Annika Luukkainen

Indoleamine 2,3-dioxygenase expression is associated with chronic rhinosinusitis with nasal polyps and antrochoanal polyps.

Chronic rhinosinusitis without and with nasal polyps (CRSwNP and CRSsNP), and antrochoanal polyps are different phenotypes with different pathomechanisms. Indoleamine 2,3-dioxygenase (IDO) is an enzyme expressed in many cells involved in the catabolism of the essential amino acid tryptophan to kynurenine. IDO might have a role in allergic airway inflammation. The aim was to evaluate if IDO expression is associated with CRSsNP, CRSwNP, or ACP. One hundred fifty specimens from the nasal cavity and sinus mucosa were immunohistochemically stained with mAb anti-IDO. The expression of epithelial and leukocyte IDO was associated with CRSwNP and ACP. The presence of ASA intolerance, asthma, atopy, smoking and use of medication did not significantly change the results. The different expression of IDO could putatively indicate the differences in the pathomechanisms of CRSsNP, CRSwNP and ACP. Further studies on the role of IDO in upper airways pathologies are required.

Relationships of indoleamine 2,3-dioxygenase activity and cofactors with asthma and nasal polyps.

Background Asthma and chronic rhinosinusitis with nasal polyps (CRSwNPs) are coexisting diseases that are multifactorial. The rural environment seems to protect from atopy, but its relation with nonatopic airway inflammations has been less investigated. Indoleamine 2,3-dioxygenase (IDO) is an enzyme involved in the catabolism of the essential amino acid tryptophan (Trp) to kynurenine (Kyn). Low IDO activity has been previously observed in atopy and asthma. The objective was to investigate the relationships of IDO activity, eosinophils, and cofactors during asthma and/or CRSwNPs. Methods A Finnish population-based cohort of adult asthmatic patients (n = 245) and nonasthmatic patients (n = 405) was used. The presence of asthma and atopy were based on patient history and standardized diagnostic tests. The presence of acetyl salicylic acid intolerance, doctor-diagnosed NPs, and countryside environment during childhood were based on a questionnaire report. Serum IDO activity was evaluated by assessing the Kyn/Trp ratio by liquid chromatography. Results Low IDO activity was associated significantly with atopy, CRSwNPs, and an urban background. IDO activity did not correlate with pulmonary function. As expected, CRSwNPs was more frequent among asthmatic patients. A rural background has a protective effect from atopy and atopic asthma but it did not affect the prevalence of CRSwNPs or nonatopic asthma. Conclusion Low IDO activity might result from the urban environment and influence the development of the atopic phenotype. On the other hand, low IDO activity, found in CRSwNPs, does not seem to be related to the urban background an us may result from other, still unknown, factors.

Indoleamine 2,3-dioxygenase expression in patients with allergic rhinitis: a case-control study

BackgroundIndoleamine 2,3-dioxygenase (IDO) is a tryptophan catalyzing enzyme. It has been suggested that it has a role in lower airway allergic inflammations, but its role in allergic rhinitis has not been investigated.ObjectiveOur aim was to evaluate the expression of IDO in the nasal mucosa of allergic rhinitis patients allergic to birch pollen during peak exposure to birch pollen allergen and compare it to non-atopic patients.MethodsIDO expression was immunohistochemically evaluated from nasal specimens obtained in- and off-season from otherwise healthy non-smoking volunteers both allergic to birch pollen (having mild or moderate allergic rhinoconjunctivitis) and non-allergic controls. Results: The IDO expression levels were low in healthy controls and remained low also in patients allergic to birch pollen. There were no differences in the expression of IDO in- and off-season in either healthy or allergic subjects.ConclusionsThere is a controversy in the role of IDO in upper and lower airways during allergic airway disease. It seems that IDO is associated to allergic inflammations of the lower airways, but does not have a local role in the nasal cavity at least in mild or moderate forms of allergic rhinitis.

Satisfaction with maxillary sinus surgery might be influenced by risk factors.

