Twenty-one-year follow-up revealed guideline-concordant and non-concordant trends in intensive care of bronchiolitis

To evaluate the management of bronchiolitis in the paediatric intensive care unit (PICU) before and after publication of the national bronchiolitis guidelines in June 2015. All infants treated between 2016–2020 for bronchiolitis in the PICU of Tampere University Hospital at < 12 months of age were included. The data were retrospectively collected from electronic patient records. The current results reflecting the post-guideline era were compared with previously published results for the pre-guideline 2000–2015 period. These two studies used identical protocols. Forty-six infants treated in the PICU were included. During the post-guideline era, inhaled adrenaline was given to 26 (57%), salbutamol to 7 (15%), and hypertonic saline inhalations to 35 (75%) patients. Forty-three patients (94%) received high-flow oxygen therapy (HFOT). Seventeen patients (37%) were treated with nasal continuous positive airway pressure (CPAP) and 4 (9%) with mechanical ventilation. Conclusion: When post-guideline years were compared with pre-guideline years, the use of bronchodilators decreased in agreement, but the use of inhaled saline increased in disagreement with the guidelines. The use of respiratory support increased, evidently because of an introduction of the non-invasive HFOT treatment modality.What is Known:• Oxygen supplementation and respiratory support, when needed, are the cornerstones of bronchiolitis treatment.• Medicines are frequently given to infants with bronchiolitis, especially if intensive care is needed, although evidence of their effectiveness is lacking.What is New:• Nearly all (94%) infants who needed intensive care were treated with HFOT and 37% with nasal CPAP, and finally, only 9% were intubated, which reflects the effectiveness of non-invasive techniques.• When pre- and post-guideline eras were compared, use of racemic adrenaline decreased from 84 to 57%, but use of hypertonic saline increased up to 75%, which disagrees with the current guidelines.publishedVersionPeer reviewe

Multicenter cohort study on duration of antiarrhythmic medication for supraventricular tachycardia in infants

Antiarrhythmic medication (AM) is commonly used to prevent supraventricular tachycardia (SVT) recurrence in infants. Our aim was to determine whether a shorter duration of AM is sufficient to prevent atrioventricular reentrant tachycardia (AVRT) recurrence and evaluate risk factors for recurrence of SVT after discontinued AM.This multicenter cohort study included all infants diagnosed with SVT in the five university hospitals in Finland between 2005 and 2017. Those diagnosed between 2005 and 2012 received AM for 12 months (group 1), and those diagnosed between 2013 and 2017 received AM for 6 months (group 2). A total of 278 infants presented with AVRT (group 1, n = 181; group 2, n = 97), and the median AM duration was 12.0 months (interquartile range [IQR] 11.4-13.4) and 7.0 months (IQR 6.0-10.2), respectively. Propranolol was the most frequently used first-line AM (92% and 95%). Recurrence-free survival rates were over 88% until 12 months after AM prophylaxis in both groups, without any statistically significant difference between them. Independent risk factors for recurrence of SVT after discontinuation of AM were need of combination AM (HR 2.2, 95% CI 1.14-4.20), Wolff-Parkinson White (WPW) syndrome (HR 2.4, 95% CI 1.25-4.59), and age over 1 month at admission (HR 2.2, 95% CI 1.12-4.48). Conclusion: Shortening AM duration in infants from 12 to 6 months does not seem to lead to more frequent SVT recurrence. The risk factors for recurrence of SVT were WPW syndrome, need of combination AM, and age over 1 month.Peer reviewe

DNA methylation changes and somatic mutations as tumorigenic events in Lynch syndrome-associated adenomas retaining mismatch repair protein expression

