Acute severe complications of otitis media in children and adults

Acute otitis media (AOM) is an infection that is particularly common in children. The bacterial etiology of AOM, in both children and adults, affects its clinical picture. While in some cases the infection can simply be carefully monitored without treatment, antimicrobials are often prescribed. Caution is required, however, when prescribing antimicrobials as their excessive use has led to antimicrobial resistance; this resistance has been seen among some of the causative pathogens for these infections. Before the development of antimicrobial treatment, complications due to middle ear infections were common, potentially causing severe symptoms or even death. Some middle ear infections spread into surrounding structures, leading to intratemporal or extratemporal (extracranial or intracranial) complications. This thesis focuses on complicated otitis media and the causative factors of its complications. In the first two studies, we evaluated the medical records of all (n=100) children (0-16 years old) hospitalized at the Department of Otorhinolaryngology in the Helsinki University Hospital from 2003 to 2012 for acute mastoiditis (AM) or AOM, as well as the infection s bacteriology in relation to the patient s clinical findings and treatment. Using this information, we analyzed the differences in the etiologies and clinical pictures of those children hospitalized due to AOM compared to AM. In our third study, we examined the medical records of all (n=166) patients hospitalized at our institution from 1970 to 2012 due to intracranial abscesses (IA), including those of otogenic background (oIA). In the fourth study, we evaluated the bacteriology in relation to the patients clinical findings and treatment in all (n=160) adult patients treated at our institution from 2003 to 2012 for AOM or acute mastoid infection. In adults, acute mastoid infection was subclassified into AM, latent mastoiditis (LM), and AM following chronic middle ear infection (AMc). The clinical picture of AM in children differed according to the causative pathogen. Streptococcus pneumoniae (Pnc), especially its resistant strains, caused severe symptoms and often led to mastoidectomies. Pseudomonas aeruginosa (Ps) typically affected older children with prior tympanostomy tubes and generally caused milder symptoms. Furthermore, the bacteriological etiology of hospitalized AOM and AM patients was different compared to outpatient AOM. Two of the typical AOM pathogens, Haemophilus influenzae (Hi) and Moraxella catarrhalis (Mc), were uncommon among the hospitalized patients. Pnc, especially its resistant strains, was less common in children hospitalized for AOM compared to AM, and less common in adults than children. Streptococcus pyogenes (StrA) and Ps were both linked to otorrhea and were found only in older children. Over our 42 year study period, oIAs became less common and typically developed following chronic middle ear infections, often in connection with cholesteatoma. In adults, the bacteriological etiology and clinical picture of AMc differed from AOM as well as the other acute mastoid infection types (AM, LM). AOM and AM led to less surgical procedures than the more prolonged forms of acute mastoid infection (LM, AMc). In children, the hospitalized cases of AOM and AM differed from outpatient AOM. In adults, severe AOM, AM, and LM seem to compose a continuum that may lead to chronic otitis media and its acute complications, including oIAs. Otogenic IAs are quite rare, however, and became less common over our study period.Äkillinen välikorvatulehdus on yksi lasten tavallisimmista taudeista; aikuisilla se on lapsia harvinaisempi. Vaikka pelkkä seuranta voi riittää äkillisen välikorvatulehduksen hoidoksi, usein hoitona käytetään antibioottia. Välikorvatulehdus voi levitä välikorvaa ympäröiviin rakenteisiin aiheuttaen vakaviakin komplikaatioita (esim. kartiolisäketulehdus, aivopaise). Ennen antibioottien kehittämistä välikorvatulehduksen komplikaatioita esiintyi nykyistä enemmän. Turhaa antibioottien käyttöä on vältettävä, mutta komplisoitunutta tautia sairastavat potilaat on tunnistettava varhain ja hoidettava tehokkaasti. Tässä tutkimuksessa selvitettiin komplisoituneen välikorvatulehduksen taustatekijöitä. Äkillisen kartiolisäketulehduksen tai välikorvatulehduksen vuoksi HUS:n Korvaklinikalle sairaalahoitoon vuosina 2003 2012 joutuneiden potilaiden (100 lasta, 160 aikuista) sairauskertomustiedot käytiin läpi. Bakteereiden suhdetta taudinkuvaan ja hoitoon arvioitiin, ja potilasryhmien tietoja vertailtiin keskenään. Kaikkien aivopaiseen vuoksi sairaalahoitoon HUS:n Neurokirurgian klinikalle vuosina 1970 2012 joutuneiden potilaiden (166) sairauskertomustiedot käytiin läpi. Aineistoon sisältyivät myös korvaperäiset aivopaiseet. Streptococcus pneumoniae on tavallinen välikorvatulehduksen taudinaiheuttaja, myös tässä tutkimuksessa. Erityisesti kartiolisäketulehdusta sairastavilla lapsipotilailla esiintyi muita lapsia ja aikuisia enemmän tavallisille korvatulehduksen hoidossa käytettäville antibiooteille vastustuskykyisiä Streptococcus pneumoniae -kantoja. Nämä johtivat muita taudinaiheuttajia useammin kartiolisäkkeen puhdistusleikkauksiin. Kaksi tavallisimmista äkillisen välikorvatulehduksen taudinaiheuttajista, Haemophilus influenzae ja Moraxella catarrhalis, olivat sen sijaan harvinaisia komplisoitunutta välikorvatulehdusta sairastavilla potilailla. Aikuisilla pitkäkestoisten välikorvatulehdusten äkillisiin komplikaatioihin liittyi enemmän leikkaushoidon tarvetta kuin äkillisten välikorvatulehdusten komplikaatioihin. Korvaperäiset aivopaiseet harvinaistuivat ajan kuluessa, ja ne liittyivät yleensä pitkäkestoiseen välikorvatulehdukseen ja helmiäiskasvamaan. Avohoidossa hoidettava välikorvatulehdus eroaa sairaalahoitoon johtaneesta välikorvatulehduksesta ja kartiolisäketulehduksesta. Välikorvatulehduksen komplikaatiot voivat johtaa pitkäkestoiseen välikorvatulehdukseen ja sen akuutteihin komplikaatioihin, myös aivopaiseisiin. Korvaperäiset aivopaiseet olivat tutkimusaineistossa kuitenkin harvinaisia, ja niiden määrä vähentyi tutkimusjakson kuluessa

