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:

• Sarcoidosis
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Systemic sclerosis
• Polymyositis
• Dermatomyositis
• Antisynthetase syndrome

• Inorganic
  • Silicosis
  • Asbestosis
  • Berylliosis
  • Industrial printing chemicals (e.g. carbon black, ink mist)
• Organic
  • Hypersensitivity pneumonitis (extrinsic allergic alveolitis)

• Antibiotics (e.g., nitrofurantoin and sulfa drugs)
• Chemotherapeutic drugs
• Antiarrhythmic agents
• Cigarette smoking[10]
  • Smoking-related interstitial fibrosis (SRIF) is an example of a type of interstitial lung disease known to be caused by smoking.

• Coronavirus disease 2019 (COVID-19)[11]
• Atypical pneumonia
• Pneumocystis pneumonia (PCP)
• Tuberculosis
• Chlamydia trachomatis
• Respiratory syncytial virus

• Lymphangitic carcinomatosis

• Diffuse developmental disorders
• Growth abnormalities and deficient alveolarisation
• Infant conditions of undefined cause
• ILD related to alveolar surfactant region

Most patients with suspected ILD are likely to undergo complete pulmonary function testing. These tests are useful in diagnosis and determining severity of the disease.[12]

Although there is large diversity in interstitial lung disease, most follow a restrictive pattern. Restrictive defects are defined by decreased TLC (total lung capacity), RV (residual volume), FVC (forced vital capacity) and FEV1 (forced expiratory volume in one second). As both FVC and FEV1 are reduced, the FVC to FEV1 ratio remains normal or is increased.[12]

As disease progression increases and the lungs become stiffer lung volumes will continue to decrease; lower TLC, RV, FVC and FEV1 scores are associated with a more severe disease progression and poorer prognosis.[12]

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.[13][14]

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.[13][15]

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.[13]

Interstitial lung diseases can be classified according to radiologic patterns.[13]

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 idiopathic pulmonary fibrosis (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[13]

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 (ILD-CTD)
• Asbestosis
• Chronic aspiration

Central predominance (perihilar)

• Sarcoidosis
• Berylliosis

Peripheral predominance

• Idiopathic pulmonary fibrosis
• Chronic eosinophilic pneumonia
• Cryptogenic organizing pneumonia[13]

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[13]

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 and/or 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)

Oxygen therapy at home is recommended in those with significantly low oxygen levels.[17]

Pulmonary rehabilitation appears to be useful with the benefits being sustainable longer term with improvement in exercise capacity, dyspnoea, and quality of life.[18] Lung transplantation is an option if the ILD progresses despite therapy in appropriately selected patients with no other contraindications.[19][20]

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.[21]