Interstitial lung disease is difficult to understand. There are numerous different types and subtypes, and the nomenclature and classification are confusing. To complicate matters further, there is variability within and overlap between types and subtypes.
Essentially, abnormal fibroblastic activity occurs in the lung interstitial tissue. This is usually initiated by an environmental trigger and is thought to develop in individuals with some sort of genetic predisposition. The resultant fibrosis can lead to impairment of lung structure and function.
Different types of interstitial lung disease have different patterns of fibrosis. In idiopathic pulmonary fibrosis, there is a diffuse network of fibrosis in affected areas of lung. In coal workers pneumoconiosis, there are focal deposits of fibrous tissue. These can increase in size to form nodules or large masses.
Interstitial lung disease characteristically causes a restrictive deficit in lung function. However, in many patients there is a degree of airway obstruction.
Most interstitial lung diseases are more common in smokers.
THE MAIN TYPES OF INTERSTITIAL LUNG DISEASE
- Interstitial lung disease of unknown cause i.e. idiopathic pulmonary fibrosis.
- Interstitial lung disease associated with connective tissue disorders i.e. scleroderma.
- Interstitial lung disease associated with antigen inhalation i.e. farmers lung.
- Interstitial lung disease associated with inorganic dust inhalation i.e. coal workers pneumoconiosis.
- Interstitial lung disease associated with sarcoidosis.
- Interstitial lung disease associated with drugs.
- Interstitial lung disease associated with radiotherapy.
As you can imagine, when assessing a patient with suspected interstitial lung disease, it is very important to check for symptoms or signs that may indicate an underlying connective tissue disorder or sarcoidosis, possible exposure to organic antigens such as moulds, exposure to mineral dusts, medication use and any history of radiotherapy.
To start with, I am going to describe idiopathic pulmonary fibrosis in detail. After that, I will briefly discuss the other main types of interstitial lung disease and how they differ from this.
IDIOPATHIC PULMONARY FIBROSIS
Idiopathic pulmonary fibrosis is rare. It affects men more than women and is commonest in the elderly.
According to the UK Interstitial Lung Disease Registry 2025 [1], the condition is three times as common in men as women and the mean age of presentation is 73.6 years.
THE UNDERLYING DISEASE MECHANISM
When we look at idiopathic pulmonary fibrosis, in addition to the interstitial tissue itself, we need to consider the alveoli, the smaller airways and the capillaries as they can all be affected.
The lungs are divided into secondary lobules, each bordered by intralobular septa. These secondary lobules vary in size. They can be up to 25 mm in diameter. Each contain thousands of alveoli (air sacs). The lobules have a central artery and bronchiole. Intralobular septa run within them.
Lung tissue is a bit like sponge. It is made up of millions of alveoli. An alveolus is a polyhedral, sac-like structure composed of single layer of alveolar epithelial cells (pneumocytes). The alveoli are reached through a succession of airways. The smaller airways, in diminishing order of size are the terminal bronchioles, respiratory bronchioles and alveolar ducts. Capillaries run over the outer surfaces of the alveoli and the smaller airways.
In the context of idiopathic pulmonary fibrosis, the interstitial tissue that we are primarily concerned about is the thin layer of connective tissue that lies between the alveoli and around the smaller airways and capillaries. It helps support and protect these fragile structures. The interlobular and intralobular septa can also be affected in interstitial lung disease.
The main function of lung tissue is to allow the exchange of the gases, oxygen and carbon dioxide. Oxygen moves along its concentration gradient from inhaled air in the alveoli into the capillaries. Carbon dioxide travels in the opposite direction.
For efficient exchange of gases, the barrier between the inhaled air and the capillary blood needs to be as thin as possible. This barrier consists of a single alveolar epithelial cell, a layer of interstitial tissue and a single capillary endothelial cell.
Interstitial tissue is made up of extracellular matrix containing collagen, elastin and immune cells including macrophages and fibroblasts. The elastin fibres provide a degree of elasticity that allows the lungs to expand when we breathe in and contract when we breathe out.
