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Article ; Online: Inheritance of NSAID-Exacerbated Respiratory Disease.

Suikkila, Anna / Lyly, Annina / Hafrén, Lena / Saarinen, Riitta / Klockars, Tuomas

Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery

2023 Volume 168, Issue 3, Page(s) 540–543

Abstract: Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) has been considered an acquired condition. Positive first-degree family history has been reported in 1% of cases. The geographic and genetic isolation of the Finnish ... ...

Abstract	Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) has been considered an acquired condition. Positive first-degree family history has been reported in 1% of cases. The geographic and genetic isolation of the Finnish population offers exceptional opportunities for inheritance studies. In this questionnaire study, we explored the familial aggregation of N-ERD in 66 Finnish families of patients with N-ERD. The majority of patients (67%) had a positive family history of NSAID intolerance, asthma, nasal polyposis, or N-ERD. Furthermore, 55% had a positive first-degree family history of asthma, 21% nasal polyposis, 20% NSAID intolerance, and 11% N-ERD. The prevalence of asthma, nasal polyposis, NSAID intolerance, and N-ERD among first-degree relatives was 13%, 5%, 4%, and 2%, respectively. We present the pedigrees of the 44 affected families. According to our findings, Finnish patients with N-ERD seem to have a genetic susceptibility to it.
MeSH term(s)	Humans ; Aspirin ; Sinusitis/surgery ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Asthma/epidemiology ; Nasal Polyps/chemically induced ; Nasal Polyps/genetics ; Nasal Polyps/epidemiology ; Asthma, Aspirin-Induced/epidemiology ; Asthma, Aspirin-Induced/genetics
Chemical Substances	Aspirin (R16CO5Y76E) ; Anti-Inflammatory Agents, Non-Steroidal
Language	English
Publishing date	2023-01-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	392085-9
ISSN	1097-6817 ; 0161-6439 ; 0194-5998
ISSN (online)	1097-6817
ISSN	0161-6439 ; 0194-5998
DOI	10.1177/01945998221102085
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Article ; Online: Pathomechanisms of AERD-Recent Advances.

Lyly, Annina / Laidlaw, Tanya M / Lundberg, Marie

Frontiers in allergy

2021 Volume 2, Page(s) 734733

Abstract: The pathomechanisms behind NSAID-exacerbated respiratory disease are complex and still largely unknown. They are presumed to involve genetic predisposition and environmental triggers that lead to dysregulation of fatty acid and lipid metabolism, altered ... ...

Abstract	The pathomechanisms behind NSAID-exacerbated respiratory disease are complex and still largely unknown. They are presumed to involve genetic predisposition and environmental triggers that lead to dysregulation of fatty acid and lipid metabolism, altered cellular interactions involving transmetabolism, and continuous and chronic inflammation in the respiratory track. Here, we go through the recent advances on the topic and sum up the current understanding of the background of this illness that broadly effects the patients' lives.
Language	English
Publishing date	2021-09-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ISSN	2673-6101
ISSN (online)	2673-6101
DOI	10.3389/falgy.2021.734733
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Article ; Online: Patient-Reported Control of Asthma, Nasal Polyposis, and Middle-Ear Symptoms in NSAID-Exacerbated Respiratory Disease.

Suikkila, Anna / Hafrén, Lena / Lyly, Annina / Klockars, Tuomas / Saarinen, Riitta

Frontiers in allergy

2021 Volume 2, Page(s) 716169

Abstract: Non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) is an adult-onset inflammatory condition of the upper and lower airways. It is characterized by the co-existence of asthma, nasal polyposis, and hypersensitivity to ... ...

