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1. DIAGNOSIS AND TREATMENT OF PREMALIGNANT CHANGES OF PHOTODAMAGED SKIN: Novel Hyperspectral Imaging and New Therapeutical Aspects

Author: Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos, Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin, University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Department of Dermatology, Allergology and Venereology, University of Helsinki and Helsinki University Central Hospital, Päijät-Häme Central Hospital, Neittaanmäki-Perttu, Noora, Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos, Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin, University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Department of Dermatology, Allergology and Venereology, University of Helsinki and Helsinki University Central Hospital, Päijät-Häme Central Hospital, and Neittaanmäki-Perttu, Noora
Abstract: Background and purpose: As the skin cancer burden continues to increase, there is an urgent need for novel methods for the early detection of skin cancers, and for new cost-effective treatments. The hyperspectral imaging system (HIS) is a novel technique which offers the dual advantages of allowing the imaging of large skin areas rapidly and non-invasively. Daylight photodynamic therapy (DL-PDT), with the advantages of excellent tolerability and convenience, is an attaractive therapy for actinic keratoses (AK) and field cancerization.This thesis aimed to enable early and effective treatment of common premalignancies of photo-damaged skin.The first purpose of this thesis was to evaluate the feasibility of HIS in the detection of field cancerized skin and in the detection of ill-defined borders of lentigo maligna (LM) and lentigo maligna melanoma (LMM). In addition, this thesis aimed to further develop the treatment of field cancerized skin with photodynamic therapy using a novel photosensitizer in combination with daylight (DL-PDT), and to evaluate the cost-effectiveness of DL-PDT. Methods: This thesis included four non-sponsored prospective clinical studies. The novel prototype HIS, used in studies I-II, was developed for the study at the VTT Technical Research Centre of Finland. The technique enabled in vivo imaging of the skin prior to surgical procedures and produced abundance maps of the affected skin areas. The results were verified by histopathology. Study III was randomized double-blinded intra-individual split-face trial comparing novel photosensitizer formulation, 5-aminolaevulinate nanoemulsion (BF-200 ALA) with methyl-5-aminolaevulinate (MAL) in DL-PDT of AKs. In addition to blinded clinical and histological treatment efficacy, tolerability of the treatment was assessed. Study IV evaluated the cost-effectiveness of MAL-DL-PDT compared to conventional MAL-LED-PDT. Results: In studies I-II HIS showed its feasibility in both the detection of subclin, TIIVISTELMÄ Ihosyöpien määrä on jatkuvassa räjähdysmäisessä kasvussa maailmanlaajuisesti. Tämä kuormittaa terveydenhuoltoa merkittävästi. Taudinmäärityksen kehittäminen, siten että ihosyövät pystytään tunnistamaan jo varhaisessa vaiheessa sekä hoitoalueiden aiempaa tarkempi määrittäminen lisähoitojen välttämiseksi, ovat keskeisiä keinoja rajoittaa hoitokustannuksia. Lisäksi on tarve uusille, helposti toteutettaville ja kustannusvaikuttaville hoitomuodoille. Väitöstyössä tutkittiin uutta Suomessa kehitettyä hyperspektritekniikkaa ihon okasolusyövän varhaisasteiden, ns. subkliinisten aktiinikeratoosien, tunnistamisessa, sekä huonosti rajautuvien ihon pintamelanoomien, ns. lentigo malignojen, rajojen määrittämisessä lisäleikkausten välttämiseksi. Väitöstyössä selvitettiin myös uuden päivänvalolla toteutettavan fotodynaamisen hoidon (päivänvalo-PDT) tehoa ja turvallisuutta, sekä kustannusvaikuttavuutta ihon okasolusyövän esiasteiden eli aktiinikeratoosien hoidossa. Tutkimuksessa tutkittiin kahta iholle levitettävää valoherkistäjävoidetta, joista toista ei aiemmin ole käytetty tällä indikaatiolla. Tutkimuksella haluttiin kehittää ihosyöpien varhaisvaiheiden hoitoprosessia resursseja ja kustannuksia säästäväksi, sekä löytää uusia, hyvin siedettyjä mutta tehokkaita hoitomuotoja. Väitöskirjatyöhön sisältyi neljä prospektiivista kliinistä tutkimusta. Hyperspektrikuvantaminen todettiin hyödylliseksi varhaisten, silmälle vielä näkymättömien, aktiinikeratoosien havaitsemisessa. Lisäksi hyperspektrikuvantamisen avulla kyettiin havaitsemaan silmälle näkymättömiä lentigo maligna-kasvainten rajoja. Tämä auttaa entistä tarkemmin määrittämään hoitoalueet ja saattaa mahdollistaa entistä tarkemman hoidon seurannan. Turhilta lisäleikkauksilta saatetaan välttyä. Päivänvalo-PDT osoittautui tehokkaaksi, turvalliseksi ja paremmin siedetyksi kuin perinteinen fotodynaaminen hoito (keinovalo-PDT), missä valolähteenä on keinovalo. Päivänvalo-PDT vei vähemmän sekä poliklinikan henkilökunnan että
Published: 2015

2. Early life determinants of atopy : A 20-year prospective follow-up study on unselected, healthy newborns

Author: Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos, Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin, University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Department of Dermatology, Allergology and Venereology, Helsinki University Central Hospital, Skin and Allergy Hospital; University of Helsinki, Department of Pediatrics; Helsinki University Central Hospital, Hospital for Children and Adolescents, Pesonen, Maria, Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos, Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin, University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Department of Dermatology, Allergology and Venereology, Helsinki University Central Hospital, Skin and Allergy Hospital; University of Helsinki, Department of Pediatrics; Helsinki University Central Hospital, Hospital for Children and Adolescents, and Pesonen, Maria
Abstract: Atopy-related allergic diseases, i.e. allergic rhinoconjunctivitis, atopic dermatitis and asthma, have increased in frequency in the industrialized countries. In order to reverse this trend, effective preventive strategies need to be developed. This requires a better understanding of the early-life events leading to the expression of the atopic phenotype. The present study has aimed at defining early-life factors and markers associated with the subsequent development of allergic diseases in a cohort of 200 healthy, unselected Finnish newborns prospectively followed up from birth to age 20 years. Their mothers were encouraged to start and maintain exclusive breastfeeding as long as it was nutritionally sufficient for the infant. Consequently, all the infants received some duration of exclusive breastfeeding, 58% of the infants were on exclusive breastfeeding for the first 6 months of life, and 18% received this feeding at least for the first 9 months. Of the infants, 42% had a family history of allergy. After the first year of follow-up, the children were re-assessed at ages 5, 11 and 20 years with clinical examination, skin prick testing, and parental and personal interviews. Exclusive breastfeeding for over 9 months was associated with atopic dermatitis and symptoms of food hypersensitivity at age 5 years, and with symptoms of food hypersensitivity at age 11 years in the children with a familial allergy. Subjects with allergic symptoms or a positive skin prick test in childhood or adolescence had lower retinol concentrations during their infancy and childhood than others. An elevated cord serum immunoglobulin E concentration predicted subsequent atopic manifestations though with modest sensitivity. Children and adolescents with allergic symptoms, skin prick test positivity and an elevated IgE had lower total cholesterol levels in infancy and childhood than the nonatopic subjects. In conclusion, prolonging strictly exclusive breastfeeding for over 9 months of age wa, Allerginen herkistyminen ja allerginen nuha, astma ja atooppinen ihottuma ovat lisääntyneet viime vuosikymmeninä. Näistä sairauksista kärsii jopa miljoona suomalaista. Allergisten sairauksien puhkeamiseen johtava kehitys riippuu perimästä ja alkaa jo varhaislapsuudessa, mutta siihen vaikuttavat tekijät tunnetaan vielä puutteellisesti. Tutkimuksessa selvitettiin yksinomaisen, pitkäkestoisen rintaruokinnan vaikutusta allergisten sairauksien kehittymiseen sekä etsittiin muita vauvaiän tekijöitä, jotka liittyvät myöhemmän iän allergisiin sairauksiin. Aineistona on 200 suomalaisen terveen vastasyntyneen ryhmä, jota on seurattu syntymästä 20 vuoden ikään saakka. 42 % osallistujista oli allergiaperheiden lapsia. Kaikkien vauvojen äitejä kannustettiin aloittamaan yksinomainen rintaruokinta ja ylläpitämään sitä niin kauan kuin se oli lapselle ravitsemuksellisesti riittävää. Lapsista 58 % oli yksinomaisella rintaruokinnalla 6 kuukauden ikään asti, ja 18 % 9 kuukauden ikään asti tai pidempään. Lasten allergiaoireet tutkittiin haastattelun, kliinisen tutkimuksen ja ihokokeiden avulla 5, 11 ja 20 vuoden iässä. Napaverestä mitatun immunoglobuliini E:n korkea pitoisuus ennusti allergiaoireiden kehittymistä, mutta sen herkkyys ja tarkkuus eivät olleet riittävät, jotta se soveltuisi allergiataipumuksen seulontatestiksi. Lapsilla, jotka olivat olleet yksinomaisella rintaruokinnalla yli 9 kuukauden ikään, todettiin enemmän atooppista ihottumaa ja ruoka-aineyliherkkyysoireita 5-vuotiaana kuin lyhyemmän aikaa yksinomaista rintaruokintaa saaneilla. Ruokayliherkkyysoireiden ylimäärä oli havaittavissa näillä lapsilla vielä 11 vuoden iässä. Kahden kuukauden iässä mitatun plasman retinolin (a-vitamiini) todettiin olevan verraten matala lapsilla, joille myöhemmin kehittyi allergiaoireita. Kolesterolipitoisuus oli vauvaiästä alkaen matalampi lapsilla, joille kehittyi allergiaoireita 20 vuoden ikään mennessä. Tulokset viittaavat siihen, että yksinomaisen rintaruokinnan pitkittäminen yli nykyist
Published: 2008

3. Identification of novel target genes in different subtypes of cutaneous T-cell lymphoma

Author: University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Department of Dermatology, Allergology and Venereology, Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos, Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin, Hahtola, Sonja, University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Department of Dermatology, Allergology and Venereology, Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos, Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin, and Hahtola, Sonja
Abstract: Ihon T-solulymfoomat (cutaneous T-cell lymphoma, CTCL) ovat ryhmä imukudossyöpiä, joiden esiintyvyys on nousussa erityisesti länsimaissa. Taudin syntymekanismit ovat suurelta osin tuntemattomat, diagnostiikka on vaikeaa ja siksi usein viivästynyttä eikä parantavaa hoitoa ole. CTCL ilmenee iho-oirein, vaikka syöpäsolut eivät ole iholla normaalisti esiintyviä soluja, vaan elimistön puolustusjärjestelmän soluja, jotka ovat tuntemattomasta syystä vaeltaneet iholle. Syöpäsolut ovat kypsiä T-auttajasoluja (Th-soluja) ja ilmentävät tyypin 2 immuunivasteelle ominaisia sytokiineja. Kromosomaalinen epästabiilius on tautiryhmän keskeinen piirre. CTCL-potilailla on lisääntynyt riski sairastua myös muihin syöpiin, erityisesti keuhkosyöpään ja non-Hodgkin –lymfoomiin. Väitöskirjatutkimuksen tavoitteena oli havaita CTCL:n syntymekanismeja selvittäviä kromosomi- ja geenimuutoksia. Erityisesti tavoitteena oli identifioida molekyylejä, jotka soveltuisivat diagnostisiksi merkkiaineiksi tai täsmähoidon kohteeksi. Työssä on tutkittu kahta tautiryhmän yleisintä muotoa, mycosis fungoidesta (MF) ja Sezaryn syndroomaa (SS) sekä harvinaisempaa vaikeasti diagnosoitavaa subkutaanista pannikuliitin kaltaista T-solulymfoomaa (SPTL). Lisäksi on tutkittu CTCL:ään liittyvää keuhkosyöpää ja verrattu sitä tavalliseen (primaariin) keuhkosyöpään. Tutkimusmenetelminä on käytetty esimerkiksi molekyylisytogeneettisiä metodeja ja mikrosiruja. Väitöskirjatyössä havaittiin ensimmäinen CTCL:lle ominainen toistuva geenitason muutos: puutos- tai katkoskohta NAV3-geenissä. Tämän geenipoikkeavuuden havaittiin esiintyvän useissa taudin alaryhmissä (MF, SS, SPTL). NAV3-geenipuutoksen osoittaminen FISH-tekniikalla on sovellettavissa kliiniseen diagnostiikkaan. Tutkimukset geenipuutoksen aiheuttamista toiminnallisista seurauksista ovat käynnissä. Työssä saatiin myös uutta tietoa taudin syntymekanismeista havaitsemalla useiden Th1-tyypin immuunivasteelle ominaisten geenien alentunut ilmeneminen CTCL-potilailla. Tämän, Cutaneous T-cell lymphomas (CTCL) represent a group of non-Hodgkin lymphomas showing a growing incidence especially in the Western world. The mechanisms leading to the disease are largely unknown, diagnosis is difficult and therefore often delayed, and no curative therapy exists. CTCL presents with skin symptoms although the malignant cells are not derived of human skin but of human immune system instead. The malignant cells are mature T helper memory cells, and preferentially express cytokines characteristic to T-helper 2 (Th2) type immune response. Chromosomal instability is a typical feature of CTCL. Some secondary cancers occur in CTCL patients more often than in general population, the most common of which are lung cancers and non-Hodgkin lymphomas. The aim of the study was to identify genes relevant to CTCL pathogenesis to clarify the poorly understood pathomechanisms behind the disease group. The two most common subgroups of CTCL, mycosis fungoides (MF) and Sezary syndrome (SS), as well as the difficult to diagnose subcutaneous panniculitis like T-cell lymphoma (SPTL), were studied. To reveal the molecular pathogenesis underlying CTCL-associated lung cancer, CTCL-associated lung cancer samples were analysed and compared to primary / reference lung cancer samples. Identification of potential novel diagnostic markers as well as target molecules for therapy was a special focus of the study. To achieve this, patient derived material was studied with molecular cytogenetic techniques, microarrays and gene expression analyses. This study identified the first specific, recurrent gene-level aberration in CTCL, namely the deletion / translocation of neuron navigator 3 (NAV3) gene, characteristic to many different CTCL subgroups, namely MF, SS, and SPTL. NAV3 is a putative haploinsufficient tumor suppressor influencing the differentiation of T-helper cells. The pathways affected by its aberrant function, are currently being studied. Novel insights to CTCL pathogenesis w
Published: 2008

4. Tumour necrosis factor receptor-associated periodic syndrome (TRAPS) : Identification of novel TNFRSF1A mutations and intracellular signalling defects

Author: Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos, Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin, University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Department of Dermatology, Allergology and Venereology, Stjernberg-Salmela, Susanna, Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos, Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin, University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Department of Dermatology, Allergology and Venereology, and Stjernberg-Salmela, Susanna
Abstract: The systemic autoinflammatory disorders are a group of rare diseases characterized by periodically recurring episodes of acute inflammation and a rise in serum acute phase proteins, but with no signs of autoimmunity. At present eight hereditary syndromes are categorized as autoinflammatory, although the definition has also occasionally been extended to other inflammatory disorders, such as Crohn s disease. One of the autoinflammatory disorders is the autosomally dominantly inherited tumour necrosis factor receptor-associated periodic syndrome (TRAPS), which is caused by mutations in the gene encoding the tumour necrosis factor type 1 receptor (TNFRSF1A). In patients of Nordic descent, cases of TRAPS and of three other hereditary fevers, hyperimmunoglobulinemia D with periodic fever syndrome (HIDS), chronic infantile neurologic, cutaneous and articular syndrome (CINCA) and familial cold autoinflammatory syndrome (FCAS), have been reported, TRAPS being the most common of the four. Clinical characteristics of TRAPS are recurrent attacks of high spiking fever, associated with inflammation of serosal membranes and joints, myalgia, migratory rash and conjunctivitis or periorbital cellulitis. Systemic AA amyloidosis may occur as a sequel of the systemic inflammation. The aim of this study was to investigate the genetic background of hereditary periodically occurring fever syndromes in Finnish patients, to explore the reliability of determining serum concentrations of soluble TNFRSF1A and metalloproteinase-induced TNFRSF1A shedding as helpful tools in differential diagnostics, as well as to study intracellular NF-κB signalling in an attempt to widen the knowledge of the pathomechanisms underlying TRAPS. Genomic sequencing revealed two novel TNFRSF1A mutations, F112I and C73R, in two Finnish families. F112I was the first TNFRSF1A mutation to be reported in the third extracellular cysteine-rich domain of the gene and C73R was the third novel mutation to be reported in a Finni, Systeemiset autoinflammatoriset oireyhtymät ovat joukko harvinaisia, autosomaalisesti periytyviä tauteja, joiden oirekuvaan kuuluvat toistuvat kuumekohtaukset, muine tulehdusoireineen. 1990-lopulla lääketieteellisessä kirjallisuudessa perinnöllisiin kuumeoireyhtymiin luettiin välimerenkuume (FMF) ja hyperimmunoglobulinemia D with periodic fever syndrome (HIDS), jotka ovat peitty-västi periytyviä, sekä tumour necrosis factor receptor-associated periodic syndrome (TRAPS), joka periytyy vallitsevasti. Näihin on viime vuosina liitetty ainakin viisi vallitsevasti periytyvää oi-reyhtymää, familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) ja neonatal-onset multisystem inflammatory disorder (NOMID)/ chronic infantile neurological cutaneous and articular (CINCA) syndrome, Pyogenic sterile arthritis in combination with py-oderma gangrenosum and acne (PAPA) ja Blau oireyhtymä. Kaikissa oireyhtymissä kohdegeenin mutaatiot aiheuttavat aggressiivisen ja pitkittyneen tulehdusreaktion. Yhteistä kaikille kuumeoireyh-tymille on jaksottaisesti esiintyvä korkea kuume, peritoneumin, pleuran, perikardiumin ja nivelten tulehdus, sekä lihassärkyä ja erilaisia ihottumia. CRP ja SAA, sekä muut akuutin faasin proteiinit nousevat voimakkaasti, jonka seurauksena saattaa olla komplikaatiot, kuten AA-amyloidoosi. Var-sinkin FMF:ssa, jonka taustalla on tulehdusreaktiota ja apoptoosia säätelevää pyriiniä koodaavan MEFV geenin mutaatio, AA-amyloidoosi on yleinen komplikaatio. Kolkisiini-lääkityksen aloittami-sen myötä amyloidoositapaukset ovat vähentyneet FMF-potilaiden parissa. Vallitsevasti periytyvää kuumetta kuvattiin suomalaisessa suvussa vuonna 1992 ja vuonna 1999 tutki-musryhmämme osoitti yhteistyössä brittiläisten ja amerikkalaisten tutkijoiden kanssa vallitsevasti periy-tyvän jaksoittaisen kuumeen geneettisen taustan liittyvän kromosomiin 12p13, jossa sijaitsee mm. tuu-morinekroositekijän (TNF) tyyppi 1 reseptorin (TNFRSF1A) geeni. Oireisilla henkilöillä todettiin
Published: 2008

