Interstitial lung disease (ILD) attacks the tissue in the lungs surrounding (interstitium) the air-containing ones air sacs (alveoli), so that lung function decreases. In some cases, the lung disease progresses and the lung tissue dies away over time. It is then replaced with scar tissue in the form of pulmonary fibrosis. Among the causes are infections, chemical substances and unknown, autoimmune mechanisms. In some cases, the lung disease is related to an underlying rheumatic disease in the form of systemic connective tissue disease, Vasculitis or Rheumatoid arthritis (arthritis). Disease of the pleura (pleuritis, pleural fluid) is discussed on a separate page.
Disease in the lung tissue can be caused by infection, chemical damage, radiation damage, allergy, cancer or autoimmune disease (including rheumatic diseases). When an underlying condition cannot be found, the lung disease can be described as "idiopathic".
Signs of lung disease can develop acutely, over a few days, or insidiously, so that months pass before a person reacts. Shortness of breath, dry cough, pain in the lungs and exhaustion are often symptoms.
Medical history maps whether there are symptoms (see above) and at the same time signs of disease from the skin, muscles, joints, back and other internal organs such as the heart, oesophagus, stomach, intestines, kidneys). Other diseases and risk factors such as infections, drugs, chemical substances, radioactive radiation are requested.
Clinical assessed if there are signs of reduced oxygen uptake, such as bluish hands, feet, nose or ears and clubbing/hourglass nails on fingers. Crepitations on auscultation. Signs of right-sided heart strain: bone edema (water in the legs), congestion in the jugular veins. Joint inflammation (arthritis), skin changes and muscle weakness are examined.
Laboratory tests include lowering reaction (SR), C-reactive protein (CRP), Hemoglobin (often increased in chronic lung disease, may decrease in lung hemorrhage), white blood cells, platelets (high in inflammation, low values may be due to pulmonary haemorrhage), liver and kidney function tests, creatine kinase (CK, myositis with lung changes?), metabolism/thyroid tests, antibody tests such as ANA (antinuclear antibody) with subgroups (ENA), antisynthetase antibody (myositis panel), anti-CCP and ANCA. Urine sample (stick for protein and erythrocytes).
Lung function tests (FEV1, FVC, DLCO). Spirometry is a subset of LFT and measures the amount (volume) of air that is exhaled and the flow rate (flow) of this air. Spirometry is therefore best suited to assess obstructive pulmonary disease such as asthma and COPD. Assessment of lung function in rheumatic diseases requires additional information about the lungs' ability to absorb oxygen. This is measured indirectly by DLCO (carbon monoxide diffusing capacity) which require more advanced equipment, most often in pulmonary wards in hospitals. Definition of severely impaired lung function is partly based on reduced values in pulmonary function tests when FVC is less than 70% of expected and, together with DLCO, falls by 10% and 15% respectively per year. The degree of severity is also determined by age, other concurrent illnesses. if CT examinations show that more than 20% of the lungs have been attacked.
6-minute walking test measures how many meters you cover when you walk as fast as you can on flat ground within 6 minutes. The result reveals something about the physical form, including lung function. The test requires that one does not have physically reduced walking function for other reasons. The result varies from person to person. The test is therefore best suited to follow the performance of the individual over time. Distances of 400-700 m are considered normal for healthy people.
Imaging. A normal X-ray does not show small or incipient changes in the lung tissue. CT images are much more accurate and are therefore preferred. High Resolution CT (HRCT) presents the lung tissue well without using large doses of radiation. Fixed nodules (cancer-like) are best investigated with ordinary CT). NSIP og UIP are really lung-Tissue samples diagnoses, but suspicion is often also described on CT. The need for control of nodules in the lungs in adults can follow Fleischner's recommendations (reference: MacMahon H, 2017).
Bronchoscopy performed by pulmonologists who, via the nose or mouth, guide the bronchoscope down the trachea and on to the bronchi. The bronchoscope can be equipped with an ultrasound probe (endobronchial ultrasound = EBUS). A bronchoscope can be used to rinse bronchoalveolar lavage (BAL): Lavage fluid from the lungs is obtained via a bronchoscope for the diagnosis of infection (pneumocystis with several) and pulmonary haemorrhage.
