Environmental Noise and Childhood Asthma: A Hypothesis-Generating Review of Potential Neuro-Immune Mechanisms

Abstract

Childhood asthma is a heterogeneous prevalent chronic airway disease in paediatrics worldwide. It not only directly impairs the cardiopulmonary development, sleep rhythms and social skills of school-aged children, but also significantly increases the burden of medical care on families and the pressure on public health prevention and control. Environmental noise is a significant risk factor for allergic diseases, but its pathogenicity is not solely due to physical stimulation. Rather, it acts as a systemic stressor, reshaping the body’s pathological microenvironment through potential indirect pathways. Given the current lack of direct clinical evidence, this article conducts a hypothesis-generating review of the potential neuro-immune mechanisms by which noise may induce or exacerbate childhood asthma. At the immune-inflammatory level, noise disrupts immune homeostasis, facilitates T-helper type 2 (Th2) inflammation, disrupts the airway epithelial barrier through systemic oxidative stress, activates chemokine networks to mediate immune cell recruitment and drives non-Th2 inflammation. At the neuroendocrine level, noise leads to autonomic imbalance and receptor remodelling, triggering vagal rebound; simultaneously, it induces central sensitisation through the ‘lung–brain axis’, triggering substance P-mediated neurogenic inflammation; and it disrupts sleep rhythms, triggering airway hyperresponsiveness during the nocturnal vagal hypertonic period. Elucidating these two potential mechanisms provides a new theoretical basis for neuro-immune-targeted interventions, psychosomatic treatment and acoustic environment optimisation for childhood asthma.

KEY MESSAGES

• (1)Environmental noise may contribute to childhood asthma through systemic neuro-immune interactions rather than direct airway injury.
• (2)Immune-inflammatory mechanisms potentially involve oxidative stress together with type 2 and non-type 2 inflammatory responses.
• (3)Neuroendocrine pathways may include autonomic imbalance, lung–brain axis dysfunction and circadian disruption.
• (4)This review proposes a hypothesis-generating framework linking chronic noise exposure to asthma susceptibility and exacerbation in children.

INTRODUCTION

Bronchial asthma is a common chronic respiratory disease that affects the physical and mental health of children worldwide. Data from the global burden of disease study show that the prevalence of childhood asthma worldwide is 6–7%, with a higher prevalence in developed countries than in developing countries.[1] The prevalence of childhood asthma in China has increased over time. The latest national survey, conducted in 2010, showed that the prevalence of asthma in Chinese children aged 0–14 years reached 3.02%, and the prevalence in urban areas (3.87%) was significantly higher than that in rural areas (2.04%).[2] With timely intervention, 50–70% of children can achieve long-term remission, but once asthma persists into adulthood, only about 30% of patients can achieve long-term control. Therefore, it is very important to explore the risk factors of childhood asthma and control them in a timely manner.[3]

Although childhood asthma and adult asthma are both chronic inflammatory diseases of the airways, characterised by airway hyperresponsiveness and reversible airflow limitation, children are more susceptible to environmental exposures, because their organs are not yet fully developed and their tolerance to environmental stimuli is much lower than that of adults.[4] Among environmental factors, extensive research has focused on conventional factors such as air pollution, allergens and viral infections,[5] but clinical evidence regarding the direct effects of noise exposure on asthma remains limited, particularly in children, with some studies even suggesting that noise has no direct effect on asthma onset.[6,7,8] However, this conclusion of ‘no direct effect’ may be explained by two factors: first, traffic noise and air pollution are highly correlated in urban environments, and the strong local chemical damage caused by air pollution can easily mask the relatively subtle and non-specific biological effects of noise; second, traditional epidemiological surveys focus on the direct toxicological effects of noise on airway tissues, while overlooking its systemic effects as a physical stressor. Although noise does not directly act on the lower respiratory tract, it may affect human health through the immune, neuroendocrine and autonomic nervous systems, and the dysfunction of these systems may contribute to asthma development or exacerbation. Due to limited direct paediatric evidence, this hypothesis-generating review explores the potential neuro-immune mechanisms by which noise may induce or exacerbate childhood asthma, taking into account cross-species and cross-population evidence. By constructing this theoretical framework, we aim to provide a new perspective for the comprehensive prevention of this disease and highlight priorities for future targeted research.

