Smokers with interstitial lung abnormalities on high-resolution CT show both reduced total lung capacity and a lesser amount of emphysema, compared with those who didn’t have interstitial lung abnormalities, according to a report in the March 10 issue of the New England Journal of Medicine.
In addition, the magnitude of these two reductions is greatest among smokers who also have chronic obstructive pulmonary disease (COPD), said Dr. George R. Washko of the pulmonary and critical care division at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and his associates.
"Our findings are consistent with, and add weight to, previous studies showing that cigarette smoking is associated with both spirometric restriction and areas of high attenuation on HRCT. Since emphysema and interstitial lung abnormalities have opposing effects on lung volume, our findings suggest that HRCT may provide important diagnostic information in smokers whose total lung capacity is unexpectedly ‘normal,’ " they noted.
"We speculate that this could be clinically important to physicians who may think that a patient who does not have symptoms or characteristic abnormalities on lung function tests is disease free, when in fact the patient could be affected by two of the consequences of smoking – emphysema and interstitial lung abnormalities," Dr. Washko and his colleagues said.
The investigators examined the relationship among radiographic interstitial lung abnormalities, total lung capacity, and emphysema in a cohort of 2,416 smokers who had been recruited for an ongoing study of COPD being conducted at 21 clinical centers.
The cohort included white (75%) and black (25%) subjects aged 45-80 years who reported a history of at least 10 pack-years of smoking. Slightly more than half of the subjects were men, 44% were still actively smoking, and 41% met criteria for COPD.
The overall prevalence of interstitial lung abnormalities affecting more than 5% of any lung zone on HRCT was 8%. Another 36% of the subjects showed "indeterminate" findings, and 56% showed no interstitial lung abnormalities.
The lung abnormalities included nondependent ground-glass or reticular abnormalities, diffuse centrilobular nodularity, nonemphysematous cysts, honeycombing, and traction bronchiectasis.
Interstitial lung abnormalities were associated with both a decrease in total lung capacity and a lesser amount of emphysema. In addition, there was an inverse relationship between these abnormalities and the severity of COPD, the researchers said (N. Engl. J. Med. 2011;364:897-906).
Further follow-up is needed "to determine whether these radiographic abnormalities, and the associated reductions in lung volumes, are transient or stable, or whether they will progress to clinically significant disease," Dr. Washko and his associates said.
In an editorial accompanying the report, Dr. Talmadge E. King Jr. said that the "long-term implications of this and similar studies using HRCT scans in asymptomatic subjects are unknown. There is the concern that such scans may be overinterpreted, leading to a high rate of unnecessary diagnoses and perhaps unwarranted treatment" (N. Engl. J. Med. 2011;364:968-70). In this study, more than one-third of the HRCT scans were deemed "indeterminate" for the presence of interstitial lung abnormalities, which "probably reflects the fact that the boundary between HRCT images of the lungs in health and disease is blurred," noted Dr. King of the department of medicine at the University of California, San Francisco.
However, he thought it was noteworthy that Dr. Washko and his colleagues found that interstitial lung abnormalities were associated with less radiographic emphysema. "It is interesting to speculate that the pathobiology of smoking can lead to two distinct patterns of injury – emphysema (with destruction of the lung) or interstitial lung disease (with macrophage accumulation and fibrosis).
"Conversely ... the relative lack of emphysema could be simply a reflection of the fact that interstitial lung abnormalities mask emphysema or that more severe emphysema limits the extent of interstitial lung abnormalities," Dr. King said.
This study was supported by the National Institutes of Health and the Parker B. Francis Foundation. Dr. Washko reported ties to MedImmune, and his associates reported ties to Siemens, Actelion, Gilead, InterMune, Novartis, Perceptive Imaging, GE Medical Systems, GlaxoSmithKline, AstraZeneca, Toshiba Medical, and AZE. Dr. King reported ties to Actelion, InterMune, ImmuneWorks, Philips Respironics, CV Therapeutics, and Genzyme.