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Abstract To evaluate the genetics of chronic nonsuppurative otitis media (OM). We performed a genome-wide association study of 429,599 individuals included in the FinnGen study using three different case definitions: combined chronic nonsuppurative OM (7034 cases) (included serous and mucous chronic OM), mucous chronic OM (5953 cases), and secretory chronic OM (1689 cases). Individuals without otitis media were used as controls (417,745 controls). We used immunohistochemistry (IHC) of the murine middle ear to evaluate the expression of annexin A13. Four loci were significantly associated (p

Abstract Patient‐reported outcome measures (PROMs) are used to assess a patient's health status at a particular point in time. They are essential in the development of person‐centred care. This paper reviews studies performed on PROMs for assessing AR and asthma control, in particular VAS scales that are included in the app MASK‐air® (Mobile Airways Sentinel networK) for asthma and rhinitis. VASs were initially developed on paper and pencil and tested for their criterion validity, cut‐offs and responsiveness. Then, a multicentric, multinational, double‐blind, placebo‐controlled, randomised control trial (DB‐PC‐RCT) using an electronic VAS form was carried out. Finally, with the development of MASK‐air® in 2015, previously validated VAS questions were adapted to the digital format and further methodologic evaluations were performed. VAS for asthma, rhinitis, conjunctivitis, work and EQ‐5D are included in the app. Additionally, two control‐medication scores for allergic symptoms of asthma (e‐DASTHMA) were validated for their criterion validity, cut‐offs and responsiveness.

PTPRF interacting protein alpha 1 (PPFIA1) encodes for liprin‐α1, a member of the leukocyte common antigen–related protein tyrosine phosphatase (LAR‐RPTPs)‐interacting protein family. Liprin‐α1 localizes to adhesive and invasive structures in the periphery of cancer cells, where it modulates migration and invasion in head and neck squamous cell carcinoma (HNSCC) and breast cancer. To study the possible role of liprin‐α1 in anticancer drug responses, we screened a library of oncology compounds in cell lines with high endogenous PPFIA1 expression. The compounds with the highest differential responses between high PPFIA1‐expressing and silenced cells across cell lines were inhibitors targeting mitogen‐activated protein kinase kinase (MEK)/extracellular signal‐regulated kinases (ERK) signaling. KRAS proto‐oncogene, GTPase (KRAS)‐mutated MDA‐MB‐231 cells were more resistant to trametinib upon PPFIA1 knockdown compared with control cells. In contrast, liprin‐α1‐depleted HNSCC cells with low RAS activity showed a context‐dependent response to MEK/ERK inhibitors. Importantly, we showed that liprin‐α1 depletion leads to increased p‐ERK1/2 levels in all our studied cell lines independent of KRAS mutational status, suggesting a role of liprin‐α1 in the regulation of MAPK oncogenic signaling. Furthermore, liprin‐α1 depletion led to more pronounced redistribution of RAS proteins to the cell membrane. Our data suggest that liprin‐α1 is an important contributor to oncogenic RAS/MAPK signaling, and the status of liprin‐α1 may assist in predicting drug responses in cancer cells in a context‐dependent manner.

ABSTRACTBackground The adoption of avoidance diets by adult-onset asthmatics has not previously been studied. We hypothesized that avoidance diets would associate with adult-onset asthma, allergy, and aspirin-exacerbated respiratory disease (AERD).Methods A total of 1247 subjects with adult-onset asthma (age range: 31–91) from the Finnish national registry, and age- and sex-matched controls (n = 1970) participated in a questionnaire study in 1997. We estimated the association between asthma/allergy/AERD and avoidance diets, adjusting for potential confounding factors and validated the results in two retrospective cohorts of 5080 rhinitis/rhinosinusitis patients and 167 AERD patients from 2019 to 2020.Results The presence of asthma positively associated with adoption of any avoidance diet (adjusted OR [CI95%] 1.24 [1.02–1.51], p = 0.029) as did allergic disease and self-reported AERD within the asthmatic group (1.79 [1.29–2.48], p = 0.001 and 1.69 [1.15–2.49], p = 0.007, respectively). Asthmatics and allergic asthmatics were more likely to report avoidance of fish, fruits and vegetables, and spices (p ≤ 0.03) compared to controls and non-allergic asthmatics. The adjusted OR for multiple diets among AERD patients was 2.57 [1.34–4.95] p = 0.005. In the validation, 26.2% of the allergic asthmatics and 10.8% of AERD patients had documented avoidance diets.Conclusions Our study shows a positive association between avoidance diets and adult-onset asthma, and with allergic disease or AERD within asthmatic patients. Although we lack information on the reason patients chose to observe a specific diet, our results reinforce the importance of asking patients about their diet and if needed, giving dietary advice for adult asthma patients to help them avoid the adoption of unnecessarily restrictive diets.