Abstract	Non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) is an adult-onset inflammatory condition of the upper and lower airways. It is characterized by the co-existence of asthma, nasal polyposis, and hypersensitivity to NSAIDs. Over one-fourth of patients also have symptoms of chronic middle-ear infection. The clinical course of NERD is often severe and generally requires multimodal treatment with recurrent surgical measures. Studies presenting the disease burden and subjective symptom control of NERD are limited. In this qualitative questionnaire study, we present the clinical characteristics of asthma, nasal polyposis, NSAID intolerance and possible recurrent or chronic middle-ear infection of 66 confirmed NERD patients treated at our tertiary referral center between January 2016 and May 2017. Additionally, we present the patient-reported disease control of asthma, nasal polyposis, and middle-ear symptoms on a four-category Likert scale. The proportion of NERD patients with recurrent or chronic middle-ear infection was 18%. The proportion of good or very good subjective disease control was 83% for asthma, 58% for nasal polyposis, and 33% for chronic middle-ear infection, if present. Chronic middle-ear infection is common among NERD patients and should more often be recognized as part of the entity. Together with nasal polyposis, chronic middle-ear infection seems to affect patients more than asthma. The patient's perspective of disease control should be considered when planning the interdisciplinary follow-up and treatment of NERD.
Language	English
Publishing date	2021-07-15
Publishing country	Switzerland
Document type	Journal Article
ISSN	2673-6101
ISSN (online)	2673-6101
DOI	10.3389/falgy.2021.716169
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Article: Lung function and side effects of Aspirin desensitization: a real world study.

Heikki, Turpeinen / Anu, Laulajainen-Hongisto / Annina, Lyly / Jura, Numminen / Elina, Penttilä / Sahlman, Johanna / Sanna, Toppila-Salmi / Paula, Kauppi

European clinical respiratory journal

2021 Volume 8, Issue 1, Page(s) 1869408

Abstract: ... ...

Abstract	Introduction
Language	English
Publishing date	2021-01-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2834928-3
ISSN	2001-8525 ; 1399-3003 ; 2001-8525 ; 0903-1936
ISSN (online)	2001-8525 ; 1399-3003
ISSN	2001-8525 ; 0903-1936
DOI	10.1080/20018525.2020.1869408
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Article ; Online: Real-Life Experience of Biologic Treatment for Asthma on Chronic Rhinosinusitis: A Finnish Cohort.

Lyly, Annina / Genberg, Emma / Kauppi, Paula / Virkkula, Paula / Lee, Stella E / Laidlaw, Tanya M / Toppila-Salmi, Sanna / Lundberg, Marie

International archives of allergy and immunology

2022 Volume 184, Issue 2, Page(s) 149–160

Abstract: Introduction: Biologics are used in the treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The purpose of this retrospective study was to evaluate the effects of biologics initiated for asthma on coexistent CRS and the ... ...

Abstract	Introduction: Biologics are used in the treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The purpose of this retrospective study was to evaluate the effects of biologics initiated for asthma on coexistent CRS and the influence of comorbid factors, including aspirin-exacerbated respiratory disease (AERD) and secretory otitis media (SOM). Methods: A review of electronic health records (2009-2020) at a Finnish tertiary center was conducted to identify CRS patients treated with biologics for their asthma. We identified the type of biologic and treatment response, by comparing nasal polyp score (NPS), sinonasal outcome test (SNOT)-22, need for oral corticosteroids (OCS) and antibiotics, frequency of visits, and endoscopic sinus surgeries (ESS) pretreatment and during treatment. Results: 55 patients were treated with anti-immunoglobulin E (IgE) (n = 18) or anti-interleukin-5/5-receptor (IL-5/5R) (n = 37) biologics. Treatment lasted for an average of 4.1 years. Seventy-five percent (n = 41) had CRSwNP and 25% (n = 14) had CRSsNP. Of all patients, 24% (n = 13) had comorbid AERD and 22% (n = 12) had SOM. Biologic therapy reduced the need for OCS courses (anti-IgE, n = 17, p = 0.03; anti-IL-5/5R, n = 35, p = 0.01) and for daily OCS in anti-IL-5/5R (n = 35, p = 0.001) but not in anti-IgE patients (n = 16, p = 0.07). Biologics also improved NPS by 0.5 point (n = 32, p = 0.009) and SNOT-22 by 14 points (n = 7, p = 0.02) in CRSwNP patients. The overall discontinuation rate was 37.7% (n = 20) and was independent of type of biologic. Conclusion: Treatment with anti-IgE and/or anti-IL-5/5R biologics reduced the overall need for OCS medication in individuals with asthma and concomitant CRS, but despite this, the discontinuation rate was high.
MeSH term(s)	Humans ; Adrenal Cortex Hormones/therapeutic use ; Asthma/complications ; Asthma/drug therapy ; Asthma/epidemiology ; Asthma, Aspirin-Induced/complications ; Biological Products/therapeutic use ; Chronic Disease ; Finland/epidemiology ; Immunoglobulin E ; Nasal Polyps/drug therapy ; Nasal Polyps/epidemiology ; Retrospective Studies ; Rhinitis/drug therapy ; Rhinitis/epidemiology ; Rhinitis/complications ; Sinusitis/drug therapy ; Sinusitis/epidemiology
Chemical Substances	Adrenal Cortex Hormones ; Biological Products ; Immunoglobulin E (37341-29-0)
Language	English
Publishing date	2022-11-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1108932-5
ISSN	1423-0097 ; 1018-2438
ISSN (online)	1423-0097
ISSN	1018-2438
DOI	10.1159/000526365
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Article ; Online: Monoclonal Antibodies and Airway Diseases.