5. Transforming growth factor -beta signaling through Smad3 in allergy : Studies in the mechanisms of asthma, atopic dermatitis and allergic contact reactions

Author: Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos, Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin, University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Department of Dermatology, Allergology and Venereology, Finnish Institute of Occupational Health, Anthoni, Minna, Helsingin yliopisto, lääketieteellinen tiedekunta, kliininen laitos, Helsingfors universitet, medicinska fakulteten, institutionen för klinisk medicin, University of Helsinki, Faculty of Medicine, Institute of Clinical Medicine, Department of Dermatology, Allergology and Venereology, Finnish Institute of Occupational Health, and Anthoni, Minna
Abstract: Transforming growth factor β signalling through Smad3 in allergy Allergic diseases, such as atopic dermatitis, asthma, and contact dermatitis are complex diseases influenced by both genetic and environmental factors. It is still unclear why allergy and subsequent allergic disease occur in some individuals but not in others. Transforming growth factor (TGF)-β is an important immunomodulatory and fibrogenic factor that regulates cellular processes in injured and inflamed skin. TGF-β has a significant role in the regulation of the allergen-induced immune response participating in the development of allergic and asthmatic inflammation. TGF-β is known to be an immunomodulatory factor in the progression of delayed type hypersensitivity reactions and allergic contact dermatitis. TGF-β is crucial in regulating the cellular responses involved in allergy, such as differentiation, proliferation and migration. TGF-β signals are delivered from the cytoplasm to the nucleus by TGF-β signal transducers called Smads. Smad3 is a major signal transducer in TGF-β -signalling that controls the expression of target genes in the nucleus in a cell-type specific manner. The role of TGF-β-Smad3 -signalling in the immunoregulation and pathophysiology of allergic disorders is still poorly understood. In this thesis, the role of TGF-β-Smad -signalling pathway using Smad3 -deficient knock out mice in the murine models of allergic diseases; atopic dermatitis, asthma and allergic contact reactions, was examined. Smad3-pathway regulates allergen induced skin inflammation and systemic IgE antibody production in a murine model atopic dermatitis. The defect in Smad3 -signalling decreased Th2 cytokine (IL-13 and IL-5) mRNA expression in the lung, modulated allergen induced specific IgG1 response, and affected mucus production in the lung in a murine model of asthma. TGF-β / Smad3 -signalling contributed to inflammatory hypersensitivity reactions and disease progression via modulation of chemokine and c, Atooppiset taudit yleistyvät - tutkimus paljastaa uutta tietoa tautien syntymekanismeista Väitöskirjatutkimuksessa on onnistuttu immuno- ja molekyylibiologisin keinoin selvittämään solunsisäisen valkuaisaineen, Smad3:n, merkitystä allergisten tautien, atooppisen astman ja ihottuman, synnylle. Tutkimuksen tulokset auttavat kehittämään allergisten tautien hoitokeinoja. Atooppiset taudit ovat kroonisia ja monitekijäisiä tiloja, jotka yleistyvät jatkuvasti. On arvioitu, että lähitulevaisuudessa kolmannes länsimaailman väestöstä tulee kärsimään näistä. Atooppinen astma on krooninen tulehduksellinen tauti hengitysteissä, jolle on tyypillistä hengitysteiden ahtautuminen, hengitysteiden yliärtyvyys, lisääntynyt limaneritys ja limakalvovaurioita. Atooppinen ihottuma, dermatiitti, on kutiava tulehdus, jota esiintyy 10-15 % kaikista länsimaailman lapsista. Tämä tila on yhteydessä muihin allergisiin tiloihin myöhemmissä elinvaiheissa. Elimistössä esiintyvä TGF-beta-valkuaisaine vaikuttaa merkittävästi allergisen tulehduksen syntyyn. Kyseistä valkuaisainetta erittyy eri solutyypeistä ja sillä on hyvin laaja vaikutuskirjo. Yleensä tämän valkuaisaineen tehtävänä elimistössä on vähentää tulehdusreaktioita. Tutkimuksessa selvitettiin TGF-beta-valkuaisaineen vaikutuksia keskeisesti välittävän solunsisäisen välittäjäproteiinin, Smad3:n, merkitystä TGF-beta-valkuaisaineen toiminnalle allergisessa tilassa. Normaalisti toimiessaan Smad3 aktivoi solun tumassa erilaisten proteiinien tuotantoa, millä on merkitystä allergisen tulehduksen syntymisessä ja etenemisessä. Tutkimuksessa on saatu uutta tietoa siitä, mitkä sytokiinit ja kemokiinit (solujen liikkeisiin vaikuttavia pienimolekyylisiä aineita) reagoivat Smad3-välittäjäaineen puuttumiseen ja sitä kautta on tullut merkittävästi tietoa atooppisen astman ja dermatiitin syntyyn vaikuttavista tekijöistä. Tämä tieto auttaa tutkijoita tehokkaampien hoitomuotojen kehittämistyössä allergisia tauteja vastaan.
Published: 2008

6. Systemic treatment of children and adolescents with atopic dermatitis aged ≥2 years: a Delphi consensus project mapping expert opinion in Northern Europe

Author: M. de Graaf, S.R. Janmohamed, M.L.A. Schuttelaar, T. Agner, J.H. Alfonso, S. De Schepper, M. Deleuran, K. Despontin, V. Elenius, P.‐D. Ghislain, L. Huilaja, E.K. Johansson, B.K. Kvenshagen, J.M. Mandelin, H. Olset, A. Svensson, A.M. van Tuyll van Serooskerken, J.P. Thyssen, C. Vestergaard, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Dermatologie, Clinical sciences, Gerontology, Dermatology, Skin function and permeability, and Public Health Research (PHR)
Subjects: Adolescent, Child, preschool, Methotrexate/therapeutic use, ECZEMA, Dermatology, GUIDELINES, DISEASE, RECOMMENDATIONS, Dermatitis, Atopic, STEROID PHOBIA, QUALITY-OF-LIFE, Delphi technique, Azathioprine, Medicine and Health Sciences, MANAGEMENT, Janus Kinase Inhibitors, Humans, Dermatitis, Atopic/therapy, POSITION, Child, Expert Testimony, Quality Of Life, Cyclosporine/therapeutic use, Janus Kinases, Biological Products, Janus Kinase Inhibitors/therapeutic use, THERAPEUTIC PATIENT EDUCATION, Mycophenolic Acid, Mycophenolic Acid/therapeutic use, Methotrexate, Infectious Diseases, PERSPECTIVES, 3121 General medicine, internal medicine and other clinical medicine, Cyclosporine, PAPER, Azathioprine/therapeutic use, Biological Products/therapeutic use, POSITION PAPER
Abstract: Publisher Copyright: © 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology. Background: Paediatric atopic dermatitis (AD) can be burdensome, affecting mental health and impairing quality of life for children and caregivers. Comprehensive guidelines exist for managing paediatric AD, but practical guidance on using systemic therapy is limited, particularly for new therapies including biologics and Janus kinase (JAK) inhibitors, recently approved for various ages in this indication. Objectives: This expert consensus aimed to provide practical recommendations within this advancing field to enhance clinical decision-making on the use of these and other systemics for children and adolescents aged ≥2 years with moderate-to-severe AD. Methods: Nineteen physicians from Northern Europe were selected for their expertise in managing childhood AD. Using a two-round Delphi process, they reached full or partial consensus on 37 statements. Results: Systemic therapy is recommended for children aged ≥2 years with a clear clinical diagnosis of severe AD and persistent disease uncontrolled after optimizing non-systemic therapy. Systemic therapy should achieve long-term disease control and reduce short-term interventions. Recommended are cyclosporine A for short-term use (all ages) and dupilumab or methotrexate for long-term use (ages ≥6 years). Consensus was not reached on the best long-term systemics for children aged 2–6 years, although new systemic therapies will likely become favourable: New biologics and JAK inhibitors will soon be approved for this age group, and more trial and real-world data will become available. Conclusions: This article makes practical recommendations on the use of systemic AD treatments for children and adolescents, to supplement international and regional guidelines. It considers the systemic medication that was available for children and adolescents with moderate-to-severe AD at the time this consensus project was done: azathioprine, cyclosporine A, dupilumab, methotrexate, mycophenolate mofetil and oral glucocorticosteroids. We focus on the geographically similar Northern European countries, whose healthcare systems, local preferences for AD management and reimbursement structures nonetheless differ significantly.
Published: 2022

7. Development and validation of combined symptom-medication scores for allergic rhinitis*

Author: Bernardo Sousa‐Pinto, Luís Filipe Azevedo, Marek Jutel, Ioana Agache, G. Walter Canonica, Wienczyslawa Czarlewski, Nikolaos G. Papadopoulos, Karl‐Christian Bergmann, Philippe Devillier, Daniel Laune, Ludger Klimek, Aram Anto, Josep M. Anto, Patrik Eklund, Rute Almeida, Anna Bedbrook, Sinthia Bosnic‐Anticevich, Helen A. Brough, Luisa Brussino, Victoria Cardona, Thomas Casale, Lorenzo Cecchi, Denis Charpin, Tomás Chivato, Elisio M. Costa, Alvaro A. Cruz, Stephanie Dramburg, Stephen R. Durham, Giulia De Feo, Roy Gerth van Wijk, Wystke J. Fokkens, Bilun Gemicioglu, Tari Haahtela, Maddalena Illario, Juan Carlos Ivancevich, Violeta Kvedariene, Piotr Kuna, Désirée E. Larenas‐Linnemann, Michael Makris, Eve Mathieu‐Dupas, Erik Melén, Mario Morais‐Almeida, Ralph Mösges, Joaquim Mullol, Kari C. Nadeau, Nhân Pham‐Thi, Robyn O’Hehir, Frederico S. Regateiro, Sietze Reitsma, Boleslaw Samolinski, Aziz Sheikh, Cristiana Stellato, Ana Todo‐Bom, Peter Valentin Tomazic, Sanna Toppila‐Salmi, Antonio Valero, Arunas Valiulis, Maria Teresa Ventura, Dana Wallace, Susan Waserman, Arzu Yorgancioglu, Govert De Vries, Michiel van Eerd, Petra Zieglmayer, Torsten Zuberbier, Oliver Pfaar, João Almeida Fonseca, Jean Bousquet, Internal Medicine, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, University of Helsinki, Ear, Nose and Throat, AII - Inflammatory diseases, Publica, Sousa-Pinto, B., Azevedo, L. F., Jutel, M., Agache, I., Canonica, G. W., Czarlewski, W., Papadopoulos, N. G., Bergmann, K. -C., Devillier, P., Laune, D., Klimek, L., Anto, A., Anto, J. M., Eklund, P., Almeida, R., Bedbrook, A., Bosnic-Anticevich, S., Brough, H. A., Brussino, L., Cardona, V., Casale, T., Cecchi, L., Charpin, D., Chivato, T., Costa, E. M., Cruz, A. A., Dramburg, S., Durham, S. R., De Feo, G., Gerth van Wijk, R., Fokkens, W. J., Gemicioglu, B., Haahtela, T., Illario, M., Ivancevich, J. C., Kvedariene, V., Kuna, P., Larenas-Linnemann, D. E., Makris, M., Mathieu-Dupas, E., Melen, E., Morais-Almeida, M., Mosges, R., Mullol, J., Nadeau, K. C., Pham-Thi, N., O'Hehir, R., Regateiro, F. S., Reitsma, S., Samolinski, B., Sheikh, A., Stellato, Cristiana, Todo-Bom, A., Tomazic, P. V., Toppila-Salmi, S., Valero, A., Valiulis, A., Ventura, M. T., Wallace, D., Waserman, S., Yorgancioglu, A., De Vries, G., van Eerd, M., Zieglmayer, P., Zuberbier, T., Pfaar, O., Almeida Fonseca, J., and Bousquet, J.
Subjects: Work, medication score, quality-of-life, rhinitis, symptom score, work, Respiratory Medicine and Allergy, Immunology, QUESTIONNAIRE, RESPONSIVENESS, Humans, Immunology and Allergy, IMMUNOTHERAPY, VALIDITY, Lungmedicin och allergi, Rhinitis, Medication score, EQ-5D, Reproducibility of Results, IMPAIRMENT, Rhinitis, Allergic, WORK PRODUCTIVITY, Symptom score, rhiniti, TRIALS, 3121 General medicine, internal medicine and other clinical medicine, RELIABILITY, Quality of Life, ASTHMA, Quality-of-life, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
Abstract: Background: Validated combined symptom-medication scores (CSMSs) are needed to investigate the effects of allergic rhinitis treatments. This study aimed to use real-life data from the MASK-air® app to generate and validate hypothesis- and data-driven CSMSs. Methods: We used MASK-air® data to assess the concurrent validity, test-retest reliability and responsiveness of one hypothesis-driven CSMS (modified CSMS: mCSMS), one mixed hypothesis- and data-driven score (mixed score), and several data-driven CSMSs. The latter were generated with MASK-air® data following cluster analysis and regression models or factor analysis. These CSMSs were compared with scales measuring (i) the impact of rhinitis on work productivity (visual analogue scale [VAS] of work of MASK-air®, and Work Productivity and Activity Impairment: Allergy Specific [WPAI-AS]), (ii) quality-of-life (EQ-5D VAS) and (iii) control of allergic diseases (Control of Allergic Rhinitis and Asthma Test [CARAT]). Results: We assessed 317,176 days of MASK-air® use from 17,780 users aged 16-90 years, in 25 countries. The mCSMS and the factor analyses-based CSMSs displayed poorer validity and responsiveness compared to the remaining CSMSs. The latter displayed moderate-to-strong correlations with the tested comparators, high test-retest reliability and moderate-to-large responsiveness. Among data-driven CSMSs, a better performance was observed for cluster analyses-based CSMSs. High accuracy (capacity of discriminating different levels of rhinitis control) was observed for the latter (AUC-ROC = 0.904) and for the mixed CSMS (AUC-ROC = 0.820). Conclusion: The mixed CSMS and the cluster-based CSMSs presented medium-high validity, reliability and accuracy, rendering them as candidates for primary endpoints in future rhinitis trials.
Published: 2022

8. DSP c.6310delA p.(Thr2104Glnfs*12) associates with arrhythmogenic cardiomyopathy, increased trabeculation, curly hair, and palmoplantar keratoderma

