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Background

  • Interstitial lung diseases (ILDs) are a group of over 200 disease entities which affect the lung interstitium and share similar clinical and radiological manifestations
  • ILDs cause morbidity and mortality in all age groups
  • Idiopathic pulmonary fibrosis (IPF) is the most common ILD in older adults, and is often associated with a poor prognosis
  • Sarcoidosis is more common in younger adults and generally has a more benign prognosis

Discussion

  • Because ILD can progress to pulmonary fibrosis, early detection is important
  • The clinical course of ILD varies considerably, largely determined by the underlying cause
  • While some forms of ILD remain essentially untreatable, many forms respond well to treatment
  • It is imperative that a prompt and accurate diagnosis of the underlying cause is made

Interstitial Lung Disease Incidence

  • Extrapolating from population based registries in other countries suggests an incidence around 30 in 100 000 per year manifestations
  • Probably somewhat higher in Scandinavia where sarcoidosis is more common

Aetiology

  • ILDs with known aetiology, most commonly due to occupational and environmental exposures and ILD associated with connective tissue diseases (CTD)
  • ILDs with unknown aetiology including idiopathic pulmonary fibrosis (IPF) and sarcoidosis

A brief overview

  • Idiopathic pulmonary fibrosis (IPF) is the most common ILD in older adults (peak age of onset is 50-60 years of age group) and it has a poor prognosis (median survival 3-5 years)
  • Sarcoidosis is a multiorgan granulomatous disease which often involves the lung. It occurs in younger adults (peak incidence 20-50 years) and generally has a good prognosis. There’s treatment that most patients respond well to.
  • CTD of all types can cause ILD, with an overall incidence across the range of diseases of 15%. Prognosis and treatment vary depending vary depending upon histopathologic/ radiologic findings and the course of the underlying connective tissue disease.

CTD-associated ILD

Rheumatic disease

Frequency of ILD (%)


Systemic sclerosis

45 (clinically significant)


Rheumatoid arthritis

20 – 30


Polymyositis / dermatomyositis

20-50 (Frequency may be higher based on recent studies)


Sjögren’s syndrome

up to 25


Systemic lupus erythematosus

2-8


Mixed connective tissue disease

20-60


  • Pneumoconioses (due to inhaled inorganic dusts, eg. asbestos, coal, silica) account for a significant proportion of all ILD but their incidence is decreasing due to improved work place practises
  • Hypersensitivity pneumonitis (secondary to inhaled organic dusts / ellergens, eg. bird dander, domestic fungal spores) is important to recognize and generally has a favorable prognosis if the allergen is avoided
  • Idiopathic interstitial pneumonia (IIP) that are not IPF account for a small portion of cases and in general have a significantly better prognosis than IPF
  • Dryg induced ILDs are rare but important due to the preventable and potentially reversible nature of the exposure. Many different classes of drugs can cause ILD. A useful website describing drug induced lung diseases is available at www.pneumotox.com

How ILD comes to clinical attention

Symptoms

  • Progressive breathlessness with exercise
  • Persistent nonproductive cough
  • Symptoms related to another disease (eg. connective tissue disease)
  • The rate of progression of symptoms are generally slow (months to years)
  • Symptoms are often attributed to aging or deconditioning, resulting in a delay of diagnosis
  • Symptoms can occasionally mimic peumonia

Abnormal investigations

  • Chest X-ray
  • Lung function abnormalities – particularly a restrictive ventilatory pattern

A detailed medical history is essential

  • Any symptoms to suggest connective tissue disease? (joint pain, mouth dryness, hereditary)
  • Smoking history?
  • Medication history (Even those that are not used anymore)
  • Occupational exposures?
  • Environmental exposures?

