A N N A L E S U N IV E R S IT A T IS T U R K U E N S IS D 1 3 3 5 Jo h a n n a U itti ROLE OF SYMPTOMS IN THE DIAGNOSIS AND MANAGEMENT OF ACUTE OTITIS MEDIA IN YOUNG CHILDREN Johanna Uitti Oy, Turku , Finland 2018 ma Painosala ISBN 978-951-29-7128-2 (PRINT) TURUN YLIOPISTON JULKAISUJA – ANNALES UNIVERSITATIS TURKUENSIS ISBN 978-951-29-7129-9 (PDF) Sarja - ser. D osa - tom. 1335 | Medica - Odontologica | Turku 2018 ISSN 0355-9483 (PRINT) | ISSN 2343-3213 (PDF) ROLE OF SYMPTOMS IN THE DIAGNOSIS AND MANAGEMENT OF ACUTE OTITIS MEDIA IN YOUNG CHILDREN Johanna Uitti TURUN YLIOPISTON JULKAISUJA – ANNALES UNIVERSITATIS TURKUENSIS Sarja - ser. D osa - tom. 1335 | Medica - Odontologica | Turku 2018 University of Turku Faculty of Medicine Institute of Clinical Medicine Department of Paediatrics Doctoral Programme in Clinical Research Department of Paediatrics and Adolescent Medicine Turku University Hospital Supervised by Docent Aino Ruohola, MD, PhD Professor Olli Ruuskanen, MD, PhD Department of Paediatrics Department of Paediatrics Institute of Clinical Medicine and Adolescent Medicine University of Turku, Turku, Finland Turku University Hospital, Turku, Finland Department of Paediatrics and Adolescent Medicine Turku University Hospital, Turku, Finland Reviewed by Docent Terhi Tapiainen, MD, PhD Docent Harri Saxén, MD, PhD PEDEGO Research Unit Hospital for Children and Adolescents University of Oulu, Oulu, Finland University of Helsinki, Helsinki, Finland Department of Pediatrics and Adolescence Oulu University Hospital, Oulu, Finland Opponent Docent Marjo Renko, MD, PhD PEDEGO Research Unit University of Oulu, Oulu, Finland Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland The originality of this thesis has been checked in accordance with the University of Turku quality assurance system using the Turnitin OriginalityCheck service. ISBN 978-951-29-7128-2 (PRINT) ISBN 978-951-29-7129-9 (PDF) ISSN 0355-9483 (Print) ISSN 2343-3213 (Online) Painosalama Oy – Turku, Finland 2018 To my family Abstract ABSTRACT Johanna Uitti, MD Role of symptoms in the diagnosis and management of acute otitis media in young children University of Turku, Faculty of Medicine, Institute of Clinical Medicine, Depart- ment of Paediatrics, Doctoral Programme in Clinical Research; Department of Paediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland Annales Universitatis Turkuensis, Medica-Odontologica, Painosalama Oy, Tur- ku, Finland, 2018 Acute symptoms are required for the diagnosis of acute otitis media (AOM) and they guide the management together with the laterality of AOM. However, symp- toms are variable in young children and not diagnostic with AOM. We investigated ear pain with parentally used pain scales, clinical characteristics of bilateral and unilateral AOM, symptoms and nasopharyngeal microbes and the need for follow-up of children with AOM initially managed without antimicrobi- als. We included children (6-35 months) with respiratory tract infection (RTI) whose parents suspected AOM. In children with RTI, either with or without AOM, ear pain was assessed as moderate/severe in 80-90% with parentally used pain scales, compared with 56- 65% with parental interview. In children with bilateral vs. unilateral AOM, fever occurred in 54% vs. 36% and moderate/severe bulging of tympanic membrane in 63% vs. 40%. In children with the suspicion of AOM, respiratory symptoms were associated with the nasopharyngeal colonization of Moraxella catarrhalis in the presence of viruses and fever was associated with respiratory viruses. Of the children with AOM initially managed without antimicrobials who had symp- tomatic improvement, the otoscopic signs worsened in 3%. Majority of children with RTI suffer from moderate/severe ear pain or distress, when assessed by parents, regardless of AOM. Without pain scales, parents may underestimate children’s pain. Clinically, bilateral AOM is only slightly more severe illness than unilateral AOM. Symptoms are associated with nasopharyn- geal microbes. For children with AOM who are initially managed without anti- microbials and who are symptomatically improving, close follow-up may be un- necessary. Keywords: acute otitis media, symptoms, ear pain, pain scales, otoscopic signs, unilateral, bilateral, children, respiratory tract infection, bacteria, viruses, naso- pharynx Tiivistelmä TIIVISTELMÄ LL Johanna Uitti Oirekuvan rooli äkillisen välikorvatulehduksen diagnostiikassa ja hoidossa pienillä lapsilla Turun yliopisto, Lääketieteellinen tiedekunta, Kliininen laitos, Lastentautioppi, Turun kliininen tohtoriohjelma; Lasten ja nuorten klinikka, Turun yliopistollinen keskussairaala, Turku, Suomi Annales Universitatis Turkuensis, Medica-Odontologica, Painosalama Oy, Tur- ku, Suomi, 2018 Äkillisen välikorvatulehduksen diagnoosiin vaaditaan äkilliset infektioon viittaavat oireet. Oireet ja äkillisen välikorvatulehduksen tois- tai molemminpuolisuus vai- kuttavat välikorvatulehduksen hoitoon. Oireet ovat kuitenkin vaihtelevia pienillä lapsilla ja yksikään oireista ei ole diagnostinen äkilliselle välikorvatulehdukselle. Tutkimme korvakipua vanhempien käyttämillä kipumittareilla, tois- ja molem- minpuolisen välikorvatulehduksen kliinisiä piirteitä, oireita ja nenänielun mikro- beita, sekä seurantakäynnin tarvetta 2-3 päivän kuluttua