Abstract Background Our population‐based study has previously shown that being born in winter or spring was associated with adult‐onset asthma. The aim was to study if season of birth (SOB) is associated with airway allergy and related diseases: NSAID exacerbated respiratory disease (N‐ERD), asthma, allergic rhinitis (AR), nonallergic rhinitis (NAR), chronic rhinosinusitis with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP) in Finland. Methods A randomly sampled retrospective registry‐based follow‐up data (n = 74,868) of patients visiting Hospital District of Helsinki and Uusimaa (HUS) in Finland was used. The birth date, sex, visit date and comorbidities were collected from electronic health record data during visits from 2005 to 2019. Results The mean (SD, range) age of the sample was 34.53 (25.47, 0–102) years, with 48.7 % being men. We divided the whole population in four groups based on the season they were born (SOB‐groups). When observing these four SOB‐groups, the proportion of those having asthma was 43.1%, 42.1%, 41.1%, 42.7%, in winter, spring, summer, and autumn SOB‐groups, respectively. The proportion of those having AR was 12.6%, 12.0%, 10.7%, 12.1%, respectively. When having summer as a reference, being born in any other time of year was significantly associated with AR and, being born in autumn or winter was associated with asthma. No significant association was observed in CRS or N‐ERD or NAR groups in adjusted models. Conclusions The study suggests that early life immunological events may have a role a role in pathogenesis of asthma and AR. As no association was observed between SOB and CRSsNP, CRSwNP, N‐ERD or NAR, further studies on this are warranted.

Introduction A better understanding of the earliest stages of Alzheimer’s disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and AD-related biomarkers. Suitable candidates were identified and invited to participate in the new study among THL Biobank donors according to TWINGEN study criteria.Methods and analysis A multi-centre study (n=800) to obtain blood-based biomarkers, telephone-administered and web-based memory and cognitive parameters, questionnaire information on lifestyle, health and psychological factors, and accelerometer data for measures of physical activity, sedentary behaviour and sleep. A subcohort is being asked to participate in an in-person neuropsychological assessment (n=200) and wear an Oura ring (n=50). All participants in the TWINGEN study have genome-wide genotyping data and up to 48 years of follow-up data from the population-based older Finnish Twin Cohort (FTC) study of the University of Helsinki. The data collected in TWINGEN will be returned to THL Biobank from where it can later be requested for other biobank studies such as FinnGen that supported TWINGEN.Ethics and dissemination This recall study consists of FTC/THL Biobank/FinnGen participants whose data were acquired in accordance with the Finnish Biobank Act. The recruitment protocols followed the biobank protocols approved by Finnish Medicines Agency. The TWINGEN study plan was approved by the Ethics Committee of Hospital District of Helsinki and Uusimaa (number 16831/2022). THL Biobank approved the research plan with the permission no: THLBB2022_83.

