Interstitial lung disease

Introduction

• Usually present with exertional dyspnoea or persistent, non-productive cough
• Interstitial opacification on CXR usually leads to Ix for ILD
• Heterogenous group of disorders affecting all lung parenchymal units
• Divided into alveolitis vs. granulomatous

Classification – Alveolitis

• Alveolitis, interstial inflammation and fibrosis
  • Known cause
    • Asbestos, drugs, chemotherapeutics, radiation, aspiration pneumonia and residual of ARDS
  • Unknown cause
    • Idiopathic interstitial pneumonias (Idiopathic pulmonary fibrosis/usual interstitial pneumonia, acute interstitial pneumonia (diffuse alveolar damage), cryptogenic organising pneumonia (BOOP))
    • Connective tissue diseases (SLE, RA, AS, systemic sclerosis, Sjogren’s)
    • Pulmonary haemorrhage syndromes (Goodpasture’s)
    • Amyloidosis
    • Inherited (Tuberous sclerosis, NF)
    • GI or liver disease (Crohn’s, PBC, UC)
    • Graft-versus-host disease

Classification – granulomatous

• Granulomatous
  • Known cause
    • Hypersensitivity pneumonitis
    • Inorganic dusts e.g. beryllium or silica
  • Unknown cause
    • Sarcoidosis
    • Langerhan’s cell granulomatosis
    • Wegener’s
    • Churg-Strauss
    • Bronchocentric and lymphomatoid granulomatosis

Pathophysiology

• Granulomatous lung disease
  • Accumulation of T lymphocytes, macrophages and epithelioid cells organised into granulomas within lung parenchyma
• Inflammation and fibrosis
  • Chronic inflammation leading to interstitial fibrosis
  • Patterns of ILD:
    • Usual interstitial pneumonia (UIP)
    • Non-specific interstitial pneumonia
    • Respiratory bronchiolitis
    • Organising pneumonia (bronchiolitis obliterans with organising pneumonia)
    • Diffuse alveolar damage
    • Dequamative interstitial pneumonia
    • Lymphocytic interstitial pneumonia
  • Irreversible fibrosis of alveolar walls, airways and vasculature heralds gradual decline

Historical differentiation

• Acute presentation
  • Rare but can be seen in eosinophilic pneumonia, hypersensitivity pneumonitis, acute interstitial pneumonia and allergy
• Subacute presentation
  • Especially common in sarcoidosis, drug-induced ILD, alveolar haemorrhagic syndromes, cryptogenic organising pneumonia and SLE or polymyositis
• Chronic presentation
  • Vast majority and includes IPF, sarcoidosis, Langerhans cell histiocytosis, pneumoconioses

Age differentiation

• 20-40yo
  • Sarcoidosis
  • Connective tissue disorders
  • Familal IPF
• >50
  • IPF

Smoking history

• 66-75% of patients with IPF have a smoking history
• Almost all patients with following have a smoking history
  • Langerhans cell histiocytosis
  • Goodpasture’s
  • Desquamative interstitial pneumonia
  • Respiratory bronchiolitis
  • Pulmonary alveolar proteinosis

Lab results

• Raised LDH often found in ILD
• Raised serum ACE – Sarcoidosis
• Serum precipitins – Confirm exposure when hypersensitivity pneumonitis is suspected
• ANCA and anti-basement membrane antibodies are useful if vasculitis is suspected

CXR

• Most commonly bibasal reticular pattern
• Nodular or reticulonodular pattern may also be seen
• Nodular opacities with predilection for upper lobes in:
  • Sarcoidosis, Langerhans cell histiocytosis, chronic hypersensitivity pneumonitis, silicosis, berylliosis, RA and AS)
• CXR correlates poorly with clinical severity or histopathological stage of disease
• Honeycombing correlates with small cystic spaces and progressive fibrosis and confers a poor prognosis
• Usually CXR is non-specific

HRCT

• May preclude need for lung biopsy in:
  • IPF
  • Sarcoidosis
  • Hypersensitivity pneumonitis
  • Asbestosis
  • Lymphangitic carcinoma
  • Langerhans cell histiocytosis
• Also useful for determing best site for biopsy and delineating other disease processes