Author: Heliö, Krista, Brandt, Eveliina, Vaara, Satu, Weckström, Sini, Harjama, Liisa, Kandolin, Riina, Järviö, Johanna, Hannula-Jouppi, Katariina, Heliö, Tiina, Holmström, Miia, Koskenvuo, Juha W., HUS Heart and Lung Center, Department of Dermatology, Allergology and Venereology, HUS Inflammation Center, HUS Medical Imaging Center, HUS Diagnostic Center, Kardiologian yksikkö, Research Programs Unit, STEMM - Stem Cells and Metabolism Research Program, Clinicum, and Department of Medicine
Subjects: Myocarditis, Cardiomyopathy, 3121 General medicine, internal medicine and other clinical medicine, Arrhythmogenic cardiomyopathy, Palmoplantar keratoderma, Cmr, Dsp, Cardiology and Cardiovascular Medicine
Abstract: BackgroundPathogenic variants in DSP associate with cardiac and cutaneous manifestations including arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, curly or wavy hair, and palmoplantar keratoderma (PPK). Episodes of myocardial inflammation associated with DSP cardiomyopathy might be confused in clinical work with myocarditis of other etiologies such as viral. Cardiac magnetic resonance imaging (CMR) may help in differential diagnosis.Methods and resultsThis study comprised 49 Finnish patients: 34 participants from families with suspected DSP cardiomyopathy (9 index patients and 25 family members) and 15 patients with myocarditis. All 34 participants underwent genetic testing and cardiac evaluation, and 29 of them also underwent CMR. Participants with the DSP variant, numbering 22, were dermatologically examined. The 15 patients with myocarditis underwent CMR and were evaluated during their hospitalization.A heterozygous truncating DSP c.6310delA p.(Thr2104Glnfs*12) variant was confirmed in 29 participants. Only participants with the DSP variant had pacemakers and life-threatening ventricular arrhythmias. Of the participants with the DSP variant, 24% fulfilled cardiomyopathy criteria, and the median age at diagnosis was 53. Upon CMR, myocardial edema was found to be more common in patients with myocarditis. Both groups had a substantial percentage of late gadolinium enhancement (LGE). A ring-like LGE and increased trabeculation were observed only in participants with the DSP variant. All the studied participants with the DSP variant had PPK and curly or wavy hair. Hyperkeratosis developed before the age of 20 in most patients.ConclusionsThe DSP c.6310delA p.(Thr2104Glnfs*12) variant associates with curly hair, PPK, and arrhythmogenic cardiomyopathy with increased trabeculation. Cutaneous symptoms developing in childhood and adolescence might help recognize these patients at an earlier stage. CMR, together with dermatologic characteristics, may help in diagnosis.
Published: 2023

9. Intrahost Monkeypox Virus Genome Variation in Patient with Early Infection, Finland, 2022

Author: Hanna Vauhkonen, Hannimari Kallio-Kokko, Eija Hiltunen-Back, Lasse Lönnqvist, Jaana Leppäaho-Lakka, Laura Mannonen, Ravi Kant, Tarja Sironen, Satu Kurkela, Maija Lappalainen, Tomaž Mark Zorec, Samo Zakotnik, Doroteja Vlaj, Miša Korva, Tatjana Avšič-Županc, Mario Poljak, Teemu Smura, Olli Vapalahti, Department of Virology, HUSLAB, Medicum, Faculty Common Matters (Faculty of Biology and Environmental Sciences), Clinicum, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, Mirja Puolakkainen / Principal Investigator, Faculty Common Matters (Faculty of Medicine), Helsinki One Health (HOH), Viral Zoonosis Research Unit, Emerging Infections Research Group, Olli Pekka Vapalahti / Principal Investigator, Veterinary Microbiology and Epidemiology, and Veterinary Biosciences
Subjects: Microbiology (medical), 11832 Microbiology and virology, 3141 Health care science, Infectious Diseases, Epidemiology
Abstract: Monkeypox virus was imported into Finland during late May–early June 2022. Intrahost viral genome variation in a sample from 1 patient comprised a major variant with 3 lineage B.1.3–specific mutations and a minor variant with ancestral B.1 nucleotides. Results suggest either ongoing APOBEC3 enzyme–mediated evolution or co-infection.
Published: 2023

10. Effectiveness of mepolizumab in patients with severe eosinophilic asthma: results from real-world clinical practice in Finland

Author: Ville, Koistinen, Paula, Kauppi, Juhana, Idänpään-Heikkilä, Lauri, Veijalainen, Ilona, Iso-Mustajärvi, Tero, Ylisaukko-Oja, Juha, Mehtälä, Arja, Viinanen, Maritta, Kilpeläinen, Tampere University, Department of Respiratory medicine, Dermatology and Allergology, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, University of Helsinki, and Keuhkosairauksien yksikkö
Subjects: Pulmonary and Respiratory Medicine, therapy, IMPACT, MULTICENTER, EFFICACY, 3121 Internal medicine, Asthma, Treatment, pharmacotherapy, DOUBLE-BLIND, EXACERBATIONS, TRIALS, quality of life, Adrenal Cortex Hormones, QUALITY-OF-LIFE, 3121 General medicine, internal medicine and other clinical medicine, Pediatrics, Perinatology and Child Health, Humans, Immunology and Allergy, Anti-Asthmatic Agents, Pulmonary Eosinophilia, control, Finland, management, Retrospective Studies
Abstract: Objectives: Mepolizumab treatment provides clinical benefits for patients with severe eosinophilic asthma in randomized controlled trials. However, real-world data for patients in Finland are lacking. Methods: This retrospective, non-interventional, chart review study included patients with severe eosinophilic asthma ≥18 years of age initiating mepolizumab between January 1, 2016 and January 31, 2019 at three investigational sites in Finland. Patient characteristics during the 12 months prior to mepolizumab initiation (baseline) were recorded and primary and secondary endpoints included changes from baseline in disease outcomes during follow-up (up to 24 months following mepolizumab initiation). Exploratory endpoints included association between patient characteristics and exacerbation frequency/annual cumulative oral corticosteroid (OCS) dose. Results: Overall, 51 patients were included (mean 17.8 months follow-up). At baseline, patients had a mean (standard deviation) blood eosinophil count of 550 (410) cells/µL; impaired lung function and health-related quality of life; poor symptom control; frequent exacerbations (2.78/year); and 90% were using OCS (mean: 9.80 mg/day). At the last follow-up visit, reductions from baseline in blood eosinophil count (84%) and fractional exhaled nitric oxide (26%) were observed, as were improvements in Asthma Quality of Life Questionnaire score (36%) and Asthma Control Test score (34%). Reductions in the mean number of annual exacerbations (82%) and mean daily OCS dose (39%) were also seen; reductions were observed even after adjustment for several patient baseline characteristics. Conclusions: Results are consistent with previous randomized clinical trials, indicating that Finnish patients experience clinically relevant improvements when treated with mepolizumab in real-world clinical practice. publishedVersion
Published: 2022

11. Season of birth affects the risk of adult-onset asthma in Finland

Author: Koskinen, Anni, Lemmetyinen, Riikka, Luukkainen, Annika, Kankaanranta, Hannu, Ilmarinen, Pinja, Karjalainen, Jussi, Pekkanen, Juha, Huhtala, Heini, Haukka, Jari, But, Anna, Toppila-Salmi, Sanna, Faculty Common Matters (Faculty of Medicine), HUS Head and Neck Center, Department of Dermatology, Allergology and Venereology, University of Helsinki, Clinicum, Korva-, nenä- ja kurkkutautien klinikka, HUS Inflammation Center, Helsinki University Hospital Area, Department of Public Health, Jari Haukka / Principal Investigator, Department of Pathology, HUS Heart and Lung Center, Keuhkosairauksien yksikkö, and Medicum
Subjects: season of birth, 3121 General medicine, internal medicine and other clinical medicine, epidemiology, asthma, adult-onset asthma, DISEASE
Abstract: Non
Published: 2023

12. Tonsillar transcriptional profiles in atopic and non‐atopic subjects

Author: Hanif, Tanzeela, Ivaska, Lotta E, Ahmad, Freed, Tan, Ge, Mikola, Emilia, Puhakka, Tuomo, Palomares, Oscar, Akdis, Cezmi A, Toppila‐Salmi, Sanna, Jartti, Tuomas, University of Zurich, Hanif, Tanzeela, Department of Pathology, Medicum, HUS Inflammation Center, and Department of Dermatology, Allergology and Venereology
Subjects: EXPRESSION, 2403 Immunology, Immunology, atopy, CHILDREN, 610 Medicine & health, ASSOCIATION, VARIANTS, aeroallergen, 3142 Public health care science, environmental and occupational health, ALLERGY, IL-17, tonsil, transcriptome, 10183 Swiss Institute of Allergy and Asthma Research, CELLS, 2723 Immunology and Allergy, VIRUS, Immunology and Allergy, SIGNALING PATHWAY
Abstract: Background Emerging research suggests that local lymphatic tissue such as tonsils have important role in regulating the immune responses. However, allergen sensitization-induced alterations in transcriptome of tonsils are not known. Objectives To examine the key differences in tonsillar gene expression between atopic and non-atopic subjects and further by type of sensitization. Methods RNA-sequencing was performed on 52 tonsillar samples from atopic and non-atopic tonsillectomy patients. Sensitization to common food- and aero-allergen was defined by allergen specific IgE. Following groups were studied: (1) aero- and food-allergen sensitized (AS+FS) versus non-sensitized (NS), (2) aeroallergen-sensitized (AS) versus food-allergen sensitized (FS), (3) AS versus NS, (4) FS versus NS. Bioinformatics analysis was done using DESeq2(v3.10.2), WGCNA and GATK pipeline in R software (v3.3.1). Protein-protein interaction network was made from String database. Results We studied 13 aeroallergen-sensitized, 6 food-allergen sensitized, 4 both food-and aero-allergen-sensitized and 29 non-sensitized tonsillectomy patients. Overall, 697 unique differentially expressed genes (DEGs) were detected in all sensitized subgroups including chemokines (CXCL2, CXCL8, CXCL10, CXCL11), IL-20RA, MUC1 and MUC20. When comparing different groups, the gene expression profiles overlapped except the AS versus FS group comparison, suggesting significantly different gene expression between the two sensitization subgroups. Furthermore, aeroallergen-sensitized subjects had more prominent immune responses compared with non-sensitized and food-allergen sensitized subjects including gene expression for IL-17 pathway and Toll-like receptor signalling pathway. Conclusion Allergic sensitization is associated with extensive tonsillar transcriptomic alterations and changes in immune related genes and pathways. Distinct differences were found between aero-allergen and food-allergen sensitization., Allergy, 78 (2), ISSN:0105-4538, ISSN:1398-9995
Published: 2023

13. Molecular allergy diagnostics in predicting oral cow's milk outcome in Finnish children

Author: Nieminen, Otso, Palosuo, Kati, Kukkonen, Kaarina, Mäkelä, Mika, Medicum, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, and Clinicum
Subjects: Food challenges, Risk, Ige concentrations, Protein, 3121 General medicine, internal medicine and other clinical medicine, Double-blind, Egg, Clinical reactivity, Microarray, European academy, Tolerance
Abstract: Background: Oral food challenges (OFC) are required to diagnose food allergies but are resource-intensive. Objective: To reduce the need for OFCs, we sought to determine serum specific immunoglobulin E (sIgE) cutoff levels for cow's milk and its major allergens predicting oral milk challenge outcomes in children with suspected cow's milk allergy.Methods: A total of 135 Finnish children (median age, 1.8 years [range, 1.0-14.1 years]) with suspected cow's milk allergy underwent open OFC with unheated cow's milk. The sIgE levels to milk (f2), casein (Bos d 8), alpha-lactalbumin (Bos d 4), beta-lactoglobulin (Bos d 5), and bovine serum albumin (BSA) (Bos d 6) were measured and compared with the challenge outcomes.Results: Of the 135 OFCs, 5 were excluded from the study due to purely subjective symptoms. Of the 130 remaining OFCs, 98 results (75%) were positive. In a receiver operating characteristic analysis with 1-2-year-old children, no individual allergen sIgE had a better area under the curve than milk sIgE (0.824). A milk sIgE level > 6.30 kU/L gave 94% specificity and 33% sensitivity for positive OFCs. In 3-14-year-old children, a cutoff value >13.9 kU/L predicted a positive OFC result with 93% specificity and 25% sensitivity. Children with moderate-to-severe reactions had higher sIgE levels to milk, alpha-lactalbumin, and BSA than did children with mild reactions.Conclusion: Molecular allergy diagnostics did not improve the predictive performance compared with milk sIgE. The milk sIgE value that exceeds the cutoff for 95% specificity in combination with the clinical history may help to reduce the need for OFCs. The severity of an allergic reaction cannot reliably be predicted from sIgE measurements.
Published: 2023

14. In bronchiectasis, poor physical capacity correlates with poor quality of life

Author: Jarkko Mäntylä, Witold Mazur, Tanja Törölä, Paula Bergman, Paula Kauppi, HUS Heart and Lung Center, Department of Medicine, Keuhkosairauksien yksikkö, Clinicum, University of Helsinki, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, and Department of Public Health
Subjects: Pulmonary and Respiratory Medicine, SEVERITY INDEX, bronchiectasis severity index, exacerbation, quality of life, extensive disease, 3121 General medicine, internal medicine and other clinical medicine, QUESTIONNAIRE, VALIDATION, Bronchiectasis
Abstract: Purpose Patients with bronchiectasis (BE) who suffer frequent exacerbations are likely to experience negative effects on quality of life (QoL) and require more healthcare utilization. We aimed to discover, in a cohort of Finnish BE patients, those risk factors that influence QoL. Methods Non-cystic fibrosis BE patients of a Helsinki University Hospital cohort were examined with high-resolution computed tomography (HRCT) of the chest. They completed a disease-specific quality of life-bronchiectasis (QoL-B) questionnaire in Finnish translation. We considered scores in the lowest quarter (25%) of that QoL-B scale to indicate poor QoL. The bronchiectasis severity index (BSI), FACED score, and modified Medical Research Council (mMRC) dyspnoea scale were used. Results Overall, of 95 adult BE patients, mean age was 69 (SD +/- 13) and 79% were women. From the cohort, 82% presented with chronic sputum production and exacerbations, at a median rate of 1.7 (SD +/- 1.6). The number of exacerbations (OR 1.7), frequent exacerbations (>= 3 per year) (OR 4.9), high BSI score (OR 1.3), and extensive disease (>= 3 lobes) (OR 3.7) were all predictive of poor QoL. Frequent exacerbations were associated with bronchial bacterial colonisation, low forced expiratory volume in 1 s (FEV1), and radiological disease severity. Based on the BSI, 34.1% of our cohort had severe disease, with 11.6% classified as severe according to their FACED score. The mMRC dyspnoea score (r = -0.57) and BSI (r = -0.60) correlated, in the QoL-B questionnaire, negatively with physical domain. Conclusion The strongest determinants of poor QoL in the cohort of Finnish BE patients were frequent exacerbations, radiological disease severity, and high BSI score. Neither comorbidities nor BE aetiology appeared to affect QoL. Reduced physical capacity correlated with dyspnoea and severe disease. Study registration University of Helsinki, Faculty of Medicine, 148/16.08.2017.
Published: 2022

