A 14-year-old boy with severe erythema multiforme due to amoxicillin.

The most common cause of erythema multiforme (EM) in children is infectious diseases which account for approximately 90% of cases. Drug eruptions are another common cause. Here we are reporting about a male patient aged 14 years with lymphadenitis who developed severe diffuse erythema during the course of treatment with medications including several antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs). Based on the pathological findings of the skin biopsy, the skin rash was due to EM. Upon investigating the underlying cause of EM, viral antibody was positive for Coxsackie A6, lymphocyte transformation testing (LTT) was positive for one of the NSAIDs, and the patch test (PT) was positive for amoxicillin. Based on the pattern of distribution of the skin rash, the cause of EM was considered to be drug-induced eruption due to amoxicillin. In this case, we did not derive a diagnosis of drug eruption without investigating the possibility of drug induction, because most cases of EM in children are induced by infection and the antibody against Coxsackie A6 was elevated. To diagnose the possibility of amoxicillin-induced EM, it was important to distinguish between the distribution patterns of infectious versus drug-induced EM and to evaluate the possibility of drug induction by both LTT and PT. If the diagnosis of amoxicillin-induced EM, had not been made, the potential recurrence of EM with amoxicillin could have occurred.

Asia-Pacific survey of physicians' perceptions and managements of chronic rhinosinusitis.

BACKGROUND: The diagnosis and management of patients with chronic rhinosinusitis (CRS) may vary between otolaryngologists and allergists. Moreover, the adherence of different practitioners to European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2020 guideline recommendations has not been previously ascertained in Asia-Pacific regions. OBJECTIVE: Different specialists' perceptions and managements of CRS in Asia-Pacific regions were assessed in an attempt to gauge these practices against EPOS 2020 guidelines. METHODS: A transregional, cross-sectional survey was conducted to assess otolaryngologists' and allergists' perceptions and managements of CRS with regard to diagnosis, management and adherence to EPOS 2020 guidelines. RESULTS: Sixteen physicians in Asia-Pacific regions responded to the questionnaire. A total of 71.4% of otolaryngologists preferred to diagnose CRS with a combination of positive nasal symptoms and nasal endoscopy plus sinus CT, whereas 22.2% of allergists took such criterion to diagnose CRS. Compared to allergists, otolaryngologists more often considered the endotype classification (85.8% versus 55.5%). For the preferred first-line treatment, in addition to intranasal corticosteroids recommended by all respondents, 66.7% of allergists preferred antihistamines, whereas 71.4% of otolaryngologists preferred nasal saline irrigation. Regarding the proper timing of surgery, 71.5% of otolaryngologists reported 8-12 weeks of treatment after the initiation of medication, while more than half of the allergists recommended 4-6 weeks of medical treatment. CONCLUSIONS: This survey shows that variable perceptions and practices for CRS may exist between physicians with different specialties and highlights the need for increased communication and awareness between otolaryngologists and allergists to improve the diagnosis and treatment of CRS.

Climate Change, Air Pollution, and Biodiversity in Asia Pacific and Impact on Respiratory Allergies.

Allergic diseases are increasing globally. Air pollution, climate change, and reduced biodiversity are major threats to human health with detrimental effects on chronic noncommunicable diseases. Outdoor and indoor air pollution and climate change are increasing. Asia has experienced rapid economic growth, a deteriorating environment, and an increase in allergic diseases to epidemic proportions. Air pollutant levels in Asian countries are substantially higher than in developed countries. Moreover, industrial, traffic-related, and household biomass combustion and indoor pollutants from chemicals and tobacco are major sources of air pollutants. We highlight the major components of pollutants and their impacts on respiratory allergies.

International expert consensus on the management of allergic rhinitis (AR) aggravated by air pollutants: Impact of air pollution on patients with AR: Current knowledge and future strategies.

