Thoracic Imaging 2003 - Society of Thoracic Radiology

SUNDAY
70
The Expanded Spectrum of Smoking-Related Diseases
Rosita M. Shah, M.D.
Thomas Jefferson University Hospital
Philadelphia, PA
The Pathogenicity of Cigarette Smoke
The constituents of cigarette smoke are frequently divided
into gas and particulate phases, with greater than 3500 compounds
known to exist in cigarette smoke. Over 40 of these
compounds are known carcinogens, some of which have been
shown to directly interact with plasmid DNA and produce irreversible
injury. Many of the gas phase components are extremely
short lived and the following discussion is directed at the particulate
phase.
The term ‘tar’ is applied to the particulate components of
cigarette smoke of which 50% of inhaled particles are deposited
in the lung. Particles less than 5um easily bypass normal pulmonary
defenses and frequently aggregate near respiratory
bronchioles where reduced airway diameter results in reduced
particle speed. Deposition of these particles is greatest in the
lower lobes, paralleling ventilation. However, as with other diseases
associated with particle deposition including silicosis, the
greatest concentrations of deposited particulate material are
recovered in the upper lobes. This may be explained by the relatively
reduced lymphatic clearance in the upper lung zones. It
follows that smoking-related lung pathology is most common in
the upper lung zones.
The accumulation of particulate matter in the lung parenchyma
is associated with several physiologic responses. Smokers
have significantly elevated systemic and intra-pulmonary neutrophil
counts as well as a peribronchiolar accumulation of
macrophages. Release of elastase from activated neutrophils is
the principal factor in the development of emphysema.
Per gram of TAR, there are greater than 10 17 radicals.
These radicals are likely contributors to the carcinogenicity of
cigarette smoke and also result in the oxidation of intra-pulmonary
enzymes, including alpha-1-anti-trypisin. Subsequently
reduced levels or the presence of non-functioning anti-proteases
in the lung augment the effect of elevated elastase levels.
Pathologic and Physiologic Changes in Smoker’s Lungs
Consistent pathology identified in smoker’s lungs include
submucosal gland hypertrophy and goblet cell hyperplasia
resulting in an elevated Reid index, smooth muscle hypertrophy,
bronchiolar inflammation and respiratory bronchiolitis. Mucus
hypersecretion occurs predominantly at a large airway level and
is usually reversible. Airway obstruction occurs primarily secondarily
to small airway and airspace pathology, and results in
irreversible abnormalities.
Neoplastic Smoking-related Disease
Smoking is associated with a 10-25 fold increase in lung
cancer deaths and accounts for 75-90% of the lung cancer risk.
Twenty percent of smokers will develop bronchogenic carcinoma
, indicating the obvious significance of other factors including
individual susceptibility. Smoking has also resulted in a 10-
30 fold increase in lung cancer deaths in non-smokers and a 50
fold increase in upper respiratory tract and esophageal malignancies.
Non-neoplastic Smoking-related Lung Disease
Chronic Obstructive Pulmonary Disease
The association of smoking with COPD is more than convincing.
The literature has repeatedly demonstrated a direct
relation between the degree of emphysema and reduced FEV1
with the number packs smoked per day. Smoking is associated
with an annual reduction in FEV1 of 50ml. Smoking cessation
does not improve FEV1 but may slow the rate of decline.
Emphysema is defined by the permanent enlargement of air
spaces distal to terminal bronchioles. Destruction of alveolar
walls without significant fibrosis results from the elastolytic
effect of neutrophilic byproducts, including elastase, following
the activation cytokine networks. The development of emphysema
is potentiated by low levels of alpha-1-anti-trypsin, with significant
emphysema developing in 15-20% of smokers.
Previous literature has shown significantly greater degrees of
emphysema and air-trapping in smoking vs nonsmoking
patients.
Correlative HRCT-pathologic studies have demonstrated that
imaging will miss or undercall the extent of emphysema in
50%. Centrilobular emphysema is the form of emphysema most
closely associated with smoking. Imaging findings include
focal lucencies without visible walls and the visualization of
residual centrilobular anatomy.
An upper lung predominance is usual.
Panlobular emphysema may also develop in smokers and
coexist with centrilobular emphysema. Imaging features
include diffuse areas of reduced attenuation with reduced vessel
size in a lower lung zone distribution. Panlobular emphysema is
to be differentiated from advanced centrilobular emphysema or
air-trapping.
Chronic bronchitis is defined by persistent productive cough
for 3 consecutive months over 2 consecutive years. Pathologic
findings in the airways of patients with chronic bronchitis and
asymptomatic smokers may overlap, including an elevated Reid
index with submucosal and goblet gland hyperplasia and an
increased mucus volume
Smoking-related Interstitial Lung Disease
Langerhans’ Cell Histiocytosis
Pulmonary Langerhans’ histiocytosis represents approximately
5% of cases of chronic infiltrative interstitial lung disease
diagnosed by biopsy. Nearly all patients are smokers and
disease progression is characteristic in patients who continue the
habit. The Langerhans’ cell represents an immunologically
functioning histiocyte derived from the monocytesmacrophages.
Immune-mediators can be isolated from BAL
fluid and the histiocytic lesions, including growth factors, granulocyte
colony stimulating factor and tumor necrosis factor.
The lesions of langerhans’ histiocytosis are peribronchiolar
and characterized by a collection of Langerhans’ cells,
macrophages and eosinophils. The inflammation typically
extends into the adjacent interstitium, including alveolar and
interlobular septae. The adjacent lung parenchyma commonly
demonstrates an associated organizing pneumonia and respiratory
bronchiolitis.
Imaging findings include an upper lung predominant, irregular
nodular abnormality. Costophrenic angles are spared. A
peribronchiolar distribution is usually readily apparent.
Cavitation is common, frequently consisting of unusually
shaped lucencies. Earlier in the disease course, nodules dominate
the radiographic picture, whereas in later stages, the cystic
component is most prominent. An accompanying interstitial
abnormality may be observed.