Publications by authors named "Paula Kauppi"

54 Publications

Lung function and side effects of Aspirin desensitization: a real world study.

Eur Clin Respir J 2021 Jan 11;8(1):1869408. Epub 2021 Jan 11.

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

: NSAID-exacerbated respiratory disease (N-ERD) is mainly treated with topical and oral corticosteroids, as well as acetylsalicylic acid (ASA) treatment after desensitization (ATAD). During desensitization and ATAD, it is common to experience an exacerbation of respiratory symptoms and other side effects, which may lead to cessation of treatment. : The aim of this retrospective follow-up study was to evaluate the effect of ATAD on lung functions and respiratory symptoms, and to clarify the occurrence of adverse events. s: We analysed the patient data of 67 patients treated with ASA desensitization between 2006 and 2016 in three hospitals, concerning adverse events, respiratory symptoms, lung function tests, and reasons for discontinuation. : 26 patients discontinued AD or ATAD. The most common reasons for discontinuation were lack of response (9%) and side effects (18%). ATAD did not affect lung function values in the follow-up of up to 5 years. Upper respiratory symptoms improved in 31 (52%) and lower respiratory symptoms (LRS) in 7 (10%) cases. Side effects occurred in 42 (63%) cases, the most common being dyspepsia and lower respiratory symptoms. : Our study suggests that ATAD has little effect on lower airway functions. Side effects were common, and discontinuation rates high.
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http://dx.doi.org/10.1080/20018525.2020.1869408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808387PMC
January 2021

Factors affecting upper airway control of NSAID-exacerbated respiratory disease: A real-world study of 167 patients.

Immun Inflamm Dis 2021 Mar 5;9(1):80-89. Epub 2021 Jan 5.

Inflammation Center, Skin and Allergy Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Nonsteroidal anti-inflammatory drug (NSAID) exacerbated respiratory disease (N-ERD) is a triad with asthma, chronic rhinosinusitis with nasal polyps, and NSAID intolerance. Uncontrolled N-ERD forms a major public health problem due to frequent and difficult-to-treat exacerbations and/or requiring putatively frequent endoscopic sinus surgeries (ESS). Our aim was to study factors affecting control of N-ERD.

Methods: Retrospective patient record data (patient characteristics, prior sinus surgeries, follow-up data in 2020) from 167 N-ERD patients undergoing consultation at three tertiary hospitals from 2001 to 2017 was used. Outcome measurements reflecting uncontrolled N-ERD were revision ESS, corticosteroids/biological therapy, and antibiotic courses during 2016-2020. Associations were analyzed by using nonparametric tests, Cox's proportional hazard, and binary logistic regression models.

Results: Nasal polyp eosinophilia increased the risk of revision surgery during the follow-up (adjusted hazard ratio [aHR] 3.21, confidence interval 1.23-8.38). Also baseline oral corticosteroids (OCS; HR, 1.73, 1.04-2.89) and baseline surgery without total ethmoidectomy increased the risk of revision ESS (HR, 2.17, 1.07-4.42) in unadjusted models. In addition, both baseline OCS (adjusted odds ratio [aOR] 2.78, 1.23-6.26) and a history of ≥4 previous ESS (aOR, 2.15, 0.98-4.70) were associated with the use of OCS/biological therapy during the follow-up, but not with high number of antibiotics.

Conclusions: Nasal polyp eosinophilia, baseline OCS, and a history of recurrent ESS predict uncontrolled N-ERD. These factors might be clinically useful in risk-estimation of uncontrolled disease and for organizing follow-ups. Prospective cohort studies with larger sample size are needed to further study the factors affecting the upper airway control of N-ERD.
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http://dx.doi.org/10.1002/iid3.347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860608PMC
March 2021

Monoclonal Antibodies and Airway Diseases.

Int J Mol Sci 2020 Dec 13;21(24). Epub 2020 Dec 13.

Inflammation Centre, Skin and Allergy Hospital, Helsinki University Hospital, University of Helsinki, P.O. Box 160, 00029 HUS Helsinki, Finland.

Monoclonal antibodies, biologics, are a relatively new treatment option for severe chronic airway diseases, asthma, allergic rhinitis, and chronic rhinosinusitis (CRS). In this review, we focus on the physiological and pathomechanisms of monoclonal antibodies, and we present recent study results regarding their use as a therapeutic option against severe airway diseases. Airway mucosa acts as a relative barrier, modulating antigenic stimulation and responding to environmental pathogen exposure with a specific, self-limited response. In severe asthma and/or CRS, genome-environmental interactions lead to dysbiosis, aggravated inflammation, and disease. In healthy conditions, single or combined type 1, 2, and 3 immunological response pathways are invoked, generating cytokine, chemokine, innate cellular and T helper (Th) responses to eliminate viruses, helminths, and extracellular bacteria/fungi, correspondingly. Although the pathomechanisms are not fully known, the majority of severe airway diseases are related to type 2 high inflammation. Type 2 cytokines interleukins (IL) 4, 5, and 13, are orchestrated by innate lymphoid cell (ILC) and Th subsets leading to eosinophilia, immunoglobulin E (IgE) responses, and permanently impaired airway damage. Monoclonal antibodies can bind or block key parts of these inflammatory pathways, resulting in less inflammation and improved disease control.
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http://dx.doi.org/10.3390/ijms21249477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763928PMC
December 2020

Genomics of asthma, allergy and chronic rhinosinusitis: novel concepts and relevance in airway mucosa.

Clin Transl Allergy 2020 Oct 28;10(1):45. Epub 2020 Oct 28.

