of human peripheral blood mononuclear cells (PBMCs) was studied prospectively. Proliferating cells were examined for CD3, CD4, CD8, and CD25 expression. Relevant clinical characteristics, fungal allergy, detection of fungi in sinuses, and CD4+ and CD8+ composition of sinus T cells were also examined. CD4+ T-cell division to fungi occurred in all samples, regardless of fungal allergy or CRS. Fungal-specific CD8+ T-cell division occurred in all ARFA and control samples and the majority of CRSwNP patients; however, CD8+ T cells failed to proliferate in AFRS and EMCRS patients. The CD8+ T cells from AFRS patients also did not up-regulate the activation marker, CD25, with fungal antigen exposure. Presence of A. alternata– and A. fumigatus–specific CD4+ and CD8+ T-cell proliferation in healthy individuals, ARFA, and CRSwNP patients suggests that both T-cell subsets may be important in immune responses to these fungi. In AFRS and EMCRS patients, only fungal-specific CD4+ T-cell proliferation occurred; hence, a lack of CD8+ T-cell proliferation and activation in the presence of sinus eosinophilic mucus in these patients, regardless of fungal allergy, is a novel finding. This raises the question whether a dysfunctional CD8+ T-cell response predisposes to ineffective clearance and accumulation of fungi in the sinuses of susceptible patients.

Fungal allergy in asthma-state of the art and research needs.

Sensitization to fungi and long term or uncontrolled fungal infection are associated with poor control of asthma, the likelihood of more severe disease and complications such as bronchiectasis and chronic pulmonary aspergillosis. Modelling suggests that >6.5 million people have severe asthma with fungal sensitizations (SAFS), up to 50% of adult asthmatics attending secondary care have fungal sensitization, and an estimated 4.8 million adults have allergic bronchopulmonary aspergillosis (ABPA). There is much uncertainty about which fungi and fungal allergens are relevant to asthma, the natural history of sensitisation to fungi, if there is an exposure response relationship for fungal allergy, and the pathogenesis and frequency of exacerbations and complications. Genetic associations have been described but only weakly linked to phenotypes. The evidence base for most management strategies in ABPA, SAFS and related conditions is weak. Yet straightforward clinical practice guidelines for management are required. The role of environmental monitoring and optimal means of controlling disease to prevent disability and complications are not yet clear. In this paper we set out the key evidence supporting the role of fungal exposure, sensitisation and infection in asthmatics, what is understood about pathogenesis and natural history and identify the numerous areas for research studies.

Demonstration of aeroallergenicity of fungal hyphae and hyphal fragments among allergic rhinitis patients using a novel immunostaining technique

Abstract More than 80 species of fungi are suspected of inducing immunoglobulin E (IgE)-mediated hypersensitivity. Exposure to airborne fungal conidia has been linked to the respiratory symptoms in individuals with fungal allergy; however, the contribution of airborne fungal hyphae and hyphal fragments to allergic diseases is poorly understood. We sought to investigate the expression of allergens from airborne fungal hyphae and hyphal fragments using the halogen immunoassay, which uses patients’ serum IgE to immunostain immobilized allergens extracted from individual fungal particles. Airborne fungi were collected from the nasal cavities of 25 patients and 10 controls using the refined nasal wash technique, fixed on mixed cellulose ester protein-binding membranes, incubated overnight in a humid chamber to promote the germination of conidia, and immunostained with the participants own serum IgE. The samples were examined by means of light microscopy, and positively immunostained fungal particles were classified and counted. All samples contained fungal particles that expressed soluble allergens and were significantly higher in concentration than counts of conidia of individual well-characterized allergenic genera (P < 0.05). Resultant immunostaining of fungal hyphae was heterogeneous, and ∼27% of all hyphae expressed detectable allergens compared with nonstained hyphae (P < 0.05). This study conclusively demonstrates that fungal hyphae and fragments are underestimated sources of aeroallergens because positively immunostained hyphal fragments were detected in all samples and the number of the detected fungal hyphae in any of the individual protein-binding membranes was significantly higher than the conidial counts in any of the commonly recognized aeroallergenic species.

