My Clinical Notes

• A heterogenous group of disorders characterised by involvement of the pulmonary connective tissue, principally affecting the delicate interstitum of the alveolar walls
• Result in restrictive lung disease
• Radiological appearance is of diffuse infiltrates or ground glass shadowing
• Can differentate between early stages but not late due to scarring and gross destruction of the lung, referred to as ‘honeycomb lung’
• Seconday pulmonary hypertension and cor pulmonale

 

Pathogenesis

• The initial event is epithelial or endothelial injury by inhaled or blood-borne toxins
• Earliest common manifestation is alveolitis – accumulation of inflammatory cells within the alveola walls and spaces
• This distorts the normal alveolar structures and casues the release of mediators whih injure parenchymal cells and cause fibrosis
• This results in an end stage fibrotic lung in which the alveoli are replaced by cystic spaces separated by thick bands of CT interspersed by inflammatory cells

 

Categories of chronic interstitial lung disease

• Fibrosing
  • Idiopathic pulmonary fibrosis
  • Non-specific interstitial pneumonia
  • Cryptogenic organising pneumonia
  • Those associated with collagen vascular diseases
  • Pneumoconiosis
  • Drug reactions
  • Radiation pneumonitis
• Granulomatous
  • Sarcoidosis
  • Hypersensitivity pneumonitis
• Eosinophilic
• Smoking related
  • Desquamative interstitial pneumonia
  • Respiratory bronchiolitis-associated lung disease
• Other
  • Pulmonary alveolar proteinosis

 

Fibrosing diseases

 

Idiopathic pulmonary fibrosis

• Also called cytogenic fibrosing alveolitis
• A disorder of unknown cause characterised by progressive pulmonary interstitial fibrosis resulting in hypoxaemia
• Repeated cycles of alveolitis are postulated to cause abnormal wound healing resulting in excessive fibroblast proliferation
• The inflammatory response is of a Th2 nature – eosinophils, mast cells and Il-4 and IL-13

 

• Morphology
  • The histological pattern is denoted as usual interstitial pneumonia (UIP)
  • There is patchy interstitial fibrosis with characteristic subpleural and interlobular septal distribution and lower lobe predominance
  • New fibroblastic foci, typically in bronchiolar walls, occur within older fibrotic areas
  • Ongoing lung destruction leads to honeycomb lung with dense fibrosis and cystic spaces lined by type II pneumocytes or bronchiolar epithelium
  • There is mild to moderate inflammation within the fibrotic areas consisting of lymphocytes, neutrophils, eosinophils and mast cells
• Clinical
  • Insidious onset with gradual SOB on exertion and a dry cough
  • Most present between ages of 40 to 70
  • Mean survival is 3 years or less
  • Only definite treatment is lung transplantation

 

Non-specific interstitial pneumonia (NSIP)

• Diffuse interstitial lung disease of unknown origin which fails to show the diagnostic features of any of the well characterised interstitial diseases
• Histologically it can be divided into cellular and fibrosing patterns
• The cellular pattern consists of patchy mild to moderate chronic interstitial inflammation 
• The fibrosing pattern consists of diffuse interstitial fibrosis without the temporal heterogeneity that is characteristic of UIP
• Fibrotic foci are absent
• Patients have a better outcome than those with UIP

 

Cyptogenic Organising Pneumonia (COP)

• May be idiopathic or a response to infection of inflammation
• Clinically there is cough, dyspnoea and often a recent RTI
• Other aetiological associations include, inhaled toxins, drugs, collagen vascular disease, GvHD
• Patients may improve gradually or with steroid treatment
• Pathologically there are loose fibrous tissue plugs within the bronchioles, alveolar ducts and alveolar

 

Pulmonary involvement of collagen vascular diseases

• Many collagen vascular diseases can involve the lung. These include;

• • SLE
  • RA
  • Systemic sclerosis
  • Dermatomyositis-polymyositis
• Patterns include NSIP, UIP, vascular sclerosis, organising pneumonia and bronchiolitis

 

Pneumoconiosis

• See occupational lung disease notes

 

 

Drug induced disease

• Ranging from acute bronchitis to pneumonitis to fibrosis

 

Radiation induced lung disease

• Acute pneumonitis occurs 1-6 months after therapy (usually for thoracic tumours)

 

Granulomatous diseases

 

Sarcoidosis

• Systemic disease of unknown origin characterised by noncaseating granulomas in many tissues and organs
• See sarcoidosis notes

 

Hypersensitivity Pneumonitis

• Immunologically mediated disorder caused by chronic inhalation of dusts and related occupational antigens
• Involves both immune complex and delayed hypersensitivity reactions
• It is important to identify these diseases as progressive fibrotic lung disease can be prevented by removal of the environmental agent
• Specific syndrome include;
  • Farmers lung – spores of thermophilic actinomyces in hay
  • Pigeon breeders lung – protein from bird feathers or excreta
  • Air conditioner lung – thermophilic bacteria in heated water reservoirs
• Histological changes include bronchiolocentric interstitial pneumonitis and fibrosis with variable numbers of non-caseating granulomas

 

Pulmonary eosinophilia

 

• Diverse group of conditions characterised by eosinophilic infiltrates in pulmonary interstitial and alveolar spaces. It can be divided into 5 categories;
  • Acute eosinophilic pneumonia with respiratory failure - acute disease of unknown  causes
  • Simple pulmonary eosinophilia or Loeffler syndrome – aetiology unknown, transient, benign infiltrates with prominent eosinophilia in the blood and lung
  • Tropical eosinophilia – caused by microfilariae infection
  • Secondary eosinophilia – induced by infections, hypersensitivity, asthma and ABPA
  • Idiopathic chronic eosinophilic pneumonia – unknown aetiology manifested by focal lung consolidation with extensive lymphocyte and eosinophil infiltration

 

Smoking related interstitial diseases

 

Desquamative interstitial Pneumonia

• Not really desquamative – instead associated with large intra-alveolar collections of brown smokers macrophages with mild interstitial inflammation and minimal fibrosis
• Emphysema is often present
• Respond well to steroid treatment and smoking cessation

 

Respiratory Bronchiolitis – associated interstitial lung disease

• Common histological lesion found in smokers
• Characterised by the presence of pigmented intraluminal macrophages within first and second order bronchioles
• Associated with peribronchiolar infiltrate of lymphocytes and macrophages and fibrosis

 

Pulmonary Alveolar Fibrosis

 

• Rare disease with 3 forms;
  • Acquired PAP – accounts for 90% of cases.
    • Autoimmune anti-GM-CSF antibodies may be pathogenic leading to impaired surfactant clearance by pulmonary macrophages
  • Congenital PAP
    • Occurs in newborns and is rapid fatal. At least 3 gene mutations have been identified, surfactant protein B, GM-CSF, GM receptor β chain
  • Secondary PAP
    • Following exposure to irritating dusts of chemicals or occurs in immunosuppressed individuals
• Clinically patients have respiratory difficulty, cough and sputum containing gelatinous material
• Radiologically there is diffuse pulmonary opacification
• Histologically there is accumulation of dense amorphous PAS positive lipid laden material in the intra-alveolar spaces
• This alveolar protein exudates consists of granular acellular surfactant

 

 

 

This entry was posted on Tuesday, February 19th, 2008 at 12:06 pm and is filed under Respiratory. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.