Lyly, Annina / Laulajainen-Hongisto, Anu / Gevaert, Philippe / Kauppi, Paula / Toppila-Salmi, Sanna

International journal of molecular sciences

2020 Volume 21, Issue 24

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Antibodies, Monoclonal/therapeutic use ; Asthma/drug therapy ; Asthma/immunology ; Cytokines/metabolism ; Humans ; Immunity, Innate ; Inflammation/immunology ; Inflammation/metabolism ; Respiration Disorders/drug therapy ; Respiration Disorders/immunology ; Rhinitis, Allergic/drug therapy ; Rhinitis, Allergic/immunology ; Sinusitis/drug therapy ; Sinusitis/immunology ; Sinusitis/metabolism ; T-Lymphocytes, Helper-Inducer/immunology
Chemical Substances	Antibodies, Monoclonal ; Cytokines
Language	English
Publishing date	2020-12-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21249477
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Article ; Online: Plunging ranula - patient characteristics, treatment, and comparison between different populations.

Lyly, Annina / Castrén, Eeva / Aronniemi, Johanna / Klockars, Tuomas

Acta oto-laryngologica

2017 Volume 137, Issue 12, Page(s) 1271–1274

Abstract: Objectives: To review our clinical experience and characteristics of Finnish patients with plunging ranula and compare our results with reports from other populations.: Design: A retrospective study from the electronic hospital records between 2005 ... ...

Abstract	Objectives: To review our clinical experience and characteristics of Finnish patients with plunging ranula and compare our results with reports from other populations. Design: A retrospective study from the electronic hospital records between 2005 and 2016. Setting: The Department of Otorhinolaryngology and Head and Neck Surgery of Helsinki University Hospital, Finland. Results: We describe the characteristics and treatment of 41 patients with MRI-confirmed plunging ranula. Most of our patients were young adults and 88% of them were male. Surgery and sclerotherapy were used for treatment. Conclusions: The vast majority of Finnish plunging ranula patients in our cohort were male, suggesting significant population-related differences in plunging ranula gender distribution. Transoral surgery seemed to result in lowest recurrence rate and was the most common treatment in our clinic.
Language	English
Publishing date	2017-12
Publishing country	England
Document type	Journal Article
ISSN	1651-2251
ISSN (online)	1651-2251
DOI	10.1080/00016489.2017.1357082
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Article ; Online: Monoclonal Antibodies and Airway Diseases

Annina Lyly / Anu Laulajainen-Hongisto / Philippe Gevaert / Paula Kauppi / Sanna Toppila-Salmi

International Journal of Molecular Sciences, Vol 21, Iss 9477, p

2020 Volume 9477

Abstract	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.
Keywords	airways ; asthma ; chronic rhinosinusitis ; biologicals ; monoclonal antibody ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Childhood nontuberculous mycobacterial lymphadenitis-observation alone is a good alternative to surgery.

Lyly, Annina / Kontturi, Antti / Salo, Eeva / Nieminen, Tea / Nokso-Koivisto, Johanna

International journal of pediatric otorhinolaryngology

2019 Volume 129, Page(s) 109778

Abstract: Objective: Cervicofacial lymphadenitis caused by nontuberculous mycobacteria (NTM) is commonly treated with surgery or antimicrobial therapy. The aim of this study was to analyze the utility of our new blood-based diagnostic method and the treatment ... ...