Tissue sample (biopsy) is rarely necessary, but is used where it is necessary for the diagnosis, provided that one expects a therapeutic benefit. Classification of tissue samples (NSIP, UIP and more) is described here (Wikipedia, English). Open lung biopsy may be necessary if tissue changes are localized so that a transbronchial tissue sample is not possible and a closer assessment is necessary for the treatment.
Nonspecific interstitial pneumonitis (NSIP) is the most common manifestation in the lung tissue of those Systemic connective tissue diseases that Systemic sclerosis, Antisynthetase syndrome / myositis, hypersensitivity pneumonitis og Sarcoidosis. NSIP can be divided into two types, of which the inflammatory, inflammatory can be treated with corticosteroids such as prednisolone and other immunosuppressive drugs, while the fibrotic form is more permanent scar tissue. NSIP can be detected from medical history, clinical examination and CT images, but additional examinations to rule out infection, bleeding or cancer may be necessary in some cases. Tissue samples are not always necessary. The distribution of NSIP is even (homogeneous), patchy and can vary in distribution unlike UIP (see below). In the case of underlying rheumatic disease, NSIP and UIP most often begin in the lower (basal) parts of both lungs.
"Matt glass" (or "milk glass") is diffusely thickened lung tissue seen on CT examinations, to a lesser extent on plain X-rays. Ground-glass changes may be a transient condition and consistent with NSIP (see above) or an early stage on the way to fibrosis (see below). Infections, chemical exposure, allergic reactions and lung haemorrhages can also cause ground glass changes in the lungs.
Usual Interstitial Pneumonitis (UIP) are changes in the lung tissue that cannot be expected to reverse. UIP can follow from untreated NSIP (see above) or develop directly, as in idiopathic pulmonary fibrosis (IPF) which is the most common condition of pulmonary fibrosis. IPF also has the worst prognosis.
UIP also occurs with far reaching Systemic connective tissue diseases: that Systemic sclerosis, Antisynthetase syndrome / myositis with multiple drug side effects, Sarcoidosis and inhaled harmful substances. During clinical examination, crackling sounds (crepitations) are detected over the lungs on auscultation. Also lung function tests shows reduced results in DLCO and FVC. Medicines (pirfenidone and nintedanib) have become available that can reduce the development of pulmonary fibrosis. Early diagnosis is therefore important.
Pumonary fibrosis: Connective tissue with no special function and which usually remains despite treatment.
Honeycombing: Widespread fibrosis (connective tissue) with cavities (cysts) in the lung tissue that resemble a honeycomb. Many cysts/cavities cause the lungs to lose their function.
Nodules (noduli) occurs in the lung tissue in various diseases and is detected incidentally in approx. 1% of all CT examinations, more often in various lung diseases. A large nodulus is 1-3 cm, small nodulus is less than 1 cm: Micronodulus is less than 3 mm. Micronodules are rarely malignant, but larger nodules must be assessed/followed up to rule out cancer. Fleischner recommendations (reference: MacMahon H, 2017). Other causes are infection and benign thickenings such as granulomas, small lymph nodes or varicose veins.
Ljuvenile cysts are round cavities that develop in place of normal lung tissue. If the cysts are numerous or large, lung function will be affected. In addition, lung cysts can burst and trigger a punctured lung (pneumothorax). Lymphoid interstitial pneumonia (LIP) is characterized by benign lymphocyte infiltrates, nodules and lymphoid follicles in the lung tissue. Often the changes are asymptomatic. CT images show multiple thin-walled cysts (Gupta N, 2016). LIP is typically seen in Sjögren's syndrome, Differential diagnoses in multiple lung cysts (adapted from Berger I et al, Journal of Medical Research, 2020).
