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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

Microscopic findings:

Bronchiolocentric distribution

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)

Clinical findings:

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.

Radiology:

Chest x-rays are normal. CT scan shows lower lung ground-glass opacifications

Microscopic findings:

Diffuse process

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

Special stains:

Smoker’s macrophages cytoplasm stains positively with PAS-D and the brown pigment stains with Prussian blue

D/D:

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

Prognosis:

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.

Clinical findings:

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

Radiologically:

Diffuse bilateral interstitial abnormalities in lower lungs

Honey-comb lung in worsened conditions

Reticular opacities and sub-pleural honey-comb changes on HRCT

Pathogenesis:

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

Environmental factors:

    • Cigrattee smoking
    • Metal fumes
    • Wood dust
    • Occupational exposures in farming, hair-dressing and stone polishing

Genetic factors:

    • 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

Age:

    • 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.

Gross findings:

Cobble-stoned pleural surface

On cut-surface white, rubbery and firm surface representing fibrosis is seen.

Microscopic findings:

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

Squamous metaplasia

Hyperplastic smooth muscle proliferation around terminal bronchioles

Remolded lung with honey-comb appearance

Absence of marked interstitial fibrosis

Prognostic factors:

it is slowly progressive disease. Following factors worsen the prognosis,

Older age

Cigarette smoking

Decreased pulmonary function tests

Severity of imaging studies

Greater number of fibroblastic foci

Shortnessof breath

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

 

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