Fibroblasts are involved in tissue maintenance, tissue repair and scar formation. Part of their role involves the production of the extracellular matrix. Fibroblasts become activated and proliferate in the presence of tissue injury.
In idiopathic pulmonary fibrosis, interstitial fibroblasts become activated and proliferate abnormally. Excessive amounts of extracellular matrix are produced within the interstitial areas.
It is more difficult for oxygen and carbon dioxide to diffuse through this thicker, denser interstitial tissue and gas exchange is reduced.
Having a higher proportion of collagen, fibrotic tissue is less elastic than normal interstitial tissue. It restricts the expansion of the lungs. Patients cannot breathe as much air in.
The fibrotic process can progress and distort the normal architecture of the lung tissue. Pneumocytes are damaged and alveoli break down producing bigger air spaces. The resulting enlarged airs spaces are bordered by thickened interstitial tissue and known as honeycomb cysts. Alveolar breakdown reduces the effective surface area available for gaseous exchange. Traction due to shrinkage of fibrous tissue causes traction bronchiectasis (dilation of the smaller airways).
In idiopathic pulmonary fibrosis, the effectiveness of respiration is reduced by impaired gas exchange, restriction of lung expansion and distortion of the architecture of lung tissue.
The cause of abnormal fibroblast activity in idiopathic pulmonary fibrosis is unknown. It has been suggested it may be due to an exaggerated response to the repetitive, low grade alveolar epithelial cell injury that is an everyday occurrence in normal lungs. In connective tissue disease and hypersensitivity pneumonitis, it appears to be part of the abnormal inflammatory response. Once started, abnormal fibroblast activation may be sustained by the ongoing tissue damage that it causes – a self-perpetuating cycle.
In the long term, patients may develop pulmonary hypertension and right heart failure. It is thought that pulmonary hypertension is caused by a combination of pulmonary arteriolar vasoconstriction and remodelling secondary to chronic hypoxia along with injury to small vessels due to interstitial fibrosis.
CLINICAL FEATURES
The onset of symptoms is usually gradual. They include a persistent dry cough, breathlessness and tiredness. As the condition progresses, patients become more breathless with decreasing exercise tolerance. Damaged areas of lung increase susceptibility to intercurrent chest infection. Patients lose weight and muscle bulk.
A proportion of patients are picked up incidentally before they have developed significant symptoms following chest x-rays or computerised tomography scans done for other reasons.
Examination findings depend on how far advanced the patient’s disease is. In the early stages, physical examination is often normal.
Patients with more advanced disease are breathless on exertion or at rest and may be centrally cyanosed. Finger clubbing occurs.
Examination of the chest may demonstrate reduced expansion. Fine, end-inspiratory crackles can be heard over areas of fibrosis. These are said to sound ‘dry’ unlike the ‘wet’ or ‘moist’ crackles of pulmonary oedema which are due to fluid in the alveoli. Crackles in interstitial lung disease can be compared to ‘Velcro’ fastening being opened. These ‘Velcro’ crackles are thought to be due to the sound made by fibrosed alveoli opening as we breathe in. Some patients will have wheezing.
INVESTIGATIONS
BLOOD TESTS
Routine blood tests are usually normal. They have an important role in excluding other causes for the patient’s symptoms such as heart failure or malignancy. They may be useful when connective tissue disease or hypersensitivity pneumonitis is suspected.
RESPIRATORY FUNCTION TESTS
Fibrosis in the interstitial tissue reduces the elasticity of the alveoli and restricts lung expansion. Total lung capacity (TLC), vital capacity (VC) and forced vital capacity (FVC) are all reduced. Air flow is normal or slightly reduced in a purely restrictive defect, and so forced expiratory volume in 1 second (FEV1) is normal or slightly reduced. This means that the FEV1/FVC ratio will be normal or increased.
Standard spirometry measures forced expiratory volume in 1 second and forced vital capacity. A normal or increased FEV1/FVC is suggestive of restrictive lung disease. However, lung volume tests (plethysmography) with measurement of total lung capacity should be carried out to confirm this.
