Abstract
The most recent guidelines define COPD in a multidimensional way, nevertheless the diagnosis is still linked to the limitation of airflow, usually measured by the reduction in the FEV1/FVC ratio below 70%. However, the severity of obstruction is not directly correlated to symptoms or to invalidity determined by COPD. Thus, besides respiratory function, COPD should be evaluated based on symptoms, frequency and severity of exacerbations, patient’s functional status and health related quality of life [HRQoL]. Therapy is mainly aimed at increasing exercise tolerance and reducing dyspnea, with improvement of daily activities and HRQoL. This can be accomplished by a drug-induced reduction of pulmonary hyperinflation and exacerbations frequency and severity. All guidelines recommend bronchodilators as baseline therapy for all stages of COPD, and long-acting inhaled bronchodilators, both beta-2 agonist [LABA] and antimuscarinic [LAMA] drugs, are the most effective in regular treatment in the clinically stable phase. The effectiveness of bronchodilators should be evaluated in terms of functional [relief of bronchial obstruction and pulmonary hyperinflation], symptomatic [exercise tolerance and HRQoL], and clinical improvement [reduction in number or severity of exacerbations], while the absence of a spirometric response is not a reason for interrupting treatment, if there is subjective improvement in symptoms. Because LABA and LAMA act via different mechanisms of action, when administered in combination they can exert additional effects, thus optimizing [i.e. maximizing] sustained bronchodilation in COPD patients with severe airflow limitation, who cannot benefit [or can get only partial benefit] by therapy with a single bronchodilator. Recently, a fixed combination of ultra LABA/LAMA [indacaterol/glycopyrronium] has shown that it is possible to get a stable and persistent bronchodilation, which can help in avoiding undesirable fluctuations of bronchial calibre.
Review
Although the AGENAS guidelines [//www.agenas.it/images/agenas/pnlg/BPCO.pdf], the inter-societal document [//www.aimarnet.it/wordpress/up-contente/uploads/2013/11/Gestione-BPCO_04_layout-1-blk.pdf] and the latest GOLD guidelines define COPD in a multidimensional way, for its diagnosis it is still necessary to detect a functional characteristic: the limitation of airflow, usually measured by the reduction in the FEV1/FVC ratio below 70%.
Obstructive abnormalities of the small airways with a reduction in their caliber and destructive phenomena of the parenchyma with reduced lung elastic recoil, represent the two pathophysiological mechanisms responsible for airflow limitation.
The fact that the small airways are the compartment where the histopathological damage occurs for the two above cited mechanisms, was demonstrated many years ago in a group of COPD patients who died because of cardiac failure. The prevalence of one of the two histopathological alterations [bronchial inflammation or parenchymal destruction] corresponded to different clinical phenotypes: these were functionally distinguished by a different alteration of the parameters indicative of hyperinflation and impaired gas exchange more than by the parameters indicative of obstruction [1].
Another important pathophysiological consequence of the bronchial tree involvement in COPD is the marked increase in resistance, up to 40 times more than normal, due to the presence of mucus hypersecretion, with obstruction and obliteration of the small airways. The consequence is that the time needed for these obstructed lung units to empty [or wash-out] their volume and to achieve their passive equilibrium point at the end of a normal expiration maneuver, is significantly increased. Many of those units do not reach their relaxation volume before a new inspiration is initiated. As a result, part of the gas that would have been expired in a normal lung, remains “trapped” in patients with COPD causing hyperinflation. This condition is more severe during exercise, when more and more units are unable to empty [or wash-out] their gas, as expiratory time decreases when the respiratory rate increases and such hyperinflation represents the pathophysyological basis of dyspnea on effort that is the most invalidating symptom in COPD.
The critical points of the physiopathological approach to the illness can be summarized in this way:
the FEV1/FVC is an index of bronchial obstruction that does not reflect alterations in the small caliber airways described by pathological anatomy and already present in the first phases of the illness; FEV1 does not define the prevalent phenotype of the illness
the study of the peripheral airways is not easily done in a normal clinical routine
the distal airway involvement is associated with increased static lung volumes [hyperinflation], as well as destruction of the vascular capillary pulmonary zone and alterations in gas exchange. All these physiopathological alterations together are responsible for the symptoms and clinical course of the illness
COPD is a complex illness that goes beyond the simple functional definition. The contribution of pathophysiology to this definition cannot, however, disregard to perform a global spirometry test and a diffusion test
Is bronchial obstruction a necessary and sufficient condition for a COPD diagnosis?
The spirometric evidence of a not completely reversible obstruction is a necessary condition for the diagnosis of COPD which could be better supported by a nitrogen wash-out test. However, the seriousness of the obstruction is not directly correlated to the symptoms or invalidity determined by the COPD; indeed, “similar levels of obstruction can correspond to very different levels of invalidity and prognosis”[2].
The seriousness of the patient’s condition appears to be determined not only by the deterioration of pulmonary function, but also by the symptoms, the propensity for exacerbations, the nutritional status, and the presence of other diseases [comorbidities] [3].
Therefore, even COPD’s progression should be evaluated and monitored not only with regards to respiratory function, but also looking at other parameters, such as the type and intensity of symptoms, the frequency and severity of exacerbations, the functional status of the patient, the use of drugs and the quality of life.
Which pathophysiological parameters is bronchial obstruction evaluated on?
- 1]
There are two criteria to evaluate bronchial obstruction: “Fixed ratio” [FEV1/FVC