The best magazine
Discussion
Main Findings
This population-based prospective 20-year cohort study provides evidence that hereditary asthma and allergic diseases are consistently determinants of different subtypes of asthma, especially persistent rather than transient and early-onset rather than late-onset persistent asthma. The effect related to paternal asthma seemed to remain more constant over time as that of maternal asthma as shown in Figure 1. Both of these findings are consistent with the results of a Finnish population-based case–control study of adult-onset asthma, where paternal asthma was shown to have a stronger effect of adult onset asthma compared with maternal asthma. Interestingly, paternal allergic diseases didn't seem to follow this pattern and showed small, non-significant effects on all of the subtypes studied with early-onset persistent asthma being the only subtype with an elevated risk ratio. (Figure 1; Table 3 and Table 4).
Validity of Results
According to our systematic literature search, the current study has the longest follow-up of the studies concerning heredity and development and dynamics of asthma. This enabled us to assess the role of hereditary asthma in both early- versus late-onset as well as persistent versus transient asthma up to adulthood. As shown in Table 1, the baseline - and the 20-year follow-up populations were similar, which assures that selection bias is not an issue in this study.
The definition of asthma was based on parent- or self-reported doctor-diagnosed asthma. Due to the national health care system the access to medical care has excellent coverage in Finland, and the special reimbursement provided nationally for asthma medications provides an economic incentive for actually having potential asthma diagnosed by a physician. These factors are likely to reduce misclassification of asthma in our study population. In addition, according to the study of Pattaro et al. utilizing the age of asthma onset in the analyses improves the validity of the estimate of the incidence of asthma. Most of the previous studies on this subject focus on childhood wheezing patterns, since the diagnosis of asthma is difficult among children. In our study, the participants have been followed for 20 years and thus making verification of their asthma diagnosis easier especially for more persistent type of asthma. Also, the classification of persistent asthma required both a positive answer to the question on asthma diagnosis as well as symptoms or medication use, making the diagnosis even stronger.
Having information on the age of onset enabled us to categorize the asthma subtype into early- and late-onset asthma. We used the cut-off point of 13 years for this, which is consistent with a previous study suggesting that asthma starting earlier than 12 years forms a different phenotype. The categorization into transient and persistent asthma was based on the diagnosis of asthma in combination with information on asthma symptoms and/or medication use, which were also collected with the questionnaire.
As sensitivity analyses, we also used eight years as the cut-off point, which resulted in the following crude effect estimates: early-onset: maternal asthma 2.87, 95% CI 1.54–5.36, and paternal asthma 1.72, 95% CI 0.63–4.68; late-onset: maternal asthma 1.47, 95% CI 0.71–3.03, and paternal asthma 2.42, 95% CI 1.19–4.89. The same risk ratios for maternal allergic disease was for early-onset asthma 3.36, 95% CI 1.64–6.87 and for late-onset asthma 2.59, 95% CI 1.37–4.91 and for paternal allergic disease early-onset asthma adjusted RR = 2.16, 95% CI 0.97–4.78 and late-onset 0.95, 95% CI 0.37–2.47. This strengthens the evidence that the influence of paternal asthma continues also after childhood as seen in our analyses in Table 4 and that when studying younger age categories, maternal effect is even stronger than with our cut-off of 13 years.
We also had the possibility to take into account several potential confounding factors. In order to ensure the relevance of confounders, we focused on early-life factors and exposures that took place before the onset of asthma.
Synthesis With Previous Knowledge
Our finding of the importance of maternal asthma for early-onset persistent asthma is consistent with the results from the two previous 6-year longitudinal studies as well as from the two cross-sectional studies. The Tasmanian Longitudinal Health Study provides complementary evidence of the role of maternal asthma in reducing experience of remission in adulthood.
London et al. reported that siblings with asthma predict different clinical types of asthma. However, contrary to their results we found that also siblings strongly predicted persistent asthma and early-onset persistent asthma and not late-onset persistent asthma. We also found an elevated risk ratio between siblings with asthma and transient asthma which is partially reflected in the results of London et al. in that they found an association between siblings with asthma and wheeze and asthma-like illness without diagnoses which might be close to our subgroup of transient asthmatics.
In one previous study the risk factors of transient wheeze were studied during the first 4 years of life. Also here it was shown that parental asthma and allergic eczema and allergic rhinitis were not related to transient wheezing. This study strengthens the hypothesis, that transient asthma is more related to environmental exposures, since they found e.g. that maternal active smoking in pregnancy and childhood day care center attendance generated a risk for transient wheeze.
As in the studies of London et al. and Rusconi et al. we found that hereditary allergic diseases also play a role in the development of the different phenotypes of asthma. However, contrary to their results we didn't find an association between parental allergic disease and late-onset asthma. This is partly due to our cut-off point between early- and late-onset asthma.
As our study covered the age ranges up to 27 years, our choice of the cut-off point is supported by the study of Miranda et al. finding that children with asthma onset before the age of 12 years have more allergen sensitivity and allergic symptoms than those with a later onset, so this could form its own phenotype. The differences in hereditary patterns related to early- and late-onset persistent asthma could be partly due to different inflammatory mechanisms, as suggested by the results of Miranda et al.
Our study suggests that both paternal and maternal asthma are related to personal asthma of the child. The results concerning paternal asthma are consistent with a recent population-based case–control study on adult-onset asthma from Finland, but contrary to some studies focusing only on childhood asthma, where paternal asthma showed either no significant effect on small children's asthma or was not analyzed.
Additionally, our study provides evidence that the effect of paternal asthma continues longer than that of maternal asthma (Figure 1). One study conducted on children has also found an impact of paternal asthma on late-onset wheezing when looking at children 6–7 years of age and new-onset wheezing in the previous 12 months. Our findings are in line with a hypothesis that gene-environment interaction is more prominently related to paternally inherited genes. A recent review proposed that maternal influence on IgE-levels of the child begins from antenatal stage and lasts through childhood, while paternal effect on IgE begins later in childhood and increases later on. However, this gives no explanation to the fact that the influence of paternal allergic diseases doesn't continue to young adulthood underlining the complexity of hereditary patterns in asthma and allergic diseases.
Source: ...