Background: DNA mismatch repair (MMR) defects are a major factor in colorectal tumorigenesis in Lynch syndrome (LS) and 15% of sporadic cases. Some adenomas from carriers of inherited MMR gene mutations have intact MMR protein expression implying other mechanisms accelerating tumorigenesis. We determined roles of DNA methylation changes and somatic mutations in cancer-associated genes as tumorigenic events in LS-associated colorectal adenomas with intact MMR. Methods: We investigated 122 archival colorectal specimens of normal mucosae, adenomas and carcinomas from 57 LS patients. MMR-deficient (MMR-D, n 49) and MMR-proficient (MMR-P, n 18) adenomas were of particular interest and were interrogated by methylation-specific multiplex ligation-dependent probe amplification and Ion Torrent sequencing. Findings: Promoter methylation of CpG island methylator phenotype (CIMP)-associated marker genes and selected colorectal cancer (CRC)-associated tumor suppressor genes (TSGs) increased and LINE-1 methylation decreased from normal mucosa to MMR-P adenomas to MMR-D adenomas. Methylation differences were statistically significant when either adenoma group was compared with normal mucosa, but not between MMR-P and MMR-D adenomas. Significantly increased methylation was found in multiple CIMP marker genes (1612, NEUROGI,CRABP1, and CDKN2A) and TSGs (SERPI and SFRP2) in MMR-P adenomas already. Furthermore, certain CRC-associated somatic mutations, such as KRAS, were prevalent in MMR-P adenomas. Interpretation: We conclude that DNA methylation changes and somatic mutations of cancer-associated genes might serve as an alternative pathway accelerating LS-associated tumorigenesis in the presence of proficient MMR. Fund: Jane and Aatos Erkko Foundation, Academy of Finland, Cancer Foundation Finland, Sigrid juselius Foundation, and HiL1FE. (C) 2019 Published by Elsevier B.V.Peer reviewe

DNA hypermethylation appears early and shows increased frequency with dysplasia in Lynch syndrome-associated colorectal adenomas and carcinomas

Abstract Background Lynch syndrome (LS) is associated with germline mutations in DNA mismatch repair (MMR) genes. The first “hit” to inactivate one allele of the predisposing MMR gene is present in every cell, contributing to accelerated tumorigenesis. Less information is available of the nature, timing, and order of other molecular “hits” required for tumor development. To this end, MMR protein expression and coordinated promoter methylation were examined in colorectal specimens prospectively collected from LS mutation carriers (n = 55) during colonoscopy surveillance (10/2011–5/2013), supplemented with retrospective specimens. Results Loss of MMR protein corresponding to the gene mutated in the germline increased with dysplasia, with frequency of 0 % in normal mucosa, 50–68 % in low-grade dysplasia adenomas, and 100 % in high-grade dysplasia adenomas and carcinomas. Promoter methylation as a putative “second hit” occurred in 1/56 (2 %) of tumors with silenced MMR protein. A general hypermethylation tendency was evaluated by two gene sets, eight CpG island methylator phenotype (CIMP) genes, and seven candidate tumor suppressor genes linked to colorectal carcinoma (CRC). Hypermethylation followed the same trend as MMR protein loss and was present in some low-grade dysplasia adenomas that still expressed MMR protein suggesting the absence of a “second hit.” To assess prospectively collected normal mucosa for carcinogenic “fields,” the specimen donors were stratified according to age at biopsy (50 years or below vs. above 50 years) and further according to the absence vs. presence of a (previous or concurrent) diagnosis of CRC. In mutation carriers over 50 years old, two markers from the candidate gene panel (SFRP1 and SLC5A8) revealed a significantly elevated average degree of methylation in individuals with CRC diagnosis vs. those without. Conclusions Our findings emphasize the importance and early appearance of epigenetic alterations in LS-associated tumorigenesis. The results serve early detection and assessment of progression of CRC

Exome and immune cell score analyses reveal great variation within synchronous primary colorectal cancers