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

Genome wide association studies (GWASs) have revealed several airway disease-associated risk loci. Their role in the onset of asthma, allergic rhinitis (AR) or chronic rhinosinusitis (CRS), however, is not yet fully understood. The aim of this review is to evaluate the airway relevance of loci and genes identified in GWAS studies. GWASs were searched from databases, and a list of loci associating significantly (p < 10) with asthma, AR and CRS was created. This yielded a total of 267 significantly asthma/AR-associated loci from 31 GWASs. No significant CRS -associated loci were found in this search. A total of 170 protein coding genes were connected to these loci. Of these, 76/170 (44%) showed bronchial epithelial protein expression in stained microscopic figures of Human Protein Atlas (HPA), and 61/170 (36%) had a literature report of having airway epithelial function. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses were performed, and 19 functional protein categories were found as significantly (p < 0.05) enriched among these genes. These were related to cytokine production, cell activation and adaptive immune response, and all were strongly connected in network analysis. We also identified 15 protein pathways that were significantly (p < 0.05) enriched in these genes, related to T-helper cell differentiation, virus infection, JAK-STAT signaling pathway, and asthma. A third of GWAS-level risk loci genes of asthma or AR seemed to have airway epithelial functions according to our database and literature searches. In addition, many of the risk loci genes were immunity related. Some risk loci genes also related to metabolism, neuro-musculoskeletal or other functions. Functions overlapped and formed a strong network in our pathway analyses and are worth future studies of biomarker and therapeutics.
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http://dx.doi.org/10.1186/s13601-020-00347-6DOI Listing
October 2020

Genomics of asthma, allergy and chronic rhinosinusitis: novel concepts and relevance in airway mucosa.

Clin Transl Allergy 2020 28;10:45. Epub 2020 Oct 28.

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

Genome wide association studies (GWASs) have revealed several airway disease-associated risk loci. Their role in the onset of asthma, allergic rhinitis (AR) or chronic rhinosinusitis (CRS), however, is not yet fully understood. The aim of this review is to evaluate the airway relevance of loci and genes identified in GWAS studies. GWASs were searched from databases, and a list of loci associating significantly (p < 10) with asthma, AR and CRS was created. This yielded a total of 267 significantly asthma/AR-associated loci from 31 GWASs. No significant CRS -associated loci were found in this search. A total of 170 protein coding genes were connected to these loci. Of these, 76/170 (44%) showed bronchial epithelial protein expression in stained microscopic figures of Human Protein Atlas (HPA), and 61/170 (36%) had a literature report of having airway epithelial function. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses were performed, and 19 functional protein categories were found as significantly (p < 0.05) enriched among these genes. These were related to cytokine production, cell activation and adaptive immune response, and all were strongly connected in network analysis. We also identified 15 protein pathways that were significantly (p < 0.05) enriched in these genes, related to T-helper cell differentiation, virus infection, JAK-STAT signaling pathway, and asthma. A third of GWAS-level risk loci genes of asthma or AR seemed to have airway epithelial functions according to our database and literature searches. In addition, many of the risk loci genes were immunity related. Some risk loci genes also related to metabolism, neuro-musculoskeletal or other functions. Functions overlapped and formed a strong network in our pathway analyses and are worth future studies of biomarker and therapeutics.
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http://dx.doi.org/10.1186/s13601-020-00347-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592594PMC
October 2020

Correction to: A comparison of biologicals in the treatment of adults with severe asthma - real-life experiences.

Asthma Res Pract 2020 2;6:10. Epub 2020 Oct 2.

Respiratory Diseases and Allergology, University of Helsinki and Helsinki University Hospital, Inflammation Center, Meilahdentie 2, FI-00029 HUS, P.O. Box 160, Helsinki, Finland.

[This corrects the article DOI: 10.1186/s40733-020-00055-9.].
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http://dx.doi.org/10.1186/s40733-020-00063-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532111PMC
October 2020

Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA), Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI), Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA), Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI), Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI), Österreichische Gesellschaft für Pneumologie (ÖGP) in co-operation with the German, Austrian, and Swiss ARIA groups, and the European Academy of Allergy and Clinical Immunology (EAACI).

Authors:
Ludger Klimek Oliver Pfaar Margitta Worm Thomas Eiwegger Jan Hagemann Markus Ollert Eva Untersmayr Karin Hoffmann-Sommergruber Alessandra Vultaggio Ioana Agache Sevim Bavbek Apostolos Bossios Ingrid Casper Susan Chan Alexia Chatzipetrou Christian Vogelberg Davide Firinu Paula Kauppi Antonios Kolios Akash Kothari Andrea Matucci Oscar Palomares Zsolt Szépfalusi Wolfgang Pohl Wolfram Hötzenecker Alexander R Rosenkranz Karl-Christian Bergmann Thomas Bieber Roland Buhl Jeroen Buters Ulf Darsow Thomas Keil Jörg Kleine-Tebbe Susanne Lau Marcus Maurer Hans Merk Ralph Mösges Joachim Saloga Petra Staubach Uta Jappe Klaus F Rabe Uta Rabe Claus Vogelmeier Tilo Biedermann Kirsten Jung Wolfgang Schlenter Johannes Ring Adam Chaker Wolfgang Wehrmann Sven Becker Laura Freudelsperger Norbert Mülleneisen Katja Nemat Wolfgang Czech Holger Wrede Randolf Brehler Thomas Fuchs Peter-Valentin Tomazic Werner Aberer Antje-Henriette Fink-Wagner Fritz Horak Stefan Wöhrl Verena Niederberger-Leppin Isabella Pali-Schöll Wolfgang Pohl Regina Roller-Wirnsberger Otto Spranger Rudolf Valenta Mübecell Akdis Paolo M Matricardi François Spertini Nicolai Khaltaev Jean-Pierre Michel Larent Nicod Peter Schmid-Grendelmeier Marco Idzko Eckard Hamelmann Thilo Jakob Thomas Werfel Martin Wagenmann Christian Taube Erika Jensen-Jarolim Stephanie Korn Francois Hentges Jürgen Schwarze Liam O Mahony Edward F Knol Stefano Del Giacco Tomás Chivato Pérez Jean Bousquet Anna Bedbrook Torsten Zuberbier Cezmi Akdis Marek Jutel

Allergol Select 2020 7;4:53-68. Epub 2020 Sep 7.

European Academy of Allergy and Clinical Immunology (EAACI).