This narrative review did not employ a systematic search strategy with strict inclusion and exclusion criteria, as its aim was conceptual integration rather than exhaustive evidence synthesis. The cited literature was primarily drawn from peer-reviewed studies indexed in PubMed, Google Scholar and Web of Science published over the past two decades, with a focus on recent advances in acoustics, neuroimmunology and childhood asthma.

NOISE MAY TRIGGER OR EXACERBATE CHILDHOOD ASTHMA THROUGH THE IMMUNE-INFLAMMATORY PATHWAY

Th2 Inflammation

In the immunological classification, asthma can be divided into T helper 2 (Th2)-type asthma (usually characterised by an eosinophilic phenotype and type 2 inflammation) and non-Th2-type asthma (usually associated with neutrophilic or paucigranulocytic phenotypes).[9] Approximately, 80% of childhood asthma is Th2-type asthma, which is mainly mediated by Th2 cells and is often accompanied by eosinophilia and an atopic predisposition.[10] Although long-term noise stress does not directly act on the airway, as a chronic environmental stressor, it can induce the formation of a low-grade systemic inflammatory microenvironment, thereby disrupting immune tolerance and increasing the risk of allergic diseases.[11] A Korean study pointed out that nighttime noise exposure may increase the risk of allergic diseases in children [odds ratio(OR) = 1.077, 95% confidence interval(CI) 1.057–1.099], including atopic dermatitis, asthma and allergic rhinitis.[12] Tobias et al.[13] also reported that exposure to traffic noise was significantly associated with increased respiratory mortality in older adults (>65 years), and the mechanism may be related to immune system dysfunction. In addition, an animal study has shown that noise exposure may lead to an increase in peripheral blood eosinophils and monocytes.[14] Pathological studies of asthma have shown that granule proteins released by eosinophils can directly damage the airway epithelium, triggering an inflammatory cascade and airway spasm.[15] Although large-scale clinical studies on the direct effects of noise on systemic type 2 inflammation in children are currently lacking, cross-species and cross-population evidences provide support for this pathway. Given that both childhood and adult Th2 asthma are caused by allergic inflammatory responses, it is plausible to hypothesise that noise may contribute to asthma development or exacerbation by disrupting systemic immune homeostasis, potentially facilitating or amplifying Th2-type airway inflammatory responses in susceptible children.

Non-Th2 Inflammation

Activation of non-Th2 inflammatory responses in asthma involves immune cells (e.g., Th1 and Th17 cells and neutrophils) and cytokines (e.g., interleukin [IL]-1β, IL-8, and IL-17). Non-Th2-type asthma is usually less associated with allergies and is often triggered by infection, pollution, obesity or psychological stress.[16,17] Compared with Th2-type asthma, non-Th2-type asthma may be more closely related to the neuro-immune mechanisms of noise exposure.

Multiple animal experiments have shown that noise can activate chemokine families (e.g., CC, CX3C and CXC), recruit monocytes and macrophages, promote the secretion of inflammatory cytokines, such as IL-1β and IL-18, and enhance neutrophil infiltration, causing damage to local tissues such as the cochlea.[18,19,20,21] It is worth noting that this noise-induced immune cascade response is not unique to the auditory system. In the pathological mechanism of childhood asthma, chemokine ligands, such as CX3CL1 and CCL2, are key hubs driving the amplification of the airway inflammatory cascade.[22] A study in Zhejiang University clarified that elevated CCL2 levels in airway epithelial cells can trigger macrophages to release severe pro-inflammatory mediators, such as IL-1β and tumour necrosis factor α (TNF-α), causing increased airway reactivity.[23] Other studies have reported that the CC and CXC chemokine families can cause acute exacerbations of childhood asthma, and Th1-related chemokines such as CXCL10 and CXCL11 may be related to the development of childhood asthma and allergic reactions.[24] In addition, Steven et al.[20] reported that exposure to airplane noise can cause mononuclear cell and neutrophil infiltration in the blood vessels of mice, leading to endothelial dysfunction and inflammatory response, while endothelial dysfunction is common in children with asthma, and serum soluble intercellular adhesion molecule-1 and E-selectin levels are significantly elevated during acute exacerbations.[25,26]