DIFFUSING CAPACITY OF LUNGS FOR CARBON MONOXIDE (DLCO)
Gas transfer can be assessed by measuring the diffusion capacity of the lungs for carbon monoxide. This acts as a surrogate measurement for oxygen transfer.
The thickened, denser interstitial tissue reduces gaseous exchange or gas transfer. Reduced gas transfer can occur early in interstitial lung disease, before symptoms develop.
RADIOLOGICAL FINDINGS
Chest x-ray is often normal in the early stages of interstitial lung disease. High resolution computerised tomography (HRCT) scanning is more sensitive.
If you take a cross section through the lung, which is essentially what a computerised tomography scan does, you will find millions of tiny airspaces (alveoli and small airways) between a network of fine interstitial tissue. In the normal lung, the walls of the alveoli, the walls of the small airways and the interstitial tissue are invisible to the naked eye. Only the black air will show up on the radiological images.
In idiopathic pulmonary fibrosis, the thickened, denser interstitial tissue will be seen as a white network (reticular pattern) with black air spaces in between. The distribution of this fibrotic tissue is patchy within affected areas of lung. Individual alveoli are about 0.2 mm diameter, so that the network we are seeing will be around groups of alveoli rather than individual alveoli.
As the fibrosis progresses, the interstitial tissue becomes thicker and individual alveoli break down to form larger ‘cystic’ spaces – honeycomb cysts. Contraction of the fibrotic tissue pulls the small airways, dilating them – traction bronchiectasis.
Patients may have evidence of inflammatory change seen as ground glass opacities, although this is usually minimal in idiopathic pulmonary fibrosis. Any ground glass opacities that are present are almost always in areas of reticular fibrosis. More extensive ground glass opacities are suggestive of other types of interstitial lung disease.
Ground glass opacities are hazy, diffuse shadows that are not dense enough to obscure the underlying bronchovascular markings. They indicate fluid or inflammatory material in the alveoli or interstitial space. They can be caused by pulmonary oedema.
In idiopathic pulmonary fibrosis, these radiological findings tend to be situated in the lower lobes of the lungs around the periphery, close to the pleura i.e. they are subpleural.
The pattern of reticular fibrosis, honeycomb cysts and traction bronchiectasis in the subpleural areas of the lower lobes along with the absence of changes indicating other types of interstitial lung disease is known as usual interstitial pneumonia (UIP).
The changes described above correlate with the pathological changes seen in lung tissue.
BRONCHIO-ALVEOLAR LAVAGE
The predominant cells found in washings taken from normal lungs during bronchoscopy are alveolar macrophages. In interstitial lung disease, cell counts are abnormal with increased inflammatory cells – neutrophils, eosinophils or lymphocytes. These abnormalities are non-specific and not diagnostic. In idiopathic pulmonary fibrosis, neutrophil and eosinophil counts tend to be raised. Bronchio-alveolar lavage has a role in ruling out other conditions such as infection or malignancy.
LUNG BIOPSY
Lung biopsy is only required in a proportion of cases where there is diagnostic uncertainty. It is risky, particularly if respiratory function is already compromised. Ideally, samples need to be taken from different sites. Complications of lung biopsy include pneumothorax, bleeding and infection.
DIAGNOSIS
Taken alone, none of the above investigations is completely conclusive. It is recommended that the diagnosis of interstitial lung disease should be made using a multidisciplinary approach. The multidisciplinary team might include respiratory physicians, radiologists, pathologists and specialist nurses. In most patients, a diagnosis can be made on the basis of the clinical features, laboratory tests, lung function tests and high resolution computerised tomography scanning along with the absence of features that suggest a different type of interstitial lung disease. Occasionally, further tests such as bronchio-alveolar lavage and lung biopsy may be required.
TREATMENT
The prognosis of idiopathic pulmonary fibrosis is poor. Median survival is three years from diagnosis.
Patients should be advised to stop smoking and offered pulmonary rehabilitation. Vaccinations against influenza, pneumococcal pneumonia and Covid-19 are recommended. Prompt treatment of intercurrent infections will help avoid additional deterioration in lung function.
Severely affected patients may benefit from supplemental oxygen. Palliative care is an option in the later stages.