15. Management of anaphylaxis due to COVID-19 vaccines in the elderly

Author: Paulo Augusto Moreira Camargos, Radolslaw Gawlik, Mirko Petrovic, Gunter J. Sturm, Kristof Nekam, Sergio Bonini, Zhanat Ispayeva, Marilyn Urrutia Pereira, Jean Bousquet, Antti Lauerma, Menachem Rottem, Arzu Yorgancioglu, Hubert Blain, Antonio Cherubini, Mário Morais-Almeida, Nathalie Salles, Charlotte G. Mortz, Sylwia Smolinska, Davor Plavec, A. Bedbrook, Torsten Zuberbier, Helga Kraxner, M. Beatrice Bilò, Sinthia Bosnic-Anticevich, Gaëtan Gavazzi, Finbarr C. Martin, Alvaro A. Cruz, K. S. Bennoor, Isabella Annesi-Maesano, Mohamed H. Shamji, Karin Hoffmann-Sommergruber, Marina Atanaskovic-Markovic, Carsten Bindslev-Jensen, Lan Tt Le, Isabel Skypala, Ana Todo-Bom, Vincenzo Patella, Lorenzo Cecchi, Charlotte Suppli Ulrik, Oscar Palomares, Joaquin Sastre, Hans Jürgen Hoffmann, Knut Brockow, Eva Untersmayr, Martin Hrubisko, Bernadette Eberlein, Aziz Sheikh, Milan Sova, Osman M. Yusuf, Violeta Kvedariene, G. Walter Canonica, Dana Wallace, Ioana Agache, Milena Sokolowska, Jos M. G. A. Schols, Susan Waserman, Stéphanie Miot, Carla Irani, Regina E Roller-Winsberger, Michael Levin, Yves Rolland, Emma Montella, Bilun Gemicioglu, Bolesław Samoliński, Stefano Del Giacco, Madda lenaIllario, Yehia El-Gamal, Olga Lourenço, Jean-Christoph Roger J-P Caubet, Luisa Brussino, Marysia Recto, De Yun Wang, Igor Kaidashev, Renaud Louis, Antonino Romano, Mario E. Zernotti, Jacques Reynes, Pedro Carreiro-Martins, Alexandra F. Santos, Marek Niedoszytko, M. Gotua, Musa Khaitov, Thomas B. Casale, Andrea Matucci, Bernardo Sousa-Pinto, Rafael Stelmach, Dejan Dokic, Joana Vitte, Motohiro Ebisawa, Maria Teresa Ventura, Joaquim Mullol, Tomas Chivato, Petr Panzner, Oliver Pfaar, Sanna Toppila-Salmi, Ioanna Tsiligianni, Wytske Fokkens, Alessandra Vultaggio, H. Neffen, Juan Carlos Ivancevich, Ya-dong Gao, Anna Sediva, Maja Hofmann, Ana Maria Carriazo, João Fonseca, Marek Jutel, A. Benetos, Nhân Pham-Thi, Mona Al-Ahmad, Arunas Valiulis, Mihaela Zidarn, Elizabeth Angier, Yoshitaka Okamoto, Montserrat Fernandez-Rivas, Cezmi A. Akdis, Philip W. Rouadi, Olivier Guérin, John Farrell, Mikaela Odemyr, George Christoff, Vera Mahler, Claus Bachert, Edward F. Knol, Wienczyslawa Czarlewski, Robyn E O'Hehir, Victoria Cardona, Ludger Klimek, Tari Haahtela, Vincent Le Moing, Branislava Milenkovic, Carmen Rondon, Kaja Julge, Jolanta Walusiak-Skorupa, Nikolaos G. Papadopoulos, Aslı Gelincik, Markus Ollert, Piotr Kuna, Leyla Namazova-Baranova, Margitta Worm, Annick Barbaud, Elena Camelia Berghea, Todor A. Popov, Derek K. Chu, María José Torres, Faradiba Sarquis Serpa, Nicola Scichilone, Amir Hamzah Abdul Latiff, Frederico S. Regateiro, Gianni Passalacqua, Humboldt-Universität zu Berlin, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Center for Rhinology and Allergology Wiesbaden, University Hospital Mannheim, Humboldt University Of Berlin, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Transylvania University, Wrocław Medical University, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Cagliari, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Università Politecnica delle Marche [Ancona] (UNIVPM), Medical Consulting Czarlewski, Universiti Putra Malaysia, University of Southampton, Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Belgrade [Belgrade], Ghent University Hospital, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Dhaka Shishu Hospital [Bangladesh], University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), Odense University Hospital (OUH), Italian National Research Council, National Research Council [Italy] (CNR), The University of Sydney, Technische Universität München = Technical University of Munich (TUM), Università degli studi di Torino = University of Turin (UNITO), Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil] (UFMG), IRCCS Research Hospital, Milan, Vall d'Hebron University Hospital [Barcelona], Centro Hospitalar de Lisboa Central E.P.E, University of South Florida [Tampa] (USF), Geneva University Hospital (HUG), Azienda Usl Toscana centro [Firenze], Софийски университет = Sofia University, McMaster University [Hamilton, Ontario], State University of Bahia, Institute of Public Health of Republic of North Macedonia [Skopje], Ain Shams University (ASU), Sagamihara National Hospital [Kanagawa, Japan], Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Amsterdam UMC - Amsterdam University Medical Center, Universidade do Porto = University of Porto, Wuhan University [China], CHU Grenoble, Silesian University of Medicine, Istanbul Faculty of Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Centre Hospitalier Universitaire de Nice (CHU Nice), Helsinki University Hospital [Helsinki, Finlande], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Medizinische Universität Wien = Medical University of Vienna, Aarhus University [Aarhus], Oncology Institute of St Elisabeth, University of Naples Federico II = Università degli studi di Napoli Federico II, St Joseph University, Hôtel-Dieu de France (HDF), Université Saint-Joseph de Beyrouth (USJ), Kazakh National Medical University, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Tartu University Institute of Clinical Medicine, Ukrainina Medical Stomatological Academy [Poltava, Ukraine], Federal Medicobiological Agency [Moscow, Russian Federation], University Medical Center [Utrecht], Semmelweis University [Budapest], Medical University of Łódź (MUL), Vilnius University [Vilnius], University of Medicine and Pharmacy (VIETNAM), University of Cape Town, CHU Sart Tilman, Université de Liège, University of Beira Interior [Portugal] (UBI), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), uBibliorum, Ear, Nose and Throat, AII - Inflammatory diseases, CHU Montpellier, Wroclaw Medical University [Wrocław, Pologne], University of Bari Aldo Moro (UNIBA), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sagamihara National Hospital, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Toulouse [Toulouse], RS: CAPHRI - R1 - Ageing and Long-Term Care, Health Services Research, Bousquet J., Agache I., Blain H., Jutel M., Ventura M.T., Worm M., Del Giacco S., Benetos A., Bilo B.M., Czarlewski W., Abdul Latiff A.H., Al-Ahmad M., Angier E., Annesi-Maesano I., Atanaskovic-Markovic M., Bachert C., Barbaud A., Bedbrook A., Bennoor K.S., Berghea E.C., Bindslev-Jensen C., Bonini S., Bosnic-Anticevich S., Brockow K., Brussino L., Camargos P., Canonica G.W., Cardona V., Carreiro-Martins P., Carriazo A., Casale T., Caubet J.-C., Cecchi L., Cherubini A., Christoff G., Chu D.K., Cruz A.A., Dokic D., El-Gamal Y., Ebisawa M., Eberlein B., Farrell J., Fernandez-Rivas M., Fokkens W.J., Fonseca J.A., Gao Y., Gavazzi G., Gawlik R., Gelincik A., Gemicioglu B., Gotua M., Guerin O., Haahtela T., Hoffmann-Sommergruber K., Hoffmann H.J., Hofmann M., Hrubisko M., Illario M., Irani C., Ispayeva Z., Ivancevich J.C., Julge K., Kaidashev I., Khaitov M., Knol E., Kraxner H., Kuna P., Kvedariene V., Lauerma A., Le L.T.T., Le Moing V., Levin M., Louis R., Lourenco O., Mahler V., Martin F.C., Matucci A., Milenkovic B., Miot S., Montella E., Morais-Almeida M., Mortz C.G., Mullol J., Namazova-Baranova L., Neffen H., Nekam K., Niedoszytko M., Odemyr M., O'Hehir R.E., Okamoto Y., Ollert M., Palomares O., Papadopoulos N.G., Panzner P., Passalacqua G., Patella V., Petrovic M., Pfaar O., Pham-Thi N., Plavec D., Popov T.A., Recto M.T., Regateiro F.S., Reynes J., Roller-Winsberger R.E., Rolland Y., Romano A., Rondon C., Rottem M., Rouadi P.W., Salles N., Samolinski B., Santos A.F., S Sarquis F., Sastre J., M. G. A. Schols J., Scichilone N., Sediva A., Shamji M.H., Sheikh A., Skypala I., Smolinska S., Sokolowska M., Sousa-Pinto B., Sova M., Stelmach R., Sturm G., Suppli Ulrik C., Todo-Bom A.M., Toppila-Salmi S., Tsiligianni I., Torres M., Untersmayr E., Urrutia Pereira M., Valiulis A., Vitte J., Vultaggio A., Wallace D., Walusiak-Skorupa J., Wang D.-Y., Waserman S., Yorgancioglu A., Yusuf O.M., Zernotti M., Zidarn M., Chivato T., Akdis C.A., Zuberbier T., Klimek L., HUS Inflammation Center, University of Helsinki, and Department of Dermatology, Allergology and Venereology
Subjects: Male, Allergy, Pediatrics, Eaaci Position Paper, COVID-19 vaccines, older (adults, GUIDELINES, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine and Health Sciences, Immunology and Allergy, Medicine, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Geriatrics, MESH: Aged, RISK, Vaccines, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, people), EPINEPHRINE, Epinephrine, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, COVID -19 vaccines, Anaphylaxis, medicine.drug, older (adults/people), medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), MESH: Covid-19, MESH: Epinephrine, Immunology, adrenaline, anaphylaxis, Aged, COVID-19 Vaccines, Humans, SARS-CoV-2, COVID-19, Settore MED/10 - Malattie Dell'Apparato Respiratorio, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Diabetes mellitus, Anaphylaxis/etiology, MESH: SARS-CoV-2, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, COVID‐19 vaccines, Older - Adults/people, Asthma, MESH: Humans, business.industry, adrenaline, anaphylaxis, COVID-19 vaccines, older (adults/people), medicine.disease, Obesity, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, MESH: Anaphylaxis, Older, 3121 General medicine, internal medicine and other clinical medicine, business, MESH: Covid-19 vaccines, 030215 immunology
Abstract: Submitted by (omml@ubi.pt) on 2021-07-05T10:47:24Z No. of bitstreams: 1 2021_Bousquet J_A_COVID anaphylaxis.pdf: 12561118 bytes, checksum: 2f801ee76ad2cb3cbdaa02ffabea8e09 (MD5) Approved for entry into archive by Pessoa (pfep@ubi.pt) on 2021-07-05T10:49:11Z (GMT) No. of bitstreams: 1 2021_Bousquet J_A_COVID anaphylaxis.pdf: 12561118 bytes, checksum: 2f801ee76ad2cb3cbdaa02ffabea8e09 (MD5) Rejected by Pessoa (pfep@ubi.pt), reason: Rever os nomes dos autores. Depois da correção é só voltar a submeter. on 2021-07-05T10:54:19Z (GMT) Submitted by (omml@ubi.pt) on 2021-07-05T11:52:24Z No. of bitstreams: 1 2021_Bousquet J_A_COVID anaphylaxis.pdf: 12561118 bytes, checksum: 2f801ee76ad2cb3cbdaa02ffabea8e09 (MD5) Approved for entry into archive by Pessoa (pfep@ubi.pt) on 2021-07-05T13:34:51Z (GMT) No. of bitstreams: 1 2021_Bousquet J_A_COVID anaphylaxis.pdf: 12561118 bytes, checksum: 2f801ee76ad2cb3cbdaa02ffabea8e09 (MD5) Approved for entry into archive by Pessoa (pfep@ubi.pt) on 2021-07-05T13:35:49Z (GMT) No. of bitstreams: 1 2021_Bousquet J_A_COVID anaphylaxis.pdf: 12561118 bytes, checksum: 2f801ee76ad2cb3cbdaa02ffabea8e09 (MD5) Made available in DSpace on 2021-07-05T13:35:49Z (GMT). No. of bitstreams: 1 2021_Bousquet J_A_COVID anaphylaxis.pdf: 12561118 bytes, checksum: 2f801ee76ad2cb3cbdaa02ffabea8e09 (MD5) Previous issue date: 2021-04-02 info:eu-repo/semantics/publishedVersion
Published: 2021

16. Atopic dermatitis in adults: a population‐based study in Finland

Author: Markku Heliövaara, Paivikki Susitaival, Ville Kiiski, Alexander Salava, Satu Barnhill, Anita Remitz, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, and Clinicum
Subjects: DIAGNOSTIC-CRITERIA, Living environment, Adult population, CHILDREN, ECZEMA, Dermatology, Daily smoking, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, medicine, VITAMIN-D, Socioeconomic status, National health, Serum vitamin, business.industry, PERSISTENCE, ASSOCIATION, Atopic dermatitis, medicine.disease, PREVALENCE, 3. Good health, Population based study, 030228 respiratory system, ADOLESCENCE, DISEASES, 3121 General medicine, internal medicine and other clinical medicine, FOLLOW-UP, business, Demography
Abstract: Background The prevalence of atopic dermatitis (AD) has increased, but studies in adult or elderly populations are sparse. Methods We investigated 12-month and lifetime prevalences of AD in the Finnish adult population ≥30 years of age and analyzed living environment factors, socioeconomic factors, lifestyle-related factors, and serum vitamin D levels for their associations with AD in a national health examination survey. Results The lifetime prevalence was 21.9% and 12-month prevalence 10.1%. The highest prevalence (lifetime 28.6%, 12-month 15.4%) was seen in subjects 30-39 years of age. Prevalence decreased with age. Subjects with highly educated parents were more likely to have active AD, though there was no effect of higher education in subjects themselves. Younger age and being an ex-smoker were associated with active AD. Female sex and daily smoking increased the risk in subjects 30-49 years of age. There was no dose– response relationship to serum vitamin D levels and no association with the living environment. Conclusions Our data show that the number of adult patients with atopic dermatitis has grown and prevalence numbers of AD in Finnish adults are among the highest reported. Together with the aging of the society, the burden of AD is not limited to childhood.
Published: 2021

17. Supportive care in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis

Author: Neil H. Shear, P. Joly, Alain Brassard, P. Wolkenstein, Kanade Shinkai, L. S. Vidal, K. Zaghbib, C. Salavastru, J. Newman, A. Colin, J.N. Bouwes Bavinck, N. Hama, Arturo R. Dominguez, J. T. Schulz, Roni P. Dodiuk-Gad, Lars E. French, Emanual Michael Maverakis, D. Meyersburg, Chia-Yu Chu, K. Pallesen, M. C. Brüggen, R. Le Floch, Robert G. Micheletti, E. Bequignon, B. Milpied, Tetsuo Shiohara, Benjamin H. Kaffenberger, Paolo Romanelli, C. Bodemer, S. L. Chua, Arash Mostaghimi, E. Howard, Elizabeth J. Phillips, Annamari Ranki, Mirjam Nägeli, R. Sheridan, J. Gueudry, S. Ingen-Housz-Oro, Barbara Horváth, A. Toussi, Amy S. Paller, Jonathan Cotliar, Anette Bygum, Danielle M. Tartar, N. de Prost, Robert S. Stern, S. Walsh, Wen-Hung Chung, Scott Worswick, Riichiro Abe, M. Arden-Jones, Megan H. Noe, C. Moss, George-Sorin Tiplica, E. Brezinova, B. Didona, S. T. Le, Hôpital Henri Mondor, Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, Helsinki University Hospital Area, University of Helsinki, Translational Immunology Groningen (TRIGR), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Université de Reims Champagne-Ardenne (URCA)
Subjects: Adult, medicine.medical_specialty, Consensus, education, MEDLINE, Dermatology, Phase (combat), 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Multidisciplinary approach, Humans, Medicine, Infection control, Child, Retrospective Studies, computer.programming_language, Modalities, business.industry, Research, Stevens johnson, 16. Peace & justice, medicine.disease, Toxic epidermal necrolysis, 3. Good health, Stevens-Johnson Syndrome, 3121 General medicine, internal medicine and other clinical medicine, Family medicine, business, computer, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Delphi
Abstract: Background Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking.Objectives Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN.Methods Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method.Results Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements.Conclusions We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.
Published: 2021

18. Pilot study in human healthy volunteers on the use of magnetohydrodynamics in needle-free continuous glucose monitoring

Author: Hakala, Tuuli A., Zschaechner, Laura K., Vänskä, Risto T., Nurminen, Teemu A., Wardale, Melissa, Morina, Jonathan, Boeva, Zhanna A., Saukkonen, Reeta, Alakoskela, Juha-Matti, Pettersson-Fernholm, Kim, Haeggström, Edward, Bobacka, Johan, Perez, Alejandro Garcia, Department of Physics, Faculty of Medicine, Department of Dermatology, Allergology and Venereology, HUS Inflammation Center, Department of Medicine, and HUS Abdominal Center
Subjects: Blood Glucose, Glucose, Diabetes Mellitus, Type 1, Multidisciplinary, 3121 General medicine, internal medicine and other clinical medicine, Blood Glucose Self-Monitoring, Humans, Pilot Projects, 114 Physical sciences, Healthy Volunteers
Abstract: The benefits of continuous glucose monitoring (CGM) in diabetes management are extensively documented. Yet, the broader adoption of CGM systems is limited by their cost and invasiveness. Current CGM devices, requiring implantation or the use of hypodermic needles, fail to offer a convenient solution. We have demonstrated that magnetohydrodynamics (MHD) is effective at extracting dermal interstitial fluid (ISF) containing glucose, without the use of needles. Here we present the first study of ISF sampling with MHD for glucose monitoring in humans. We conducted 10 glucose tolerance tests on 5 healthy volunteers and obtained a significant correlation between the concentration of glucose in ISF samples extracted with MHD and capillary blood glucose samples. Upon calibration and time lag removal, the data indicate a Mean Absolute Relative Difference (MARD) of 12.9% and Precision Absolute Relative Difference of 13.1%. In view of these results, we discuss the potential value and limitations of MHD in needle-free glucose monitoring.
Published: 2022

19. Cohort study of diagnostic delay in the clinical pathway of patients with chronic wounds in the primary care setting

Author: Kirsti Ahmajärvi, Kirsi Isoherranen, Maarit Venermo, Department of General Practice and Primary Health Care, Helsinki University Hospital Area, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, University of Helsinki, Verisuonikirurgian yksikkö, HUS Abdominal Center, and Clinicum
Subjects: Delayed Diagnosis, Primary Health Care, Records, General Medicine, Primary care, Cohort Studies, Diabetic foot, Vascular surgery, 3121 General medicine, internal medicine and other clinical medicine, Critical Pathways, Quality in health care, Humans, Health & safety, Wound management
Abstract: ObjectivesExact wound diagnosis is essential for successful wound management and a holistic care of the patient suffering from a wound. Wound management has been traditionally seen as a nursing area, but this can lead to considerable delays in wound diagnostics. A diagnostic delay has been recognised as an element of diagnostic error, which, in turn, affects patient safety. The aim of this cohort study was to examine diagnostic delays of chronic wound within primary care.SettingA specialised diagnostic unit, a wound care team, was established in the primary healthcare with the objective of reducing diagnostic and treatment delays in primary care.ParticipantsThe data consists of 197 consecutive patients attending their first appointment with the wound care team in 2016. The collected data included basic demographics, information about the clinical pathway, including doctor’s appointments in primary and specialised care, as well as the International Classification of Diseases 10th Revision (ICD-10) diagnostic codes.Primary and secondary outcome measuresThe diagnostic delays were calculated in days and divided into three groups: (1) patient-related delay, (2) diagnostic delay and (3) organisational delay.ResultsThe median duration of a patient-related delay was 2 days (IQR 0–14), whereas a physician’s first evaluation was performed at a median of 8 (1–32) days from wound appearance and the correct diagnosis by the wound care team was established in a median of 57 (33–100) days. The organisational delay from first contact to diagnosis was a median of 41 (22–80) days. Only one in three patients had a diagnostic delay of less than 4 weeks.ConclusionsAccording to this study, the diagnostic delay occurs within primary care, as an organisational delay from first contact to correct diagnosis. It is possible to arrange an optimal pathway of care in which a holistic wound care process starts within primary care.
Published: 2022

