CAN ASTHMA AFFECT BRAIN ACTIVITY AND VICE VERSA?

Letter to the Editor

K. Metodiev^1* and A. Younes²

¹ Medical University, Department of Preclinical and Clinical Sciences, Varna, Bulgaria;
² Department of Anesthesia and Reanimation, Popoli Civil Hospital, Popoli, Italy.

*Correspondence to:
Prof. Krassimir Metodiev,
Medical University,
Department of Preclinical and Clinical Sciences,
Varna, Bulgaria.
e-mail: kr.metod@gmail.com

Received: 28 October, 2024 Accepted: 27 December, 2024

2974-6345 (2024) Copyright © by BIOLIFE This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. Unauthorized reproduction may result in financial and other penalties. Disclosure: all authors report no conflicts of interest relevant to this article.

KEYWORDS: Asthma, CNS, brain, inflammation, chronic disease, neurotransmitter

INTRODUCTION

Asthma is a recurrent lung disease characterized by respiratory noises, paroxysmal coughing and dyspnea due to hyperactivity with bronchospasm of the tracheobronchial airways that results in difficulty in breathing (1). Asthma is a chronic inflammatory disease of the airways which affects the respiratory system but also has complex interrelationships with the brain through biochemical and neuroimmune pathways (2). Chronic asthma affects neurotransmitters such as serotonin, dopamine, and gamma-aminobutyric acid (GABA), which are essential for mood regulation and cognition.

The onset of the disease can occur at any age but is more frequent between the ages of three to eight years old, with a higher incidence in males. Some risk factors for asthma include low birth weight, living in urban areas, and a family history of asthma or allergies (3). The etiology is multifactorial, from exposure to inhaled or ingested allergens, to infections, smoking, or inhalation of airway irritants. Two-thirds of subjects have allergic diathesis with immune responses mediated by IgE (4). Some studies have highlighted the role of gastroesophageal reflux in adenoid hypertrophy and chronic sinusitis (5).

The symptomatology of asthma is characterized by dyspneic crises with prolonged, labored, and noisy expiration, accompanied by rhonchi, rales, and wheezing. During the attack, the patient may become cyanotic, with sweating, bradycardia, and emission of fluid and bronchial secretion. Critical episodes may be rare or frequent and may involve the heart and pulmonary circulation, which could possibly lead to cardiac failure in the most serious cases (6).

DISCUSSION

Asthma and the central nervous system (CNS) are linked because the CNS regulates the airway muscles and inflammatory responses (7). Stress or anxiety can trigger asthma symptoms or worsen them by affecting airway control and inflammation (8). In fact, CNS activity can influence asthma symptoms, primarily through the interaction between the nervous and respiratory systems. Stress and emotional distress are processed in the CNS and can cause hyperventilation or airway constriction, leading to asthma exacerbation. Stress triggers the release of cortisol and other hormones, worsening airway inflammation (9). The autonomic nervous system regulates airway tone. Overactivation of the parasympathetic nervous system can lead to bronchoconstriction, while sympathetic stimulation may affect airway relaxation (10). Some medications that act on the CNS, such as sedatives or certain opioids, may depress respiratory drive or affect airway responsiveness, potentially triggering symptoms in asthmatic individuals (11).

CNS-driven hyperventilation can irritate the airways, reduce CO2 levels in the blood, and cause bronchoconstriction. This can mimic or worsen asthma symptoms. Asthma is linked to higher rates of anxiety, depression, and cognitive impairments, likely through the shared inflammatory and neurochemical pathways. Activated Th2 immune responses lead to the elevation of IL-4, IL-5, IL-13, and IgE levels, contributing to lung inflammation and potentially signaling neuroimmune changes (12).

Some activated immune cells, such as mast cells (MCs) in the airways and brain, can release neuropeptides on site, causing airway inflammation, mucus production, and constriction, which worsens asthma symptoms (13). Asthma, MCs, and the brain are interconnected in ways that highlight the intricate link between the immune system, inflammation, and the nervous system (14). MCs are white blood cells involved in allergic reactions and are central to asthma pathophysiology. They reside in tissues like the airway epithelium, where they release histamine, leukotrienes, and cytokines in response to allergens. MCs contribute to bronchoconstriction, airway inflammation, and mucus overproduction, which are all hallmarks of asthma (15). MCs are present in the brain, especially near blood vessels and the meninges and contribute to neuroinflammation by releasing histamine and cytokines that may potentially influence conditions like migraine, multiple sclerosis, and mood disorders (16).

Inflammatory signals from MCs in asthma may influence the blood-brain barrier (BBB), leading to increased neuroinflammation (15). Their overactivation has been implicated in neuropsychiatric conditions such as autism spectrum disorders, anxiety, and post-traumatic stress disorder. Understanding the interrelationship between asthma, MCs, and the brain allows for a better understanding of asthma management by considering not only respiratory symptoms, but also the broader systemic and neurological impacts. The interaction between Th2 immune responses, asthma, and brain function is an important area that still needs to be explored further (17).

T helper cells (CD4+ T cells) are a subset of Th2 cells that orchestrate immune responses against extracellular pathogens. In allergic asthma, Th2 cells are central to allergic responses, driving IgE production and recruitment of other immune cells such as eosinophils and MCs (18). Th2 cells drive IgE production and recruitment of other immune cells. Th2 cells secrete cytokines such as IL-4 that promote IgE class switching in B cells. Inflammatory mediators in asthma, such as IL-1, IL-6, and TNF, might affect cognitive function, mood, and behavior (19). Stress or neural dysfunction can exacerbate asthma by promoting Th2-biased immune responses.

IL-4 and IL-13 are mediators of allergic asthma inflammation and may restrict the brain by promoting systemic inflammation (20). IL-6, although not strictly related to Th2 cells, may have downstream effects on both asthma and neuroinflammation, while IL-33, an alarmin cytokine, may be involved in Th2-mediated responses and neuroimmune interactions.

There’s also evidence that asthma can influence brain function, possibly due to low oxygen during severe attacks or chronic inflammation (21). Asthma inflammation can increase the BBB’s permeability, allowing systemic inflammatory mediators such as cytokines and chemokines to enter the brain and affect its homeostasis. This may exacerbate neuroinflammation, cognitive decline, or psychiatric disorders. Asthma triggers oxidative stress in both lung and brain tissues due to excessive production of reactive oxygen species (ROS), which can impair mitochondrial function in neurons and contribute to neurodegeneration.  Pro-inflammatory cytokines can decrease serotonin availability, contributing to depression or anxiety, which are common comorbidities of asthma.

CONCLUSIONS

Novel therapies focusing on vagal nerve stimulation or antioxidants might benefit asthma and brain dysfunction. Anti-inflammatory drugs including corticosteroids and biologics targeting cytokine mediators might also indirectly improve brain health. Anti-IgE treatments such as omalizumab (a monoclonal antibody used during the treatment of severe-to-moderate persistent asthma in patients who cannot control symptoms with corticosteroids) reduce the symptoms of allergic asthma. Cytokine inhibitors are now also used in severe asthma. In addition, addressing stress and improving mental health can modulate immune responses and potentially improve asthma outcomes.

Conflict of interest

The authors declare that they have no conflict of interest.

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