Asthma is one of the most common chronic, non-communicable diseases in children and adults. It is a consequence of complex gene–environment interactions, with heterogeneity in clinical presentation and the type and intensity of airway inflammation and remodelling.

Airway hyperresponsiveness is a feature present in asthma phenotypes with or without granulocytic inflammation in children and adults.

The goal of asthma treatment is to achieve good asthma control: To minimise symptoms and exacerbations. Anti-inflammatory and bronchodilator treatments are the mainstay of asthma therapy and are used in a stepwise approach. Airway hyper-responsiveness is a feature present in asthma phenotypes with or without granulocytic inflammation in children and adults.

In asthma, the airway smooth muscle is hypercontractile, which is amplified by co-located activated mast cells and possibly by mechano-transduction independent of airway inflammation. Airway remodelling can present early in childhood, suggesting it is not simply a consequence of inflammation.

Remodelling characteristics lead to thickening of the airway wall, luminal narrowing on quantitative CT, and mucus plugging, with small airway obliteration. Pharmacological treatment is based on a cycle of assessment and re-evaluation of symptom control, risk factors, comorbidities, side-effects and patient satisfaction by means of shared decisions.

The condition is classed as severe when high-intensity treatment is needed to keep it under control, or if it remains uncontrolled despite treatment. New biological therapies for treatment of severe asthma, together with developments in biomarkers, present opportunities for phenotype-specific interventions and realisation of more personalised treatment.

PATHOGENESIS OF ASTHMA

Asthma is a heterogeneous condition in both children and adults. The phenotypes of asthma – including clinical features of the disease and their underlying mechanisms are complex. Genome-wide association studies of asthma in children and adults have identified an association between polymorphisms for IL33, IL1RL1/IL18R1, HLA-DQ, SMAD3, and IL2RB and the locus on chromosome 17q21 including the genes ZPBP2, GSDMB, and ORMDL3.

These genes implicate abnormalities in epithelial barrier function and innate and adaptive immune responses as contributing to asthma. Progress has been made in our understanding of the heterogeneity of immunology in asthma. Sputum cytology provides evidence of eosinophilic, neutrophilic and mixed complex inflammation, as well as few inflammatory cells in some patients (paucigranulocytic).

Transcriptomic profiles of bronchoscopic samples have led to identification of molecular phenotypes consistent with high type 2 immunity and low type 2 immunity asthma, as well as others. Because of the limitations of sampling the airway in children, particularly with invasive procedures, there is a paucity of data in this age group.

Eosinophilic, high type 2 airway inflammation is present in around 50% of adults with asthma, but corticosteroid withdrawal studies often reveal eosinophilic airway inflammation, suggesting its prevalence might be underestimated. Atopy is present in 50%-60% of adults and children with asthma, but is more common in severe asthma among children and among adults with childhood-onset versus late-onset disease.

Following allergic sensitisation and consequent stimulation by dendritic cells in the presence of coactivators such as epithelium-derived thymic stromal lymphopoietin, adaptive T helper 2 cells produce interleukin-5, interleukin-4, and interleukin-13. Interleukin-5 is an obligate cytokine for the survival and maturation of eosinophils. Recruitment of eosinophils to the lung mucosa is mediated via C-C motif chemokine receptor 3 chemokines and other eosinophil chemo-attractants, such as mast cell-derived prostaglandin D2.

Interleukin-4 drives B-cell isotype switching and IgE synthesis, which binds to mast cell high affinity IgE receptors, leading to mast cell activation following allergen-mediated IgE cross-linking. In non-allergic eosinophilic asthma, innate lymphoid cells produce interleukin-5 and interleukin-13 in response to prostaglandin D2 and epithelium-derived alarmins interleukin-33, interleukin-25, and thymic stromal lymphopoietin released after epithelial damage by pollutants and microbes.

Non-eosinophilic asthma has been described in adults and children but is poorly understood. Some patients have neutrophil predominant disease with release of cytokines from T helper 1 cells, T helper 17 cells, 21 or type 3 innate lymphoid cells, with activation of macrophages and release of neutrophil chemokines such as C-X-C motif chemokine ligand 8. However, with bronchiectasis as a common comorbidity of severe asthma in adults, a neutrophilic response could reflect bacterial colonisation or effects of corticosteroids on promotion of neutrophil survival and suppression of type 2 immunity, leading to upregulation of type 1 or type 17 immunity.

The allergic-dependent and allergic-independent mechanisms that drive eosinophilic inflammation and noneosinophilic asthma can occur in concert, leading to mixed granulocytic inflammation or changes in the inflammatory profile over time.

A COMPREHENSIVE APPROACH TO ASTHMA TREATMENT

Asthma treatment involves a personalised approach, which includes self-management education, a written asthma action plan, and inhaler training (for children, this includes parents, caregivers and teachers), treatment of comorbidities and modifiable risk factors, nonpharmacological treatment (eg, avoidance of tobacco exposure, weight loss, sublingual immunotherapy for certain patients, removal from occupational exposures, avoidance of aspirin and other non-steroidal anti-inflammatory drugs in patients with aspirin-exacerbated respiratory disease, and remediation of mould or damp), as well as pharmacological treatment, which can be adjusted to find each patient’s minimum effective dose.

Adjustment of treatment is based on a cycle of assessment and reassessment of each patient’s symptom control, risk factors, comorbidities, side-effects, and patient or parent satisfaction. Shared decision making is associated with improved patient-centred outcomes. Self-management education includes self-monitoring, a written asthma action plan so the patient (or caregiver) knows how to recognise and respond to worsening asthma, and regular clinical review.

Such education is associated with a third to two-thirds reduction in urgent health-care, work or school absences, and night waking. Inhaler training with physical demonstration is essential, as incorrect technique is extremely common and associated with an increased risk of exacerbations. In adults, regularly repeated inhaler training leads to improved asthma control. Various methods are used to treat concomitant clinical conditions such as allergic rhinitis, obesity, obstructive sleep apnoea, gastro-oesophageal reflux disease, mental disorders and asthma COPD overlap.