Volume 120, Issue 2 , Pages 388-395, August 2007
Interactive effect of family history and environmental factors on respiratory tract–related morbidity in infancy
Article Outline
Background
Family and environmental factors affect the development of respiratory morbidity. How these factors interact is unclear.
Objective
We sought to clarify the interactive effect of family history of asthma and environmental factors on the occurrence of respiratory morbidity.
Methods
Two hundred twenty-one infants with a positive family history of asthma (PFH) and 308 with a negative family history of asthma (NFH) were prenatally selected and followed until the age of 2 years. Exposure to environmental factors and the occurrence of respiratory morbidity were recorded. By using multiple logistic regression analysis, increased risk was expressed in odds ratios (ORs) adjusted for relevant covariables.
Results
Infants with a PFH had more respiratory morbidity than infants with an NFH. Adjusted ORs ranged from 1.7 (95% CI, 1.0-2.8) for expiratory wheezing to 4.9 (95% CI, 1.7-13.6) for croup. Parental smoking increased the OR of a PFH for wheezing ever (OR, 5.8 [95% CI, 2.5-13.8]) and attacks of wheezing (OR, 6.8 [95% CI, 2.7-16.9]), as did Der p 1 (OR, 10.2 [95% CI, 2.8-36.3] and OR, 7.1 [95% CI, 7.1-21.0], respectively). Exposure to both parental smoking and Der p 1 further increased this OR (OR, 30.8 [95%, CI, 6.9-137.2] and OR, 26.2 [95% CI, 5.9-115.6], respectively). Breast-feeding decreased the ORs of PFH for tonsillitis and acute otitis media: the increased ORs for these diagnoses in formula-fed infants with PFHs versus those with NFHs (OR, 9.2 [95% CI, 2.1-39.7] and OR, 2.9 [95% CI, 1.1-7.2], respectively) was attenuated in breast-fed infants (OR, 1.8 [95% CI, 0.8-3.8] and OR, 0.7 [95% CI, 0.4-1.3]).
Conclusion
Parental smoking and Der p 1 increase the effect of a PFH on respiratory morbidity. Breast-feeding reduces this effect.
Clinical implications
Extra attention should be given to stimulate mothers to breast-feed their children in case they cannot stop smoking or taking sanitation measures.
Key words: Genetic predisposition to asthma, risk factors, respiratory signs and symptoms, infants, parental smoking, house dust mite, breast-feeding
Abbreviations used: GP, General practitioner, NFH, Negative family history of asthma, OR, Odds ratio, PFH, Positive family history of asthma, PPS, Postnatal parental smoking
Asthma is one of the most important chronic diseases in childhood.1 The prevalence of childhood asthma is high.2 For several decades, a steady increase in the prevalence has been observed worldwide.3, 4 However, recently the first signs of a stabilization5 or even a decrease in prevalence2 have been reported. Asthma exerts a great burden on patients, their family members, health care services, and society. Asthma is the main cause of school absence.6 The number of asthma-related contacts and hospitalizations is high, which results in substantial costs of treating asthma (20.4% of the total health care costs in 0-year-old babies and 24.1% in infants and children aged 1-14 years in the Netherlands).7 The chance to develop asthma is determined by genetic, as well as environmental, factors. Because specific genes for asthma have not been identified completely, the focus has been on a family history of asthma.
Studies performed thus far have indicated a wide range for the association of a positive family history of asthma (PFH) with a diagnosis of asthma (odds ratios [ORs] ranging from 1.5-9.7).8 This might be explained by varying definitions of family history and definitions of asthma in these studies. Moreover, the definition of asthma in first-degree family members was mainly based on parental report, which could introduce reporting bias. Finally, the differences might be explained by the differences in potential confounders or effect modifiers that were included in the models.
With regard to the environmental factors, passive smoking and house dust mite, cat, and dog allergens are thought to be associated with sensitization and allergic disease, whereas breast-feeding is thought to have a protective effect.9, 10, 11, 12, 13 However, some authors have shown opposite effects with regard to these factors.14, 15, 16
Whether environmental factors modify the effect of a PFH on respiratory tract–related morbidity has been studied by others.17, 18, 19, 20 However, the definition of a family history of asthma was not always clear. For example, in none of these studies was asthma in siblings included in the definition of a family history of asthma.17, 18, 19, 20 Moreover, in the studies of Celedón et al,17, 18 infants without a history of atopy were not included.
