1. RESTRICTIVE LUNG DISEASE
Lect-7&8

2. Background The lung volumes are reduced either because of:
1. Alteration in lung parenchyma.
2. Diseases of the pleura, chest wall or neuromuscular
apparatus.
Physiologically restrictive lung diseases are defined by reduced total lung capacity, vital capacity and functional residual capacity, but with preserved air flow.

3. Restrictive lung diseases may be divided into the following groups:
Intrinsic lung diseases (diseases of the lung parenchyma)
Extrinsic disorders (extra-parenchymal diseases)

4. Diseases of the Lung Parenchyma

5. Diffuse Interstitial Pulmonary Fibrosis
Synonyms: idiopathic pulmonary fibrosis, interstitial pneumonia, cryptogenic fibrosing alveolitis.
It is a group of diseases characterized by diffuse and usually chronic involvement of the pulmonary connective tissue, principally the most peripheral and delicate interstitium in the alveolar walls.
Thickening of interstitium.
Initially, infiltration with lymphocytes and plasma cells.
Later fibroblasts lay down thick collagen bundles.
These changes occur irregularly within the lung.
Eventually alveolar architecture is destroyed – honeycomb lung.

6. Pathogenesis:
The earliest common manifestation of most of the interstitial diseases is alveolitis = (accumulation of inflammatory cells within the alveolar walls and spaces).
Normally these cells is less than 7% of total lung population (macrophages 93%, lymphocytes 7%, neutrophils less than 1%), but in this disease there is increase in these cells.

7. These have two effects:
1- Distort the normal alveolar structures.
2- Injure the parenchymal cells by mediators and stimulate fibrosis.
The end result is fibrotic lung in which the alveoli are replaced by cystic spaces separated by thick bands of connective tissue interspersed with inflammatory cells.

8. Etiology
Unknown, may be immunological reaction.

9. Clinical Features Uncommon disease, affects adults in late middle age.
Progressive exertional dyspnea, later at rest, tachypnea and eventual cyanosis without wheezing or obstruction. .
Non-productive cough.
Physical examination shows finger clubbing, fine inspiratory crackles throughout both lungs.
Patient may develop respiratory failure terminally, secondary pulmonary hypertension and right sided heart failure with core pulmonale.
C X ray show diffuse infiltration by small nodules, irregular lines or ground glass shadows.
The disease progresses insidiously, median survival 4-6 years.

14. Pulmonary Function
Spirometry reveals a restrictive pattern. FVC is reduced, but FEV1/FVC supernormal.
All lung volumes – TLC, FRC, RV – are reduced.
Pressure volume curve of the lung is displaced downward and flattened.

15. Diagnosis
Diagnosis is often suggested by history, chest radiograph and high resolution CT scan of the lungs.
If old chest x-rays show classical disease, absence of other disease processes on history and no occupational or environmental exposure – clinical diagnosis can be made.
In other cases a surgical lung biopsy is obtained.

16. Pneumoconiosis
It is the non neoplastic lung reaction to inhalation of mineral dusts (e.g. coal dust, silica, asbestos, and beryllium) commonly encountered in the workspace.
The term broadened to include diseases induced by organic as well as inorganic particles and chemical fumes and vapors.

17. The development of the disease depend on:
1- amount of dust.
2- size and shape.
3- particulate solubility and physicochemical reactivity.
4- possible additional effects of other irritants e.g. tobacco smoke.

18. 1- Amount of the dust: retained in the lungs is determined by:
1- dust concentration in the ambient air.
2- the duration of the exposure,
& 3- the effectiveness of clearance mechanisms which affected by smoking that affects the mucociliary integrity.
2- Size: the most dangerous particles range from 1-5 micrometer in diameter because they may reach the terminal small airways and alveolar sacs and settle in their linings.

19. 3- The solubility and cytotoxicity of particles: is influenced by their size, where the small particles are more soluble in the pulmonary fluids and reach a toxic level more rapidly.
Large particles persist and resist dissolution and evoke a fibrosing collagenous pneumoconiosis.

