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Table 1. 
Child and Family Characteristics of 3754 Preschool Children in Oslo, Norway
Child and Family Characteristics of 3754 Preschool Children in Oslo, Norway
Table 2. 
The Distribution of Upper Respiratory Tract Infections in 3754 Preschool Children in the Last Month and the Last Year*
The Distribution of Upper Respiratory Tract Infections in 3754 Preschool Children in the Last Month and the Last Year*
Table 3. 
Pearson Correlations Between Upper Respiratory Tract Infections During the Last Year in 3754 Preschool Children*
Pearson Correlations Between Upper Respiratory Tract Infections During the Last Year in 3754 Preschool Children*
Table 4. 
Crude and Adjusted Odds Ratios and Adjusted Risk Ratios for Acute Otitis Media and Tonsillopharyngitis by the Presence of Other Upper Respiratory Tract Infections in 3754 Preschool Children During the Last Year*
Crude and Adjusted Odds Ratios and Adjusted Risk Ratios for Acute Otitis Media and Tonsillopharyngitis by the Presence of Other Upper Respiratory Tract Infections in 3754 Preschool Children During the Last Year*
Table 5. 
Crude and Adjusted Odds Ratios for Upper Respiratory Tract Infections During the Last Year in 3754 Preschool Children*
Crude and Adjusted Odds Ratios for Upper Respiratory Tract Infections During the Last Year in 3754 Preschool Children*
1.
Wald  ERGuerra  NByers  C Upper respiratory tract infections in young children: duration of and frequency of complications. Pediatrics. 1991;87129- 133
2.
Schilder  AGZielhuis  GAStraatman  HSvan den Broek  P An epidemiological approach to the etiology of middle ear disease in the Netherlands. Eur Arch Otorhinolaryngol. 1992;249370- 373Article
3.
van Cauwenberge  PB Otitis media in relation to other upper respiratory tract infections. Sade  Jed.Acute and Secretory Otitis Media. Amsterdam, the Netherlands Kügler Publications1986;129- 134
4.
Alho  OPKoivu  MSorri  MRantakallio  P Risk factors for recurrent acute otitis media and respiratory infection in infancy. Int J Pediatr Otorhinolaryngol. 1990;19151- 161Article
5.
Hardy  AMFowler  MG Child care arrangements and repeated ear infections in young children. Am J Public Health. 1993;831321- 1325Article
6.
Kero  PPiekkala  P Factors affecting the occurrence of acute otitis media during the first year of life. Acta Paediatr Scand. 1987;76618- 623Article
7.
Andrade  MAHoberman  AGlustein  JParadise  JLWald  ER Acute otitis media in children with bronchiolitis. Pediatrics. 1998;101617- 619Article
8.
Kvaerner  KJNafstad  PHagen  JAMair  IWJaakkola  JJ Early acute otitis media and siblings' attendance at nursery. Arch Dis Child. 1996;75338- 341Article
9.
Uhari  MMantysaari  KNiemela  M A meta-analytic review of the risk factors for acute otitis media. Clin Infect Dis. 1996;221079- 1083Article
10.
Wald  ERGuerra  NByers  C Upper respiratory tract infections in young children: duration of and frequency of complications. Pediatrics. 1991;87129- 133
11.
Ruuskanen  OArola  MPutto-Laurila  A  et al.  Acute otitis media and respiratory virus infections. Pediatr Infect Dis J. 1989;894- 99
12.
Rovers  MMZielhuis  GAIngels  Kvan der Wilt  GJ Day-care and otitis media in young children: a critical overview. Eur J Pediatr. 1999;1581- 6Article
13.
Paradise  JLRockette  HEColborn  DK  et al.  Otitis media in 2253 Pittsburgh-area infants: prevalence and risk factors during the first two years of life. Pediatrics. 1997;99318- 333Article
14.
Rubin  DHLeventhal  JMKrasilnikoff  PA  et al.  Relationship between infant feeding and infectious illness: a prospective study of infants during the first year of life. Pediatrics. 1990;85464- 471
15.
Nafstad  PHagen  JAOie  LMagnus  PJaakkola  JJ Day care centers and respiratory health. Pediatrics. 1999;103753- 758Article
16.
Ingvarsson  LLundgren  KOlofsson  B Epidemiology of acute otitis media in children in an urban population. Auris Nasus Larynx. 1985;12(suppl 1)S105- S107
17.
Sipilä  MPukander  JKarma  P Incidence of acute otitis media up to the age of 1 1/2 years in urban infants. Acta Otolaryngol. 1987;104138- 145Article
18.
Nyquist  ACGonzales  RSteiner  JFSande  MA Antibiotic prescribing for children with colds, upper respiratory tract infections, and bronchitis. JAMA. 1998;279875- 877Article
19.
Zhang  JYu  KF What's the relative risk? a method of correcting the odds ratio in cohort studies of common outcomes. JAMA. 1998;2801690- 1691Article
20.
Louhiala  PJJaakkola  NRuotsalainen  RJaakkola  JJK Form of day care and respiratory infections among Finnish children. Am J Public Health. 1995;851109- 1112Article
21.
Berner  R Otitis media and tonsillitis: 2 of the most frequent pediatric diagnoses. Ther Umsch. 1998;5513- 17
22.
Doyle  WJAlper  CMBuchman  CAMoody  SASkoner  DPCohen  S Illness and otological changes during upper respiratory virus infection. Laryngoscope. 1999;109 ((2 pt 1)) 324- 328Article
23.
Lanphear  BPByrd  RSAuinger  PHall  CB Increasing prevalence of recurrent otitis media among children in the United States. Pediatrics. 1997;99E1Article
24.
Bernstein  JPrellner  KRynnell-Dagöö  BSipilä  PPalva  T Otitis media: the immunological factor. Sade  Jed.Acute and Secretory Otitis Media. Amsterdam, the Netherlands Kügler Publications1986;203- 209
Original Article
October 2000