In studying young children, it is not possible to use asthma as an objective outcome measure because it cannot be diagnosed objectively in the first years of life. Therefore in our study we used outcome measures that are considered to be related to the development of asthma (ie, all respiratory tract–related morbidity [especially wheezing], as well as eczema). The general practitioner (GP) and the parents registered these data prospectively during the first 2 years of the infants' lives. In this respect our study differs from most other studies, in which information concerning morbidity in the children is based exclusively on parental reports, physical examination at the end of the study period, or both.21, 22, 23 Moreover, the Dutch health care system is organized in such a way that every citizen is registered in a general practice, and the GP keeps complete medical records of all families in the registered general population; this makes Dutch general practice an outstanding setting in which to assess comprehensively whether an unborn child has a PFH and is therefore at high risk of asthma. We capitalized on this opportunity by carrying out a primary care–based study.24
It is supposed that infants with a PFH and infants with a negative family history of asthma (NFH) have different genetic backgrounds, which might result in different responses to environmental factors.25 Therefore we hypothesized that the effect of a PFH on respiratory tract– and asthma-related morbidity is modified by relevant environmental factors, such as parental smoking, allergen exposure, and breast-feeding.
Methods
Recruitment of subjects
As previously described,26 793 children were recruited prenatally in primary care for a prospective birth cohort study. Twenty-seven infants were excluded because of intrauterine death, major language problems in the family, serious birth defects, or moving abroad. Fifteen infants were lost to follow-up. Four hundred forty-three infants had a PFH and participated in a randomized controlled prevention trial, the Primary Prevention of Asthma in Children study. Two hundred twenty-two infants from the randomized controlled prevention trial who were allocated to the intervention group were not included in the present study. The remaining 221 who were allocated to a control group and 308 with an NFH received usual care (according to the Guidelines of the Dutch College of General Practitioners).27 In our study a PFH was defined as “at least 1 first-degree family member (ie, the pregnant woman, the biologic father of the unborn child or a sibling) with GP-registered asthma,”28 whereas NFH was defined as “absence of GP-registered asthma in first-degree family members.” Asthma was defined according to the International Classification of Primary Care29 as recurrent episodes of reversible acute bronchial obstruction with wheeze, dry cough, or both.
Data collection
Parental registered morbidityAt 6 months, 1 year, and 2 years of age, parents completed the Dutch version of the International Study of Asthma and Allergies in Childhood questionnaire.26
GP-registered morbidityStandardized information on respiratory symptoms and diagnoses was prospectively registered in a standardized manner by the GP at every consultation during the 2 years.26 All problems were coded by using the International Classification of Primary Care29 according to the criteria of the International Classification of Health Problems in Primary Care.30
Definition of outcome measures
Symptoms reported at 6, 12, and 24 months included various types of coughing and wheezing. Diagnoses reported at 6, 12, and 24 months were allergic rhinitis, allergic rhinoconjunctivitis, physician-diagnosed otitis media, physician-diagnosed tonsillitis, and flu or serious cold. Physical examination findings and diagnoses registered by the GP at every consultation included expiratory wheezing, acute bronchitis, bronchiolitis, pneumonia, croup, otitis media, tonsillitis, eczema, and asthma.
Potential confounders and effect modifiers
Potential confounders of the relationship between family history and respiratory morbidity, as well as effect modifiers, were considered. The number of older siblings was documented at inclusion. Characteristics registered at birth included sex, birth weight, and birth season. Perinatal and other factors were registered by use of questionnaires at 6 months and 1 year of age and included prenatal maternal smoking, postnatal parental smoking (PPS), and breast-feeding. Day-care attendance was registered in weekly reports.