Allergic rhinitis affects the quality of life of millions of people worldwide. Air pollution not only causes morbidity, but nearly 3 million people per year die from unhealthy indoor air exposure. Furthermore, allergic rhinitis and air pollution interact. This report summarizes the discussion of an International Expert Consensus on the management of allergic rhinitis aggravated by air pollution. The report begins with a review of indoor and outdoor air pollutants followed by epidemiologic evidence showing the impact of air pollution and climate change on the upper airway and allergic rhinitis. Mechanisms, particularly oxidative stress, potentially explaining the interactions between air pollution and allergic rhinitis are discussed. Treatment for the management of allergic rhinitis aggravated by air pollution primarily involves treating allergic rhinitis by guidelines and reducing exposure to pollutants. Fexofenadine a non-sedating oral antihistamine improves AR symptoms aggravated by air pollution. However, more efficacy studies on other pharmacological therapy of coexisting AR and air pollution are currently lacking.

Drug hypersensitivity reactions in Asia: regional issues and challenges.

There are geographical, regional, and ethnic differences in the phenotypes and endotypes of patients with drug hypersensitivity reactions (DHRs) in different parts of the world. In Asia, aspects of drug hypersensitivity of regional importance include IgE-mediated allergies and T-cell-mediated reactions, including severe cutaneous adverse reactions (SCARs), to beta-lactam antibiotics, antituberculous drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) and radiocontrast agents. Delabeling of low-risk penicillin allergy using direct oral provocation tests without skin tests have been found to be useful where the drug plausibility of the index reaction is low. Genetic risk associations of relevance to Asia include human leucocyte antigen (HLA)-B*1502 with carbamazepine SCAR, and HLA-B*5801 with allopurinol SCAR in some Asian ethnic groups. There remains a lack of safe and accurate diagnostic tests for antituberculous drug allergy, other than relatively high-risk desensitization regimes to first-line antituberculous therapy. NSAID hypersensitivity is common among both adults and children in Asia, with regional differences in phenotype especially among adults. Low dose aspirin desensitization is an important therapeutic modality in individuals with cross-reactive NSAID hypersensitivity and coronary artery disease following percutaneous coronary intervention. Skin testing allows patients with radiocontrast media hypersensitivity to confirm the suspected agent and test for alternatives, especially when contrasted scans are needed for future monitoring of disease relapse or progression, especially cancers.

Asia Pacific Association of Allergy Asthma and Clinical Immunology White Paper 2020 on climate change, air pollution, and biodiversity in Asia-Pacific and impact on allergic diseases.

Air pollution, climate change, and reduced biodiversity are major threats to human health with detrimental effects on a variety of chronic noncommunicable diseases in particular respiratory and cardiovascular diseases. The extent of air pollution both outdoor and indoor air pollution and climate change including global warming is increasing-to alarming proportions particularly in the developing world especially rapidly industrializing countries worldwide. In recent years, Asia has experienced rapid economic growth and a deteriorating environment and increase in allergic diseases to epidemic proportions. Air pollutant levels in many Asian countries especially in China and India are substantially higher than are those in developed countries. Moreover, industrial, traffic-related, and household biomass combustion, indoor pollutants from chemicals and tobacco are major sources of air pollutants, with increasing burden on respiratory allergies. Here we highlight the major components of outdoor and indoor air pollutants and their impacts on respiratory allergies associated with asthma and allergic rhinitis in the Asia-Pacific region. With Asia-Pacific comprising more than half of the world's population there is an urgent need to increase public awareness, highlight targets for interventions, public advocacy and a call to action to policy makers to implement policy changes towards reducing air pollution with interventions at a population-based level.

A case of anhidrotic ectodermal dysplasia presenting with pyrexia, atopic eczema, and food allergy.

Anhidrotic ectodermal dysplasia (AED) is a rare hereditary disorder with a triad of sparse hair, dental hypoplasia, and anhidrosis. Here we report a case of AED with food allergy and atopic eczema. The patient was a 11-month-old boy admitted to our hospital with pyrexia for 2 weeks. He presented with a history of dry skin, eczema, and food allergy to egg. On clinical examination, his body temperature was 38.8°C, with dry skin and eczema almost all over the body, sparse eyebrows, and scalp hair. Laboratory investigations and physical examination did not show any evidence of infection. Radioallergosorbent test was positive to egg yolk, egg white, ovomucoid, milk, house dust, and house dust mite. As the child did not sweat despite the high fever, we performed the sweat test which revealed a total lack of sweat glands. Genetic examination revealed a mutation of the EDA gene and he was diagnosed as AED. His pyrexia improved upon cooling with ice and fan. His mother had lost 8 teeth and her sweat test demonstrated low sweating, suggestive of her being a carrier of AED. Atopy and immune deficiencies have been shown to have a higher prevalence in patients with AED. Disruption of the skin barrier in patients with AED make them more prone to allergic diseases such as atopic eczema, bronchial asthma, allergic rhinitis and food allergy. Careful assessment of the familial history is essential to differentiate AED when examining patients with pyrexia of unknown origin and comorbid allergic diseases.