Abstract	Objective: Cervicofacial lymphadenitis caused by nontuberculous mycobacteria (NTM) is commonly treated with surgery or antimicrobial therapy. The aim of this study was to analyze the utility of our new blood-based diagnostic method and the treatment protocol, surgery or observation alone, in NTM lymphadenitis in children. Methods: All patients under 16 years of age with cervicofacial NTM lymphadenitis diagnosed and treated at Children's Hospital or at the Department of Otorhinolaryngology, Helsinki University Hospital (Helsinki, Finland) in 2007-2017 were retrospectively reviewed. Results: Fifty-two patients, 33 (63%) of whom were girls, were included in the study. The median age at initial presentation of the NTM lymphadenitis was 2.9 years. The novel blood-test had been performed on 49 (94%) of the patients and in all of them it was indicative of NTM infection. A sample for mycobacterial culture was available from 34 patients, and Mycobacterium avium was the most common species detected. Most patients (n = 33, 63%) were treated conservatively with observation alone. Of these, nine patients (27%) did not develop a skin fistula, and the lymphadenitis resolved without drainage. Conclusions: The novel blood test is clinically feasible method for diagnosing childhood cervicofacial NTM lymphadenitis noninvasively. Observation alone is a good alternative to surgery, without the risk of complications.
MeSH term(s)	Child ; Child, Preschool ; Drainage ; Face ; Female ; Humans ; Infant ; Lymphadenitis/microbiology ; Lymphadenitis/therapy ; Male ; Mycobacterium Infections, Nontuberculous/blood ; Mycobacterium Infections, Nontuberculous/complications ; Mycobacterium Infections, Nontuberculous/diagnosis ; Mycobacterium Infections, Nontuberculous/therapy ; Neck ; Retrospective Studies ; Watchful Waiting
Language	English
Publishing date	2019-11-12
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	754501-0
ISSN	1872-8464 ; 0165-5876
ISSN (online)	1872-8464
ISSN	0165-5876
DOI	10.1016/j.ijporl.2019.109778
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Article: The relative proportion of comorbidities among rhinitis and rhinosinusitis patients and their impact on visit burden.

Nuutinen, Mikko / Lyly, Annina / Virkkula, Paula / Hytönen, Maija / Saarentaus, Elmo / Mäkitie, Antti / Palotie, Aarno / Torkki, Paulus / Haukka, Jari / Toppila-Salmi, Sanna

Clinical and translational allergy

2022 Volume 12, Issue 7, Page(s) e12181

Abstract: Background: The aim was to evaluate the relative proportion of Non-steroidal anti-inflammatory drug exacerbated respiratory disease (NERD) and other comorbidities, and their impact on the burden of outpatient visits due to allergic rhinitis (AR), non- ... ...

Abstract	Background: The aim was to evaluate the relative proportion of Non-steroidal anti-inflammatory drug exacerbated respiratory disease (NERD) and other comorbidities, and their impact on the burden of outpatient visits due to allergic rhinitis (AR), non-allergic rhinitis (NAR), acute rhinosinusitis (ARS), and chronic rhinosinusitis with nasal polyps (CRSwNP) and without (CRSsNP). Methods: We used hospital registry data of a random sample of 5080 rhinitis/rhinosinusitis patients diagnosed during 2005-2019. International Statistical Classification of Diseases and Related Health Problems (ICD10) diagnoses, visits, and other factors were collected from electronic health records by using information extraction and data processing methods. Cox's proportional hazards model was used for modeling the time to the next outpatient visit. Results: The mean (±standard deviation) age of the population was 33.6 (±20.7) years and 56.1% were female. The relative proportion of AR, NAR, ARS, CRSsNP and CRSwNP, were 33.5%, 27.5%, 27.2%, 20.7%, and 10.9%, respectively. The most common other comorbidities were asthma (44.4%), other chronic respiratory diseases (38.5%), musculoskeletal diseases (38.4%), and cardiovascular diseases (35.7%). Non-steroidal anti-inflammatory drug exacerbated respiratory disease existed in 3.9% of all patients, and 17.7% of the CRSwNP group. The relative proportion of subjects having 1, 2, 3 and ≥ 4 other diseases were 18.0%, 17.6%, 17.0%, 37.0%, respectively. All diseases except AR, ARS, and mouth breathing, were associated with a high frequency of outpatient visits. Conclusions: Our results revealed a high relative proportion of NERD and other comorbidities, which affect the burden of outpatient visits and hence confirm the socioeconomic impact of upper airway diseases.
Language	English
Publishing date	2022-07-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2630865-4
ISSN	2045-7022
ISSN	2045-7022
DOI	10.1002/clt2.12181
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