Although clinical evidence demonstrating that of noise exposure directly affects respiratory system through non-Th2 pathways remains limited, based on the commonalities of the cross-organ immune mechanisms, it can be inferred that noise-induced chemokine secretion and immune cell infiltration represent components of a systemic innate inflammatory response, which is potentially be reenacted locally in the airways without direct exposure to allergens. This conceptual link represents a theoretical bridge in our model and may serve as a potential indirect pathway through which noise contributes to the development or exacerbation of non-Th2 asthma in children, pending future experimental validation.

Oxidative Stress

Noise exposure, as a systemic physical stress, can induce the production of excessive reactive oxygen species (ROS, including superoxide anion, hydroxyl radicals and hydrogen peroxide) and reactive nitrogen species (RNS, including nitric oxide and peroxynitrite).[27] Meanwhile, noise exposure also consumes endogenous antioxidants (e.g., superoxide dismutase [SOD] and catalase [CAT] and induces damage to the mitochondrial electron transport chain, leading to a disruption of the systemic oxidation–antioxidant balance.[28] Although the existing evidence is mostly derived from animal models due to ethical and operational difficulties in human trials, these studies have involved various mammals such as rodents,[27,28] artiodactyls[29] and primates,[30] revealing the high conservation of noise-induced oxidative damage. Based on the mechanisms reported in these animal studies, noise exposure may also induce a similar systemic oxidative stress response in the human body.

Research on the pathogenesis of asthma has shown that excessive production of ROS in the airways can stimulate macrophage activation, prompting the release of pro-inflammatory mediators, including TNF-α, IL-1β, IL-6 and IL-8, which may exacerbate airway inflammation.[31] Notably, noise-induced increases in systemic ROS levels can affect the respiratory system through blood circulation and neuro-immune crosstalk. This systemic oxidative load not only exacerbates local airway inflammation but also affects the cytoskeletal integrity of airway epithelial cells in children by activating innate immune pathways, such as TLR4, leading to increased barrier permeability.[32] A pathological study on childhood asthma showed that excessive accumulation of ROS and RNS not only directly oxidises cell membrane lipids, proteins and DNA, but also triggers redox-dependent changes in cell signalling, involving nicotinamide adenine dinucleotide phosphate oxidase dysregulation, mitochondrial dysfunction and endoplasmic reticulum stress, thereby becoming a key driver of airway inflammation amplification, airway remodelling and airway hyperresponsiveness.[33]

Although clinical cohort data on noise-induced systemic oxidative stress in children are currently lacking, considering the cross-species inferences and the unique physiological characteristics of children, the pathogenicity of this indirect pathway may be largely amplified in children. While adults may partially tolerate noise-induced subclinical oxidative stress through mature compensatory mechanisms, children’s early-life antioxidant defence systems, such as antioxidant capacity and SOD and CAT activity, and airway epithelial barriers are not yet fully developed, resulting in a lower capacity to clear ROS/RNS than adults. Therefore, the latent oxidative damage caused by long-term noise exposure is more likely to penetrate the vulnerable airway barriers in children, which may be an important potential indirect pathway for early airway remodelling in preschool children before a clinical diagnosis of asthma.