Background: Since the beginning of the COVID-19 pandemic, the treatment of patients with allergic and atopy-associated diseases has faced major challenges. Recommendations for "social distancing" and the fear of patients becoming infected during a visit to a medical facility have led to a drastic decrease in personal doctor-patient contacts. This affects both acute care and treatment of the chronically ill. The immune response after SARS-CoV-2 infection is so far only insufficiently understood and could be altered in a favorable or unfavorable way by therapy with monoclonal antibodies. There is currently no evidence for an increased risk of a severe COVID-19 course in allergic patients. Many patients are under ongoing therapy with biologicals that inhibit type 2 immune responses via various mechanisms. There is uncertainty about possible immunological interactions and potential risks of these biologicals in the case of an infection with SARS-CoV-2.

Materials And Methods: A selective literature search was carried out in PubMed, Livivo, and the internet to cover the past 10 years (May 2010 - April 2020). Additionally, the current German-language publications were analyzed. Based on these data, the present position paper provides recommendations for the biological treatment of patients with allergic and atopy-associated diseases during the COVID-19 pandemic.

Results: In order to maintain in-office consultation services, a safe treatment environment must be created that is adapted to the pandemic situation. To date, there is a lack of reliable study data on the care for patients with complex respiratory, atopic, and allergic diseases in times of an imminent infection risk from SARS-CoV-2. Type-2-dominant immune reactions, as they are frequently seen in allergic patients, could influence various phases of COVID-19, e.g., by slowing down the immune reactions. Theoretically, this could have an unfavorable effect in the early phase of a SARS-Cov-2 infection, but also a positive effect during a cytokine storm in the later phase of severe courses. However, since there is currently no evidence for this, all data from patients treated with a biological directed against type 2 immune reactions who develop COVID-19 should be collected in registries, and their disease courses documented in order to be able to provide experience-based instructions in the future.

Conclusion: The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontaneous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. If available, it is recommended to prefer a formulation for self-application and to offer telemedical monitoring. Treatment should aim at the best possible control of difficult-to-control allergic and atopic diseases using adequate rescue and add-on therapy and should avoid the need for systemic glucocorticosteroids. If SARS-CoV-2 infection is proven or reasonably suspected, the therapy should be determined by weighing the benefits and risks individually for the patient in question, and the patient should be involved in the decision-making. It should be kept in mind that the potential effects of biologicals on the immune response in COVID-19 are currently not known. Telemedical offers are particularly desirable for the acute consultation needs of suitable patients.
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http://dx.doi.org/10.5414/ALX02166EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480069PMC
September 2020

Occupational health check-ups and health-promoting programs and asthma.

BMC Public Health 2020 Aug 31;20(1):1313. Epub 2020 Aug 31.

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

Background: The focus in occupational health check-ups is in work and health, but they offer also a possibility to assess health behavior and give guidance e.g. on weight control. We wanted to study whether having occupational health checks-up, receiving physicians' advice to change health behavior or participation in health promotion programs had an effect on obesity in a five-year follow-up from 1998 to 2003 in asthmatic and non-asthmatic workers.

Methods: Altogether 23,220 individuals aged 20-54 years were picked up from a randomized Finnish population sample. Univariate and multivariate logistic regression analysis was used to calculate the risk for obesity in 2003. The variables used in the modelling were gender, age, smoking, asthma, depression, and physical workload.

Results: Both asthmatic and non-asthmatic workers gained weight during the follow-up. Of the asthmatics 48 and 47% of the non-asthmatics had occupational health-check-up in the last 5 years. Of the asthmatics 18 and 14% of the non-asthmatics had received physician's advice to change their health behavior (p < 0.001). Associated factors for obesity (BMI > 30) in 2003 were gender (men OR 1.19), older age (OR 1.25), smoking (OR 1.07) or depression (OR 1.44).

Conclusions: Results show that having occupational health checks-up or receiving physicians' advice to change health behavior or participation in health promotion programs did not stop gain of weight during a five-year follow-up. Asthmatic workers did not differ from non-asthmatics. Male gender, older age, smoking, and depression were associated with obesity but not the physical workload.
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http://dx.doi.org/10.1186/s12889-020-09403-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457532PMC
August 2020

High Discontinuation Rates of Peroral ASA Treatment for CRSwNP: A Real-World Multicenter Study of 171 N-ERD Patients.

J Allergy Clin Immunol Pract 2020 Nov - Dec;8(10):3565-3574. Epub 2020 Jul 18.

Inflammation Centre, Skin and Allergy Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Medicum, Haartman Institute, University of Helsinki, Helsinki, Finland.

Background: Nonsteroidal anti-inflammatory drug (NSAID) exacerbated respiratory disease (N-ERD) consists of chronic rhinosinusitis with nasal polyposis (CRSwNP), asthma, and NSAID intolerance. Acetylsalicylic acid treatment after desensitization (ATAD) is a treatment option for uncontrolled N-ERD.

Objective: To evaluate peroral ATAD's long-term effectiveness on CRSwNP disease control.

Methods: The retrospective data (patient characteristics, sinus surgeries before ATAD, ATAD, follow-up data [2019]) were collected from patient records of 171 patients with N-ERD (102 ATAD patients, 69 controls with CRSwNP+N-ERD without ATAD) who underwent tertiary hospital consultation from 2001 to 2017. Outcome measurements were ATAD discontinuation, revision sinus surgery, and corticosteroid and antibiotic courses for airway infections during 2016-2019. Associations were analyzed by survival and nonparametric methods.

Results: The ATAD group had more tissue eosinophilia, symptoms, and sinus surgeries before ATAD than others. The ATAD discontinuation rate was 63%, independent of ATAD dose or duration, usually due to side effects. Compared with the N-ERD group without ATAD, ATAD (mean duration, 2.9 years) did not affect the revision endoscopic sinus surgery rate (P = .21, by the log-rank test) or the number of peroral corticosteroid courses per year (P > .05, by the Mann-Whitney U-test) during the follow-up (mean, 7.6 years) despite the dose or duration of ATAD.

