Olof Kalm

Recurrent Acute Otitis Media: A Prospective Study of Children during the First Three Years of Life

To evaluate possible risk factors for developing recurrent acute otitis media (rAOM), 113 children were followed prospectively from birth to the age of 3 years. One of the aims was to determine whether such risk factors could be identified before the onset of the recurrences, so that optimal care and prophylactic measures could be made available at an early stage in such cases, on the basis of continuous follow-up by an ENT specialist. During the follow-up, 13 children developed rAOM, defined as six or more episodes of acute otitis media (AOM) during a 12-month period, 57 children had occasional episodes of AOM, and 43 children had no AOM at all. Of the children with onset of AOM before 6 months of age, 80% developed frequent episodes of AOM. The frequency of other respiratory tract infections and of family histories of otitis-proneness was higher among rAOM children than among the other children. The development of rAOM was unrelated to such factors as sex, familial history of allergy, duration of breast-feeding, or domestic environment. Nor could attendance at day-care centres be concluded as constituting a risk factor for the development of rAOM. An onset of AOM before 6 months of age was highly predictive of subsequent recurrent bouts of AOM, which emphasizes the importance of correct diagnosis in infants.

Pneumococcal antibodies and complement during and after periods of recurrent otitis

Streptococcus pneumoniae frequently accounts for acute purulent otitis media (AOM) episodes. Recurrences are common and are most often caused by pneumococci of groups 6, 19 and 23. In 15 two-year-old children with recurrent AOM ( rAOM ) complement (C) components and antibodies against various pneumococcal capsular polysaccharides were analyzed during the acute phase of an AOM episode and 6 years later. Comparison was made with findings in non-otitis-prone children of comparable age. In contrast to non-otitis-prone children, 60% of children with rAOM had no detectable IgG antibodies against the pneumococcal capsular polysaccharides 6A or 19F. Analysis of C1 subcomponent complexes together with the finding of relatively low C1q concentrations gave evidence of disturbed C1 function in the acute phase of rAOM . At the 6-year follow-up antibodies against all the investigated pneumococcal capsular polysaccharides had increased in most of the children, but low IgG antibodies to type 6A polysaccharide were still more frequently found in the former rAOM children than in non-otitis-prone children. The C profiles had normalized at follow-up. These findings indicate a reduced ability in rAOM children to respond adequately with IgG antibodies to pneumococcal types encountered in rAOM . The combination of low antibody concentrations and the interference with the complement system and efficient opsonization through classical pathway activation could possibly contribute to the development of rAOM .

Pneumococcal serum antibody concentrations during the first three years of life: a study of otitis-prone and non-otitis-prone children

One hundred and thirteen children were followed prospectively from birth until the age of 3, serum being obtained from cord blood, and at the ages of 3, 6, 12, 18, 24, 30 and 36 months. Thirteen children developed recurrent acute otitis media (rAOM), 29 remained very healthy and the remaining children formed an intermediate group. Cord serum concentrations were determined of total IgG class, of IgG1 and IgG2 subclasses, as well as of specific IgG antibodies against the pneumococcal capsular types, 3, 6A and 19F. The specific pneumococcal IgG as well as IgA and IgM antibodies were also followed in the sequential serum samples up to the age of 3 in the rAOM and healthy children. Despite total IgG class and IgG1 and IgG2 subclass concentrations being of the same magnitude in cord serum of rAOM (median: 11.15, 7.48 and 2.16 g/l for IgG, IgG1 and IgG2, respectively) as in that of healthy children (median: 10.21, 8.16 and 2.16 g/l, respectively), both in cord serum and in most serum samples drawn during the first year of life, specific IgG antibodies against types 6A and 19F, but not against type 3, were significantly lower in the rAOM group than in the healthy children. In the intermediate group, cord serum concentrations of specific IgG antibodies to type 6A were of the same magnitude as in the healthy children. The only significant difference in specific IgM and IgA antibody concentrations against types 3, 6A and 19F between the two groups was noted for type 6A antibodies at 36 months of age where rAOM children exhibited lower values. The results indicate an association between pre-existing low specific IgG antibody levels against AOM-associated pneumococcal types and the development of rAOM.

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.

