Karin Prellner

Language development in children with recurrent acute otitis media during the first three years of life. Follow-up study from birth to seven years of age

From a cohort of 113 children, followed prospectively from birth during the first three years of life regarding different aspects of acute otitis media (AOM), two study groups were selected for the present investigation: 13 children with recurrent AOM (rAOM, i.e. at least six episodes of AOM during a 12-month period), and 29 children without any AOM episode. The purpose of this study was to analyse the possible effects of early onset rAOM on language development as assessed at four and seven years of age at phoniatric and linguistic examinations performed blindly. There were no differences between the two groups on any of the linguistic analyses performed, although the rAOM group manifested a somewhat better performance on auditory discrimination tests at four years of age. The results of the present study show that rAOM during the first three years of life, in otherwise healthy children, does not cause a detectable delay of language development at four and seven years of age.

Nontypeable and encapsulated Haemophilus influenzae yield different clinical courses of experimental otitis media

Middle ears of male Sprague-Dawley rats were injected with suspensions of thirteen Haemophilus influenzae strains of different sero- and biotypes and at various concentrations. Systemic and local changes were monitored by clinical observations, otomicroscopy, and analysis of bacterial samples from blood and middle ears. Two patterns of response were recognized, a nontypeable and an encapsulated pattern. The nontypeable H. influenzae middle ear infection required a high bacterial dose and was well past its peak 8 days after challenge, when the encapsulated H. influenzae otitis media was still purulent. The most severe infections were caused by H. influenzae type b strains. The overall mortality rate was zero and the animals recovered without permanent deterioration or otomicroscopically discernable changes. The results of this study show the rat to be a suitable animal model for the study of H. influenzae otitis media.

Incidence, Aetiology, and Prognosis of Acute Epiglottitis in Children and Adults in Sweden

A retrospective study of the incidence, aetiology and case fatality rate of acute epiglottitis in children and adults was performed. The study covered the whole of Sweden (population 8.4 million) during the years 1987-89, before general vaccination against Haemophilus influenzae (Hi) type b was started. Patients were included if it was documented that they fulfilled all 3 of the following criteria: (a) red and swollen epiglottis visualized by indirect laryngoscopy, (b) inspiratory stridor or difficulties in swallowing, and (c) a temperature > or = 38 degrees C. A total of 306 children and adolescents (0-19 years) and 502 adults (> or = 20 years) were found. The age-specific incidence was highest in children aged 0-4 years, (14.7/100,000 per year). The total incidence was 3.2/100,000 per year. In the age group 0-19 years, blood cultures had been obtained from 195 (64%) and Hi was isolated from 154 (79%). In adults (> or = 20 years), 114 of 298 blood cultures yielded Hi, while pneumococci were isolated from 5 and group A streptococci from 3 patients. A total of 220 children (72%) and 114 adults (23%) needed an artificial airway. Five children and 12 adults died. In conclusion, the incidence of acute epiglottis in Sweden is very high. Compared to a previous country-wide study covering the years 1981-83 that used the same methods for case finding and case definition, the incidence in children had decreased while the incidence in adults had increased.

Polyp pathogenesis--a histopathological study in experimental otitis media.

We examined the mucosa of 50 rat middle ears in an experimental model of acute otitis media, in order to obtain information on the mechanisms of polyp formation. The right middle ear of 25 rats was inoculated with type 3 pneumococci, and the left ear served as a control. The animals were killed, the middle ear bulla removed, and the mucosa was dissected from the bone, stained PAS-alcian blue and embedded as a whole-mount. The whole-mounts were examined in a light microscope for polypous mucosal prominences. Serial sections were made of all polyps, and of relevant parts of the mucosa. 15 polyps were found in 11 (44%) of 25 infected ears; none were found in normal control ears. Goblet cell density was increased in polyps and the surrounding epithelium. Epithelial microruptures were seen in areas with widespread intra-epithelial liquid vacuoles and subepithelial accumulation of liquids, luminally migrating inflammatory cells, increased vascularization and edema. Connective tissue of the lamina propria was prolapsed through most ruptures. Some prolapses showed signs of re-epithelialization, while others had a full epithelial lining that resembled a fully developed polyp. Our findings support our earlier theory on nasal polyp pathogenesis, based on the following stages: i) Localized rupture of the epithelial lining. ii) Luminal protrusion of the lamina propria through the epithelial defect. iii) Re-epithelialization of protruded tissue, and formation of a polyp.(ABSTRACT TRUNCATED AT 250 WORDS)

Auditory consequences of recurrent acute purulent otitis media

To investigate whether recurrent purulent otitis media results in permanent hearing loss, we studied 2 subgroups of children from a cohort, earlier prospectively followed from birth to the age of 3 years. One subgroup had recurrent acute otitis media (n = 12), and the other had no acute otitis media at all (“healthy” children; n = 21). At follow-up of these subgroups at the age of 10, no child had acute otitis media or secretory otitis media. There was no difference between the groups in hearing level thresholds at the frequencies 125 Hz to 8 kHz. However, in the children with recurrent acute otitis media, as compared with the controls, the hearing levels at high frequencies (8 to 16 kHz) and the acoustic middle ear reflex thresholds were elevated, the middle ear compliance was higher, and click-evoked otoacoustic emission response levels and middle ear pressures were lower. The results suggest that the middle ear mechanics of children with recurrent acute otitis media are affected, and also that their cochlear function might be disturbed.