NOISE MAY INDUCE OR EXACERBATE ASTHMA THROUGH THE NEUROENDOCRINE PATHWAY

Autonomic Dysfunction and Receptor Remodelling

The contraction and relaxation of airway smooth muscle are regulated by both the sympathetic and parasympathetic nerves, particularly the vagus nerve, and maintaining a dynamic balance between these systems is the basis for airway patency. Noise exposure, as a strong sensory stimulus, can be projected directly to the autonomic regulatory centres of the brainstem via the auditory pathway, disrupting this balance and potentially contributing to asthma development or exacerbation.[34,35]

The autonomic nervous system is strongly activated by acute noise exposure. Extreme sympathetic nerve excitation is often accompanied by compensatory vagal rebound. This transient increase in vagal tone may contribute to airway smooth muscle spasm and increased mucus secretion.[36] More importantly, long-term exposure may induce autonomic receptor remodelling, characterised by downregulation and desensitisation of β2-adrenergic receptors, which mediate relaxation of airway smooth muscle, due to sustained sympathetic activation, whereas M3 muscarinic receptors, which mediate contraction, may be upregulated due to continuous vagal hyperactivity.[37] This remodelling at the autonomic nerve receptor level tilts the airway’s neural regulatory balance towards contraction and spasm, representing an important peripheral neural mechanism for noise-mediated airway hyperresponsiveness. It should be noted that the above evidence mainly comes from animal models and mechanism studies of adult asthma, and its applicability in children’s airways still needs direct experimental validation.

Lung–Brain Axis and Psychological Stress

Unlike the above-mentioned brainstem autonomic reflexes, noise, as a typical environmental psychological stressor, has a more profound impact on the intervention of higher brain centres. Noise can hyperactivate emotion-related brain regions such as the amygdala, triggering negative emotions such as anxiety, irritability and subjective restlessness.[38] In recent years, the concept of ‘lung–brain axis’ has provided a new framework for the understanding how non-traditional factors such as noise may influence asthma.[39] The groundbreaking study by Dill-McFarland et al.[40] confirmed that airway inflammation in asthma can reversely regulate the activity of the brain salience network through interorgan communication, meaning that the nervous system of children with asthma may be in a state of heightened sensitisation to stimuli. In this context, environmental noise, as a continuous source of emotional stress, is input into this sensitive lung–brain circuit, which is very likely to trigger a descending neuro-immune amplification effect.

The inflammatory cascade effect of psychological stress is first mediated through the neuroendocrine pathway. Chronic psychological stress leads to the continuous activation of the hypothalamic–pituitary–adrenal (HPA) axis and long-term abnormal fluctuations in cortisol. This dysregulation of endogenous hormone regulation can cause downregulation of local glucocorticoid receptor expression in the airway, inducing hormone resistance. In addition, the abnormal cortisol rhythm may relieve the physiological inhibition of Th2 inflammation, leading to poorer asthma control in children.[41]

In addition, psychological stress amplifies non-Th2 responses through immune-inflammatory crosstalk. Zhang et al.[42] showed through mediation analysis that depressive symptoms can mediate neutrophilic inflammation by inducing the release of IL-1β and TNF-α. Animal studies have also shown that noise exposure leads to an increase in pro-inflammatory cytokines such as IL-1β and IL-6.[43] Given that noise-induced irritability and depression are highly consistent in activating pro-inflammatory pathways, IL-1β and TNF-α are very likely to be key mediators for noise-induced exacerbation of non-Th2 asthma.

Moreover, nerve impulses triggered by psychological stress can directly control the airway and cause neurogenic inflammation. Psychological stress prompts sensory nerves to release neuropeptides, such as calcitonin gene-related peptide and substance P.[44] In mice, substance P binds to Neurokinin 1 Receptor and activates the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor kappa B (NF-κB) pathway, triggering the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 inflammasome-mediated apoptosis of bronchial epithelial cells.[45] This local inflammation mediated by neuropeptides constitutes a ‘neuro-immune direct coupling’ pathway in which psychological stress directly leads to airway damage.

Despite the lack of clinical evidence that noise directly affects the lung–brain axis in children, children’s central nervous system and emotional and cognitive regulation mechanisms are still in the developmental stage and are more vulnerable to environmental stress. Consequently, their HPA axis may be more susceptible to persistent dysregulation and have limited capacity for spontaneous recovery under chronic noise stress.[46] Therefore, we hypothesise that noise-induced psychological stress may also disrupt the homeostasis of the lung–brain axis in children, potentially contributing to neurogenic inflammation and hyperresponsiveness of the airway.