20. Chemical characterization of inks in skin reactions to tattoo

Author: Hester Colboc, Dominique Bazin, Solenn Reguer, Ivan T. Lucas, Philippe Moguelet, Reyhan Amode, Chantal Jouanneau, Angèle Soria, François Chasset, Emmanuelle Amsler, Catherine Pecquet, Sélim Aractingi, Ludovic Bellot-Gurlet, Lydia Deschamps, Vincent Descamps, Nicolas Kluger, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, Clinicum, and University of Helsinki
Subjects: Nuclear and High Energy Physics, Tattoos, Radiation, Tattooing, Spectrometry, X-Ray Emission, X-ray absorption spectroscopy, Spectrum Analysis, Raman, X-ray fluorescence spectroscopy, Soot, 3121 General medicine, internal medicine and other clinical medicine, Raman spectroscopy, Humans, Ink, Instrumentation, Cutaneous hypersensitivity reactions
Abstract: Skin reactions are well described complications of tattooing, usually provoked by red inks. Chemical characterizations of these inks are usually based on limited subjects and techniques. This study aimed to determine the organic and inorganic composition of inks using X-ray fluorescence spectroscopy (XRF), X-ray absorption spectroscopy (XANES) and Raman spectroscopy, in a cohort of patients with cutaneous hypersensitivity reactions to tattoo. A retrospective multicenter study was performed, including 15 patients diagnosed with skin reactions to tattoos. Almost half of these patients developed skin reactions on black inks. XRF identified known allergenic metals – titanium, chromium, manganese, nickel and copper – in almost all cases. XANES spectroscopy distinguished zinc and iron present in ink from these elements in endogenous biomolecules. Raman spectroscopy showed the presence of both reported (azo pigments, quinacridone) and unreported (carbon black, phtalocyanine) putative organic sensitizer compounds, and also defined the phase in which Ti was engaged. To the best of the authors' knowledge, this paper reports the largest cohort of skin hypersensitivity reactions analyzed by multiple complementary techniques. With almost half the patients presenting skin reaction on black tattoo, the study suggests that black modern inks should also be considered to provoke skin reactions, probably because of the common association of carbon black with potential allergenic metals within these inks. Analysis of more skin reactions to tattoos is needed to identify the relevant chemical compounds and help render tattoo ink composition safer.
Published: 2022

21. Presentation of airway and general symptoms in COVID-19 caused by dominant SARS-CoV-2 variants : A follow-up on ARIA consensus

Author: Jan, Hagemann, Gabrielle, Onorato, Christopher, Seifen, Sven, Becker, Tilman, Huppertz, Heidi, Olze, Piotr, Kuna, Joaquim, Mullol, Sanna, Toppila Salmi, Joao, Fonseca, Philip, Rouadi, Torsten, Zuberbier, Jean, Bousquet, Ludger, Klimek, Yoshitaka, Okamoto, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, and University of Helsinki
Subjects: 3121 General medicine, internal medicine and other clinical medicine, Immunology, Immunology and Allergy
Published: 2022

22. Factors associated with severity of atopic dermatitis – a Finnish cross-sectional study

Author: A. Salava, V. Salo, J. Leppänen, A. Lauerma, A. Remitz, Faculty Common Matters (Faculty of Medicine), Teachers' Academy, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, and Clinicum
Subjects: Male, Dermatology, Immunoglobulin E, Asthma, Dermatitis, Atopic, SENSITIZATION, Infectious Diseases, Cross-Sectional Studies, NULL MUTATIONS, 3121 General medicine, internal medicine and other clinical medicine, DISEASE SEVERITY, Humans, COHORT, Finland, Retrospective Studies
Abstract: Publisher Copyright: © 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology. Background: Severity-associated factors in atopic dermatitis (AD) have focussed on early onset, concomitant atopic diseases, markers of Th2-shifted inflammation and filaggrin mutations. Objectives: To investigate factors associated with severe AD in Finnish patients. Methods: We conducted a single-centre, cross-sectional observational study with 502 AD patients aged 4.79 to 79.90 years (mean 32.08 years). Disease severity was assessed with the Rajka–Langeland severity score and EASI and associated clinical signs were evaluated. Data regarding onset, relatives, atopic and other comorbidities was gathered retrospectively. We investigated total serum IgE-levels, a panel of filaggrin null mutations and functional variants of genes associated with skin barrier defects. Results: Factors more frequent in severe AD included early onset (P = 0.004, 95%CI 0.000–0.024), male sex (P = 0.002, 95%CI 0.000–0.11), history of smoking (P = 0.012, 95%CI 0.000–0.024), concomitant asthma (P = 0.001, 95%CI 0.000–0.011), palmar hyperlinearity (P = 0.013, 95%CI 0.014–0.059), hand dermatitis (P = 0.020, 95%CI 0.000–0.029) and history of contact allergy (P = 0.042, 95%CI 0.037–0.096). Body mass indices (P < 0.000, 95%CI 0.000–0.011) and total serum IgE-levels (P < 0.000, 95%CI 0.000–0.011) were higher in severe AD. No differences were observed for allergic rhinitis, allergic conjunctivitis, food allergy, peanut allergy, prick positivity, keratosis pilaris, history of herpes simplex infections, filaggrin null mutations and other gene variants. Conclusions: Severity determinants in Finnish patients seem to be early-onset, male sex, smoking, overweight, concomitant asthma, palmar hyperlinearity, hand dermatitis and high IgE-levels. A sub-typing of patients in relation to confirmed severity determinants may be useful for course prediction, prognosis and targeted AD management.
Published: 2022

23. Case report: A novel de novo IGF2 missense variant in a Finnish patient with Silver-Russell syndrome

Author: Loid, Petra, Lipsanen-Nyman, Marita, Ala-Mello, Sirpa, Hannula-Jouppi, Katariina, Kere, Juha, Mäkitie, Outi, Muurinen, Mari, Clinicum, HUS Children and Adolescents, Children's Hospital, Medicum, University of Helsinki, CAMM - Research Program for Clinical and Molecular Metabolism, Lastentautien yksikkö, HUSLAB, Department of Medical and Clinical Genetics, Helsinki University Hospital Area, Department of Dermatology, Allergology and Venereology, HUS Inflammation Center, Research Programs Unit, STEMM - Stem Cells and Metabolism Research Program, and Juha Kere / Principal Investigator
Subjects: short stature, intrauterine growth restriction, 3123 Gynaecology and paediatrics, Pediatrics, Perinatology and Child Health, IGF2, Silver-Russell, IGF2 MUTATION, exome sequencing
Abstract: Silver-Russell syndrome (SRS, OMIM 180860) is a rare imprinting disorder characterized by intrauterine and postnatal growth restriction, feeding difficulties in early childhood, characteristic facial features, and body asymmetry. The molecular cause most commonly relates to hypomethylation of the imprinted 11p15.5 IGF2/H19 domain but remains unknown in about 40% of the patients. Recently, heterozygous paternally inherited pathogenic variants in IGF2, the gene encoding insulin-like growth factor 2 (IGF2), have been identified in patients with SRS. We report a novel de novo missense variant in IGF2 (c.122T > G, p.Leu41Arg) on the paternally derived allele in a 16-year-old boy with a clinical diagnosis of SRS. The missense variant was identified by targeted exome sequencing and predicted pathogenic by multiple in silico tools. It affects a highly conserved residue on a domain that is important for binding of other molecules. Our finding expands the spectrum of disease-causing variants in IGF2. Targeted exome sequencing is a useful diagnostic tool in patients with negative results of common diagnostic tests for SRS.
Published: 2022

24. Bronchial hyperresponsiveness and asthma during oral immunotherapy for egg or peanut allergy in children

Author: Janne Burman, Kati Palosuo, Anna Pelkonen, Pekka Malmberg, Sami Remes, Kaarina Kukkonen, Mika J. Mäkelä, Department of Dermatology, Allergology and Venereology, Clinicum, Helsinki University Hospital Area, and HUS Inflammation Center
Subjects: EXHALED NITRIC-OXIDE, Pulmonary and Respiratory Medicine, bronchial hyperresponsiveness, food allergy, 3121 General medicine, internal medicine and other clinical medicine, Immunology, oral immunotherapy, Immunology and Allergy, asthma, methacholine challenge test, POPULATION
Abstract: Background Bronchial hyperresponsiveness (BHR) and asthma are frequently present in children with food allergy. We assessed BHR in children receiving oral immunotherapy (OIT) for persistent egg or peanut allergy and examined whether OIT affects asthma control. Methods Methacholine challenge testing was performed in 89 children with persistent egg or peanut allergy diagnosed by double-blind, placebo-controlled food challenge and 80 control children without food allergy. Of the 89 food-allergic children, 50 started OIT for egg allergy and 39 for peanut allergy. Sensitization to aeroallergens was evaluated by skin prick testing. Forty of the 89 children with regular controller treatment for asthma underwent methacholine challenge testing and 34 measurement of exhaled nitric oxide (FeNO) at baseline and after 6-12 months of OIT. Results Methacholine challenge testing revealed significant BHR in 29/50 children (58%) with egg allergy, 15/39 children (38%) with peanut allergy, and 6/80 controls (7.5%). The mean cumulative dose of methacholine causing a 20% fall in FEV1 differed significantly between the egg and peanut-allergic versus the control children (1009 mu g, 1104 mu g, and 2068 mu g, respectively, p < 0.001). Egg or peanut OIT did not affect lung function, the degree of BHR or FeNO levels in children with asthma and had no adverse effect on asthma control. Lung function or BHR did not associate with the OIT outcome. Conclusion BHR was significantly more frequent in children with persistent egg or peanut allergy than in children without food allergy. Oral immunotherapy did not increase BHR and was safe for children on regular asthma medication.
Published: 2022

25. Management of allergic rhinitis symptoms in the pharmacy Pocket guide 2022

Author: Lourenço, Olga, Cvetkovski, Biljana, Kritikos, Vicky, House, Rachel, Scheire, Sophie, Costa, Elísio, Fonseca, Joao A, Menditto, Enrica, Bedbrook, Anna, Bialek, Slawomir, Briedis, Vitalis, Boussery, Koen, Canonica, G. Walter, Haahtela, Tari, Kuna, Piotr, Mullol, Joaquim, Orlando, Valentina, Samolinski, Boleslaw, Wallace, Dana, Duggan, Catherine, Paulino, Ema, Pinto, Gonçalo S., Söderlund, Lars‐Åke, Bousquet, Jean, Bosnic‐Anticevich, Sinthia, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, Helsinki University Hospital Area, Clinicum, University of Helsinki, uBibliorum, and Publica
Subjects: Pulmonary and Respiratory Medicine, allergic rhinitis, Allergy, IMPACT, pharmacist, Immunology, Biology and Life Sciences, QUALITY-OF-LIFE, 3121 General medicine, internal medicine and other clinical medicine, Medicine and Health Sciences, Immunology and Allergy, community pharmacy, ASTHMA, EPIDEMIOLOGY
Abstract: This research received no specific grant from any funding agency in the public, commercial, or not‐for‐profit sectors. Open access funding enabled and organized by Projekt DEAL, Background: Allergic rhinitis (AR) management requires a coordinated effort from healthcare providers and patients. Pharmacists are key members of these integrated care pathways resolving medication-related problems, optimizing regimens, improving adherence and recommending therapies while establishing liaisons between patients and physicians. Methods: Allergic Rhinitis and its Impact on Asthma (ARIA) first published a reference document on the pharmacist's role in allergic rhinitis management in 2004. Several guidelines were developed over the past 20 years improving the care of allergic rhinitis patients through an evidence-based, integrated care approach. Results: This ARIA/EAACI/FIP Position Paper is based on the latest ARIA in the Pharmacy guidelines and provides: (a) a structured approach to pharmacists identifying people with AR and/or allergic conjunctivitis as well as those at risk of poor disease control; (b) an evidence-based clinical decision support tool for optimising the management of allergic rhinitis in the community pharmacy; and (c) a framework of referral to the physician. Conclusion: This document is not intended to be a mandatory standard of care but is provided as a basis for pharmacists and their staff to develop relevant local standards of care for their patients, within their local practice environment. Pharmacy care varies between countries, and the guide should be adapted to the local situation.
Published: 2022

26. Long-term changes in milk component immunoglobulins reflect milk oral immunotherapy outcomes in Finnish children

Author: Tiina Kaisa Kauppila, Victoria Hinkkanen, Terhi Savinko, Piia Karisola, Anna Kaarina Kukkonen, Marita Paassilta, Anna S. Pelkonen, Mika J. Mäkelä, Tampere University, Clinical Medicine, Department of Respiratory medicine, Dermatology and Allergology, Department of Dermatology, Allergology and Venereology, HUS Inflammation Center, HUMI - Human Microbiome Research, Clinicum, Helsinki University Hospital Area, University of Helsinki, HUS Children and Adolescents, and Children's Hospital
Subjects: COWS, Immunology, immunoglobulins, oral immunotherapy, long-term follow-up, NATURAL-HISTORY, 3121 Internal medicine, cow's milk allergy, DESENSITIZATION, ALLERGY, DOUBLE-BLIND, 3121 General medicine, internal medicine and other clinical medicine, milk components, Immunology and Allergy, CASEIN, TOLERANCE
Abstract: Background: Milk oral immunotherapy (OIT) may increase the amount of milk protein that can be ingested without triggering an allergic reaction. It is important to understand why some patients benefit from the treatment while others do not. Objective: The aim was to define the differences in the milk allergen component-specific (casein, α-lactalbumin, ß-lactoglobulin) immunoglobulin (sIg [sIgE, sIgG4, and sIgA]) levels relative to the long-term outcomes of milk OIT. Methods: In this long-term, open-label follow-up study, 286 children started milk OIT between 2005 and 2015. Follow-up data were collected at two points: the post-buildup phase and long term (range 1–11 years, median 6 years). Comparisons of sIg levels were made among three outcome groups of self-reported long-term milk consumption (high-milk dose, low-milk dose, and avoidance). Results: A total of 168 (59%) of the 286 patients on OIT participated. Most patients (57%) were in the high-dose group; here, 80% of these patients had a baseline casein sIgE value less than 28 kUA/L, they had the lowest casein sIgE levels at all time (p
Published: 2022

27. Early-onset atopic dermatitis and food hypersensitivity increase the risk of atopic march

Author: Pesonen, Maria, Kallio, Markku J. T., Ranki, Annamari, Siimes, Martti A., Järvinen, Kirsi M., HUS Children and Adolescents, Children's Hospital, University of Helsinki, Helsinki University Hospital Area, Department of Dermatology, Allergology and Venereology, and HUS Inflammation Center
Subjects: ALLERGY, skin prick test, children, recurrent wheezing, 3121 General medicine, internal medicine and other clinical medicine, allergic rhinoconjunctivitis, adolescents, asthma, sensitization
Abstract: Non
Published: 2022

28. Keratosis pilaris and filaggrin loss-of-function mutations in patients with atopic dermatitis - Results of a Finnish cross-sectional study

Author: Alexander Salava, Ville Salo, Anita Remitz, Department of Dermatology, Allergology and Venereology, University of Helsinki, HUS Inflammation Center, and Clinicum
Subjects: filaggrin, VULGARIS, atopic dermatitis, Dermatology, General Medicine, Filaggrin Proteins, GENE, Dermatitis, Atopic, Cross-Sectional Studies, Intermediate Filament Proteins, CLINICAL CHARACTERISTICS, 3121 General medicine, internal medicine and other clinical medicine, Humans, Abnormalities, Multiple, Genetic Predisposition to Disease, observational study, Eyebrows, keratosis pilaris, mutation, Darier Disease, Finland
Abstract: Keratosis pilaris (KP) associates with epidermal barrier defects in atopic dermatitis (AD) but its role in disease severity and concomitant atopic diseases seems to vary between populations. We performed a cross-sectional observational study with 502 randomly selected AD patients of a Finnish tertiary health care center. At a single clinical examination, disease severity (Rajka Langeland severity score and EASI), clinical signs and patient history were evaluated and total IgE levels and frequent filaggrin (FLG) loss-of-function mutations were investigated. There was no link with disease severity (p = 0.649, 95% CI 0.569-0.654), asthma (p = 0.230, 95% CI 0.206-0.281) or atopic sensitization (p = 0.351, 95% CI 0.309-0.392). Keratosis pilaris was significantly associated with palmar hyperlinearity (p < 0.000, 95% CI 0.000-0.006, OR 4.664, 95% CI 2.072-10.496) and the filaggrin loss-of-function mutation 2282del4 (p < 0.000, 95% CI 0.000-0.009, OR 4.917, 95%CI 1.961-12.330). The prevalence of KP in the cohort was generally low and KP seems to be infrequent in Finnish AD patients. This may be explained by the fact that the tested FLG loss-of-function mutations are rarer in the Finnish population compared for example, with central Europe or Asia. Mutations in other locations of the FLG gene or other genes of the epidermal barrier may play a more important role.
Published: 2022