Treatment Failure in Acute Otitis Media: A Clinical Study of Children during Their First Three Years of Life

Although little is known about the occurrence of treatment failure in acute otitis media (AOM), available data suggest that it may be over-diagnosed. In the present study the frequency of treatment failure in AOM was determined in 113 children followed for 3 years from birth. Of 300 AOM episodes, 293 (in 70 children) were treated with oral antibiotics, and children under 10-11 months of age usually underwent myringotomy as well. During the observation period, there were 22 instances (in 16 children) of failure to respond to the primary antibiotic treatment of the AOM episodes. The annual frequency of treatment failure was 18.5%, 4.5% and 4.2% during the first, second and third years of life, respectively. The risk of failure to respond to antibiotic treatment was greater during the first year of life than during the following 2 years. The bacteria isolated and the choice of drug seemed to be of secondary importance.

Prevention of recurrent acute otitis media in otitis-prone children by intermittent prophylaxis with penicillin

The question whether penicillin V (pcV) given intermittently upon signs of upper respiratory tract infections (URTI) in otitis-prone children might prevent recurrent bouts of acute purulent otitis media (AOM) is addressed. As compared with continuous long-term antibiotic treatment as prophylaxis in otitis-prone children, intermittent administration would reduce the overall consumption of antibiotics. Seventy-six otitis-prone children less than 18 months of age were included in this double-blind, randomized, placebo-controlled multicentre study. Follow-up was from January till June. One hundred and twenty-three episodes of AOM occurred. The number of AOM episodes was reduced by 50% in the children on pcV during URTI episodes as compared with those on placebo. No obvious ecological drawbacks were noted. Thus, the described mode of pcV administration seems to be a rational and safe way to reduce the number of AOM episodes in otitis-prone children.

HLA frequency in patients with chronic secretory otitis media

It is well established that relationships exist between the frequencies of certain HLA antigens and various disease entities. In an earlier study we found a significant correlation between the frequency of HLA-A2 and HLA-A3 and recurrent acute otitis media (rAOM). Of 34 HLA antigens analysed, HLA-A2 occurred in 80.0% and HLA-A3 in only 11.1% of children with rAOM as compared to 55.9% and 27.5%, respectively, in healthy controls. In the present study we investigated the frequencies of the same 34 HLA antigens in 40 children who had been regularly controlled at our clinic for chronic secretory otitis media (SOM) for at least 6 years. HLA-A2 was found in 52.0% (21/40) and HLA-A3 in 27.5% (11/40) of these children, figures on a par with those of healthy controls. The HLA-A2 frequency was significantly lower in chronic SOM patients than in rAOM children. Some other non-significant differences were also found between these two groups. The results indicate a difference in hereditary influence on the pathogenesis of rAOM and that of chronic SOM.

The effect of intravenous immunoglobulin treatment in recurrent acute otitis media

The effect of serial intravenous infusion of human immunoglobulin on the frequency of acute otitis media (AOM) episodes and on other upper respiratory tract infections was prospectively studied in a group of 22 otitis-prone children, 1-4 years old. After pair-matching, the children were allocated to immunoglobulin treatment or to a control group. Increased specific IgG antibody activities against pneumococcal types associated with recurrent AOM (rAOM) were generally achieved, but no significant difference was noted in the frequency of AOM attacks or other respiratory tract infections between the immunoglobulin-treated children and their pair-matched untreated controls. The results indicate that, although serum antibody activities against bacteria associated with AOM are increased by immunoglobulin infusions, this does not prevent the development of AOM in children suffering from rAOM.

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.

Recurrent otitis media : genetic immunoglobulin markers in children and their parents

The likelihood that hereditary factors play a significant role in the development of recurrent acute otitis media (rAOM) in children has been suggested. The genetically determined immunoglobulin variants, Gm and Km, are useful tools for mapping out the genetic loci involved in antibody responses. Certain Gm and Km types, G2m(23) and Km(1), appear to be linked to genes which regulate the concentrations of antibodies to pneumococcal polysaccharide antigens in adults. Our aim was to identify such immunoglobulin markers in rAOM children, since these children have extremely low concentrations of IgG antibodies against the pneumococcal types associated with this disease. The markers G1m(1), G1m(2), G1m(3), G2m(23) and Km(1) were identified in 20 families, each comprising 1 parent and 1 child with a history of rAOM and 1 parent free from rAOM. In addition, G2m(23) was identified in 47 children without AOM. The distribution of Gm and Km markers between rAOM and healthy subjects did not differ significantly. If anything, rAOM children exhibited a high rate of the G2m(23) marker, whereas earlier observations in adults have demonstrated low responders to polysaccharide antigens to be preferentially G2m(-23). Our findings indicate that mechanisms responsible for the low concentrations of antibodies to pneumococcal polysaccharides in rAOM children may differ from those causing certain adults to be low responders when exposed to pneumococcal polysaccharides.