1 Department of Epidemiology Research, Danish Epidemiology Science Centre, Statens Serum Institut, Copenhagen, Denmark.
2 Department of Otolaryngology, Head and Neck Surgery, National University Hospital (H:S/Rigshospitalet), Copenhagen, Denmark.
3 Clinic of Pediatrics II, National University Hospital (H:S/Rigshospitalet), Copenhagen, Denmark.
4 Sisimiut Health Centre, Sisimiut, Greenland.
Received for publication April 3, 2002; accepted for publication January 23, 2003.
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
child; cohort studies; Eskimos; infection; respiratory tract infection; risk factors
Abbreviations: Abbreviation: CI, confidence interval.
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
During the last decades, Inuit populations in Greenland, Canada, and Alaska have undergone development from traditional hunting and fishing societies to modern, Western societies where most people occupy jobs in trade, administration, and services, a development also reflected in housing and living conditions in general. Thus, although respiratory tract infections both in earlier days and at present are frequent, the risk factor pattern may have changed with the living conditions, and risk factors for acute respiratory infections in todays Greenland might be closer to those pertinent to Western countries than to poor societies.
A longitudinal population-based cohort study of acute respiratory infections among children aged 02 years in the West Greenlandic town of Sisimiut was established with the specific objective to determine risk factors for acute upper and lower respiratory tract infections. Special emphasis was on the roles of age, gender, birth characteristics, ethnicity, breastfeeding, socioeconomic factors, housing conditions, crowding, passive smoking, and child care.
![]() |
MATERIALS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
As previously described in detail elsewhere (1), an open cohort of children aged 02 years was formed by April 1, 1996, comprising all children living in the town as of April 1, 1996, and all children either born in or moving into Sisimiut in the subsequent period until June 1, 1998, irrespective of ethnicity and other factors. The cohort was monitored weekly from July 30, 1996, to August 13, 1998, by specially trained Danish medical students and local interpreters supervised by Danish physicians.
Surveillance program and case definitions
Children were enrolled as soon as possible after identification but, in general, not prior to 6 weeks after birth, and they were excluded at 2 years of age. The children were visited weekly, and information on symptoms of acute respiratory infections was obtained. If symptoms were reported, a clinical examination including tympanometry was carried out. If any of the following signs were recorded, the episode, modified from the description by Selwyn (11), was characterized as a lower respiratory tract infection: respiratory rate of >50/minute and cough or difficult breathing, rales, stridor, wheezing, cyanosis, or subcostal chest indrawing. If none of these but any of the following were recorded, the episode was characterized as an upper respiratory tract infection (again modified from Selwyns description (11)): purulent nasal discharge, cough, red and bulging tympanic membrane with loss of normal landmarks and abnormal tympanometry compliance, purulent ear discharge, or pharyngo-tonsillar erythema or exudate. Clear nasal secretion as the only finding was excluded from definitions (11). Together, episodes of upper and lower respiratory tract infections constituted episodes of acute respiratory infection. If health center attention was sought during an episode of respiratory symptoms, physicians diagnoses of the episode as croup, bronchitis, bronchiolitis, or pneumonia were considered lower respiratory tract infections, and physicians diagnoses of the episode as rhinitis, pharyngitis, tonsillitis, or acute otitis media were considered upper respiratory tract infections. A 7-day, symptom-free interval had to elapse before a new episode could occur. Days at risk for acute respiratory infections were counted as days free from symptoms, including the first day of a new episode but exclusive of the 7 days free from symptoms following an episode.
Risk factors
At enrollment, a standardized questionnaire was used to collect information on risk factors within the following item categories: ethnicity, socioeconomic factors, birth history, crowding, housing, smoking, child care, and breastfeeding. A similar interview carried out at the end of the study period validated the enrollment information. Information on child care and breastfeeding was additionally obtained at the monthly morbidity visits. Official files and registers kept by the Chief Medical Officer of Greenland and by the Sisimiut community validated the information on birth history, use of public child care, change of address, housing construction, and water supply. For all risk factors, the information obtained at the time of enrollment was used, except for information on breastfeeding and child care, which was updated monthly and treated as a time-dependent variable in each case. Because factors concerning crowding, housing, and smoking in the household would invariably change in the case of a change of address, information on these variables was used only for the period prior to moving. This caused a reduction in the time at risk for these variables of approximately 10 percent.
Ethnicity was defined as Greenlandic, Danish, or mixed according to the biologic parents place of birth. Social class was on the basis of vocational training and employment status classified according to the Danish social classification system (12), with hunters/fishers classified as unskilled workers. The effect of social class was assessed only in families with both a mother and a father. Child care was divided into home care, day care (being looked after outside the home but not in a child-care center), or child-care centers.
