E pluribus plurima: Multidimensional indices and clinical phenotypes in COPD

Chronic Obstructive Pulmonary Disease (COPD) is a disorder of the respiratory system characterized by progressive and only partially reversible airflow obstruction, due to a varying combination of large (bronchitis) and small airways (small airway disease) damage, and lung parenchymal and vascular destruction [1]. We prefer the term obstruction to airflow limitation because the latter is a physiologic event which occurs also in normals at high levels of ventilation, for example during exercise. The correct definition should be “excessive airflow limitation” to indicate that the reduction in airflow occurs at lower level of ventilation than in normal condition. The diagnostic procedure for COPD starts from the recognition of risk factors (cigarette smoking “in primis”, but also outdoor and indoor air pollution [2]) and the presence of symptoms such as chronic cough and phlegm and reduced exercise tolerance. The lifestyle is important for the reveal of symptoms: dyspnea occurs later in a sedentary person than in an active individual. The objective demonstration of airflow obstruction by spirometry is mandatory to establish the diagnosis. A post-bronchodilator FEV1/FVC < 0.70 is considered sufficient to define airflow obstruction and to confirm the diagnosis [3,4]. FVC = forced vital capacity; FEV1 = forced expiratory volume in the 1st second; VC = (slow) vital capacity. Some Guidelines requires that FEV1/FVC < 0.70 [5] should be associated with a FEV1 < 80% of the predicted value [1,6]. Many Authors [7], however, and some official documents [8,9] do not accept the fixed “cut-off” and indicate the FEV1/VC < lln (lower limit of normality) as a more correct documentation of airflow obstruction. The debate is still ongoing [10]. However, it seems to be a general agreement to use the value of FEV1%predicted to stage the severity of the disease. Neverthless, it would be more appropriate to accept the use of that measurement for staging only the severity of airflow obstruction, not the whole disease state. In fact COPD is a heterogeneous disorder with diverse pathophysiological manifestations at the level of the respiratory system as well as at systemic level with complications and comorbidities. Not surprisingly, the FEV1 is rather insufficient to assess the status and progress of the disease as well as the effects of therapies. Although very helpful and valuable, the FEV1 has several limitations which should be taken into account when interpreting its value and changes. First of all it should be remembered that FEV1 results from two undisclosed determinants, i.e. the caliber of the large airways and the lung elastic recoil. The latter is poorly sensitive to treatments whereas the former can be improved by either pharmacological [11] and/or non pharmacological [12] treatments. Therefore, the individual response to therapies depends upon which determinant drives the FEV1 reduction more. Furthermore, the FEV1 is rather insensitive to small airway disease, which is an important pathology of COPD [13] and may be extensively present when spirometry is still within the normal range [14].