Abstract Background Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the nose and paranasal sinuses lasting ≥12 weeks. CRS may exist with (CRSwNP) or without (CRSsNP) nasal polyps. The aim was to evaluate conditions associated with CRS in a randomized hospital cohort. We hypothesized that comorbidities and surgical procedures differ between pediatric and adult patients. Methods This study consisted of hospital registry data of a random sample of rhinosinusitis patients (age range 0–89 years) with the diagnosis of J32 or J33, correspondingly, registered during outpatient visits from 2005 to 2019 (n = 1461). The covariates of interest were collected from electronic health records based on ICD‐10 codes and keyword searches. Results Among pediatric patients (n = 104), the relative proportions of CRSsNP and CRSwNP were 86% and 14% respectively. The relative proportions of adult patients (n = 1357) with CRSsNP and CRSwNP were 60% and 40%, respectively. The following comorbidities significantly differed (p

The shared genetics between upper respiratory diseases have not been well studied. Here, the authors find shared and distinct genetic loci for pharyngeal and sinonasal inflammatory conditions, which show shared heritability with autoimmune conditions and immune deficiency, highlighting the TNFR2 pathway.

Abstract Background Asthma with NSAID‐exacerbated respiratory disease (NERD) is associated with uncontrolled or severe asthma. NERD patients are more prone to severe allergic reactions and their asthma exacerbations lead to hospitalisations twice as often compared to patients with non‐NERD‐asthma. NERD patients are prone to recurrent nasal polyposis requiring frequent endoscopic sinus surgeries. However, the early risk factors of NERD are not fully understood. The aim was to identify risk factors of NERD among patients with adult‐onset asthma. Methods We used data from 1350 population‐based adult asthmatics with adult‐onset asthma from Finnish national registers. NERD was defined as self‐reported wheeze or other typical respiratory symptoms after ingestion of NSAIDs. Thirty‐six covariates covering several domains (personal characteristics, life‐style, early life factors, asthma characteristics and multimorbidities) were selected based on literature and were studied in association with NERD using logistic regressions. Results The study population included 153 (11.3%) asthmatics with NERD. Thirty‐six covariates were entered in univariate logistic regression analysis, in which 23 were associated with NERD (p

BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) and asthma frequently co-exist and share pathologic features. Taking a “global” treatment approach benefits diagnosis and treatment of both, but care is often siloed by specialty: joined-up clinics are uncommon. Our objectives were to explore expert opinion to give practical suggestions to identify adults needing global airways care; enhance cross-specialty working; and widen knowledge to support diagnosis and management, integrate with existing care pathways, and supplement existing guidelines.MethodsSixteen practicing physicians from northern Europe were invited for their national and/or international standing in treating asthma and/or chronic rhinosinusitis. Appreciative Inquiry techniques were used to guide their discussions.ResultsKey themes arising were screening and referral, collaboration on management, awareness and education, and research. Provided are screening criteria and suggestions for specialist referrals, and pointers for physicians to optimize their knowledge of global airways disease. Collaborative working is underscored, and practical suggestions are given for multidisciplinary teamworking within global airways clinics. Research gaps are identified.ConclusionThis initiative provides practical suggestions for optimizing the care of adults with CRSwNP and asthma. Discussion of the role of allergy and drug exacerbations on these conditions, and care for patients with other global airways diseases were beyond scope; however, we expect some principles of our discussion will likely benefit patients with related conditions. The suggestions bridge asthma and CRSwNP management guidelines, envisioning interdisciplinary, global airway clinics relevant to various clinical settings. They highlight the value of joint screening for early recognition and referral of patients.

Abstract MASK‐air®, a validated mHealth app (Medical Device regulation Class IIa) has enabled large observational implementation studies in over 58,000 people with allergic rhinitis and/or asthma. It can help to address unmet patient needs in rhinitis and asthma care. MASK‐air® is a Good Practice of DG Santé on digitally‐enabled, patient‐centred care. It is also a candidate Good Practice of OECD (Organisation for Economic Co‐operation and Development). MASK‐air® data has enabled novel phenotype discovery and characterisation, as well as novel insights into the management of allergic rhinitis. MASK‐air® data show that most rhinitis patients (i) are not adherent and do not follow guidelines, (ii) use as‐needed treatment, (iii) do not take medication when they are well, (iv) increase their treatment based on symptoms and (v) do not use the recommended treatment. The data also show that control (symptoms, work productivity, educational performance) is not always improved by medications. A combined symptom‐medication score (ARIA‐EAACI‐CSMS) has been validated for clinical practice and trials. The implications of the novel MASK‐air® results should lead to change management in rhinitis and asthma.