Conclusions: The discontinuation rate of ATAD was high (63%), and ATAD did not affect revision sinus surgery rate nor the need of peroral corticosteroids during follow-up. However, the remaining 37% of the ATAD group did continue the treatment, indicating that they may have benefited from ATAD.
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http://dx.doi.org/10.1016/j.jaip.2020.06.063DOI Listing
July 2020

Anwendung von Biologika bei allergischen und Typ-2-entzündlichen Erkrankungen in der aktuellen Covid-19-Pandemie: Positionspapier des Ärzteverbands Deutscher Allergologen (AeDA)A, der Deutschen Gesellschaft für Allergologie und klinische Immunologie (DGAKI)B, der Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)C, der Österreichischen Gesellschaft für Allergologie und Immunologie (ÖGAI)D, der Luxemburgischen Gesellschaft für Allergologie und Immunologie (LGAI)E, der Österreichischen Gesellschaft für Pneumologie (ÖGP)F in Kooperation mit der deutschen, österreichischen, und schweizerischen ARIA-GruppeG und der Europäischen Akademie für Allergologie und Klinische Immunologie (EAACI)H.

Allergo J 2020 24;29(4):14-27. Epub 2020 Jun 24.

Zentrum für Rhinologie & Allergologie, An den Quellen 10, 65183 Wiesbaden, Germany.

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http://dx.doi.org/10.1007/s15007-020-2553-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289636PMC
June 2020

Considerations on biologicals for patients with allergic disease in times of the COVID-19 pandemic: An EAACI statement.

Allergy 2020 11;75(11):2764-2774

Translational Medicine Program, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON, Canada.

The outbreak of the SARS-CoV-2-induced coronavirus disease 2019 (COVID-19) pandemic re-shaped doctor-patient interaction and challenged capacities of healthcare systems. It created many issues around the optimal and safest way to treat complex patients with severe allergic disease. A significant number of the patients are on treatment with biologicals, and clinicians face the challenge to provide optimal care during the pandemic. Uncertainty of the potential risks for these patients is related to the fact that the exact sequence of immunological events during SARS-CoV-2 is not known. Severe COVID-19 patients may experience a "cytokine storm" and associated organ damage characterized by an exaggerated release of pro-inflammatory type 1 and type 3 cytokines. These inflammatory responses are potentially counteracted by anti-inflammatory cytokines and type 2 responses. This expert-based EAACI statement aims to provide guidance on the application of biologicals targeting type 2 inflammation in patients with allergic disease. Currently, there is very little evidence for an enhanced risk of patients with allergic diseases to develop severe COVID-19. Studies focusing on severe allergic phenotypes are lacking. At present, noninfected patients on biologicals for the treatment of asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, or chronic spontaneous urticaria should continue their biologicals targeting type 2 inflammation via self-application. In case of an active SARS-CoV-2 infection, biological treatment needs to be stopped until clinical recovery and SARS-CoV-2 negativity is established and treatment with biologicals should be re-initiated. Maintenance of add-on therapy and a constant assessment of disease control, apart from acute management, are demanded.
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http://dx.doi.org/10.1111/all.14407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300800PMC
November 2020

A comparison of biologicals in the treatment of adults with severe asthma - real-life experiences.

Asthma Res Pract 2020 13;6. Epub 2020 May 13.

1Respiratory Diseases and Allergology, University of Helsinki and Helsinki University Hospital, Inflammation Center, Meilahdentie 2, FI-00029 HUS, P.O. Box 160, Helsinki, Finland.

Background: Anti-IgE (omalizumab) and anti-IL5/IL5R (reslizumab, mepolizumab and benralizumab) treatments are available for severe allergic and eosinophilic asthma. In these patients, studies have shown beneficial effects in oral corticosteroid use and exacerbations. The aim of this retrospective single-center study was to evaluate the effect of biological therapy on severe asthma and to compare different therapies.

Methods: We collected and analysed results of anti-IL5/IL5R and anti-IgE therapies for asthma from January 2009 until October 2019 in specialized care. We compared number of exacerbations, asthma symptoms and use of per oral corticosteroids and antimicrobics because of asthma before and during biological therapy, and in a separate analysis need for per oral corticosteroids, antimicrobics or surgery due to upper respiratory tract diseases in asthmatics receiving biologicals. The analyses were done using the Chi square test, T-test or Mann-Whitney U -test, the Kruskall-Wallis test or the Wilcoxon test.

Results: Of 64 patients, 40 used continuous per oral corticosteroid therapy prior to biological therapy. The mean daily dose of per oral corticosteroid was reduced in those with anti-IL5/IL5R therapy (- 3.0 mg,  = 0.02). The number of annual per oral corticosteroid courses decreased in both the anti-IL5/IL5R (- 2.8 courses,  < 0.05) and anti-IgE groups (- 1.3 courses,  < 0.05). The number of annual antibiotic courses (- 0.7 courses,  = 0.04) and total number of exacerbation events (- 4.4 events/year,  < 0.05) were reduced in the anti-IL5/IL5R group. In the 55 asthma patients analysed for upper respiratory tract findings, the results suggested a reduction in need for chronic rhinosinusitis surgery during biological therapy.

Conclusions: Results with biological therapies in this real-life clinical setting are comparable to those reported in clinical trials. Biological therapy reduces exacerbations and per oral corticosteroid use.

Trial Registration: NCT04158050, retrospectively registered 6.11.2019.
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http://dx.doi.org/10.1186/s40733-020-00055-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222440PMC
May 2020

Biologicals in atopic disease in pregnancy: An EAACI position paper.

Allergy 2021 01;76(1):71-89

Division of Immunology and Allergy, Food Allergy and Anaphylaxis Program, The Hospital for Sick Children, Toronto, ON, Canada.

Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of approved biologicals for the treatment of atopic diseases is continuously increasing. Although atopic diseases are among the most common diseases in the reproductive age, investigations, and information on half-life, pharmacokinetics defining the neonatal Fc receptors (FcRn) and most important safety of biologicals in pregnancy are lacking. Given the complex sequence of immunological events that regulate conception, fetal development, and the intrauterine and postnatal maturation of the immune system, this information is of utmost importance. We conducted a systematic review on biologicals in pregnancy for indications of atopic diseases. Evidence in this field is scarce and mainly reserved to reports on the usage of omalizumab. This lack of evidence demands the establishment of a multidisciplinary approach for the management of pregnant women who receive biologicals and multicenter registries for long-term follow-up, drug trial designs suitable for women in the reproductive age, and better experimental models that represent the human situation. Due to the very long half-life of biologicals, preconception counseling and healthcare provider education are crucial to offer the best care for mother and fetus. This position paper integrates available data on safety of biologicals during pregnancy in atopic diseases via a systematic review with a detailed review on immunological considerations how inhibition of different pathways may impact pregnancy.
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http://dx.doi.org/10.1111/all.14282DOI Listing
January 2021

Asthma as aetiology of bronchiectasis in Finland.

Respir Med 2019 06 30;152:105-111. Epub 2019 Apr 30.

University of Helsinki and Helsinki University Hospital, Respiratory Diseases and Allergology, Helsinki, Finland.

Background: By definition bronchiectasis (BE) means destructed structure of normal bronchus as a consequence of frequent bacterial infections and inflammation. In many senses, BE is a neglected orphan disease. A recent pan-European registry study, EMBARC, has been set up in order to better understand its pathophysiology, better phenotype patients, and to individualize their management.

Aim: To examine the aetiology and co-morbidity of BE in the capital area in Finland.

Methods: Two hundred five patients with BE diagnosis and follow up visits between 2016 and 2017 in Helsinki University Hospital were invited to participate in the study. Baseline demographics, lung functions, imaging, microbiological, and therapeutic data, together with co-morbidities were entered into EMBARC database. Clinical characteristics, aetiologic factors, co-morbidities, and risk factors for extensive BE were explored.

Results: To the study included 95 adult patients and seventy nine percent of the BE patients were women. The mean age was 69 years (SD ± 13). Asthma was a comorbid condition in 68% of the patients but in 26% it was estimated to be the cause of BE. Asthma was aetiological factor for BE if it had been diagnosed earlier than BE. As 41% BE were idiopathic, in 11% the disorder was postinfectious and others were associated to rheumatic disease, Alpha-1-antitrypsin deficiency, IgG deficiency and Kartagener syndrome. The most common co-morbidities in addition to asthma were cardiovascular disease (30%), gastroesophageal reflux disease (26%), overweight (22%), diabetes (16%), inactive neoplasia (15%), and immunodeficiency (12%). Extensive BE was found in 68% of BE patients in whom four or more lobes were affected. Risk factors for extensive BE were asthma (OR 2.7), asthma as aetiology for BE (OR 4.3), and rhinosinusitis (OR 3.1).

Conclusions: Asthma was associated to BE in 68% and it was estimated as aetiology in every fourth patient. However, retrospectively, it is difficult to exclude asthma as a background cause in patients with asthma-like symptoms and respiratory infections. We propose asthma as an aetiology factor for BE if it is diagnosed earlier than BE. Asthma and rhinosinusitis were predictive for extensive BE.
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http://dx.doi.org/10.1016/j.rmed.2019.04.022DOI Listing
June 2019

Inspiratory and Expiratory Flow Changes, Voice Symptoms and Laryngeal Findings during Histamine Challenge Tests.

Folia Phoniatr Logop 2020 24;72(1):29-35. Epub 2019 Apr 24.

Department of Otorhinolaryngology and Phoniatrics, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Objective: The aim of this study was to analyse the associations between the spirometry parameter changes in relation to laryngeal finding changes and self-reported voice and throat symptom changes among patients undergoing a histamine challenge test.

Patients And Methods: Thirty adult patients with a chronic cough underwent a histamine challenge test. Videolaryngostroboscopy and voice and throat symptoms were assessed using a visual analogue scale immediately before and after the challenge test. Correlations between the relative changes in spirometry values in relation to the change in vocal fold oedema and redness and self-reported voice and throat symptom changes during the challenge test were assessed.

Results: A correlation between the relative change in inspiratory and expiratory air flow values and the change in voice and throat symptoms during the histamine challenge test was found. The vocal fold oedema, visible on videolaryngostroboscopy, caused by the histamine challenge did not significantly affect the spirometry air flow values.

Conclusion: The relative changes in inspiratory and expiratory air flow and voice and throat symptoms during the histamine challenge test correlated. The vocal fold oedema caused by the histamine challenge, visible on videolaryngostroboscopy, did not significantly affect the spirometry air flow values.
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http://dx.doi.org/10.1159/000495783DOI Listing
April 2019

Multimorbidity in Asthma, Allergic Conditions and COPD Increase Disease Severity, Drug Use and Costs: The Finnish Pharmacy Survey.

Int Arch Allergy Immunol 2019 18;179(4):273-280. Epub 2019 Apr 18.

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

Background: Asthma, allergic conditions, and COPD overlap, but the effect of them and their combinations on disease severity, need for drugs, use of healthcare, and costs is poorly known.

Objective: To study how different allergic diseases co-occur in asthma and allergy patients and evaluate the use of medication well as drug and healthcare costs.

Methods: Nationwide Allergy Barometer Survey was carried out in the Finnish pharmacies during 1 week in September 2016. Altogether, 956 patients (5-75 years) who purchased asthma or allergy drugs with prescription participated in 351 pharmacies.

Results: Of the participants, 78% reported physician-diagnosed asthma, 57% allergic rhinitis, 24% atopic eczema, 21% food allergy, 20% allergic conjunctivitis, 8% anaphylaxis, and 8% COPD. One-third of the patients had at least three conditions, and multimorbidity was common across all age groups. Disease severity increased with the number of coexisting conditions, and asthma severity also with age. Patients with asthma alone used on average 3.8 drugs with the annual costs of EUR 661. This increased to 4.9 drugs and EUR 847 in asthmatics with multimorbidity. For all participants, costs of drugs and healthcare services together during the preceding year were on average EUR 1,214, of which 56% were drug costs. The costs doubled to EUR 2,714 in 65 subjects (7%) who had both asthma and COPD.

