• Minimal chronic symptoms
• Minimal exacerbations
• No emergency visits
• Minimal (ideally no) use of rescue medications
• No limitations on activities
• PEF circadian variation of less than 20%
• (Near) normal PEF

As anticipated, with regard to asthma therapy, a stepwise approach is generally adopted: thus, whenever control is not achieved or is lost (presence and persistence of symptoms, increased use of rapid-acting bronchodilators, lung-functions worsening - PEF values decrease) with the current treatment, the patient’s disease severity is considered to have moved one step forward, and a stronger treatment is consequently requested. Thus, starting from intermittent asthma, a progressively increasing number of drugs are prescribed to asthmatic patients, in order to realize an optimal control of the disease. On the other side, of course, with such an approach to therapy, once control of asthma is achieved, the dose of medication should be carefully titrated to the minimum dose (step-down approach) required to maintain control, thus reducing the potential for adverse effects.

Table 5: GINA, 2010 Update

For guidelines on management of asthma in children 5 years and younger, please refer to the Global strategy for the Diagnosis and Management of Asthma in Children 5 Years and younger, available at http://www.ginasthma.org/.

Details about the specific treatments suggested for every severity level of the disease are reported in the following corresponding insights:

• INTERMITTENT ASTHMA (Step 1): Due to the low frequency of the symptomatic episodes and normal lung functions in between exacerbations, no long-term treatment with a controller medication should be started. However the administration of a rapid-acting inhaled β₂-agonist prior to exercise as needed or upon allergen exposure (cromones or leukotriene modifiers) is warmly recommended.
  
  Furthermore, rescue medications, such as short-acting inhaled β2-agonists, may also be taken as needed to relieve asthma symptoms; inhaled anticholinergic, short-acting oral β2-agonist, or short-acting theophylline may be considered as alternatives to short-acting inhaled β2-agonists, although characterized by a slower onset of action and/or a higher risk for side effects.


• MILD PERSISTENT ASTHMA (Step2): Patients with mild persistent asthma require controller medication every day. The primary therapy for mild persistent asthma is daily use of anti-inflammatory medication, such as inhaled glucocorticosteroid. Alternative controller medications are sustained-release theophylline, cromones and leukotriene modifiers, although their effectiveness in patients with mild persistent asthma should be further proved. In addition to regular controller therapy, rescue medications (rapid-acting inhaled β₂-agonist) should be taken as needed to relieve symptoms.


• MODERATE PERSISTENT ASTHMA (Step 3): Patients with moderate persistent asthma require controller medication every day. If asthma control is not achieved with low doses of inhaled glucocorticosteroids, a regular treatment with a long-acting inhaled β₂-agonist should be added, rather than increasing the dose of inhaled glucocorticosteroid. Therefore, generally, the preferred controller treatment for moderate persistent asthma is a combination of an inhaled glucocorticosteroid and a long-acting inhaled β₂-agonist twice daily. Although combination therapy of a glucocorticosteroid and a long-acting inhaled β₂-agonist is most effective and is the preferred option, alternative add-on therapies include sustained-release theophylline, long-acting oral β₂-agonist, leukotriene modifier.
  
  Relievers, as seen also for previous severity steps, should be taken on an as-needed basis.


• SEVERE PERSISTENT ASTHMA (Steps 4 and 5): In severe persistent asthma, multiple daily controller medications are usually required. Primary therapy includes inhaled glucocorticosteroids at higher doses (> 1000 μg/day of BDP or equivalent) plus a long-acting inhaled β₂-agonist twice daily, as preferred add-on treatment. However, alternative additional therapeutic agents are sustained-release theophylline, leukotriene modifiers, or long-acting oral β₂-agonist. These medications may also be added to the combination therapy.
  
  Rescue medications should be taken as needed.
  
  If necessary, long-term oral glucocorticosteroids should be used in the lowest possible dose.
  
  Steroid-sparing therapies may be considered in patients with severe persistent asthma, whose disease can be controlled with oral glucocorticosteroids, experiencing therefore systemic side effects from this treatment. Such steroid-sparing therapies include methotrexate, cyclosporin A and oral gold. These treatments are poorly effective and their side effects are often more troublesome than those of steroids. They should therefore only be used if there is clear evidence of benefit.
  
  A schematic representation of this stepwise approach to therapy in asthma is reported in Fig. 2.

Figure 2: Treatment hierarchy used to add further drugs as asthma becomes increasingly severe ²