1. Restrictive Lung Diseases
Dr. Raid Jastania

2. “Don’t forget the homework”

3. Restrictive Lung Diseases
Definition:
Reduced lung compliance
More pressure needed to expand lungs
Lungs are stiff
Pulmonary function test: Low VEV1, Low FVC (the ratio FEV1/FVC is normal)

4. Restrictive Lung Diseases
Types:
Chest wall abnormality (not primary lung)
Deformities, kyphoscoliosis
Neuromuscular disease
Primary lung disease
Acute: Acute Respiratory Distress Syndrome ARDS
Chronic:
Occupational: Asbestosis, silicosis, coal worker pneumoconiosis
Interstitial lung disease (interstitial pneumonia), Idiopathic pulmonary fibrosis
Immune diseases: Sarcoidosis, SLE, RA, Wegener
Physical injury: : Radiation
Drugs: Chemotherapy, methotrexate

5. Restrictive Lung Diseases
Gas exchange barrier:
Basement membrane
Interstitial tissue
Endothelial cell
Epithelial cell

6. Restrictive Lung Diseases
Initial injury to cells: endothelial, epithelial
This is followed by reaction that end by interstitial fibrosis – stiff lung – dyspnea
Damage to epithelium and vessels – abnormal ventilation-perfusion – Hypoxia – cyanosis
Pulmonary hypertension – cor pulmonale

7. Acute Lung Injury – Acute Respiratory Distress Syndrome ARDS

8. Acute Lung Injury – Acute Respiratory Distress Syndrome ARDS
Continuum of the same condition
Characterized by progressive respiratory failure:
Acute onset dyspnea
Decreased arterial oxygen pressure (hypxemia)
Bilateral pulmonary infiltrates (edema)
Absence of evidence of left-sided heart failure
Most common cause of non-cardiogenic pulmonary edema

9. Acute Lung Injury – Acute Respiratory Distress Syndrome ARDS
Can be caused by many conditions:
Direct injury to lung:
Pneumonia, aspiration, pulmonary contusion (trauma), fat embolism, near-drowning, inhalation injury, post-lung transplant
Indirect Lung injury:
Sepsis, severe trauma with shock, cadiopulmonary bypass, acute pancreatitis, transfusion, uremia

10. Acute Lung Injury – Acute Respiratory Distress Syndrome ARDS
Pathogenesis:
Epithelial or endothelial injury
Inflammation: increased vascular permeability, edema, fluid in alveoli, loss of diffusion capacity, loss of surfactant, damage of typeII pneumocytes
Proinflammatory cytokines>> Anti-inflammatory cytokines
Cytokines:
IL-8: Chemotaxis of neutrophils
IL-1, TNF
Neutrophils:
Oxidative damage
Attract other inflmmatory cells: IL-1, TNF
Fibrosis/Repair: TGF-alpha, PDGF

11. Acute Lung Injury – Acute Respiratory Distress Syndrome ARDS
Morphology:
Diffuse alveolar damage
1. Exudative phase
2. Proliferative phase
3. Fibrotic phase

12. Acute Lung Injury – Acute Respiratory Distress Syndrome ARDS
1. Exudative phase
Lung is dark, red, firm
0-7 days
Capillary congestion
Necrosis of epithelial cells
Interstitial, alveolar edema, hemorrhage
Collection of neutrophils
Alveolar collapse (loss of surfactant)
Fibrin thrombi
Hyaline membrane lining alveolar ducts

17. Acute Lung Injury – Acute Respiratory Distress Syndrome ARDS
2. Proliferative phase
1-3 weeks
Proliferation of type II pneumocytes
Macrophages, removing cell debris
3. Fibrotic phase
Resolution with minimal fibrosis
Repair/Fibrosis, thick alveolar walls
Progressive fibrosis (honeycomb lung) Rare

18. Acute Lung Injury – Acute Respiratory Distress Syndrome ARDS
Clinical:
Mortality was 100%
Now 30-40% with good ICU support
Poor prognosis: old age, multisystem failure, high levels of IL-1

19. Chronic Restrictive Lung Diseases

20. Chronic Restrictive Lung Diseases
Group of different diseases
Similar clinical, pulmonary function test and pathological findings
Represent 15% of non-infectious diseases of lungs
End-stage: diffuse interstitial pulmonary fibrosis (Honeycomb lung)

21. Restrictive Lung Diseases
Primary lung disease
Acute: Acute Respiratory Distress Syndrome ARDS
Chronic:
Occupational: Asbestosis, silicosis, coal worker pneumoconiosis
Interstitial lung disease (interstitial pneumonia), Idiopathic pulmonary fibrosis
Immune diseases: Sarcoidosis, SLE, RA, Wegener
Physical injury: : Radiation
Drugs: Chemotherapy, methotrexate