Upper Respiratory Morbidity in Preschool ChildrenA Cross-sectional Study

Author Affiliations

From the Department of Otorhinolaryngology, Ullevål University Hospital, Oslo, Norway (Dr Kværner); the Section of Epidemiology, National Institute of Public Health, Oslo, Norway (Dr Nafstad); and the Department of Epidemiology, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, Md (Dr Jaakkola).

Arch Otolaryngol Head Neck Surg. 2000;126(10):1201-1206. doi:10.1001/archotol.126.10.1201
Abstract

Objectives  To estimate the occurrence of and associations between upper respiratory tract infections in preschool children, and to assess constitutional and environmental factors as determinants of these infections.

Design  Population-based cross-sectional study.

Setting  Oslo, Norway.

Participants  Preschool children, aged 4 to 5 years (3853 completed questionnaires).

Main Outcome Measures  Acute and recurrent acute otitis media, tonsillopharyngitis, common cold, and rhinitis.

Results  Upper respiratory tract infections were common at age 4 years. During the last month, 7.1% of the children had acute otitis media and 7.5% experienced tonsillopharyngitis. Corresponding figures for common cold and rhinitis were 58.3% and 16.4%, respectively. During the last 12 months, 9.5% of the children experienced more than 1 bout of acute otitis media, 6.9% had more than 1 tonsillopharyngitis episode, 47.7% contracted more than 2 common colds, and 3.2% had rhinitis weekly or monthly. The lifetime prevalence of recurrent acute otitis media (≥4 episodes in any 12-month period) was 12.7% (n = 473). Bivariate correlations showed small-to-moderate relationships between the infections. Common cold was only weakly related to otitis media, tonsillopharyngitis, and chronic rhinitis. The probability for developing acute otitis media was almost 4-fold increased in children who had tonsillopharyngitis in the last year (adjusted odds ratio = 4.19; 95% confidence interval, 3.09-5.66). In logistic regression analysis, atopic disease was a strong determinant of all upper respiratory tract infections. Low birth weight increased the risk of acute otitis media. Day care attendance and the presence of siblings, which were considered to be indicators of exposure to respiratory pathogens, increased the risk of upper respiratory tract infections.

Conclusions  In preschool children, acute otitis media, tonsillopharyngitis, and common cold were quite common, while chronic rhinitis was less prevalent and strongly associated with atopic disease. Attendance at day care centers increased the risk of upper respiratory tract infections in this age group, although the effect was weaker than that in younger children.

