Aetiology

Viral infection is the most common trigger in children.[5][6]​ Although individual allergenic triggers exist, most asthma exacerbations have multiple precipitants and occur in children known to have asthma or other atopic conditions (e.g., eczema or allergic rhinitis). Triggers include the following:[7]

  • Viral upper respiratory tract infection: triggers up to 80% of asthma exacerbations in children; rhinovirus, respiratory syncytial virus, pertussis, influenza, parainfluenza, and human metapneumovirus trigger most exacerbations.[6][8][9]​​ Rhinovirus is the most common cause.[9] Seasonal variation in acute asthma exacerbations is directly related to seasonal variation in these viral infections; viruses are associated with a 'back to school' effect each autumn.[10]

  • Bacterial infection: less common, but may precipitate acute exacerbations.[11] Generally caused by atypical bacteria, such as Mycoplasma pneumoniae.[12]

  • Inhaled allergens: house dust mites, pets (especially cats and dogs), pollen (tree, weed, and grass), food allergens, fungi (Alternaria), and cockroaches. Sensitisation to environmental allergens affects disease control and exacerbations, and sensitisation to the fungus Alternaria is associated with more severe asthma exacerbations.[13][14][15]

  • Air pollution (indoor and outdoor): a significant association has been shown between air pollutants and both emergency department visits and hospitalisations for asthma.[16][17]​​​​ Air pollutants include sulfur dioxide, nitrous dioxide, ozone, environmental tobacco smoke, evaporative volatile organic compounds, cooking- and heating-related particles, and particulate matter with aerodynamic diameter ≤10 micrometres or ≤2.5 micrometres.[17][18]​ Exacerbations are associated with living in areas near traffic or where wildfires occur.[2][17][19][20][21]

  • Emotion: anger, anxiety, and even the act of laughing can trigger an acute exacerbation.

  • Exercise: evaporative water loss from the airway surface stimulates airway obstruction.[22]

  • Medications: non-steroidal anti-inflammatory drugs may trigger asthma exacerbations. Rare in children.

  • Poor asthma control: strongly related to exacerbations and may reflect poor adherence to regular preventive therapy, poor access to health care, recent treatment discontinuation, or sub-optimal treatment.[23][24]

Other atopic diseases (e.g., eczema, allergic rhinitis, and food allergies) and obesity are associated with prominent respiratory symptoms and more frequent asthma exacerbations.[25][26][27]​ 

One systematic review and meta-analysis reported a modest association between gastro-oesophageal reflux disease and asthma exacerbation in paediatric patients.[28] Vaping is associated with higher rates of self-reported asthma and asthma exacerbations, and even reports of status asthmaticus.[29]​ 

Pathophysiology

Asthma is characterised by bronchoconstriction, airway inflammation, and mucus production that affects both the large and the small airways. The pathophysiological changes seen in acute asthma can be divided into early and late responses.

The early response is driven by airway hyper-responsiveness, a key component of asthma. This is an exaggerated airway response to an endogenous or exogenous stimulus that causes acute bronchospasm.

The late response is characterised by airway inflammation. This is driven by helper T cells (predominantly type 2) and lymphocytes, but it also involves a number of other cells (including eosinophils, mast cells, macrophages, and neutrophils) and a complex series of mediators (including cytokines, interleukins, prostaglandins, and leukotrienes). Inflammation causes swelling of the airway epithelium and smooth muscle hypertrophy, which causes airway narrowing even in the absence of exacerbating factors. Stimulation of mucus secretion and mucous cell hyperplasia can also cause mucus plugging. Airway inflammation can damage the epithelium indirectly, while viral and bacterial infection can cause direct damage, potentially resulting in cell debris being deposited in the airway lumen.

Acute exacerbations are associated with varying degrees of inflammatory and immunological cell infiltration and activation, depending on the trigger.[11] For example, neutrophils are the dominant cell found in viral and bacterial infections, whereas eosinophils predominate in allergen-associated exacerbations.[11]

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