Chronic rhinosinusitis (CRS) is an inflammation of the nose and paranasal sinuses lasting for ≥12 weeks. Endoscopic sinus surgery (ESS) is considered during difficult to treat CRS. The minimally invasive technique focuses on the transition areas rather than on the ostia. The aim of this study was to evaluate symptoms, the number of acute sinusitis episodes, and satisfaction after ESS with either preservation or enlargement of the maxillary sinus ostium. Thirty patients with moderate nonpolypous CRS were enrolled. Uncinectomy only and additional middle meatal antrostomy were randomized for each side of each patient and performed single blindly. The symptoms questionnaires were filled at four time intervals. Significant symptom reduction was achieved independently of operation technique. The number of acute sinusitis episodes indicating the exacerbation rate decreased significantly at 9 and, on average, 68 months postoperatively. However, the exacerbation rate began to increase after 9 months postoperatively. Three revisions were performed on the side with uncinectomy only and one on the side with additional antrostomy. Most patients reported good satisfaction with both procedures. There was a trend for patients with asthma and/or job exposure to report insignificantly more frequently no satisfaction with surgery, especially with the uncinectomy-only procedure. Both procedures seem to be efficient in providing symptom relief and satisfaction. More studies are needed to evaluate if patients with risk factors benefit more from an ostium-enlarging procedure.Chronic rhinosinusitis (CRS) is an inflammation of the nose and paranasal sinuses lasting for ≥12 weeks. Endoscopic sinus surgery (ESS) is considered during difficult to treat CRS. The minimally invasive technique focuses on the transition areas rather than on the ostia. The aim of this study was to evaluate symptoms, the number of acute sinusitis episodes, and satisfaction after ESS with either preservation or enlargement of the maxillary sinus ostium. Thirty patients with moderate nonpolypous CRS were enrolled. Uncinectomy only and additional middle meatal antrostomy were randomized for each side of each patient and performed single blindly. The symptoms questionnaires were filled at four time intervals. Significant symptom reduction was achieved independently of operation technique. The number of acute sinusitis episodes indicating the exacerbation rate decreased significantly at 9 and, on average, 68 months postoperatively. However, the exacerbation rate began to increase after 9 months postoperatively. Three revisions were performed on the side with uncinectomy only and one on the side with additional antrostomy. Most patients reported good satisfaction with both procedures. There was a trend for patients with asthma and/or job exposure to report insignificantly more frequently no satisfaction with surgery, especially with the uncinectomy-only procedure. Both procedures seem to be efficient in providing symptom relief and satisfaction. More studies are needed to evaluate if patients with risk factors benefit more from an ostium-enlarging procedure.

Self-Reported Allergic Rhinitis and/or Allergic Conjunctivitis Associate with IL13 rs20541 Polymorphism in Finnish Adult Asthma Patients

Background: Our aim was to observe factors associated with IL13 rs20541 polymorphism and other factors with or without allergic comorbidities such as subject-reported allergic rhinitis (AR) and/or allergic conjunctivitis (AC) symptoms in adult asthmatics. Methods: A population-based sample of Finnish adult asthma patients (n = 1,156) and matched controls (n = 1,792) filled in a questionnaire. Asthma was diagnosed based on a typical history of asthma symptoms and lung function tests. Skin prick tests with 17 aeroallergens and blood tests including analysis of interleukin 13 (IL13) rs20541 (G/A) genotypes were performed for a subsample (n = 193). Results: The proportion of asthmatics reporting AR was 61.9% and reporting AC was 40.7%. After adjustments, the presence of the IL13 rs20541A- allele (OR 3.06, 95% CI 1.42-6.58, p = 0.004) or multisensitization (adjusted OR 4.59, 95% CI 1.48-14.26, p = 0.008) was associated with AR/AC asthma. Nasal polyps and acetylsalicylic acid-exacerbated respiratory disease was also associated with AR/AC asthma. Conclusions: Adult AR/AC asthma could putatively be a phenotype, characterized by the presence of atopic and/or eosinophilic factors and a high prevalence of the IL13 rs20541A- allele. Studies on the mechanisms behind this and in other populations are needed.

Endoscopic Sinus Surgery with Antrostomy Has Better Early Endoscopic Recovery in Comparison to the Ostium-Preserving Technique

Background. Endoscopic sinus surgery (ESS) is considered for chronic rhinosinusitis (CRS) after failure of conservative therapy. Objective. The aim of this study was to evaluate endoscopically ostium patency and mucosal recovery after ESS, with either maxillary sinus ostium-preserving or -enlarging techniques. Materials and Methods. Thirty patients with non-polypous CRS were enrolled. Uncinectomy-only and additional middle meatal antrostomy were randomly and single-blindly performed for each side. Pre- and postoperative endoscopic scores were semi-quantitatively determined according to findings in the ostiomeatal complex area. Adhesions, maxillary sinus mucosal swelling, secretions, and ostium obstruction were also endoscopically evaluated. In addition, symptoms were asked and computed tomography scans were taken preoperatively and 9 months postoperatively. Results. At 16 days postoperatively, a better endoscopic score and a less obstructed ostium were found with antrosomy. At 9 months postoperatively the endoscopic score improved significantly and identically with both procedures, however, obstructed ostia and sinus mucosal swelling/secretions were insignificantly more frequently found on the uncinectomy-only side. Endoscopic and radiologic findings of the maxillary sinus mucosa and ostium correlated significantly 9 months postoperatively. Conclusion. There was a good long-term mucosal recovery with both surgical procedures. In terms of early mucosal recovery and ostium patency, antrostomy might be slighly superior.

The expression and prognostic relevance of indoleamine 2,3-dioxygenase in tongue squamous cell carcinoma.

