Summary
Interstitial lung diseases (ILDs) are a heterogeneous group of disorders marked by inflammatory changes in the alveoli. ILDs may be idiopathic or due to secondary causes such as autoimmune disease, pharmacotherapeutic changes, or exposure to toxic substances. These changes can cause irreversible fibrosis and impaired pulmonary function. The main symptoms are exertional dyspnea and a dry cough. Bibasilar inspiratory crackles or rales are usually heard on auscultation. Treatment is based on the underlying cause. Immune modulators and corticosteroids are used in cases of unknown etiology. In advanced stages of disease ILD can result in pulmonary insufficiency and respiratory heart failure with right ventricular insufficiency.
Etiology
Occupational, environmental, and iatrogenic causes
- Pneumoconioses
- Radiation pneumonitis
Drugs
- Chemotherapeutic agents
- Other agents
Secondary to underlying disease
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Granulomatous ILD
- Sarcoidosis: noncaseating granulomas in multiple organs, including the lung
- Pulmonary Langerhans cell histiocytosis
- Granulomatosis with polyangiitis
- Eosinophilic granulomatosis with polyangiitis
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Hypersensitivity reactions
- Hypersensitivity pneumonitis
- Eosinophilic pneumonia
- Connective tissue disorders
- Infectious diseases
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Alveolar filling diseases
- Goodpasture syndrome
- Idiopathic pulmonary hemosiderosis
- Pulmonary alveolar proteinosis
- Bronchoalveolar carcinoma
Idiopathic ILDs
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Idiopathic pulmonary fibrosis (IPF)
- Most common
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Risk factors
- Cigarette smoking
- Environmental and occupational exposures
- Chronic aspiration
- Genetic predisposition
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Other idiopathic subtypes
- Acute interstitial pneumonia (AIP): an idiopathic, interstitial lung disease with an acute onset that can progress rapidly to respiratory failure
- Cryptogenic organizing pneumonia (COP): a rare, noninfectious type of pneumonia that is characterized by inflammation of the bronchioles and the surrounding structures
- Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD)
- Desquamative interstitial pneumonia (DIP)
- Nonspecific interstitial pneumonia (NSIP)
- Lymphoid interstitial pneumonia (LIP)
- Idiopathic pleuroparenchymal fibroelastosis
References:[1]
Pathophysiology
Repeated cycles of tissue injury in the lung parenchyma with aberrant wound healing → collagenous fibrosis → remodeling of the pulmonary interstitium [2]
Clinical features
-
Main symptoms
- Exertional dyspnea that progresses to dyspnea at rest: Short shallow breaths may be taken by the patient to avoid dyspnea. [3]
- Persistent nonproductive cough
- Bibasilar, inspiratory crackles or rales on auscultation
- Fatigue
-
Later stages of disease
- Digital clubbing due to chronic hypoxia
- Loud inspiratory squeaks
Diagnostics
Due to the wide variety of subtypes and symptoms, there is no generally recommended diagnostic algorithm. Physical examination, serology, pulmonary function tests, and imaging (chest X-ray, CT scan) is performed almost always, while lavage or biopsy depend on the individual case.
-
Pulmonary function tests
- Restrictive lung disease (e.g., low lung volumes, high/normal FEV1/FVC ratio)
- Decreased diffusing capacity for CO (DLCO): highly sensitive parameter
-
Laboratory tests
- Arterial blood samples show elevated alveolar-arterial partial pressure of oxygen gradient and decreased partial pressure of oxygen.
- Screen for rheumatic and autoimmune diseases.
-
Chest X-ray
- Normal in approx. 10% of patients
- Increase in reticular opacities (sign of fibrosis)
- Ground-glass opacities
-
CT or HR-CT
- Honeycombing: multiple cystic lesions within the lung parenchyma due to fibrosis
- Traction bronchiectasis: irreversible dilatation of the bronchi and bronchioles due to fibrosis
- Irregular thickening of the interlobular septa
-
Biopsy
- Indications: atypical or rapidly progressive symptoms
- In patients with minimal signs or symptoms and stable disease, close observation (e.g., PFTs, HR-CTs over several months) may be sufficient.
-
Bronchoalveolar lavage [4]
- May be indicated in patients with acute and rapidly progressive respiratory symptoms, sarcoidosis, hypersensitivity pneumonitis, or IPF
- Less invasive than lung biopsy
Overview of pneumoconioses
- Etiology: : mostly occupational exposure
- Pathophysiology: inhalation of dust particles →; phagocytosis by alveolar macrophages → destruction of alveolar macrophages, inflammatory reaction → scarring, granuloma formation
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Common clinical features
- Cough and progressive exertional dyspnea are the most common symptoms.
- Pulmonary fibrosis, cor pulmonale, lung cancer, and Caplan syndrome are possible complications of all types of pneumoconioses. [5]
| Differential diagnoses of pneumoconioses [6] | ||||
|---|---|---|---|---|
| Type | Etiology | Population at risk | Clinical features | Chest x-ray |
| Asbestosis |
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| Silicosis |
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| Aluminosis [7][8] |
|
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| Anthracosis [9][10] |
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| Coal workers' pneumoconiosis [9][10] |
|
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| |
| Berylliosis |
|
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| Pulmonary siderosis [13][14] |
|
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Although coal is mined from under the earth, the upper lobes of the lungs are primarily affected.
Treatment
- In secondary disease, the first step is to limit exposure to the toxic substance, cease therapy with the drug causing symptoms, or treat the underlying disease.
- Antibiotics if bacterial interstitial pneumonia is suspected
- Corticosteroids and immune modulators
- Pirfenidone and nintedanib are commonly used for ILD.
- Oxygen for symptomatic or end-stage ILD
- Lung transplantation in end-stage ILD
- The majority of patients with IPF (> 70%) do not respond to therapy and experience progressive respiratory failure.
References:[1][15]