Abstract
In COPD, exacerbations caused mainly by infections of the tracheobronchial tree or inhalation of toxic gases, are an important characteristic of the disease. During an exacerbation a remarkable worsening of a patient’s baseline symptoms is observed. Furthermore, the number of past exacerbations has been related both to the risk of future recurrent exacerbations and to relapse following treatment. Thus, frequent exacerbations followed by incomplete recovery may be an important risk factor of lung function decline. However, the influence of exacerbations on the progression of the COPD has not been well established. The hypothesis (British Hypothesis) that repetitive chest infections or chronic airway infection might be the cause of airway obstruction was tested in the past. The conclusions of the landmark study of Fletcher and Peto published in seventies were that exacerbations had no effect on the annual rate of change of FEV1. However, this study was performed only in patients with mil ...
In COPD, exacerbations caused mainly by infections of the tracheobronchial tree or inhalation of toxic gases, are an important characteristic of the disease. During an exacerbation a remarkable worsening of a patient’s baseline symptoms is observed. Furthermore, the number of past exacerbations has been related both to the risk of future recurrent exacerbations and to relapse following treatment. Thus, frequent exacerbations followed by incomplete recovery may be an important risk factor of lung function decline. However, the influence of exacerbations on the progression of the COPD has not been well established. The hypothesis (British Hypothesis) that repetitive chest infections or chronic airway infection might be the cause of airway obstruction was tested in the past. The conclusions of the landmark study of Fletcher and Peto published in seventies were that exacerbations had no effect on the annual rate of change of FEV1. However, this study was performed only in patients with mild COPD. Other studies on lung function decline which have used different methodology have come to the opposite conclusion. In this setting, questions still remain due to small number of carefully designed studies of appropriate patients with varying disease severity. The primary aim in this study is to investigate whether an increased frequency of exacerbations is associated with an accelerated rate of FEV₁ decline in a population of COPD of varying severity. Data on exacerbations were collected using diary cards, which is a sensitive and accepted method of their monitoring. In addition, secondary aims were to identify risk factors for increased exacerbation frequency and to investigate whether an increased frequency of exacerbations affects significantly the quality of life of COPD patients. This prospective investigation included one hundred and two patients with COPD who were followed for a total of three years. Every six months patients were assessed clinically and underwent post bronchodilation spirometry following premedication with 200μg salbutamol. Quality of life was assessed every six months with the Saint George Respiratory Questionnaire. The definition of an exacerbation was based on criteria described previously by Anthonisen requiring either, increase of at least two major respiratory symptoms (dyspnea, sputum amount, and sputum purulence) or, increase of one major symptom in addition to at least one minor symptom (wheeze, cough, fever, nasal discharge, sore throat), for at least two consecutive days. A patient directed diary card and hospital-outpatient clinic data were used to identify exacerbations. All patients were instructed to record, at the end of each day, any increase in major and minor symptoms with regard to the last 24 hours marking the corresponding area on the diary card, when they perceived an increase over their normal, stable condition in chronic symptoms or symptoms of new onset. Otherwise they had to mark the area of “no increase perception/no new onset”. Patients were also instructed to call members of the medical team and to attend unscheduled visits whenever they noticed deterioration in symptoms. In these cases, their symptoms were validated and exacerbations were termed as “reported exacerbations”. Accordingly, patients were grouped into two categories according to the annual rate of total number of exacerbations experienced. Those experiencing more than the median annual exacerbation rate were termed “frequent exacerbators” whereas the other were considered “infrequent exacerbators”. Logistic regression analysis was used to assess the risk for increased exacerbation frequency and a random effects modelling was used to investigate the possible relationship between exacerbation frequency and lung function decline. The following results were found: according to the GOLD severity of COPD 22 (21.5%) patients were stage 0-I, 33 (32.5%) were stage II, 29 (28.5%) were stage III, 18(17.5%) were stage IV. The overall median [mean (95%CI)] annual exacerbation rate was 2.85 [3.1 (2.7-3.6)]. The exacerbation rates were 3 [3.3 (3-3.9)], 3 [2.8 (2.5-3.2)] and 2 [2.3 (1.8-2.8)] for the first, second and third year respectively. The GOLD severity scale of the disease was associated with the number of exacerbations and the number of admissions to hospital (p-values 0.007 and 0.0005, respectively). FEV₁ (% pred) and the presence of respiratory symptoms at baseline were found to be independent factors of risk for increased exacerbation frequency and admissions. The estimated effect of smoking, adjusting for exacerbation status, added to the three-year average decline in FEV₁ (% pred) -1.8 (-2.1, -1.5) percentage units per year (p=0.004). The estimated effect of frequent exacerbations added to average FEV₁ (% pred) decline -1.4 (-1.05, -1.75) percentage units (p=0.02). In summary, the findings of this study show that disease severity and presence of chronic respiratory symptoms were independent risk factors for increased exacerbation frequency and hospitalization in COPD patients. Although the data suggest that continuing smoking is the major determinant of accelerating loss of lung function, an increased frequency of exacerbations appears also to accelerate the decline of lung function. In addition, increased exacerbation frequency may affect significantly the quality of life of COPD patients. Thus, not only smoking cessation but also a decrease frequency of exacerbations should be a major target of treatment in COPD.
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