Idiopathic Interstitial Pneumonia

Group of diffuse parenchymal lung diseases of unclear aetiology that are characterised by:

• Expansion of the pulmonary interstitial compartment
• Inflammatory infiltrate

This classification encompasses a a number of subsidiary interstitial diseases including:

Acute interstitial pneumonia is also known as Hamman-Rich syndrome.

• Acute interstitial pneumonia
  Variant characterised by:
  • Acute onset
    7-14 days.
  • Rapidly progressive course
    Generally require intubation within a few days.
  • Diffuse lung injury
• Organising pneumonia
  Inflammatory lung disease characterised by granulation in small airways and alveoli. Subdivided into:
  • Cryptogenic organising pneumonia
    No obvious cause.
  • Secondary organising pneumonia
    Following previous alveolar injury, including:
    • Post-infectious
      See below.
    • Drugs
    • Connective tissue disorders
      • Rheumatoid arthritis
      • Systemic sclerosis
      • Lupus
      • Inflammatory bowel disease
      • Vasculitis
        • Granulomatosis with polyangitis
        • Eosinophilic granulomatosis with polyangitis
    • Transplantation
    • Malignancy
      • Haematological
    • Radiotherapy
      • Thoracic malignancy
        Generally 3-6 months.
    • Chemotherapy
    • Allogenic BMT
    • Industrial chemical exposure
• Lymphoid interstitial pneumonia

Cryptogenic organising pneumonia was formerly known as bronchiolitis obliterans organising pneumonia (BOOP).

Epidemiology and Risk Factors

AIP:

• Associated with:
  • Rheumatoid arthritis
  • SLE
  • Dermatomyositis
  • Sjögren’s syndrome

COP:

• ~1-5/100,000

Pathophysiology

Poorly understood, features include:

• Inflammation
• Intra-alveolar fibroproliferation
  • May be reversible
• Fibrinous remodelling

Aetiology

Precipitants of Secondary Organising Pneumonia

Infection	Drug
Bacteria: Gram negative cocci: Chlamydia pneumoniae Gram negative bacilli: Burkholderia cepacia Coxiella burnetii Legionella pneumophila Pseudomonas aeruginosa Serratia marcescens Gram positive cocci: S. aureus S. pneumoniae Gram-positive bacilli: Nocardia asteroides Other Mycoplasma pneumoniae	Common: Amiodarone Clopidogrel Dabigatran Hydralazine Risperidone Sertraline Sirolimus Statins Methotrexate
Viruses: DNA Viruses: Adenovirus CMV HHV-7 HSV RNA Viruses: COVID-19 HIV Influenza Virus Parainfluenza Virus RSV	Immune and cancer: Chemotherapies Bleomycine Cyclophosphamide FOLFIRI FOLFOX Hydroxyurea Leflunomide Oxiplatin Checkpoint inhibitors Monoclonal antibodies
Parasites: Malaria P. vivax Dirofilaria immitis	Recreational: Synthetic marijuana Vaping Freebased cocaine
Fungi: Aspergillus Cryptococcus neoformans Pneumocystis jirovecii	Chemical: Textile die Mustard gas

Atypical infections are more likely to be the primary precipitant.

Clinical Features

Typically subacute presentation with:

• Dry cough
• Progressive dyspnoea
• Constitutional symptoms
  • Fever
  • Malaise
  • Weight loss

Features by Cause

Cause	Onset	Cough
AIP	Days-weeks
COP	Weeks-months	Unrelenting Dry

Assessment

History

Exam

• Bilateral diffuse crepitations

Investigations

Bedside:

• Bronchoscopy
  • BAL
    To evaluate for eosinophilic pneumonia and alveolar haemorrhage.

Laboratory:

• Blood
  • FBE
    Mild leukocytosis is common.
  • BNP
    Exclude CCF.
  • Cultures
  • Rheumatological screen
  • Connective tissue disease screen
• Sputum
  • Culture
    • Fungal
    • Atypical organisms
  • Viral PCR
    • Influenza
• Urine
  • Legionella PCR

A rheumatological screen consists of:

• Initial investigations:
  • FBE
  • UEC
  • ESR
  • CRP
  • LFT
  • ANA
  • Rheumatoid factor
  • Anti-CCP antibodies
  • Vitamin D
  • Urinealysis
• Second-line investigations
  For patients with strong clinical suspicion:
  • Anti-synthetase antibodies
  • Creatine kinase
  • Aldolase
  • Sjögren’s antibodies
    • SS-A
    • SS-B
  • Scleroderma antibodies
    • Anti-topoisomerase (Scl-70)
    • Anti-PM-1 antibody
    • Anti-centromere
  • Anti-dsDNA antibodies
  • Myositis-associated antibodies
    • Jo-1
    • PL-7
    • PL-12
  • ANCA
  • Anti-melanoma differentiation-associated gene 5
  • Overlap antibodies
    PM-1.

Imaging:

Organising Pneumonias

• CXR
  • Consolidative opacities with normal lung volumes
    Figure A.
• High-resolution CT
  • Multifocal consolidation
  • Peripheral nodulation
    Figure C.
  • Migratory opacities are classical for organising pneumonia
    Figure D and E are the same patient at different time points.
  • Atoll sign
    Rim of consolidation with central ground-glass opacities, which is rare but highly specific.

Other:

• Bronchoscopy
  • BAL
    Evaluate for:
    • Diffuse alveolar haemorrhage
    • Eosinophilia
    • Malignant infiltrates

Diagnostic Approach and DDx

Key differentials include:

• CAP
  Absence of antibiotic response suggests organising pneumonia.
• Hypersensitivity pneumonitis
• Eosinophilic pneumonia
• Diffuse Alveolar haemorrhage
• Vasculitis
• Pulmonary lymphoma
• Invasive mucinous adenocarcinoma
• Pulmonary sarcoidosis

Management

• Broad-spectrum antimicrobials
• Immunosuppression with corticosteroids

Resuscitation:

Specific therapy:

• Pharmacological
  • Antibiotics
    Commenced empirically until infectious causes are excluded.
  • Corticosteroids
    1mg/kg prednisolone daily up to 60mg per day, for 2-4 weeks followed by a 3-5 month taper.
• Procedural
  • Lung transplantation
• Physical

Supportive care:

Disposition:

Preventative:

Marginal and Ineffective Therapies

Anaesthetic Considerations

Complications

• Death
  • AIP
    ~50% by 6 months.
• B
  • Chronic interstitial lung disease
  • Relapse
    • Particularly with organising pneumonia

Prognosis

Key Studies

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References

1. King TE, Lee JS. Cryptogenic Organizing Pneumonia. New England Journal of Medicine. 2022;386(11):1058-1069. doi:10.1056/NEJMra2116777
2. Mrad A, Huda N. Acute Interstitial Pneumonia. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Sep 30].