Abstract Conclusion IDO might be useful for predicting progression of primary tumor stage T2 and T3 in tongue squamous cell carcinoma (TSCC), but does not seem like a specific biomarker for diagnosing TSCC and predicting patient survival. Objectives Indoleamine 2,3-dioxygenase (IDO) is expressed in many cells and it catabolises the essential amino acid tryptophan to kynurenine. IDO acts as an immune modulator through suppression of T-cell immunity and other pathways. In cancer cells, IDO has been proposed to promote tumor progression by enabling malignant cells to escape from the immune system. The aim of this study was to evaluate the association and prognostic relevance of IDO expression in TSCC. Method One hundred and eight retrospective tongue and lymph node specimens were stained immunohistochemically with monoclonal antibody anti-indoleamine 2,3-dioxygenase. The relative abundance of IDO positive epithelial cells, IDO staining intensity, and inflammation were assessed semi-quantitatively with light microscopy. Results IDO was expressed stronger in tongue hyperplasia than in TSCC. However, IDO expression associated with poor survival in the sub-groups with primary tumor stage T2–T4 and in the sub-group with strong inflammation in tumors’ invasive front.

Birth decade affects the sensitization pattern and asthma-risk in Finnish adult population

We have previously shown that sensitizations to several types of allergens distinguish subjects with and without adult‐onset asthma in Finland. The aim was to analyze how age affects sensitization and asthma risk. We used previous population‐based case‐control data (N=456) from Finnish adult asthma patients with one or two matched controls. Asthma was diagnosed based on a typical history of asthmatic symptoms and lung function tests. Allergic sensitization was determined by skin prick test (SPT) to 17 aeroallergens. Information on demographics was obtained by a questionnaire. Sensitization to more than one allergen type and the number of positive SPT reactions associated with younger age and asthma. Atopic subjects aged 65 and above were characterized by sensitization to only one to two allergens, with very few animal danders and without an association with asthma. Multiple sensitizations and animal dander sensitization are more common among Finnish asthmatic adults aged under 56 than among older asthmatics. Cohort studies are needed to understand timing of host‐environmental interactions behind this.

The expression of cancerous inhibitor protein phosphatase 2A in chronic rhinosinusitis with nasal polyps

Abstract Conclusion: The study suggests that cancerous inhibitor of protein phosphatase 2A (CIP2A) expression and eosinophilia associate with chronic rhinosinusitis with nasal polyps with aspirin exacerbated respiratory disease (CRSwNP + AERD). Further studies with a larger sample size are needed to evaluate further the role of CIP2A and related pathways in CRSwNP + AERD. Objectives: Low prostaglandin E2 levels putatively associate with CRSwNP + AERD and decreased c-Myc levels. The aim of this study was to evaluate the expression and revision-predictive role of oncoprotein CIP2A, another c-Myc modulator, in CRSwNP with/without AERD, and in antrochoanal polyps. Method: Ninety retrospective archival objective glasses of nasal polyp tissue from CRSwNP or ACP patients were used for assessing mucosal eosinophilia. Of this population, 90 archival nasal polyp specimens were available for immunohistochemical staining with a polyclonal anti-CIP2A antibody, together with 19 control nasal mucosa specimens. CIP2A staining intensity and tissue eosinophilia were assessed by two blinded observers with a light microscope. Subject characteristics from 90 patients and 19 controls were obtained from patient records and additionally by a questionnaire from controls. The follow-up data was available from patient records of 84 patients and 16 controls. Results: The expression of epithelial CIP2A was detected both in control inferior turbinate mucosa and nasal polyps. The expression was significantly lower in the CRSwNP + AERD group compared to controls and CRSwNP without AERD (p < 0.01). High mucosal eosinophilia associated with CRSwNP (p < 0.01). Neither CIP2A nor eosinophilia predicted the need for revision surgery (p > 0.05), whereas previous surgery, allergic rhinitis, and use of corticosteroids did predict the need for revision surgery (p < 0.05).

Indoleamine 2,3-dioxygenase expression is associated with chronic rhinosinusitis: review of the evidence.

Purpose of reviewIndoleamine 2,3 dioxygenase (IDO), the key metabolic enzyme implicated in tryptophan catabolism has been studied extensively during the past years in cancer, infections and autoimmunity. This review summarizes the findings of the immunomodulatory effects of IDO. In addition, the possible role of IDO in chronic rhinosinusitis (CRS) is discussed. Recent findingsEpithelial and leukocyte IDO expression is pronounced in CRS with nasal polyps and antrochoanal polyps. Although IDO associates with atopic disorders of the lower respiratory tract, we were not able to find an association between IDO and allergic rhinitis in the sinonasal mucosa. SummaryIDO might have a distinct role in the upper and lower respiratory tract. Future studies need to identify whether the IDO found in sinonasal mucosa is active and if it is a cause or a reason in the development of CRS with nasal polyps.