Otitis media with effusion and atopy: is there a causal relationship?

Otitis Media with Effusion (OME) is an inflammatory condition of the middle ear cleft, acute or chronic, with collection of fluid in the middle ear with an intact tympanic membrane. It is a very common disease in childhood, the most frequent cause of hearing loss in childhood and often requiring surgery. OME is called chronic when the fluid in the middle ear persists for more than three months or when the episodes recur six or more times in one year. The current article covers various aspects of OME including definition, epidemiology. Pathomechanisms, risk factors, role of allergy in OME, impact of upper airway disease on OME, eosinophilic otitis media and management of OME.

The paradigm of cytokine networks in allergic airway inflammation.

PURPOSE OF REVIEW: Cytokines are immunomodulatory proteins important in cell signaling. Complex interactions of innate and adaptive immune cells, as well as structural cells and their cytokines, play crucial roles in regulating allergic airway inflammation. Here, we summarize current knowledge about the potential roles of known and newly identified helper T cells and epithelial cell-derived cytokines [interleukin (IL)-9, IL-17, IL-22, IL-25, and IL-33] in allergic rhinitis and asthma. RECENT FINDINGS: Although T-helper (Th)2 cells were considered to be the main orchestrators of allergic airway inflammation, recent studies have revealed the potential interaction of other helper T cells and their cytokines in this process. Th17 cells may have a role in allergic rhinitis and asthma, and chronic rhinosinusitis with nasal polyps. An IL-9-producing subset called Th9 cells, Th22 cells which primarily secrete IL-22, IL-13, tumor necrosis factor-α, Th25 cells via producing IL-25 and epithelial cell-derived thymic stromal lymphopoietin, IL-33, IL-31, and IL-25 are believed to be important for the initiation of allergic reactions and inducing airway inflammation. SUMMARY: A new paradigm of an interplay of cytokines is important in allergic rhinitis and asthma in orchestrating the allergic inflammatory response. Potential therapeutic applications emerging from the roles of these cytokines are promising, but need further research.

Rhinosinusitis and asthma-microbiome and new perspectives.

PURPOSE OF REVIEW: Microbiome is one of the new perspectives in human health research, including airway diseases. There are several publications about the relationship of the microbiome and allergic diseases. Although pathogenesis of chronic rhinosinusitis (CRS) as well as its relationship with asthma has been widely investigated, the relationship of the microbiome and CRS is not yet well known. RECENT FINDINGS: The relationship between the hygiene hypothesis and microorganisms inside the human body and in the environment around it has been clearly shown. Furthermore, several researchers have reported that the microorganisms in the gut play a major role in regulating the immune cells that are of relevance to asthma and allergic diseases, such as Th1, Th2, Th17, Treg and dendritic cells as well as Toll-like receptors. Reduced contact of people with natural environmental features and biodiversity may adversely affect the human commensal microbiota and its immunomodulatory capacity.Some studies have shown a close relationship between CRS and Staphylococcus aureus, anaerobes and so on in the nasal cavity or paranasal sinuses, although the relationship between CRS and microorganisms in the gut has not been demonstrated. SUMMARY: In this review, we summarized about the microbiome, mainly in asthma and allergic diseases. The relationship between asthma and CRS has been clearly shown, and in particular, CRS with nasal polyps (CRSwNP) has been considered to be Th2-dominant. Studies examining environmental microbial exposure in populations at risk for CRS are necessary to improve our understanding of the role this factor plays in disease development.