It is generally accepted that the degree of inflammation in idiopathic pulmonary fibrosis is low. Not surprisingly, corticosteroids and other drugs acting on the immune system have been shown to be ineffective as disease modifiers.
ANTIFIBROTIC AGENTS
NINTENDANIB and PIRFENIDONE are antifibrotic agents. They are thought to act on inflammatory mediators involved in the signalling mechanisms that control the activity of fibroblasts. They inhibit fibroblast activity and, consequently, inhibit the resulting fibrosis. They have been shown to reduce the annual decline in forced vital capacity. They slow the rate of the disease progression [2].
LUNG TRANSPLANT
Lung transplant is an option for some patients with advanced interstitial lung disease. However, even with a successful transplant, the prognosis remains poor.
ACUTE EXACERBATION OF IDIOPATHIC PULMONARY FIBROSIS
Patients can develop acute exacerbations of idiopathic pulmonary fibrosis. They present with acute respiratory distress. Radiologically, there is more evidence of inflammatory change in the lungs with ground glass opacities and consolidation. It is important to exclude other conditions such as infection or heart failure. Drugs acting on the immune system and antifibrotic treatment have been tried with limited benefit. Acute exacerbations have a high mortality.
INTERSTITIAL LUNG DISEASE ASSOCIATED WITH CONNECTIVE TISSUE DISEASE
Interstitial lung disease is a common cause of morbidity and mortality in connective tissue disease. It may present in patients with undiagnosed connective tissue disease, and so it is always important to look for features that may suggest this. Patients are likely to be younger than patients with idiopathic pulmonary fibrosis and there is a higher proportion of females.
THE UNDERLYING DISEASE MECHANISM
The pathological changes depend on the specific connective tissue disease. In general, there is thought to be a greater inflammatory element. This is seen radiologically as ground glass opacities. A common pattern is non-specific interstitial pneumonia (NSIP). This is slightly different to the usual interstitial pneumonia seen in idiopathic pulmonary fibrosis. Inflammatory change is prominent. The reticular network is less marked. Honeycomb cysts are normally absent but there is usually evidence of traction bronchiectasis. There may be a nodular element to the fibrosis. The changes tend to occur in the lower lobes of the lungs.
Some patients may have the usual interstitial pneumonia pattern: others have less common patterns of interstitial lung disease or a mixed picture.
INVESTIGATIONS
In patients with newly diagnosed interstitial lung disease who do not have an established diagnosis of connective tissue disease, international guidelines recommend a serum autoantibody screen [3].
Bronchio-alveolar lavage may show increased numbers of inflammatory cells: lymphocytes, neutrophils or eosinophils.
Lung function tests show a restrictive deficit.
TREATMENT
The prognosis tends to be better than for idiopathic pulmonary fibrosis. Fortunately, not all patients with evidence of interstitial lung disease develop progressive lung fibrosis. Patients have been shown to respond to drugs acting on the immune system and antifibrotic therapy. Optimum treatment regimens are not yet well understood. Lung transplant is an option for some severely affected patients.
Interstitial lung disease is a side-effect of many drugs that act on the immune system. It can occur, for example, with methotrexate and several of the newer preparations. In patients who develop interstitial lung disease whilst on immunological treatment, it can be difficult to be sure whether the underlying connective tissue disease or the treatment is responsible.
INTERSTITIAL LUNG DISEASE ASSOCIATED WITH SCLERODERMA (SCLERODERMA-ILD)
Although scleroderma is rare, its pulmonary manifestations are common. Interstitial lung disease tends to occur in the first few years after diagnosis. It is a major cause of disability and death.
Patients with interstitial lung disease associated with scleroderma usually have non-specific interstitial pneumonia. This may progress into a usual interstitial pneumonia, although some patients have this pattern from the beginning.
It is important to remember that pulmonary hypertension is common in scleroderma. In some patients, it is secondary to worsening lung fibrosis. However, in many patients it is due to a direct effect of scleroderma on the pulmonary arterioles and unrelated to the lung fibrosis.
