Asthma as a risk factor for autism?

I start with a quote from the paper by Po-Hsin Tsai and colleagues [1]: "This prospective study indicated a temporal relation between asthma and subsequent ASD [autism spectrum disorder] diagnosis, supporting the immune hypothesis of ASD pathogenesis". Based on a familiar collaboration residing in Taiwan (see here and see here for some discussions on previous data), yet more evidence is emerging of a correlation between immune function, physiology and behavioural / developmental conditions.

Chen Cheng-po @ Wikipedia 

I say more evidence because as per the links above, I've posted about other research from this group looking at the comorbidity of allergic and autoimmune diseases in cases of autism [2] and more recently evidence linking early life asthma with a heightened risk of subsequent attention-deficit hyperactivity disorder (ADHD) [3].

So here goes with yet more data from this group based on their analysis of the National Health Insurance Research Database (NHIRD) in Taiwan. Natasa also receives a thank you for bringing the full-text of this paper to my [virtual] desk.

• An asthma cohort was plucked from the NHIRD based on the random selection of 1 million persons on the database. Those aged between 0-3 years and with a physician diagnosis of asthma (ICD diagnosis) (n=2134) were age- and sex-matched with 4 control patients (1:4 ratio) with no asthma and no recorded history of psychiatric disorder (n=8536). Researchers then looked at the frequency of "Psychiatrists diagnosed ASD" (ICD-9 autism) up to some 8 years later. Other variables were also recorded for participants including other atopic/allergic diseases and level of urbanisation.
• Results: well, as per the headline: "The asthmatic group exhibited higher incidence rates of ASD (1.3% vs 0.7%, P=.007)". As perhaps one would expect, levels of other allergic diseases were also more frequently reported for the asthma group. Also, the asthma group were slightly more likely to be living in urban areas than controls, although urbanisation was not reported to significantly increase the risk of ASD (see a related post here).
• Interestingly, the authors also suggest that the presence of asthma "influences the manifestation pattern of ASD" based on the fact that asthmatics tended to be diagnosed with ASD later than those who were diagnosed with ASD in the control group (although this difference was not statistically significant: 5.6 years experimental group vs. 4.5 years control group).

As the authors point out, there is some noticeable methodological strength in their findings based on the database used, the numbers of participants included and the prospective nature of their inquiry. They do however caution that a cause-and-effect relationship between asthma and autism is not proved from their data. This same sentiment could also be applied to the recent attention given to the study by D’Onofrio and colleagues [4] on that age-old (pardon the pun) issue of older dads and autism risk.

I've talked about asthma and autism previously on this blog (see here) and how there may indeed be some overlapping features when it comes to the two conditions. I also hark back to some of the work by Kevin Becker (see this post) and his speculations on autism, asthma, inflammation and the Hygiene hypothesis [5] (open-access) which may well have been borne out to some degree by the Tsai data. If you want to get even more speculative, you might also have a look at my past post talking about the opinions of Moises Velasquez-Manoff and the immune roots of autism (see here)... [sorry for the sweeping generalisation by the way].

The only other things I'll add to the authors speculations about the 'mast cell activation' hypothesis (see here) as being linked to the findings is the possibility of a couple of other variables being potentially related too. So, how about medication being a common factor as per the preliminary work throwing prenatal paracetamol (acetaminophen) into the research limelight? Or, with my sunshine vitamin interest in mind, how about vitamin D as being something to tie the two conditions together [6]? And then there's the bank of evidence talking about maternal infection being linked to offspring asthma [7] which invites further study of a growing area of interest with autism in mind. Finally, there is all the chatter about environmental exposures and asthma [8] (open-access) some of which, without making a sweeping generalisation about the definition of 'environmental exposure', may overlap with some autism discussions [9]. Quite a few lines of potential further investigation methinks.

Outside of the need for quite a lot more study on this association (importantly, replication with other geographical datasets) including disentangling the very complicated issue of immune function and autism, there is a potentially important message to take from the Tsai data. Although perhaps only a small increased risk where early asthma is present, one might think about some additional screening for conditions like autism or ADHD just in case?

-----------

[1] Tsai PH. et al. Increased risk of autism spectrum disorder among early life asthma patients: An 8-year nationwide population-based prospective study. Research in Autism Spectrum Disorders. 2014; 8: 381-386.

[2] Chen MH. et al. Comorbidity of allergic and autoimmune diseases in patients with autism spectrum disorder: A nationwide population-based study. Research in Autism Spectrum Disorders. 2013; 7: 205-212.

[3] Chen MH. et al. Asthma and attention-deficit/hyperactivity disorder: a nationwide population-based prospective cohort study. J Child Psychol Psychiatry. 2013 Nov;54(11):1208-14.

[4] D’Onofrio BM. et al. Paternal Age at Childbearing and Offspring Psychiatric and Academic Morbidity. JAMA Psychiatry. 2014. February 26.

[5] Becker KG. Autism, Asthma, Inflammation, and the Hygiene Hypothesis. Med Hypotheses. 2007; 69(4): 731–740.

[6] Gupta A. et al. Vitamin D and asthma in children. Paediatr Respir Rev. 2012 Dec;13(4):236-43

[7] Illi S. et al. Perinatal influences on the development of asthma and atopy in childhood. Annals of Allergy, Asthma & Immunology. 2014; 112: 132-139.

[8] Matsui EC. Environmental exposures and asthma morbidity in children living in urban neighborhoods. Allergy 2014; DOI: 10.1111/all.12361.

[9] Grandjean P. & Landrigan PJ. Neurobehavioural effects of developmental toxicity. Lancet Neurol. 2014 Mar;13(3):330-338.

----------

Po-Hsin Tsai, Mu-Hong Chen, Tung-Ping Su, Ying-Sheue Chen, Ju-Wei Hsu, Kai-Lin Huang, Wen-Han Chang, Tzeng-Ji Chen, & Ya-Mei Bai (2014). Increased risk of autism spectrum disorder among early life asthma patients: An 8-year nationwide population-based prospective study. Research in Autism Spectrum Disorders DOI: 10.1016/j.rasd.2013.12.022