Perspectivas atuais sobre inflamação e remodelamento das vias aéreas na asma e na rinite alérgica / Current perspectives on airway inflammation and remodelling in asthma and allergic rhinitis

O desenvolvimento da rinite alérgica (RA) e da asma requer uma interação entre ambiente, sistema imunológico e susceptibilidade genética. Enquanto a rinite induzida por pólen é a mais característica doença alérgica mediada pela imunoglobulina E, na RA perene os desencadeantes da alergia são mais contínuos e levam à inflamação constante. Várias células e mediadores coordenam e mantêm essa inflamação. Embora a histamina ainda seja um dos principais mediadores da reação alérgica, muitos outros mediadores produzidos por diferentes tipos celulares estão envolvidos. Assim, a intrincada interação entre esses mediadores, citocinas, quimiocinas, neuropeptídeos, moléculas de adesão e várias células na forma de uma rede complexa leva ao desenvolvimento de sintomas específicos e à hiper-reatividade não específica presente na RA. A asma é caracterizada por graus variáveis de inflamação crônica e alterações estruturais nas vias aéreas que incluem denudação epitelial, metaplasia das células caliciformes, espessamento subepitelial, aumento da massa do músculo liso nas vias aéreas, aumento das glândulas brônquicas, angiogênese, e alterações nos componentes da matriz extracelular envolvendo as pequenas e grandes vias aéreas. Acredita-se que a inflamação crônica inicie e perpetue ciclos de dano e reparo tecidual na asma, embora o remodelamento também possa ocorrer em paralelo com a inflamação. Ao mesmo tempo em que RA e asma apresentam várias semelhanças em termos de perfil e resposta das células inflamatórias e dos mediadores, o remodelamento como observado na asma não é característico da RA. Na asma, as relações entre inflamação e remodelamento das vias aéreas e função pulmonar estão sendo melhor compreendidas. Uma variedade de células inflamatórias e células estruturais atuam na coordenação da inflamação e das mudanças estruturais na asma. O aumento da responsividade das vias aéreas é um marcador substituto de inflamação e pode refletir o desenvolvimento de mudanças estruturais nas vias aéreas. Tal aumento persistente da responsividade brônquica aponta para a ocorrência de remodelamento parcialmente resistente à terapia.

The development of AR and asthma requires an interaction between the environment, imune system and genetic susceptibility. While pollen-induced rhinitis is the most characteristic IgE mediated allergic disease, in perennial allergic rhinitis the allergic triggers are more continuous, and lead to on going inflammation. Several cells and mediators orchestrate and maintain this inflammation. Although histamine is still one of the major mediators of the allergic reaction, many other mediators produced by different cell types are involved. Thus, the intricate interaction amongst these mediators, cytokines, chemokines, neuropeptides, adhesion molecules and various cells in the form of a complex network leads to the development of specific symptoms and the non specific hyperreactivity of allergic rhinitis. Asthma is characterized by variable degrees of chronic inflammation and structural alterations in the airways which include epithelial denudation, goblet cell metaplasia, subepithelial thickening, increased airway smooth muscle mass, bronchial gland enlargement, angiogenesis, and alterations in extracellular matrix components, involving large and small airways. Chronic inflammation is thought to initiate and perpetuate cycles of tissue injury and repair in asthma, although remodeling may also occur in parallel with inflammation. While AR and asthma share several similarities in the inflammatory cell and mediator profiles and responses, remodeling as seen in asthma is not characteristic of AR. In asthma, the relationships of airway inflammation, remodeling and lung function are becoming better understood. A variety of inflammatory cells and structural cells play a role in orchestrating the inflammation and structural changes in asthma. Increased airway responsiveness is a surrogate marker of inflammation and may reflect the development of structural changes in the airways. Such persistent increased bronchial responsiveness indicates remodeling which is partly resistant to therapy.

Indications, efficacy, and safety of intranasal corticosteriods in rhinosinusitis.

