Aetiology

The aetiology of asthma is complex and multifactorial. Features associated with asthma include episodic symptoms, wheeze confirmed by a healthcare professional, diurnal variability, and a history of atopy.[1][8]

Various antenatal and early postnatal exposures are associated with childhood asthma. Both in utero and postnatal tobacco smoke exposure are important contributing aetiological risk factors.[9]​ In utero exposure to vitamin D and air pollution, together with the maternal and infant microbiome (including antibiotic exposure), may also contribute to childhood asthma.[10][11][12][13][14][15]​ Preterm birth, low birth weight, and bronchopulmonary dysplasia are associated with childhood wheezing and asthma.[16][17][18]​​​​

Twin studies estimate that genetics account for up to 75% of the variance in risk.[19]​ Multiple gene polymorphisms have been associated with the development of childhood asthma.[20][21][22][23]​​​​​​ Genes likely exert their effects by interacting with environmental exposures, such as allergens and viral infections, in early childhood.[18][24]​​

Atopic disease (e.g., eczema, atopic dermatitis, allergic rhinitis, and food allergy) is strongly associated with asthma. Progression from eczema/atopic dermatitis to allergic rhinitis to subsequent asthma has been termed 'the allergic march', although the temporal associations between allergic phenotypes may evolve along multiple pathways.[18][25][26]​​[27]​​​​ Exposure and sensitisation to aeroallergens (e.g., house dust mites or pollens) and certain foods is a recognised risk factor for developing asthma (e.g., a positive skin prick test to house dust mites or specific pollens).[28]

Children younger than 5 years often present with recurrent wheezing due to frequent upper respiratory tract infections (URTIs).[1][29]​​ URTIs and lower respiratory tract infections in early life increase the risk of later asthma, particularly when caused by respiratory syncytial virus or rhinovirus.[30][31]​​​

Environmental exposures and air quality are important. Passive and active smoking, including vaping, lead to poor asthma control and increase symptoms (e.g., cough, wheeze, and dyspnoea).[9][32]​​[33][34][35][36]​​​​ Outdoor air pollution is associated with an increased risk of both asthma and loss of asthma control in children.[18][37][38][39]​​​​​​​​​​[40]​ Consistent with this, there is a higher risk of childhood asthma in urban compared with rural areas.[41]​ Pesticide exposure has been associated with a twofold greater risk of developing or exacerbating childhood asthma.[42][43]

Socio-economically disadvantaged groups are more likely to live in areas with the poorest air quality and worst housing conditions, while being exposed to more psychosocial stress and having poorer diets.[44]​ These factors increase the risk of asthma, poor asthma control, and acute exacerbations.

Pathophysiology

Asthma is a disease characterised by chronic airway inflammation. A number of different inflammatory cells are involved: neutrophils, eosinophils, lymphocytes, and mast cells with complex mediator pathways that involve various cytokines and T cells (predominantly TH-2 mediated).

Airway inflammation and airway (or bronchial) hyper-responsiveness to various inhaled stimuli lead to symptoms of reversible airway obstruction and altered lung function, which may evolve into a variety of phenotypes. Airway obstruction is caused by bronchospasm (smooth muscle contraction) and inflammatory changes such as airway wall oedema and mucus hypersecretion.

Relative contributions may differ between individuals and between episodes depending on the precipitating factor. Airway narrowing occurs in a heterogeneous manner in both the large and the small airways. Impaired ability to expel air results in audible wheezing and increased work of breathing, potential gas trapping, clinical hyperinflation, and alveolar hypoventilation.

In a proportion of cases, chronic structural changes occur and may be present by early childhood.[45] These include thickening of the epithelial reticular basement membrane (due to collagen deposition), hypertrophy and airway smooth muscle hyperplasia, extracellular matrix deposition, and hypertrophy of mucus-secreting glands. These changes may influence asthma outcome and predispose to a more severe, irreversible asthma phenotype.

Classification

International guidance from the Global Initiative for Asthma (GINA) recommends assessing asthma severity retrospectively when the patient has been on controller treatment for several months and, if appropriate, a step down in treatment has been attempted.[1] However, there is continued debate about the utility of this retrospective diagnosis for mild asthma.[1][2][3]​​ International, national, and local guidelines should be consulted as appropriate. 

GINA criteria for the severity of non-acute asthma[1]

This retrospective approach is suitable for children aged ≥6 years after treatment initiation; GINA does not recommend an approach for children <6 years. Asthma severity may change over time.

Mild asthma:

  • Asthma that is well controlled with step 1 or step 2 treatment, for example, with as-needed inhaled corticosteroid (ICS)-formoterol or with low-dose ICS plus as-needed short-acting beta-agonist (SABA).

  • GINA discourages using the term 'mild asthma' because it incorrectly implies a low risk of poor outcomes. Instead, clinicians should focus on symptom control and the continued risk of severe or fatal exacerbations, even with infrequent or mild symptoms.

Moderate asthma:

  • Asthma that is well controlled on treatment step 3 or 4, for example, low- or medium-dose ICS plus long-acting beta agonist (ICS-LABA).

Severe asthma:

  • Asthma that remains uncontrolled despite optimised treatment with high dose ICS-LABA, or that requires high-dose ICS-LABA to stop it from becoming uncontrolled.

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