Interstitial lung disease (ILD), or diffuse parenchymal lung disease (DPLD),
is a group of
respiratory diseases affecting the
interstitium
The interstitium is a contiguous fluid-filled space existing between a structural barrier, such as a cell membrane or the skin, and internal structures, such as organs, including muscles and the circulatory system. The fluid in this space is cal ...
(the tissue and space around the
alveoli Alveolus (; pl. alveoli, adj. alveolar) is a general anatomical term for a concave cavity or pit.
Uses in anatomy and zoology
* Pulmonary alveolus, an air sac in the lungs
** Alveolar cell or pneumocyte
** Alveolar duct
** Alveolar macrophage
* ...
(air sacs)) of the
lung
The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
s.
It concerns
alveolar Alveolus (; pl. alveoli, adj. alveolar) is a general anatomical term for a concave cavity or pit.
Uses in anatomy and zoology
* Pulmonary alveolus, an air sac in the lungs
** Alveolar cell or pneumocyte
** Alveolar duct
** Alveolar macrophage
* ...
epithelium
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...
, pulmonary
capillary endothelium,
basement membrane
The basement membrane is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between Epithelium, epithelial tissues including mesot ...
, 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
Obstructive lung disease is a category of respiratory disease characterized by airway obstruction. Many obstructive diseases of the lung result from narrowing (obstruction) of the smaller bronchi and larger bronchioles, often because of excessive ...
.
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
Sarcoidosis (also known as ''Besnier-Boeck-Schaumann disease'') is a disease involving abnormal collections of inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph nodes. Less commonly af ...
, 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
An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
**
Sarcoidosis
**
Rheumatoid arthritis
**
Systemic lupus erythematosus
Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...
**
Systemic sclerosis
**
Polymyositis
**
Dermatomyositis
**
Antisynthetase syndrome
Anti-synthetase syndrome is an autoimmune disease associated with interstitial lung disease, dermatomyositis, and polymyositis.
Signs and symptoms
As a syndrome, this condition is poorly defined. Diagnostic criteria require one or more antisynth ...
* Inhaled substances (
Pneumoconiosis
Pneumoconiosis is the general term for a class of interstitial lung disease where inhalation of dust ( for example, ash dust, lead particles, pollen grains etc) has caused interstitial fibrosis. The three most common types are asbestosis, silicos ...
)
** Inorganic
***
Silicosis
Silicosis is a form of occupational lung disease caused by inhalation of crystalline silica dust. It is marked by inflammation and scarring in the form of nodular lesions in the upper lobes of the lungs. It is a type of pneumoconiosis. Silicos ...
***
Asbestosis
***
Berylliosis
*** Industrial printing chemicals (e.g. carbon black, ink mist)
** Organic
***
Hypersensitivity pneumonitis (extrinisic allergic alveolitis)
* Drug-induced
**
Antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
s
**
Chemotherapeutic drugs
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
**
Antiarrhythmic agents
* Cigarette smoking
* Infection
**
Coronavirus disease 2019
Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease quickly ...
**
Atypical pneumonia
**
Pneumocystis pneumonia (PCP)
''Pneumocystis'' pneumonia (PCP), also known as ''Pneumocystis jirovecii'' pneumonia (PJP), is a form of pneumonia that is caused by the yeast-like fungus ''Pneumocystis jirovecii''.
''Pneumocystis'' specimens are commonly found in the lungs of ...
**
Tuberculosis
** ''
Chlamydia trachomatis''
**
Respiratory Syncytial Virus
* Malignancy
**
Lymphangitic carcinomatosis
* Predominately in children
**
Diffuse developmental disorders
Diffusion is the net movement of anything (for example, atoms, ions, molecules, energy) generally from a region of higher concentration to a region of lower concentration. Diffusion is driven by a gradient in Gibbs free energy or chemica ...
**
Growth abnormalities 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.
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, 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 B is an essential lipid-associated protein found in pulmonary surfactant. Without it, the lung would not be able to inflate after a deep breath out. It rearranges lipid molecules in the fluid lining the lung so that tiny air sa ...
)
Surfactant-Protein-C Deficiency (Mutations in
SFTPC
Surfactant protein C (SP-C), is one of the pulmonary surfactant proteins. In humans this is encoded by the ''SFTPC'' gene.
It is a membrane protein.
Structure
SFTPC is a 197-residue protein made up of two halves: a unique N-terminal propept ...
)
ABCA3-Deficiency (Mutations in
ABCA3
ATP-binding cassette sub-family A member 3 is a protein that in humans is encoded by the ''ABCA3'' gene.
The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins ...
)
Brain Lung Thyroid Syndrome (Mutations in
TTF1)
Congenital Pulmonary Alveolar Proteinosis (Mutations in CSFR2A, CSFR2B)
Diffuse developmental disorder
Alveolar Capillary Dysplasia (Mutations in
FoxF1
Forkhead box protein F1 (FOXF1) is a protein that in humans is encoded by the ''FOXF1'' gene.
Function
This gene belongs to the forkhead family of transcription factors which is characterized by a distinct forkhead domain. FOX1 protein is imp ...
)
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
A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...
cause is suspected, that drug should be discontinued.
Many cases due to
unknown or
connective tissue
Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...
-based causes are treated with
corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...
s,
such as
prednisolone. Some people respond to
immunosuppressant treatment.
Oxygen therapy
Oxygen therapy, also known as supplemental oxygen, is the use of oxygen as medical treatment. Acute indications for therapy include hypoxemia (low blood oxygen levels), carbon monoxide toxicity and cluster headache. It may also be prophylactica ...
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, 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), 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