Abstract Digital health is an umbrella term which encompasses eHealth and benefits from areas such as advanced computer sciences. eHealth includes mHealth apps, which offer the potential to redesign aspects of healthcare delivery. The capacity of apps to collect large amounts of longitudinal, real‐time, real‐world data enables the progression of biomedical knowledge. Apps for rhinitis and rhinosinusitis were searched for in the Google Play and Apple App stores, via an automatic market research tool recently developed using JavaScript. Over 1500 apps for allergic rhinitis and rhinosinusitis were identified, some dealing with multimorbidity. However, only six apps for rhinitis (AirRater, AllergyMonitor, AllerSearch, Husteblume, MASK‐air and Pollen App) and one for rhinosinusitis (Galenus Health) have so far published results in the scientific literature. These apps were reviewed for their validation, discovery of novel allergy phenotypes, optimisation of identifying the pollen season, novel approaches in diagnosis and management (pharmacotherapy and allergen immunotherapy) as well as adherence to treatment. Published evidence demonstrates the potential of mobile health apps to advance in the characterisation, diagnosis and management of rhinitis and rhinosinusitis patients.

Abstract Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is commonly associated with asthma. Treatment of CRSwNP includes intranasal and systemic corticosteroids, with non‐responsive patients commonly considered for endoscopic sinus surgery (ESS). This nationwide register‐based study evaluated the incidence, prevalence, and treatment burden of CRSwNP in Finland, and their association with the presence and severity of comorbid asthma. Methods Electronic health records of patients diagnosed with CRSwNP between 1.1.2012 and 31.12.2018 in Finnish specialty and primary care were included in the study. The patients were divided into subgroups based on presence, severity, and control of asthma: no asthma, mild to moderate asthma, severe controlled asthma, and severe uncontrolled asthma. A mean cumulative count of ESS was calculated over time per subgroup. Results The prevalence of CRSwNP increased from 602.2 to 856.7 patients per 100,000 population between years 2012 and 2019 (p

Objectives To recontact biobank participants and collect cognitive, behavioural and lifestyle information via a secure online platform.Design Biobank-based recontacting pilot study.Setting Three Finnish biobanks (Helsinki, Auria, Tampere) recruiting participants from February 2021 to July 2021.Participants All eligible invitees were enrolled in FinnGen by their biobanks (Helsinki, Auria, Tampere), had available genetic data and were >18 years old. Individuals with severe neuropsychiatric disease or cognitive or physical disabilities were excluded. Lastly, 5995 participants were selected based on their polygenic score for cognitive abilities and invited to the study. Among invitees, 1115 had successfully participated and completed the study questionnaire(s).Outcome measures The primary outcome was the participation rate among study invitees. Secondary outcomes included questionnaire completion rate, quality of data collected and comparison of participation rate boosting strategies.Results The overall participation rate was 18.6% among all invitees and 23.1% among individuals aged 18–69. A second reminder letter yielded an additional 9.7% participation rate in those who did not respond to the first invitation. Recontacting participants via an online healthcare portal yielded lower participation than recontacting via physical letter. The completion rate of the questionnaire and cognitive tests was high (92% and 85%, respectively), and measurements were overall reliable among participants. For example, the correlation (r) between self-reported body mass index and that collected by the biobanks was 0.92.Conclusion In summary, this pilot suggests that recontacting FinnGen participants with the goal to collect a wide range of cognitive, behavioural and lifestyle information without additional engagement results in a low participation rate, but with reliable data. We suggest that such information be collected at enrolment, if possible, rather than via post hoc recontacting.