Editorial introductions

Current Opinion in Allergy and Clinical Immunology was launched in 2001. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The fields of allergy and clinical immunology are divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Bruce D. MazerBruce D. MazerDr Bruce Mazer is a Professor of Pediatrics in the Faculty of Medicine, McGill University, Canada. He completed his medical training at McGill University and the Montreal Children's Hospital, Canada, and was a fellow in allergy and immunology at the National Jewish Health Center in Denver CO, USA. Dr Mazer is currently the Division Head of Allergy and Immunology and the Associate Chair for Research at the McGill University Health Center-Montréal Children's Hospital. He is also Chair of the Research Council at the Research Institute of the McGill University Health Center. He has a busy clinical practice following children with Immune Deficiency, severe asthma and food allergies. His research interests include regulation of IgE, B-lymphocyte development in Airway tissues, and immune regulation in asthma and food allergy. He is funded by the Canadian Institutes for Health Research, The National Sciences and Engineering Council of Canada, Les Fonds Des Recherech du Quebec en Sante and the National Center of Excellence -ALLERGEN program. Ramsay L. FuleihanRamsay L. FuleihanRamsay L. Fuleihan, MD, is Associate Professor at Northwestern University Feinberg School of Medicine, USA and Attending Physician at the Ann & Robert H. Lurie Children's Hospital of Chicago, Illinois, USA, where he is also Director of Primary Immunodeficiency Clinical Services and Director of the Jeffrey Modell Foundation Diagnostic Center for Primary Immunodeficiencies. In addition, Dr Fuleihan is Associate Director of the Allergy and Clinical Immunology Training Program at the Northwestern University Feinberg School of Medicine, USA. Dr Fuleihan received his medical degree at the American University of Beirut in Lebanon. He then trained in pediatrics at Duke University Medical Center in Durham, North Carolina, USA and in allergy and immunology at the Children's Hospital Boston at Harvard Medical School in Massachusetts, USA. A Diplomate of the American Board of Allergy and Immunology, Dr Fuleihan is a member of several professional societies, including the American Academy of Allergy, Asthma and Immunology, the European Society for Immunodeficiencies, the Clinical Immunology Society, and the Society for Pediatric Research. He is a member of the steering committee of the US Immunodeficiency Network and a member of the Medical Advisory Committee of the Immune Deficiency Foundation. Giovanni PassalacquaGiovanni PassalacquaDr Passalacqua was born in Genoa in 1964. He graduated in 1990 from the Genoa University Medical School, Italy, and received the full specialty degrees in Allergy and in Respiratory Medicine in 1994 and 2002. Under the chairmanship of Prof. Giorgio Walter Canonica, he contributed to investigations in the mechanisms of allergic inflammation, the treatment of respiratory allergy and developed sublingual immunotherapy. Currently he is Associate Professor of Respiratory Medicine, for which he also chairs the Specialty School at the University of Genoa. Dr Passalacqua has coauthored more than 300 publications in peer reviewed journals. He serves on the board of experts of Allergic Rhinitis and its Impact on Asthma (ARIA), and is co-Chairman of the immunotherapy committee of the World Allergy Organization. Robert BushRobert BushDr Robert Bush received his MD degree from West Virginia University, USA. After completing his residency in internal medicine and fellowship in allergy and immunology at the University of Wisconsin – Madison, USA, he joined the faculty. He is currently Professor (Emeritus) of Medicine and was the former Chief of Allergy at the William S Middleton VA Hospital, Madison, Wisconsin, USA. His research interests include sublingual immunotherapy, allergen characterization, fungal allergy, food allergy, and occupational asthma.

The Editor takes a closer look at some of this month's articles

The Editor takes a closer look at some of this month's articles

A Study of Airborne Fungal Spores of Anyigba, Kogi State, Nigeria

Airborne fungal spores of Anyigba, Dekina Local Government Area, Kogi State, Nigeria during the months of March – December, 2012 were trapped,acetolysed and analysedpalynologically to determine the genera of airborne fungal spores and/or particles present in the atmosphere. A total of 9491 fungal spores were counted. The predominant spore types include those of Botryodiplodia, Curvularia, Gliomastix, Drechslera/Helminthosporium, Neurospora, Nigrospora, Pithomyces, Teliospore andStemphylum. The presence of fungal spores in the atmosphere affirms the great influence of anthropogenic activities on the local vegetation. Analysis of variance for the various airborne fungal spores showed that there was no significant difference (P>0.05) between the various groups. This study would provide a good template thatcould be used to monitor the frequency and intensity of fungal allergies and various disease conditions of plants, animals and man in the surrounding Savanna environment, and provide adequate restoration and conservation measures for safety health and environmental sustainability.