Circadian Rhythm Disruption and Sleep Deprivation

The World Health Organization (WHO) environmental noise guidelines point out that noise substantially affects the sleep quality of residents, leading to difficulty initiating sleep, increased awakenings and altered sleep structure.[47] Sleep deprivation itself is a significant physiological stressor that can lead to systemic chronic low-grade inflammation and may increase the risk of asthma.[48] A cross-sectional study involving 16,487 subjects showed that parasomnia was significantly associated with an increased risk of wheezing and/or asthma in childhood (OR = 4.55; 95% CI 1.69–12.25), and the association was stronger in preterm infants (relative excess risk due to interaction = 1.43; 95% CI 0.41–2.45).[49] Clinical surveys have also shown that clinically significant insomnia is reported by nearly twice as many adolescents with the severe asthma group as those with mild or no asthma.[50]

In addition to affecting sleep duration and quality, noise exposure can also interfere with the circadian rhythm. Fontana et al.[51] reported that noise exposure may induce abnormal expression of circadian genes and circadian clock disturbances. Yaşar et al.[52] found that circadian clock disturbances may lead to a decrease in pulmonary function parameters (e.g., forced expiratory volume exhaled in the first second [FEV1], the ratio of forced expiratory volume in the first second to the total forced vital capacity [FEV1/FVC] and peak expiratory flow) and a reduction in asthma control rate. The concept of the lung–brain axis provides a potential explanation for the clinically challenging observation that nighttime environmental noise is difficult to control and aggravates asthma symptoms. Under normal physiological conditions, nighttime is the period when vagal nerve tone is the highest and airway calibre is the smallest; under pathological conditions, however, the central nervous system re-evaluates interoception (such as mild airway inflammation). When children with asthma experience sleep fragmentation or awakenings due to nighttime noise, the salience network, which was originally disturbed by the underlying inflammatory processes including Th17-related inflammation, is more easily overactivated by noise stimulation during sleep without conscious inhibition. This central sensitisation effect may amplify weak airway signals into disproportionate perceptions of respiratory distress, and then induce bronchoconstriction through descending vagal reflexes.[40] Therefore, nighttime noise not only deprives sleep but also triggers airway hyperresponsiveness during the most vulnerable window of the neuroimmune system.

CONCLUSION AND IMPLICATIONS FOR CLINICAL PRACTICE

Conclusion: A Dual-Pathway Hypothesis for Noise-induced or Exacerbated Childhood Asthma

Traditionally, environmental noise has been considered primarily an auditory hazard or a physical irritant to the respiratory system. However, this review, based on an interdisciplinary chain of evidence, proposes a conceptual framework to explore the potential indirect pathways through which noise exposure may induce or aggravate childhood asthma [Figure 1].

Figure 1.

The potential mechanisms by which noise may induce or exacerbate childhood asthma.

Noise does not necessarily directly invade the airways but rather acts as a systemic stressor—an environmental stimulus that, despite localised sensory reception, triggers widespread neuroendocrine and systemic immune cascades. Through this mechanism, noise exposure reshapes the pathophysiological microenvironment through two core pathways: first, the immune-inflammatory pathway, in which noise induces systemic oxidative stress, damaging the epithelial barrier and specifically activating key chemokine networks to mediate immune cell recruitment and pro-inflammatory cytokines, such as IL-1β/TNF-α, thereby driving non-Th2 inflammation or facilitating Th2 hypersensitivity responses by disrupting immune homeostasis; second, the neuro-endocrine interaction pathway, in which chronic noise exposure leads to autonomic imbalance (including vagal rebound and receptor remodelling), triggering altered airway sensations and descending neural amplification through the lung–brain axis, while the release of neuropeptides such as substance P induced by psychological stress may contribute to airway neurogenic inflammation. These two pathways intertwine, ultimately disrupting airway homeostasis in susceptible children, triggering or exacerbating asthma attacks and progression.