BACKGROUND: Approximately 4% of colorectal cancer (CRC) patients have at least two simultaneous cancers in the colon. Due to the shared environment, these synchronous CRCs (SCRCs) provide a unique setting to study colorectal carcinogenesis. Understanding whether these tumours are genetically similar or distinct is essential when designing therapeutic approaches. METHODS: We performed exome sequencing of 47 primary cancers and corresponding normal samples from 23 patients. Additionally, we carried out a comprehensive mutational signature analysis to assess whether tumours had undergone similar mutational processes and the first immune cell score analysis (IS) of SCRC to analyse the interplay between immune cell invasion and mutation profile in both lesions of an individual. RESULTS: The tumour pairs shared only few mutations, favouring different mutations in known CRC genes and signalling pathways and displayed variation in their signature content. Two tumour pairs had discordant mismatch repair statuses. In majority of the pairs, IS varied between primaries. Differences were not explained by any clinicopathological variable or mutation burden. CONCLUSIONS: The study shows major diversity within SCRCs. Rather than rely on data from one tumour, our study highlights the need to evaluate both tumours of a synchronous pair for optimised targeted therapy.Peer reviewe

Eleven Candidate Susceptibility Genes for Common Familial Colorectal Cancer

Peer reviewe

Exome-wide somatic mutation characterization of small bowel adenocarcinoma

Small bowel adenocarcinoma (SBA) is an aggressive disease with limited treatment options. Despite previous studies, its molecular genetic background has remained somewhat elusive. To comprehensively characterize the mutational landscape of this tumor type, and to identify possible targets of treatment, we conducted the first large exome sequencing study on a population-based set of SBA samples from all three small bowel segments. Archival tissue from 106 primary tumors with appropriate clinical information were available for exome sequencing from a patient series consisting of a majority of confirmed SBA cases diagnosed in Finland between the years 2003-2011. Paired-end exome sequencing was performed using Illumina HiSeq 4000, and OncodriveFML was used to identify driver genes from the exome data. We also defined frequently affected cancer signalling pathways and performed the first extensive allelic imbalance (Al) analysis in SBA. Exome data analysis revealed significantly mutated genes previously linked to SBA (TP53, KRAS, APC, SMAD4, and BRAF), recently reported potential driver genes (SOX9, ATM, and ARID2), as well as novel candidate driver genes, such as ACVR2A, ACVR1B, BRCA2, and SMARCA4. We also identified clear mutation hotspot patterns in ERBB2 and BRAF. No BRAF V600E mutations were observed. Additionally, we present a comprehensive mutation signature analysis of SBA, highlighting established signatures 1A, 6, and 17, as well as U2 which is a previously unvalidated signature. Finally, comparison of the three small bowel segments revealed differences in tumor characteristics. This comprehensive work unveils the mutational landscape and most frequently affected genes and pathways in SBA, providing potential therapeutic targets, and novel and more thorough insights into the genetic background of this tumor type.Peer reviewe