|Diagnosis||Cyst contour||Distribution||Additional findings in the thorax|
|Lymphoid interstitial pneumonia (LIP)||Round, oval, irregular. The size varies||Diffuse peribroncovascular, subpleural, basal||Mattgalssfortetninger. Noduli in acute stages. Ev. Sjögren's syndrome|
|Lymphangioleiomyomatosis (LAM)||Round, small. Irregular in advanced disease||Diffuse, more central||Ev. nodules. Matt glass densities. Chylothorax|
|Neurofibromatosis Complex (NFC)||Round, small||Diffuse, few||Nodules|
|Pulmonary Lung Cell Histiocytosis (PLCH)||Round, oval, Irregular / bizarre||Upper and middle lung fields. Recess of costophrenic angle||Small, star-shaped nodules. Varying thickness of cyst walls|
|Birt-Hogg-Dube Syndrome (BHD)||Round, oval. Irregular. Varies in size||Middle and lower lung fields. Subpleurally, peribronovascular||No|
The treatment options for lung disease depend entirely on the underlying cause of the lung disease. In case of infection it can be antibiotics against bacteria, in rheumatic inflammation prednisolone or other immunosuppressive treatment. There are also medicines for pulmonary fibrosis.
Regardless of the cause of illness and special treatment, the following applies:
- Nicotine (smoking) must stop
- Other concomitant diseases must be treated as best as possible, including:
- Stomach acid reflux (acid reflux)
- Heart disease
- Obesity must be reduced
Interstitial lung disease (ILD) diseases (a selection)
- Alveolar proteinosis is due to the storage of PAS positive lipoproteins in the lungs. Heavy breathing and coughing. CT with infiltrates in the central, middle and basal (lower) parts of the lungs "Bat distribution"
- Antisyntetase syndrome (100%) (Systemic connective tissue disease)
- Aspiration (chronic aspiration pneumonia)
- Behcet's disease Aneurysm-bleeding (also in the lungs). Blood clots (blood clots), pulmonary emboli.
- Berylliosis: Mining, occupational disease
- Bronchiolitis (obliterative bronchiolitis) Obstructive pulmonary disease. No effect of asthma medication. HRCT shows "air trapping" in expiratory images. Many possible reasons.
- COPA (Autoinflammatory fever syndrome: Small children with polyarticular arthritis and lung disease)
- Eosinophil granulomatosis with angiitis (EGPA, Churg-Strauss syndrome) Vasculitis diseases. Volatile pulmonary embolisms. Emphysema (often after many years of Asthma and / or COPD)
- Eosinophilic pneumonia
- fistula: Malformation with connection between esophagus and trachea.
- Gaucher's disease Pulmonary infiltrates. Liver disease (hepato-pulmonary syndrome).
- Goodpastures (anti-glomerular basal membrane antibody) disease Kidney affection.
- Granulomatosis with polyangiitis (GPA, Wegener's granulomatosis) Vasculitis diseases. Pulmonary Haemorrhage (frosted glass-like). Granulomas (Tumor-like)
- Hemosiderosis / iron deposits in lungs (idiopathic) Hemorrhagia / Pneumonia
- Hypersensitivity alveolitis (allergy)
- Hypersensitivity pneumonia can be caused by a strong reaction to various inhaled substances (mushrooms, bacteria, chemical products and more).
- Infections, opportunism; can cause similar symptoms, especially among patients with a weakened immune system. The treatment is antibiotics with possibilities of healing. Aspergillosis (overlap). Aspiration pneumonia. Atypical bacterial pneumoniae. Pneumocystis jirovecii (matte glass in immunosuppressed people). Viral pneumonias COVID-19 (coronavirus), MERS (Middle East Respiratory Syndrome) Fever, cough, difficulty breathing and muscle aches
- Interstitial pneumonia, idiopathic (no known cause)
- "Interstitial Pneumonia with Autoimmune Features" (IPAF)
- MDA5 antibody syndrome
- Rapidly increasing lung disease
- Arthritis or joint pain
- Skin abnormalities
- Please read more about the MDA5 syndrome on its own page here
- Microscopic Polyangiitis (MPA) Vasculitis diseases. MPO-ANCA: Elevated in blood test, ILD may precede vasculitis symptoms. Occurrence of ILD can adversely affect the prognosis of MPA. Pulmonary Haemorrhage (frosted glass-like opacities) occurs
- Myositis / dermatomyositis / Antisynthetase syndrome In particular, in the antisynthetase syndrome, lung changes can be rapidly increasing and very severe. Early treatment is important to maintain lung function
- Langerhans histiocytosis; Eosinophils granulomas
- Pulmonary fibrosis, Idiopathic (IPF) (for no known reason).