Implications for Childhood Asthma Treatment Strategies

Based on the aforementioned non-traditional pathogenic mechanisms, the conceptual framework for managing children with asthma who are chronically exposed to high-noise environments or have suboptimal responses to conventional treatments can potentially be expanded beyond simple anti-allergy and anti-inflammatory approaches towards a bidirectional neuro-immune regulatory perspective. However, it must be clear that there is currently no clinical evidence supporting specific interventions for noise exposure-related asthma. These implications represent a theoretical deduction based on mechanistic hypotheses, intended to provide further insights for future precision intervention research and requiring rigorous validation through experimental and clinical studies.

(1) Emphasise targeted intervention for non-Th2 inflammation and neurogenic inflammation. For asthmatic children with significant environmental stress or psychological disorders, their airway inflammation is often not simply eosinophil infiltration. Future pharmacological research could explore targeting non-Th2 inflammatory pathways (e.g., neutrophil-related cascades) or neurogenic inflammation (e.g., modulating sensory neptide signalling), rather than relying exclusively on traditional anti-eosinophilic biologics.

(2) Pay attention to glucocorticoid resistance and early use of neuromodulators. HPA axis disorders and β2 receptor desensitisation associated with long-term noise exposure are potential causes of hormone resistance and decreased bronchodilator sensitivity in children. For these children, early combined use of anticholinergic drugs (blocking vagal rebound) may be more effective than simply increasing the dose of inhaled glucocorticoids.

(3) Mind–body treatment based on the lung–brain axis. Given the ‘amplifier’ effect of emotional networks such as the amygdala in acute asthma attacks, non-pharmacological approaches such as cognitive behavioural therapy, mindfulness-based stress reduction or biofeedback training may hold auxiliary value for asthmatic children with high noise exposure or subjective noise-induced irritability. By potentially reducing central sensitisation, these methods might help to break the upstream psychological stress–airway spasm reflex arc, though their specific efficacy in noise-related asthma warrants dedicated clinical evaluation.

Implications for Childhood Asthma Prevention Strategies

The implications for prevention may be particularly relevant for public health, with an emphasis on interrupting the noise-stress chain at its source:

(1) Incorporate acoustic environment assessment into guidelines for the management of childhood asthma. During clinical history taking in paediatric respiratory patients, in addition to routinely inquiring about allergens and tobacco exposure, nighttime residential noise levels and subjective noise-induced agitation can be included as supplementary screening items. For preschool children, special attention may be warranted regarding nighttime noise exposure, when a nighttime residential noise exposure exceeding 40 dB(A) at night − the threshold recommended by WHO guidelines for community noise.[53]

(2) Prioritise optimising the nighttime acoustic environment. Given that nighttime is the period of highest vagal tone and the lung–brain axis is most sensitive to airway resistance, the core of preventing noise-induced asthma lies in ensuring acoustic quality during sleep. To promote healthy sleep in children, the WHO guidelines for community noise recommend that nighttime noise levels in bedrooms remain below 30 dB(A) and individual sound events should not exceed 45 dB(A).[53] Parents are advised to take physical noise-reduction measures, such as soundproof doors and windows, using earplugs, to minimise nocturnal noise stimuli that may trigger vagal reflexes and reduce nighttime awakenings and sleep fragmentation.

(3) Promote the integration between urban planning and public health policies. Greater adherence to the WHO environmental noise guidelines should be encouraged in the planning of urban residential areas, schools and hospitals. Specifically, urban policies could aim to ensure that nighttime residential noise exposure remain below 40 dB(A) and that average 24-hour road traffic noise remain below 53 dB(A).[53] Furthermore, for residents around major traffic arteries where these thresholds are frequently exceeded, consideration could be given to noise isolation belts or building sound insulation renovations to reduce environmental noise exposure that may contribute to childhood asthma.

LIMITATIONS

Although this paper systematically constructs a theoretical framework for how noise affects childhood asthma through an indirect immune-neuroendocrine pathway, current research in this field still has several limitations.