20. Coal worker’s pneumoconiosis
A form of combustible carbon mined for fuel and has a spectrum of lung findings:
1- Asymptomatic anthracosis: seen as carbon pigmentation and save and seen as carbon pigment ingested by the macrophages .

21. 2- Simple coal worker’s pneumoconiosis:
characterized by coal macules about 1-2 mm in diameter or large coal nodules, both are aggregates of carbon laden macrophages with delicate collagen fibers. Affects mostly the upper lobes and the upper zones of the lower lobes. At the site there is also dilatation of adjacent alveoli (centrilobular emphysema still uncertain).
Occur with little or no pulmonary dysfunction.

22. 3- Complicated coal worker’s pneumoconiosis:
Many years to develop and characterized by intensely blackened scars larger than 2 cm, and may reach to 10 cm, multiple and seen microscopically as dense collagen with pigment with central necrosis due to ischemia. The fibrosis will be extensive result in progressive massive fibrosis (which is seen in other types of pneumoconiosis). Occur in less than 10% of cases of simple CWP.

23. The coexistence of rheumatoid arthritis with pneumoconiosis is known as Caplan’s syndrome lead to development of nodular pulmonary lesions like rheumatoid nodules. ( seen in CWP, asbestosis and silicosis).
Pathogenesis is still incompletely understood.
The disease is benign, but there may be increasing pulmonary dysfunction, pulmonary HT and core pulmonale. Also there is increased TB, CB and E.

24. Silicosis
Caused by inhalation of silica particles (crystalline silicon dioxide). The most prevalent chronic occupational disease in the world. Usually presents decades after exposure as slowly progressive nodular fibrosing pneumoconiosis.
The silica causes activation and release of mediators by viable macrophages, which initiate injury and fibrosis.

25. Morphology:
Gross: tiny, barely palpable, discrete pale to blackened nodules in upper zones of the lungs which then coalesce into hard collagenous scars. Some nodules have central softening and cavitation due to superimposed TB or to ischemia result in honey comb lungs. Fibrotic lesions may occur in hilar lymph nodes and pleura, and with calcification seen as egg shell calcification.
Microscopically: concentric layers of hyalinized collagen surrounded by dense capsule of more condensed collagen, seen in polarized microscope as birefringent silica particles.

26. Asbestos related diseases
Asbestos is a family of crystalline hydrated silicates that form fibers. RESULT IN:
1- Localized fibrous plaques, or diffuse pleural fibrosis.
2- Pleural effusion.
3- Parenchymal interstitial fibrosis (asbestosis).
4- Bronchogenic carcinoma.
5- Mesotheliomoa.
6- Laryngeal and extrapulmonary neoplasm.

27. Pathogenesis:
According to type, the serpentine type is flexible and stay in upper airways.
But the amphibole type is straight, stiff and brittle, is more pathogenic, reach to pleura and causes malignant pleural tumors.
The particles are both initiator and promoter for carcinoma development. Also with the adsorption of carcinogens in tobacco smoke result in synergistic effect and also by ingestion by macrophages lead to release of mediators which induces fibrosis.
Asbestosis start in the lower lobes and subpleurally.

28. Berylliosis: It is caused by induction of cellular immunity.
Occur in only 2% of workers.
Characterized by the presence of non caseating granulomas in the lungs, hilar lymph nodes or less commonly in the spleen, liver, kidney, adrenals and distant lymph nodes.
Then they become fibrotic, irregular fine nodules of densities seen in x ray.
Also associated with increase risk of lung cancer.

29. Sarcoidosis
A disease characterized by the presence of granulomatous tissue.
This is a systemic disease which involves eyes, brain, heart, lungs, bones and kidneys, skin, liver and spleen.
On pathology a non- caseating granuloma composed of histiocytes, giant cells and lymphocytes.
In advanced lung disease fibrotic changes are seen.

