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Smoking belies milder disease but worse prognosis for IPF patients

January 15, 2008

Smokers and ex-smokers with idiopathic pulmonary fibrosis (IPF), an untreatable progressive lung disease that usually leads to death within a few years of diagnosis, have a worse prognosis than non-smokers, according to research from London.

Previous research had counter-intuitively suggested that current smokers with IPF might live longer than ex-smokers, but the new study establishes that the data likely reflected a healthy smoker effect.

The study appears in the second issue for January of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

"Smoking is associated with a higher mortality in IPF, and an earlier finding, suggesting the contrary, was almost certainly due to the fact that smokers tend to stop smoking when disease becomes more severe-and so current smoking is linked to milder disease," said Athol U. Wells, M.D., of the Interstitial Lung Disease Unit at the Royal Brompton Hospital in London, who headed the research.

The investigators studied the medical records of 249 patients with IPF, and analyzed the extent and severity of their disease, smoking history and survival. Their initial findings, unadjusted for disease severity, were similar to the earlier study- namely that smokers had longer survival times than ex-smokers. But when they adjusted their data to reflect the extent and severity of the disease at presentation, their findings shed a new light on the previous finding.

"We established that current smokers live longer, but this is mostly because they have much milder disease. Clearly, many patients stop smoking precisely because their disease is getting worse. This is the 'healthy smoker' effect: that current smoking is a marker for milder disease because advancing disease causes smoking cessation," said Dr. Wells. "Symptomatic patients with more severe disease may be more likely to stop smoking for perceived health reasons. It can, therefore, be argued that current smoking might be a marker of less severe disease, associated with better survival."

Using the composite physiologic index (CPI), an index of disease severity that takes into account lung function and diffusion capacity as well as the confounding functional effects of concurrent emphysema, they found that survival was better in non-smokers than in the two smoking groups.

"We speculate as to whether this reflects disease co-morbidity-that is, excess mortality from non-pulmonary disease ascribable to smoking- or an effect of smoking in driving progression of lung disease," said Dr. Wells.

The researchers have several ongoing studies to determine the precise linkage between smoking damage such as smoking-related emphysema, IPF and other forms of fibrotic lung disease.

"The next step is to pursue the idea that mechanisms linked to smoking cause progression of pulmonary fibrosis," says Dr. Wells. "If we can then understand these mechanisms better, this may give us new treatment options."

American Thoracic Society