Interstitial lung disease
Interstitial lung disease (ILD), or diffuse parenchymal lung disease (DPLD), is a group of respiratory 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 is disrupted, 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 disease presents itself with the following symptoms: shortness of breath, nonproductive coughing, fatigue, and weight loss, which tend to develop slowly, over several months. The average rate of survival for someone with this disease is between three and five years. The term ILD is used to distinguish these diseases from obstructive airways diseases.

There are specific types in children, known as children's interstitial lung diseases. The acronym ChILD is sometimes used for this group of diseases.

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.

Causes 

An ILD may be classified as to whether its cause is not known (idiopathic) or known (secondary).

Idiopathic
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). They were subclassified by the American Thoracic Society in 2002 into 7 subgroups:
 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
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 (e.g., nitrofurantoin and sulfa drugs)
 Chemotherapeutic drugs
 Antiarrhythmic agents
 Cigarette smoking
 Smoking-related interstitial fibrosis (SRIF) is an example of a type of interstitial lung disease known to be caused by smoking.

Infection
 Coronavirus disease 2019 (covid-19)
 Atypical pneumonia
 Pneumocystis pneumonia (PCP)
 Tuberculosis
 Chlamydia trachomatis
 Respiratory syncytial virus

Malignancy
 Lymphangitic carcinomatosis

Childhood interstitial lung disease and ILD predominately in children 

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

Diagnosis 

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.

Pulmonary function testing 
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.

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.

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.

X-ray and CT (radiography and computed tomography) 
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.

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.

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.

Interstitial lung diseases can be classified according to radiologic patterns.

Pattern of opacities 
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

Distribution 

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

Associated findings 

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

Genetic testing 

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 and/or 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)

Treatment 

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

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

Antibodies and inhibitors 
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.

References

External links 

 

Respiratory diseases principally affecting the interstitium
Lung disorders