Interstitial lung disease

Idiopathic interstitial pneumonia is the term given to ILDs with an unknown cause. They represent the majority of cases of interstitial lung diseases (up to two-thirds of cases).[8] They were subclassified by the American Thoracic Society in 2002 into 7 subgroups:[9]

• Idiopathic pulmonary fibrosis (IPF): the most common subgroup
• Desquamative interstitial pneumonia (DIP)
• Acute interstitial pneumonia (AIP): also known as Hamman-Rich syndrome
• Nonspecific interstitial pneumonia (NSIP)
• Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD)
• Cryptogenic organizing pneumonia (COP): also known by the older name bronchiolitis obliterans organizing pneumonia (BOOP)
• Lymphoid interstitial pneumonia (LIP)

Secondary ILDs are those diseases with a known etiology, including:

• Connective tissue and Autoimmune diseases
  • Sarcoidosis
  • Rheumatoid arthritis
  • Systemic lupus erythematosus
  • Systemic sclerosis
  • Polymyositis
  • Dermatomyositis
  • Antisynthetase syndrome
• Inhaled substances (Pneumoconiosis)
  • Inorganic
    • Silicosis
    • Asbestosis
    • Berylliosis
    • Industrial printing chemicals (e.g. carbon black, ink mist)
  • Organic
    • Hypersensitivity pneumonitis (extrinisic allergic alveolitis)
• Drug-induced
  • Antibiotics
  • Chemotherapeutic drugs
  • Antiarrhythmic agents
• Infection
  • Coronavirus disease 2019[10]
  • Atypical pneumonia
  • Pneumocystis pneumonia (PCP)
  • Tuberculosis
  • Chlamydia trachomatis
  • Respiratory Syncytial Virus
• Malignancy
  • Lymphangitic carcinomatosis
• Predominately in children
  • Diffuse developmental disorders
  • Growth abnormalities deficient alveolarisation
  • Infant conditions of undefined cause
  • ILD related to alveolar surfactant region

Chest radiography is usually the first test to detect interstitial lung diseases, but the chest radiograph can be normal in up to 10% of patients, especially early in the disease process.[12][13]

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.[12][14]

Radiologic appearance alone however is not adequate and should be interpreted in the clinical context, keeping in mind the temporal profile of the disease process.[12]

Interstitial lung diseases can be classified according to radiologic patterns.[12]

Consolidation

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

Chronic: Lymphangitic carcinomatosis, pulmonary alveolar proteinosis, sarcoidosis, pulmonary veno occlusive disease[12]

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)

Sarcoidosis, berylliosis

Peripheral predominance

Idiopathic pulmonary fibrosis, chronic eosinophilic pneumonia, cryptogenic organizing pneumonia[12]

Pleural effusion or thickening

Pulmonary edema, connective tissue diseases, asbestosis, lymphangitic carcinomatosis, lymphoma, lymphangioleiomyomatosis, drug-induced lung diseases

Lymphadenopathy

Sarcoidosis, silicosis, berylliosis, lymphangitic carcinomatosis, lymphoma, lymphocytic interstitial pneumonia[12]

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

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)

Alveolar Capillary Dysplasia (Mutations in FoxF1)

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)