Interstitial lung disease
Interstitial lung disease (ILD), or diffuse parenchymal lung disease (DPLD), is a group of lung diseases affecting the interstitium (the tissue and space around the alveoli (air sacs of the lungs). It concerns alveolar epithelium, pulmonary capillary endothelium, basement membrane, and perivascular and perilymphatic tissues. It may occur when an injury to the lungs triggers an abnormal healing response. Ordinarily, the body generates just the right amount of tissue to repair damage, but in interstitial lung disease, the repair process goes awry and the tissue around the air sacs (alveoli) becomes scarred and thickened. This makes it more difficult for oxygen to pass into the bloodstream. The term ILD is used to distinguish these diseases from obstructive airways diseases.
|Interstitial lung disease|
|Other names||Diffuse parenchymal lung disease (DPLD)|
|End-stage pulmonary fibrosis of unknown origin, taken from an autopsy|
|Frequency||1.9 million (2015)|
Prolonged ILD may result in pulmonary fibrosis, but this is not always the case. Idiopathic pulmonary fibrosis is interstitial lung disease for which no obvious cause can be identified (idiopathic) and is associated with typical findings both radiographic (basal and pleural-based fibrosis with honeycombing) and pathologic (temporally and spatially heterogeneous fibrosis, histopathologic honeycombing, and fibroblastic foci).
In 2015, interstitial lung disease, together with pulmonary sarcoidosis, affected 1.9 million people. They resulted in 122,000 deaths.
- Inhaled substances
- Connective tissue and Autoimmune diseases
- Predominately in children
- Diffuse developmental disorders
- Growth abnormalities deficient alveolarisation
- Infant conditions of undefined cause
- ILD related to alveolar surfactant region
Investigation is tailored towards the symptoms and signs. A proper and detailed history looking for the occupational exposures, and for signs of conditions listed above is the first and probably the most important part of the workup in patients with interstitial lung disease. Pulmonary function tests usually show a restrictive defect with decreased diffusion capacity (DLCO).
A lung biopsy is required if the clinical history and imaging are not clearly suggestive of a specific diagnosis or malignancy cannot otherwise be ruled out. In cases where a lung biopsy is indicated, a trans-bronchial biopsy is usually unhelpful, and a surgical lung biopsy is often required.
High resolution CT of the chest is the preferred modality, and differs from routine CT of the chest. Conventional (regular) CT chest examines 7–10 mm slices obtained at 10 mm intervals; high resolution CT examines 1-1.5 mm slices at 10 mm intervals using a high spatial frequency reconstruction algorithm. The HRCT therefore provides approximately 10 times more resolution than the conventional CT chest, allowing the HRCT to elicit details that cannot otherwise be visualized.
Pattern of opacities
Acute: Alveolar hemorrhage syndromes, acute eosinophilic pneumonia, acute interstitial pneumonia, cryptogenic organizing pneumonia
Chronic: Chronic eosinophilic pneumonia, cryptogenic organizing pneumonia, lymphoproliferative disorders, pulmonary alveolar proteinosis, sarcoidosis
- Linear or reticular opacities
Acute: Pulmonary edema
Chronic: Idiopathic pulmonary fibrosis, connective tissue associated interstitial lung diseases, asbestosis, sarcoidosis, hypersensitivity pneumonitis, drug-induced lung disease
- Small nodules
Acute: Hypersensitivity pneumonitis
Chronic: Hypersensitivity pneumonitis, sarcoidosis, silicosis, coal workers pneumoconiosis, respiratory bronchiolitis, alveolar microlithiasis
- Cystic airspaces
Chronic: Pulmonary langerhans cell histiocytosis, pulmonary lymphangioleiomyomatosis, honeycomb lung caused by IPF or other diseases
Ground glass opacities
Acute: Alveolar hemorrhage syndromes, pulmonary edema, hypersensitivity pneumonitis, acute inhalational exposures, drug-induced lung diseases, acute interstitial pneumonia
Chronic: Nonspecific interstitial pneumonia, respiratory bronchiolitis associated interstitial lung disease, desquamative interstitial pneumonia, drug-induced lung diseases, pulmonary alveolar proteinosis
- Thickened alveolar septa
Acute: Pulmonary edema
- Upper lung predominance
Pulmonary Langerhans cell histiocytosis, silicosis, coal workers pneumoconiosis, carmustine related pulmonary fibrosis, respiratory broncholitis associated with interstitial lung disease.
- Lower lung predominance
Idiopathic pulmonary fibrosis, pulmonary fibrosis associated with connective tissue diseases, asbestosis, chronic aspiration
- Central predominance (perihilar)
- Peripheral predominance
- Pleural effusion or thickening
Pulmonary edema, connective tissue diseases, asbestosis, lymphangitic carcinomatosis, lymphoma, lymphangioleiomyomatosis, drug-induced lung diseases
For some types of paediatric ILDs and few forms adult ILDs, genetic causes have been identified. These may be identified by blood tests. For a limited number of cases this is a definite advantage, as a precise molecular diagnosis can be done; frequently then there is no need for a lung biopsy. Testing is available for
ILDs related to alveolar surfactant region
Surfactant-Protein-B Deficiency (Mutations in SFTPB)
Surfactant-Protein-C Deficiency (Mutations in SFTPC)
ABCA3-Deficiency (Mutations in ABCA3)
Brain Lung Thyroid Syndrome (Mutations in TTF1)
Congenital Pulmonary Alveolar Proteinosis (Mutations in CSFR2A, CSFR2B)
Diffuse developmental disorder
Alveolar Capillary Dysplasia (Mutations in FoxF1)
Idiopathic pulmonary fibrosis
Mutations in telomerase reverse transcriptase (TERT)
Mutations in telomerase RNA component (TERC)
Mutations in the regulator of telomere elongation helicase 1 (RTEL1)
Mutations in poly(A)-specific ribonuclease (PARN)
ILD is not a single disease, but encompasses many different pathological processes. Hence treatment is different for each disease.
If a specific occupational exposure cause is found, the person should avoid that environment. If a drug cause is suspected, that drug should be discontinued.
Many cases due to unknown or connective tissue-based causes are treated with corticosteroids, such as prednisolone. Some people respond to immunosuppressant treatment. Oxygen therapy at home is recommended in those with significantly low oxygen levels.
Pulmonary rehabilitation appears to be useful. Lung transplantation is an option if the ILD progresses despite therapy in appropriately selected patients with no other contraindications.
On October 16, 2014, the Food and Drug Administration approved a new drug for the treatment of Idiopathic Pulmonary Fibrosis (IPF). This drug, Ofev (nintedanib), is marketed by Boehringer Ingelheim Pharmaceuticals, Inc. This drug has been shown to slow the decline of lung function although the drug has not been shown to reduce mortality or improve lung function. The estimated cost of the drug per year is approximately $94,000.
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