The physical examination

  • Inspiratory crackles and digital clubbing (common in IPF and asbestosis and rare in sarcoidosis and hypersensitivity pneumonitis)
  • Examination looking for potential underlying causes, such as connective tissue diseases and sarcoidosis

Investigations

Lung function tests (spirometry, all lung volumes and DLCO)

  • Most patients have a restrictive lung defect with a reduction in lung volumes, and a decrease in DLCO
  • Obstructive or mixed lung function defects are seen in some ILDs such as sarcoidosis
Pulsoximetry during 6MWT (= 6 minute walk test)
  • Hypoxemia at rest or on exercise may be present
Chest X-ray
  • Usually the first radiological investigation ordered
  • Has limited diagnostic sensitivity and specificity in ILD (one can have a normal X-ray yet still have a lung disease)
  • Many ILDs remain occult or are not correctly diagnosed on chest x-ray, appearing as a nonspecific “reticulonodular pattern”
  • Usually adequate to follow disease development
High resolution computed tomography (HRCT) 
  • Has a greater diagnostic accuracy than X-ray
  • Is the imaging of choice when ILD is suspected
  • Some patterns are suggestive, or even diagnostic, and may avoid the need of further investigations
  • Ask for images at full inspiration and expiration (air trapping)
Bronchoscopy
  • Bronchoalveolar lavage (BAL) is useful to exclude infections (which can masquerade as ILD)
  • The diagnostic yield of transbronchial biopsies is much lower than surgical lung biopsy. Can be used to diagnose sarcoidosis and hypersensitivity pneumonitis, and to exclude malignancy
  • Bronchoscopy is performed as a day procedure and requires only mild sedation
Surgical lung biopsy
  • Is required to diagnose most types of ILD
  • Is most commonly performed with video assisted thoracic surgery (VATS), preferentially the left lung and not the lingula segment
  • Requires general anasthesia and mechanical single lung ventilation during the procedure
  • In some cases of IPF with classical radiologic features lung biopsies is not needed for diagnosis

Management

  • Once ILD is suspected on clinical features, HRCT scan and lung function tests, prompt referral to a respiratory specialist is warranted
  • The management is complex and varies depending on the underlying diagnosis
  • There are general measures that apply for most forms of ILD

General measures

  • Pulmonary rehabilitation is beneficial for most ILD patients
  • Smoking cessation is of paramount importance
  • Oxygen therapy may be considered if there is significant hypoxia at rest or on exercise
  • Identify and treat other commonly associated diseases such as gastroesophageal reflux disease, pulmonary hypertension, depression and anxiety

 Specific measures

Idiopathic pulmonary fibrosis

  • N-acetyl cysteine in high dosage
  • Pirfenidon, this is a new drug. Have a slightly effect but is not a miracle drug.
  • Lung transplantation, especially in young people
  • End of life care (best supportive care)
Sarcoidosis & connective tissue diseases
  • Prednisolone combined with different immunosuppressive agents
Hypersensitivity pneumonitis
  • Avoidance of the antigen
  • Prednisolone is often also required

IPF- Pathogenesis

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Diagnostic algorithm for IPF

 

Natural history of IPF

The disease progression can vary considerably between different patients. But a thumb of rule is that if the vital capacity worsen >10 % over the first 6 months, then patient has a worse prognosis.

Acute interstitial pneumonia, AIP

Normal lung

AIP

Shows alveolar septa thickening resulting from proliferating spindle cells. There is only a minor infiltrate of mononuclear inflammatory cells. The thickened alveolar septa are lined by hyperplastic pneumocytes. That is there is a shortage of inflammatory cells and abundance of fibroblasts.

 

Is IPF exacerbation / AIP due to recruited fibrocytes?

Increase of lungfibroblasts (and subsequent collagen deposition) by:

1. Proliferation of resident fibroblasts

2. Epithelial – mesenchymal transition (EMT)

3. Recruitment of mesenchymal progenitor cells (fibrocytes)

More than 5% fibrocytes in blood predicts IPF with worse prognosis. (Press for larger pic)

Take home messages

  • ILDs are a variety of lung conditions that primarily affect the lung interstitium
  • IDL should be considered in any person presenting with breathlessness or cough along with abnormal chest radiology or lung function tests
  • HRTC is the best imaging modality
  • Early referral to a respiratory specialist for multidisciplinary management
  • Simvastatin can give rise to fibrosis

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