Publications by authors named "Annika Luukkainen"

12 Publications

  • Page 1 of 1

Maternal smoking during pregnancy affects adult onset of asthma in offspring: a follow up from birth to age 46 years.

Eur Respir J 2020 06 11;55(6). Epub 2020 Jun 11.

Environment Health Unit, National Institute for Health and Welfare, Kuopio, Finland.

Rationale: Environmental tobacco smoke (ETS) exposure increases asthma risk in children. There is limited knowledge of prenatal ETS for adult-onset asthma.

Objectives: To determine the association between prenatal ETS and adult onset asthma.

Measurements And Main Results: The questionnaire and clinical data of 5200 people, free of physician-diagnosed asthma by 31 years of age, who were included in the Northern Finland Birth Cohort 1966 Study was used. The association of maternal smoking during the last 3 months of pregnancy with onset of physician-diagnosed asthma and with lung function in adult offspring was studied using adjusted multivariate regression analyses. The cumulative incidence of physician-diagnosed asthma between the ages of 31 and 46 years was 5.1% among men and 8.8% among women. Gestational smoke exposure was associated with adult-onset asthma among offspring (adjusted OR 1.54, 95% CI 1.04-2.29), namely among offspring who reported either past non-diagnosed asthma (OR 9.63, 95% CI 2.28-40.67) or past cough with wheeze (3.21, 95% CI 1.71-6.05). A significant association was detected between gestational smoke exposure and the offspring's forced expiratory volume in 1 s (FEV)/forced vital capacity (FVC) ratio at 31 years of age. In offspring with the haplotype rs11702779-AA of , gestational smoke exposure was associated with adult-onset asthma (5.53, 95% CI 2.11-14.52, adjusted p-value for interaction 0.10).

Conclusion: Maternal smoking during pregnancy is associated with the cumulative incidence of asthma in offspring between the ages of 31 and 46 years. The association was accentuated in offspring who at age 31, reported having past respiratory problems and/or who had haplotype rs11702779-AA. A reduction in FEV/FVC ratio was also observed at age 31 years in offspring with gestational smoke exposure. These results could reflect the early vulnerability of offspring's airways to ETS and its putative long-term effects.
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http://dx.doi.org/10.1183/13993003.01857-2019DOI Listing
June 2020

Airway Epithelial Dynamics in Allergy and Related Chronic Inflammatory Airway Diseases.

Front Cell Dev Biol 2020 27;8:204. Epub 2020 Mar 27.

Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.

Allergic rhinitis, chronic rhinosinusitis, and asthma are highly prevalent, multifactorial chronic airway diseases. Several environmental and genetic factors affect airway epithelial dynamics leading to activation of inflammatory mechanisms in the airways. This review links environmental factors to host epithelial immunity in airway diseases. Understanding altered homeostasis of the airway epithelium might provide important targets for diagnostics and therapy of chronic airway diseases.
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http://dx.doi.org/10.3389/fcell.2020.00204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118214PMC
March 2020

Hierarchical clustering in evaluating inflammatory upper airway phenotypes; increased symptoms in adults with allergic multimorbidity.

Asian Pac J Allergy Immunol 2020 Dec;38(4):239-250

Haartman Institute, Medicum, University of Helsinki, Helsinki, Finland.

Background: Inflammatory upper airway diseases cause significant morbidity. They include phenotypes with different treatment; allergic or non-allergic rhinitis (AR, nAR), and chronic rhinosinusitis with or without nasal polyps (CRSwNP, CRSsNP). In clinical practice, these phenotypes are often difficult to distinguish and may overlap.

Objective: To evaluate if hierarchical clustering can be used to distinguish these phenotypes based on the presence of nasal polyps, off-seasonal allergic symptoms, and self-reported background characteristics - e.g. atopic dermatitis (AD); and to further analyse the obtained clusters.

Methods: We studied a random sample of 74 CRS (chronic rhinosinusitis) patients, and a control group of 80 subjects without CRS with/without AR (tertiary hospitals, 2006-2012). All underwent interview and nasal examination, and filled a questionnaire. Variables regarding demographics, off-seasonal symptoms, and clinical findings were collected. Hierarchical clustering was performed, the obtained clusters were cross-tabulated and analysed.

Results: Four clusters were identified; 1: "Severe symptoms and CRSwNP" (n = 29), 2: "Asymptomatic AR and controls" (n = 39), 3: "Moderate symptoms and CRSsNP" (n = 36), and 4: "Symptomatic and AD" (n = 50). Cluster 1 had most sinonasal symptoms, cluster 3 had a high prevalence of facial pain. The presence of AR did not distinguish CRS groups. Of the AR subjects, 51 % belonged to cluster 4, where AR with off-seasonal airway symptoms and AD predominated.