29. SARS-CoV-2 requires acidic pH to infect cells

Author: Alex J.B. Kreutzberger, Anwesha Sanyal, Anand Saminathan, Louis-Marie Bloyet, Spencer Stumpf, Zhuoming Liu, Ravi Ojha, Markku T. Patjas, Ahmed Geneid, Gustavo Scanavachi, Catherine A. Doyle, Elliott Somerville, Ricardo Bango Da Cunha Correira, Giuseppe Di Caprio, Sanna Toppila-Salmi, Antti Mäkitie, Volker Kiessling, Olli Vapalahti, Sean P.J. Whelan, Giuseppe Balistreri, Tom Kirchhausen, Department of Virology, HUS Head and Neck Center, Korva-, nenä- ja kurkkutautien klinikka, Faculty Common Matters (Faculty of Medicine), HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, Clinicum, Veterinary Biosciences, Veterinary Microbiology and Epidemiology, Helsinki One Health (HOH), Viral Zoonosis Research Unit, HUSLAB, Olli Pekka Vapalahti / Principal Investigator, and Helsinki Institute of Sustainability Science (HELSUS)
Subjects: Furin, 11832 Microbiology and virology, Multidisciplinary, SARS-CoV-2, Serine Endopeptidases, infection route, COVID-19, Hydrogen-Ion Concentration, Virus Internalization, virus entry, Article, live-cell imaging, 3D imaging, Spike Glycoprotein, Coronavirus, Humans, 3125 Otorhinolaryngology, ophthalmology, Nasal Cavity
Abstract: SARS-CoV-2 cell entry starts with membrane attachment and ends with spike-protein (S) catalyzed membrane fusion depending on two cleavage steps, one usually by furin in producing cells and the second by TMPRSS2 on target cells. Endosomal cathepsins can carry out both. Using real-time 3D single virion tracking, we show fusion and genome penetration requires virion exposure to an acidic milieu of pH 6.2-6.8, even when furin and TMPRSS2 cleavages have occurred. We detect the sequential steps of S1-fragment dissociation, fusion, and content release from the cell surface in TMPRRS2 overexpressing cells only when exposed to acidic pH. We define a key role of an acidic environment for successful infection, found in endosomal compartments and at the surface of TMPRSS2 expressing cells in the acidic milieu of the nasal cavity.Significance StatementInfection by SARS-CoV-2 depends upon the S large spike protein decorating the virions and is responsible for receptor engagement and subsequent fusion of viral and cellular membranes allowing release of virion contents into the cell. Using new single particle imaging tools, to visualize and track the successive steps from virion attachment to fusion, combined with chemical and genetic perturbations of the cells, we provide the first direct evidence for the cellular uptake routes of productive infection in multiple cell types and their dependence on proteolysis of S by cell surface or endosomal proteases. We show that fusion and content release always require the acidic environment from endosomes, preceded by liberation of the S1 fragment which depends on ACE2 receptor engagement.One sentence summaryDetailed molecular snapshots of the productive infectious entry pathway of SARS-CoV-2 into cells
Published: 2022

30. Bet v 1 triggers antiviral-type immune signalling in birch-pollen-allergic individuals

Author: Lukas Wisgrill, Nanna Fyhrquist, Joseph Ndika, Laura Paalanen, Angelika Berger, Tiina Laatikainen, Piia Karisola, Tari Haahtela, Harri Alenius, HUMI - Human Microbiome Research, Medicum, HUS Inflammation Center, and Department of Dermatology, Allergology and Venereology
Subjects: EXPRESSION, Adolescent, Immunology, immune network, systems immunology, Antiviral Agents, DENDRITIC CELLS, DISPARITIES, Bet v 1, Hypersensitivity, Immunology and Allergy, Humans, TRANSCRIPTOME, DNA METHYLATION, Betula, Plant Proteins, T-CELL RESPONSES, CHILDHOOD ASTHMA, Allergens, Antigens, Plant, Immunoglobulin E, MICROBIOTA, macrophages, SENSITIZATION, GENOME, 3121 General medicine, internal medicine and other clinical medicine, Leukocytes, Mononuclear, Pollen, birch allergy
Abstract: Background In allergic patients, clinical symptoms caused by pollen remind of symptoms triggered by viral respiratory infections, which are also the main cause of asthmatic exacerbations. In patients sensitized to birch pollen, Bet v 1 is the major symptom-causing allergen. Immune mechanisms driving Bet v 1-related responses of human blood cells have not been fully characterized. Objective To characterize the immune response to Bet v 1 in peripheral blood in patients allergic to birch pollen. Methods The peripheral blood mononuclear cells of birch-allergic (n = 24) and non-allergic (n = 47) adolescents were stimulated ex-vivo followed by transcriptomic profiling. Systems-biology approaches were employed to decipher disease-relevant gene networks and deconvolution of associated cell populations. Results Solely in birch-allergic patients, co-expression analysis revealed activation of networks of innate immunity and antiviral signalling as the immediate response to Bet v 1 stimulation. Toll-like receptors and signal transducer transcription were the main drivers of gene expression patterns. Macrophages and dendritic cells were the main cell subsets responding to Bet v 1. Conclusions and clinical relevance In birch-pollen-allergic patients, the activated innate immune networks seem to be, in part, the same as those activated during viral infections. This tendency of the immune system to read pollens as viruses may provide new insight to allergy prevention and treatment.
Published: 2022

31. Managing the allergy and asthma epidemic in 2020s-Lessons from the Finnish experience

Author: Haahtela, Tari, Jantunen, Juha, Saarinen, Kimmo, Tommila, Erja, Valovirta, Erkka, Vasankari, Tuula, Makela, Mika J., HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, and Clinicum
Subjects: RISK, allergy campaign, allergy prevention, PROGRAM 2008-2018, public health, CHILDREN, PEANUT ORAL IMMUNOTHERAPY, FINLAND, PREVENTION, SENSITIZATION, allergy epidemic, allergy programme, 3121 General medicine, internal medicine and other clinical medicine, ECONOMIC BURDEN, ARA H 2, HEALTH, biodiversity
Abstract: In Finland, a systematic public health programme was implemented from 2008 to 2018 to mitigate the burden of allergic disorders by revisiting the prevention strategy. Allergy health and contacts with natural environment were emphasized to promote immunological and psychological resilience instead of poorly justified avoidance. Allergy management practices were improved and low-valued recommendations for care, for example for food allergy, were revised. Patients and families were empowered to use guided self-management to proactively stop symptom exacerbations. A professional non-governmental organization implemented the nationwide education for healthcare and patient NGOs for patients, families and lay public. In healthcare, the work supporting allergic patients and families was organized towards common goals and integrated into everyday work without extra costs. Reaching the predefined goals was followed by employing the national healthcare registers and questionnaire surveys. Governmental bodies contributed with kick-off funding, which was supplemented by private funding. International collaboration, for example with the European patient organization (EFA), increased awareness of the Finnish action and predisposed it for peer review. The 10-year results are favourable, patients are less disabled, practices and attitudes in healthcare have changed, and major cost savings have been obtained. Views of the lay public and patients are slow to move, however. Local multidisciplinary allergy teams were set up to continue the activities also after the Programme. Changes in environment and lifestyle in the last 50 years are the main reasons for the allergy rise. The Finnish experience may help to manage allergic diseases, improve nature relatedness in the fast-urbanizing world, combat nature loss and reduce the disease burden.
Published: 2022

32. Pandemic tattoos : A review of 329 #covidtattoo on Instagram

Author: Kluger, Nicolas, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, and University of Helsinki
Subjects: tattoo, tattooing, SARS-CoV-2, social media, 3121 General medicine, internal medicine and other clinical medicine, Instagram, COVID-19
Abstract: Non
Published: 2022

33. A case of acrocyanosis in a painting of the 17th century

Author: Kluger, Nicolas, HUS Inflammation Center, and Department of Dermatology, Allergology and Venereology
Subjects: 3121 General medicine, internal medicine and other clinical medicine
Abstract: Non
Published: 2022

34. Exiting the Anthropocene : Achieving personal and planetary health in the 21st century

Author: Prescott, Susan L., Logan, Alan C., Bristow, Jamie, Rozzi, Ricardo, Moodie, Rob, Redvers, Nicole, Haahtela, Tari, Warber, Sara, Poland, Blake, Hancock, Trevor, Berman, Brian, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, and University of Helsinki
Subjects: ALLERGY, Biodiversity hypothesis, TOBACCO, climate change, MICROBIOME, FOOD, 3121 General medicine, internal medicine and other clinical medicine, Nature-relatedness, planetary health, noncommunicable diseases (NCDs)
Abstract: Planetary health provides a perspective of ecological interdependence that connects the health and vitality of individuals, communities, and Earth's natural systems. It includes the social, political, and economic ecosystems that influence both individuals and whole societies. In an era of interconnected grand challenges threatening health of all systems at all scales, planetary health provides a framework for cross-sectoral collaboration and unified systems approaches to solutions. The field of allergy is at the forefront of these efforts. Allergic conditions are a sentinel measure of environmental impact on human health in early life-illuminating how ecological changes affect immune development and predispose to a wider range of inflammatory noncommunicable diseases (NCDs). This shows how adverse macroscale ecology in the Anthropocene penetrates to the molecular level of personal and microscale ecology, including the microbial systems at the foundations of all ecosystems. It provides the basis for more integrated efforts to address widespread environmental degradation and adverse effects of maladaptive urbanization, food systems, lifestyle behaviors, and socioeconomic disadvantage. Nature-based solutions and efforts to improve nature-relatedness are crucial for restoring symbiosis, balance, and mutualism in every sense, recognizing that both personal lifestyle choices and collective structural actions are needed in tandem. Ultimately, meaningful ecological approaches will depend on placing greater emphasis on psychological and cultural dimensions such as mindfulness, values, and moral wisdom to ensure a sustainable and resilient future.
Published: 2022

35. Short interruptions of TNF-inhibitor treatment can be associated with treatment failure in patients with immune-mediated diseases

Author: BLING Res Grp, Lamberg, Tea, Sipponen, Taina, Valtanen, Sanna, Eklund, Kari K., Mälkönen, Tarja, Aalto, Kristiina, Mikola, Katriina, Kolho, Kaija-Leena, Leinonen, Sanna, Isomäki, Pia, Mäkinen, Heidi, Vidqvist, Krista-Liisa, Kokko, Arto, Huilaja, Laura, Kyllönen, Minna, Keskitalo, Paula, Sard, Sirja, Vähäsalo, Paula, Koskela, Ritva, Kröger, Liisa, Lahtinen, Perttu, Haapala, Anna-Maija, Korkatti, Katja, Sokka-Isler, Tuulikki, Jokiranta, T. Sakari, HUSLAB, University of Helsinki, Clinicum, Gastroenterologian yksikkö, HUS Abdominal Center, HUS Inflammation Center, Department of Medicine, Reumatologian yksikkö, Department of Dermatology, Allergology and Venereology, HUS Children and Adolescents, Children's Hospital, HYKS erva, Päijät-Häme Welfare Consortium, Medicum, Tampere University, Clinical Medicine, Eye Centre, Department of Internal medicine, and Department of Clinical Microbiology
Subjects: rheumatoid arthritis, Immunology, DISCONTINUATION, 3121 Internal medicine, THERAPY, BIOLOGICS, Rheumatic Diseases, adalimumab, Humans, Immunology and Allergy, DRUGS, Treatment Failure, Finland, Retrospective Studies, ulcerative colitis, REGISTER, Drug Substitution, treatment interruption, immunisation, Crohn disease, Infliximab, RHEUMATOID-ARTHRITIS, Case-Control Studies, 3121 General medicine, internal medicine and other clinical medicine, ANTIBODIES, juvenile idiopathic arthritis, Tumor Necrosis Factor Inhibitors, INFLAMMATORY-BOWEL-DISEASE
Abstract: Introduction: The prevalence of immune-mediated diseases has increased in the past decades and despite the use of biological treatments all patients do not achieve remission. The aim of this study was to characterise the reasons for short interruptions during treatment with two commonly used TNF-inhibitors infliximab and adalimumab and to analyse the possible effects of the interruptions on immunisation and switching the treatment. Material and methods: This case-control study was based on retrospective analyses of patient records and a questionnaire survey to clinicians. A total of 370 patients (194 immunised cases and 172 non-immunised controls, 4 excluded) were enrolled from eight hospitals around Finland. Eleven different diagnoses were represented, and the largest patient groups were those with inflammatory bowel or rheumatic diseases. Results: Treatment interruptions were associated with immunisation in patients using infliximab (p
Published: 2022

36. Proposal for a 6-step approach for differential diagnosis of neonatal erythroderma

Author: Cuperus, E., Bygum, A., Boeckmann, L., Bodemer, C., Bolling, M. C., Caproni, M., Diociaiuti, A., Emmert, S., Fischer, J., Gostynski, A., Guez, S., van Gijn, M. E., Hannula-Jouppi, K., Has, C., Hernandez-Martin, A., Martinez, A. E., Mazereeuw-Hautier, J., Medvecz, M., Neri, I., Sigurdsson, V., Suessmuth, K., Traupe, H., Oji, V., Pasmans, S. G. M. A., Department of Dermatology, Allergology and Venereology, and HUS Inflammation Center
Subjects: GAUCHER-DISEASE, ICHTHYOSIFORM ERYTHRODERMA, NETHERTON-SYNDROME, 3121 General medicine, internal medicine and other clinical medicine, VERSUS-HOST-DISEASE, OMENN SYNDROME, AEC SYNDROME, PRIMARY IMMUNODEFICIENCY DISORDERS, CHANARIN-DORFMAN SYNDROME, HAIR SAMPLES, COLLODION BABY
Abstract: The broad differential diagnosis of neonatal erythroderma often poses a diagnostic challenge. Mortality of neonatal erythroderma is high due to complications of the erythroderma itself and the occasionally severe and life-threatening underlying disease. Early correct recognition of the underlying cause leads to better treatment and prognosis. Currently, neonatal erythroderma is approached on a case-by-case basis. The purpose of this scoping review was to develop a diagnostic approach in neonatal erythroderma. After a systematic literature search in Embase (January 1990 - May 2020, 74 cases of neonatal erythroderma were identified, and 50+ diagnoses could be extracted. Main causes were the ichthyoses (40%) and primary immunodeficiencies (35%). Congenital erythroderma was present in 64% (47/74) of the cases, predominantly with congenital ichthyosis (11/11; 100%), Netherton syndrome (12/14, 86%) and Omenn syndrome (11/23, 48%). Time until diagnosis ranged from 102 days to 116 days for cases of non-congenital erythroderma and congenital erythroderma respectively. Among the 74 identified cases a total of 17 patients (23%) died within a mean of 158 days and were related to Omenn syndrome (35%), graft-versus-host disease (67%) and Netherton syndrome (18%). Disease history and physical examination are summarized in this paper. Age of onset and a collodion membrane can help to narrow the differential diagnoses. Investigations of blood, histology, hair analysis, genetic analysis and clinical imaging are summarized and discussed. A standard blood investigation is proposed, and the need for skin biopsies with lympho-epithelial Kazal-type related Inhibitor staining is highlighted. Overall, this review shows that diagnostic procedures narrow the differential diagnosis in neonatal erythroderma. A 6-step flowchart for the diagnostic approach for neonatal erythroderma during the first month of life is proposed. The approach was made with the support of expert leaders from international multidisciplinary collaborations in the European Reference Network Skin-subthematic group Ichthyosis.
Published: 2022

37. The relative proportion of comorbidities among rhinitis and rhinosinusitis patients and their impact on visit burden

Author: Mikko Nuutinen, Annina Lyly, Paula Virkkula, Maija Hytönen, Elmo Saarentaus, Antti Mäkitie, Aarno Palotie, Paulus Torkki, Jari Haukka, Sanna Toppila‐Salmi, Medicum, Clinicum, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, HUS Head and Neck Center, Korva-, nenä- ja kurkkutautien klinikka, Genomics of Neurological and Neuropsychiatric Disorders, Centre of Excellence in Complex Disease Genetics, Research Programs Unit, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Helsinki Institute of Life Science HiLIFE, Department of Public Health, Jari Haukka / Principal Investigator, Department of Pathology, HUS Heart and Lung Center, and Keuhkosairauksien yksikkö
Subjects: Pulmonary and Respiratory Medicine, EUROPE, chronic rhinosinusitis, Immunology, asthma, PREVALENCE, non-steroidal anti-inflammatory drug exacerbated respiratory disease, ALLERGY, rhinitis, REGULARIZATION PATHS, DISEASES, 3121 General medicine, internal medicine and other clinical medicine, Immunology and Allergy, NONALLERGIC RHINITIS
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.
Published: 2022

