Clinical and pathogenic aspects of otitis media

One study on clinical treatment strategies in otitis media and two studies elucidating immunological events in otitis media in vitro, were conducted and joined in this thesis. First, topical treatment with or without systemic antibiotics against tube associated otorrhea in children with recurrent acute otitis media was evaluated. There was no difference between the two treatment groups as measured in duration of otorrhea. Bacterial cultures from ear discharge showed mainly pathogens typical of acute otitis media. The results indicate that even though tube associated otorrhea episodes reflect episodes of acute otitis media, topical treatment without systemic antibiotics will suffice in most cases.

The second study explored immunological activities in the adenoid during otitis media with effusion (OME), focusing on Toll-like receptors (TLRs) and the nitric oxide (NO) inducing enzymes eNOS and iNOS. TLR4, TLR7, eNOS and iNOS mRNA and protein could be demonstrated in all adenoids tested. Adenoids from children with OME had higher expression of TLR7 and lower expression of iNOS than controls. TLR7 interacts with viral RNA so it is possible that viral infections, via TLR7, trigger immune reactions in the adenoid that contribute to the development of OME. A reduced ability to produce NO, reflected in low iNOS levels, might imply an increased risk for developing middle ear disease.

A third study compared the expression of TLRs and Nod-like receptors (NLRs) in mucosa from ears with chronic middle ear disease (CMED) to healthy ears. TLR3, TLR4, TLR5, TLR7, Nod2 and NALP3 mRNA and proteins were found in all middle ear mucosa samples tested. Patients with CMED had lower expression of TLR4, TLR5, TLR7 and Nalp3 than controls, whereas Nod2 was up-regulated. The hereby established presence together with the observed differences of TLRs and NLRs expression in healthy and diseased human middle ear mucosa contributes to the understanding of immune activation pathways and pathogenesis of otitis media, with special reference to CMED.

eNOS mRNA was detected in the middle ear mucosa of all tested samples, whereas the iNOS expression was low. Patients with CMED had lower levels of eNOS than the controls. Gas sampled from the middle ear contained more NO than gas sampled from the ear canal of the contra lateral ear. Together this indicates that NO might be a natural component of the middle ear gas milieu with importance for maintaining a healthy local environment.

List of scientific papers

I. Granath A, Rynnel-Dagöö B, Backheden M, Lindberg K (2008). "Tube associated otorrhea in children with recurrent acute otitis media; results of a prospective randomized study on bacteriology and topical treatment with or without systemic antibiotics." Int J Pediatr Otorhinolaryngol 72(8): 1225-33.
https://pubmed.ncbi.nlm.nih.gov/18565598

II. Granath A, Uddman R, Cardell LO (2010). "Increased TLR7 expression in the adenoids among children with otitis media with effusion." Acta Otolaryngol 130: 57-61, Epub ahead of print
https://pubmed.ncbi.nlm.nih.gov/19452306

III. Granath A, Norrby-Teglund A, Uddman R, Cardell LO (2010). "Reduced iNOS expression in adenoids from children with otitis media with effusion." Pediatric Allergy and Immunology. [Accepted]
https://pubmed.ncbi.nlm.nih.gov/21073541

IV. Granath A, Uddman R, Cardell LO (2010). "Deranged Toll- and Nod-like receptor expression in the middle ear mucosa in patients with chronic middle ear disease." [Submitted]

V. Granath A, Weitzberg E, Cardell LO (2010). "Nitric oxide production in human middle ear mucosa." [Manuscript]