Association of epilepsy and asthma: a population-based retrospective cohort study

Chiang, Kuo-Liang; Kuo, Fang-Chuan; Lee, Jen‐Yu; Huang, Chin‐Yin

doi:10.7717/peerj.4792

Cited by 13 publications

(6 citation statements)

References 73 publications

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“…Previous studies among US children aged 0-17 years reported that the lifetime prevalence of asthma was related to a higher risk of epilepsy (2.30 [1.50-3.52]) ( 8 ). Similarly, a recent cohort study including 150,827 asthma patients showed that the asthma patients had an increased risk of epilepsy than health controls (hazard ratio=1.39) ( 9 ). All these findings indicated that asthma was associated with the risk of epilepsy, which was consistent with the results of our MR study based on data from the ILAEC and FinnGen Consortium.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, two previously published population-based studies of adults revealed that patients with epilepsy were often accompanied by physical comorbidities such as asthma ( 6 , 7 ). In addition, numerous case-control studies have announced that the prevalence of asthma was related to higher odds of epilepsy either in children ( 8 ) or in adults ( 9 ). These data suggest that asthma might be associated with high susceptibility to epilepsy.…”

Section: Introductionmentioning

confidence: 99%

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Mendelian randomization study shows a causal effect of asthma on epilepsy risk

Tang

Guo²,

Li³

et al. 2023

Front. Immunol.

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ObjectiveThe relationship between asthma and epilepsy in observational studies is controversial. The purpose of this Mendelian randomization (MR) study is to investigate whether asthma causally contributes to epilepsy susceptibility.MethodsIndependent genetic variants strongly (P<5E-08) associated with asthma were from a recent meta-analysis of genome-wide association studies on 408,442 participants. Two independent summary statistics of epilepsy obtained from the International League Against Epilepsy Consortium (ILAEC, Ncases=15,212, and Ncontrols=29,677) and FinnGen Consortium (Ncases=6,260 and Ncontrols=176,107) were used in the discovery and replication stage, respectively. Several sensitivity analyses and heterogeneity analyses were further conducted to assess the stability of the estimates.ResultsUsing the inverse-variance weighted approach, genetic predisposition to asthma was associated with an elevated risk of epilepsy in the discovery stage (ILAEC: odds ratio [OR]=1.112, 95% confidence intervals [CI]= 1.023-1.209, P = 0.012), but not verified in the replication stage (FinnGen: OR=1.021, 95%CI= 0.896–1.163, P =0.753). However, a further meta-analysis of both ILAEC and FinnGen showed a similar result (OR=1.085, 95% CI: 1.012-1.164, P = 0.022). There were no causal associations between the age onset of asthma and epilepsy. Sensitivity analyses yielded consistent causal estimates.ConclusionThe present MR study suggests that asthma is associated with an increased risk of epilepsy independent of the age onset of asthma. Further studies are warranted to explain the underlying mechanisms of this association.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mendelian randomization study shows a causal effect of asthma on epilepsy risk

Tang

Guo²,

Li³

et al. 2023

Front. Immunol.

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“…Asthma is associated with multiple neuropsychiatric disorders in children and adults, some of which are anxiety, attention deficit hyperactivity disorder, autism, and depression. Interestingly, the retrospective cohort analysis of 150,827 patients demonstrated that Asthma may be associated with high epilepsy risk, and epilepsy may be associated with high asthma risk among children [28]. Proinflammatory cytokines play neuromodulatory functions, in addition to contributing to aberrant neuronal excitability underlying seizure disorders.…”

Section: Discussionmentioning

confidence: 99%

A Novel Link between Early Life Allergen Exposure and Neuroimmune Development in Children

