SMOKING RELATED LUNG DISEASES:
In addition to the cancers of lung that are caused by smoking, there are numerous other benign smoking related lung diseases. These can be divided into restrictive and obstructive lung diseases.
Restrictive or interstitial lung diseases: These include Respiratory bronchiolitis, Respiratory bronchiolitis-interstitial lung disease (RB-ILD), Desquamative interstitial pneumonia (DIP) and Usual interstitial pneumonia.
Obstructive lung disease: this includes Emphysema and chronic bronchitis
1.RESPIRATORY BRONCHIOLITIS (RB) AND RESPIRATORY BRONCHIOLITIS-INTERSTITIAL LUNG DISEASE (RB-ILD):
Clinical and radiological findings:
The distinction between RB and RB-ILD is purely clinical. Histologically these two lesions are same. In RB the patients are asymptomatic. On pulmonary fuction tests they can show airflow obstruction. CT scan shows centrilobular nodules and ground-glass opacities. In RB-ILD the patients complain of dysnea and cough. Men are affected more. On pulmonary function test markedly reduced diffusing capacity is present. On Ct scan groung-glass opacities are seen or centrilobular nodules with reticulation
Increased numbers of macrophages in respiratory bronchioles and surrounding alveolar sacs.
The macrophages contain aggregates of dusty brown pigmented cytoplasmic granules and thus are called smoker’s macrophages
Type II pneumocyte hyperplasia of affected airspaces is seen.
Patchy submucosal and peribronchiolar infiltrate of lymphocytes and histiocytes
Peri-bronchial fibrosis is noted as well.
2. DESQUAMATIVE INTERSTITIAL PNEUMONIA: (DIP)
Fourth or fifth decades of life with equal distribution in males and females are usually affected. Mostly the patients are smokers with minority of patients with no history of smoking and history of drugs and viral or autoimmune disease are also affected. Pulmonary function test show normal lung volume usually and diffusion capacity is decreased.
Chest x-rays are normal. CT scan shows lower lung ground-glass opacifications
Alveolar spaces are filled with large number of macrophages having abundant eosinophilic cytoplasm and finely dispersed dusty brown pigment. These macrophages are known as smoker’s macrophages.
Alveolar walls show plasma cells, few eosinophils and lymphoid aggregates
Type II pneumocyte hyperplasia is also seen
Smoker’s macrophages cytoplasm stains positively with PAS-D and the brown pigment stains with Prussian blue
Desquamative interstitial pneumonia is like the RB-ILD morphologically as well as radiographically. The differentiaiting point are:
DIP is diffuse process whereas RB-ILD is bronchiole-centric in distribution
Lymphoid aggregates are present in DIP
The absence of fibroblastic foci help to differentiate it from usual interstitial pneumonia
In active non-specific interstitial pneumonia (NSIP) prominent intra-alveolar macrophages are not seen
DIP has much better prognosis than UIP and NSIP
3.USUAL INTERSTITIAL PNEUMONIA:
The clinical term of Idiopathic pulmonary fibrosis is used for a clinic-pathological condition that is marked by progressive interstitial fibrosis and respiratory failure having radiologic and histologic pattern of UIP but in absence of discernible etiology.
Middle to old age patients
Gradual onset of exertional dyspnea
Fine end-inspiratory crackles on examination
Pulmonary function tests:
Reduction in diffusion capacity initially on exertion which later occurs at rest as well
Diffuse bilateral interstitial abnormalities in lower lungs
Honey-comb lung in worsened conditions
Reticular opacities and sub-pleural honey-comb changes on HRCT
Though the exact etiology is unknown but it appears that the fibrosis arises in genetically predisposed patients with aberrant repair system of epithelia when exposed to environmental insults
- Cigrattee smoking
- Metal fumes
- Wood dust
- Occupational exposures in farming, hair-dressing and stone polishing
- Germline loss-of-function mutation of TERT and TERC genes that encode components of telomerase ( telomerase mutation)
- MUC5B variant
- Surfactant mutations
- Abnormal signalling pathway (PI3K-AKT pathway0
- It is disease of older age and rarely appears before 50 so may be the aging related telomere shortening mand other effects f aging may have some role. But these associations are not known yet.
Cobble-stoned pleural surface
On cut-surface white, rubbery and firm surface representing fibrosis is seen.
Patchy subplerural and paraseptal distribution
Fibroblastic foci that are actually the scattered foci of immature fibrosis especially at interface of fibrotic and normal lung tissue
Fibromyxoid connective tissue composed of loose myxoid stroma and spindled cells located in interstitium and not in alveolar spaces
Hyperplastic smooth muscle proliferation around terminal bronchioles
Remolded lung with honey-comb appearance
Absence of marked interstitial fibrosis
it is slowly progressive disease. Following factors worsen the prognosis,
Decreased pulmonary function tests
Severity of imaging studies
Greater number of fibroblastic foci
UIP pattern seen in other conditions: the UIP pattern can be seen in conditions like connective tissue diseases, chronic hypersensitivity disease and asbestosis. The clinical findings, laboratory and histological findings help to differentiate it from idiopathic pulmonary fibrosis.
The other lung conditions associated with cigarette smoking will be in following articles.
Dr Saadia Hafeez