Dust sampling
Dust samples were collected to measure postnatal exposure to inhaled house dust mite (Der p 1), cat (Fel d 1), and dog (Can f 1) allergens when the infants were 6 to 9 months of age in a standardized manner.31 Samples were taken with a vacuum cleaner (BSA1100 1300 Watt, Bosch, Hoofddorp, The Netherlands) with a special cassette (ALK Abelló, Hørsholm, Denmark) containing a Whatman GF/F 70-mm filter from the living room floor (2 × 1 m2), the parents' mattress (1 m2), and the baby's mattress (whole mattress). The samples were kept at 4°C until they were analyzed by use of ELISA.
For statistical analysis, the individual concentrations in nanograms per gram of dust of the 3 locations were added, and weighted averages were taken. The weighted averages were based on information concerning the time an infant spends on average at every location.32, 33 Because Der p 1, Fel d 1, and Can f 1 were not normally distributed, even after logarithmic transformation, these variables were categorized into 2 categories: less than 2000 ng/g dust and 2000 ng/g dust or greater.34
Ethics
Ethical approval for this study was obtained from the ethics committees of the participating institutes. All participating parents provided written informed consent.
Statistical methods
In bivariate analysis means for continuous, normally distributed variables were compared with the Student t test. Differences in proportions between the PFH and NFH groups for dichotomous variables were evaluated by using the χ2 test.
In multiple logistic regression analyses the simultaneous contributions of the studied risk factors with correction for potential confounders (day-care attendance, number of siblings, sex, birth season, birth weight, breast-feeding, prenatal maternal smoking, PPS, Der p 1, Fel d 1, and Can f 1) to the various outcome variables were evaluated. First-order interactions between family history of asthma and breast-feeding, prenatal maternal smoking, PPS, Der p 1, Fel d 1, and Can f 1 were included to assess effect modification. Interaction terms that were not statistically significant were dropped from the model in a stepwise backward manner. Because of multiple testing, corrections according to the Bonferroni method were considered. However, we did not perform them because the method is too conservative, and our study is aimed to test separately specified hypotheses.
P values of less than .05 were considered statistically significant. Statistical analysis was performed with SPSS version 11.0 (SPSS, Inc, Chicago, Ill).
Results
General characteristics
Ten infants from the PFH group and 15 from the NFH group were premature at birth (<37 weeks), of which 8 and 6 infants, respectively, were born before 36 weeks of gestation. As shown in Table I, infants with and NFH were mostly born in spring and summer, whereas birth of infants with a PFH was approximately equally distributed for all seasons (P = .01). Infants in the PFH group had significantly more siblings and lower levels of Der p 1 and Can f 1 than infants in the NFH group (P = .02, P = .006, and P = .001, respectively). For the other characteristics analyzed, the groups were similar. The imbalanced characteristics were included in the multiple logistic regression analyses.
Table I. Demographic characteristics of the study population
| PFH | NFH | |
|---|---|---|
| N | 221 | 308 |
| Mother's age (y; mean ± SD) | 31 (4) | 31 (4) |
| Father's age (y; mean ± SD) | 33 (4) | 34 (4) |
| Female sex (n [%]) | 112 (50.7) | 162 (52.6) |
| Birth weight (g; mean ± SD | 3494 (533) | 3455 (579) |
| Gestational age (wk; mean ± SD) | 39.7 (1.7) | 39.8 (1.7) |
| Birth season∗ (n [%]) | ||
 Spring | 51 (23.1) | 94 (30.5) |
| Summer | 61 (27.6) | 104 (33.8) |
| Autumn | 48 (21.7) | 55 (17.9) |
| Winter | 61 (27.6) | 55 (17.9) |
| Siblings∗ (n [%]) | ||
| 0 | 84 (38.0) | 140 (45.5) |
| 1 | 85 (38.5) | 127 (41.2) |
| 2 | 40 (18.1) | 33 (10.7) |
| 3 | 8 (3.6) | 8 (2.6) |
| 4 | 2 (0.9) | |
| 5 | 2 (0.9) | |
| Allergen exposure | ||
| Breast-feeding ever (n [%]) | 157 (75.5) | 225 (74.3) |
| Prenatal smoking by the mother (n [%]) | 22 (10.8) | 35 (11.7) |
| PPS (n [%]) | 61 (29.9) | 95 (31.7) |
| Der p 1 (ng/g dust)† | ||
| Geometric mean | 291 | 455 |
| Median | 321 | 685 |
| Maximum | 74,463 | 21,395 |
| Fel d 1 (ng/g dust) | ||
| Geometric mean | 672 | 518 |
| Median | 447 | 504 |
| Maximum | 665,385 | 18,479 |
| Can f 1 (ng/g dust)† | ||
| Geometric mean | 430 | 682 |
| Median | 229 | 798 |
| Maximum | 333,782 | 44,477 |
∗P < .05. |
†P < .01. |
Family history of asthma
Infants in the PFH group had significantly more respiratory tract– and asthma-related symptoms than infants in the NFH group, except for a GP's diagnosis of bronchitis, otitis media with effusion, and eczema (Table II).
