Interstitial Lung Disease

 

• Background

  Definition

  • Disease affecting lung interstitium – the connective tissue between the alveolar epithelium and capillary endothelium – along with cellular infiltration of alveoli and distal airways.
  • Can lead to pulmonary fibrosis (PF), which was formerly known as 'fibrosing alveolitis'.

  Causes

  Primary lung diseases:

  • Idiopathic pulmonary fibrosis (IPF).
  • Pneumoconiosis: lung disease cause by inhalation of non-organic (mineral) dust. Common types are asbestosis, coal worker's pneumoconiosis, and silicosis.
  • Hypersensitivity pneumonitis.
  • Infections: TB, RSV, PCP, atypicals.

  Multi-system disease:

  • Sarcoidosis
  • Connective tissue disease: SLE, RA, ankylosing spondylitis, systemic sclerosis, dermatomyositis.
  • Vasculitis

  Iatrogenic, BARMAN:

  • Bleomycin
  • Amiodarone
  • Radiation
  • Methotrexate
  • Aspirin and ACEi.
  • Nitrofurantoin

• Signs and symptoms

  Symptoms:

  • Progressive SOB, dry cough, failure to respond to treatment for other conditions.
  • Systemic: weight loss, fatigue.
  • Chest pain is rare, so its presence may suggest mesothelioma.

  Signs:

  • Crackles: bilateral fine end-inspiratory crackles in IPF. In asbestosis and hypersensitivity pneumonitis, there may also be wheeze and squeaks.
  • Other signs: ↑RR, ↓O2 sats, clubbing, peripheral cyanosis, ↓chest expansion.
  • There are very likely to be signs in IPF and asbestosis, while there are often no signs – despite a +ve CXR – in simple CWP, simple silicosis, and sarcoidosis.

• Smoking and ILD

  • Exacerbates most causes and should be stopped.
  • However, it reduces the risk of hypersensitivity pneumonitis and sarcoidosis.

• Idiopathic pulmonary fibrosis (IPF)

  • Commonest cause of interstitial lung disease, but a diagnosis of exclusion.
  • Characterised by dysregulated fibroblasts and myofibroblasts.
  • Commoner in males, with mean onset at 65. Prevalence 1/3000.
  • Complications: pulmonary HTN, cor pulmonale, lung cancer.
  • Prognosis: mean survival is 3 years.

• Asbestosis

  Key features

  • Due to heavy asbestos exposure. Latency period usually >10 years.
  • Spreads from lower zones to the whole lung.
  • A type of pneumoconiosis.
  • Employers must inform the HSE when they are aware of a case in an employee.

  Complications and prognosis

  • Highly variable prognosis.
  • 40% develop lung cancer, especially those who smoke.
  • A smaller proportion develop malignant mesothelioma.

  Other asbestos-related disease

  Note, these are not types of ILD:

  • Pleural plaques: asymptomatic pleural thickening on CXR, including the diaphragm. 'Holly leaf' appearance if on anterior pleura. Not an independent risk factor for other asbestos-related disease, but a marker of exposure so 15% develop mesothelioma.
  • Pleural fibrosis: secondary to pleural effusion, usually on one side and later the other. 'Benign' disease in that it rarely progresses, but does cause SOB.

• Silicosis and coal worker's pneumoconiosis (CWP)

  Background

  • Pathologically similar diseases with distinct etiologies.
  • Types of pneumoconiosis.
  • Employers must inform the HSE when they are aware of a case in an employee.

  Pathophysiology

  • Silicosis can result from any industrial processes involving sand, which settles in the lungs causing dense fibrosis with birefringent particles.
  • CWP: coal dust accumulates in distal bronchioles, leading to fibrosis.
  • Both spread from upper zones to whole lung.

  Clinical features

  • Simple CWP or simple chronic silicosis can be relatively benign conditions, with few or no symptoms. Results from long-term (10-20 years) low-level exposure.
  • Complicated CWP or accelerated silicosis can lead to progressive massive fibrosis, characterised by large fibrotic masses in the upper lobes. Results from shorter-term, higher exposures.

  Complications and prognosis

  • Highly variable prognosis, with some cases rapidly fatal and others not progressing at all.
  • Both conditions are linked to COPD, rheumatoid arthritis (Caplan's syndrome), and systemic sclerosis.
  • Silicosis is also linked to TB, lung cancer, and CKD.