Editorial introductions

Current Opinion in Allergy and Clinical Immunology was launched in 2001. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The fields of allergy and clinical immunology are divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Amos EtzioniAmos EtzioniAmos Etzioni, MD is a Professor of Pediatrics and Immunology at the Faculty of Medicine, Technion in Haifa, Israel and is the Director of the Children's hospital at the Rambam Health Campus in Haifa, Israel. After finishing a residency in pediatrics in Haifa, he did a fellowship in immunology in Philadelphia, USA and upon his return in 1982 opened the first center for primary immunodeficiency in Israel. His main interest in the field of primary immunodeficiency (PID) is in the leukocyte adhesion molecules defects, in which he described two new conditions LAD II and III. He has published more than 200 papers and has written many reviews and chapters in books. He was invited as a speaker to numerous international meetings in the field of immunodeficiency. He is currently the President of the Israeli Immunology Society as well as the President of the European Society for Immunodeficiency (ESID). Ramsay L. FuleihanRamsay L. FuleihanRamsay L. Fuleihan, MD, is Associate Professor at Northwestern University Feinberg School of Medicine, USA and an Attending Physician at the Ann & Robert H. Lurie Children's Hospital of Chicago, Illinois, USA, where he is also Director of Primary Immunodeficiency Clinical Services and Director of the Jeffrey Modell Foundation Diagnostic Center for Primary Immunodeficiencies. In addition, Dr Fuleihan is Associate Director of the Allergy and Clinical Immunology Training Program at the Northwestern University Feinberg School of Medicine. Dr Fuleihan received his medical degree at the American University of Beirut in Lebanon. He then trained in pediatrics at Duke University Medical Center in Durham, North Carolina, USA and in allergy and immunology at the Children's Hospital Boston at Harvard Medical School in Massachusetts, USA. A Diplomate of the American Board of Allergy and Immunology, Dr Fuleihan is a member of several professional societies, including the American Academy of Allergy, Asthma and Immunology, the European Society for Immunodeficiencies, the Clinical Immunology Society, and the Society for Pediatric Research. He is a member of the steering committee of the US Immunodeficiency Network and a member of the Medical Advisory Committee of the Immune Deficiency Foundation. Giovanni PassalacquaGiovanni PassalacquaDr Passalacqua was born in Genoa in 1964. He graduated in 1990 from the Genoa University Medical School, Italy, and received specialty degrees in Allergy and in Respiratory Medicine in 1994 and 2002. Under the chairmanship of Prof. Giorgio Walter Canonica, he contributed to investigation into the mechanisms of allergic inflammation, the treatment of respiratory allergy and developed sublingual immunotherapy. Currently he is Professor of Respiratory Medicine and Allergy at the Respiratory Diseases Clinic of the University of Genoa. Dr Passalacqua has coauthored more than 200 publications in peer reviewed journals. He serves on the board of experts of Allergic Rhinitis and its Impact on Asthma (ARIA), and is co-Chairman of the immunotherapy committee of the World Allergy Organization. Robert BushRobert BushDr Robert Bush received his MD degree from West Virginia University, USA. After completing his residency in internal medicine and fellowship in allergy and immunology at the University of Wisconsin – Madison, USA, he joined the faculty. He is currently Professor (Emeritus) of Medicine and was the former Chief of Allergy at the William S Middleton VA Hospital, Madison, Wisconsin, USA. His research interests include sublingual immunotherapy, allergen characterization, fungal allergy, food allergy, and occupational asthma.

