Over the past decades, the pharmacological management of chronic obstructive pulmonary disease (COPD) has undergone significant advancements. Initially, treatment decisions were predominantly guided by patients’ respiratory function.1 However, the parameters influencing optimal therapeutic choices have expanded considerably.2 This complexity arises from the continuous development of new therapeutic options and an enhanced understanding of the diverse clinical phenotypes of COPD and their prognostic implications. Consequently, clinicians must now consider a myriad of disease-specific factors when tailoring treatment plans for individual patients, posing a significant challenge in real-world clinical practice.

Current guidelines for COPD management primarily rely on therapeutic algorithms derived from clinical trials that assess the efficacy and safety of treatments under controlled conditions. This evidence-based approach serves as a cornerstone for developing standardized recommendations, offering clear directives on when and how to use specific therapies. However, it is well recognized that clinical trials often fail to fully represent the complexity of real-world COPD. Studies reveal that the representativeness of real-world patients in clinical trials remains alarmingly low.3 This gap can be attributed to two primary factors. First, clinical trials are designed to meet regulatory requirements for drug approval, which may not align with evaluating real-world effectiveness. Second, strict eligibility criteria in these trials aim to isolate therapeutic effects within narrowly defined clinical contexts.4 As a result, the application of trial-based guidelines frequently falls short in addressing the nuanced realities faced by practicing clinicians.5,6 In routine clinical practice, numerous factors influencing pharmacological prescriptions are seldom addressed in guideline documents. These include comorbidities, patients’ social circumstances, previous treatment experiences, and the rate of disease progression, to mention a few. Faced with these complexities, clinicians often find themselves compelled to intensify treatment in the absence of definitive guidance, hoping to elicit a favorable response.

Given these considerations, rigid, dogmatic guidelines may not adequately address the needs of real-world COPD patients. Instead, a more individualized approach—considering a range of patient-specific variables—may optimize therapeutic outcomes while minimizing polypharmacy. Among these variables, four stand out as critical for guiding inhaled therapy in COPD: (1) the clinical impact of the disease on daily activities, (2) the presence of T2 inflammation, (3) the risk of adverse effects, and (4) the potential consequences of treatment failure. These variables can be envisioned as elements of a “kaleidoscope” (Fig. 1), wherein each case requires a unique combination of factors to guide clinical decisions. For instance, patients experiencing significant symptomatic burden may benefit from more intensive bronchodilator therapy. Similarly, the risk of therapeutic failure, particularly in individuals with extensive comorbidities or severe disease, warrants careful consideration to prevent adverse outcomes. The presence of T2 inflammation serves as another pivotal determinant, often indicated by peripheral blood eosinophil counts—a surrogate marker recommended by current guidelines. Although the utility and precision of T2 markers remain a topic of ongoing debate,7,8 advancements in this area may soon provide more reliable indicators. Additionally, a history of adverse reactions to inhaled corticosteroids (ICS) should influence treatment selection, underscoring the importance of balancing efficacy with safety.

Fig. 1.

The COPD kaleidoscope. LABD: long-acting bronchodilators; LABA: long-acting β2 agonist; LAMA: long-acting muscarinic antagonist; ICS: inhaled corticosteroids.

(0.21MB).

The ongoing debate regarding whether COPD treatment should commence with maximal therapy or follow a stepwise escalation highlights the need for flexible, evidence-informed decision-making.9 Beyond this dichotomy, clinicians must adopt a more adaptable framework, refining treatment plans as clinical determinants unfold over time. In a disease characterized by its progressive nature, selecting appropriate maintenance therapy is critical for achieving sustained control over clinical manifestations. This perspective challenges static, dogmatic treatment paradigms. Instead, COPD management should embrace a dynamic, patient-centered approach, adapting therapeutic strategies to evolving clinical scenarios.

Drawing inspiration from the popular television series Breaking Bad, we advocate “breaking bad” from rigid therapeutic recommendations that portray COPD management as static and universally applicable. Effective clinical practice demands a dual focus: integrating insights from clinical trials while acknowledging the multifaceted nature of COPD in real-world settings. By understanding the interplay of pharmacological mechanisms, disease characteristics, and patient-specific factors, clinicians can make informed decisions that pave the way for truly personalized medicine, enabling patients to lead active and fulfilling lives.