Table II. Respiratory tract– and asthma-related morbidity in infants with a PFH or an NFH in the first 2 years of life, as documented by the parents and the GP
| n | PFH n (%) | n | NFH n (%) | Adjusted OR (95% CI)∗ | |
|---|---|---|---|---|---|
| Parental report | |||||
| Wheezing ever | 200 | 113 (56.5) | 295 | 88 (29.8) | 1.9 (1.1-3.4) |
| Attacks of wheezing ever | 197 | 105 (53.3) | 294 | 70 (23.8) | 2.3 (1.2-4.1) |
| Awakening by wheezing ever | 192 | 74 (38.5) | 292 | 43 (14.7) | 3.8 (2.2-6.7) |
| Awakening by cough ever | 186 | 85 (45.7) | 276 | 64 (23.2) | 2.9 (1.7-4.8) |
| Nonproductive cough at night | 190 | 101 (53.2) | 276 | 79 (28.6) | 3.0 (1.8-5.0) |
| Allergic rhinitis | 197 | 139 (70.6) | 298 | 132 (44.3) | 3.1 (1.9-4.9) |
| Allergic rhinoconjunctivitis | 182 | 45 (24.7) | 291 | 29 (10.0) | 2.7 (1.4-5.1) |
| Physician-diagnosed otitis media | 186 | 70 (37.6) | 291 | 67 (23.0) | 3.5 (1.3-9.4) |
| Physician-diagnosed tonsillitis | 188 | 37 (19.7) | 291 | 26 (8.9) | 9.2 (2.1-39.7) |
| Flu or serious cold | 207 | 161 (77.8) | 294 | 151 (51.4) | 3.3 (2.0-5.3) |
| GP records | |||||
| Expiratory wheezing | 221 | 73 (33.0) | 308 | 60 (19.5) | 1.7 (1.0-2.8) |
| Acute bronchitis | 221 | 43 (19.5) | 308 | 48 (15.6) | 1.5 (0.8-2.8) |
| Bronchiolitis | 221 | 19 (8.6) | 308 | 11 (3.6) | 3.3 (1.2-9.1) |
| Pneumonia | 221 | 13 (5.9) | 308 | 5 (1.6) | 3.8 (1.3-10.8)† |
| Croup | 221 | 22 (10.0) | 308 | 7 (2.3) | 4.9 (1.7-13.6) |
| Acute otitis media | 221 | 64 (29.0) | 308 | 72 (23.4) | 2.9 (1.1-7.2) |
| Otitis media with effusion | 221 | 35 (15.8) | 308 | 32 (10.4) | 1.2 (0.4-3.9) |
| Tonsillitis | 221 | 11 (5.0) | 308 | 2 (0.6) | 8.0 (1.8-36.5)† |
| Eczema | 221 | 52 (23.5) | 308 | 48 (15.6) | 1.7 (1.0-3.1) |
| Asthma | 221 | 63 (28.5) | 308 | 24 (7.8) | 4.4 (2.3-8.4) |
∗Adjustment for day-care attendance, number of siblings, sex, breast-feeding, birth season, birth weight, prenatal maternal smoking and PPS, Der p 1, Fel d 1, and Can f 1. |
†There were not enough infants with the diagnoses of pneumonia and tonsillitis to perform a multiple logistic regression analysis. Therefore the unadjusted ORs are given for pneumonia and tonsillitis. |
Interaction between family history and environmental exposure
Statistically significant interactions between family history and postnatal exposure to Der p 1, as well as parental smoking, were seen for wheezing ever (P = .015 and P = .023, respectively) and attacks of wheezing (P = .046 and P = .033, respectively). PPS and Der p 1 modified the effect of a PFH on wheezing ever and attacks of wheezing. Exposure to PPS or Der p 1 increased the ORs of PFH for wheezing ever and attacks of wheezing. Moreover, when infants were exposed to both PPS and Der p 1, the ORs for these symptoms were even further increased (Fig 1, Fig 2).