30. Etiology Unknown, likely immunological basis. Clinical Features
Four stages are identified:
Stage 0: No obvious intrathoracic involvement
Stage 1: Bilateral hilar lymphadenopathy, often accompanied by arthritis, uveitis and erythema nodosum.
Stage 2: Pulmonary parenchyma is also involved, changes in mid and upper zones.
Stage 3: Pulmonary infiltrates and fibrosis without adenopathy.

31. Non- caseating granulomas in Sarcoidosis

32. Stage I (bilateral hilar adenopathy)

33. Stage II Reticular nodules and BHL

34. HRCT – subpleural nodules

35. Hypersensitivity Pneumonitis
Also known as extrinsic allergic alveolitis.
Hypersensitivity reaction in the lung occurs in response to inhaled organic dust.
Example is farmer’s lung.
The exposure may be occupational or environmental.
The disease occurs from type III and type IV hypersensitivity reactions.
Farmer’s lung is due to thermophilic actinomyces in moldy hay.
Bird fancier’s lung is caused by avian antigen.

36. Pathology There are loosely formed granulomas.
There is infiltration of alveolar walls with lymphocytes, plasma cells and histiocytes.
There are loosely formed granulomas.
Fibrotic changes occur in advanced disease.

38. Clinical Features Acute HP
The disease may occur in acute or chronic forms.
Acute HP
Dyspnea, fever, malaise and cough appear 4-6 hours after exposure.
These symptoms continue for hours.
Physical examination shows fine crackles throughout the lungs.
These patients present with progressive dyspnea over a period of years.
Chest radiograph may be normal, but may show reticular nodular infiltration.

39. HRCT in Acute HP

40. These patients present with progressive dyspnea.
Chronic HP
These patients present with progressive dyspnea.
Physical examination shows bilateral inspiratory crackles.
Chest x-ray shows reticular nodular infiltration and fibrosis predominantly in upper lobes.
Pulmonary function tests – restrictive pattern.
Gas exchange shows hypoxemia which worsens on exercise.

41. Interstitial Disease Caused by Drugs, Poisons and Radiation
Various drugs cause acute pulmonary reaction – proceeding to interstitial fibrosis.
These drugs are busulfan, nitrofurantoin, amiodarone, bleomycin.
High oxygen concentration – interstitial fibrosis.
Radiation exposure – acute pneumonitis – fibrosis.

42. Collagen Vascular Diseases
Several collagen vascular diseases particularly systemic sclerosis and lupus and rheumatoid arthritis may lead to systemic sclerosis.
Dyspnea is often severe.
A definite diagnosis requires surgical lung biopsy.
Treatment is corticosteroids plus cytotoxic therapy.

43. Pleural Diseases Pneumothorax could be either primary or secondary.
Pleural effusion can be acute or chronic.
Pleural effusion is divided into exudate and transudate.
Pleural thickening – longstanding pleural effusion results in fibrotic pleura which splints the lung and prevents its expansion.
If the disease is bilateral – may cause restrictive lung disease.
Treatment may be decortication.

44. Diseases of the Chest Wall
Deformity of thoracic cage such as kyphoscoliosis and ankylosing spondylitis.
Scoliosis – lateral curvature of spine, kyphosis – posterior curvature.
Cause is unknown, polio and previous tuberculosis.
Patients develop exertional dyspnea, rapid shallow breathing.
Hypoxemia, hypercapnia and cor-pulmonale supervene.
Pulmonary function tests show RVP with normal diffusion.
Cause of death is respiratory failure or intracurrent pulmonary infection.
Treatment is non-invasive or invasive chronic ventilation.

46. Neuromuscular Disorders
Diseases affecting muscles of respiration or their nerve supply.
Poliomyelitis, Guillain-Barre syndrome, ALS, myasthenia gravis, muscular dystrophies.
All these lead to dyspnea and respiratory failure.
PFT’s show reduced FVC, TLC and FEV1.
The progress of disease can be monitored by FVC and blood gases.
Maximal inspiratory and expiratory pressures are reduced.
Treatment is either treating the underlying cause or assisted ventilation.