Bone modeling dynamics in acute otitis media

Objective: A number of middle ear diseases are associated with pathologic bone modeling, either formative or resorptive. As such, the pathogenesis of a sclerotic mastoid has been controversial for decades. Experimental studies on acute middle ear infection have shown varying degrees of both osteoresorption and osteoneogenesis. This study presents data on the dynamics of bone modeling in a rat model of acute pneumococcal otitis media, studied longitudinally from day 1 through 6 months after inoculation. Results: Qualitative, as well as quantitative histopathology revealed initial osteoresorption, followed by increasing apposition of new bone in the middle ear cavity, initiated at the outer periosteum. Measured bone thickness in four anatomically distinct locations peaked 3 months after inoculation, followed by some degree of normalization. However, bone thickness was still massively increased 6 months after the acute incident. Except in perilymphatic spaces of the otic capsule, resorptive and formative activity were found in all bone tissue structures surrounding the middle ear cavity, including the bony external auditory canal and the ossicles. Conclusion: These findings may support the existence of a perilymphatic barrier of specialized bone and suggest that even a single episode of acute infection may alter properties of ossicular chain conduction. The authors conclude that acute otitis media is accompanied by massive and progressing net osteoneogenesis, already evident at 3 days and peaking 3 months after inoculation, followed by some degree of normalization. This is conceivably in support of the environmental theory of mastoid pneumatization, claiming inflammatory disease as the cause of a sclerotic mastoid.

Pathogenesis of Middle Ear Adhesions

Middle ear adhesions are well‐known to the ear surgeon, although data on etiology, pathogenesis, and significance are lacking in current literature. This study on experimental acute otitis media presents histopathological data on these aspects. Pneumococci were inoculated in the right middle ear bulla of 25 rats; the left ear served as control. At days 4, 8, 16, 90, and 180, respectively, 5 rats were decapitated, and the bullae were removed, opened, and stained with periodic acid‐Schiff (PAS)/alcian blue. The entire middle ear mucosae were dissected from the bone, embedded as whole mounts in colophonium chambers, and examined by light microscopy. Representative parts of the mucosae were sectioned and examined in the same way. All inoculated ears from day 8 and later (20 in total), contained mucosal adhesions of various sizes, shapes, and locations. None were found in control ears. The site of predilection for the development of adhesions was the hypotympanum, followed by the anterior epitympanum, the attic, the drum, the interossicular spaces, and the tubal orifice. Based on present histopathological findings, we conclude that the middle ear adhesion is a pathological phenomenon caused by infection, and we propose a six‐stage hypothesis of pathogenesis: 1. Localized epithelial rupture; 2. Prolapse of subepithelial tissue; 3. Epithelialization of the prolapse, resulting in a polypous/fold‐like prominence; 4. Growth and elongation of the prominence; 5. Fusion of the end/tip of the prominence with another part of the mucosa; 6. Formation of an adhesion.

Responses to Rubella, Tetanus, and Diphtheria Vaccines in Otitis-Prone and Non-Otitis-Prone Children

Delayed immunologic maturation — Among other things based on a selective lack of antibodies against some acute purulent otitis media (AOM)–associated pneumococcal types — has been proposed in children with recurrent AOM (rAOM). To further elucidate the immunologic response in these children, we compared the antibody responses to diphtheria, tetanus, and rubella vaccinations in 13 children with rAOM and 29 children without AOM. The children took part in a prospective study from birth to the age of 3 years. The antibody response to the rubella vaccine was significantly lower in the children with rAOM. The responses to tetanus and to diphtheria did not differ between children with and without rAOM. Thus, the results indicate that in addition to the known lack of antibodies against pneumococcal polysaccharide antigens, a lower antibody response against at least one protein antigen may exist in otitis-prone children.

Serum antibodies against respiratory tract viruses: A prospective three-year follow-up from birth

Acute otitis media (AOM) has been epidemiologically related to viral respiratory tract infections, and viral antigens have also been detected in middle ear secretion in some AOM episodes. Successive serum samples from children followed prospectively for three years from birth were analysed for IgG antibodies against respiratory syncytial virus (RSV), adenoviruses and influenza A virus. Values from serum antibody activity gradually decreased during the first six months of life, followed by a gradual increase. Various relationships were found to obtain between age and the increases of antibody activity against the different viruses. Thus, three quarters of those tested had manifested increased antibody activity against RSV by 18 months of age, and against adenoviruses by 30 months of age. No increase of antibody activity against influenza A was noted before 12 months of age, and then only seen in two thirds of those tested during the entire three-year observation period. With regard to age, however, the proportion of children with increased antibody activity to RSV, adenoviruses or influenza A virus did not differ between otitis-prone and non-otitis-prone children. Thus, as compared to non-otitis-prone children, development of the ability to produce antibodies against these viruses was not found to be delayed in otitis-prone children.

Intra- and interstrain differences of virulence among nontypeable Haemophilus influenzae strains

Nontypeable Haemophilus influenzae (NTHi) is sometimes the causative agent of invasive diseases, and it has been suggested that there may be differences in virulence among NTHi strains. Whilst studying clinical isolates of NTHi in a rat model of acute otitis media, intra‐ and interstrain differences in virulence were observed. Two strains with suddenly reduced capacity to cause middle ear infections and one highly virulent strain with dose requirements comparable only to encapsulated H. influenzae strains were further investigated, together with 15 other H. influenzae strains. The strains were characterized by analyzing the lipopolysaccharide, the outer membrane proteins, the hemagglutinating ability, and the polymerase chain reaction products after amplification of a gene sequence associated with encapsulation. The pathogenic capacity was assessed in two different in vivo models. It was found that the two strains with reduced pathogenic capacity could regain their virulence after animal passage. The LPS analysis and the results from the chicken embryo model suggested that the observed change in virulence might be associated with the lipopolysaccharide. For the non‐animal‐passaged strain 3655 there were indications that an undefined factor(s) contributed to its relatively potent virulence. As all three strains lacked genes necessary for encapsulation, in no case could any part of the increased virulence be attributed to the expression of small amounts of capsule.