Pulmonary function tests

• Spirometry
  • Restrictive defect with reduced TLC, functional residual capacity and residual volume
  • FEV1 and FVC are reduced by FEV1:FVC ratio may be increased
  • Have prognostic value in IPF or non-specific interstitial pneumonia
• Diffusing capacity
  • DLCO reduction is common but not specific
  • Due to VQ mismatch primarily
  • Severity does not correlate with disease stage
• ABG
  • A normal PaO2 does not rule significant hypoxaemia during exercise or sleep

Cardiopulmonary exercise testing

• ABG after exercise
• Desaturation, failure to decrease dead space with exercise and excessive increase in RR with exercise with lower-than expected recruitment of tidal volume
• 6 min walk test obtains global evaluation of submaximal exercise capacity in patients with ILD

Bronchoalveolar lavage

• May be useful in diagnosis for:
  • Sarcoidosis
  • Hypersensitivity pneumonitis
  • Diffuse alveolar haemorrhage
  • Cancer
  • Pulmonary alveolar proteinosis

Tissue and cellular examination

• This is the most effective method for confirming diagnosis and assessing disease activity
• May identify more treatable condition than previously thought:
  • Sarcoidosis
  • Hypersensitivity pneumonitis
  • Respiratory bronchiolitis
• Should obtain biopsy before treatment
• Definitive diagnosis avoids confusion and anxiety down the track if patient does not respond to therapy

Treatment of ILD

• Therapy does not reverse fibrosis so goal is to remove offending agent and aggressive suppression of the acute and chronic inflammatory process
• Corticosteroids
  • The mainstay of therapy for suppression of alveolitis in ILD but success rate is low
  • No direct evidence of survival benefit in many of the diseases
  • Recommended for symptomatic ILD with eosinophilic pneumonias, COP, connective tissue diseases, sarcoidosis, inorganic duse exposures, acute radiation pneumonitis, diffuse alveolar haemorrhage and drug-induced ILD
  • Common starting dose is 0.5-1mg/kg prednisone continued for 4-12 weeks then tapered to maintenance level
  • If continues to decline, second agent is added and prednisone dose loweered to 0.25mg/kg/day
    • Cyclophosphamide and azathioprine have had variable success

Idiopathic pulmonary fibrosis (IPF)

• Most common form of idiopathic interstitial pneumonia
• Has a distinctly poor response to therapy and a bad prognosis so must look for more treatable diagnoses
• Clinical
  • HRCT – Patchy, predominantly basilar, subpleural reticular opacities, often with traction bronchiectasis and honeycombing
  • Atypical findings (suggesting alternative diagnosis) include nodular opacities, extensive ground-glass changes, upper or mid-zone predominance, prominent hilar lymphadenopathy
• Histological findings
  • Must have usual interstitial pneumonia pattern
  • Surgical biopsy is usually required as opposed to transbronchial biopsy
• May suffer acute deteriorations due to PE, infections, pneumothorax or heart failure. Also often suffer an accelerated phase of rapid decline associated with a poor prognosis
  • Worsening of dyspnoea over days to 4 weeks, newly developing diffuse CXR changes, worsening hypoxaemia and absence of alternative cause
  • Get diffuse alveolar damage histological changes overlying background UIP
• No therapy has been found to work for acute exacerbations
• Consider lung transplant for progressive deterioration despite medical management

Non-specific interstitial pneumonia (NSIP)

• Subacute restrictive process with presentation like IPF but in younger people, mostly women who have never smoked
• Often associated with a febrile illness
• HRCT – Bilateral, subpleural ground-glass opacities with lower lobe volume loss. Honeycombing is unusual
• Get uniform interstitial involvement histologically
• Majority of patients have good prognosis (5-year mortality 15%) with most showing response to steroids +- azathioprine

Acute interstitial pneumonia (AIP)

• Aka Hamman-Rich syndrome
• Rare, fulminant form of lung injury with diffuse alveolar damage on biopsy
• Patient are >40 and presents like ARDS, often requiring mechanical ventilation and with >60% mortality rate
• Those who recover often show substantial improvement
• Not clear if glucocorticoids are effective