Fig 1.
Wheezing ever. Effect of family history on wheezing ever in infants (not) exposed to Der p 1 and PPS. 95% CI (Der p 1 < 2000/PPS no), 1.1-3.4; 95% CI (Der p 1 < 2000/PPS yes), 2.5-13.8; 95% CI (Der p 1 ≥ 2000/PPS no), 2.8-36.3; 95% CI (Der p 1 ≥ 2000/PPS yes), 6.9-137.2. Adjusted for other reported risk factors.
Fig 2.
Attacks of wheezing. Effect of family history on attacks of wheezing in infants (not) exposed to Der p 1 and PPS. 95% CI (Der p 1 < 2000/PPS no), 1.2–4.1; 95% CI, (Der p 1 < 2000/PPS yes), 2.7-16.9; 95% CI (Der p 1 ≥ 2000/PPS no), 2.4-21.0; 95% CI Der p 1 ≥ 2000/PPS yes), 5.9-115.6. Adjusted for other reported risk factors.
Significant interactions between family history and breast-feeding were also observed for parentally reported tonsillitis and otitis media (P = .042 and P = .046, respectively), as well as for GP-registered acute otitis media (P = .011). The ORs of PFH compared with NFH for (acute) otitis media and tonsillitis were significantly higher than 1.0 in formula-fed infants, although not in breast-fed infants (Fig 3).
Fig 3.
Effect of family history on parentally reported tonsillitis and otitis media, as well as GP-registered acute otitis media, in infants who were breast-fed or received formula feeding. No BF, Exclusively formula feeding; BF, breast-feeding. Tonsillitis: 95% CI (No BF), 2.1–39.7; 95% CI (BF yes), 0.8–3.8. Parentally reported otitis media: 95% CI (No BF), 1.3–9.4; 95% CI, (BF yes), 0.6–2.0. GP-registered acute otitis media: 95% CI (No BF), 1.1–7.2; 95% CI (BF yes), 0.4-1.3. Adjusted for other reported risk factors.
Discussion
Family history of asthma as determined in primary care was a significant risk factor for the occurrence of respiratory tract– and asthma-related morbidity during the first 2 years of life. Our most intriguing finding was that the relation between PFH and respiratory morbidity was modified by postnatal exposure to parental smoking, house dust mite, and breast-feeding. Parental smoking and house dust mite exposure increased the effect of PFH on wheezing ever and attacks of wheezing. Moreover, when these infants were exposed to both PPS and house dust mite, this increase was even more pronounced. Finally, the effect of PFH compared with NFH on tonsillitis and (acute) otitis media in formula-fed infants disappeared in breast-fed infants. In infants in the PFH group, the effect of breast-feeding compared with formula feeding was lowered for (acute) otitis media, indicating that breast-feeding is protective in these infants.
Family history of asthma
We found that a family history of asthma was a significant risk factor for the occurrence of respiratory tract– and asthma-related morbidity. Our findings are in agreement with those of Bosken et al,35 who demonstrated that more infants with a parental history of asthma had respiratory tract–related morbidity during the first 18 months of life than infants without such a history. Other groups showed similar results in populations using other definitions of family history.21, 22 In contrast to the Isle of Wight21 and NacMaas22 studies, we observed only a marginal effect of PFH on a physician's diagnosis of eczema. In the NacMaas study22 the appearance of eczema was observed only with a bivariate analyzing technique. Using this technique, we confirmed a significant effect of PFH on a physician's diagnosis of eczema (OR, 1.7 [95% CI, 1.1-2.6]). However, this effect disappeared when confounding and effect modification were taken into account. A difference with the Isle of Wight study21 is that the researchers included other potential confounders in their study, which might be an explanation for the differences in results. However, the most important reason for the differences observed is likely the definition of family history.