MOST UPPER respiratory tract infections are viral.1 Generally, viral infections are associated with little morbidity but predispose a child to complications, such as otitis media, tonsillitis, and sinusitis, that further contribute to morbidity.26

Risk factors for acute otitis media and other upper respiratory tract infections in children up to age 2 years are well documented.2,79 There is evidence that attendance at day care centers is an important contributing factor during the first years of life.4,10,11 It has been suggested that the number of contacts with other children is proportional to the effect, probably due to increased exposure to respiratory pathogens.8,12 While the presence of siblings and a family history clearly are risk factors for otitis media, there is disagreement about the significance of breastfeeding and parental smoking,4,6,9,13,14 most likely because the effects are small and difficult to assess because of the length of time between the risk exposure and subsequent morbidity. Furthermore, such effects are likely to be attributable to sociodemographic differences.13

In older children, less is known about risk factors and the distribution of upper respiratory tract infections. With the maturation of the immune system and the development of the nasopharynx and eustachian tube, these factors become correspondingly less evident. For instance, although day care attendance is a risk factor for upper respiratory tract symptoms in all preschool children, the association is stronger in those who enter day care at an earlier age.15 Furthermore, even though a subsequent reduction in these infections has been shown with age,16,17 antibiotics are prescribed more often for children aged 5 to 11 years than for younger children.18 In fact, prescriptions for colds and upper respiratory tract infections that do not respond to antibiotics represent a substantial proportion of the total antibiotic prescription in children.18 Because of the growing concern about the spread of antibiotic-resistant bacteria associated with such practice,18 data are needed on the percentage of children with common cold who subsequently are diagnosed with otitis media or tonsillitis. Thus, population-based estimates on upper respiratory morbidity may provide valuable information about the comorbidity of respiratory tract infections.

The present study evaluated the risk factors for upper respiratory tract infections in preschool children. With cross-sectional data on 4-year-old children, we first examined the distribution of acute otitis media, tonsillopharyngitis, common cold, and rhinitis during the last month and the last year. We then studied associated morbidity between common cold, rhinitis, and subsequent otitis media or tonsillopharyngitis. Finally, we estimated risk factors for recurrent upper respiratory tract infections still present in children at age 4 years.

PARTICIPANTS AND METHODS
STUDY POPULATION AND DATA COLLECTION

The study population included children born in Oslo, Norway, a city of approximately 500,000 inhabitants, in 1992. There were 4863 children with at least 1 Norwegian parent and an available address from the National Census Registry who were eligible for the study. Self-administered questionnaires were mailed to the parents during November and December 1996, when the children were between the age of 4 and 5 years. The questionnaires included questions about family characteristics, health outcomes, and details on day care arrangements and environmental exposures. The response rate was 79.2%, with 3853 families returning the questionnaires. The exclusion of 99 children, 98 of whom had been enrolled in day care due to long-standing illness, left 3754 children for the present analysis. The study population is more thoroughly described by Nafstad et al.15

OUTCOME MEASURES, EXPOSURE ASSESSMENT, AND DETERMINANTS

The main outcomes of interest were upper respiratory tract infections during the previous month and 12 months, including acute otitis media, tonsillopharyngitis, common cold, and chronic rhinitis. Chronic rhinitis was defined as daily or weekly nasal secretion without coexistent common cold. Acute otitis media and tonsillopharyngitis during the last year were defined as more than 1 infection during the last 12 months; yearly common colds were defined as more than 2 colds during the last year. Lifetime recurrent acute otitis media was defined as 4 or more episodes during any 12-month period.

The determinants of interest were constitutional factors, such as sex, birth weight, and atopic disease; environmental exposures, such as parental smoking, number of siblings, and type of day care (as proximate exposures to infectious agents); and parental education, as an indicator of socioeconomic status. This article mainly focused on current day care arrangements, divided into 3 categories: home care (at home with mother or father, at home with a nursing assistant, or at home but attending organized playgrounds with other children); family day care (in a family or private nursery outside the home); and day care center (owned by the municipality or privately owned). For this study, atopic disease was defined as any experience of physician-diagnosed asthma, allergic conjunctivitis, or rhinitis. The determinants and their distributions are listed in Table 1.