Statistical methods
Incidence ratios and 95 percent confidence intervals were used as measures of relative risk. Incidence was calculated as the number of episodes divided by the time at risk. The number of episodes and days at risk for each child were calculated on a monthly basis, assuming a constant incidence within each month. Because each child could contribute with respiratory events in different calendar months, the model had to account for the possible correlation between episodes from the same child. Therefore, a generalized estimating equation method with correlation structure between measurements from the same child was used in a Poisson regression model. A banded Toeplitz correlation structure with five bands was applied. With this correlation structure, episodes with a maximal interval of 6 months from the same child were considered correlated, while those with larger intervals were regarded as independent. Relative risk estimates were obtained from the generalized estimating equation model, and confidence intervals were calculated using a robust covariance estimator for the estimated effects. Walds test was used to test the effect of any risk factor, using the fact that estimates based on the generalized estimating equation method are asymptotically normally distributed (13). In tests for trend, the categorized variable was treated as continuous using the median within each category as the score. The GENMOD procedure in SAS version 6.12 was used for the generalized estimating equation model (14).
Risk factor analyses as both univariate and multivariate analyses were carried out using the generalized estimating equation model. To allow dependence upon age, gender, ethnicity of the interviewer, and calendar period (year and month), we adjusted for these factors in all the analyses. Each risk factor was analyzed separately in a univariate model and, based on these results, a multivariate generalized estimating equation regression model was constructed. From this common model, multivariate analyses for upper and lower respiratory tract infections were carried out separately, removing the variables stepwise according to the highest p value for each step ("backwards elimination"), until all the p values had reached levels below 0.10.
The population-attributable risk, an estimate of the fraction of the total number of acute respiratory infections that would not have happened if the effect of a specific risk factor had been eliminated, was estimated as described by Bruzzi et al. (15) on the basis of the adjusted relative risks and the distribution of exposure in the episodes.
Prior to initiation, the study was approved by the Scientific Ethics Committee for Greenland.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Tables 1, 2, 3, and 4 present risk factor distributions. The median household was a family of four persons (interquartile range, 45) including two children, one of whom was less than 5 years of age. The median number of persons per room per household was 1.5, and the median number of rooms per household was three (interquartile range, 34). Almost all houses had electric cooking and running water or tank water, and all had central heating. Most (87 percent) houses had a flush toilet, while 13 percent had a plastic bag toilet.
|
|
|
|
Most (83 percent) of the children were taken care of outside their homes during the monitoring period. Of these, 26 percent had at some point attended day care, and 70 percent attended child-care centers. The median age at the start of day care was 170 days (interquartile range, 131286 days), and the age at the start of child-care center attendance was 244 days (interquartile range, 185364 days). The median number of children in day care including the child was four (interquartile range, 34).
Five of the 288 children had never been breastfed. Of 110 children at 3 months of age, 45 were exclusively breastfed, 43 were partly breastfed, 19 were weaned, and three had never been breastfed. Of 139 children at 6 months of age, six were exclusively breastfed, 84 were partly breastfed, 46 were weaned, and three had never been breastfed. The median age at weaning was determined to be 154 days for the 198 children, who stopped breastfeeding in the monitoring period and before turning 2 years of age.
Risk factor analyses
Tables 1, 2, 3, and 4 present the results of the univariate risk factor analyses. A number of factors within all item groups were significantly associated with increased risk of upper or lower respiratory tract infections or both (age, gender, ethnicity, gestational age, social class, nighttime crowding, passive smoking, type of child care, and lack of breastfeeding). In contrast, weight at birth, weight for gestational age, year of construction of house, heating facilities, cooking gear, type of toilet, and water supply were not associated with increased risk of upper or lower respiratory tract infections (not shown in tables), nor was calendar period (calendar month and year) associated with either upper (p = 0.57 and p = 0.20, respectively) or lower (p = 0.11 and p = 0.35, respectively) respiratory tract infections. The interviewer was associated with an increased risk of upper respiratory tract infections (p = 0.002) but not with lower respiratory tract infections (p = 0.91).
The common multivariate generalized estimating equation model consisted of the following 12 variables: ethnicity, social class of the household, mothers and fathers education, gestational age, mothers age at the childs birth, number of children aged 05 years and number of adults sleeping in the same room as the child, type of house, smokers in household, child care, and breastfeeding, besides the five variables that were similarly adjusted for in the univariate analyses (age, gender, year, month, and interviewer). Most of the 12 variables were chosen as those with a p value of less than 0.10 in the univariate analyses. The mothers education was chosen as it showed the same, although not significant, trend for upper respiratory tract infections as did the fathers education. Breastfeeding was chosen because this variable showed a clear trend in relative risk for lower respiratory tract infections, in particular for children less than half a year of age. For the breastfeeding variable, children never breastfed were included in the group designated "stopped." No restrictions were made for the other variables.