Conclusions: In asthma and allergy, multimorbidity and polypharmacy are major concerns. Disease severity, drug use, and costs increased with multimorbid conditions. To reduce the burden, allergy management should be better integrated and more comprehensive.
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http://dx.doi.org/10.1159/000498861DOI Listing
September 2019

Severe Occupational Asthma: Insights From a Multicenter European Cohort.

J Allergy Clin Immunol Pract 2019 Sep - Oct;7(7):2309-2318.e4. Epub 2019 Mar 23.

Division of Asthma and Allergy, Department of Chest Diseases, University Hospital of Strasbourg and Fédération de Médecine translationnelle, Strasbourg University, Strasbourg, France.

Background: Although sensitizer-induced occupational asthma (OA) accounts for an appreciable fraction of adult asthma, the severity of OA has received little attention.

Objective: The aim of this study was to characterize the burden and determinants of severe OA in a large multicenter cohort of subjects with OA.

Methods: This retrospective study included 997 subjects with OA ascertained by a positive specific inhalation challenge completed in 20 tertiary centers in 11 European countries during the period 2006 to 2015. Severe asthma was defined by a high level of treatment and any 1 of the following criteria: (1) daily need for a reliever medication, (2) 2 or more severe exacerbations in the previous year, or (3) airflow obstruction.

Results: Overall, 162 (16.2%; 95% CI, 14.0%-18.7%) subjects were classified as having severe OA. Multivariable logistic regression analysis revealed that severe OA was associated with persistent (vs reduced) exposure to the causal agent at work (odds ratio [OR], 2.78; 95% CI, 1.50-5.60); a longer duration of the disease (OR, 1.04; 95% CI, 1.00-1.07); a low level of education (OR, 2.69; 95% CI, 1.73-4.18); childhood asthma (OR, 2.92; 95% CI, 1.13-7.36); and sputum production (OR, 2.86; 95% CI, 1.87-4.38). In subjects removed from exposure, severe OA was associated only with sputum production (OR, 3.68; 95% CI, 1.87-7.40); a low education level (OR, 3.41; 95% CI, 1.72-6.80); and obesity (OR, 1.98; 95% CI, 0.97-3.97).

Conclusions: This study indicates that a substantial proportion of subjects with OA experience severe asthma and identifies potentially modifiable risk factors for severe OA that should be targeted to reduce the adverse impacts of the disease.
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http://dx.doi.org/10.1016/j.jaip.2019.03.017DOI Listing
October 2020

Birch pollen allergen immunotherapy reprograms nasal epithelial transcriptome and recovers microbial diversity.

J Allergy Clin Immunol 2019 06 12;143(6):2293-2296.e11. Epub 2019 Feb 12.

Haartman Institute, University of Helsinki, Helsinki, Finland; Skin and Allergy Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2019.02.002DOI Listing
June 2019

Are high- and low-molecular-weight sensitizing agents associated with different clinical phenotypes of occupational asthma?

Allergy 2019 02 25;74(2):261-272. Epub 2018 Nov 25.

Division of Asthma and Allergy, Department of Chest Diseases, University Hospital of Strasbourg and Fédération de Médecine translationnelle, Strasbourg University, Strasbourg, France.

Background: High-molecular-weight (HMW) proteins and low-molecular-weight (LMW) chemicals can cause occupational asthma (OA) although few studies have thoroughly compared the clinical, physiological, and inflammatory patterns associated with these different types of agents. The aim of this study was to determine whether OA induced by HMW and LMW agents shows distinct phenotypic profiles.

Methods: Clinical and functional characteristics, and markers of airway inflammation were analyzed in an international, multicenter, retrospective cohort of subjects with OA ascertained by a positive inhalation challenge response to HMW (n = 544) and LMW (n = 635) agents.

Results: Multivariate logistic regression analysis showed significant associations between OA caused by HMW agents and work-related rhinitis (OR [95% CI]: 4.79 [3.28-7.12]), conjunctivitis (2.13 [1.52-2.98]), atopy (1.49 [1.09-2.05]), and early asthmatic reactions (2.86 [1.98-4.16]). By contrast, OA due to LMW agents was associated with chest tightness at work (2.22 [1.59-3.03]), daily sputum (1.69 [1.19-2.38]), and late asthmatic reactions (1.52 [1.09-2.08]). Furthermore, OA caused by HMW agents showed a higher risk of airflow limitation (1.76 [1.07-2.91]), whereas OA due to LMW agents exhibited a higher risk of severe exacerbations (1.32 [1.01-1.69]). There were no differences between the two types of agents in the baseline sputum inflammatory profiles, but OA caused by HMW agents showed higher baseline blood eosinophilia and a greater postchallenge increase in fractional nitric oxide.

Conclusion: This large cohort study describes distinct phenotypic profiles in OA caused by HMW and LMW agents. There is a need to further explore differences in underlying pathophysiological pathways and outcome after environmental interventions.
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http://dx.doi.org/10.1111/all.13542DOI Listing
February 2019

Maternal asthma is associated with increased risk of perinatal mortality.

PLoS One 2018 18;13(5):e0197593. Epub 2018 May 18.

Department of Paediatrics, Children's Hospital Helsinki University Hospital, Helsinki, Finland.

Background: Asthma is the most common chronic disease during pregnancy and it may have influence on pregnancy outcome.

Objectives: Our goal was to assess the association between maternal asthma and the perinatal risks as well as possible effects of asthma medication.

Methods: The study was based on a nationwide Finnish register-based cohort between the years 1996 and 2012 in the Drug and Pregnancy Database. The register data comprised 962 405 singleton live and stillbirths, 898 333 (93.3%) pregnancies in mothers with neither confirmed asthma nor use of asthma medication (controls), and 26 674 (2.8%) pregnancies with confirmed maternal asthma. 71% of mothers with asthma used asthma medication. The diagnosis of asthma was based on the mothers' right for subsidised medication which is carefully evaluated by strict criteria including pulmonary function testing. Odds ratio was used in comparison. Premature birth (PB), low birth weight, small for gestational age (SGA), neonatal death were the main outcome measures.

