COPD: Moving Beyond Physiological Reductionism.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality throughout the world: it is the fourth leading cause of death in the world and further increases in prevalence and mortality can be predicted in the coming decades(1,2). The Global Initiative for Chronic Obstructive Lung Disease (GOLD) has significantly contributed to increasing awareness of COPD in order to decrease morbidity and mortality from the disease(3). In the first GOLD consensus report clear management goals are put forward. Effective management should be aimed to relieve symptoms, prevent disease progression, improve exercise tolerance, improve health status, prevent and treat complications, prevent and treat exacerbations and reduce mortality(3).

Airflow limitation, not fully reversible and usually progressive over time, is still considered as the key characteristic of COPD. This airflow limitation is assumed to be associated with an abnormal inflammatory response of the lungs to noxious particles or gases(3). This physiological approach putting forward abnormalities in the structure and function of the lungs fits with the medical anthropological approach in the 20th century that physicians need to diagnose and treat “diseases”, while the illness, experiences of disvalued changes in states of being and states of social function, belong to the patient(4). Irreversibility in this approach is the product of lung function technology and vagueness about the limits of reversibility is still existing. Chronicity is defined as an accelerated declination of lung function impairment over time, and during many decades pharmacological treatment was directed to attenuate this decline in airflow limitation.

Indeed, such a singular concept of airflow limitation is easily to grasp and still dominates the therapeutic approach of COPD. Although guidelines as GOLD formulate that assessment of COPD severity needs to be based on the patient's level of symptoms, the presence of complications, the level of airflow limitation is still considered as the key component in the assessment of COPD severity(5). Important to notify is that applied cut-off points to define different levels of severity are used for purposes of simplicity and have not been clinically validated(5). This approach can be considered as a form of reductionism: an attempt to explain a complex set of facts, entities, phenomena, or structures by another simpler set. Stressing in this context the dominant role of FEV1 can be defined as a form of single factor reductionism. This single factor approach has created an excellent therapeutic target but disregards dynamics, interactions, and the undeniable inherent complexity of biological systems.

The simplified spirometric staging of COPD is still the basis for the formulation of so-called evidence based recommendations for pharmacological management of COPD. This evidence based approach assumes that a knowable modification of a known malfunction as airflow limitation will result in linear, predictable results(6). Importantly to note is that even airflow limitation is a summative outcome parameter in COPD, reflecting airway inflammation, airway remodelling and changes in elastic recoil. Based on this disease driven approach the general principle is that pharmacological treatment tends to be cumulative with more medications being required as the spirometrically defined disease state worsens(5). Otherwise, current guidelines agree that currently available pharmacological medications for COPD do not modify the long-term decline in lung function and recognize the poor relationship between lung function and symptoms and/or complications in COPD(7). Furthermore, while evidence-based decision making assumes linear, predictable improvement in identified malfunctions, most therapeutic recommendations are largely based on scientific data reporting changes in a variety of summative outcomes in COPD patients but without clearly proven cause and effect relationships.

Besides the changes in the respiratory system, guidelines as the GOLD document consider COPD as a treatable disease with some significant extra-pulmonary effects that may contribute to the severity in individual patients(5). These extra-pulmonary effects and significant co-morbidities must be taken into account in a comprehensive diagnostic assessment of severity and in determining appropriate treatment(5). These co-morbidities are serious medical conditions that are not directly related to the primary diagnosis itself but involve any other major organ system. In the linear model of the human body as a machine and illness as due to malfunction of its parts, clinical care will be break down into ever smaller divisions and guidelines based on such model will express with great accuracy and precision the intervention to be undertaken for each malfunction(6). This mechanical concept of COPD and other disease conditions is only valid when the effects of these malfunctions are constant, independent and predictable(8). The heterogeneity of COPD illustrates that this machine metaphor lets us down badly.

The science of complex adaptive systems potentially provides important concepts to deal with this disease complexity. A complex adaptive system is a collection of individual agents with freedom to act in ways that are not always totally predictable, and whose actions are interconnected so that one agent's actions changes the context for other agents(8).

In terms of complexity science, the human body can be considered as being composed of multiple interacting and self- regulating physiological systems including biochemical, cellular, physiological, psychological and social systems. All these interacting systems are dynamic and fluid. Illness arises from dynamic interactions within and between these systems, and not from failure of a single component. (6,8) In this concept, health can only be re-established through a holistic approach that accepts unpredictability and builds on subtle emergent forces within the overall system(9). In the un-ordered domain of complex relationships, cause and effect relationships are only coherent in retrospect and do not repeat. In such a complex system, the decision model will be to create probes to make the patterns or potential patterns more visible. Decision-making will be based on stabilizing those patterns we find desirable, by destabilizing those patterns we do not want, and by seeding the space in such away that patterns we want are more likely to emerge(9,10). Clinical judgment will be more important in such a complex model than analytic evidence-based care (9). This clinical judgment will involve an irreducible element of factual uncertainty, and will rely to a greater or lesser extent on intuition and the interpretation of the wider history of the illness(11). Accepting the complexity of COPD, requires that linear models need to be abandoned and that unpredictability in the outcome of interventions, built on subtle emergent forces within the overall system, are accepted(6,8).

Considering COPD as a complex disease requires redefinition of COPD from a treatable disease into a manageable disease. Health care providers need to manage a diseased person and not to treat a disease: this needs to become a mental attitude which the health care provider will increasingly have to make his own. This attitude requires an individualized patient-centred management plan, supported by a personalized pharmaco-therapeutical regimen in order to create added value for the COPD patient. Complexity science suggests that readiness to change occurs when a system is in a state far from equilibrium: in such circumstances a small influence can have large effects(12,13). Future guidelines need to incorporate this dynamic, individualized and patient centred view on COPD as a complex disease: this will become the enormous challenge for COPD care in the 21th century!