Abstract Background The aim was to identify risk factors for severe adult-onset asthma. Methods We used data from a population-based sample (Adult Asthma in Finland) of 1350 patients with adult-onset asthma (age range 31–93 years) from Finnish national registers. Severe asthma was defined as self-reported severe asthma and asthma symptoms causing much harm and regular impairment and ≥ 1 oral corticosteroid course/year or regular oral corticosteroids or waking up in the night due to asthma symptoms/wheezing ≥ a few times/month. Sixteen covariates covering several domains (personal characteristics, education, lifestyle, early-life factors, asthma characteristics and multiple morbidities) were selected based on the literature and were studied in association with severe asthma using logistic regressions. Results The study population included 100 (7.4%) individuals with severe asthma. In a univariate analysis, severe asthma was associated with male sex, age, a low education level, no professional training, ever smoking, ≥ 2 siblings, ≥ 1 chronic comorbidity and non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) (p

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.

Abstract Background Anaphylaxis has increased over the last two decades in Europe, reaching an estimated prevalence of 0.3% and an incidence of 1.5–7.9 per 100,000 person‐years. Allergic multimorbidity is associated with asthma severity, yet its role in anaphylaxis is not fully understood. Our aim was to study association between allergic multimorbidity and anaphylaxis in adults. Methods We used population‐based data from the Finnish Allergy Barometer Study (n = 2070, age range: 5–75). Food allergy (FA), atopic dermatitis (AD), allergic rhinitis (AR) and allergic conjunctivitis (AC), were defined from a self‐completed questionnaire. A logistic regression adjusted on potential confounders (sex, age, smoking status) was applied to estimate the anaphylaxis risk associated with allergic multimorbidity. Results 1319 adults with at least one allergic disease (FA, AD, AR, AC) with/without asthma (AS) were included. Of these, 164 had self‐reported anaphylaxis [mean (SD, min‐max) 54 (14, 22–75) years, 17% men]. AS, FA, AR, AC, or AD were reported by 86.0%, 62.2%, 82.3%, 43.3%, and 53.7% of subjects with anaphylaxis and respectively by 67.8%, 29.5%, 86.2%, 29.4%, and 34.4% of subjects without anaphylaxis. Compared with subjects exhibiting only one allergic disease, the risk of anaphylaxis increased with the number of allergic diseases; adjusted odds ratios (OR) [CI95%] for two, three, four and five coinciding allergic diseases were 1.80 [0.79–4.12], 3.35 [1.47–7.66], 7.50 [3.25–17.32], and 13.5 [5.12–33.09], respectively. The highest risk of anaphylaxis (6.47 [4.33–9.92]) was associated with FA + AS or their various variations with AR/AC/AD embodied, when compared with AR, AC, and AS separately or their combinations. Conclusions Anaphylaxis was positively associated with the number of allergic diseases a subject exhibited and with subgroups including FA and/or AS. The results can be applied when estimating the risk of anaphylaxis for individual patients.

Abstract 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.

Objectives To explore the opinions, the usage and the patient education given on nasal saline irrigation by physicians and pharmaceutical personnel working in Finland. Design An internet-based survey with predetermined, multiple-choice answers. Setting Primary care centres, occupational health centres and private care centres in Eastern Finland as well as pharmacies in Finland. Main outcome measures Healthcare professionals views, practice and general knowledge of nasal irrigation for sinonasal symptoms and conditions. Results We received 595 completed surveys (110 physicians, 485 pharmacists). The majority of the respondents recommended nasal saline irrigation for their patients either as a symptomatic treatment (98.0%) or to treat a specific condition (97.5%) such as acute rhinosinusitis, chronic rhinosinusitis and allergic rhinitis. Nasal saline irrigation was also often recommended as a prophylaxis for airway-infections (71.9%) and to enhance the health of the nasal mucosa (58.2%). In general, the possible adverse effects were recognised poorly by both professions. There was a clear difference between the two professions, as physicians were more conservative in recommending nasal saline irrigation and recognised possible adverse effects, such as epistaxis, pain, and dryness of the nose, better (75% vs. 59%, p = 0.002). Conclusions Nasal saline irrigation seems to be a popular treatment recommended by many health care professionals in Finland. Physicians and pharmaceutical personnel had variable opinions on the indications, utility and risks of nasal saline irrigation. There are also clear differences between physicians and pharmaceutical personnel’s practices. There is a need to better educate professionals about nasal saline irrigation and to further study whether nasal saline irrigation is efficient and safe option for the different common sinonasal conditions.KEY POINTS Little information is available on how physicians and pharmacists recommend nasal saline irrigation as a symptomatic treatment. Physicians and pharmacists seem to have variable opinions about the indications, utility and safety of nasal saline irrigation. The patient education given is in general very heterogenous. Both professions require more education to ensure that the usage remains as safe as possible for the patient.