äkillisen välikorvatuleh- duksen diagnoosista niillä lapsilla, joita seurataan ilman mikrobilääkehoitoa. Tutkimukseen otettiin mukaan 6-35 kuukauden ikäisiä lapsia, joilla oli hengitys- tieinfektio ja joilla vanhemmat epäilivät äkillistä välikorvatulehdusta. Hengitystieinfektiota sairastavilla lapsilla, joilla joko oli tai ei ollut äkillistä väli- korvatulehdusta, vanhemmat arvioivat kipumittareita käyttäessään korvakivun kohtalaiseksi/vaikeaksi 80-90%:lla.Kun vanhempia haastateltiin, vastaava luku oli 56-65%. Molemminpuolista välikorvatulehdusta ja toispuolista välikorvatulehdus- ta sairastavilla lapsilla oli kuumetta 54%:lla ja 36%:lla ja tärykalvon kohtalaista tai merkittävää pullotusta 63%:lla ja 40%:lla. Lapsilla, joilla epäiltiin äkillistä väli- korvatulehdusta, flunssaoireet olivat yhteydessä nenänielun Moraxella catarrhalis- bakteerikantajuuteen virusten ohella ja kuumeella oli yhteys hengitystieviruksiin. Äkillistä välikorvatulehdusta sairastavilla lapsilla, joita seurattiin ilman mikrobi- lääkehoitoa ja joiden yleisvointi parani, korvatulehduslöydökset pahenivat 3%:lla. Valtaosa hengitystieinfektiota sairastavista lapsista kärsii vanhempien arvion mu- kaan kohtalaisesta tai vaikeasta korvakivusta tai tuskaisuudesta, riippumatta siitä, onko lapsella äkillistä välikorvatulehdusta vai ei. Ilman kipumittareita vanhemmat saattavat aliarvioivat lastensa kipua. Molemminpuolinen välikorvatulehdus on kliinisesti vain lievästi vaikeampi kuin toispuolinen välikorvatulehdus. Oireet ovat yhteydessä nenänielun mikrobeihin. Lapset, joiden äkillistä välikorvatulehdusta seurataan ilman mikrobilääkehoitoa ja joiden yleisvointi on paranemassa, eivät välttämättä tarvitse seurantakäyntiä 2-3 päivän kuluttua diagnoosista. Avainsanat: äkillinen välikorvatulehdus, oireet, korvakipu, kipumittarit, tärykal- volöydökset, toispuoleinen välikorvatulehdus, molemminpuolinen välikorvatu- lehdus, lapset, hengitystieinfektio, bakteerit, virukset, nenänielu Table of contents TABLE OF CONTENTS ABSTRACT ............................................................................................................ 4  TIIVISTELMÄ ....................................................................................................... 5  ABBREVIATIONS ................................................................................................ 9  LIST OF ORIGINAL PUBLICATIONS .............................................................. 10  1  INTRODUCTION ............................................................................................ 11  2  REVIEW OF LITERATURE ........................................................................... 13  2.1  Definitions ................................................................................................. 13  2.2  Epidemiology ............................................................................................ 13  2.3  Etiology ..................................................................................................... 14  2.3.1  Bacteria ........................................................................................... 14  2.3.2  Viruses ............................................................................................ 15  2.4  Pathogenesis .............................................................................................. 18  2.4.1  Anatomy .......................................................................................... 18  2.4.2  Function of the Eustachian tube ...................................................... 19  2.4.3  Nasopharyngeal colonization .......................................................... 19  2.4.4  Viral respiratory tract infection ....................................................... 20  2.4.5  Immunology .................................................................................... 21  2.5  Risk factors ................................................................................................ 24  2.6  Symptoms .................................................................................................. 25  2.6.1  Ear-related symptoms ..................................................................... 28  2.6.1.1  Pain scales ......................................................................... 31  2.6.2  Fever................................................................................................ 32  2.6.3  Non-specific symptoms .................................................................. 33  2.6.4  Respiratory symptoms .................................................................... 34  2.6.5  Gastrointestinal symptoms .............................................................. 34  2.6.6  Duration of symptoms ..................................................................... 34  2.6.7  Severity of symptoms and viral load .............................................. 35  2.6.8  Symptom severity scores ................................................................ 36  2.6.9  Association with bacteria and respiratory viruses .......................... 41  2.6.10 Laterality of acute otitis media ....................................................... 43  2.7  Diagnostics ................................................................................................ 