Rhinosinusitis is a significant health problem, causing significant morbidity and resulting in considerable financial cost. Some patients suffer persistent or recurrent symptoms despite receiving optimal medical and surgical treatment. Rhinosinusitis can be acute or chronic, acute often due to viral or bacterial infections and chronic which is classified into chronic with nasal polyposids or chronic rhinosinusitis without nasal polyposis. The disease affects the quality of life significantly and presents a significant burden on health costs globally. The anatomical linkage of the nose with the paranasal sinuses facilitates a common pathology in both organs. Chronic rhinosinusitis (CRS) has heterogeneous origins, including viruses, bacteria, fungal infections, anatomical abnormalities, polyposis, and aspirin sensitivity. Other conditions such as human immunodeficiency virus acquired immunodeficiency and cystic fibrosis may also be predisposing factors. Nasal polyposis is often associated with increased numbers of Th2 lymphocytes, fibroblasts, goblet cells, mast cells, and eosinophils, with upregulation of IL-13 and the release of specific IgE to staphylococcal enterotoxins. There is recent evidence that antibiotic treatment may not be as effective as higher doses of intranasal steroids in acute uncomplicated rhinosinusitis, especially in those with allergic disease. The broad inflammatory basis of the pathology of CRS also reveals a cellular infiltrate theoretically suppressed by intranasal corticosteroids. This has been confirmed in recent clinical studies of CRS with or without polyps. A treatment approach based on such studies reported in the European Position Paper on Rhinosinusitis guidelines and a guideline summary are presented. The current review represents the proceedings of a session (3 talks) by the authors at the first Middle East-Asia Allergy, Asthma, Immunology Congress in 2009.

Expression and Roles of MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2 in Allergic Nasal Mucosa.

PURPOSE: Allergic rhinitis (AR) and asthma share many characteristics, but structural changes are observed far less often in AR. Matrix metalloproteinases (MMPs) constitute a family of Zn-dependent endopeptidases that can decompose the extracellular matrix and basement membrane, and regulate cell infiltration. We analyzed the expression of MMPs and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), in allergic nasal mucosa after nasal allergen challenge (NAC) and determined their relationship to inflammatory cells. METHODS: Nasal mucosa specimens were obtained at surgery performed for hypertrophied turbinates. We performed NAC with house dust mite (HDM) allergen disks and control disks, and took biopsies at 30 minutes, 6 hours, and 12 hours after NAC. Cells expressing MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2, as well as eosinophils and mast cells, were analyzed immunohistochemically. The MMPs and TIMPs in allergic nasal mucosa were quantified using enzyme-linked immunosorbent assays. RESULTS: At 30 minutes post-NAC, HDM-exposed nasal mucosa exhibited significantly more MMP-2+, MMP-9+, MMP-13+, TIMP-1+, and TIMP-2+ cells compared with control mucosa, and the numbers of MMP-9+ and TIMP-1+ cells correlated strongly with the number of mast cells. At 6 hours post-NAC, the numbers of MMP+ and TIMP+ cells did not differ significantly between HDM-exposed mucosa and control mucosa, but the ratios of MMP+ cells to TIMP+ cells were higher in HDM-exposed mucosa. At 12 hours post-NAC, the number of MMP-13+ cells tended to be higher in HDM-exposed mucosa and was strongly correlated with the number of eosinophils. Quantitatively, the levels of MMP-2 and MMP-13 were significantly higher than the MMP-9 level, and the TIMP-2 level was significantly higher than the TIMP-1 level in allergic nasal mucosa. CONCLUSIONS: We demonstrated increased expression of MMP-2, MMP-9, and MMP-13 in allergic nasal mucosa, high MMPs-to-TIMP-1 ratios, and a strong correlation between MMP-9 and mast cells and between MMP-13 and eosinophils. The imbalance between MMPs and TIMPs may contribute to the migration of inflammatory cells such as eosinophils and mast cells to the nasal mucosa of AR patients, suggesting a possible active role of MMPs in AR.

Decreased Expression of FOXP3 in Nasal Polyposis.