The β-Glucan Receptor Dectin-1 Promotes Lung Immunopathology during Fungal Allergy via IL-22

Sensitization to fungi, such as the mold Aspergillus fumigatus, is increasingly becoming linked with asthma severity. We have previously shown that lung responses generated via the β-glucan receptor Dectin-1 are required for lung defense during acute, invasive A. fumigatus infection. Unexpectedly, in an allergic model of chronic lung exposure to live A. fumigatus conidia, β-glucan recognition via Dectin-1 led to the induction of multiple proallergic (Muc5ac, Clca3, CCL17, CCL22, and IL-33) and proinflammatory (IL-1β and CXCL1) mediators that compromised lung function. Attenuated proallergic and proinflammatory responses in the absence of Dectin-1 were not associated with changes in Ido (IDO), Il12p35/Ebi3 (IL-35), IL-10, or TGF-β levels. Assessment of Th responses demonstrated that purified lung CD4(+) T cells produced IL-4, IL-13, IFN-γ, and IL-17A, but not IL-22, in a Dectin-1-dependent manner. In contrast, we observed robust, Dectin-1-dependent IL-22 production by unfractionated lung digest cells. Intriguingly, the absence of IL-22 alone mimicked the attenuated proallergic and proinflammatory responses observed in the absence of Dectin-1, suggesting that Dectin-1-mediated IL-22 production potentiated responses that led to decrements in lung function. To this end, neutralization of IL-22 improved lung function in normal mice. Collectively, these results indicate that the β-glucan receptor Dectin-1 contributes to lung inflammation and immunopathology associated with persistent fungal exposure via the production of IL-22.

The Editor takes a closer look at some of this month's articles

The Editor takes a closer look at some of this month's articles

P67-phox (NCF2) Lacking Exons 11 and 12 Is Functionally Active and Leads to an Extremely Late Diagnosis of Chronic Granulomatous Disease (CGD)

Two brothers in their fifties presented with a medical history of suspected fungal allergy, allergic bronchopulmonary aspergillosis, alveolitis, and invasive aspergillosis and pulmonary fistula, respectively. Eventually, after a delay of 50 years, chronic granulomatous disease (CGD) was diagnosed in the index patient. We found a new splice mutation in the NCF2 (p67-phox) gene, c.1000+2T→G, that led to several splice products one of which lacked exons 11 and 12. This deletion was in frame and allowed for remarkable residual NADPH oxidase activity as determined by transduction experiments using a retroviral vector. We conclude that p67-phox which lacks the 34 amino acids encoded by the two exons can still exert considerable functional activity. This activity can partially explain the long-term survival of the patients without adequate diagnosis and treatment, but could not prevent progressing lung damage.

Identification of Critical Amino Acids in an Immunodominant IgE Epitope of Pen c 13, a Major Allergen from Penicillium citrinum

BackgroundPen c 13, identified as a 33-kDa alkaline serine protease, is a major allergen secreted by Penicillium citrinum. Detailed knowledge about the epitopes responsible for IgE binding would help inform the diagnosis/prognosis of fungal allergy and facilitate the rational design of hypoallergenic candidate vaccines. The goal of the present study was to characterize the IgE epitopes of Pen c 13.Methodology/Principal FindingsSerum samples were collected from 10 patients with mold allergy and positive Pen c 13 skin test results. IgE-binding epitopes on rPen c 13 were mapped using an enzymatic digestion and chemical cleavage method, followed by dot-blotting and mass spectrometry. A B-cell epitope-predicting server and molecular modeling were used to predict the residues most likely involved in IgE binding. Theoretically predicted IgE-binding regions were further confirmed by site-directed mutagenesis assays. At least twelve different IgE-binding epitopes located throughout Pen c 13 were identified. Of these, peptides S16 (A148–E166) and S22 (A243–K274) were recognized by sera from 90% and 100% of the patients tested, and were further confirmed by inhibition assays. Peptide S22 was selected for further analysis of IgE-binding ability. The results of serum screening showed that the majority of IgE-binding ability resided in the C-terminus. One Pen c 13 mutant, G270A (T261–K274), exhibited clearly enhanced IgE reactivity, whereas another, K274A, exhibited dramatically reduced IgE reactivity.Conclusions/SignificanceExperimental analyses confirmed in silico-predicted residues involved in an important antigenic region of Pen c 13. The G270A mutant of Pen c 13 has the potential to serve as an additional tool for the diagnosis/prognosis of mold allergy, and the K274A mutant, as a hypoallergenic form of the epitope, may provide a framework for the design and development of a safe and efficient therapeutic strategy for treating human allergic diseases.

