Previous research has indicated that there was no statistical relationship between attention deficit hyperactivity disorder (ADHD) and asthma, arguing against a substantial etiological or pathophysiological relationship between the two conditions [1-4]. However, other findings have suggested that behavioral disorders, including ADHD, are recurrent in children being treated for asthma [5,6].

ADHD has been linked to other behavioral disorders and allergic disorders, such as mood orders and asthma [7,8]. For example, two-thirds of children with ADHD experience co-morbidities [9]. Furthermore, ADHD symptoms should not be dismissed as part of asthma symptomatology or as a consequence of its treatment [10[, Additionally, ADHD is associated positively with asthma [9] and pediatric asthmatic patients have a higher chance to develop ADHD and other behavioral disorders and the severity of asthma symptoms is strongly correlated with the severity of ADHD symptoms [11,12]. An important common denominator between ADHD and allergic disorders is the probable effect of prenatal stress on both; findings suggest that ADHD children born preterm and/or with mothers who have experienced moderate to acute stress during pregnancy, have a significantly higher chance of acquiring asthma as compared to children born in term and whose mothers were exposed to little stress or no stress at all [13]. Finally, lifetime prevalence rates of asthma in ADHD patients was 36.6%, compared to a prevalence of 24.3% in control subjects. In this study, we examined the relationship between Asthma and ADHD in a population, with a focus on the temporal association between these two disorders in children similar to other studies [14], however, without any focus on the influence of other family factors [15-17]. The hypothesis tested in this report employing two sampling methods for comparison was that there is a significant temporal relationship between Asthma and ADHD.

Data source was Alberta health physician visit and diagnosis data for the Calgary Health Zone in Alberta Canada (Ethics ID: REB15-1057). The data constituted a sixteen-year population dataset consisting of 95,846,511 (36% male) physician International Classification of Disease (ICD-9) diagnoses and visit dates for 768,460 (46% male) individuals spanning 1993-2010. These data served as the basis for constructing the dataset employed in this analysis. All individuals in this dataset (whole sample) were labelled as having neither Asthma nor ADHD (a), Asthma only (b), ADHD only (c) or both Asthma and ADHD (d). These four groups, represented the two by two cell counts (a, b, c, d) of unique individuals, formed the basis of calculating the odds ratios {OR=[(ad)/(bc)]} for each sex describing the association of Asthma and ADHD within each of the sample frames described below.

From this population dataset, a subset of those under the age of 5 years between 1993 and 1996 was extracted, and these individuals’ Asthma and ADHD diagnoses were labelled as being from the prospective cohort within the whole sample from first to last visits up to 2010, with the oldest in December 1995 begin less than 18 years of age in 2010 (<18 years cohort) and the oldest in 1993 begin less than 22 years in 2010 (<22 years cohort). Similarly, other cross-sectional age strata (<22 years from the whole sample, and the whole sample) were labelled to examine the effects of sampling frame and age on the relationship between ADHD and asthma in comparison with the prospective cohorts employing odds ratio calculations respective to each sample frame. A separate label was created for the unique individuals in each of the four groups. All diagnoses for these individuals within the large dataset were then labelled in order to link and examine the specific associations between Asthma and ADHD within each group of over time.

Based on the age (<5 years) and time (1993-1996) constraints, it was possible to evaluate the data for a temporal association between Asthma and ADHD in the group with both Asthma and ADHD employing a comparison of proportions where Asthma preceded or followed ADHD, in addition to an overall association employing the odds ratios. For each sample, in the group with both ADHD and Asthma, the data was compared further on the basis of the temporal co-occurrence of the index diagnoses of either Asthma or ADHD, based on the index (first) diagnosis date among those with Asthma and ADHD, two groups were identified with respect to whether or not Asthma arose before or after ADHD. Proportions and 95% confidence intervals formulated the basis for comparison of the temporal co-occurrence of Asthma and ADHD. Significant statistical differences between proportions in were estimated by comparison of the 95% confidence intervals using the standard formula, wherein non-overlapping 95% confidence intervals represent significant differences (p<0.05, with z set to 1.96).

Therefore, the null hypothesis was constructed on the assumption that, based on chance alone, the respective proportion occurring before or after either disorder would not be significantly different from one another (e.g., non-overlapping 95% confidence intervals).

There has been a resurgence of interest in the relationship between Asthma and ADHD in recent years [4,18] and has identified a need for further investigation [19]. While small clinical samples have also provided evidence of an association [20] the study of populations, similar as the present report, has advanced an understanding of the association between Asthma and ADHD [21]. A range of identified factors appear to contribute to the identified association [16]. As with the range of associated mental and physical disorders, the interaction amongst measured variables and factors in ADHD/Asthma study is complex [22], with relatively clear evidence of a genetic association [23]. Genome-wide cross-trait analysis that identifies shared genetics hold the potential to study causal links between asthma and ADHD, among other mental disorders.

As mentioned in the results section, more individuals were diagnosed with ADHD as compared to asthma. In addition, ADHD was more prevalent in males and asthma was more prevalent in females. Results also showed that boys and girls with both ADHD and Asthma are significantly different than boys and girls with ADHD or Asthma alone. These results are consistent with previous literature where ADHD has been linked to allergic diseases such as asthma [7,8].

Asthma also occurred significantly more frequently after ADHD for both males and females, with a higher male occurrence as compared to females. These results are novel, as previous literature has suggested that ADHD symptoms could be a part of asthma symptomatology or as a consequence of its treatment [10] and asthmatic children may have a higher chance to develop ADHD and other behavioral disorders [11].

In conclusion, more research is needed to further understand the etiological relationship in relationship to the combined risk of ADHD and asthma. More recent research has investigated the effect of the effect of prenatal stress and suggesting that ADHD children born preterm and/or with mothers who have experienced moderate to acute stress during pregnancy have a significantly higher chance of acquiring asthma [13]. Research focusing on maternal stress, gestation, and risk for ADHD and asthma in children [15] brings forward a novel model and evidence illustrating the importance of examining early childhood comorbidities. To some extent the more sophisticated population studies [23] provide support of such epigenetic models. The present study establishes the relevance of temporal-hyper-morbidity in any understanding of Asthma and ADHD.