Bronkioliitti : Hoito ja riskitekijät vaikealle taudinkuvalle

Bronkioliitti eli ilmatiehyttulehdus on yleisin alle vuoden ikäisten lasten sairaalahoidon syy. Sen aiheuttajana on useimmiten respiratory syncytial virus. Vaikka bronkioliitti on tavallinen ja hyvin tunnistettu tauti, ei sille ole kansainvälisesti yhtenäistä määritelmää tai yhtenäisiä hoitosuosituksia. Bronkioliitin ensimmäiset oireet muistuttavat tavallista ylähengitystieinfektiota ja vasta muutaman päivän sisällä ilmaantuvat alahengitystieinfektion oireet: hengityksen tihentyminen, kylkivälivetäymät ja poikkeava keuhkojen kuuntelulöydös. Kolme prosenttia alle vuoden ikäisistä lapsista tarvitsee sairaalahoitoa bronkioliitin vuoksi ja heistä 2-6 prosenttia tarvitsee tehohoitoa. Viimeisten vuosikymmenten aikana bronkioliittia on hoidettu monenlaisilla lääkkeillä kuten kortikosteroideilla, hengitettävillä lääkkeillä salbuta¬molilla, adrenaliinilla ja keittosuolalla ja antikolinergeillä. Kaikki nämä on todettu tutkimuksissa kuitenkin tehottomiksi. Tämänhetkiset näyttöön perustuvat hoitosuositukset suosittelevat supportiivista hoitoa. Hengitysvaikeutta hoidetaan tarvittaessa hengitystuella. Tutkimusten mukaan näytteenoton vähentäminen, lääkehoitojen karsiminen ja non-invasiivisten hengitystukihoitojen käyttö eivät johda huonompaan lopputulokseen. Väitöskirjani tavoitteena on kuvata bronkioliitin määritelmää, hoitoa sekä hoidon muutosta suhteessa näyttöön perustuviin hoitosuosituksiin. Lisäksi työssä arvioidaan vaikean tehohoitoa vaativan bronkioliitin ilmaantuvuutta ja riskitekijöitä tehohoitoon joutumiselle ja hengitystukihoidolle. Kyselykaavake lähetettiin kaikkiin lastensairaaloihin Suomessa ja Ruotsissa ja bronkioliitin hoidosta vastaavaa lastenlääkäriä pyydettiin vastaamaan bronkioliitin määritelmää ja hoitoa koskevaan kyselyyn. Vastaukset painotettiin alueella asuvien alle vuoden ikäisten lasten määrän mukaan. Kyselyalueet kattoivat 74 prosenttia Ruotsin ja 100 prosenttia Suomen alle vuoden ikäisistä lapsista. Retrospektiivisen tapaus-verrokkitutkimuksen aineisto kerättiin Tampereen yliopistollisesta sairaalasta vuosilta 2000-2015. Tutkimuksessa kartoitettiin tehohoitoon ja hengitystukihoitoon joutumisen riskitekijöitä bronkoliittipotilailla. Yhteensä 16 vuoden aikana 105 lasta oli hoidettu teho-osastolla bronkioliitin vuoksi. Jokaista tehohoidettua potilasta kohden kerättiin kaksi bronkioliittia sairastanutta verrokkia päivystyspoliklinikka käynneistä: yksi ennen tapausta ja yksi tapauksen jälkeen. Tapaus-verrokkiaineistosta tutkittiin tehohoidon muutosta jakamalla aineisto kolmeen ajanjaksoon: 2000-2005, 2006-2010 ja 2011-2015. Aineisto raseemisen adrenaliinin käytöstä kerättiin neljän yliopistosairaalan sairaala-apteekkien rekistereistä vuosilta 2012-2016. Bronkioliitin määritelmän yläikärajan keskiarvo oli 12.7 kk Suomessa ja 12.5 kk Ruotsissa. Adrenaliini-inhalaatioiden käyttö oli yleistä molemmissa maissa, mutta Ruotsissa lastenlääkärit suosivat levo-adrenaliinia, kun taas Suomessa suosittiin raseemista adrenaliinia. Kortikosteroideja käytettiin harvoin. Alle vuoden ikäisillä lapsilla keskimääräinen ikävakioitu ilmaantuvuus vaikealle tehohoitoa vaativalle bronkioliitille oli 1.5/1000/vuosi. Itsenäisiä riskitekijöitä tehohoidolle olivat alle 2 kuukauden ikä, syntymäpaino alle 2000 g, synnynnäiset