Allergien auf Tiere und Pilze

Allergies to animals are behind the house-dust mite allergy the most frequent cause for indoor allergic respiratory symptoms. In case of persistent allergen exposure symptoms like rhinitis, itch of the skin or asthma are usually not perceived intensively and, thus, can not assigned to an animal or an animal source. In many cases animal allergies are based on a perennial allergen exposure. Although most likely all animals may be the cause of a respiratory allergy, cats, dogs, and horses are the most frequent elicitors. The diagnosis of an allergy to an animal needs to be set with due care, since it often causes emotional reactions, diverse conflicts, but also lack of understanding. Rarer are allergies to fungi even though fungi as allergen sources since decades belong to the differential diagnosis in respiratory allergies particularly in case of late summer asthma. Fungi are ubiquitous and present indoors as well as outdoors. Unfortunately the field of fungal allergy is not well explored and diagnostic possibilities are limited. The most promising therapy in both allergy to animals and fungi would be complete avoiding of contact with the respective allergen source. Indeed many preventive recommendations are given; however, realization is often not successful. In selected cases specific immunotherapy for both animal and fungal allergies is a potential therapeutic option.

Evaluation of Fungal Sensitivity in the Greater New Orleans Area

In post-Katrina New Orleans, there was an increase in atmospheric fungal exposure. Fungal allergy is associated with increased severity of rhinitis and asthma. Our institution's allergen panel was expanded in response to possible increases in fungal sensitization. However, recent studies have shown that fungal sensitization in New Orleans is not above the national average as was once hypothesized. We retrospectively examined skin test results with the intention of simplifying our testing of fungal allergy and eliminating redundancy.

Ex Vivo Characterization of the Epitope-Specific T Cell Response to Alternaria

Specific immunotherapy for fungal allergy has seen limited success, partly due to the difficulty in obtaining fungal extract of standardized quality. Peptide immunotherapy would circumvent this problem and would limit IgE reactivity, potentially reducing the adverse events associated with SIT. Peptides could also potentially increase the efficacy of SIT, as they could be selected based on their ability to elicit the desired response.

SP-A and SP-D in host defense against fungal infections and allergies

Innate immunity mediated by pattern recognition proteins is relevant in the host defense against fungi. SP-A and SP-D are two such proteins belonging to the class of collagen domain containing C-type lectins, or collectins. They bind to the sugar moieties present on the cell walls of various fungi in a dose dependent manner via their carbohydrate recognition domain (CRD). SP-A and SP-D directly interact with alveolar macrophages, neutrophils, lymphocytes. We review these roles of SP-A and SP-D against various clinically relevant fungal pathogens and fungal allergens. SP-A and SP-D gene deficient mice showed increased susceptibility/ resistance to various fungal infections. Patients of fungal infections and allergies are reported with alterations in the serum or lung lavage levels of SP-A and SP-D. There are studies associating the gene polymorphisms in SP-A and SP-D with alterations in their levels or functions or susceptibility of the host to fungal diseases. In view of the protective role of SP-D in murine models of Aspergillus fumigatus infections and allergies, therapeutic use of SP-D could be explored further.

SP-A and SP-D in host defense against fungal infections and allergies

Innate immunity mediated by pattern recognition proteins is relevant in the host defense against fungi. SP-A and SP-D are two such proteins belonging to the class of collagen domain containing C-type lectins, or collectins. They bind to the sugar moieties present on the cell walls of various fungi in a dose dependent manner via their carbohydrate recognition domain (CRD). SP-A and SP-D directly interact with alveolar macrophages, neutrophils, lymphocytes. We review these roles of SP-A and SP-D against various clinically relevant fungal pathogens and fungal allergens. SP-A and SP-D gene deficient mice showed increased susceptibility/ resistance to various fungal infections. Patients of fungal infections and allergies are reported with alterations in the serum or lung lavage levels of SP-A and SP-D. There are studies associating the gene polymorphisms in SP-A and SP-D with alterations in their levels or functions or susceptibility of the host to fungal diseases. In view of the protective role of SP-D in murine models of Aspergillus fumigatus infections and allergies, therapeutic use of SP-D could be explored further.