Summary: Background: In the current century, sleep apnoea has become a significant public health problem due to the obesity epidemic. To increase awareness, improve diagnostics, and improve treatment, Finland implemented a national sleep apnoea programme from 2002 to 2010. Here, we present changes in the societal burden caused by sleep apnoea from 1996 to 2018. Methods: National register data were collected from the Care Register for Health Care, Statistics Finland, the Social Insurance Institution of Finland, and the Finnish Centre for Pensions. Disease prevalence, use of healthcare and social services, and societal costs were estimated. Findings: The number of sleep apnoea patients increased in secondary care from 8 600 in 1996 to 61 000 in 2018. There was a continuous increase in outpatient visits in secondary care from 9 700 in 1996 to 122 000 in 2018 (1 160%) and in primary care from 10 000 in 2015 to 29 000 in 2018 (190%). Accordingly, the cumulative annual number of days off work for sleep apnoea increased from 1 100 to 46 000. However, disability pensions for sleep apnoea decreased from 820 to 550 (33%) during the observation period. Societal costs per patient decreased over 50% during the observation period (€2 800 to €1 200). Interpretation: The number of sleep apnoea patients in Finland increased remarkably during the observation period. To control this burden, diagnostic methods and treatment were revised and follow up was reorganised. Consequently, there was a significant decrease in societal costs per patient. The decrease in disability pensions suggests earlier diagnosis and improved treatment. The national sleep apnoea programme was one of the initiators for these improved outcomes. Funding: The Finnish Institute for Health and Welfare and the Hospital District of Helsinki and Uusimaa (HUH), Helsinki, Finland.

Abstract Background Evidence regarding the effectiveness of allergen immunotherapy (AIT) on allergic rhinitis has been provided mostly by randomised controlled trials, with little data from real‐life studies. Objective To compare the reported control of allergic rhinitis symptoms in three groups of users of the MASK‐air® app: those receiving sublingual AIT (SLIT), those receiving subcutaneous AIT (SCIT), and those receiving no AIT. Methods We assessed the MASK‐air® data of European users with self‐reported grass pollen allergy, comparing the data reported by patients receiving SLIT, SCIT and no AIT. Outcome variables included the daily impact of allergy symptoms globally and on work (measured by visual analogue scales—VASs), and a combined symptom‐medication score (CSMS). We applied Bayesian mixed‐effects models, with clustering by patient, country and pollen season. Results We analysed a total of 42,756 days from 1,093 grass allergy patients, including 18,479 days of users under AIT. Compared to no AIT, SCIT was associated with similar VAS levels and CSMS. Compared to no AIT, SLIT‐tablet was associated with lower values of VAS global allergy symptoms (average difference = 7.5 units out of 100; 95% credible interval [95%CrI] = −12.1;−2.8), lower VAS Work (average difference = 5.0; 95%CrI = −8.5;−1.5), and a lower CSMS (average difference = 3.7; 95%CrI = −9.3;2.2). When compared to SCIT, SLIT‐tablet was associated with lower VAS global allergy symptoms (average difference = 10.2; 95%CrI = −17.2;−2.8), lower VAS Work (average difference = 7.8; 95%CrI = −15.1;0.2), and a lower CSMS (average difference = 9.3; 95%CrI = −18.5;0.2). Conclusion In patients with grass pollen allergy, SLIT‐tablet, when compared to no AIT and to SCIT, is associated with lower reported symptom severity. Future longitudinal studies following internationally‐harmonised standards for performing and reporting real‐world data in AIT are needed to better understand its ‘real‐world’ effectiveness.