INTERSTITIAL LUNG DISEASE ASSOCIATED WITH RHEUMATOID ARTHRITIS (RHEUMATOID-ILD)
Rheumatoid arthritis is a common condition. Many patients develop associated lung disease which can include pleural inflammation, pleural effusion, bronchiolitis, bronchiectasis, interstitial lung disease, pulmonary vasculitis and pulmonary hypertension.
The commonest pattern of interstitial lung disease is usual interstitial pneumonia. Non-specific interstitial pneumonia can also occur.
RHEUMATOID NODULES
Some patients will develop pulmonary rheumatoid nodules. These are clusters of immune cells with a fibrotic periphery. They range in size from a few millimetres to several centimetres. Nodules may be asymptomatic. The central area can become necrotic, and they may cavitate or rupture. Cavitated lesions can become infected. In patients with nodules, alternative diagnoses such as lung cancer need to be considered.
CAPLAN’S SYNDROME
Patients with rheumatoid arthritis and pneumoconiosis due to coal dust, silica or asbestos sometimes develop multiple nodules which can grow rapidly. These nodules are similar to rheumatoid nodules but contain dust particles. They may coalesce or cavitate.
Other connective tissue diseases that can cause interstitial lung disease include dermatomyositis, polymyositis, Sjogren’s syndrome, systemic lupus erythematosus and mixed connective tissue disease.
INTERSTITIAL LUNG DISEASE ASSOCIATED WITH ANTIGEN INHALATION (HYPERSENSITIVITY PNEUMONITIS)
Hypersensitivity pneumonitis has been shown to be associated with numerous antigens. Some of the more well-known sources of antigens are moulds in hay that cause farmer’s lung, bacteria in humidifiers that cause humidifier lung and avian (bird) proteins that cause bird fancier’s lung.
Disease progression is likely to be dependent on the intensity and frequency of antigen exposure, but the exact relationship is not clear.
Identifying possible antigens plays an important part in the diagnosis of hypersensitivity pneumonitis. However, in a proportion of patients with suspected hypersensitivity pneumonitis, there is no obvious antigen.
Some chemicals can cause hypersensitivity pneumonitis by acting as haptens. Haptens are small molecules that are not immunogenic in themselves. However, they bind to proteins and, in combination, can cause immune reactions. Isocyanates used in the manufacture of polyurethane, paint and plastics occasionally cause hypersensitivity pneumonitis.
In the past, hypersensitivity pneumonitis has been divided into acute, subacute and chronic types. In 2020, The American Thoracic Society [4] suggested that division into two subtypes, nonfibrotic hypersensitivity pneumonitis and fibrotic hypersensitivity pneumonitis, was more appropriate.
THE UNDERLYING DISEASE MECHANISM
In nonfibrotic hypersensitivity pneumonitis, the disease is mainly inflammatory. Ground glass opacities are present along with centrilobular nodules thought to represent lymphocytic granulomatous inflammation around bronchioles. Granulomas are clusters of immune cells which form to contain and isolate antigenic material. These peribronchiolar granulomas can cause a degree of airway obstruction and air trapping. The pathological changes may give rise to a mosaic radiological pattern with a patchwork of areas of lower lung density (blacker) due to air trapping, areas of normal lung density and areas of higher lung density (whiter) due to inflammatory infiltrate.
In fibrotic hypersensitivity pneumonitis, the disease has both inflammatory and fibrotic elements, each of variable severity. Fibrotic changes include a reticular pattern, traction bronchiectasis and honeycomb cysts.
The changes tend to occur predominantly in the upper lobes of the lungs.
CLINICAL FEATURES
Because there are so many possible causative antigens, antigen exposure questionnaires may be used to assess patients.
The clinical picture may be acute, chronic or somewhere in between. Acute symptoms are thought to occur several hours after exposure. Patients may develop a cough, breathlessness, fever, shivering and general malaise. These symptoms settle quickly and repeat episodes can occur following further antigen exposure. In chronic disease, the features may more like those of idiopathic pulmonary fibrosis. At present, there does not appear to be a clear correlation between the clinical picture and the subsequent course of the disease.
