COPD is an important cause of death and leads to a substantial disability. By the year 2020, COPD might become the fifth-leading cause of combined mortality and disability worldwide. Therefore, determining factors that might influence the course and prognosis of this disease is essential for making treatment decisions.
Several studies have been performed to establish parameters associated with an increased risk of death in COPD patients. A low FEV1> and cigarette smoking are the most important factors related to mortality. A number of other variables, such as hypercapnia, hypoxemia, body mass index (BMI), environmental exposures, bronchial responsiveness, a1-antitrypsin deficiency, lower social economic status, and the presence of comorbidities are also considered to be related to poor prognosis. Regarding treatment options, long-term oxygen therapy (LTOT) improves outcome in severely hypoxemic COPD patients. Nevertheless, the course and prognosis of COPD are still partially unclear, and some factors associated with death remain controversial.
Previous studies determining predictors of survival in COPD patients have mostly been conducted in normocapnic patients or in severe hypoxemic patients requiring LTOT. Survival studies among hypercapnic COPD patients have focused on hypercapnia acquired during an acute exacerbation of the disease. Costello et al, as well as Saryal et al, included COPD patients during an acute exacerbation, and classified them into three patient groups: normocapnic, reversible hypercapnic, and chronic hypercapnic COPD. Costello et al found a higher mortality rate in patients with chronic hyper-capnia after 5 years of follow-up. Saryal et al were not able to demonstrate a difference in survival between groups after 10 years of follow-up.
Hypercapnia is an expression of alveolar hypoventilation resulting from an imbalance between load on the ventilatory pump vs its capacity. The load on the ventilatory pump is determined by airway resistance or the degree of hyperinflation. The capacity of the pump depends on chemoreceptor drive, the strength and endurance of its respiratory muscles, and on the acid-base status of the muscles. A rise in PaC02 causes a disturbance in the acid-base equilibrium, manifested in plasma pH changes in the acute phase before renal compensation has occurred. These pH changes are sensed by central as well as peripheral chemoreceptors and initiate a respiratory response. A stimulation of ventilation follows, resulting in a higher Pa02 and an increased CO2 washout. In COPD patients with a chronic CO2 retention, this ventilatory response is often diminished. Do you want to know more about Treatment of diabetes?
We hypothesized that respiratory muscle failure and a diminished ventilatory response to CO2 might be predictors of survival of chronic hypercapnic COPD patients because these factors may sustain or augment hypercapnia. Beside these parameters, already known factors related to a poor prognosis in normocapnic COPD patients, such as the severity of hypoxemia, the severity of airway obstruction, BMI, smoking status, and comorbidity, were analyzed as well.
A cohort of 47 chronic hypercapnic COPD patients (28 male; mean age, 66.3 ± 6.7 years [± SD]) recruited for other trials, of 1 to 3 weeks in duration, in our institute between January 1996 and February 2000 was prospectively followed up, yielding 178.8 person-years in total. Follow-up time ranged from 3.1 to 7.1 years among survivors.
COPD was defined according to the standards of the American Thoracic Society. Chronic hypercapnia was defined as Paco2 > 45.0 mm Hg recorded twice with an interval of at least 6 weeks. At time of entry, all patients were in clinically stable condition (ie, no changes in medication dosage or frequency, and no exacerbations of disease or hospital admissions in the preceding 6 weeks). Patients with sleep-related breathing disorders or chronic renal or liver failure were excluded. During follow-up, patients received their usual medical care, and adjustments were made if necessary, according to Global Initiative for Chronic Obstructive Lung Disease standards. Subjects were included after giving written informed consent. The study was evaluated and approved by the local Medical Ethics Committee.
The following data were collected: anthropometric parameters (including age, gender, and BMI), smoking status (described as smoking one or more cigarettes per day at study entry), the presence of significant comorbidity (defined as the existence of malignancies, cardiovascular disease, diabetes mellitus, rheuma-tologic diseases, or immunosuppression), use of medication (maintenance of oral steroids > 5 mg/d, inhaled steroids, theophylline, diuretics, and LTOT), pulmonary function parameters, arterial blood gas values, respiratory muscle strength (maximum inspiratory mouth pressure [Plmax], maximum expiratory mouth pressure [PEmax]), and ventilatory response data.
Analyses were performed using statistical software (SPSS for Windows, Version 10.0; SPSS; Chicago, IL; and Egret, Version 2.0.3; CYTEL Software; Cambridge, MA). Descriptive data are presented as mean ± SD or as number (percentage). Survival was analyzed using the Cox proportional hazards model. Due to a small number of deaths, risk factors were analyzed one by one. Comorbidity and use of diuretics were the only parameters analyzed simultaneously because we reasoned that the presence of cardiovascular disease would be related with the use of diuretics. All survival analyses were optimally adjusted for age and gender simultaneously, by taking age as staggered entry-time variable while stratifying by gender. Estimated hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated; p < 0.05 was considered significant.