An integrated approach in the diagnosis of smoking-related interstitial lung diseases

Abstract

Cigarette smoke consists of several chemical compounds with a variety of effects in many organs. In the lung, apart being the main cause of chronic obstructive pulmonary disease, carcinoma and idiopathic spontaneous pneumothorax, tobacco smoke is associated with interstitial lung diseases (ILDs), including respiratory bronchiolitis-associated ILD (RB-ILD), desquamative interstitial pneumonia (DIP), pulmonary Langerhans' cell histiocytosis (PLCH), idiopathic pulmonary fibrosis, acute eosinophilic pneumonia, ILD in rheumatoid arthritis and pulmonary haemorrhage in Goodpasture syndrome. This review will focus on the diseases with a stronger epidemiological association with tobacco smoke, namely RB-ILD, DIP and PLCH. Although the exact pathogenetic evidence linking smoking with these disorders is still not completely understood, there is growing evidence that tobacco smoke targets the terminal or respiratory bronchioles in these diseases, and the differences are reflective of the degree of severity of small airway and parenchymal reaction to the smoke exposure. Despite considerable clinical, radiological and histological overlap between RB-ILD, DIP and PLCH, it is useful to retain the separate classifications for prognostic and therapeutic implications.

Conflict of interest statement

Statement of Interest

S. Harari has relationships with drug companies including Actelion, InterMune and GSK. In addition to being an investigator in trials involving these companies, relationships include consultancy service and membership of scientific advisory boards.

Figures

Figure 1.

a) Respiratory bronchiolitis: the intra-alveolar accumulation of finely pigmented macrophages (smoker’s macrophages) (haematoxylin and eosin, 400×). Generally smoker's macrophages have a strict bronchiolocentric distribution (b; haematoxylin and eosin 40×), but occasionally they involve the entire lobule (c; haematoxylin and eosin, 20×). d) Respiratory bronchiolitis in a 63-yr-old heavy smoker who was asymptomatic at the time of computed tomography. The high-resolution computed tomography image shows bilateral poorly defined centrilobular nodules in the upper lobes. e) Occasionally, particularly in desquamative interstitial pneumonia, a relatively large number of eosinophils are present and the limits with chronic eosinophilic pneumonia are sometimes blurred (haematoxylin and eosin, 200×).

Figure 2.

Smoking-related fibrosis with dense acellular fibrosis that frequently surrounds cystic emphysematous spaces, both in a) centrilobular (haematoxylin and eosin, 40×) and b) sub-pleural parenchyma (haematoxylin and eosin, 20×). c) Specific smoking-related interstitial abnormalities in a heavy smoker with dyspnoea. A high-resolution computed tomography image showing mild ground-glass opacity and reticulation circumscribing emphysematous areas.

Figure 3.

a) Pulmonary Langerhans’ cell histiocytosis (PLCH) is characterised by an increased number of CD1a+ Langerhans’ cells in the bronchiolar wall (200×). b) In the early/active phase of PLCH stellate cellular nodules with a bronchiolocentric distribution can be seen (haematoxylin and eosin, 10×). c) A stellate fibrotic nodule suggestive of healed PLCH is present on the left and is associated with an extensive accumulation of smoker's macrophages (haematoxylin and eosin, 20×). d) Classical example of PLCH in its mature phase consisting of multiple bronchiolocentric cellular nodules, some of which are fibrotic and irregularly cavitated (haematoxylin and eosin, 10×). e) A high-resolution computed tomography image at the level of the upper lobes showing numerous irregularly marginated bilateral nodules; a few cysts are visible. f) Chronic PLCH showing stellate scars with paracicatricial emphysema (haematoxylin and eosin, 40×).