Cryptogenic organising pneumonia (COP)

• Also known as idiopathic bronchiolitis obliterans with organising pneumonia (idiopathic BOOP)
• Onset in 5^th or 6^th decade with flu-like illness and restrictive defect
• CXR is distinctive
  • Bilateral, patchy or diffuse alveolar opacities with normal lung volume
• HRCT – Ground-glass opacification, small nodular opacities and bronchial wall thickening and dilatation
• Lung biopsy shows granulation tissue within small airways
• Glucocorticoid therapy effective in 2/3 of patients

Smoking-associated ILD

• Desquamative interstitial pneumonia (DIP)
  • Rare entity found exclusively in smokers
  • Macrophages in intra-alveolar spaces with minimal interstitial fibrosis
  • Diffuse hazy opacities on CXR or HRCT
  • 10-year survival 70% and better response to smoking cessation and steroids than IPF
• Respiratory bronchiolitis-associated ILD
  • Subset of DIP with macrophages in peribronchial alveoli
  • Resolves with smoking cessation alone

Smoking-associated ILD

• Pulmonary langerhans cell histiocytosis (PLCH)
  • Rare diffuse lung disease in men aged 20-40
  • Pneumothorax occurs in 25% of patients
  • Ill-defined or stellate nodules (2-10mm), reticular or nodular opacities, bizarre-shaped upper zone cysts, preservation of lung volume and sparing of costophrenic angles
  • HRCT that shows combination of nodules and thin-walled cysts is virtually diagnostic
  • Get marked reduction in diffusion capacity with some restrictive impairment
  • Cessation of smoking leads to improvement in 1/3 of patients
  • Most suffer progressive or persistent disease

ILD associated with connective tissue disease

• Progressive systemic sclerosis
  • Pulmonary involvement seen in 50%
• Rheumatoid arthritis
  • More common in men
• SLE
  • Pleuritis is the most common manifestation
• Polymyositis/dermatomyositis
• Sjogren’s syndrome
  • Hoarseness, cough and bronchitis due to dryness

Drug-induced ILD

• Usually non-productive cough and progessive dyspnoea
• Huge range of potential agents
• May be acute or insidious in onset

Syndromes of ILD with diffuse alveolar haemorrhage

• Often abrupt onset of cough, fever, dyspnoea and haemoptysis
• Haemoptysis absent in 1/3 of cases initially
  • Suggested by new alveolar opacifications, drop in Hb and haemorrhagic BAL
• Recurrent episodes lead to fibrosis
• Evaluation of lung or renal tissue will often provide diagnosis
  • Wegener’s, connective tissue disorders, Goodpasture’s, HSP
• Mainstay of therapy is IV methylprednisolone 0.5-2g daily in divided doses for up to 5 days
• Other immunosuppressive agents may be indicated

ILD with granulomatous response

• Inhalation of organic dusts
• Sarcoidosis
• Granulomatous vasculitides
  • Pulmonary angiitis
  • Wegener’s granulomatosis
  • Churg-Strauss syndrome

Bronchocentric granulomatosis

• Descriptive histological term that describes an uncommon and non-specific pathological response to a variety of airway injuries
• Seen as hypersensitivity reaction to Aspergillus in asthmatic patients
• 50% of patients have chronic asthma with severe wheeze and peripheral eosinophilia
• Probably one manifestation of ABPA

Sarcoidosis

• Multisystem granulomatous disease usually manifesting in lungs of younger people
• 90% of patients have some lung involvement
• Skin, eyes, liver in about a 1/3 each
• May have organ-specific symptoms or B symptoms
• Skin lesions
  • Non-specific: Erythema nodosum, erythema multiforme, nummular eczema, calcinosis cutis, pruritis
  • Specific: Lupus pernio on nose/face, purple/red plaques, maculopapular eruptions, subcutaneous nodules or scar sarcoidosis
• Raised serum calcium due to Vitamin D production occurs in up to 60% of patients with subsequent nephrocalcinosis

Last Updated on October 29, 2020 by Andrew Crofton