Characterization of CD19+CD23+ B2 Lymphocytes in the Allergic Airways of BALB/c Mice in Response to the Inhalation of Aspergillus fumigatus Conidia§

Fungal sensitization in patients with asthma often indicates an unusual disease course in which traditional asthma treatments have little effect and in which morbidity is particularly severe. Airway hyperresponsiveness (AHR), inflammatory infiltrates, smooth muscle hyperplasia, and irreversible fibrotic remodeling of the bronchial architecture are features of allergic fungal asthma. The systemic production of IgE has long been associated with the immunopathogenesis of allergic asthma; however, the role of B lymphocytes and their products in the response to fungal allergens remains unclear. In the present study, we hypothesize that B lymphocytes are recruited to the allergic lung to impact the allergic response. Using a murine fungal aeroallergen model to mimic the human syndrome, we characterized the B cell population in the lung after fungal challenge and found that CD19(+)CD23(+) B2 lymphocyte numbers are increased in the allergic lung in a dynamic process. IgA, IgG(2a), and IgE were prominent in the serum and bronchoalveolar lavage fluid of allergic animals. It was evident that a tissue-centric production of these antibodies was possible. IgA-, IgG-, and IgE-producing cells from the allergic lung were identified by flow cytometry and immunohistochemistry. This study shows for the first time that CD19(+)CD23(+) B2 lymphocyte numbers change in the lung in a dynamic process after inhalation of fungal conidia and their increase has a significant impact on the Ab production in the pulmonary compartment in the context of fungal allergy.

Editorial introductions

Current Opinion in Allergy and Clinical Immunology was launched in 2001. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The fields of allergy and clinical immunology are divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. Section Editors Amos EtzioniAmos EtzioniAmos Etzioni, MD is a Professor of Pediatrics and Immunology at the Faculty of Medicine, Technion in Haifa, Israel and is the Director of the Children's hospital at the Rambam Health Campus in Haifa, Israel. After finishing a residency in pediatrics in Haifa, he did a fellowship in immunology in Philadelphia, USA and upon his return in 1982 opened the first center for primary immunodeficiency in Israel. His main interest in the field of PID is in the leukocyte adhesion molecules defects, in which he described two new conditions LAD II and III. He has published more than 200 papers and has written many reviews and chapters in books. He was invited as a speaker to numerous international meetings in the field of immunodeficiency. He is currently the President of the Israeli Immunology Society as well as the President of the European Society for Immunodeficiency (ESID). Ramsey FuleihanRamsey FuleihanRamsay L. Fuleihan, MD, is Associate Professor at Northwestern University Feinberg School of Medicine and Attending Physician at Children's Memorial Hospital in Chicago, Illinois, USA, where he is also Director of Primary Immunodeficiency Clinical Services and Director of the Jeffrey Modell Foundation Diagnostic Center for Primary Immunodeficiencies. In addition, Dr Fuleihan is Associate Director of the Allergy and Clinical Immunology Training Program at the Northwestern University Feinberg School of Medicine, USA. Dr Fuleihan received his medical degree at the American University of Beirut in Lebanon. He then trained in pediatrics at Duke University Medical Center in Durham, North Carolina, USA and in allergy and immunology at the Children's Hospital Boston at Harvard Medical School in Massachusetts, USA. A Diplomate of the American Board of Allergy and Immunology, Dr Fuleihan is a member of several professional societies, including the American Academy of Allergy, Asthma and Immunology, the European Society for Immunodeficiencies, the Clinical Immunology Society, and the Society for Pediatric Research. He is a member of the steering committee of the US Immunodeficiency Network and a member of the Medical Advisory Committee of the Immune Deficiency Foundation. Giovanni PassalacquaGiovanni PassalacquaDr Passalacqua was born in Genoa in 1964. He graduated in 1990 from the Genoa University Medical School, Italy, and received specialty degrees in Allergy and in Respiratory Medicine in 1994 and 2002. Under the chairmanship of Prof. Giorgio Walter Canonica, he contributed to investigate the mechanisms of allergic inflammation, the treatment of respiratory allergy and developed sublingual immunotherapy. Currently he is Professor of Respiratory Medicine and Allergy at the Respiratory Diseases Clinic of the University of Genoa. Dr Passalacqua has coauthored more than 200 publications in peer reviewed journals. He serves on the board of experts of Allergic Rhinitis and its Impact on Asthma (ARIA), and is co-Chairman of the immunotherapy committee of the World Allergy Organization. Robert BushRobert BushDr Robert Bush received his MD degree from West Virginia University, USA. After completing his residency in Internal Medicine and fellowship in Allergy and Immunology at the University of Wisconsin – Madison, USA, he joined the faculty. He is currently Professor (Emeritus) of Medicine and was the former Chief of Allergy at the William S Middleton VA Hospital, Madison, Wisconsin, USA. His research interests include sublingual immunotherapy, allergen characterization, fungal allergy, food allergy, and occupational asthma. He is certified by the American Board of Allergy and Immunology.

