Smokers with radiographic evidence of interstitial lung abnormalities were less likely to have emphysema and more likely to have reduced total lung capacity than were smokers without interstitial findings, researchers said.
But these smokers are not without risk, cautioned Ivan O. Rosas, MD, of Brigham and Women’s Hospital in Boston, and colleagues in the COPDGene Investigators group.
Patients with interstitial abnormalities had higher rates of restrictive lung deficit, they wrote in the March 10 issue of the New England Journal of Medicine.
Moreover, they noted, following these individuals over time may show that the interstitial abnormalities “will progress to clinically significant disease” such as idiopathic pulmonary fibrosis.
Rosas and colleagues indicated that smoking is a well-known contributing factor to emphysema and the pulmonary hyperinflation that results, but a role for smoking in promoting interstitial lung abnormalities — reflecting areas of increased lung density — has only recently been recognized.
Moreover, there have been hints that smokers with these abnormalities are less prone to emphysema and elevated lung capacity.
To explore the issue, they obtained high-resolution CT chest scans for 2,416 long-term smokers who were participating in a genetic study of COPD, and analyzed them for the presence of several types of interstitial lung abnormalities.
These included ground-glass or reticular abnormalities, diffuse centrilobular nodularity, nonemphysematous cysts, honeycombing, and traction bronchiectasis. Three readers looked for these features affecting at least 5% of any lung zone. If abnormalities were found but affected less than 5% of a lung zone, the findings were classified as indeterminate.
Interstitial abnormalities meeting the 5% threshold were found in 194 patients. Findings were indeterminate in another 861.
Data on participants, who all had a smoking history of at least 10 pack-years, also included quantitative measures of lung capacity and emphysema burden.
After adjusting for smoking history in pack-years, age, sex, body mass index, and other potential confounders, Rosas and colleagues found that the presence of interstitial abnormalities was inversely related to the burden of emphysema and elevated lung capacity.
Compared with the patients who had no evidence of interstitial disease, mean lung capacity in those with the abnormalities was 0.444 L lower (95% CI 0.292 to 0.596).
Their percentage of emphysema, as defined by a lung-attenuation threshold of -950 Hounsfield units, was also three points lower (95% CI 2 to 4), or 10 points lower with a threshold of -910 Hounsfield units (95% CI 8 to 12).
In addition, patients with abnormalities were less likely to have COPD with a GOLD stage of 2 or more (32% versus 41%, P=0.02).
But spirometric restriction was more common in the patients with interstitial abnormalities, occurring in 42% versus 30% in those without the abnormalities (P=0.002).
Rosas and colleagues also found that, among those with interstitial abnormalities who also had COPD, the reduction in lung capacity and emphysema burden was actually the greatest.
The investigators noted that heart failure, artifacts from bullous emphysema, or atelectasis might have limited categorizing CT as having interstitial abnormalities.
Other potential limitations included use of CT, not plethysmography, for total lung capacity determinations and lack of generalizability to the general population since they oversampled for smokers with COPD.
In an accompanying editorial, Talmadge King Jr., MD, of the University of California San Francisco, raised the possibility “that the pathobiology of smoking can lead to two distinct patterns of injury.”
He suggested that the damage may either be overt and destructive, which is emphysema, or it may be more subtle in the form of interstitial lung disease.
But King also noted that the study’s methodology could not rule out the possibility that interstitial lung disease simply masks emphysema — or that interstitial disease is inherently limited in patients with severe emphysema.
Observing that many subclinical effects of smoking may be reversible when people quit, King urged that clinicians not prescribe aggressive treatments for interstitial disease on the basis of high resolution chest CT.
“The findings of this study, while intriguing, should not change clinical practice — except to intensify our efforts in smoking prevention and cessation,” King wrote.
The study was funded by the National Institutes of Health and the Parker B. Francis Foundation.
Rosas and colleagues reported consulting fees from Medimmune, Actelion, Gilead, Intermune, Novartis, Perceptive Imaging, GlaxoSmithKline, and AstraZeneca and research funding from Siemens, GE Medical Systems, GSK, AZE, and Toshiba Medical.
King reported that Actelion, InterMune, ImmuneWorks, Philips Respironics, CV Therapeutics, and Genzyme had made payments to his institution for consulting work.