Kushnir-Sukhov

2020

JCEI

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As COVID-19 unprecedented situation significantly increased the time families spend indoors, the awareness of unhealthy living conditions negatively impacting immune system and early neurodevelopment of children is of crucial importance. We retrospectively reviewed unrelated cases of the children with confirmed multiple indoor allergen sensitization due to prolonged exposure to unhealthy indoor environment with infestation and water damage, who, in addition to multiple health problems related to allergy and asthma, also developed neuroimmune complications and growth delay. Documented early in life atypical neurologic and behavioral changes were common in all cases. Clinical analysis did not establish other causative reason aside from prenatal and early life exposure to unhealthy living conditions. Alternaria Alternara and Penicillium/Aspergillus molds were found in all homes and sensitization was confirmed in all cases. Significant similarities in the symptoms recorded in all three families led us to a hypothesis that, likely, a significant level of the immune response to external immunogenic pathological stimulus such as mold spore protein, mycotoxin protein, dust mite protein, decay-related volatile particles (VOC) skewed a balance of the neuroimmune interactions, and further affected neuronal network establishment. As all children exhibited significant spectrum of the systemic inflammatory conditions early in life, coupled with inability to follow normal neurodevelopment, we hypothesize that an overwhelming activation of the aggressive immune mechanisms by the epigenetic factors led to glia activation, cytokine storm and break of tolerance. We hypothesize that developing immune system exhibited aggressive responses due to environmental danger signals; subsequently TH-1 or TH-2 switch enables multiple clinical syndromes development with atypical presentation due to the described novel mechanism. An increased due to the COVID-19 lock-down may increase an amount of exposure of vulnerable people to indoor biological particles and volatile organic compounds present in unhealthy buildings. It is of crucial importance to identify and remediate indoor exposure factors that can decrease immune protection, especially against infectious pathogens such as novel coronavirus.

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“…Other commonly diagnosed comorbidities in epilepsy include migraine, cardiovascular diseases, stroke, respiratory diseases (e.g., asthma), gastrointestinal conditions, allergies, bone diseases, and increased premature mortality [33,[63][64][65][66][67][68][69][70][71]. Diabetes represents another comorbidity, with epilepsy patients being at a higher risk of contracting diabetes and adverse postdiabetes outcomes [72].…”

Section: Comorbidities In Epilepsymentioning

confidence: 99%

Beyond Seizure Control: Treating Comorbidities in Epilepsy via Targeting of the P2X7 Receptor

Gil

Smith

Tang

et al. 2022

IJMS

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Epilepsy is one of the most common chronic diseases of the central nervous system (CNS). Treatment of epilepsy remains, however, a clinical challenge with over 30% of patients not responding to current pharmacological interventions. Complicating management of treatment, epilepsy comes with multiple comorbidities, thereby further reducing the quality of life of patients. Increasing evidence suggests purinergic signalling via extracellularly released ATP as shared pathological mechanisms across numerous brain diseases. Once released, ATP activates specific purinergic receptors, including the ionotropic P2X7 receptor (P2X7R). Among brain diseases, the P2X7R has attracted particular attention as a therapeutic target. The P2X7R is an important driver of inflammation, and its activation requires high levels of extracellular ATP to be reached under pathological conditions. Suggesting the therapeutic potential of drugs targeting the P2X7R for epilepsy, P2X7R expression increases following status epilepticus and during epilepsy, and P2X7R antagonism modulates seizure severity and epilepsy development. P2X7R antagonism has, however, also been shown to be effective in treating conditions most commonly associated with epilepsy such as psychiatric disorders and cognitive deficits, which suggests that P2X7R antagonisms may provide benefits beyond seizure control. This review summarizes the evidence suggesting drugs targeting the P2X7R as a novel treatment strategy for epilepsy with a particular focus of its potential impact on epilepsy-associated comorbidities.

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Association of epilepsy and asthma: a population-based retrospective cohort study

Cited by 13 publications

References 73 publications

Mendelian randomization study shows a causal effect of asthma on epilepsy risk

Mendelian randomization study shows a causal effect of asthma on epilepsy risk

A Novel Link between Early Life Allergen Exposure and Neuroimmune Development in Children

Beyond Seizure Control: Treating Comorbidities in Epilepsy via Targeting of the P2X7 Receptor

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