Difficult-to-treat COPD: from concept to practice

Most patients with Chronic Obstructive Pulmonary Disease (COPD) can be managed effectively through standard therapeutic strategies. However, a significant proportion remains symptomatic, experiences recurrent exacerbations, or shows accelerated lung function decline despite apparently appropriate care. These patients often fall into what could be referred to as "difficult-to-treat COPD", a term still lacking formal definition. Drawing parallels with asthma, this article proposes to consider the concept of disease control in COPD as a key driver of COPD management, not representing a fixed target but a dynamic construct reflecting daily impact and long-term stability. We provide a structured framework for reassessing diagnosis accuracy, evaluating treatment adequacy, and identifying unresolved pathophysiological drivers in patients who remain uncontrolled. Core domains include persistent dyspnea, chronic bronchitis, frequent or severe exacerbations, and rapid lung function decline. Each is explored with a focus on clinical reasoning, diagnostic tools, and phenotype- or endotype-based treatable trait-specific strategies. Importantly, the article argues that in patients remaining uncontrolled despite guideline-concordant care, the clinical response paradigm should shift from escalation to recharacterization. Practical pathways beyond standard care such as biologic therapy, lung volume reduction and transplantation, access to research protocols, and early integration of palliative care are reviewed. In the conclusion, we advocate for broader implementation of multidisciplinary case discussions and for using loss of disease control as a clinical trigger to prompt timely reassessment. Rather than defining a new phenotype, the aim is to promote a dynamic, precision-based approach to COPD management that aligns therapeutic strategies with evolving disease trajectories.