8. Restrictive lung diseases

Question 1

Definition of restrictive lung diseases

Answer 1

Characterized by reduced expansion of the lung parenchyma due to decrease compliance & decreased total lung capacity; restrictive defects occur in two general conditions, of which only the latter will be discussed here:

(i) chest wall disorders – neuromuscular disorders, kyphoscoliosis, pleural diseases, obesity
(ii) interstitial lung disease;

Question 2

2 clinical patterns of restrictive pulmonary disease

Answer 2

1. Acute restrictive lung disease
   - Characterised by protein exudation & edema
   - E.g acute respiratory distress syndrome
2. Chronic restrictive lung disease
   - Characterised by inflammation & fibrosis
   - E.g chronic interstitial lung disease, pneumoconiosis

Question 3

Common End Result of Chronic Interstitial Lung Diseases

Answer 3

1. Honeycomb lung
   - Cut surface of lung resembles honeycomb
2. Complications
   - Chronic respiratory impairment
   - Pulmonary hypertension
   - Right ventricular hypertrophy
   - Cor pulmonale

Question 4

Definition of Acute respiratory distress syndrome

Answer 4

Characterized by the sudden onset of significant hypoxemia & diffuse pulmonary infiltrates in the absence of cardiac failure

Question 5

Causes of acute respiratory distress syndrome

Answer 5

1. Septicaemia*
2. Diffuse pulmonary infections*
   - Viral, Mycoplasma, Pneumocystis, miliary tuberculosis
3. Severe trauma*
4. Aspiration of gastric contents*
5. Inhalation of toxic fumes, chemical injury
6. Acute pancreatitis
7. Uremia

• more than 50% of acute respiratory distress syndromes are associated with these four conditions

Question 6

Morphology of acute respiratory distress syndrome

Answer 6

[Histology]

• Diffuse alveolar damage
• Alveolar walls line with waxy hyaline membrane, composed of fibrin rich edema fluid & necrotic epithelial cell debris

Question 7

Pathological Effects & Complications of acute respiratory distress syndrome

Answer 7

1. Acute respiratory failure

2. Interstitial fibrosis (with failure of resolution)

Question 8

Definition of chronic interstitial lung disease

Answer 8

Heterogeneous group of disorders characterized by inflammation & fibrosis of the pulmonary connective tissue, principally the most peripheral & delicate interstitium in the alveolar walls

Question 9

Types of chronic interstitial lung disease

Answer 9

1. Idiopathic Interstitial Pneumonitis
2. Systemic Connective Tissue Diseases
3. Complications of Therapies
4. Complication of Atypical Pneumonias
5. External Allergic Alveolitis (Hypersensitivity Pneumonitis)
6. Sarcoidosis
7. Pneumoconiosis

Question 10

How does Idiopathic Interstitial Pneumonitis results in restrictive lung disease

Answer 10

1. Postulated to be due to repeated cycles of epithelial injury or activation by some unidentified agents
2. Clinical features:
   - Initially, increasing dyspnea on exertion & dry cough
   - Later, hypoxemia, cyanosis & clubbing
   - Mean survival of 3 years or less
   - Lung transplant as only definitive treatment

Question 11

How does Systemic Connective Tissue Diseases results in restrictive lung disease?

Answer 11

1. Rheumatoid arthritis
   - Pulmonary involvement occurs in 30-40% of cases
   - Presents as (i) chronic pleuritis with/without effusion, (ii) diffuse interstitial pneumonitis & fibrosis (iii) intrapulmonary rheumatoid nodules, or (iv) pulmonary hypertension
2. Systemic lupus erythematosus
   - Presents as diffuse interstitial fibrosis
3. Systemic sclerosis
   - Presents as patchy, transient parenchymal infiltrates & occasionally severe lupus pneumonitis

Question 12

How does the Complication of therapies results in restrictive lung disease?

Answer 12

1. Drug-induced lung diseases
   - Chemotherapeutic agents (e.g. bleomycin), anti-arrhythmic drug (e.g. amiodarone)
   - Cause significant pneumonitis in some patients
2. Radiation-induce lung diseases (radiation pneumonitis)
   - Results from therapeutic radiation of thoracic tumours (lung, esophageal, breast, mediastinal)

Question 13

How does Complication of Atypical Pneumonias results in restrictive lung disease?