sydänsairaudet, hengitys¬katkokset ja hengityksen vinkumisen puuttuminen. Lisäksi itsenäisiä riskitekijöitä hengitystuen tarpeelle olivat alle 2 kk:n ikä, syntymäpaino alle 2000 g ja synnynnäinen sydänsairaus. Ajanjaksoina 2000-2005, 2006-2010 ja 2011-2015, inhaloitavien beeta-agonistien ja systeemisen kortikosteroidin käyttö laski. Sen sijaan raseemisen adrenaliinin ja hypertonisten keittosuolainhalaatioiden käyttö lisääntyi Tampereen yliopistollisessa sairaalassa. Raseemisen adrenaliinin käyttö kuitenkin väheni yliopistollisissa sairaaloissa vuosina 2012-2016. Tämä muutos näkyi selvimmin sairaaloissa, joissa käyttö oli ollut yleisintä. Yhteenvetona bronkioliitin määritelmä ja annettu hoito olivat hyvin yhdenmukaisia Suomessa ja Ruotsissa. Nuori ikä, alhainen syntymäpaino ja synnynnäinen sydänsairaus olivat itsenäisiä riskitekijöitä vaikealle tehohoitoa ja hengitystukea vaativalle taudille. Vuosien 2000-2015 aikana tehottomaksi todetut hoidot vähenivät tutkimustiedon ja hoitosuositusten vaikutuksen myötä. Neljässä yliopistollisessa sairaalassa raseemisen adrenaliinin käyttö vaihteli merkittävästi. Käypä hoito -suosituksen myötä raseemisen adrenaliinin käyttö väheni sairaaloissa ja merkittävin muutos oli nähtävissä yksiköissä, joissa käyttö oli ollut runsainta.Bronchiolitis is the primary reason for the hospitalisation of infants younger than 12 months worldwide and respiratory syncytial virus its most common causative agent. Even though bronchiolitis is both common and clinically important, there is no unified consensus on either its treatment or its diagnostic criteria. Its primary symptoms resemble those of an upper respiratory tract infection prior to the onset of typical symptoms of breathing difficulty—such as tachypnoea, chest retraction and auscultatory findings. Hospitalisation due to bronchiolitis is required for 3% of infants less than 12 months of age, of which 2-6% necessitate admission to the paediatric intensive care unit (PICU). For decades, bronchiolitis has been treated with different medications that included corticosteroids, inhaled agents (such as salbutamol, adrenaline, and saline) and anticholinergic agents, while respiratory failure has been treated with non-invasive and invasive support if needed. However, most of the medications previously used have failed to improve the course of the disease and opting fewer diagnostic tests and less invasive respiratory supports has not led to worse outcomes. Hence, the current guidelines recommend only supportive treatment for bronchiolitis. The aim of this thesis is to describe a definition for bronchiolitis and its management in Finland and Sweden, as well as to evaluate the changes in its management with a special focus on the influence of evidence-based clinical practice guidelines. In addition, this thesis also examines the incidences of severe bronchiolitis treated in the Tampere district PICU, the risk factors for PICU admission and the need for respiratory support in infants with bronchiolitis. Several methods have been used to conduct the research and gather the data for this thesis. A questionnaire on treatment strategies and bronchiolitis definition was sent to paediatricians who were responsible for the treatment of bronchiolitis in Finland and Sweden. Their responses were weighted by the number of