INVESTIGATIONS
Pulmonary function tests may show a restrictive pattern, an obstructive pattern or a mixed picture. Bronchioalveolar lavage tends to show increased numbers of lymphocytes in patients with chronic lung fibrosis. Lung biopsy may show the inflammatory or fibrotic changes discussed above. Immunoglobulin G (IgG) tests are often carried out to check for antibodies to suspected antigens, but they are not diagnostic. They are now thought to be more suggestive of antigen exposure than active disease.
TREATMENT
Eliminating antigen exposure is the mainstay of treatment but not always possible. Many patients respond to this. In those that do not, drugs acting on the immune system or antifibrotic agents can be tried. Lung transplant is an option for some patients with advanced disease.
INTERSTITIAL LUNG DISEASE ASSOCIATED WITH INORGANIC DUST INHALATION (PNEUMOCONIOSIS)
The inhalation of a variety of dusts or fibres can result in interstitial lung disease. The most important examples are coal dust, silica dust and asbestos fibres. These pneumoconioses require relatively high levels of dust inhalation over many years and are, largely, occupational.
In some patients, fibrotic lung disease will continue to progress after dust exposure ceases.
LIMITING WORKPLACE DUST INHALATION
Measures to limit workplace dust inhalation have an important role in the prevention of the pneumoconioses. These include monitoring of workplace dust levels, ventilation, dust extraction, water suppression of dust and personal protective equipment. Workers should be regularly monitored for early evidence of pneumoconiosis and redeployed when this is considered significant.
The information here relates to coal workers pneumoconiosis and silicosis. Asbestosis will be discussed in a separate article.
THE UNDERLYING DISEASE MECHANISM
The underlying disease mechanisms for coal workers pneumoconiosis and silicosis are similar.
Inhaled dust particles are filtered by nasal hairs. Some are expelled by coughing. Others land in the airways and are removed by the mucociliary escalator.
Mucous is produced by goblet cells within the mucosal lining of the airways. Mucous is sticky and can trap particulate matter including inhaled dust, cellular debris and microorganisms. It contains a number of substances with antibacterial properties.
The mucosal lining of the airways also contains ciliated cells. The cilia are hairlike projections that beat continuously in a coordinated fashion to carry mucous secretions and trapped particles upwards where they can be expelled by coughing.
Some inhaled dust particles reach the respiratory bronchioles, alveolar ducts and alveoli. Those that cannot be removed by the mucociliary escalator are engulfed by interstitial macrophages.
Coal dust particles cannot be digested by macrophages, and they remain within these cells in the lung parenchyma, clustered around the respiratory bronchioles. Collections of coal dust laden macrophages are called coal dust macules. Over time, fibroblasts lay down fibrous tissue around these deposits of dust (possibly trying to wall them off) to form nodules.
Silica is toxic and causes macrophage cell death and the secretion of inflammatory mediators which may have a role in initiating fibrosis. Cell death releases the silica particles which are taken up by further macrophages perpetuating the process. Eventually, fibrosis occurs, and small, grey nodules are formed. Silica appears to be more fibrogenic than coal dust.
In a proportion of patients, abnormal fibroblast activity causes the nodules to increase in size. They may cause obstruction of small airways. Respiratory bronchioles are dilated and create areas of focal emphysema. Diffuse interstitial deposition of fibrotic material may also occur.
Large nodules may continue to increase in size or coalesce to form masses. This is associated with destruction of normal lung tissue.
Not all patients with simple pneumoconiosis go on to progressive lung fibrosis
The pathological changes occur predominantly in the upper lobes of the lungs.
INVESTIGATIONS
COMPLICATIONS
Chronic obstructive airways disease is common, sometimes partly due to smoking. Secondary infection may occur in large, necrotic masses. Breakdown of these masses can lead to pneumothorax. In severe disease, there may be pulmonary hypertension and right ventricular failure.
TREATMENT
At present, there is no disease modifying treatment for coal worker’s pneumoconiosis or silicosis. Lung transplant is an option for some patients with advanced disease.