Answer 13

1. Atypical pneumonias present as interstitial pneumonitis which principally involves inflammatory infiltration of the alveolar septum & interstitium
2. With failure to fully resolve, organization of interstitial infiltration & exudation results in interstitial fibrosis

Question 14

How does External Allergic Alveolitis (Hypersensitivity Pneumonitis) results in restrictive lung disease

Answer 14

1. Involves types III & IV hypersensitivity reactions towards inhaled organic agents
   - In contrast to asthma which involves the small
   airways, external allergic alveolitis primarily affects
   the alveoli
2. Specifically named syndromes include:
   - Farmer’s lung (results from exposure to dusts generated from harvested humid & warm hay which permits the rapid proliferation of the spores of thermophilic actinomycetes)
   - Bird fancier’s disease (provoked by proteins from serum, excreta or feathers of birds)
   - Humidifier lung (caused by thermophilic bacteria in heated water reservoirs)

Question 15

How does Sarcoidosis results in restrictive lung disease?

Answer 15

1. Idiopathic systemic disease characterized by formation of non-caseating granulomas in multiple tissues & organs
   - Lungs, eye, skin, lymph nodes, bone marrow, heart, kidney, central nervous system, endocrine glands etc
2. Pulmonary involvement results in:
   - Respiratory insufficiency
   - Progressive pulmonary fibrosis
   - Cor pulmonale

Question 16

Definition of Pneumoconiosis

Answer 16

Pulmonary diseases caused by the inhalation of inorganic dusts

Question 17

Pathogenesis of Pneumoconiosis

Answer 17

1. Development of a pneumoconiosis depends on:
   - Amount of dust retained in lung & airways (depends on dose of inhalation & effectiveness of clearance mechanisms such as the mucociliary escalator)
   - Size & shape of particles (smaller & more streamlined particles tend to reach the terminal alveoli more easily where they can settle in the alveolar linings)
   - Solubility of particles (the less soluble, the more likely it is to persist in the lung parenchyma to evoke a fibrosis collagenous pneumoconiosis)
   - Possible additional effects of other irritants (e.g. smoking, which paralyses the mucociliary escalator)
2. Lung damage occurs due to alveolar macrophage response to dust particles, producing a chronic interstitial lung disease
   - Release of cytokines promoting inflammation
   - Organization over time to produce fibrosis
3. End result is a restrictive lung disease

Question 18

Types of pneumoconiosis

Answer 18

1. Coal Workers’ Pneumoconiosis
2. Silicosis
3. Abestosis

Question 19

Coal Workers’ Pneumoconiosis

Answer 19

1. Due to exposure to coal dust
2. Presents in a variety of ways:
   - Asymptomatic anthracosis (ingestion of inhaled carbon by alveolar macrophages, which then accumulate in the connective tissue; also seen in urban dwellers & smokers)
   - Simple CWP (presents with small, scattered, nodular lung lesions comprising carbon-laden macrophages, primarily located adjacent to respiratory bronchioles in the upper lobes & upper zone of lower lobes)
   - CWP with progressive massive fibrosis (presents with large nodular lesions comprising dense collagen & pigment with central ischemic necrosis; progression of disease results in fibrosis)
3. Pathological effects & complications:
   - Centrilobular emphysema (with simple CWP, due to
   eventual dilation of respiratory bronchioles)
   - Progression of progressive pulmonary fibrosis to increasing pulmonary dysfunction, pulmonary hypertension & eventual cor pulmonale

Question 20

Silicosis

Answer 20

1. Due to inhalation of silicon dioxide
   - Individuals working in granite quarrying, stone masonry & slate mining are at risk
2. Presentation:
   - Short exposure → alveolar exudation (acute silicosis)
   - Prolonged exposure → simple nodular silicosis (typically in upper lobes) & progressive massive fibrosis as individual lesions expand & coalesce
3. Pathological Effects & Complications:
   - Tuberculosis (postulated to be due to silica inhibition
   of pulmonary macrophage ability to kill phagocytosed mycobacteria; forms silicotuberculous nodules with central caseous necrosis)

Question 21

Abestosis

Answer 21

1. Due to exposure to asbestos fibres, which occurs in two morphological forms:
   - Serpentine: more common, flexible & curled structure, usually not pathogenic (as it is large & irregular in shape, making it more easily arrested in the upper airways to be swept upwards by the mucociliar escalator, decreasing the time it resides within the lung)
   - Amphibole: less common, straight & stiff structure, main cause of asbestosis (as it is smaller and more streamlined, hence able to travel to periphery and accumulate within the interstitium)
2. At risk groups: individuals who work in mining & refining of asbestos, building industry, shipyards
3. Risk & progression of disease depend on:
   - Duration & intensity of asbestos exposure
   - Concomitant cigarette smoking (as carcinogens are adsorbed onto surface of asbestos fibres)
4. Presentation:
   - Progressive fibrosis of lung
   - Pleural effusion & pleural thickening
   - Benign fibrous plaques of pleura
5. Pathological effects & complications
   - Carcinoma of lung (risk amplified by smoking - asbestos only = 5x; asbestos + smoking = 55x)
   - Mesothelioma of pleura (risk is not amplified by smoking)