38. Exploratory evaluation of tolerability, performance, and cosmetic acceptance of dexpanthenol-containing dermo-cosmetic wash and sun-care products for tattoo aftercare

Author: Daphné A. Schmid, Marisa P. Domingues, Alina Nanu, Nicolas Kluger, Raffaella de Salvo, Sonja Trapp, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, and University of Helsinki
Subjects: dexpanthenol, moisturization, wash, COMPLICATIONS, sun-care, BARRIER FUNCTION, 3121 General medicine, internal medicine and other clinical medicine, tattoo aftercare, General Medicine, tolerability, SKIN
Abstract: Background and Aims Tattoo prevalence has significantly increased over the last decades. Proper tattoo aftercare, such as cleansing, moisturizing, and protection against sunlight, is essential to prevent complications and to keep the beauty of the tattoo. The tolerability, performance, and cosmetic acceptability of two dexpanthenol-containing dermo-cosmetic products, a wash and a sun-care, were investigated on tattooed skin in two separate trials. Methods Two single-center, exploratory, open-label cosmetic studies were conducted between August and November 2020 to evaluate the dexpanthenol-containing dermo-cosmetic products. In the first study, healthy adults applied the 2.5% dexpanthenol-containing wash right after their tattoo session daily for 14 consecutive days. In the second study, healthy adults applied the 2.5% dexpanthenol-containing sun-care sun protection factor 50+ cream on existing tattoos that were daily exposed to sunlight for 28 consecutive days. Clinical examination by a dermatologist and self-assessment through subject questionnaires were used to assess the tolerability, acceptance, ease of use, and cosmetic outcomes of both products. Additionally, transepidermal water loss and moisturization assessments were performed to evaluate skin hydration after use of the sun-care product. Results Both study products were well tolerated, and no product related adverse events were reported during the studies. At least 90% of the study participants appreciated the performance of the dexpanthenol-containing wash and sun-care product, including moisturizing properties, relief of unpleasant sensations, and preservation of the cosmetic appearance of the tattoo. For the sun-care, it was shown that its application supported maintaining the skin barrier of tattooed skin, while keeping it hydrated. Conclusion The 2.5% dexpanthenol-containing wash and sun-care products are well tolerated and appreciated by tattooed subjects. Hence, they represent valid options for tattoo aftercare in line with current recommendations and practice.
Published: 2022

39. Age-dependent Distribution of Atopic Dermatitis in Primary Care: A Nationwide Population-based Study from Finland

Author: Salava, Alexander, Rieppo, Ruut, Lauerma, Antti, Salo, Ville, Department of Dermatology, Allergology and Venereology, University of Helsinki, HUS Inflammation Center, Faculty of Medicine, and Clinicum
Subjects: Adult, Male, atopic dermatitis, Primary Health Care, Dermatology, General Medicine, Dermatitis, Atopic, primary care, Age Distribution, 3121 General medicine, internal medicine and other clinical medicine, Humans, age group, Female, BURDEN, Child, SKIN CONDITIONS, Referral and Consultation, Finland, Aged
Abstract: The burden of atopic dermatitis (AD) appears to be increasing in adult and elderly patients. The aim of this study was to analyse the nationwide database of the Finnish Institute for Health and Welfare regarding the number of patients with AD and of general practitioner consultations in Finland during 2018. The database comprised the main diagnoses of all visits to public primary healthcare. There were 2,094,673 primary care patients (males/females 43.19/56.81%) and 20,905 patients with AD (1.00%) and 24,180 consultations due to AD (0.45%). The highest numbers of patients with AD were in the age groups 0–14 years (9,922 patients, 47.46%) and 15–65 years (9,144 patients, 43.74%). A substantial proportion of patients with AD were aged > 50 years (3,515 patients, 16.81%) or >65 years (1,947 patients, 9.31%). Regression analysis indicated a statistically significant association of age group with patient numbers (p = 0.032) and number of consultations (p = 0.030). There were no differences between direct age group comparisons (p = 0.303), sex (p = 0.389), or number of consultations/patient (p = 0.235). Patients with AD are prevalent in all age groups in Finnish primary care. Patient numbers were also relatively high in groups other than childhood, indicating that age-related distribution in primary care may be shifting to older ages.
Published: 2022

40. Data-driven comorbidity analysis of 100 common disorders reveals patient subgroups with differing mortality risks and laboratory correlates

Author: Miika Koskinen, Jani K. Salmi, Anu Loukola, Mika J. Mäkelä, Juha Sinisalo, Olli Carpén, Risto Renkonen, HUSLAB, Medicum, University of Helsinki, Research Programs Unit, Bio Bank, Precision Cancer Pathology, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, Clinicum, HUS Heart and Lung Center, Department of Medicine, Department of Pathology, Olli Mikael Carpen / Principal Investigator, HUS Diagnostic Center, Department of Bacteriology and Immunology, Risto Renkonen / Principal Investigator, and Infection Biology Research Program
Subjects: Multidisciplinary, 3121 General medicine, internal medicine and other clinical medicine, Humans, Co-morbidity, Comorbidity, Discovery, Retrospective Studies
Abstract: The populational heterogeneity of a disease, in part due to comorbidity, poses several complexities. Individual comorbidity profiles, on the other hand, contain useful information to refine phenotyping, prognostication, and risk assessment, and they provide clues to underlying biology. Nevertheless, the spectrum and the implications of the diagnosis profiles remain largely uncharted. Here we mapped comorbidity patterns in 100 common diseases using 4-year retrospective data from 526,779 patients and developed an online tool to visualize the results. Our analysis exposed disease-specific patient subgroups with distinctive diagnosis patterns, survival functions, and laboratory correlates. Computational modeling and real-world data shed light on the structure, variation, and relevance of populational comorbidity patterns, paving the way for improved diagnostics, risk assessment, and individualization of care. Variation in outcomes and biological correlates of a disease emphasizes the importance of evaluating the generalizability of current treatment strategies, as well as considering the limitations that selective inclusion criteria pose on clinical trials.
Published: 2022

41. Tattoo aftercare management with a dermo‐cosmetic product: Improvement in discomfort sensation and skin repair quality

Author: Michèle Sayag, Säde Sonck, Marlène Chavagnac-Bonneville, Nicolas Kluger, Aurélie Fauger, Clinicum, Department of Dermatology, Allergology and Venereology, and HUS Inflammation Center
Subjects: discomfort, medicine.medical_specialty, medicine.medical_treatment, Sensation, Cosmetics, Dermatology, tattooing, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Edema, medicine, Humans, dermo&#8208, cosmetic, Skin repair, COMPLICATIONS, business.industry, Skin Transplantation, 3. Good health, Tolerability, repair, 3121 General medicine, internal medicine and other clinical medicine, 030220 oncology & carcinogenesis, Itching, Tingling, Moisturizer, medicine.symptom, business, aftercare
Abstract: Background A moisturizer application during the healing process after a tattoo session is a common practice to help wound healing and to reduce discomfort sensations. This practice was recently recommended by the standard European guidelines on tattoos, with the use of an adapted ointment to keep the site moist. Aims To assess the efficacy and the tolerability of a specific dermo-cosmetic product (Cicabio Pommade, Laboratoire Bioderma, NAOS, France) in tattoo aftercare. Patients/Methods Thirty subjects included in this survey applied the product immediately after the tattoo session for 14 days. The objective symptoms (redness, edema, skin repair quality) were assessed by the tattooist and the subjects. The subjective symptoms, discomfort sensations (pain, itching, burning sensations, tingling), soothing, moisturizing, and undesirable effects were assessed by the tattooed individuals. Results After 14 days of application, redness was absent for 100% and 96% of subjects according to the tattoo artist and the subjects, respectively, and edema had completely disappeared for both assessors. Most of the subjects rated the skin quality repair and the aesthetic outcomes as very good to excellent. Soothing and moisturizing effects were observed as early as the first day. The effects were maintained over 14 days. Discomfort sensations were judged absent to slight in 96%-100% of cases after 7 days. They were assessed as absent to slight in all cases for pain, itching, and tingling, and in 96% for burning sensations after 14 days. The product was very well tolerated by 87% of the subjects. Conclusions Our survey demonstrates that this dermo-cosmetic product is suitable for tattooed skin aftercare as it reduced skin discomfort as soon as the first day and led to a good skin quality repair while being well tolerated.
Published: 2021

42. Management of patients with chronic rhinosinusitis during the COVID‐19 pandemic—An EAACI position paper

Author: Jean Bousquet, Adam Chaker, Cezmi A. Akdis, Claus Bachert, Peter Valentin Tomazic, Marek Jutel, Sanna Toppila-Salmi, Valérie Hox, Wytske Fokkens, Carmen Rondon, Barbara Wollenberg, Banu Bozkurt, Jan Hagemann, Aspasia Karavelia, U Förster-Ruhrmann, Ralph Mösges, Cemal Cingi, Tilman Huppertz, Philippe Gevaert, Ioana Agache, Sven Becker, Ludger Klimek, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, University of Helsinki, and Helsinki University Hospital Area
Subjects: 0301 basic medicine, medicine.medical_specialty, education, Immunology, MEDLINE, Cochrane Library, 03 medical and health sciences, Nasal Polyps, 0302 clinical medicine, Adrenal Cortex Hormones, Pandemic, medicine, Humans, Immunology and Allergy, biologics, Nasal polyps, Sinusitis, Risk factor, Intensive care medicine, Rhinitis, Biological Products, SARS-CoV-2, business.industry, chronic rhinosinusitis, Standard treatment, COVID-19, CRSwNP, medicine.disease, Dupilumab, Asthma, 3. Good health, 030104 developmental biology, 030228 respiratory system, 3121 General medicine, internal medicine and other clinical medicine, Chronic Disease, Position paper, business
Abstract: BackgroundChronic rhinosinusitis is regarded as a chronic airway disease. According to WHO recommendations, it may be a risk factor for COVID-19 patients. In most CRSwNP cases, the inflammatory changes affecting the nasal and paranasal mucous membranes are type-2 (T2) inflammation endotypes. MethodsThe current knowledge on COVID-19 and on treatment options for CRS was analyzed by a literature search in Medline, Pubmed, international guidelines, the Cochrane Library and the Internet. ResultsBased on international literature, on current recommendations by WHO and other international organizations as well as on previous experience, a panel of experts from EAACI and ARIA provided recommendations for the treatment of CRS during the COVID-19 pandemic. ConclusionIntranasal corticosteroids remain the standard treatment for CRS in patients with SARS-CoV-2 infection. Surgical treatments should be reduced to a minimum and surgery preserved for patients with local complications and for those with no other treatment options. Systemic corticosteroids should be avoided. Treatment with biologics can be continued with careful monitoring in noninfected patients and should be temporarily interrupted during the course of the COVID-19 infection.
Published: 2021

43. COVID-19 pandemic

Author: W. J. Fokkens, Jürgen Schwarze, Cezmi A. Akdis, J Mullol, W. Czarlewski, Claudia Traidl-Hoffmann, Claus Bachert, D. Larenas-Linnemann, Tomas Chivato, M. Gotua, Mateo Bonini, Ludger Klimek, Vincenzo Patella, A. A. Cruz, Stephanie Dramburg, Kari C. Nadeau, H W Fritsch, K. Ohta, Thomas Eiwegger, Robert M. Naclerio, Antti Lauerma, A. Yorgancioglu, Aslı Gelincik, Piotr Kuna, Oliver Pfaar, Carmen Riggioni, Violeta Kvedariene, Markus Ollert, Sinthia Bosnic-Anticevich, V. Cardona, S. Del Giacco, Sanna Toppila-Salmi, Helen A. Brough, Heimo Breiteneder, Valérie Hox, B. Samolinski, Zuzana Diamant, G.W. Canonica, Lihong Zhang, María José Torres, Y. Okamoto, Liam O'Mahony, Radosław Gawlik, Jolanta Walusiak-Skorupa, Sharon Chinthrajah, Winfried Rief, T. Haatela, M. Morais-Almeida, Ioana Agache, Manfred Schedlowski, I Skypala, R. Brehler, D. Y. Wang, João Fonseca, I. J. Ansotegui, Robyn E O'Hehir, Oscar Palomares, Charlotte G. Mortz, J. C. Ivancevich, C. Suppli Ulrik, M. T. Ventura, P M Matricardi, S Untersmayr, Gabrielle L. Onorato, Amir Hamzah Abdul Latiff, Frederico S. Regateiro, Vanitha Sampath, Arũnas Valiulis, Marek Jutel, Luisa Brussino, Pedro Carreiro-Martins, Jean Bousquet, Nikolaos G. Papadopoulos, A. Bedbrook, Torsten Zuberbier, Karin Hoffmann-Sommergruber, Edward F. Knol, Ear, Nose and Throat, AII - Inflammatory diseases, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (SLuc) Service d'oto-rhino-laryngologie, Philipps Universität Marburg = Philipps University of Marburg, Allergologie, Stimm und Sprachstörungen [Wiesbaden, Germany], Zentrum für Rhinologie und Allergologie [Wiesbaden, Germany], University of Wrocław [Poland] (UWr), ALL-MED, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Medizinische Universität Wien = Medical University of Vienna, Stanford University, Skane University Hospital [Malmo], Lund University [Lund], Charles University [Prague] (CU), University Medical Center Groningen [Groningen] (UMCG), Univ Toronto, Hosp Sick Children, Peter Gilgan Ctr Res & Learning, Mol Med, Toronto, ON M5G 0A4, Canada, The Hospital for sick children [Toronto] (SickKids), University of Toronto, Amsterdam UMC - Amsterdam University Medical Center, Alfred Health, Victoria University [Melbourne], University College Cork (UCC), Sean N. Parker Center for Allergy and Asthma Research [Stanford], Stanford Medicine, Stanford University-Stanford University, University Clinics of Essen, University of Essen, Allergy Unit [Malaga, Spain] (National Network ARADyAL), Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], Helmholtz Zentrum München = German Research Center for Environmental Health, University Hospital Augsburg, National University of Singapore (NUS), Beijing Tongren Hospital, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Evelina London Children's Hospital, King‘s College London, CEU-San Pablo University and HM-Hospitals School of Medicine, University of Cagliari, Medical University of Silesia (SUM), Istanbul University, Cliniques Universitaires Saint-Luc [Bruxelles], University Medical Center [Utrecht], Helsinki University Central Hospital, University of Helsinki, Odense University Hospital (OUH), Luxembourg Institute of Health (LIH), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Hospital Sant Joan de Déu [Barcelona], Institut de Recerca Pediàtrica Hospital Sant Joan de Déu [Barcelona, Spain], University of Edinburgh, NHS Foundation Trust [London], The Royal Marsden, Nofer Institute of Occupational Medicine (NIOM), Hospital Quirónsalud Bizkaia [Bilbao], Ghent University Hospital, Sun Yat-Sen University [Guangzhou] (SYSU), Karolinska Institutet [Stockholm], Woolcock Institute of Medical Research [Sydney], The University of Sydney, University of Turin, Mauriziano Umberto I Hospital, Humanitas University [Milan] (Hunimed), Vall d'Hebron University Hospital [Barcelona], Hospital de Dona Estefania, NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Federal University of Bahia School of Medicine, Global Alliance Against Chronic Respiratory Diseases (GARD-WHO), Medical Consulting Czarlewski, Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, MEDIDA, Lda, David Tvildiani Medical University (DTMU), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Barlicki University Hospital, Vilnius University [Vilnius], Hospital Medica Sur [Mexico City, Mexico], Pantai Hospital [Kuala Lumpur], Hospital CUF Descobertas, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), CIBER de Epidemiología y Salud Pública (CIBERESP), Johns Hopkins University School of Medicine [Baltimore], Fukujuji Hospital, Tokyo National Hospital, Chiba Rosai Hospital, Chiba University Hospital, Royal Manchester Children's Hospital, University of Manchester [Manchester], General Children's Hospital of Athens P & A Kyriakou, 'Santa Maria della Speranza' Hospital, Centro Hospitalar e Universitário [Coimbra], Coimbra Institute for Clinical and Biomedical Research [Coimbra, Portugal] (iCBR - Faculty of Medicine), University of Coimbra [Portugal] (UC), Medical University of Warsaw - Poland, Hvidovre Hospital, University of Copenhagen = Københavns Universitet (UCPH), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Manisa Celal Bayar University, Transilvania University of Brasov, Salvy-Córdoba, Nathalie, Department of Dermatology, Allergology and Venereology, and HUS Inflammation Center
Subjects: 0301 basic medicine, viruses, Eaaci Position Paper, Medizin, Cochrane Library, GUIDELINES, FOOD ALLERGY, allergen immunotherapy, allergy clinic, anaphylaxis, asthma, clinical trials, COVID-19, Position Paper, psychological impact, SARS-CoV-2, Allergists, Health Personnel, Humans, Hypersensitivity, Information Technology, Patient Care Team, Triage, SARS‐CoV‐2, DESENSITIZATION, 0302 clinical medicine, MESH: Patient Care Team, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, HDE ALER, Pandemic, Health care, Immunology and Allergy, ATOPIC-DERMATITIS, MESH: COVID-19, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, allergen immunotherapy (AIT), virus diseases, DRUG HYPERSENSITIVITY REACTIONS, 3. Good health, INFECTIONS, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Triage, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, Allergen immunotherapy, medicine.medical_specialty, MESH: Information Technology, MESH: Hypersensitivity, Immunology, education, MEDLINE, DIAGNOSIS, psychological COVID, 03 medical and health sciences, MESH: Allergists, COVID‐19, medicine, MESH: SARS-CoV-2, ddc:610, RHINOSINUSITIS, MESH: Humans, business.industry, Clinical trial, Coronavirus, EXACERBATIONS, 030104 developmental biology, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Family medicine, 3121 General medicine, internal medicine and other clinical medicine, Position paper, MESH: Health Personnel, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: BackgroundThe Coronavirus disease 2019 (COVID‐19) has evolved as a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS‐CoV‐)2. Allergists and other health care providers (HCPs) in the field of allergies and associated airway diseases are in the front line, taking care of patients potentially infected with SARS‐CoV‐2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics.MethodThe scientific information on COVID‐19 was analyzed by a literature search in Medline, Pubmed, national and international guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library and the Internet.ResultsBased on diagnostic and treatment standards developed by EAACI, on international information regarding COVID‐19, on guidelines of the World Health Organization (WHO) and other international organizations as well as on previous experience, a panel of experts including clinicians, psychologists, IT experts and basic scientists along with EAACI and the “Allergic Rhinitis and its Impact on Asthma (ARIA)” inititiative have developed recommendations for the optimal management of allergy clinics during the current COVID‐19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies.ConclusionsThis international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients whilst ensuring necessary safety in the current COVID‐19 pandemic.
Published: 2021