Abstract 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

Background: Periodontal diseases are a major public health problem with a 70% prevalence in adults. This retrospective controlled study aimed at studying radiologic periodontal findings in chronic rhinosinusitis with nasal polyps (CRSwNP) and without nasal polyps (sNP). Methodology: Radiologic and patient record data of CRSsNP (n=66) and CRSwNP (n=78) patients undergoing sinus surgery consultation in 2005-18 were used. Chronic rhinitis/oral disease patients served as a control group (n=52). Radiologic periodontal findings referring to chronic periodontitis of maxillary premolar and molar region and Lund-Mackay (LM) scores were analyzed blinded from sinus computed tomography (CT) scans. Results: The prevalence of ≥1 periapical radiolucency was 4.0 % in controls, 14.5% in CRSsNP and 25.4% in CRSwNP group, however this difference became insignificant when adjusted by age. In multivariable linear regression model, the presence of ≥1 other radiologic periodontal finding than periapical radiolucency, was significantly associated with high Total LM score. About half (47%) of the sinus CT scans did not visualize cemento-enamel-junction because of limiting radiation. Conclusions: Radiologic periodontal findings were significantly associated with an increment of Total LM score. Detection of radiologic periodontal findings in CRS patients seems to be possible, if adding the maxillary bone region in sinus CT scans.

Abstract 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, p = 0.02). The number of annual per oral corticosteroid courses decreased in both the anti-IL5/IL5R (− 2.8 courses, p

Abstract Because of the inflammatory mechanisms of most chronic upper airway diseases such as rhinitis and chronic rhinosinusitis, systemic steroids have been used for their treatment for decades. However, it has been very well documented that—potentially severe—side-effects can occur with the accumulation of systemic steroid courses over the years. A consensus document summarizing the benefits of systemic steroids for each upper airway disease type, as well as highlighting the potential harms of this treatment is currently lacking. Therefore, a panel of international experts in the field of Rhinology reviewed the available literature with the aim of providing recommendations for the use of systemic steroids in treating upper airway disease.

BackgroundRevision endoscopic sinus surgery (ESS) is often considered for chronic rhinosinusitis (CRS) if maximal conservative treatment and baseline ESS prove insufficient. Emerging research outlines the risk factors of revision ESS. However, accurately predicting revision ESS at the individual level remains uncertain. This study aims to examine the prediction accuracy of revision ESS and to identify the effects of risk factors at the individual level.MethodsWe collected demographic and clinical variables from the electronic health records of 767 surgical CRS patients ≥16 years of age. Revision ESS was performed on 111 (14.5%) patients. The prediction accuracy of revision ESS was examined by training and validating different machine learning models, while the effects of variables were analysed using the Shapley values and partial dependence plots.ResultsThe logistic regression, gradient boosting and random forest classifiers performed similarly in predicting revision ESS. Area under the receiving operating characteristic curve (AUROC) values were 0.744, 0.741 and 0.730, respectively, using data collected from the baseline visit until six months after baseline ESS. The length of time during which data were collected improved the prediction performance. For data collection times of 0, 3, 6 and 12 months after baseline ESS, AUROC values for the logistic regression were 0.682, 0.715, 0.744 and 0.784, respectively. The number of visits before or after baseline ESS, the number of days from the baseline visit to the baseline ESS, patient age, CRS with nasal polyps (CRSwNP), asthma, non-steroidal anti-inflammatory drug exacerbated respiratory disease and immunodeficiency or suspicion of it all associated with revision ESS. Patient age and number of visits before baseline ESS carried non-linear effects for predictions.ConclusionsIntelligent data analysis identified important predictors of revision ESS at the individual level, such as the frequency of clinical visits, patient age, Type 2 high diseases and immunodeficiency or a suspicion of it.