Laser, radiofrequency or tympanostomy knife? : Comparison of surgical methods in tympanostomy treatment of young children and predictive value of tympanometry

Objectives: To investigate tympanostomy tube (TT) treatment in young children, with special interest in bloodless surgical methods (laser and radiofrequency), myringosclerosis formation and tympanometric testing.Methods: This prospective study includes 76 children whose 121 ears with middle ear effusion were treated with tympanostomy tubes. Myringotomy was performed with CO2 laser in 37, radiofrequency in 40 and myringotomy knife in 44 ears. The ears were evaluated with otomicroscopy and tympanometry preoperatively and post-operatively every 3-4 months until spontaneous tube extrusion.Results: All tubes extruded spontaneously (mean 12.8 months, range 3-36 months), with no persistent perfora-tions or cholesteatomas. CO2 laser and radiofrequency inserted tympanostomy tubes extruded faster (mean 11 months) compared to incisional myringotomy (mean 15 months, p = 0.002). Myringosclerosis was noted in 25 (21%) ears after treatment. There was a tendency to less myringosclerosis with bloodless techniques, but the difference was not significant. Flat tympanograms on the day of procedure predicted continuation of ventilation problems also after TT treatment (p = 0.003). Ears with preoperative type B tympanogram had significantly more myringosclerosis 21/75 (28%) compared with type A and C tympanograms 4/41 (10%) (p = 0.032).Conclusions: While all myringotomy methods were effective and safe, the traditional incisional myringotomy with a tympanostomy knife is still a good, feasible and cost-effective myringotomy method. No surgical removal of tympanostomy tubes is needed before 3 years of uncomplicated tympanostomy treatment. Tympanometry turned out to be a useful tool in prediction of post TT treatment ventilation problems of the middle ear.Peer reviewe

Differentiating Acute Otitis Media and Acute Mastoiditis in Hospitalized Children

Acute otitis media is a common infection in children. Most acute otitis media episodes can be treated at an outpatient setting with antimicrobials, or only expectant observation. Hospital treatment with parenteral medication, and myringotomy or tympanostomy, may be needed to treat those with severe, prolonged symptoms, or with complications. The most common intratemporal complication of acute otitis media is acute mastoiditis. If a child with acute mastoiditis does not respond to this treatment, or if complications develop, further examinations and other surgical procedures, including mastoidectomy, are considered. Since the treatment of complicated acute otitis media and complicated acute mastoiditis differs, it is important to differentiate these two conditions. This article focuses on the differential diagnostics of acute otitis media and acute mastoiditis in children.Peer reviewe

Airway Epithelial Dynamics in Allergy and Related Chronic Inflammatory Airway Diseases

