Review

The role of the lung-brain axis in asthma exacerbations

  • Published: 22 May 2026
  • Asthma is a heterogeneous pulmonary disease characterized by airway hyperresponsiveness and chronic inflammation, and affects from 1% to 29% of the population in different countries. The pathogenesis of this disease is multifaceted; in addition to the crucial role of the immune system, its development involves environmental and genetic factors. Asthma is manifested by wheezing, shortness of breath, and chest tightness, and characteristic of this disease is that symptoms vary over time and in intensity. Studies have suggested that the special communication, lung-brain axis, has a potential role in the course of pulmonary diseases, including asthma. This term relates to the bidirectional relationship between the brain and the lung, which has communication comprising the central and peripheral nervous systems, the endocrine system, the immunological systems, and microbiota. These elements cooperate to create a complex system of bilateral interactions between the lung and the central nervous system. Our aim of this article was to summarize and organize knowledge about the role of the lung-brain axis during asthma exacerbation, a state which is defined as the worsening of a patient's symptoms and lung function parameters over a defined period.

    Citation: Kamil Marszałek, Klaudia Dobrowolska, Natalia Krupińska. The role of the lung-brain axis in asthma exacerbations[J]. AIMS Allergy and Immunology, 2026, 10(2): 52-70. doi: 10.3934/Allergy.2026006

    Related Papers:

  • Asthma is a heterogeneous pulmonary disease characterized by airway hyperresponsiveness and chronic inflammation, and affects from 1% to 29% of the population in different countries. The pathogenesis of this disease is multifaceted; in addition to the crucial role of the immune system, its development involves environmental and genetic factors. Asthma is manifested by wheezing, shortness of breath, and chest tightness, and characteristic of this disease is that symptoms vary over time and in intensity. Studies have suggested that the special communication, lung-brain axis, has a potential role in the course of pulmonary diseases, including asthma. This term relates to the bidirectional relationship between the brain and the lung, which has communication comprising the central and peripheral nervous systems, the endocrine system, the immunological systems, and microbiota. These elements cooperate to create a complex system of bilateral interactions between the lung and the central nervous system. Our aim of this article was to summarize and organize knowledge about the role of the lung-brain axis during asthma exacerbation, a state which is defined as the worsening of a patient's symptoms and lung function parameters over a defined period.


    Abbreviations

    ACC

    Anterior cingulate cortex

    ACT

    Asthma control test

    AEs

    Asthma exacerbations

    ATP

    Adenosine triphosphate

    BALF

    Bronchoalveolar lavage fluid

    BBB

    Blood–brain barrier

    BDNF

    Brain-derived neurotrophic factor

    CCL11

    C-C motif chemokine ligand 11, eotaxin-1

    CFU

    Colony-forming unit

    CGRP

    Calcitonin gene-related peptide

    CMV

    Cytomegalovirus

    CNS

    Central nervous system

    CRSwNP

    Chronic rhinosinusitis with nasal polyps

    CS

    Cytokine storm

    CXCL-1, -2, -8, -9, -10

    Chemokine (C-X-C motif) ligand -1, -2, -8, -9, -10

    E

    Epinephrine

    EAACI

    European Academy of Allergy and Clinical Immunology

    ECM1

    Extracellular matrix protein 1

    ERS

    European Respiratory Society

    FEF25–75%

    Forced Expiratory Flow 25–75%

    FEV1

    Forced Expiratory Volume in 1 second

    FRC

    Functional Residual Capacity

    GERD

    Gastroesophageal reflux disease

    GINA

    Global Initiative for Asthma

    HBI

    Hypoxic brain injury

    HPA axis

    Hypothalamic–pituitary–adrenal axis

    ICS

    Inhaled corticosteroids

    IFN

    Interferon

    IgE

    Immunoglobulin E

    IL-1α

    Interleukin-1α

    IL-1β

    Interleukin-1β

    IL-4

    Interleukin-4

    IL-5

    Interleukin-5

    IL-6

    Interleukin-6

    IL-8

    Interleukin-8

    IL-13

    Interleukin-13

    IL-17

    Interleukin-17

    IL-22

    Interleukin-22

    IL1R1

    Interleukin-1 receptor type 1

    IMV

    Invasive mechanical ventilation

    LBA

    Lung–brain axis

    LPS

    Lipopolysaccharide

    MDD

    Major depressive disorder

    MERS-CoV-1

    Middle East respiratory syndrome coronavirus-1

    MIP-1β

    Macrophage inflammatory protein-1 beta

    MMP-9

    Matrix metalloproteinase 9

    NE

    Norepinephrine

    NGF

    Nerve growth factor

    NIV

    Non-invasive ventilation

    NK cells

    Natural killer cells

    NMDA

    N-methyl-D-aspartate

    NO

    Nitric oxide

    NOS

    Nitric oxide synthetase

    NOTCH-1

    Notch receptor 1

    NPY

    Neuropeptide Y

    NT3

    Neurotrophin 3

    NT4

    Neurotrophin 4

    NTs

    Neurotrophins

    OMVs

    Outer-membrane vesicles

    PCFs

    Bronchopulmonary C-fibres (PCFs)

    PD-L1

    Programmed death-ligand 1

    PDLIM4

    PDZ and LIM domain protein 4

    PEF

    Peak Expiratory Flow

    PGD2

    Prostaglandin D2

    PNECs

    Pulmonary neuroendocrine cells

    ROS

    Reactive oxygen species

    RS

    Respiratory system

    SAE

    Sepsis-associated encephalopathy

    SARS-CoV-1

    Severe Acute Respiratory Syndrome coronavirus 1

    SARS-CoV-2

    Severe Acute Respiratory Syndrome coronavirus 2

    SBP-Ag

    Staphylococcal bacterial protein antigen

    SP

    Substance P

    SpO2

    Peripheral Capillary Oxygen Saturation

    Treg cells

    Regulatory T cells

    TNF-α

    Tumour necrosis factor alpha

    TRPV1

    Transient receptor potential vanilloid 1

    V/Q

    ventilation-perfusion ratio

    VEGF-A

    Vascular endothelial growth factor A

    VIP

    Vasoactive intestinal peptide

    VN

    Vagus nerve

    VNS

    Vagus nerve stimulation

    WHO

    World Health Organization

    加载中


    Conflict of interest



    All authors declare no conflicts of interest in this paper.

    Author contributions



    Conceptualization: KM, Writing an original draft: KM, NK, Review and Editing: KD.

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