The final reduced multivariate models for upper and lower respiratory tract infections are shown in tables 5 and 6, respectively. The variables with the lowest p values at removal were, for upper respiratory tract infections, ethnicity (p = 0.14) and, for lower respiratory tract infections, mothers education (p = 0.35).
|
|
There was a population-attributable risk of lower respiratory tract infections of 10.6 percent associated with children aged 05 months sleeping in the same room as the index child, of 47.1 percent associated with smokers in the house, and of 48.3 percent associated with child care.
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The risk factors for upper respiratory tract infections were age (higher risk among children aged 623 months than among children aged 05 months), attending child-care centers, and sharing a bedroom with adults. For lower respiratory tract infections, the risk factors were young age (being 05 months of age compared with being older), male gender, attending child-care centers, passive smoking, and sharing a bedroom with other children aged 05 years. These findings are important from a public health perspective, as the risk factors except for age and gender are possible targets for intervention.
Attending a child-care center was a strong risk factor for both upper and lower respiratory tract infections and the strongest one for lower respiratory tract infections, confirming findings from other parts of the world (2126). Studies from Finland and Norway have reported relative risks and odds ratios of 0.951.99 for upper respiratory tract infections and of 0.96.69 for lower respiratory tract infections among children aged 12 and 45 years in child-care centers (24, 25) and, among children aged 1.517 months from the United States, odds ratios of respiratory illness in general of 1.6 have been reported (26). Although difficult to compare because of the different methodologies, outcome measures, and age groups involved, our risk estimates seem to be relatively high.
Passive smoking was a strong risk factor for lower, but not for upper, respiratory tract infections (27). Indeed, our risk estimate of 2.13 for lower respiratory tract infections associated with smokers in the household was high compared with estimates of 1.541.71 for lower respiratory tract infections among children aged 02 years observed in both community- and hospital-based studies from Western countries (28). An explanation may be that passive smoking in itself does not increase the risk of infection, as manifested by the lack of effect on upper respiratory tract infections, but increases the risk of complications to upper respiratory tract infections, in this case lower respiratory tract infections. The mechanism behind this may be the known inhibitory effects of smoking on ciliary activity and other local protective mechanisms (29). The risk of passive smoking for lower respiratory tract infections was higher, although not significantly (data not shown), among children in home care compared with children in child-care centers and among children aged 01 year compared with children aged 12 years, most likely because of increased exposure and increased vulnerability, respectively. Tobacco use in Greenland is very high. On a nationwide scale, 77 percent are smokers (30), which is comparable to the number of smoking parents in our study (66 percent of mothers and 68 percent of fathers). With a population-attributable risk of 47.1 percent of episodes of lower respiratory tract infections associated with passive smoking, this represents a major public health intervention area.
Nighttime crowding was a risk factor for both upper and lower respiratory tract infections, but surprisingly the other crowding parameters were not. In contrast, studies from the Board on Science and Technology for International Development (11) found mixed results for nighttime crowding, mostly showing lack of association. An explanation for our findings could be that, with a Western lifestyle, the effects of crowding during daytime are in fact limited in a family with parents working outside the home and children attending child-care centers, while exposure to infectious agents in the family may be most intense when sharing a bedroom with others. Unlike the common notions that houses in Greenland are small and that airtight housing standards have improved considerably in recent years, most children in Sisimiut (76 percent) now live in ventilated apartments or terraced houses built mainly after 1970 according to Western standards. The mean area of a dwelling was 74.7 m2, and the median number of rooms per household was three (equivalent numbers for Denmark: 98 m2 and three rooms per household (31)). Thus, with the average house size in Greenland, it may be possible to reduce the number of persons sleeping in the same rooms.
Age was a strong risk factor for both upper and lower respiratory tract infections, with the highest risk found among children aged 611 months. The age between 6 and 18 months has indeed been termed the period of vulnerability (11, 32). Possible mechanisms for this increased risk include degradation of maternal antibodies, immaturity of the adaptive immune system, cessation of breastfeeding, and start at child-care centers. The finding of the inverse relative risk of upper and lower respiratory tract infections for children aged 05 months in the multivariate analyses has been observed previously (11). Thus, the risk of transmission of infectious agents may be smaller in the youngest age group, as seen by the lower risk of upper respiratory tract infections, but when infected, this youngest age group experiences severity that is worse in terms of a higher rate of lower respiratory tract infections.
