Familial risks of COPD

Clinical bottom line

Siblings of patients with severe COPD who smoke have a five-fold higher risk of airflow obstruction and COPD than age and sex matched smoking controls. There is a significant familial component to chronic obstructive airways disease.

Reference

SC McCloskey et al. Siblings of patients with severe chronic obstructive pulmonary disease have a significant risk of airflow obstruction. Am J Respir Crit Care Med 2001 164: 1419-1424.

Study

This study was done in East Anglia where index cases with severe COPD were identified from chest clinics and lung function laboratories, and from referrals to a regional unit for lung surgery. Patients had to:

have FEV1 of less than 60% of predicted, and be younger than 56 years old,
have FEV1 less than 40% of predicted and be 56 to 60 years
have FEV1 less than 20% of predicted and be 61-65 years

plus having other criteria and having a chest radiograph compatible with COPD.

These patients were asked to complete a respiratory questionnaire (American Thoracic Society), with details on demographics, medical history, and smoking history.

Parents and siblings of cases were contacted and invited to a clinic run by their general practitioner or research nurse for simple tests of lung function, with hospital follow up if needed.

Control subjects were randomly selected from a population-based study.

Results

There were 152 cases, and 150 were enrolled. The mean age was 52 years, with slightly more men than women. They had smoked an average of about 40 pack years of cigarettes, 45% had chronic bronchitis, and about 30% reported chest problems before the age of 16. About a third reported a mother to have bronchitis or emphysema, and about the same proportion reported a father to have bronchitis or emphysema.

In total there were 173 siblings who completed the questionnaire and the study. Of these, 126 were present or ex-smokers, and 47 had never smoked. Of the 173, 44 had airflow obstruction (FEV1/FVC <70%) and 12 had emphysema and airflow obstruction.

There were 111 current or ex-smoking siblings and 419 controls matched for age, sex and smoking habit. Airflow obstruction was present in 41% of the siblings, compared with 12% of the controls (Figure 1), and COPD was present in 32% and 9% respectively. The odds ratio for the COPD was 4.7 (2.6 to 8.4) for siblings compared with controls. There was also a significant association with family history (odds ratio 4.6, 95% confidence interval 2.5 to 8.1), and this was found irrespective of number of pack-years smoked.

Figure 1: Siblings and age, sex, and smoking matched controls

Comment

This is a really interesting piece of public health, examining genetic and environmental aspects of chronic obstructive disease. There is a significant familial risk of airflow obstruction in siblings of patients with severe COPD whoop smoke.