Allergic rhinitis, chronic rhinosinusitis, and asthma are highly prevalent, multifactorial chronic airway diseases. Several environmental and genetic factors affect airway epithelial dynamics leading to activation of inflammatory mechanisms in the airways. This review links environmental factors to host epithelial immunity in airway diseases. Understanding altered homeostasis of the airway epithelium might provide important targets for diagnostics and therapy of chronic airway diseases.Peer reviewe

Monoclonal Antibodies and Airway Diseases

Monoclonal antibodies, biologics, are a relatively new treatment option for severe chronic airway diseases, asthma, allergic rhinitis, and chronic rhinosinusitis (CRS). In this review, we focus on the physiological and pathomechanisms of monoclonal antibodies, and we present recent study results regarding their use as a therapeutic option against severe airway diseases. Airway mucosa acts as a relative barrier, modulating antigenic stimulation and responding to environmental pathogen exposure with a specific, self-limited response. In severe asthma and/or CRS, genome–environmental interactions lead to dysbiosis, aggravated inflammation, and disease. In healthy conditions, single or combined type 1, 2, and 3 immunological response pathways are invoked, generating cytokine, chemokine, innate cellular and T helper (Th) responses to eliminate viruses, helminths, and extracellular bacteria/fungi, correspondingly. Although the pathomechanisms are not fully known, the majority of severe airway diseases are related to type 2 high inflammation. Type 2 cytokines interleukins (IL) 4, 5, and 13, are orchestrated by innate lymphoid cell (ILC) and Th subsets leading to eosinophilia, immunoglobulin E (IgE) responses, and permanently impaired airway damage. Monoclonal antibodies can bind or block key parts of these inflammatory pathways, resulting in less inflammation and improved disease control

Monoclonal Antibodies and Airway Diseases

Monoclonal antibodies, biologics, are a relatively new treatment option for severe chronic airway diseases, asthma, allergic rhinitis, and chronic rhinosinusitis (CRS). In this review, we focus on the physiological and pathomechanisms of monoclonal antibodies, and we present recent study results regarding their use as a therapeutic option against severe airway diseases. Airway mucosa acts as a relative barrier, modulating antigenic stimulation and responding to environmental pathogen exposure with a specific, self-limited response. In severe asthma and/or CRS, genome–environmental interactions lead to dysbiosis, aggravated inflammation, and disease. In healthy conditions, single or combined type 1, 2, and 3 immunological response pathways are invoked, generating cytokine, chemokine, innate cellular and T helper (Th) responses to eliminate viruses, helminths, and extracellular bacteria/fungi, correspondingly. Although the pathomechanisms are not fully known, the majority of severe airway diseases are related to type 2 high inflammation. Type 2 cytokines interleukins (IL) 4, 5, and 13, are orchestrated by innate lymphoid cell (ILC) and Th subsets leading to eosinophilia, immunoglobulin E (IgE) responses, and permanently impaired airway damage. Monoclonal antibodies can bind or block key parts of these inflammatory pathways, resulting in less inflammation and improved disease control

Monoklonaaliset vasta-aineet pitkittyneen polypoottisen sivuontelotulehduksen ja astman hoidossa

Vertaisarvioitu.Hengitysteiden limakalvolla muodostuu normaalitilanteessa tulehdusvasteita muun muassa viruksia, alkueläimiä, bakteereja ja sieniä vastaan. Kun tulehduksen aiheuttaja saadaan poistettua, tulehdusvaste sammuu. Astmassa ja pitkittyneessä polypoottisessa sivuontelotulehduksessa tulehdus on krooninen, ja sen oletetaan syntyvän geneettisen alttiuden ja ympäristötekijöiden yhteisvaikutuksesta. Suurimmalla osalla potilaista tulehdus on tyypin 2 sytokiinien välittämä, ja siihen liittyvät interleukiinit (IL) 4, 5 ja 13. Tyypin 2 sytokiinien välittämä tulehdus johtaa eosinofiliaan ja immunoglobuliini E (IgE) -vasteisiin, ja se voi hoitamattomana johtaa hengitysteiden pysyviin rakenteellisiin ja toiminnallisiin muutoksiin. Biologisessa hoidossa käytetyt monoklonaaliset vasta-aineet estävät näitä tyypin 2 sytokiinien välittämiä tulehdusvasteita, vähentävät hengitysteiden tulehdusta ja parantavat sen hallintaa.Peer reviewe

