Why can some people smoke their whole life without developing either cancer or chronic obstructive pulmonary disease (COPD)? This type of question lays a smokescreen about how important quitting smoking is. A new study now shows that a blood test can measure how the body reacts to the presence of cigarette smoke in the lungs. A high concentration of a specific protein in the blood is associated with a greatly increased risk of COPD – many years before the disease develops. The researchers hope that this test can become a regular part of a health check-up and thereby help to motivate smokers to quit their risky habit.
When smokers inhale hot cigarette smoke into their lungs, the immune system promptly tries to protect them. A major component of this defence is surfactant protein D (SP-D), a soluble innate immune factor produced by the surfaces of the airways. SP-D protects against infections but also against smoke-induced inflammation of the airways. For smokers, however, SP-D moves from the lung tissue into the blood, thus weakening the protection of the lungs. However, the serum level of SP-D appears to be useful in assessing whether chronic lung damage is developing.
“Studies have shown that the smokers with the highest concentrations of serum SP-D had the worst lung function. In our new study, we investigated whether smokers’ SP-D concentration can predict whether they would develop COPD. The experiments show that a blood test for SP-D can identify high-risk smokers. We hope that these tests can eventually become standard in health check-ups, so that they can help to promote smoking cessation or early treatment,” explains an author behind the study, Grith Lykke Sørensen, Professor, Department of Molecular Medicine, University of Southern Denmark, Odense.
Changes among smokers
COPD is actually an umbrella term for chronic lung diseases, but tobacco smoking causes most cases of COPD today. In severe cases, COPD makes breathing so difficult that a person needs oxygen to survive. Globally, COPD is the third most common cause of death and the fifth leading cause of lost quality-adjusted life-years.
“COPD is the disease that contributes most to social inequality in health. Researchers have therefore intensely searched for biomarkers that can determine whether people are developing COPD. Scientists have been seeking inflammatory mediators, including some known as microvesicles and micro-RNA, but none of these were significant enough. When I was previously involved in other studies, I became aware of SP-D because of its special properties,” says Grith Lykke Sørensen.
SP-D is usually located on the surface of the lungs, where it protects them from external threats such as infections or environmental effects such as tobacco smoke. However, these effects apparently influence the location of SP-D.
“Cigarette smoking causes SP-D to move from the lungs into the bloodstream. We therefore hypothesised that measuring SP-D in serum might be an early indicator of whether COPD is developing. We followed a group of smokers for 12 years to assess whether serum SP-D levels could predict the future risk of developing COPD,” explains Grith Lykke Sørensen.
The new study showed that SP-D in the blood is a good indicator of both whether you smoke or not and whether you develop chronic smoke-induced lung damage or not. The concentration of SP-D was more than 50% higher among smokers (1289 ng/ml) than among nonsmokers (833 ng/ml), and former smokers had only slightly higher levels (877 ng/ml). The researchers also found a convincing association between lung function and SP-D concentration.
“The relative risk for smokers of developing COPD over 12 years increased by almost 10% if the concentration of SP-D in the blood doubled, so SP-D was clearly associated with the risk of developing COPD,” says Grith Lykke Sørensen, who adds that the risk should be viewed based on the fact that COPD often progresses slowly and throughout life.
May soon show its value
Although the results are undoubtedly convincing, the researchers remain somewhat cautious about using SP-D to indicate the development of COPD. The study included only 756 pairs of twins, so it initially only indicates that SP-D can be used as a biomarker for the risk of COPD among smokers.
“SP-D is definitely a weaker indicator of COPD than direct measurements such as spirometry, which directly measures the volume of air exhaled. The advantage of measuring SP-D in blood, however, is that high concentrations can be measured much earlier than spirometry and that a blood test is a much easier method. Checking more frequently whether early stages of COPD are developing may eventually prove to be easier,” explains Grith Lykke Sørensen.
And Grith Lykke Sørensen says that COPD needs to be viewed as a disease that often begins early in life. Frequently measuring SP-D can immediately identify people with pre-COPD and thus be able to motivate them to adopt a healthier lifestyle without cigarettes.
“Blood tests for SP-D clearly have great potential to indicate lung disease among high-risk smokers, but this requires clinical trials. Until these are completed, we hope that companies testing drugs for the early stages of COPD will adopt the test as an easy and direct way to measure the effectiveness of their drug candidates. This is how the SP-D test may soon show its value,” concludes Grith Lykke Sørensen.
