Literature Review

Asthma Inflammation and Brain Disease - Linked?

New research published in The Journal of Allergy and Clinical Immunology by Dill-McFarland et. al. uncovers fascinating links between asthma related lung inflammation and emotional well-being in adults. As you will see, these findings are most definitely translatable to children based on my clinical experience.

From the paper: "Our results identify a specific inflammatory pathway linking asthma-related airway inflammation and emotion-related neural function. Systemically, TH17-type inflammation has been implicated in both depression and neuroinflammation, with impacts on long-term brain health. Thus, our data emphasize that inflammation in the lung in asthma may have profound effects outside of the lung that may be targetable with novel therapeutic approaches." (Dill-McFarland et. al. 2023)

It has been known for years that patients with allergies, asthma and atopy have associated comorbid mood and emotional problems over their lifetime. (Chen et. al. 2025) The reasons have often been debated, with few convincing explanations beyond those rooted in immune-related disease. This data set offers a more direct "connect the dots" pattern of why. These diseases all have immune based inflammation at the root where immune cytokines can travel via the blood stream from the location of irritation to the brain.

This study is fascinating as asthma and allergic patients are immunologically often TH2 or T helper cell type 2 polarized and that those inflammation based cell types had little to do with brain inflammation. It was actually TH17 or T helper cell 17, which is associated with autoimmunity and obesity, that rose in lock step with brain irritation. The historical reality here is that IL17 and TH17 activity is mostly associated with TH2 low asthma, patients with obesity and steroid resistant disease. This leads me to believe that nutrition and other drivers of obesity are the main link to mood inflammation in asthma.

They write: "Collectively, our data support previous observations that allergen-driven eosinophilic inflammation is associated with enhanced reactivity in brain networks important in regulating emotion. Here, we further provide a proposed mechanism of action wherein TH17 inflammation, linked to expression of neuronal and vascular signaling molecules in the lung, promotes neuroinflammation, and ultimately emotional and cognitive dysfunction." (Dill-McFarland et. al. 2023)

"Interestingly, during stress or episodes of inflammation, TH17 cells can accumulate in the brain. This is noteworthy because systemic administration of IL-17 in animal models evokes depressive-like behavior and anti–IL-17 confers resistance". This is fascinating for me as the accumulation of a chemical inflammation cytokine in the brain in response to stress and lifestyle choices is possibly the most important lever to pull on for mitigation.

This study reminds us that chronic conditions like asthma don’t just impact physical health, they can influence emotional and mental well-being too. By identifying molecular pathways connecting the lungs and the brain through the immune system, we can start to go farther upstream to look for mitigation strategies.

In our clinic, we are starting to look at metabolic labs in overweight asthmatic children as a proxy for inflammation precursors in the immune system which will predispose to mental health concerns.

The next frontier in asthma care is to address emotional health as part of the standard treatment plan because lungs and minds are more connected than we thought.

Dr. M

Dill McFarland JACI

Chen J Affective Disorders

For those that want the immune details in the discussion: "The eosinophil-associated pathways reflected in the EOS02 module and associated proteins emerged as the molecular signature of airway inflammation most closely associated with affect-related changes in SN function. These data are consistent with previous work and importantly advance our understanding of the specific biology linking lower airway inflammation with neural changes in patients with asthma but also add an important level of molecular specificity. The genes and proteins functionally central to this module were linked more to a TH17 response with mixed inflammatory and proliferative pathways rather than to the canonical type 2 inflammatory pathways typically associated with eosinophils and asthma. Indeed, type 2 pathways (ie, EOS01 module and IL-4, IL-5, and IL-13 proteins) were not strongly associated with increased activation in the SN in the present study. We similarly did not detect significant associations with other aspects of asthma-related inflammation, including mast cell genes or IL-6 signaling, although these also increased following SBP-Ag. The absence of a mast cell signal may relate to the timing of sample collection at 48 hours postchallenge. TH17 inflammation has been variably associated with eosinophilic or neutrophilic asthma and can be coincident with type 2 inflammation. In a previous work, we showed that eosinophils spontaneously release IL-1β to increase the production of IL-17A by activated memory CD4+ T cells, which is consistent with our current data showing that the IL-17A signal is closely linked with an eosinophilic response rather than with neutrophils. The baseline percentage of TH17 cells in circulation has been shown to be elevated, even in mild asthma, and to increase, together with IL-17 expression, following allergen challenge. Interestingly, during stress or episodes of inflammation, TH17 cells can accumulate in the brain. This is noteworthy because systemic administration of IL-17 in animal models evokes depressive-like behavior and anti–IL-17 confers resistance. Consistent with its effect in animal models, IL-17 expression is elevated in depression in humans and is associated with depression that is treatment-resistant. Taken together, our results provide a potential direct link between asthma and depression through TH17 rather than through canonical type 2 inflammation."(Dill-McFarland et. al. 2023)