The risk of lower respiratory tract infections was increased for boys compared with girls, but not for upper respiratory tract infections. A similar pattern has been observed in some studies (11, 20), although a reverse pattern may be seen in older children (33). In previous studies from Greenland, no gender difference has been observed with respect to otitis media (34, 35) or common illness including common cold and earache (36).
For the risk of lower respiratory tract infections, we found a protective (but insignificant because of low power) effect of being exclusively breastfed compared with being partly breastfed or having stopped. The effect was strongest among children aged 05 months, corresponding to the age interval of the majority of breastfed children. A similar protective effect has been observed in previous studies from the Arctic and other parts of the world (3741), although inconsistently (42). Indeed, the relative risk of 0.27 for lower respiratory tract infections among children aged 05 months exclusively breastfed compared with nonbreastfed children was much lower than the relative risk of 0.79 (95 percent CI: 0.67, 0.94) observed among fully breastfed children from New Mexico (38). As the official Greenlandic maternal leave is 4 months (in contrast to 6 months in Denmark), it may not at present be possible for many mothers to breastfeed for more than that period. A longer maternal leave might reduce the risk of lower respiratory tract infections, not only because of better breastfeeding conditions but also because of delaying the time of entry into child-care centers.
Danish children had a lower relative risk for upper and lower respiratory tract infections compared with Greenlandic children, but surprisingly children of mixed descent had the highest risk of lower respiratory tract infections. Although ethnicity may be defined in terms of both biology and culture, we used the biologic parents place of birth as a proxy variable for biologic ethnicity, a measure often used in Greenland (35, 43). It is difficult to separate biologic effects from those of different living patterns, but there are marked social differences between Greenlandic and Danish families, with Danish families belonging to higher social classes and having better housing conditions than Greenlanders, indicating that the differences in relative risk of acute respiratory infections reflect social factors not accounted for in the multivariate analyses.
In contrast to previous findings, none of the usual socioeconomic factors was a significant risk factor (34, 44, 45). No validated social classification system for Greenland exists, but as Greenland has undergone tremendous changes in living conditions in recent years and as a social structure much like that in Denmark has been implemented, we chose to use that of Denmark. It may not, however, reflect the social factors in Greenland adequately. In addition, the variation in social class and educational level in this population was limited, obscuring the possible effects of socioeconomic factors.
As opposed to the putative effects of primary preventive measures toward acute respiratory infections, the effect of secondary preventive measures in this population would probably be limited. Each Greenlandic town has a hospital, and the iatrogenic threshold is low in Greenland. In our study, 32 percent of the episodes of lower respiratory tract infections and 56 percent of the episodes of upper respiratory tract infections resulted in hospital visits (1), being of the same magnitude as those in the United States (16). Only 1 percent of the episodes of upper and lower respiratory tract infections resulted in hospital admittance, while in the remaining 39 percent of episodes the children were treated at the outpatient clinic. This indicates that parents are sufficiently aware of the physical signs of lower respiratory tract infections in particular to seek medical attention when necessary.
In conclusion, age and crowding measured in terms of nighttime crowding, as well as attending child-care centers, were risk factors for both upper and lower respiratory tract infections. For lower respiratory tract infections, smoking and gender had additional significant effects, while ethnicity and lack of breastfeeding were likely risk factors for lower respiratory tract infections. These findings have major public health implications. Although the burden of acute respiratory infections in Greenlandic children has for many years been high, Greenland today is a modern society. The risk factors for acute respiratory infections are related to child care, passive smoking, and in-house crowding in nuclear families rather than to poverty and a traditional way of life. Although the use of child-care centers is probably increasing in Greenland, a number of measures may reduce their effects on childrens health, including the age composition of the children in attendance, the space per child, hygienic measures, and the age at admittance. However, these factors were not evaluated in the present study and should be addressed separately. With 80 percent of the children being passive smokers, smoking in the household should be strongly discouraged. Finally, the number of persons sleeping in the same room should, whenever possible, be reduced, and especially by children less than 5 years of age. Taken together, these measures may reduce the burden of illness in the youngest group of children.
![]() |
ACKNOWLEDGMENTS |
---|
The authors thank Dr. Tine Mortensen, Dr. Hanne Elberling, Dr. Anne Mette Eriksen, Christian Malherbe, Dr. Mette Madsen, Dr. Iben Matthiesen, Dr. Lasse Høgh Andersen, Dr. Christoffer Holst Hansen, and Dr. Gitte Weinkauff Hahn for assisting in carrying out the clinical surveillance program. The staff at Sisimiut Health Center and, in particular, the late Dr. Peter Dybdahl Andersen and Ellis Thierry for providing support, logistics, and excellent working conditions during the data collection phase are also thanked. The authors thank Dr. Per Kragh Andersen for advice on the statistical aspects of this study.
![]() |
NOTES |
---|
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|