COAL WORKER’S PNEUMOCONIOSIS (BLACK LUNG DISEASE)
Although there is now very little coal mining in the United Kingdom, it is still relatively common in some countries, and coal workers pneumoconiosis remains widespread [5].
In coal miners, the development of pneumoconiosis usually takes a minimum of ten years. The prevalence of the condition then gradually increases depending on the intensity and duration of coal dust exposure. It may take between twenty and forty years for patients to develop severe disease.
In simple coal worker’s pneumoconiosis, patients may be asymptomatic or have a cough with or without black sputum. Radiology will reveal collections of coal macules along with nodules less than 10mm in size. Deposits of coal dust give the lungs a black appearance. At this stage, lung function tests are usually normal.
In complicated coal worker’s pneumoconiosis, patients develop nodules of 10mm or more and there may be areas of reticular interstitial fibrosis and emphysema. Affected coal workers are likely to have a persistent cough and breathlessness. Lung function tests are abnormal. A small proportion of patients will go on to develop progressive massive fibrosis.
In progressive massive fibrosis, large masses form in the upper lobes of the lung. The masses can become big enough to occupy the majority of the upper lobe volume. Respiratory function in patients with progressive massive fibrosis is severely impaired and their prognosis is poor.
In coal miners with rheumatoid arthritis, Caplan’s syndrome may occur.
SILICOSIS
Silica is the most abundant mineral in the Earth’s crust. It exists in several forms and is contained in many different types of rock. Silica dust is produced by a variety of industrial processes. These include mining, quarry work, tunnelling, sandblasting, cement manufacture, glass manufacture and manufacture of pottery or ceramics. Drilling, cutting and sanding stone can all produce silica dust. Crystalline silica dioxide is the most abundant variety of silica and is thought to be the most harmful.
Like coal workers pneumoconiosis, patients may progress from simple silicosis to complicated silicosis, then progressive massive fibrosis.
In silicosis, the hilar lymph nodes are often enlarged and calcified. A thin, partial or complete rim of calcification (eggshell calcification) is very suggestive of a diagnosis of silicosis.
Macrophages have an important role in our immune response to mycobacteria. Impaired macrophage function caused by silica dust may account for the increased risk of tuberculosis in patients with silicosis.
Patients with silicosis are at higher risk of lung cancer and connective tissue diseases such as systemic lupus erythematosus.
ACCELERATED SILICOSIS
Occasionally, patients suffer from an accelerated or more rapidly progressive form of silicosis.
Over recent years accelerated silicosis has been associated with the use of engineered (artificial) stone. Engineered stone has become a popular choice for kitchens and bathrooms. It is made by bonding crushed crystalline silica with resins and adding colourants. This form of silicosis is mostly associated with cutting, grinding and sanding the stone. It frequently starts in younger patients, duration of exposure may be as little as three years, and it tends to cause severe lung fibrosis much more quickly.
The clinical features and pattern of fibrosis are otherwise similar to the chronic form of silicosis.
There are several possible reasons for this type of accelerated silicosis: the silica content of engineered stone is very high (>90%), dust produced by engineered stone is finer and additives such as resins or colourants may have a role. In addition, engineered stone is often prepared in small workshops lacking proper dust control measures and employing vulnerable, migrant workers.
ACUTE SILICOSIS
This is a more acute form of silicosis associated with concentrated exposure to silica dust. It has been reported following intense sandblasting or tunnelling work. Patients can develop cough, breathlessness and constitutional symptoms within months of exposure. Radiological findings are similar to those of alveolar proteinosis with fluid and consolidation within the alveoli visible radiologically. There are limited numbers of small nodules. The disease usually progresses relentlessly. Fortunately, it is rare.
INTERSTITIAL LUNG DISEASE ASSOCIATED WITH SARCOIDOSIS
Sarcoidosis is a chronic, inflammatory disease that can affect almost any organ system. The majority of patients with sarcoidosis have enlargement of the hilar and mediastinal lymph nodes with or without involvement of the pulmonary interstitial tissue.
In a significant number of patients, sarcoidosis is asymptomatic and picked up incidentally, usually following a chest x-ray. Many patients have inactive or mild disease. In those patients with active disease, the time course is usually very slow. Active sarcoidosis can go into remission spontaneously.
