Escalation and De-escalation of Therapy in COPD: Myths, Realities and Perspectives

Chronic obstructive pulmonary disease (COPD) guidelines and strategies suggest escalating treatment, mainly depending on the severity of airflow obstruction. However, some de-escalation of therapy in COPD would be appropriate, although we still do not know when we should switch, step-up or step-down treatments in our patients. Unfortunately, trials comparing different strategies of step-up and step-down treatment (e.g. treatment initiation with one single agent and then further step-up if symptoms are not controlled versus initial use of double or triple therapy, possibly with lower doses of the individual components, or the role of N-acetylcysteine in combination therapy for a step-down approach) are still lacking. In general, there is a large and often inappropriate use of the inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) combination. However, the withdrawal of the ICS in COPD patients at low risk of exacerbation can be safe, provided that patients are under regular treatment with long-acting bronchodilators. Maximising the treatment in patients with a degree of clinical instability by including an ICS in the therapeutic regimen is useful to control the disease, but may not be needed during periods of clinical stability. In patients with severe but stable COPD, the withdrawal of the ICS from triple therapy [LABA + long-acting muscarinic antagonist (LAMA) + ICS] is possible, but not when the patient has been hospitalised for an acute exacerbation of COPD. We must still establish how long we should wait before withdrawing the ICS. It is still unclear whether the same is true when only the LABA or the LAMA is withdrawn while continuing treatment with the other bronchodilator and the ICS. In any case, we strongly believe that it is always better to avoid a therapeutic step-up progression when it is not needed rather than being forced subsequently into a step-down approach in which the outcome is always unpredictable.