infants living in their catchment areas. The questionnaire covered 74% and 100% of Swedish and Finnish infants younger than 12 months, respectively. Subsequently, a retrospective case-control study on the risk factors for intensive care admission and respiratory support requirement was performed at the Tampere University Hospital, covering the period from 2000 to 2015. All infants with bronchiolitis needing admission to the PICU were identified (n = 105), as well as two controls with bronchiolitis for each case: the first, arriving to the emergency department immediately before the case needing admission to the PICU and the second arriving immediately afterwards (n = 210). For the case-control study, the multivariable logistic regression analyses were used to identify the risk factors for PICU admission. Three time periods were distinguished (2000–2005, 2006–2010, and 2011–2015) and used to describe the changes in the management of severe bronchiolitis. The data on the use of racemic adrenaline in four attending university hospitals in Finland were collected from their hospital pharmacy registers for the 2012–2016 period. On average, the upper age limit for bronchiolitis diagnosis was 12.7 months in Finland and 12.5 months in Sweden. Adrenaline inhalations were given to patients in both countries, but the Swedish paediatricians preferred using inhaled levo-adrenaline while inhaled racemic adrenaline was the preferred choice of the Finnish paediatricians. Corticosteroids were used rarely. The average annual age-specific incidence of infants with bronchiolitis who were younger than 12 months and required admission to the PICU was 1.5/1,000/year during the 16-year follow-up period in the Tampere district. The independent significant risk factors for PICU admission included: being less than two months old, a birth weight of less than 2,000 g, a presence of congenital heart disease (CHD), a presence of apnoeas and the absence of wheezing. Correspondingly, the independent significant risk factors for respiratory support included: being less than two months old, a birth weight of less than 2,000 g and a presence of CHD. When the three study periods (2000-2005, 2006-2010 and 2011-2015) were compared, the use of inhaled beta-agonists and systemic corticosteroids decreased, while the use of racemic adrenaline and hypertonic saline inhalations increased in the Tampere University Hospital. In contrast, the use of racemic adrenaline was reduced in the four attending university hospitals during the 2012-2016 study period, particularly in the two hospitals where the baseline consumption was highest. The definitions of and treatment strategies for infant bronchiolitis were found to be rather similar in Finland and Sweden. A young age, low birth weight and CHD were independent significant risk factors for severe cases of the disease that need intensive care and respiratory support. During the 16-year period, the influences of the current literature and guidelines is observed in the management of the disease, as the use of unproven medications diminished. Substantial differences existed in the yearly consumption of racemic adrenaline between the four participating university hospitals, both before and after the publication of the Finnish Current Care Guidelines for bronchiolitis in 2014