Results: Maternal asthma was associated with adjusted odds ratios (aORs) for perinatal mortality 1.24 (95% CI 1.05 to 1.46), preterm birth 1.18 (1.11 to 1.25), low birth weight 1.29 (1.21 to 1.37), fetal growth restriction (SGA) 1.32, (1.24 to 1.40), and asphyxia 1.09 (1.02 to 1.17). Asthma treatment reduced the increased risk of preterm birth aOR 0.85 (95% CI 0.76 to 0.96) but mothers with treated asthma had higher risks of fetal growth restriction (SGA) aOR 1.26 (1.10 to 1.45), and asphyxia aOR 1.37 (1.17 to 1.61) than mothers with untreated asthma.

Conclusion: Asthma is associated with increased risks of perinatal mortality, preterm birth, low birth weight, fetal growth restriction (SGA), and asphyxia. Asthma treatment reduces the risk of preterm delivery, but it does not seem to reduce other complications such as perinatal mortality.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197593PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959067PMC
December 2018

The effect of oral immunotherapy treatment in severe IgE mediated milk, peanut, and egg allergy in adults.

Immun Inflamm Dis 2018 06 15;6(2):307-311. Epub 2018 Mar 15.

Respiratory Diseases and Allergology, University of Helsinki and Helsinki University Hospital, Skin and Allergy Hospital, Helsinki, Finland.

Introduction: The standard care of severe food allergy in both adults and children means avoidance of allergens. In recent years promising results of oral immunotherapy (OIT) have been reported in children. In adults, information on OIT in severe food allergy is very limited.

Objective: We aimed to study if OIT is possible in adults.

Methods: We report OIT results in 10 adult patients with milk OIT, nine adult patients with peanut OIT, and four adult patients with egg OIT. The allergy was confirmed with allergen specific IgE tests and oral food challenges (open in milk allergy and double-blind in peanut and egg allergy). The OIT was performed as open.

Results: The median dose of protein that led to discontinuation of allergen challenge because of symptoms was 7.5 mg in milk allergy, 25 mg in peanut allergy, and 15 mg in egg allergy. The median period of OIT was 515 days. Currently on OIT are 6/10 milk allergic patients, 4/9 peanut allergic patients and 3/4 egg allergic patients. The median dose of milk protein increased by 60-fold during OIT compared to the allergen challenge dose. In peanut OIT the median dose increased by eightfold and in egg allergy the dose increased with OIT by 35-fold. Local itching was the most common side effect of OIT (73.9% of the patients), four patients reported having used epinephrine autoinjector and three patients having needed emergency room treatment.

Conclusions And Clinical Relevance: OIT can be given in adult patients with severe milk, peanut, or egg allergy only in selected cases. OIT leads into desensitization but it is not clear whether persistent tolerance can be achieved. Mild adverse events during OIT are common.
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http://dx.doi.org/10.1002/iid3.218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946145PMC
June 2018

Nordic consensus statement on the systematic assessment and management of possible severe asthma in adults.

Eur Clin Respir J 2018 6;5(1):1440868. Epub 2018 Mar 6.

Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.

Although a minority of asthma patients suffer from severe asthma, they represent a major clinical challenge in terms of poor symptom control despite high-dose treatment, risk of exacerbations, and side effects. Novel biological treatments may benefit patients with severe asthma, but are expensive, and are only effective in appropriately targeted patients. In some patients, symptoms are driven by other factors than asthma, and all patients with suspected severe asthma ('difficult asthma') should undergo systematic assessment, in order to differentiate between true severe asthma, and 'difficult-to-treat' patients, in whom poor control is related to factors such as poor adherence or co-morbidities. The Nordic Consensus Statement on severe asthma was developed by the Nordic Severe Asthma Network, consisting of members from Norway, Sweden, Finland, Denmark, Iceland and Estonia, including representatives from the respective national respiratory scientific societies with the aim to provide an overview and recommendations regarding the diagnosis, systematic assessment and management of severe asthma. Furthermore, the Consensus Statement proposes recommendations for the organization of severe asthma management in primary, secondary, and tertiary care.
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http://dx.doi.org/10.1080/20018525.2018.1440868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844041PMC
March 2018

Component-resolved diagnosis in selecting patients for yellowjacket venom immunotherapy.

Ann Allergy Asthma Immunol 2018 02;120(2):184-189

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

Background: Venom immunotherapy is effective in preventing systemic allergic reactions (SARs), but the diagnosis of venom allergy is problematic.

Objective: To compare the performance of component-resolved diagnosis and conventional tests in patients referred for venom immunotherapy.

Methods: We measured serum-specific immunoglobulin E to yellowjacket and honeybee venoms (Ves v 1 and Ves v 5 and Api m 1), cross-reactive carbohydrate determinants, serum basal tryptase (ImmunoCAP, ThermoFisher Scientific, Uppsala, Sweden), and skin prick test reactions in 84 patients referred to receive venom immunotherapy. History of SAR and its severity were evaluated.

Results: Of the 78 patients with suspected yellowjacket venom (YJV) allergy, a history of SAR was confirmed in 47 (60%) and 31 (40%) had a non-SAR reaction. The most accurate tests to confirm venom allergy after a SAR were serum-specific immunoglobulin E to yellowjacket whole-venom extract spiked with Ves v 5 (area under the curve 0.87, 95% confidence interval 0.77-0.97, P < .001) and Ves v 5 (area under the curve 0.86, 95% confidence interval 0.76-0.96, P < .001). Sensitization to Ves v 1 was infrequent and its area under the curve was low (0.62, 95% confidence interval 0.47-0.76, P = .106). Sensitivity of the YJV skin prick test was 86%, but its specificity was low at 54%. Double sensitization to yellowjacket and honeybee occurred frequently in skin prick tests. Of the patients without a SAR, 26% showed a positive reaction to YJV in any serum test and 46% showed a positive reaction in skin tests.