Conclusions: Hierarchical clustering can be used to distinguish inflammatory upper airway disease phenotypes. The AR phenotype was subdivided by the presence of AD. Adult AR+ AD patients could benefit from active clinical care of the upper airways also off-season.
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http://dx.doi.org/10.12932/AP-170818-0395DOI Listing
December 2020

A Co-culture Model of PBMC and Stem Cell Derived Human Nasal Epithelium Reveals Rapid Activation of NK and Innate T Cells Upon Influenza A Virus Infection of the Nasal Epithelium.

Front Immunol 2018 8;9:2514. Epub 2018 Nov 8.

Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

We established an co-culture model involving H3N2-infection of human nasal epithelium with peripheral blood mononuclear cells (PBMC) to investigate their cross-talk during early H3N2 infection. Nasal epithelium was differentiated from human nasal epithelial stem/progenitor cells and cultured wtih fresh human PBMC. PBMC and supernatants were harvested after 24 and 48 h of co-culture with H3N2-infected nasal epithelium. We used flow cytometry and Luminex to characterize PBMC subpopulations, their activation and secretion of cytokine and chemokines. H3N2 infection of the nasal epithelium associated with significant increase in interferons (IFN-α, IFN-γ, IL-29), pro-inflammatory cytokines (TNF-α, BDNF, IL-3) and viral-associated chemokines (IP-10, MCP-3, I-TAC, MIG), detectable already after 24 h. This translates into rapid activation of monocytes, NK-cells and innate T-cells (MAIT and γδ T cells), evident with CD38+ and/or CD69+ upregulation. This system may contribute to mechanistic immunological studies bridging systemic models and possibly enable the development of targeted immunomodulatory therapies.
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http://dx.doi.org/10.3389/fimmu.2018.02514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237251PMC
October 2019

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

Int Arch Allergy Immunol 2017 9;172(2):123-128. Epub 2017 Mar 9.

Department of Ophthalmology, Hatanpää Hospital, Tampere, Finland.

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.
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http://dx.doi.org/10.1159/000456009DOI Listing
April 2017

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

Acta Otolaryngol 2016 Nov 27;136(11):1173-1179. Epub 2016 Jun 27.

a Haartman Institute, University of Helsinki , Helsinki , Finland.

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).
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http://dx.doi.org/10.1080/00016489.2016.1195918DOI Listing
November 2016

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

Acta Otolaryngol 2016 Jul 16;136(7):729-35. Epub 2016 Mar 16.

a Haartman Institute, University of Helsinki , Helsinki , Finland ;

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.
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http://dx.doi.org/10.3109/00016489.2016.1152631DOI Listing
July 2016

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

Am J Rhinol Allergy 2014 Jan-Feb;28(1):e5-10

Department of Clinical Medicine, Finn-Medi III, University of Tampere, Tampere, Finland.

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 and thus may result from other, still unknown, factors.
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http://dx.doi.org/10.2500/ajra.2014.28.4013DOI Listing
February 2015

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

Allergy Rhinol (Providence) 2013 ;4(1):e6-e12

Department of Otorhinolaryngology, University of Tampere, Tampere, Finland, ; Department of Otorhinolaryngology, Paijat-Hame Central Hospital, Lahti, Finland.

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.
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http://dx.doi.org/10.2500/ar.2013.4.0039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679571PMC
June 2013

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

Curr Opin Allergy Clin Immunol 2013 Feb;13(1):37-44

Department of Otorhinolaryngology, University of Tampere, Tampere, Finland.

Purpose Of Review: Indoleamine 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 Findings: Epithelial 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.

Summary: IDO 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.
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http://dx.doi.org/10.1097/ACI.0b013e32835b350eDOI Listing
February 2013

Endoscopic sinus surgery with antrostomy has better early endoscopic recovery in comparison to the ostium-preserving technique.

ISRN Otolaryngol 2012 18;2012:189383. Epub 2012 Jun 18.

Department of Otorhinolaryngology, University of Tampere, Finn Medi III, 4th Floor (Biokatu 10), 33520 Tampere, Finland.

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.
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http://dx.doi.org/10.5402/2012/189383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3658570PMC
June 2013

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

Clin Transl Allergy 2011 Dec 12;1(1):17. Epub 2011 Dec 12.

Helsinki University Hospital, Skin and Allergy Hospital, Helsinki, Finland.

Background: Indoleamine 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.

Objective: Our 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.

Methods: IDO 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.

Conclusions: There 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.
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http://dx.doi.org/10.1186/2045-7022-1-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299587PMC
December 2011