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 (extrinsic 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