44  2.7.1  Signs of tympanic membrane ......................................................... 44  2.7.2  Diagnostic tools .............................................................................. 47  2.8  Management .............................................................................................. 48  2.8.1  Symptomatic treatment ................................................................... 48 Table of contents 2.8.2  Antimicrobial treatment ................................................................. 49  2.8.2.1  Treatment guidelines for AOM ........................................ 53  2.9  Complications ........................................................................................... 54  3  AIMS OF THE STUDY .................................................................................. 56  4  MATERIALS AND METHODS ..................................................................... 57  4.1  Study population and study design ........................................................... 57  4.1.1  Diagnostic criteria for AOM .......................................................... 58  4.1.1.1  Bilateral and unilateral AOM ........................................... 58  4.1.2  Children with AOM and children without AOM ........................... 59  4.2  The enrolment visit (day 1) ....................................................................... 59  4.2.1  Symptom questionnaire .................................................................. 59  4.2.2  Pain scales (Study I) ....................................................................... 60  4.2.2.1  Faces Pain Scale-Revised (FPS-R)................................... 61  4.2.2.2  Face, Legs, Activity, Cry, Consolability (FLACC) Scale . 62  4.2.3  AOM-faces scale ............................................................................ 63  4.2.4  Examination .................................................................................... 63  4.2.4.1  Otoscopic signs ................................................................. 63  4.2.5  Nasopharyngeal sampling, bacterial and viral analyses (Study III) ... 65  4.2.6  Symptom scores (Studies II and III) ............................................... 65  4.3  Follow-up in children with AOM (days 2-8) ............................................ 66  4.4  Statistical analysis ..................................................................................... 67  5  RESULTS ........................................................................................................ 69  5.1  Detection of ear pain with parentally used pain scales and symptoms associated with moderate/severe pain (Study I) ....................................... 69  5.2  Symptoms and otoscopic signs of bilateral and unilateral AOM (Study II) . 73  5.3  Role of nasopharyngeal bacteria and respiratory viruses in acute symptoms of young children with the suspicion of AOM (Study III) ...... 75  5.4  Close follow-up in children with AOM initially managed without antimicrobials (Study IV) ......................................................................... 79  6  DISCUSSION .................................................................................................. 80  6.1  Detection of ear pain with parentally used pain scales and symptoms associated with moderate/severe pain (Study I) ....................................... 80  6.2  Symptoms and otoscopic signs of bilateral and unilateral AOM (Study II) . 83  6.3  Role of nasopharyngeal bacteria and respiratory viruses in acute symptoms of young children with the suspicion of AOM (Study III) ...... 86  6.4  Close follow-up in children with AOM initially managed without antimicrobials (Study IV) ......................................................................... 91 Table of contents 6.5  Role of symptoms and laterality of AOM in the management of AOM ... 93  6.6  Methodological limitations and strengths ................................................. 95  6.7  Future considerations ................................................................................ 97  7  SUMMARY AND CONCLUSIONS ............................................................... 99 ACKNOWLEDGEMENTS ................................................................................ 101 REFERENCES ................................................................................................... 105  ORIGINAL PUBLICATIONS ........................................................................... 117 Abbreviations ABBREVIATIONS AAP American Academy of Pediatrics AOM acute otitis media AOM-SOS AOM severity of symptom scale AOM-FS AOM faces scale AOM-Si AOM total severity index CI confidence interval dB decibel ET Eustachian tube ETG-5 ear treatment Group – five symptoms FLACC the Face, Legs, Activity, Cry, Consolability Scale FPS-R the Faces Pain Scale-Revised HBoV human bocavirus HMPV human metapneumovirus IL interleukin MEE middle ear effusion OM-3 otitis media symptom questionnaire, 3 items OME otitis media with effusion OR odds ratio OS-8 otoscopy scale, 8 grades of severity PCR polymerase chain reaction RR relative risk RSV respiratory syncytial virus RTI respiratory tract infection TLR Toll-like receptor TM tympanic membrane TNF tumor necrosis factor