Conclusion: Specific immunoglobulin E to the YJV spiked with Ves v 5 confirmed the allergy after a SAR. A history of SAR should be confirmed before testing, because venom sensitization is frequent in other types of reactions.
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http://dx.doi.org/10.1016/j.anai.2017.11.012DOI Listing
February 2018

Standardizing dose in dosimetric bronchial challenge tests.

Clin Physiol Funct Imaging 2018 Sep 17;38(5):903-906. Epub 2018 Jan 17.

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

Recent technical recommendations on bronchial challenge testing aim at standardized assessment of provocative dose of causing 20% decrease in FEV1 (PD20). The aim of this study was to investigate the effect of mode of nebulization on the output of a computerized dosimeter (APS) and to compare PD20 obtained by two different dosimetric systems in vivo. The output of the APS system was tested during continuous nebulization, and using simulated breaths, for intermittent actuations with four different durations. Using output data, a modified methacholine challenge protocol was applied for APS and compared with a standard set-up using Spira dosimeter in 14 asthmatic patients attending duplicate methacholine challenges using both systems, within median (range) 3 (1-6) days apart. The calculated output (mg min ) with all the intermittent mode settings was significantly higher (P<0·001) than in the continuous mode, and in the intermittent mode, the output was dependent of the pulse duration. The PD20 values assessed with the APS and Spira systems were significantly correlated (r = 0·69; P<0·007), without systematic difference in the geometric means (P = 0·10). A moderate to good agreement was found for assessment of significant hyperresponsiveness. The results suggest that in dosimetric systems for bronchial challenge tests, the output of the nebulizer is dependent on the mode of nebulization, and this should be considered when standardizing the dose between devices and protocols. As long as the delivered dose is determined for the specified nebulization mode of the protocol, it may be possible to obtain comparable results between different devices.
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http://dx.doi.org/10.1111/cpf.12498DOI Listing
September 2018

Laryngeal Mucosal Reaction during Bronchial Histamine Challenge Test Visualized by Videolaryngostroboscopy.

J Voice 2017 Jul 14;31(4):470-475. Epub 2016 Dec 14.

Department of Otorhinolaryngology and Phoniatrics, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Objectives/hypothesis: To examine the changes in the larynx, as well as self-reported voice and throat symptoms, among patients undergoing a histamine challenge test. Thus, to understand the possible clinical effects of histamine on the larynx.

Study Design: Controlled, open prospective study.

Methods: Thirty adult patients with prolonged cough and suspicion of bronchial asthma underwent a histamine challenge test. Videolaryngostroboscopy was performed immediately before and after the challenge. Voice and throat symptoms immediately before and after the challenge test were assessed using a visual analog scale.

Results: Videolaryngostroboscopy after exposure showed significant increases in edema (P < 0.001) as well as redness (P < 0.001) of the vocal folds after the exposure. Self-reported voice complaints increased significantly for 8 of 11 symptoms. A moderate positive correlation was found between the increase in edema of the vocal folds and reported heartburn/regurgitation symptoms (r = 0.42, P < 0.05). Atopy, asthma, nasal symptoms, or bronchial hyperreactivity during the histamine challenge test were not associated with laryngeal reactions.

Conclusions: According to the results, the laryngeal mucosal reaction during a histamine challenge test can be objectively visualized. Videolaryngostroboscopy findings, together with an increase in self-reported voice and throat symptoms, show that histamine has potential effects on vocal folds. The mucosal reaction seems to be pronounced among patients with reflux symptoms, probably reflecting the permeability features of the vocal folds.
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http://dx.doi.org/10.1016/j.jvoice.2016.11.011DOI Listing
July 2017

The effect of CPAP treatment for obstructive sleep apnea on asthma control-study limitations-author's response.

Sleep Breath 2016 Dec 20;20(4):1271-1272. Epub 2016 Jul 20.

Sleep Unit, Heart and Lung Centre, Helsinki University Hospital, University of Helsinki, Meilahdentie 2, P.O. Box 160, HUS, 00029, Helsinki, Finland.

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http://dx.doi.org/10.1007/s11325-016-1386-0DOI Listing
December 2016

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

Emerging Comorbidities in Adult Asthma: Risks, Clinical Associations, and Mechanisms.

Mediators Inflamm 2016 26;2016:3690628. Epub 2016 Apr 26.

Department of Respiratory Medicine, Seinäjoki Central Hospital, 60220 Seinäjoki, Finland.

Asthma is a heterogeneous disease with many phenotypes, and age at disease onset is an important factor in separating the phenotypes. Most studies with asthma have been performed in patients being otherwise healthy. However, in real life, comorbid diseases are very common in adult patients. We review here the emerging comorbid conditions to asthma such as obesity, metabolic syndrome, diabetes mellitus type 2 (DM2), and cardiac and psychiatric diseases. Their role as risk factors for incident asthma and whether they affect clinical asthma are evaluated. Obesity, independently or as a part of metabolic syndrome, DM2, and depression are risk factors for incident asthma. In contrast, the effects of comorbidities on clinical asthma are less well-known and mostly studies are lacking. Cross-sectional studies in obese asthmatics suggest that they may have less well controlled asthma and worse lung function. However, no long-term clinical follow-up studies with these comorbidities and asthma were identified. These emerging comorbidities often occur in the same multimorbid adult patient and may have in common metabolic pathways and inflammatory or other alterations such as early life exposures, systemic inflammation, inflammasome, adipokines, hyperglycemia, hyperinsulinemia, lung mechanics, mitochondrial dysfunction, disturbed nitric oxide metabolism, and leukotrienes.
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http://dx.doi.org/10.1155/2016/3690628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861800PMC
January 2017

Need for medication and stuffy nose predict the severity of allergic rhinitis.

Asia Pac Allergy 2016 Apr 28;6(2):133-5. Epub 2016 Apr 28.

University of Helsinki and Helsinki University Hospital, Respiratory Diseases and Allergology, Skin and Allergy Hospital, FI-00029 Helsinki, Finland.

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http://dx.doi.org/10.5415/apallergy.2016.6.2.133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850337PMC
April 2016