STATISTICAL METHODS

Prevalence was used as the main measure of disease occurrence. Pearson correlation coefficients were calculated to assess the association between infections. Odds ratios (ORs) were used as a measure of association between the health outcomes and their hypothesized determinants. Logistic regression analysis was applied for the adjustment of ORs. We also estimated risk ratios using the corrections suggested by Zhang and Yu.19 Based on a previous model, 3 determinants (sex, exposure to environmental tobacco smoke, and maternal education) were included in all analyses. The other determinants were included if their inclusion had an impact on the accuracy and precision of the estimate of the studied relation. When the outcome is common, the adjusted OR overestimates the risk ratio when it is greater than 1 and underestimates it when it is less than 1. Missing values in the determinants were given a separate value, and the analyses were performed with and without missing data. Both approaches gave similar results, and only the results of models including strata with missing values are presented. Commercially available software (SPSS version 8.0; SPSS Inc, Chicago, Ill) was used for all statistical analyses.

RESULTS
STUDY POPULATION

The child and family characteristics are shown in Table 1. Most children belonged to 2-parent families (83.1%), had siblings (74.2%), and had parents with more than 12 years' education. Among all children, 12.0% had physician-diagnosed lifetime asthma, allergic conjunctivitis, or rhinitis. For day care, 10.2% of the children were cared for at home, 2.0% in other private homes, 79.5% in day care centers, and 8.1% in combined day care arrangements. On average, the children in day care centers had parents with better education, fewer siblings, and an increased proportion of single parenthood.15 Most (87%) of the children attending the centers spent more than 25 hours a week in day care, and 57% were in an arrangement with more than 16 children.15 In 8.6% of the children, middle ear or pharyngeal surgery had been performed by the time of the study.

OCCURRENCE OF UPPER RESPIRATORY TRACT INFECTIONS

A total of 58.3% of the children experienced at least 1 episode of common cold during the last month, and 16.4% had symptoms of rhinitis (Table 2). For acute otitis media and tonsillopharyngitis, the corresponding figures were 7.1% and 7.5%, respectively. In the last 12 months, 9.5% of the children had experienced more than 1 episode of acute otitis media, 6.9% had had more than 1 bout of tonsillopharyngitis, 47.7% had contracted more than 2 common colds, and 3.2% had had symptoms of rhinitis weekly or monthly. The lifetime prevalence of recurrent acute otitis media (≥4 episodes in any 12-month period) was 12.7% (n = 473).

INFECTIOUS COMORBIDITY

The bivariate associations between acute otitis media, tonsillopharyngitis, common cold, and chronic rhinitis during the last year are presented as Pearson correlations in Table 3. The magnitude of the interrelationships ranged from 0.034 to 0.178. Pearson correlations between common cold and otitis media and tonsillopharyngitis were 0.139 and 0.105, respectively. In Table 4, the prevalence and adjusted ORs for children having acute otitis media and tonsillopharyngitis by the presence of other upper respiratory tract infections are shown. For children who had more than 1 otitis media episode during the last year, the adjusted OR was 4.19 (95% confidence interval, 3.09-5.66).

DETERMINANTS OF UPPER RESPIRATORY TRACT INFECTIONS AT AGE 4 YEARS

Atopic disease was a strong determinant of all upper respiratory tract infections, with adjusted ORs ranging from 1.64 to 3.29 (Table 5). Low birth weight increased the risk of acute otitis media. Day care attendance and the presence of siblings, which were considered to be indicators of exposure to respiratory pathogens, increased the risk of upper respiratory tract infections.

COMMENT

Although acute otitis media, tonsillopharyngitis, and colds are common disorders among preschool children, common cold was only weakly correlated to otitis media and tonsillopharyngitis. Atopy and day care attendance were strong determinants of respiratory tract infections, although the effect of day care was weaker than that in younger children.20

The incidence of otitis media declines after the first year of life. Compared with the 25% prevalence reported for the first year of childhood,8 our findings are in accordance with the literature. The occurrence of otitis media and tonsillopharyngitis in approximately 10% of the study population confirms that these are common diseases in pediatric clinical practice.21 Correspondingly, almost 50% of the children had more than 2 colds during the last year. The frequency similarity in our study between infections during the last month and recurrent infections during the last year reflects the seasonal occurrence of respiratory tract infections in winter, when our data were collected. Experimental studies have shown that many individuals with upper respiratory tract infections are unaware of the infection and experience no clinical symptoms despite the presence of virus.22 Some authors claim that epidemiological studies that rely on clinical symptoms in the definition of the infection are significantly biased because they underestimate the true frequency of infected individuals in the population.22 Nevertheless, the population-based estimates of disease frequency obtained from surveys do provide the clinician with background information that is useful in treating and following up patients.

