Early COPD Research Articles

Predictors of Survival in Severe, Early Onset COPD

Multiple risk factors for mortality in patients with COPD have been described, but most studies have involved older, primarily male subjects. The purpose of this study was to determine the mortality rate and predictors of survival in subjects with severe, early onset COPD. The cohort of 139 probands in the Boston Early-Onset COPD Study was recruited from lung transplant and general pulmonary clinics between September 1994 and July 2002. Subjects were < 53 years old, had an FEV(1) of < 40% of predicted, did not have severe alpha(1)-antitrypsin deficiency, and had not undergone lung transplantation. The initial evaluation included a standardized respiratory questionnaire, spirometry, and a blood sample. A follow-up telephone interview was conducted between May and December 2002. Subjects were young (mean age at enrollment, 47.9 years) and had severe airflow obstruction (mean baseline FEV(1), 19.4% predicted). A total of 72.7% of the subjects were women (p < 0.0001 [comparison to equal gender distribution]). The median estimated survival time was 7.0 years from the time of study enrollment, determined by the Kaplan-Meier method. The majority of deaths were due to cardiorespiratory illness. In a multivariable Cox proportional hazards model, adjusting for age, gender, and baseline FEV(1), lifetime cigarette consumption (hazard ratio [HR], 1.20 [per 10 pack-years]; 95% confidence interval [CI], 1.02 to 1.40) and recent smoking status (HR, 2.50; 95% CI, 1.03 to 6.05) were both significant predictors of mortality. In this cohort, recent smoking status predicted increased mortality independent of the effects of lifetime smoking intensity. Smoking cessation may confer a survival benefit even among patients with very severe COPD.

Familial aggregation of FEF(25-75) and FEF(25-75)/FVC in families with severe, early onset COPD.

The Boston Early-Onset COPD study showed that current or ex-smoking first degree relatives of severe early onset COPD probands have significantly lower forced expiratory volume in 1 second (FEV(1)) and FEV(1)/forced vital capacity (FVC) values than current or ex-smoking control subjects, which suggests the existence of genetic risk factors for the development of COPD in response to cigarette smoking. We hypothesised that first degree relatives of early onset COPD probands may also have lower values of spirometric parameters such as forced expiratory flow at the mid-portion of forced vital capacity (FEF(25-75)) and FEF(25-75)/FVC. Using generalised estimating equations, FEF(25-75) and FEF(25-75)/FVC were analysed in 333 first degree relatives of probands with severe early onset COPD and 83 population based controls; analyses were also performed on data stratified by smoking status. Narrow sense heritability estimates were calculated using a variance component approach. Significantly lower FEF(25-75) and FEF(25-75)/FVC were observed in smoking (FEF(25-75): beta -0.788 l/s (95% CI -1.118 to -0.457), FEF(25-75)/FVC: beta -20.4% (95% CI -29.3 to -11.6, p<0.0001 for both phenotypes) and non-smoking (FEF(25-75): beta -0.357 l/s (95% CI -0.673 to -0.041, p = 0.0271), FEF(25-75)/FVC: beta -9.5% (95% CI -17.1 to -1.9, p = 0.0145)) first degree relatives of early onset COPD probands. Narrow sense heritability estimates for FEF(25-75) (h(2) = 0.38) and FEF(25-75)/FVC (h(2) = 0.45) were similar to those for FEV(1) and FEV(1)/FVC. Lower values of FEF(25-75) and FEF(25-75)/FVC in non-smoking first degree relatives of early onset COPD probands than in controls suggest a genetic susceptibility to develop obstructive lung disease, independent of smoking, which is magnified by exposure to deleterious environments as suggested by the further decrements in FEF(25-75) and FEF(25-75)/FVC seen in smoking first degree relatives. FEF(25-75) and FEF(25-75)/FVC have high heritability and are important intermediate phenotypes for inclusion in genetic epidemiological studies of COPD.

BioCarta

BioCarta

EARLY INTERVENTION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE: A Review of the Lung Health Study Results

The major findings of the LHS that have been reported thus far are that an effective smoking cessation program can be developed that can produce more than a 20% success rate in getting smokers to give up the habit permanently, and that by stopping smoking, individuals with early COPD benefit by having an initial improvement in lung function and a slowing of the annual loss of their FEV1. The use of a bronchodilator has a short-term effect in improving the FEV1, but it does not affect long-term changes in lung function. AHR is common in patients with mild-to-moderate COPD. The reward for a smoker to give up the habit is an initial gain in FEV1 and a subsequent close to normal annual rate of decline of this pulmonary function parameter. These results should provide a positive incentive for smokers to quit and thereby decrease the morbidity and mortality caused by the use of tobacco.

Safety of Nicotine Polacrilex Gum Used by 3,094 Participants in the Lung Health Study

To assess cardiovascular conditions and other side effects associated with the use of nicotine polacrilex (NP), 2 mg. A multicentered randomized control trial of early intervention for the prevention of COPD. Ten university medical centers in the United States and Canada. Adult smoking volunteers with evidence of early COPD; 3,923 in intervention and 1,964 controls. Smoking cessation program, including NP. Data on hospitalizations were collected annually. Data on reported NP side effects were collected at 4-month intervals for intervention participants. The rates of hospitalization for cardiovascular conditions and cardiovascular deaths during the 5 years of the study were not related to use of NP, to dose of NP, or to concomitant use of NP and cigarettes. About 25% of NP users reported at least one side effect, but most were very minor and transient. Side effects associated with discontinuance of NP in 5% or more of users included headache, indigestion, mouth irritation, mouth ulcers, and nausea. There was no evidence that concomitant use of NP and cigarettes was associated with elevated rates of reported side effects. Participants in the smoking cessation intervention who received intensive levels of instruction and monitoring of NP use (initially at 12 meetings during 3 months) appeared to report significantly lower rates of side effects (dizziness, headache, and throat irritation) than control participants, presumed to have less instruction and monitoring. NP, as used in the Lung Health Study, appears to be safe and unrelated to any cardiovascular illnesses or other serous side effects.

The relationship between pneumonia in early childhood and impaired lung function in late adult life.

This study related respiratory illness documented in the first 2 yr of life to the lung function of 618 men and women with a mean age of 70 yr living in Derbyshire, England. Pneumonia before 2 yr of age was associated with a lower mean FEV1, adjusted for age and height. In men, the difference was -0.65L (95% CI: -1.02, -0.29; p = 0.0005). This estimate did not diminish after adjustment for smoking and asthma. In women, the reduction in mean FEV1 associated with pneumonia before 2 yr of age was smaller and nonsignificant. Bronchitis, measles, and whooping cough before 2 yr of age were not associated with diminished adult lung function in either sex. The findings in men support a causal relationship between pneumonia in early childhood and COPD in late adult life.