Bronkioliitti : Hoito ja riskitekijät vaikealle taudinkuvalle

Bronkioliitti eli ilmatiehyttulehdus on yleisin alle vuoden ikäisten lasten sairaalahoidon syy. Sen aiheuttajana on useimmiten respiratory syncytial virus. Vaikka bronkioliitti on tavallinen ja hyvin tunnistettu tauti, ei sille ole kansainvälisesti yhtenäistä määritelmää tai yhtenäisiä hoitosuosituksia. Bronkioliitin ensimmäiset oireet muistuttavat tavallista ylähengitystieinfektiota ja vasta muutaman päivän sisällä ilmaantuvat alahengitystieinfektion oireet: hengityksen tihentyminen, kylkivälivetäymät ja poikkeava keuhkojen kuuntelulöydös. Kolme prosenttia alle vuoden ikäisistä lapsista tarvitsee sairaalahoitoa bronkioliitin vuoksi ja heistä 2-6 prosenttia tarvitsee tehohoitoa. Viimeisten vuosikymmenten aikana bronkioliittia on hoidettu monenlaisilla lääkkeillä kuten kortikosteroideilla, hengitettävillä lääkkeillä salbuta¬molilla, adrenaliinilla ja keittosuolalla ja antikolinergeillä. Kaikki nämä on todettu tutkimuksissa kuitenkin tehottomiksi. Tämänhetkiset näyttöön perustuvat hoitosuositukset suosittelevat supportiivista hoitoa. Hengitysvaikeutta hoidetaan tarvittaessa hengitystuella. Tutkimusten mukaan näytteenoton vähentäminen, lääkehoitojen karsiminen ja non-invasiivisten hengitystukihoitojen käyttö eivät johda huonompaan lopputulokseen. Väitöskirjani tavoitteena on kuvata bronkioliitin määritelmää, hoitoa sekä hoidon muutosta suhteessa näyttöön perustuviin hoitosuosituksiin. Lisäksi työssä arvioidaan vaikean tehohoitoa vaativan bronkioliitin ilmaantuvuutta ja riskitekijöitä tehohoitoon joutumiselle ja hengitystukihoidolle. Kyselykaavake lähetettiin kaikkiin lastensairaaloihin Suomessa ja Ruotsissa ja bronkioliitin hoidosta vastaavaa lastenlääkäriä pyydettiin vastaamaan bronkioliitin määritelmää ja hoitoa koskevaan kyselyyn. Vastaukset painotettiin alueella asuvien alle vuoden ikäisten lasten määrän mukaan. Kyselyalueet kattoivat 74 prosenttia Ruotsin ja 100 prosenttia Suomen alle vuoden ikäisistä lapsista. Retrospektiivisen tapaus-verrokkitutkimuksen aineisto kerättiin Tampereen yliopistollisesta sairaalasta vuosilta 2000-2015. Tutkimuksessa kartoitettiin tehohoitoon ja hengitystukihoitoon joutumisen riskitekijöitä bronkoliittipotilailla. Yhteensä 16 vuoden aikana 105 lasta oli hoidettu teho-osastolla bronkioliitin vuoksi. Jokaista tehohoidettua potilasta kohden kerättiin kaksi bronkioliittia sairastanutta verrokkia päivystyspoliklinikka käynneistä: yksi ennen tapausta ja yksi tapauksen jälkeen. Tapaus-verrokkiaineistosta tutkittiin tehohoidon muutosta jakamalla aineisto kolmeen ajanjaksoon: 2000-2005, 2006-2010 ja 2011-2015. Aineisto raseemisen adrenaliinin käytöstä kerättiin neljän yliopistosairaalan sairaala-apteekkien rekistereistä vuosilta 2012-2016. Bronkioliitin määritelmän yläikärajan keskiarvo oli 12.7 kk Suomessa ja 12.5 kk Ruotsissa. Adrenaliini-inhalaatioiden käyttö oli yleistä molemmissa maissa, mutta Ruotsissa lastenlääkärit suosivat levo-adrenaliinia, kun taas Suomessa suosittiin raseemista adrenaliinia. Kortikosteroideja käytettiin harvoin. Alle vuoden ikäisillä lapsilla keskimääräinen ikävakioitu ilmaantuvuus vaikealle tehohoitoa vaativalle bronkioliitille oli 1.5/1000/vuosi. Itsenäisiä riskitekijöitä tehohoidolle olivat alle 2 kuukauden ikä, syntymäpaino alle 2000 g, synnynnäiset sydänsairaudet, hengitys¬katkokset ja hengityksen vinkumisen puuttuminen. Lisäksi itsenäisiä riskitekijöitä hengitystuen tarpeelle olivat alle 2 kk:n ikä, syntymäpaino alle 2000 g ja synnynnäinen sydänsairaus. Ajanjaksoina 2000-2005, 2006-2010 ja 2011-2015, inhaloitavien beeta-agonistien ja systeemisen kortikosteroidin käyttö laski. Sen sijaan raseemisen adrenaliinin ja hypertonisten keittosuolainhalaatioiden käyttö lisääntyi Tampereen yliopistollisessa sairaalassa. Raseemisen adrenaliinin käyttö kuitenkin väheni yliopistollisissa sairaaloissa vuosina 2012-2016. Tämä muutos näkyi selvimmin sairaaloissa, joissa käyttö oli ollut yleisintä. Yhteenvetona bronkioliitin määritelmä ja annettu hoito olivat hyvin yhdenmukaisia Suomessa ja Ruotsissa. Nuori ikä, alhainen syntymäpaino ja synnynnäinen sydänsairaus olivat itsenäisiä riskitekijöitä vaikealle tehohoitoa ja hengitystukea vaativalle taudille. Vuosien 2000-2015 aikana tehottomaksi todetut hoidot vähenivät tutkimustiedon ja hoitosuositusten vaikutuksen myötä. Neljässä yliopistollisessa sairaalassa raseemisen adrenaliinin käyttö vaihteli merkittävästi. Käypä hoito -suosituksen myötä raseemisen adrenaliinin käyttö väheni sairaaloissa ja merkittävin muutos oli nähtävissä yksiköissä, joissa käyttö oli ollut runsainta.Bronchiolitis is the primary reason for the hospitalisation of infants younger than 12 months worldwide and respiratory syncytial virus its most common causative agent. Even though bronchiolitis is both common and clinically important, there is no unified consensus on either its treatment or its diagnostic criteria. Its primary symptoms resemble those of an upper respiratory tract