• Hypersensitivity pneumonitis

  Pathophysiology

  • Non-IgE hypersensitivity reaction (type 3 or 4) to non-human protein (plant or animal) or chemicals conjugated to human protein. May lead to granuloma formation.
  • Usually affects upper lung zones.
  • Aka extrinsic allergic alveolitis.

  Causes

  There are many causes, but the following are the commonest:

  • Farmer's lung: reaction to Actinomycetes bacteria, especially Saccharopolyspora rectivirgula in hay. Gram +ve rods which form hyphae, hence the misnomer '-myces'.
  • Bird fancier's lung: reaction to avian protein.
  • Other common antigens: mold (e.g. from AC, humidifiers, ventilators; usually acute), occupational paints and plastics.

  Signs and symptoms

  Various time patterns:

  • Acute: hours post-exposure, with strong inflammatory response including non-productive cough, SOB, fevers, and malaise.
  • Subacute: weeks-months of exposure, with productive cough and SOB.
  • Chronic: months-years of exposure, often leading to fibrosis. Gradual onset of productive cough, SOB, and weight loss. Clubbing is often present.

  Prognosis

  If there is no significant fibrosis, and antigen is avoided, the prognosis is good.

• Investigations

  Chest imaging

  Anatomical locations of abnormalities:

  • Upper lobes: ank spond, hypersensitivity pneumonitis, silicosis/CWP, sarcoidosis/TB.
  • Lower lobes (commoner): IPF, asbestosis, drug-induced, connective-tissue disease (except ank spond).

  Opacification patterns:

  • Reticular: fine mesh of lines. Seen in IPF, asbestosis, and connective tissue disease.
  • Reticulonodular: multiple small nodules. Seen in pneumoconiosis and sarcoidosis.

  CXR

  • Normal in 10%.
  • IPF: small, white lungs, basal reticular opacities.
  • Asbestosis: linear fibrosis, pleural thickening.
  • CWP and silicosis: diffuse nodules if simple (also seen in sarcoidosis and TB), but solid mass in massive pulmonary fibrosis.
  • Sarcoidosis: bilateral hilar lymphadenopathy.

  High-resolution CT

  • Pulmonary fibrosis: lower zone reticular fibrosis. If extensive, cystic appearance and 'honeycombing'.
  • Asbestosis: similar to the CXR.
  • Hypersensitivity pneumonitis: ground-glass shadowing (↑opacity without obscuring vessels) in mosaic distribution (i.e. some areas affected, others not), which may come and go with symptoms.
  • Sarcoidosis: nodules beading along fissures.

  Other investigations

  Bedside:

  • O2 sats, followed by ABG if low.
  • ECG may show cor pulmonale.

  Bloods:

  • FBC: may be ↓Hb in IPF.
  • ↑ESR/CRP in acute HP and sometimes IPF.
  • If connective tissue disease suspected: ANA (SLE, systemic sclerosis), RF (RA), CK (polymyositis/dermatomyositis).
  • If sarcoid suspected: ACE, though sensitivity is low.
  • If HP suspected: antibodies to causative antigen (IgG precipitin test).

  Special tests:

  • PFT: restrictive picture, characterised by ↓FEV1, ↓FVC, ↓TLC, ↓DLCO. Sometimes mixed with obstructive picture, especially in pneumoconiosis as it may lead to COPD.
  • Lung biopsy is rarely needed, except for ambiguous IPF or suspected cancer. Carries risk of residual pain due to intercostal nerve damage.
  • Similarly, bronchoalveolar lavage may help if diagnosis is unclear, but rarely needed. Findings include ↓CD4/CD8 ratio in hypersensitivity pneumonitis, and ↑CD4/CD8 ratio in sarcoidosis.

• Management

  General measures

  • Basic care: flu and pneumococcal vaccine, smoking cessation, and pulmonary rehab.
  • If severe: O2 therapy, lung transplant.

  Specific treatments

  IPF:

  • PPI for co-morbid GORD, which may be a risk factor or complication.
  • Pirfenidone (antifibrotic) or nintendanib (tyrosine kinase inhibitor) to slow FVC decline, for patients with FVC 50-80% predicted. Pirfenidone also reduces exacerbations. Neither delay or reduce mortality.
  • Steroids in acute exacerbations, but long-term steroid monotherapy is not recommended.

  Hypersensitivity pneumonitis:

  • Avoid the antigen.
  • Prednisolone PO may reduce symptoms.