PURPOSE: The pathogenesis of nasal polyposis (NP) is unclear. Eosinophils and mast cells are considered to play important roles in this process. In addition, the levels of Th2-type cells are increased, irrespective of the atopic status of the patient with NP. In this context, we and others have shown high levels of thymus and activation-related chemokine/CCL17, macrophage-derived chemokine, eotaxin, and RANTES in patients with NP. Forkhead box P3 (FOXP3) plays a key role in CD4+CD25+ regulatory T-cell function and represents a specific marker for regulatory T cells (Tregs). Decreased expression of FOXP3 has been reported in allergic diseases. The present study was designed to evaluate the presence and potential roles of Tregs, defined by the expression of FOXP3 protein, in NP. METHODS: Using immunohistochemistry, we estimated the numbers of FOXP3+ cells in the epithelium and lamina propria of the NPs of 17 patients with chronic rhinosinusitis with NP and the nasal mucosa of 15 patients with allergic rhinitis (AR). The number of FOXP3+ cells in NPs was compared with that in the nasal mucosa of patients with AR, and the numbers of FOXP3+ cells in atopic and non-atopic NP were also compared. RESULTS: The number of FOXP3+ cells in the lamina propria of patients with NP was significantly lower than that in the nasal mucosa of the AR patients (2.79 vs. 5.99, P=0.008). There was no statistically significant difference noted for the numbers of FOXP3+ cells between the epithelium of the NP and the nasal mucosa (3.60 vs. 2.39, P=0.180). Furthermore, the numbers of CD4+FOXP3+ cells were lower in NPs than in the allergic nasal mucosa. There was no difference in the number of FOXP3+ cells between the atopic and non-atopic NP patients. CONCLUSIONS: Fewer Tregs (i.e., decreased FOXP3 expression) are found in NPs than in the nasal mucosa of AR patients. As the severity of eosinophilic, Th2-type inflammation and the levels of inflammatory mediators are much higher in NPs than in the nasal mucosa of AR patients, an inverse co-relationship may exist between these parameters and the number of Tregs. The deficiency of Tregs in NP may account for the more pronounced Th2-type inflammation seen in these patients.

Indications, efficacy, and safety of intranasal corticosteriods in rhinosinusitis.

Rhinosinusitis is a significant health problem, causing significant morbidity and resulting in considerable financial cost. Some patients suffer persistent or recurrent symptoms despite receiving optimal medical and surgical treatment. Rhinosinusitis can be acute or chronic, acute often due to viral or bacterial infections and chronic which is classified into chronic with nasal polyposids or chronic rhinosinusitis without nasal polyposis. The disease affects the quality of life significantly and presents a significant burden on health costs globally. The anatomical linkage of the nose with the paranasal sinuses facilitates a common pathology in both organs. Chronic rhinosinusitis (CRS) has heterogeneous origins, including viruses, bacteria, fungal infections, anatomical abnormalities, polyposis, and aspirin sensitivity. Other conditions such as human immunodeficiency virus acquired immunodeficiency and cystic fibrosis may also be predisposing factors. Nasal polyposis is often associated with increased numbers of Th2 lymphocytes, fibroblasts, goblet cells, mast cells, and eosinophils, with upregulation of IL-13 and the release of specific IgE to staphylococcal enterotoxins. There is recent evidence that antibiotic treatment may not be as effective as higher doses of intranasal steroids in acute uncomplicated rhinosinusitis, especially in those with allergic disease. The broad inflammatory basis of the pathology of CRS also reveals a cellular infiltrate theoretically suppressed by intranasal corticosteroids. This has been confirmed in recent clinical studies of CRS with or without polyps. A treatment approach based on such studies reported in the European Position Paper on Rhinosinusitis guidelines and a guideline summary are presented. The current review represents the proceedings of a session (3 talks) by the authors at the first Middle East-Asia Allergy, Asthma, Immunology Congress in 2009.

Increased expression and role of thymic stromal lymphopoietin in nasal polyposis.

PURPOSE: Nasal polyposis is a chronic inflammatory disease of the upper airways often associated with asthma and characterized by markedly increased numbers of eosinophils, Th2 type lymphocytes, fibroblasts, goblet cells and mast cells. Previous studies have shown elevated levels of thymic stromal lymphopoietin (TSLP) in atopic diseases like asthma, atopic dermatitis and mainly in animal models of allergic rhinitis (AR). Here, we investigated the expression of TSLP in nasal polyps from atopics and non-atopics in comparison with the nasal mucosa and its potential role in nasal polyposis. METHODS: Messenger RNA expression for TSLP, thymus and activation-regulated chemokine (TARC) and macrophage derived chemokine (MDC) in nasal polyps and nasal mucosa of atopics and non-atopics was analyzed by real time PCR. Immunoreactivity for TSLP in nasal polyps and in the nasal mucosa of patients with AR and non-allergic rhinitis (NAR) was analyzed by immunohistochemistry. Eosinophil counts was analyzed by Wright-Giemsa staining and nasal polyp tissue IgE, by ELISA. RESULTS: Messenger RNA expression for TSLP,TARC and MDC was markedly higher in nasal polyps as compared to the allergic nasal mucosa. Immunoreactivity for TSLP was detected in epithelial cells, endothelial cells, fibroblasts and inflammatory cells of the nasal mucosa and nasal polyps. The number of TSLP+ cells was significantly greater in the nasal mucosa of AR than NAR patients. The number of TSLP+ cells in nasal polyps from atopics was significantly greater than that of non-atopics and that in the allergic nasal mucosa. The number of TSLP+ cells correlated well with the number of eosinophils and the levels of IgE in nasal polyps. CONCLUSIONS: The high expression of TSLP in nasal polyps and its strong correlation to eosinophils and IgE suggest a potential role for TSLP in the pathogenesis of nasal polyps by regulating the Th2 type and eosinophilic inflammation.