44. Tumour Suppressor Neuron Navigator 3 and Matrix Metalloproteinase 14 are Co-expressed in Most Melanomas but Downregulated in Thick Tumours

Author: Bugaeva, Olga, Maliniemi, Pilvi, Prestvik, Wenche S., Leivo, Eeva, Kluger, Nicolas, Salava, Alexander, Virtanen, Sanna, Jäntti, Kirsi, Saksela, Olli, Lehti, Kaisa, Kujala, Paula, Krohn, Kai, Ranki, Annamari, Kaisa Irene Lehti / Principal Investigator, Research Programs Unit, Department of Dermatology, Allergology and Venereology, HUS Inflammation Center, Faculty Common Matters (Faculty of Medicine), Teachers' Academy, Faculty Common Matters (Faculty of Biology and Environmental Sciences), Clinicum, Tampere University, and Department of Pathology
Subjects: Mmp14, 3121 General medicine, internal medicine and other clinical medicine, 3111 Biomedicine, Dermatology, General Medicine, Copy number change, Naevus, Melanoma, Nav3
Abstract: Melanoma is a highly metastatic tumour originating from neural crest-derived melanocytes. The aim of this study was to analyse the expression of neuron navigator 3 (NAV3) in relation to membrane type-1 matrix metalloproteinase MMP14, a major regulator of inva-sion, in 40 primary melanomas, 15 benign naevi and 2 melanoma cell lines. NAV3 copy number changes were found in 18/27 (67%) primary melanomas, so that deletions dominated (16/27 of samples, 59%). NAV3 protein was found to be localized at the leading edge of migrating melanoma cells in vitro. Silencing of NAV3 reduced both melanoma cell migration in 2-dimensio-nal conditions, as well as sprouting in 3-dimensional collagen I. NAV3 protein expression correlated with MMP14 in 26/37 (70%) primary melanomas. NAV3 and MMP14 were co-expressed in all tumours with Breslow thickness < 1 mm, in 11/23 of mid-thickness tumours (1–5 mm), but in only 1/6 samples of thick (> 5 mm) melanomas. Altogether, NAV3 number changes are frequent in melanomas, and NAV3 and MMP14, while expressed in all thin melanomas, are often downregu-lated in thicker tumours, suggesting that the lack of both NAV3 and MMP14 favours melanoma progression. publishedVersion
Published: 2023

45. Long-Term Follow-Up After Maxillary Sinus Balloon Sinuplasty and ESS

Author: Matti Penttilä, Sanna Toppila-Salmi, John M. Lee, Anni Koskinen, Heini Huhtala, Karin Blomgren, Jyri Myller, Marie Lundberg, Markus Lilja, Tampere University, Department of Otology and Oral Diseases, Health Sciences, HUS Head and Neck Center, Korva-, nenä- ja kurkkutautien klinikka, HYKS erva, University of Helsinki, Päijät-Häme Welfare Consortium, HUS Inflammation Center, and Department of Dermatology, Allergology and Venereology
Subjects: medicine.medical_specialty, Maxillary sinus, Chronic rhinosinusitis, business.industry, Long term follow up, Endoscopic sinus surgery, Satisfaction, Balloon sinuplasty, 3. Good health, Surgery, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Otorhinolaryngology, 030220 oncology & carcinogenesis, Maxilla, medicine, Revision surgery, 3125 Otorhinolaryngology, ophthalmology, 030223 otorhinolaryngology, business
Abstract: Objectives: The aim of this controlled follow-up study was to compare the need for revision surgery, long-term efficacy, and satisfaction in chronic rhinosinusitis patients who had undergone maxillary sinus operation with either balloon sinuplasty or traditional endoscopic sinus surgery (ESS) technique. Methods: Thirty-nine ESS patients and 36 balloon patients of our previously described cohort, who had been primarily operated in 2008 to 2010, were contacted by phone. Symptoms, satisfaction, and need for revision surgery were asked. In addition, we collected data of patients who had undergone primary maxillary sinus balloon sinuplasty in the Helsinki University Hospital during the years 2005 to 2019. As a control group, we collected data of patients who had undergone primary maxillary sinus ESS at 3 Finnish University Hospitals, and 1 Central Hospital in years 2005, 2008, and 2011. Results: Altogether, 77 balloon patients and 82 ESS patients were included. The mean follow-up time was 5.3 years in balloon group and 9.8 years in ESS group. Revision surgery was performed on 17 balloon patients and 6 ESS patients. In the survival analysis, the balloon sinuplasty associated significantly with a higher risk of revision surgery compared to ESS. According to the phone interviews, 82% of ESS patients and 75% of balloon patients were very satisfied with the primary operation. Conclusion: Although the patient groups expressed equal satisfaction and change in symptoms after the operations, the need for revision surgery was higher after balloon sinuplasty than after ESS. This should be emphasized when counselling patients regarding surgical options.
Published: 2021

46. Patients with asthma or chronic obstructive pulmonary disease (COPD) can generate sufficient inspiratory flows via Easyhaler® dry powder inhaler: a pooled analysis of two randomized controlled trials

Author: Satu Lähelmä, Ville Vartiainen, Mikko Vahteristo, Rain Jõgi, Anna S. Pelkonen, L. Pekka Malmberg, HUS Inflammation Center, and Department of Dermatology, Allergology and Venereology
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, DEVICES, Population, Fixed-dose combination, DISKUS, device performance, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Clinical endpoint, Medicine, peak inspiratory flow (PIF), RATES, COMBINATION, Peak flow meter, education, measurement_unit, Asthma, COPD, education.field_of_study, business.industry, inhalation device, IN-VITRO, Airway obstruction, medicine.disease, Dry-powder inhaler, respiratory tract diseases, 3. Good health, 030228 respiratory system, TURBUHALER(R), RATE DEPENDENCY, 3121 General medicine, internal medicine and other clinical medicine, drug delivery, measurement_unit.measuring_instrument, Cardiology, business
Abstract: Background: To evaluate whether patients of varying ages and lung function with asthma or those with chronic obstructive pulmonary disease (COPD) can achieve sufficient inspiratory flows for effective use of the fixed-dose combination of salmeterol-fluticasone propionate and budesonide-formoterol dispensed with the Easyhaler (R) (EH) device-metered, multi-dose dry powder inhaler (DPI). Methods: A pooled analysis of two randomized, multicenter, crossover, open-label studies (NCT01424137; NCT009849061) was conducted to characterize inspiratory flow parameters across the EH, Seretide Diskus (DI) and Symbicort Turbuhaler (TH) inhalers in patients with asthma and/or COPD of varying severity. The primary endpoint was peak inspiratory flow (PIF) rate through the EH. Results: The intent-to-treat population comprised 397 patients; 383 patients were included in the per protocol (PP) population. The mean PIF (standard deviation) values through the EH in patients = 18 years of age with asthma and in those with COPD, were similar: 61.4 (11.5), 69.7 (13.5), and 61.9 (13.2) L/min, respectively. These flow rates correspond to pressure drops of 5.05 (1.80), 6.52 (2.34) and 5.19 (2.07) kPa, respectively. In total, 380 (99.2%) of patients in the PP population were able to generate a PIF rate through the EH of >= 30 L/min, which is required to enable consistent dose delivery from the DPI; there was a moderate direct association between age and PIF in younger patients with asthma, but this was inverse and less apparent in adult patients with asthma and/or those with COPD. Height and weight were also moderately correlated with PIF. Stronger associations with PIF were observed for some lung function parameters, particularly native PIF and forced inspiratory vital capacity. Conclusions: Over 99% of patients with asthma and/or COPD were able to inhale through the EH with an adequate PIF rate, irrespective of age, or severity of airway obstruction. This confirms that patients with asthma and/or COPD can achieve inspiratory flows via the EH DPI that are sufficient for its effective use.
Published: 2021

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

Author: Johanna Sahlman, Anu Laulajainen-Hongisto, Paula Kauppi, Jyri Myller, Seija Vento, Annina Lyly, Sanna Toppila-Salmi, Jura Numminen, Heikki Turpeinen, Saara Sillanpää, Tampere University, Department of Otology and Oral Diseases, Clinical Medicine, Clinicum, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, University of Helsinki, Helsinki University Hospital Area, HUS Head and Neck Center, Korva-, nenä- ja kurkkutautien klinikka, HYKS erva, Päijät-Häme Welfare Consortium, Department of Pathology, and Medicum
Subjects: lcsh:Immunologic diseases. Allergy, 0301 basic medicine, N-ERD, disease control, N‐ERD, medicine.medical_specialty, Immunology, CHRONIC RHINOSINUSITIS, 03 medical and health sciences, 0302 clinical medicine, CLINICAL CHARACTERISTICS, Internal medicine, medicine, Humans, Immunology and Allergy, Eosinophilia, Nasal polyps, Prospective Studies, 3125 Otorhinolaryngology, ophthalmology, Airway Management, RECURRENCE, Prospective cohort study, Retrospective Studies, Rhinitis, Original Research, Asthma, nasal polyps, business.industry, Anti-Inflammatory Agents, Non-Steroidal, Hazard ratio, Ethmoidectomy, Odds ratio, asthma, medicine.disease, Confidence interval, PREVALENCE, 3. Good health, ASPIRIN, REVISION RATES, 030104 developmental biology, 3121 General medicine, internal medicine and other clinical medicine, medicine.symptom, lcsh:RC581-607, business, ENDOSCOPIC SINUS SURGERY, eosinophilia, CRS, 030215 immunology
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., The patient record data of 167 patients with NSAID‐exacerbated respiratory disease was analyzed to study factors affecting the disease control. Nasal polyp eosinophilia increased the risk of revision surgery, and baseline oral corticosteroids and a history of four or more endoscopic sinus surgeries were associated with poor disease control during the follow‐up.
Published: 2021

48. Nasal saline irrigation: prescribing habits and attitudes of physicians and pharmacists

Author: Antti Hyvärinen, Sanna Toppila-Salmi, Elina Penttilä, Jesse Tapiala, Eero Suihko, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, University of Helsinki, and Helsinki University Hospital Area
Subjects: medicine.medical_specialty, Irrigation, Pharmacists, patient education, Habits, 03 medical and health sciences, 0302 clinical medicine, Physicians, medicine, Humans, 030212 general & internal medicine, Adverse effect, Research Articles, Rhinitis, business.industry, lcsh:Public aspects of medicine, 030503 health policy & services, nasal lavage, sinonasal conditions, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, Nasal saline, 3. Good health, 3141 Health care science, Attitude, sinonasal symptoms, Chronic Disease, Emergency medicine, adverse effects, Nasal Lavage, 0305 other medical science, business, Research Article, Patient education
Abstract: 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 POINTSLittle 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.
Published: 2021

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

Author: Adam Chaker, Zsolt Szépfalusi, Juan José Yepes-Nuñez, Onur Boyman, A. Vultaggio, Alexia Chatzipetrou, Oscar Palomares, Cezmi A. Akdis, Marek Jutel, Eva Untersmayr, Andrea Matucci, Mohammad Alsalamah, Alanna Marson, Sevim Bavbek, Paula Kauppi, Birgit Pfaller, Barbara Rogala, Antonios G.A. Kolios, Sarah Bendien, Susan Chan, Ioana Agache, Thomas Eiwegger, Carmen Li, Apostolos Bossios, George Du Toit, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, Helsinki University Hospital Area, University of Helsinki, University of Zurich, and Eiwegger, Thomas
Subjects: 0301 basic medicine, Allergy, Omalizumab, GUIDELINES, Inflammatory bowel disease, Biological Factors, 0302 clinical medicine, 10183 Swiss Institute of Allergy and Asthma Research, Multicenter Studies as Topic, Immunology and Allergy, atopic dermatitis, 10177 Dermatology Clinic, Atopic dermatitis, CROHNS-DISEASE, 3. Good health, biologicals, 2723 Immunology and Allergy, Female, Rituximab, pregnancy, medicine.drug, medicine.medical_specialty, 1ST TRIMESTER, Immunology, 610 Medicine & health, OMALIZUMAB USE, Dermatitis, Atopic, 03 medical and health sciences, MANAGEMENT, medicine, Humans, RITUXIMAB, REGULATORY T-CELLS, Intensive care medicine, Asthma, Biological Products, 2403 Immunology, Pregnancy, business.industry, Infant, Newborn, asthma, medicine.disease, body regions, 030104 developmental biology, 030228 respiratory system, 3121 General medicine, internal medicine and other clinical medicine, 10033 Clinic for Immunology, MODIFYING ANTIRHEUMATIC DRUGS, Position paper, business, INFLAMMATORY-BOWEL-DISEASE
Abstract: 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 scare 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, pre-conception counseling, and health care provider education is 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.
Published: 2021

50. Patient Inspiratory Maneuver Performance; Peak Lungpower, Acceleration and Volume

Author: Mikko Vahteristo, Ville Vartiainen, Satu Lähelmä, L. P. Malmberg, Jussi Haikarainen, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, University of Helsinki, and Helsinki University Hospital Area
Subjects: Pulmonary and Respiratory Medicine, Pharmaceutical Science, DISKUS(TM), FLOW-RATE DEPENDENCY, lungpower, Pulmonary Disease, Chronic Obstructive, Patient performance, Administration, Inhalation, Medicine, VOLUNTEERS, COPD, Humans, Pharmacology (medical), In patient, Metered Dose Inhalers, DRUG-DELIVERY, airflow resistance, Lung, Asthma, SALBUTAMOL, Original Research, EASYHALER(R), Inhalation, business.industry, Nebulizers and Vaporizers, dry powder inhalers, Inspiratory muscle, Peak Inspiratory Flow Rate, IN-VITRO, asthma, medicine.disease, EFFICACY, Anesthesia, 3121 General medicine, internal medicine and other clinical medicine, Salbutamol, business, RESISTANCE, airflow, medicine.drug
Abstract: Background: Use of drug delivery devices between nebulizers, dry powder inhalers (DPIs), or metered dose inhalers (MDIs), for treating patients with asthma and chronic obstructive pulmonary disease (COPD), is based on patients' capability of coordinating the inhalation maneuver and achieving sufficient airflow. There are limited data available with regard to how patients meet the requirements of successful inhalation performance, and how the concept of inspiratory lungpower could be applied. The aim of this work was to study the patient inspiratory airflow profile performance in large data sets. We analyzed how the Kamin-Haidl inhalation criteria were met by patients with DPIs such as Easyhaler for combination therapy (EH-combi), Easyhaler for monotherapy (EH-mono), Diskus, and Turbuhaler (TH), and applied peak lungpower instead of peak inspiratory flow rate as an indicator of patient performance. Materials and Methods: Data sets gathered in two previous studies for DPIs, that is, EH-combi, EH-mono, Diskus, and TH, were used to analyze how inspiratory lungpower representing inspiratory muscle power, flow acceleration, and volume after peak met the inhalation criteria. The measured patient airflow profiles through inhalers were assessed for patients with asthma or COPD. Results: Based on the Kamin-Haidl inhalation criteria, successful inhalation requirements were met with EH-combi in 96.1% and with EH-mono in 92.6% of patients. The success rates were 89.5% and 84.6% with Diskus and TH, respectively, (p
Published: 2020

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