(1) The lack of direct causal evidence and the limitations of cross-disciplinary inference. Currently, few studies directly elucidate the complete chain of mechanisms from auditory and central nervous system to airway lesions by focusing solely on environmental noise as a single exposure source. This article extensively cites literature based on psychological stress, air pollution or local cochlear damage to deduce the mechanisms of asthma. However, whether the neuro-immune cascade response triggered by noise as a specific physical stressor is entirely homologous to pure psychological stress or chemical pollution remains to be directly confirmed.

(2) Confounding interference and risk of causal inversion in epidemiological studies. Existing epidemiological studies on noise and the respiratory system are mostly cross-sectional, making it difficult to determine temporal relationships. More importantly, high-noise environments often overlap with high traffic volume and low socioeconomic status, and traffic-related air pollution (such as PM2.5 and NO₂) is a recognised trigger for asthma. Although some studies have attempted to adjust for air pollution factors, it is difficult to completely separate the two in long-term exposure. Furthermore, children with severe asthma may experience poor sleep and irritability due to the disease itself, leading to a higher subjective sensitivity to noise, potentially reversing the causal relationship.

(3) Lack of quantitative assessment through specific intermediary methods. In the complex neuro-immune network, pathways such as oxidative stress, autonomic nervous system imbalance and lung–brain axis sensitisation often intertwine and run parallel. Currently, no clinical studies can quantitatively assess which pathway dominates in noise-induced asthma, nor can the contribution weight of specific mediators (e.g., IL-1β, substance P, or CCL2) be clearly defined.

FUTURE DIRECTIONS

To address the aforementioned limitations, future research on environmental noise and childhood asthma could seek breakthroughs in the following areas:

(1) Conduct high-precision prospective studies and mediation analyses.

Large-scale, long-term prospective studies should be incorporate high spatiotemporal assessments of noise exposure, distinguishing between daytime and nighttime exposure as well as spectral characteristics. Mediation effect analyses should then be performed to quantify the proportions of the association between noise exposure and asthma onset or exacerbation that is mediated by sleep disorders, depressive and anxiety symptoms and systemic inflammatory markers, thereby helping to identify the principal mechanistic pathway.

(2) Establish dedicated animal models to validate the ‘noise stress–asthma’ mechanism

Basic research should move beyond conventional cochlear injury models by establishing a composite mouse model of chronic environmental noise exposure and airway allergen stimulation. This model could be used to characterise the dynamic changes in the chemokine–immune cell axis, vagal–macrophage crosstalk and substance P-mediated neurogenic inflammation in the airway. In addition, chemogenetic or optogenetic approaches could be used to manipulate specific neural circuits, such as salience networks, along the lung–brain axis to causally demonstrate the descending driving effect of central sensitisation on airway spasm.

(3) Explore objective biomarkers and targeted intervention strategies

Future efforts should focus on identifying objective biomarkers that can identify noise-sensitive asthma, such as serum CCL2, induced sputum neutrophil ratio, specific frequency band changes in heart rate variability or abnormal activation of the salpingoblast network in functional magnetic resonance imaging (MRI). At the intervention level, in addition to advocating for noise reduction through public policies, randomised controlled trials should be conducted to evaluate whether improving the nighttime acoustic environment, using vagus stimulation modulation devices, or early psychological and cognitive interventions can substantially reduce the frequency of acute exacerbations and hormone dependence in children with stress-induced asthma.

Availability of data and materials

All data and materials presented in this review are derived from previously published studies, which are fully cited in the reference list. No new primary data were generated during the conduct of this review.

Author contributions

Na Jing and Xianfeng Qu conceived and designed the conception and framework of this review. Na Jing, Fengxiang Zhang and Ningxia Zhao contributed to literature retrieval and screening, as well as draft of the paper. Ningxia Zhao, Xiaoyan Xu and Yu Wang were involved in the verification of search results and the synthesis of evidence. All authors contributed to critical revision of the manuscript. All authors have read and approved the final version of the manuscript.

Ethics approval and consent to participate

This study is a narrative review of existing epidemiological, mechanistic, and intervention-related literature. No original research involving human subjects or animal experiments was performed. Therefore, ethical approval and consent to participate are not applicable.

Conflicts of Interests

The authors declare that there are no conflicts of interest.

Funding Statement

None.