- Pulmonary edema (chronic)
- Lymphangioleio myomatosis (LAM) Young women
- Lymphangic carcinomatosis Late stage of cancer where cancer cells create congestion in the lungs
- Lymphomatoid granulomatosis is a rare lymphoproliferative disease with lymphoma-like granulomatosis. Biopsy (tissue sample) is essential for the diagnosis: (histology: polymorphous lymphoid infiltrates with focal necrosis). Reactivation (in case of immunosuppression and/or weakened immune system) can be triggered by infection.
- Niemann-Pick disease (various forms) is one storage disease (lipids) / sphingmyelin-cholesterol lipidosis. Neurological symptoms with cognitive changes. Enlarged liver and spleen (hepatosplenomegaly).
- Nitrofurantoin (Furananthin) can cause pulmonary fibrosis with long-term use (6 months), most frequently in women.
- Reflux Disease. Stomach acid enters the lungs via the esophagus.
- Rheumatoid Arthritis (Arthritis). Frosted glass and fibrosis in lung tissue (reference: Kelly C, 2014) occurs in 4 – 10%. Share in NSIP (often good treatment options). UIP (responds less well to drugs). Pleurisy can also be seen.
- Rheumatoid nodules (nodules) in the lung tissue (α-CCP positive Rheumatoid arthritis) with 2mm-5cm large indentions and rarely symptoms, increased occurrence below methotrexate-treatment and possibly with aTNF and leflunomide treatment. PET / CT with 18FDG examination can be useful if cancer is a differential diagnosis. Subpleural (at pleura) or in the lung fissures is the most common localization. Final diagnosis by tissue sample (fibrinoid necrosis, cellular palisade/fencing pattern)
- Medications (methotrexate, leflunoid (Arava) and TNF inhibitors can rarely cause lung symptoms.
- Sarcoidosis. Enlarged lymph nodes in the lung hilus in the early stage (possibly together with rosacea / erythema nodosum in the skin and swollen ankles (Løfgren's syndrome). Condensation in the lung tissue in the chronic stage.
- SAVI (Autoinflammatory fever syndrome with vasculitis and lung disease).
- Silicosis Work in the stone industry or porcelain.
- Sjögren's syndrome (Systemic connective tissue disease) Various types of changes in lung tissue, usually not serious.
- LIP (lymphocytic interstitial pneumonia) most often consist of partially large cysts. Histologically, infiltrations with lymphocytes, plasma cells, histiocytes and lymphoreticular cells are detected in the interstitium and in the alveoli. Multi-nuclear giant cells with granulomas possible. polyclonal B cells differ from pulmonary Lymphoma. Mostly slow progression. About 25% of all people with LIP also have Sjögren's syndrome.
- Radiation damage with pulmonary fibrosis after previous cancer treatment.
- Systemic lupus erythematosus (SLE) (Systemic connective tissue disease) with or without Antifosfolipid syndrome (ApLs) high disease activity can cause changes in the lung tissue in the form of pneumonitis with diffuse pulmonary congestion (not to be confused with pneumonia). Pulmonary Haemorrhage with ground glass-like changes occur. Lung changes in SLE are relatively uncommon. It is always important to rule out infection as an alternative cause.
- Systemic sclerosis (scleroderma) (Systemic connective tissue disease). Lung changes in approx. 50% which most often occurs early and increases gradually. For some, drugs can stop or slow down development.
- Vasculitis diseases / granulomatous ILD
- Veno-occlusive pulmonary disease (reference: Holocomb BW Jr., 2000). Causes Pulmonary hypertension with elevated postcapillary pressure measured at the right heart catheter (treatment other than PAH related to Systemic sclerosis). Chest pain. Heavy breathing / dyspnoea is typical (>95%). Bloody mucus when coughing can be seen. Right-sided heart failure is detected by heart examinations. Most often idiopathic (unknown cause), but some are genetic. Some cases with a possible association with autoimmune diseases have been published.