An amendment to this paper has been published and can be accessed via the original article.

Abstract Background In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy. Main body As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted “patient activation”, (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally-enabled, integrated, person-centred care. Conclusion In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.

Introduction: 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. Objectives: 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. Methods: 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. Results: 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. Conclusion: Our study suggests that ATAD has little effect on lower airway functions. Side effects were common, and discontinuation rates high.

The second European Rhinology Research Forum organized by the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) was held on 9-10th November 2017, combined with a specific symposium on air pollution and mobile Health technology (mHealth) with the GARD (Global Alliance against Chronic Respiratory Diseases) initiative of WHO (World Health Organization). Physicians from different specialties, researchers, as well as patients and industry representatives from more than 40 countries took part in the Forum. Relevant topics were debated with the aim of allowing the implementation of precision medicine (PM) in daily respiratory care. All debates started with positioning the current state of the art: identification of current gaps in practice, the current consensus and the need for implementation of novel approaches such as endotype-driven treatment, patient empowerment and eHealth tools. This report provides a summary of the outcomes of the brainstorming sessions of the European Rhinology Research Forum 2017, highlighting the research needs in PM, with personalized care, prediction of success of treatment, participation of the patient and prevention of disease as key drivers for improving current clinical practice.

An amendment to this paper has been published and can be accessed via the original article.

Background: The aim of this study is to investigate if using tobacco products (including snuff, smoking tobacco and dual-using) associates with periodontal health, education level and mortality in a Swedish cohort, hypothesizing that tobacco products affect periodontal health, associate with lower education and increase the risk of death. Method: Study cohort of 1080 subjects aged 31–40 years (528 men, 552 women) was clinically examined and interviewed in 1985 and followed for mortality until 2015. Subjects were classified into two groups: “tobacco users” and “non-users”. Associations between periodontal health parameters, tobacco products, education level and age of death were analysed. SPSS was used for analyses. Results: Tobacco products, as well as education level associated, with poor periodontal health. Tobacco users and lower education was linked to higher plaque-, calculus- and gingival-index scores than non-users (p < 0.001). They also had significantly higher prevalence of deep periodontal pockets (≥5 mm) (p < 0.001 and 0.010, respectively), missing teeth (p = 0.010 and 0.003, respectively) and lower education level (p < 0.001) compared with non-users. However, tobacco product users did not die significantly earlier than non-users. Conclusion: Tobacco products had a negative impact on periodontal health. Tobacco product users were less educated. However, using tobacco products may not cause premature death.

Background: We established an in vitro 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.Methods: 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.Results: 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.Conclusions: This system may contribute to in vitro mechanistic immunological studies bridging systemic models and possibly enable the development of targeted immunomodulatory therapies.

Oral infections up-regulate a number of systemic inflammatory reactions that, in turn, play a role in the development of systemic diseases. We investigated the association between oral health and autoimmune diseases in a cohort of Swedish adults. Hypothesis was that poor oral health associates with incidence of autoimmune diseases. Overall 1676 subjects aged 30–40 years old from Stockholm County (Sweden) participated in this study in 1985. Subjects were randomly selected from the registry file of Stockholm region and were followed-up for 30 years. Their hospital and open health care admissions (World Health Organization ICD 9 and 10 codes) were recorded from the Swedish national health registers. The association between the diagnosed autoimmune disease and the oral health variables were statistically analyzed. In all, 50 patients with autoimmune diagnoses were detected from the data. Plaque index was significantly higher in the autoimmune disease group (≥median 35 (70%) vs. ˂median 872 (54%), p = 0.030). No statistical difference was found in gingival index, calculus index, missing teeth, periodontal pockets, smoking or snuff use between patients with and without autoimmune disease. Our study hypothesis was partly confirmed. The result showed that subjects with a higher plaque index, marker of poor oral hygiene, were more likely to develop autoimmune diseases in 30 years.