The Nose as a Route for Therapy: Part 1. Pharmacotherapy

This article reviews nasal structure and function in the light of intranasal pharmacotherapy. The nose provides an accessible, fast route for local treatment of nose and sinus diseases, with lower doses than are necessary systemically and few adverse effects. It can also be used for other medications as it has sufficient surface area protected from local damage by mucociliary clearance, absence of digestive enzymes, responsive blood flow, and provides a rapid route to the central nervous system.Peer reviewe

Genomics of asthma, allergy and chronic rhinosinusitis : novel concepts and relevance in airway mucosa

Funding Information: The study was supported in part by research grants from Finnish Medical Foundation, the Finnish Society of Allergology and Immunology, the Jane and Aatos Erkko Foundation, the Finnish Cultural Foundation, Hospital District of Helsinki and Uusimaa (TYH2018103, TYH2019322), Paulo Foundation, the Tampere Tuberculosis Foundation, the Väinö and Laina Kivi Foundation, the Finnish ORL-HNS Foundation. Acknowledgements Publisher Copyright: © 2020, The Author(s).Genome wide association studies (GWASs) have revealed several airway disease-associated risk loci. Their role in the onset of asthma, allergic rhinitis (AR) or chronic rhinosinusitis (CRS), however, is not yet fully understood. The aim of this review is to evaluate the airway relevance of loci and genes identified in GWAS studies. GWASs were searched from databases, and a list of loci associating significantly (p <10(-8)) with asthma, AR and CRS was created. This yielded a total of 267 significantly asthma/AR-associated loci from 31 GWASs. No significant CRS -associated loci were found in this search. A total of 170 protein coding genes were connected to these loci. Of these, 76/170 (44%) showed bronchial epithelial protein expression in stained microscopic figures of Human Protein Atlas (HPA), and 61/170 (36%) had a literature report of having airway epithelial function. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses were performed, and 19 functional protein categories were found as significantly (p <0.05) enriched among these genes. These were related to cytokine production, cell activation and adaptive immune response, and all were strongly connected in network analysis. We also identified 15 protein pathways that were significantly (p <0.05) enriched in these genes, related to T-helper cell differentiation, virus infection, JAK-STAT signaling pathway, and asthma. A third of GWAS-level risk loci genes of asthma or AR seemed to have airway epithelial functions according to our database and literature searches. In addition, many of the risk loci genes were immunity related. Some risk loci genes also related to metabolism, neuro-musculoskeletal or other functions. Functions overlapped and formed a strong network in our pathway analyses and are worth future studies of biomarker and therapeutics.Peer reviewe

Factors Affecting the Control of Chronic Rhinosinusitis With Nasal Polyps : A Comparison in Patients With or Without NERD

Objectives: The aim was to compare the control of chronic rhinosinusitis with nasal polyps (CRSwNP) after endoscopic sinus surgery (ESS), in patients with/without nonsteroidal anti-inflammatory drug exacerbated respiratory disease (NERD). Study Desing: A retrospective hospital-based sample of CRSwNP patients with/without NERD with follow-up. Setting: Tertiary rhinology centers. Methods: Electronic patient record data from 116 CRSwNP patients (46 with NERD and 70 without NERD) undergoing ESS during 2001-17 were studied. Mean follow-up time was 9.9 years (range 1.1-15.3). Endpoints reflecting uncontrolled CRSwNP were revision ESS, and need for rescue/advanced therapy (e.g. antibiotics, oral corticosteroids and/or biological therapy) during follow-up. NERD was variable of interest and gender, age, asthma, allergic rhinitis (AR), smoking, Lund-Mackay (LM) score of sinus computed tomography scans previous ESS and baseline total ethmoidectomy were used as covariates. Results: Twenty-one (49.7%) NERD patients and 18 (25.7%) non-NERD patients underwent revision ESS within a mean +/- SD of 4.3 +/- 2.8 and 3.7 +/- 2.6 years, respectively (p = .013, by Logrank test). In Cox ' s regression models, NERD, female gender, young age, asthma, AR, previous ESS, and lack of total ethmoidectomy were associated with revision-ESS. In adjusted model, only the total ethmoidectomy predicted revision-free survival. In adjusted logistic regression model, there was an insignificant trend that NERD and LM score were associated with the need for rescue/advanced therapy in the follow-up. Conclusions: Patients with NERD had higher risk of uncontrolled CRSwNP than patient group without NERD, as measured by revision ESS and/or need for rescue/advanced therapy in the follow-up. In addition, baseline total ethmoidectomy was associated with revision-free survival.Peer reviewe