As previously shown,36, 37, 38 the strongest predictor for asthma or any other atopic condition is the same condition in first-degree family members. Litonjua et al36 showed that a family history of asthma increased the risk of asthma, but not eczema, whereas the greatest (family) risk associated with eczema was a family history of eczema. The underlying thought for this phenomenon is that there are different inheritance mechanisms for asthma and other allergic diseases, although these mechanisms might be interrelated with one another.38, 39, 40
The increased occurrence of respiratory morbidity in infants with a PFH compared with those with an NFH is probably a result of environmental exposure, together with genetic susceptibility. However, in addition to the combined action of genes and environment, there are other mechanisms, such as those of geometric origin, which might be involved.
It is possible that infants with a PFH have impaired airway geometry more frequently than infants with an NFH, which could result in the occurrence of more respiratory tract– and asthma-related morbidity. Dezateux et al41 studied infants who were previously healthy at 8 weeks of age. They demonstrated, before any respiratory illness, a significant diminished specific airway function in infants who had at least 1 episode of wheezing by their first birthday compared with those who did not have a wheezing episode during this period. Moreover, they showed that infants with lower levels of specific airway conductance were more likely to have recurrent wheezing in the first year and to start wheezing at an earlier age. Finally, infants with a family history of asthma had significantly reduced specific airway conductance and subsequently experience more wheezing.
If this is the case, a small trigger from, for example, an environmental origin will lead to respiratory morbidity in infants with a PFH more easily than in infants with an NFH.
Environmental factors
Parental smokingThe postnatal effects of exposure to parental smoking on children's health have long been recognized.42 We confirmed that parental smoking was associated with wheezing, but more importantly, we found that for infants exposed to parental smoking, the risk of PFH for wheezing ever and attacks of wheezing was higher than the risk in unexposed children. The association of parental smoking with wheezing was in agreement with others' finsings.43, 44
Der p 1We observed an increase in the effect between PFH and wheezing ever, as well as with attacks of wheezing, in infants who were exposed to high levels of Der p 1 compared with those exposed to low levels. In an observational study by Platts-Mills et al,45 an association was found between Der p 1 exposure with respiratory tract– and asthma-related morbidity. However, in randomized controlled intervention studies, avoidance of Der p 1 did not always result in less respiratory tract– and asthma-related morbidity in infants.21 An explanation for these inconclusive findings might be that the effect of the presence or absence of a positive family history of asthma was not always compared.
In a birth cohort study, Johnson et al46 showed that parental history was an important independent variable in the relationship between early Der p 1 exposure and atopic outcomes in children aged 6 to 7 years. Exposure to Der p 1 during infancy was associated with an increased risk for sensitization in the presence of a positive parental history but was protective among children without a parental history of atopic disease. These findings were comparable with our findings. In a birth cohort study by Polk et al19 in which a possible interaction between PFH with Der p 1 was studied, no significant interaction between these risk factors was shown. However, in this study PFH was defined as “self-reported” maternal asthma.
In contrast to Celedón et al17 and Polk et al,19 we did not observe a significant interaction between a family history of asthma and Fel d 1. In addition to differences in the definition of family history, the relatively short follow-up to the age of 2 years in our cohort compared with a longer follow-up to 4 years or older in the other cohorts might play a role.
In a post-hoc analysis we examined the interaction between Der p 1 with maternal, paternal, and sibling asthma separately. In these subgroups we could not replicate our findings, probably because splitting of the group resulted in groups that are too small, with not enough power for accurate comparisons.
Breast-feedingOur study showed a protective effect of breast-feeding as to acute otitis media in infants with a PFH. It has been shown that breast-feeding protects against several respiratory tract–related disorders, including acute otitis media.47, 48, 49 In the Tucson study an interactive effect between maternal asthma and breast-feeding was found for a diagnosis of asthma in children aged 6 years and older,20 ages at which an objective asthma diagnosis can be made. In the first 2 years of life, it is not possible to diagnose asthma with objective criteria, which might be part of the explanation for why we could not confirm an interaction between family history of asthma and breast-feeding.