There is growing concern about the spread of antibiotic-resistant bacteria, and efforts have been made to reduce the unnecessary use of antibiotics. A study of 531 pediatric office visits recently documented that antibiotics are prescribed to almost half the children presenting with upper respiratory tract infections.18 Furthermore, the researchers found that antibiotics were prescribed more often for children aged 5 to 11 years than for children aged 0 to 4 years. In a study of younger children, the frequency of complications to viral upper respiratory tract infections, such as otitis media, tonsillopharyngitis, and sinusitis, was estimated to be no higher than 30%.1 Correspondingly, although our study found a significant relationship between otitis media and tonsillopharyngitis, suggesting that even at age 4 years a few children are particularly susceptible to upper respiratory tract infections, we found only a weak relationship between common cold and otitis media and tonsillopharyngitis. Thus, our findings suggest that protracted upper respiratory tract infections do not warrant antibiotic prescription unless careful clinical examination and culture results indicate bacterial infection.18,21

Few studies have assessed risk factors for upper respiratory tract infections in older children.15 Such risk factors become less evident with age, with the immune system maturation, nasopharyngeal and eustachian tube development, and a subsequent reduction in the incidence of acute otitis media.9,16 The effect of day care attendance on susceptibility to otitis media and common cold found in our study is consistent with previous findings.20 Furthermore, Nafstad et al15 have reported that age at day care entrance is a determinant for risk of otitis media, presumably due to increased exposure to other respiratory pathogens.12 The relationship found in our study between the presence of siblings and an increased risk of acute otitis media is probably related to this phenomenon.

It has recently been suggested that the rising prevalence of recurrent otitis media in the United States is related to the use of day care and an increase in allergic conditions among children.23 In our study, atopy was a determinant for all respiratory tract infections, although there continues to be controversy about the relationship of otitis media to atopic disease. Some studies report an increased incidence of otitis media in children with allergic rhinitis, while others do not confirm these findings.4,24 In our study, we found a 4-fold increase in the risk of chronic rhinitis with the presence of atopic disease and a weaker association with other upper respiratory tract infections, suggesting that rhinitis in the absence of common cold constitutes symptoms of atopy rather than those of infectious disease.

Finally, low birth weight was related to susceptibility to otitis media, as were fewer years of maternal education and the presence of maternal smoking. The latter findings suggest a relationship between sociodemographic factors and respiratory infectious disease, which was earlier found in younger children.13 Most likely, imprecision in reporting health outcomes and exposure assessments masks an underlying effect of sociodemographic factors.

VALIDITY OF RESULTS

The study objective was to assess the frequency and determinants of upper respiratory morbidity in preschool children. Because of the cross-sectional questionnaire-based design of the study, with simultaneous collection of outcome and retrospective exposure information from the parents, selection bias cannot be excluded. For instance, it is possible that the health of children enrolled in day care outside the home differs from that of those within the home. If the more healthy children are likely to be in day care centers, we may have underestimated the relationship between disease occurrence and care in these facilities. Furthermore, increased awareness and reporting of illness as a result of many dual career families' vocalizing their concerns for healthy children may have biased the reporting of all disease symptoms, overestimating, for example, the effect of atopic disease on the occurrence of upper respiratory tract infections. Finally, adjustment in logistic regression modeling was applied to eliminate potential confounding effects.

CONCLUSIONS

Upper respiratory tract infections are still common in children at age 4 years. An exception is chronic rhinitis, which is less prevalent and strongly related to atopic disease. The weak correlation between common cold and acute otitis media and tonsillopharyngitis supports the suggestion that antibiotics should not be prescribed for children with protracted common cold, unless there is significant evidence of bacterial complications such as otitis media, tonsillitis, or sinusitis. However, the association between otitis media and tonsillopharyngitis suggests that there are still some children at age 4 years who are predisposed to infections and probably have an increased need for antibiotic treatment.

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Article Information

Accepted for publication January 26, 2000.

Corresponding author: Kari J. Kværner, MD, PhD, MHA, Department of Otorhinolaryngology, Ullevål University Hospital, N-0403 Oslo, Norway (e-mail: K.j.kvarner@ioks.uio.no).