Association between indoor fungi in Delhi homes and sensitization in children with respiratory allergy

Indoor fungi are potential sensitizing agents in children and their detection and quantification in indoor air are important in the diagnosis and environmental management of fungal allergies. The objective of this investigation was to assess the prevalence of fungal allergies in children in Delhi and to study the association between mold counts in the homes of children and their sensitization to respective fungal extracts. Fungal concentrations and seasonality were studied at two-week intervals for one year using Andersen Volumetric and Burkard Slide samplers. Sensitization to fungi frequently encountered in patients' homes was assessed by Skin Prick Tests (SPTs). Total fungal specific IgE was measured by ELISA in the sera of patients positive to fungal extracts. Skin Prick Tests revealed that 39.3% (33/84) of patients were markedly positive (2 + and above) to one or the other fungal allergens. Raised serum IgE to predominant indoor fungal species was observed in patients with marked SPT results. Highest marked skin reactivity (2 + and above) was obtained with Alternaria alternata allergens in 17.9% of the children, which was followed by the response to fungal antigens of Aspergillus fumigatus and Penicillium citrinum (15.5%). Exposure to high fungal counts of some dominant fungi (Penicillium, A. nidulans and A. fumigatus) was found associated with increased fungal sensitization in the patients. Total serum IgE level was revealed to be significantly linked with the intensity of skin reactions, as well as with skin index (r(2) = 0.052; P < 0.05). We concluded that children in Delhi are exposed to high concentrations of fungi in the indoor environment and that respiratory allergies were connected with higher prevalence of skin sensitization.

A sheep model to investigate the role of fungal biofilms in sinusitis: fungal and bacterial synergy

The role of fungi in the spectrum of chronic rhinosinusitis (CRS) is poorly understood. Fungal biofilms have recently been discovered in CRS patients. We have developed an animal model for the investigation of sinonasal fungal biofilms. The role of type I hypersensitivity and pathogenic bacteria is presented. Thirty sheep were sensitized with fungal antigens-Aspergillus fumigatus and Alternaria alternata, or control. Endoscopic surgery was performed to expose both frontal sinus ostia-1 was occluded. Fungi with or without Staphylococcus aureus were inoculated into the sinus. Skin-prick tests assessed for fungal allergy. Fungal and S. aureus biofilms, histology, and culture rates were assessed. Forty-five percent of experimental sheep were sensitized to fungal antigen. Only 1 sinus inoculated with fungus developed minimal fungal biofilm. Eighty percent developed fungal biofilm when S. aureus was co-inoculated. The presence of hypersensitivity to fungus was not related to fungal biofilm development. Significant fungal biofilm only occurred when S. aureus was the co-inoculum. Hypersensitivity was not requisite. The relationship of S. aureus to fungal biofilms is of great clinical interest. Fungi may be opportunistic pathogens that simply require inflamed mucosa with weakened innate defenses; alternatively, a cross-kingdom synergy could be contributing to fungal proliferation.