Interstitial lung disease (ILD), or diffuse parenchymal lung disease (DPLD),
is a group of
respiratory disease
Respiratory diseases, or lung diseases, are pathological conditions affecting the organs and tissues that make gas exchange difficult in air-breathing animals. They include conditions of the respiratory tract including the trachea, bronchi, bro ...
s 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 Mural cells are the vascular smooth muscle cells (vSMCs), and pericytes, of the microcirculation. Both types are in close contact with the endothelial cells lining the capillaries, and are important for vascular development and stability. Mural cel ...
and
perilymphatic
Perilymph is an extracellular fluid located within the inner ear. It is found within the scala tympani and scala vestibuli of the cochlea. The ionic composition of perilymph is comparable to that of plasma and cerebrospinal fluid. The major ca ...
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
Pulmonary fibrosis is a condition in which the lungs become scarred over time. Symptoms include shortness of breath, a dry cough, feeling tired, weight loss, and nail clubbing. Complications may include pulmonary hypertension, respiratory failu ...
, 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
Cryptogenic organizing pneumonia (COP), formerly known as bronchiolitis obliterans organizing pneumonia (BOOP), is an inflammation of the bronchioles ( bronchiolitis) and surrounding tissue in the lungs. It is a form of idiopathic interstitial pn ...
(COP): also known by the older name bronchiolitis obliterans organizing pneumonia (BOOP)
*
Lymphoid interstitial pneumonia
Lymphocytic interstitial pneumonia (LIP) is a syndrome secondary to autoimmune and other lymphoproliferative disorders. Symptoms include fever, cough, and shortness of breath. Lymphocytic interstitial pneumonia applies to disorders associated w ...
(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
Systemic scleroderma, or systemic sclerosis, is an autoimmune rheumatic disease characterised by excessive production and accumulation of collagen, called fibrosis, in the skin and internal organs and by injuries to small arteries. There are two ...
**
Polymyositis
**
Dermatomyositis
**
Antisynthetase syndrome
* Inhaled substances (
Pneumoconiosis)
** Inorganic
***
Silicosis
***
Asbestosis
***
Berylliosis
Berylliosis, or chronic beryllium disease (CBD), is a chronic allergic-type lung response and chronic lung disease caused by exposure to beryllium and its compounds, a form of beryllium poisoning. It is distinct from acute beryllium poisoning, wh ...
*** Industrial printing chemicals (e.g. carbon black, ink mist)
** Organic
***
Hypersensitivity pneumonitis
Hypersensitivity pneumonitis (HP) or extrinsic allergic alveolitis (EAA) is a syndrome caused by the repetitive inhalation of antigens from the environment in susceptible or sensitized people. Common antigens include molds, bacteria, bird dropping ...
(extrinisic allergic alveolitis)
* Drug-induced
**
Antibiotics
**
Chemotherapeutic drugs
**
Antiarrhythmic agents
Antiarrhythmic agents, also known as cardiac dysrhythmia medications, are a group of pharmaceuticals that are used to suppress abnormally fast rhythms ( tachycardias), such as atrial fibrillation, supraventricular tachycardia and ventricular ta ...
* Cigarette smoking
* Infection
**
Coronavirus disease 2019
**
Atypical pneumonia
Atypical pneumonia, also known as walking pneumonia, is any type of pneumonia not caused by one of the pathogens most commonly associated with the disease. Its clinical presentation contrasts to that of "typical" pneumonia. A variety of microorgan ...
**
Pneumocystis pneumonia (PCP)
**
Tuberculosis
** ''
Chlamydia trachomatis
''Chlamydia trachomatis'' (), commonly known as chlamydia, is a bacterium that causes chlamydia, which can manifest in various ways, including: trachoma, lymphogranuloma venereum, nongonococcal urethritis, cervicitis, salpingitis, pelvic infla ...
''
**
Respiratory Syncytial Virus
Respiratory syncytial virus (RSV), also called human respiratory syncytial virus (hRSV) and human orthopneumovirus, is a common, contagious virus that causes infections of the respiratory tract. It is a negative-sense, single-stranded RNA virus. ...
* Malignancy
**
Lymphangitic carcinomatosis
* Predominately in children
**
Diffuse developmental disorders
**
Growth abnormalities deficient alveolarisation
**
Infant conditions of undefined cause
An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...
**
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
Malignancy () is the tendency of a medical condition to become progressively worse.
Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
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.
X-rays
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
Pulmonary alveolar proteinosis (PAP) is a rare lung disorder characterized by an abnormal accumulation of surfactant-derived lipoprotein compounds within the alveoli of the lung. The accumulated substances interfere with the normal gas exchange and ...
, 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
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, 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, 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 at home is recommended in those with significantly low oxygen levels.
Pulmonary rehabilitation appears to be useful with the benefits being sustainable longer term with improvement in exercise capacity,
dyspnoea
Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing dis ...
, and quality of life.
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
Nintedanib, sold under the brand names Ofev and Vargatef, is an oral medication used for the treatment of idiopathic pulmonary fibrosis and along with other medications for some types of non-small-cell lung cancer.
In March 2020, it was appro ...
), 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
::19. ^Health, St Vincent’s Heart. “Home.” St Vincent's Lung Health, St Vincent's Heart Health, www.svhlunghealth.com.au/conditions/ild-interstitial-lung-disease.
::20. ^“Interstitial Lung Disease: Symptoms, Causes, Tests and Treatment.” Cleveland Clinic, my.clevelandclinic.org/health/diseases/17809-interstitial-lung-disease.
External links
*
{{DEFAULTSORT:Interstitial Lung Disease
Respiratory diseases principally affecting the interstitium
Lung disorders