Some of the more important manifestations of sarcoidosis are progressive lung fibrosis and respiratory failure with lung involvement, life threatening cardiac arrhythmias and heart failure with cardiac involvement, central or peripheral nervous system deficits with nervous system involvement and uveitis with eye involvement. Hypercalcaemia can occur. Skin disease is common.
THE UNDERLYING DISEASE MECHANISM
The characteristic lesion of sarcoidosis is the non-caseating or non-necrotic granuloma. This consists of a cluster of immune cells. Some granulomas may heal spontaneously and resolve. Others merge, develop surrounding rings of fibrous tissue and form nodules.
Granulomas are thought to form to try to contain or isolate antigenic material such as mycobacteria. It has been suggested that sarcoidosis may be the result of an abnormal immune response to an, as yet, unidentified mycobacterial infection.
In the lungs, these small nodules may be visible radiologically. They tend to occur in the upper lobes in a perilymphatic distribution running alongside the bronchi and vascular structures. Nodules can merge together to form masses. The interlobular septa can also become fibrosed, thickened and nodular.
Endobronchial inflammation may lead to airway narrowing and obstruction.
Note: tuberculosis typically causes caseating granulomas. These granulomas become necrotic and form a soft centre that resembles cheese.
INVESTIGATIONS IN SARCOIDOSIS
Angiotensin converting enzyme (ACE) may be produced by immune cells within sarcoid granulomas leading to increased serum levels. Angiotensin converting enzyme is not thought to be useful from a diagnostic point of view. It is sometimes used as a marker of disease activity.
Unless the clinical picture is highly characteristic of sarcoidosis, tissue biopsy is required. Ideally, to avoid complications, this should not be taken from lung tissue. Biopsy of affected lymph nodes or skin may be safer options.
TREATMENT OF SARCOIDOSIS
Many patients do not need treatment. Those that do frequently show a good response to corticosteroids or other drugs acting on the immune system. They may go into complete remission. Treatment may need to be continued for several years.
INTERSTITIAL LUNG DISEASE ASSOCIATED WITH DRUGS
Numerous drugs have been shown to cause interstitial lung disease [6]. Older drugs include nitrofurantoin, amiodarone and methotrexate. Many new drugs that act primarily on the immune system have been shown to be associated with interstitial lung disease. The clinical, radiological and pathological features are variable, and individual drugs do not cause a specific pattern of disease. It is important, therefore, to consider the possibility of an underlying drug aetiology in any new case of interstitial lung disease.
INTERSTITIAL LUNG DISEASE ASSOCIATED WITH RADIOTHERAPY
Radiotherapy to the thoracic region can cause an acute inflammatory pneumonitis or chronic fibrosis. These changes are usually but not always localised to the irradiated area.
REFERENCES
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- Raghu G, Rochwerg B, Zhang Y, et al. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline. Am J Respir Crit Care Med. 2015;192(2):e3-e19. doi:10.1164/rccm.201506-1063ST
- Raghu G, Remy-Jardin M, Myers JL, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44-e68. doi:10.1164/rccm.201807-1255ST
- Koster MA, Thomson CC, Collins BF, Jenkins AR, Ruminjo JK, Raghu G. Diagnosis of Hypersensitivity Pneumonitis in Adults, 2020 Clinical Practice Guideline: Summary for Clinicians. Ann Am Thorac Soc. 2021;18(4):559-566. doi:10.1513/AnnalsATS.202009-1195CM
- Wang Z, Zhang J, Yang Y, et al. Current status, trends, and predictions in the burden of coal worker’s pneumoconiosis in 204 countries and territories from 1990 to 2019. Heliyon. 2024;10(19):e37940. Published 2024 Sep 19. doi:10.1016/j.heliyon.2024.e37940
- Spagnolo P, Bonniaud P, Rossi G, Sverzellati N, Cottin V. Drug-induced interstitial lung disease. Eur Respir J. 2022;60(4):2102776. Published 2022 Oct 27. doi:10.1183/13993003.02776-202