Nasal polyp fibroblasts produce MIP-3alpha in response to toll-like receptor ligands and cytokine stimulation.

OBJECTIVE: Dendritic cells (DCs) play important roles in the development and perpetuation of immune responses. DCs are present in upper airway diseases such as chronic rhinosinusitis with nasal polyps. However, the mechanisms of how DCs migrate into the upper airway mucosa during upper airway inflammatory diseases remains unclear. Macrophage inflammatory protein-3alpha (MIP-3alpha) is known to be a migratory factor for immature DCs. There have been very few reports regarding cells producing this chemokine in the airways. To investigate this, we stimulated fibroblasts cultured from the nasal polyps with various toll-like receptor (TLR) ligands, which are derived from microorganisms, and IL-beta1 and TNF-alpha, which are proinflammatory cytokines, and analyzed their ability to produce MIP-3alpha. METHODS: Fibroblast lines were established from nasal polyps and stimulated with TLR2, 3, 4, 5, 7/8 and 9 ligands, IL-beta1 and TNF-alpha. MIP-3alpha mRNA expression in nasal polyp fibroblasts (NPF) was evaluated by real-time RT-PCR and the protein levels of MIP-3alpha in the supernatants of stimulated NPF was measured by ELISA. RESULTS: Stimulation with TLR2, 3, 4 and 5 ligands, IL-beta1 and TNF-alpha, induced MIP-3alpha gene expression and protein production in the cultured NPF This response was dose- and time-dependent. CONCLUSION: NPF possibly play an important role in the recruitment of DCs in upper airway diseases such as chronic rhinosinusitis with nasal polyps through the production of MIP-3alpha.

Combined stimulation with Poly(I:C), TNF-alpha and Th2 cytokines induces TARC production by human fibroblasts from the nose, bronchioles and lungs.

BACKGROUND: Th2 cells trigger allergic diseases in the respiratory tract. However, the mechanisms that cause Th2 cell infiltration remain unclear. Viral infections exacerbate allergic diseases in the respiratory tract. Thymus- and activation-regulated chemokine (TARC) recruits Th2 cells to sites of inflammation. Resident fibroblasts are thought to contribute to inflammatory cell infiltration through chemokine production. We compared the abilities of nasal, bronchiolar and lung fibroblasts to produce TARC. METHODS: Expression of TARC mRNA was evaluated by real-time RT-PCR, while the amount of TARC in supernatants was measured by ELISA. RESULTS: Costimulation with TNF-alpha and Th2 cytokines (IL-4, IL-13) or with poly(I:C) and Th2 cytokines (IL-4, IL-13) induced TARC production by nasal (polyp and normal) fibroblasts. Costimulation with TNF-alpha and Th2 cytokines (IL-4, IL-13) also induced TARC production by both bronchiolar and lung fibroblasts, but costimulation with poly(I:C) and Th2 cytokines (IL-4, IL-13) caused no induction. Combined exposure of cells to poly(I:C), TNF-alpha and Th2 cytokines (IL-4, IL-13) resulted in substantial production of TARC by nasal and lung fibroblasts, but much less by bronchiolar fibroblasts. CONCLUSIONS: TARC is directly inducible in diverse fibroblast populations from the respiratory tract (nose, bronchioles and lungs), but the mechanisms and levels of TARC production differ. Fibroblasts in the respiratory tract may contribute to Th2 cell infiltration and viral-induced exacerbation of allergic diseases, such as allergic sinusitis, asthma and allergic lung inflammation.