Asthma exacerbations continue to be a significant cause of morbidity and mortality and it is important for all healthcare workers to be aware of strategies that prevent exacerbations and of therapies that must be given to patients with acute severe asthma, which is an important medical emergency. Treatment of an acute exacerbation should quickly restore good asthma control with a minimum amount of intervention. 

In general, the goals of asthma therapy are to maintain asthma control, achieve normal lung function and allow patients a normal lifestyle with a minimum of lifestyle interference and a minimum of drug therapy. 

Asthma is a complex airway disease, characterised by chronic airway inflammation that causes airway narrowing. There are many cellular, psychological and physiologic components that cause airway narrowing and a variety of clinical symptoms in a variable fashion. Not only is asthma variable between subjects, but people with asthma characteristically have symptoms and lung function that vary over time. 

While our understanding of the biologic processes that underpin asthma is becoming more detailed, it appears that the pathways and mediators are becoming ever more complex. Although a number of cell types and mediators can cause the features of asthma, no one cell type or cytokine is both necessary and sufficient to cause asthma. There appears to be redundancy in the biologic processes that lead to asthma. 

For example, although asthma exacerbations are closely linked to sputum oeosinophil number and activation, asthma can occur in the absence of oeosinophils. The same appears to be true of mast cells, neutrophils and lymphocytes, each of which appears to play an important, but non-essential, role in the development and persistence of asthma. 

More recently an array of therapies directed at IgE, IL-5, IL-13 and other biologic components of asthma have been shown to improve outcomes in well defined subsets of patients, but they neither lead to a cure for asthma nor a complete elimination of asthma exacerbations. This supports the idea that significant redundancy exists in the cellular and biologic pathways that cause asthma in most patients. For example, a therapy that might be highly effective for an asthma patient during allergy season might be ineffective for the same patient during a viral-induced exacerbation. 

In recent years it has become clear that some newly discovered components of the innate immunity (such as iNKT cells and ILC2 cells), when activated can orchestrate rapid and powerful asthma-like responses in both animals and humans. These responses can occur in the absence of classic adaptive immune responses and may explain why some patients are resistant to therapies directed solely at allergic type (Th2-driven) asthma.

Alternatively, some undiscovered cell or mediator is the common and essential cause of asthma in most patients. In support of this idea is the theory that the airway microbiome may importantly contribute to the development of asthma. The asthmatic airway contains diverse bacterial species, which are detectable using molecular amplification technology rather than by traditional culture techniques. The profile of bacterial species in the human airway differs between patients with asthma and patients with chronic obstructive pulmonary disease (COPD) or subjects without airway disease (normal lungs) and this ‘microbiome’ may influence either the development of (or protection against the development of) asthma. The environment, including consumption of antibiotics, may have an important effect on this. 

Currently, there is not enough data to determine why the airway microbiome differs considerably between healthy subjects, patients with COPD and patients with asthma, and it remains uncertain whether antibiotic therapy significantly affects these differences.

Exacerbation-prone asthma subjects 

Most asthma exacerbations occur unpredictably. However, while any person with asthma can suffer an exacerbation after exposure to an appropriate trigger, some patients are particularly more likely to do so (see Table 1). 

Furthermore, while we would like to believe that modern inhalers and other medication can ablate asthma attacks so that the asthma patient would be exacerbation free, it appears that many of the factors that contribute to exacerbations are dependent on changes in environment and patient behaviour. 

Non-adherence (or non-compliance) to strategies that prevent exacerbations are commonly associated with poor asthma control and even asthma mortality. All patients should have a written action plan. The written action plan should contain:

• Information about the patient’s usual medication
• When and how to change asthma medication
• How best to access medical care if the asthma medication is no longer working. 

People with asthma who forget or refuse to take medication are prone to develop severe attacks. An asthma patient with a severe food allergy, who takes controller medication on a regular basis, can still suffer an acute asthma attack after ingestion of a large quantity of the offending allergen. 

Some asthma patients suffer severe attacks in spite of maximal medication and lifestyle modification. The fatality prone asthma subject is a patient who is liable to suffer fatal or near fatal asthma attacks. These patients may not have good control even with optimal medication and a good understanding of asthma. 

Environmental challenges, such as viral infections, smoke, high pollen counts can all precipitate asthma exacerbations even in patients who take their medication exactly as prescribed, but these triggers are more likely to cause an attack in patients with poor asthma control. A balance exists between the magnitude of the risk of an exacerbation and the level of asthma control. The level of asthma control depends in large part on the combined efforts of the patient and the healthcare provider. 

Definition of asthma exacerbations

Asthma exacerbations (often called asthma flare-up or attack) describes an acute worsening of asthma symptoms and lung function (peak flow measures) from a patient’s usual status. In clinical practice, a common view is that an exacerbation occurs when a change in symptoms prompts a doctor visit, a significant change in daily activity (lost work days), or an increase in medication beyond the normal variability of medication use. Exacerbations can also be classified according to their effect on a patient (lost school day, work day, hospitalisation etc.) or the effect on a healthcare system (GP visit, attendance in emergency department). 

The aim of asthma therapy is to prevent asthma exacerbations by controlling asthma symptoms. Unfortunately this remains challenging because asthma patients commonly under-report symptoms, in part because they accept their symptoms as being part of the condition of asthma, in part because not all asthma patients are aware of their cough and shortness of breath. Many patients ignore some of the most important indicators of poor asthma control: nocturnal symptoms and increasing use of short-acting bronchodilators. 

Management of asthma exacerbations 

In clinical practice the key steps in managing an exacerbation are:

• To assess the severity based on pulse and respiratory rate, ability to speak, presence of a silent chest, peak flow rate, oxygen saturations
• Consider other causes for respiratory symptoms, such as foreign body, pneumonia
• Begin high dose (nebulised) short acting beta-agonist and oxygen if available
• Consider transfer of patient for advanced therapy (respiratory ward, emergency department, hospital, ambulance)
• Monitor closely and re-assess peak flow within one hour of treatment
• Arrange to improve asthma control after the acute exacerbation has subsided – generally patients will require higher-dose ICS or a controller device for several months after an exacerbation
• Arrange follow-up within one week, in order to review strategies to prevent exacerbations, including medication use, written action plan and modification of risk factors
• Consider specialist referral or referral to a severe asthma clinic. 

Future of asthma therapy

While our understanding of asthma continues to expand, it is becoming clear that there are many subtypes of asthma. Some new therapies are directed at, and are particularly effective at treating, certain types of asthma. For example, the monoclonal antibody omalizumab was designed to reduce the amount of free IgE in circulation. Since serum IgE levels have been associated with the presence of allergic disease and with worsening asthma, a therapeutic reduction in IgE levels is thought to help to treat patients with allergic asthma and high serum IgE. Omalizumab has proven benefits, mainly in reducing exacerbation rates, and is currently available in Ireland for patients with severe asthma. 

The future promises other therapies directed at asthma subtypes (for example, non-atopic asthma, adult asthma, asthma associated with viral infections, the obese person with asthma and so on). 

Newer tools are also being developed to help train patients to improve their adherence to asthma preventing strategies. These include reminders about medication, education about triggers and actions to take early in an exacerbation. In addition, a new wave of smartphone apps and monitors is currently in development to help patients better manage their asthma. 

References

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