22. Idiopathic Pulmonary Fibrosis
Cryptogenic fibrosing alveolitis
Unknown etiology
Diffuse interstitial fibrosis
Sever hypoxemia, and cyanosis
Male>Female, 60y
Diagnosis of exclusion

23. Idiopathic Pulmonary Fibrosis
Pathogenesis:
Alveolar wall injury
Alveolitis: inflammation, edema
Neutrophil, macrophages, lymphocytes
Interstitial Fibrosis
? Immune disorder: association with immune diseases: RA, SLE, Sjogren….
Macrophages: IL-8, FGF, TGF-beta, PDGF

24. Idiopathic Pulmonary Fibrosis
Morphology:
Interstitial lung disease
Interstitial pneumonia
Usual interstitial pneumonia
Non-specific interstitial pneumonia
Desquamative interstitial pneumonia
Lymophocytic interstitial pneumonia
Bronchiolitis Obliterance Organizing Pneumonia BOOP

25. Idiopathic Pulmonary Fibrosis
Morphology:
Usual interstitial Pneumonia UIP
Random pattern of interstitial chronic inflammation, fibrosis, in variable stages
80% idiopathic, 20% associated with collagen vascular diseases

32. Idiopathic Pulmonary Fibrosis
Clinical:
Gradual, non-productive cough
Progressive Dyspnea, cyanosis
Finger clubbing
Mean survival 2-4 years

33. Sarcoidosis Multisystem disease Unknown etiology
Non-caseating granuloma in many tissues and organs
Diagnosis of exclusion

34. Sarcoidosis Presenting Picture: Bilateral hilar lymphadenopathy
Lung involvement, lung nodules
Other organs: skin, eye, any tissue
Adult, younger than <40y
Common in US blacks
Higher in non-smokers

35. Sarcoidosis Pathogenesis Unknown cause Immunologic factors
Activated CD4 T cells
Increase number of CD4 Tcells
High level f IL-2, Interferon-gamma, IL-8, TNF
Genetic factors:
Familial, racial clustering
Association with HLA-A1, HLA-B8
Environmental factors
? Viral infection, mycobacteria

36. Sarcoidosis Morphology: Non-caseating granuloma
Collection of epithelioid histiocytes rimmed by CD4 T-cells and fibroblasts
Giant cells
Schqumann bodies (calcium and protein_
Asteroid bodies (inclusions)

38. Sarcoidosis Hilar and paratracheal lymph nodes 75-90%
Lung involvement in 90%
Diffuse interstitial fibrosis 5-15%
Sking 25%
Erythema nodosum: raised, tender, nodule on anterior aspect of legs
Eye, Lacrimal glands
Iritis, loss of vision
Choroiditis, retinitis
Parotid gland 10%, Spleen 75%, Liver, Bone marrow, any organ

39. Sarcoidosis Clinical: Asymptomatic in many
Lymphadenopathy, skin, eye lesion
Respiratory disease: dyspnea, dry cough
Fever, fatigue, wt. Loss
Unpredictable course
Progressive or relapsing remitting disease
10% develop progressive fibrosis

40. Hypersensitivity Pneumonitis
Immune mediated disease
Type III and type IV hypersensitivity
Inflammatory disease
Affect alveoli (mainly) (Allergic Alveolitis)
Occupational disease
Restrictive disease

41. Hypersensitivity Pneumonitis
Presentation:
Acute: 4-6 hours following exposure, Fever, cough , dyspnea
Chronic: cough, dyspnea, wt. Loss

42. Hypersensitivity Pneumonitis
Causes
Fungal/Bacterial
Farmer lung: micropolyspora
Humidifier lung: Actinomycetes
Cheese washer’s lung: Penicillium
Animal Product
Pigeon breeder’s lung
Chemicals

43. Hypersensitivity Pneumonitis
Morphology:
Particles: not usually seen
Inflammation, edema, Peribronchial
Lymphocytes, plasma cells
Non-caseating granuloma
Fibrosis

44. Collagen Vascular Disease
Associated with interstitial Pneumonia
Similar to Idiopathic Pulmonary Fibrosis

45. Wegener Granulomatosis
Necrotizing vasculitis
Affect both upper and lower respiratory tract
Parenchymal necrotizing granuloma
URT: sinusitis, epistaxis, nasal perforation
LRT: cough, hemoptysis, chest pain