Strengths and weaknesses
Our study used a GP-registered population. We chose this design because Dutch general practice has a comprehensive overview of asthma in the families in the registered general population. In this study the GP recorded prospectively whether parents and siblings had asthma based on standardized International Classification of Health Problems in Primary Care criteria.30 In most other studies, the mother reported data on family history.21, 23, 35 Objective information concerning the father's history was therefore often lacking, which might have lead to reporting bias in these studies. This was confirmed to some extent in our study. In a subset of infants, we compared the medical records of the GP with questionnaires that were completed by the parents at inclusion. We found incomplete agreement: the highest degree of agreement was found for the presence of maternal asthma, and the lowest degree of agreement was found for the absence of sibling asthma.
A disadvantage of our study is the chance of underestimation of the asthma risk because of the selection procedure used. When asthma in siblings is involved in defining PFH, an underestimation of the risk in smaller families compared with larger families might exist. However, when the definition of PFH is based exclusively on asthma in the parents, the underestimation might be even more pronounced. Burke et al8 showed that a broader definition of PFH resulted in a higher specificity when compared with a narrow definition. To account for the possible underestimation of the risk in our design, we controlled for family size in the multiple logistic regression analysis.
In this study we had the opportunity to collect information regarding respiratory tract– and asthma-related morbidity and the occurrence of asthma in a primary care population in early infancy. Information was collected over a 2-year period at different time intervals: every 6 months during the first year and after that on an annual basis with the internationally accepted International Study of Asthma and Allergies in Childhood questionnaire and with information from the medical records.
In some cases the CIs of the ORs were fairly wide because the numbers of the subjects who are compared in those (interaction) analyses were relatively small. Despite these low numbers, the interactions studied are statistically significant, indicating real associations between the variables studied. Because of multiple testing, we considered corrections according to the Bonferroni method. However, we did not perform them because it is too conservative a method. The aim of our study was to test separately specified hypotheses. Moreover, our results were all in the same direction, and in addition, we found more significant interactions than would be expected by chance. Therefore it is not likely that the results were coincidental. A next step for future studies might be to focus on the main variables and follow the infants for a longer period to get a better impression of the effect of the different symptoms and diagnoses in the long term.
In conclusion, our study demonstrated that respiratory tract– and asthma-related morbidity occurred more often in infants with a PFH. PPS and Der p 1 increased the effect of PFH on wheezing ever and attacks of wheezing. Breast-feeding was protective against (acute) otitis media and tonsillitis in infants with a PFH.
Our findings might shed more light on the controversy concerning the effect of environmental factors. However, they need to be confirmed in other studies. If our findings are confirmed at age 6 years or older, they might have important implications for asthma health care management, such as how to advise parents of infants with a PFH or an NFH concerning preventive measures. The infants of this study should be followed until at least the age of 6 years, when an objective asthma diagnosis can be made.
This study was a joint project of the Departments of General Practice of the University of Maastricht and the University Medical Centre Nijmegen, The Netherlands. We thank the GPs, the practice assistants, and the research assistants allied to these departments and the participating midwives for recruiting eligible families. We also thank all families for their participation in the study. Thanks to Jacqueline Pisters and Dr Jildou Sijbrandij for their help in preparing the data and the statistical analyses; thanks also to Dr Wiet Koren, AllergoConsult BV, Beusichem, The Netherlands, for the analysis of the dust samples. Finally, we thank all of the other people who were scientifically involved in the study.
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Supported by the Dutch Asthma Foundation, the Prevention Fund (ZON-MW), and the Royal Netherlands Academy of Sciences (KNAW). The sponsors made no contribution to the study design or the collection, analysis, and interpretation of data. In addition, they made no contribution to the writing of the report or with regard to the decision to submit the article for publication.Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.
PII: S0091-6749(07)00637-9
doi:10.1016/j.jaci.2007.03.038
© 2007 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Volume 120, Issue 2 , Pages 388-395, August 2007