References
1.
Wald  ERGuerra  NByers  C Upper respiratory tract infections in young children: duration of and frequency of complications. Pediatrics. 1991;87129- 133
2.
Schilder  AGZielhuis  GAStraatman  HSvan den Broek  P An epidemiological approach to the etiology of middle ear disease in the Netherlands. Eur Arch Otorhinolaryngol. 1992;249370- 373Article
3.
van Cauwenberge  PB Otitis media in relation to other upper respiratory tract infections. Sade  Jed.Acute and Secretory Otitis Media. Amsterdam, the Netherlands Kügler Publications1986;129- 134
4.
Alho  OPKoivu  MSorri  MRantakallio  P Risk factors for recurrent acute otitis media and respiratory infection in infancy. Int J Pediatr Otorhinolaryngol. 1990;19151- 161Article
5.
Hardy  AMFowler  MG Child care arrangements and repeated ear infections in young children. Am J Public Health. 1993;831321- 1325Article
6.
Kero  PPiekkala  P Factors affecting the occurrence of acute otitis media during the first year of life. Acta Paediatr Scand. 1987;76618- 623Article
7.
Andrade  MAHoberman  AGlustein  JParadise  JLWald  ER Acute otitis media in children with bronchiolitis. Pediatrics. 1998;101617- 619Article
8.
Kvaerner  KJNafstad  PHagen  JAMair  IWJaakkola  JJ Early acute otitis media and siblings' attendance at nursery. Arch Dis Child. 1996;75338- 341Article
9.
Uhari  MMantysaari  KNiemela  M A meta-analytic review of the risk factors for acute otitis media. Clin Infect Dis. 1996;221079- 1083Article
10.
Wald  ERGuerra  NByers  C Upper respiratory tract infections in young children: duration of and frequency of complications. Pediatrics. 1991;87129- 133
11.
Ruuskanen  OArola  MPutto-Laurila  A  et al.  Acute otitis media and respiratory virus infections. Pediatr Infect Dis J. 1989;894- 99
12.
Rovers  MMZielhuis  GAIngels  Kvan der Wilt  GJ Day-care and otitis media in young children: a critical overview. Eur J Pediatr. 1999;1581- 6Article
13.
Paradise  JLRockette  HEColborn  DK  et al.  Otitis media in 2253 Pittsburgh-area infants: prevalence and risk factors during the first two years of life. Pediatrics. 1997;99318- 333Article
14.
Rubin  DHLeventhal  JMKrasilnikoff  PA  et al.  Relationship between infant feeding and infectious illness: a prospective study of infants during the first year of life. Pediatrics. 1990;85464- 471
15.
Nafstad  PHagen  JAOie  LMagnus  PJaakkola  JJ Day care centers and respiratory health. Pediatrics. 1999;103753- 758Article
16.
Ingvarsson  LLundgren  KOlofsson  B Epidemiology of acute otitis media in children in an urban population. Auris Nasus Larynx. 1985;12(suppl 1)S105- S107
17.
Sipilä  MPukander  JKarma  P Incidence of acute otitis media up to the age of 1 1/2 years in urban infants. Acta Otolaryngol. 1987;104138- 145Article
18.
Nyquist  ACGonzales  RSteiner  JFSande  MA Antibiotic prescribing for children with colds, upper respiratory tract infections, and bronchitis. JAMA. 1998;279875- 877Article
19.
Zhang  JYu  KF What's the relative risk? a method of correcting the odds ratio in cohort studies of common outcomes. JAMA. 1998;2801690- 1691Article
20.
Louhiala  PJJaakkola  NRuotsalainen  RJaakkola  JJK Form of day care and respiratory infections among Finnish children. Am J Public Health. 1995;851109- 1112Article
21.
Berner  R Otitis media and tonsillitis: 2 of the most frequent pediatric diagnoses. Ther Umsch. 1998;5513- 17
22.
Doyle  WJAlper  CMBuchman  CAMoody  SASkoner  DPCohen  S Illness and otological changes during upper respiratory virus infection. Laryngoscope. 1999;109 ((2 pt 1)) 324- 328Article
23.
Lanphear  BPByrd  RSAuinger  PHall  CB Increasing prevalence of recurrent otitis media among children in the United States. Pediatrics. 1997;99E1Article
24.
Bernstein  JPrellner  KRynnell-Dagöö  BSipilä  PPalva  T Otitis media: the immunological factor. Sade  Jed.Acute and Secretory Otitis Media. Amsterdam, the Netherlands Kügler Publications1986;203- 209
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