infection prior to the onset of typical symptoms of breathing difficulty—such as tachypnoea, chest retraction and auscultatory findings. Hospitalisation due to bronchiolitis is required for 3% of infants less than 12 months of age, of which 2-6% necessitate admission to the paediatric intensive care unit (PICU). For decades, bronchiolitis has been treated with different medications that included corticosteroids, inhaled agents (such as salbutamol, adrenaline, and saline) and anticholinergic agents, while respiratory failure has been treated with non-invasive and invasive support if needed. However, most of the medications previously used have failed to improve the course of the disease and opting fewer diagnostic tests and less invasive respiratory supports has not led to worse outcomes. Hence, the current guidelines recommend only supportive treatment for bronchiolitis. The aim of this thesis is to describe a definition for bronchiolitis and its management in Finland and Sweden, as well as to evaluate the changes in its management with a special focus on the influence of evidence-based clinical practice guidelines. In addition, this thesis also examines the incidences of severe bronchiolitis treated in the Tampere district PICU, the risk factors for PICU admission and the need for respiratory support in infants with bronchiolitis. Several methods have been used to conduct the research and gather the data for this thesis. A questionnaire on treatment strategies and bronchiolitis definition was sent to paediatricians who were responsible for the treatment of bronchiolitis in Finland and Sweden. Their responses were weighted by the number of infants living in their catchment areas. The questionnaire covered 74% and 100% of Swedish and Finnish infants younger than 12 months, respectively. Subsequently, a retrospective case-control study on the risk factors for intensive care admission and respiratory support requirement was performed at the Tampere University Hospital, covering the period from 2000 to 2015. All infants with bronchiolitis needing admission to the PICU were identified (n = 105), as well as two controls with bronchiolitis for each case: the first, arriving to the emergency department immediately before the case needing admission to the PICU and the second arriving immediately afterwards (n = 210). For the case-control study, the multivariable logistic regression analyses were used to identify the risk factors for PICU admission. Three time periods were distinguished (2000–2005, 2006–2010, and 2011–2015) and used to describe the changes in the management of severe bronchiolitis. The data on the use of racemic adrenaline in four attending university hospitals in Finland were collected from their hospital pharmacy registers for the 2012–2016 period. On average, the upper age limit for bronchiolitis diagnosis was 12.7 months in Finland and 12.5 months in Sweden. Adrenaline inhalations were given to patients in both countries, but the Swedish paediatricians preferred using inhaled levo-adrenaline while inhaled racemic adrenaline was the preferred choice of the Finnish paediatricians. Corticosteroids were used rarely. The average annual age-specific incidence of infants with bronchiolitis who were younger than 12 months and required admission to the PICU was 1.5/1,000/year during the 16-year follow-up period in the Tampere district. The independent significant risk factors for PICU admission included: being less than two months old, a birth weight of less than 2,000 g, a presence of congenital heart disease (CHD), a presence of apnoeas and the absence of wheezing. Correspondingly, the independent significant risk factors for respiratory support included: being less than two months old, a birth weight of less than 2,000 g and a presence of CHD. When the three study periods (2000-2005, 2006-2010 and 2011-2015) were compared, the use of inhaled beta-agonists and systemic corticosteroids decreased, while the use of racemic adrenaline and hypertonic saline inhalations increased in the Tampere University Hospital. In contrast, the use of racemic adrenaline was reduced in the four attending university hospitals during the 2012-2016 study period, particularly in the two hospitals where the baseline consumption was highest. The definitions of and treatment strategies for infant bronchiolitis were found to be rather similar in Finland and Sweden. A young age, low birth weight and CHD were independent significant risk factors for severe cases of the disease that need intensive care and respiratory support. During the 16-year period, the influences of the current literature and guidelines is observed in the management of the disease, as the use of unproven medications diminished. Substantial differences existed in the yearly consumption of racemic adrenaline between the four participating university hospitals, both before and after the publication of the Finnish Current Care Guidelines for bronchiolitis in 2014