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Fibrosing lung disease/Diffuse Parenchymal Lung Disease
- Fibrosis is a standard response to certain inflammatory processes. Localised fibrosis may be seen post pneumonia, TB or surgery or radiotherapy or any localised tissue damage
- Diffuse fibrosis of the lung is a pulmonary tissue response to various agents and ultimately leads to a restrictive lung defect with progressive hypoxia and then pulmonary hypertension and right heart failure. The end result is termed by pathologists a honeycomb lung
- Common features are with some exposure to an external agent (none has been found for Sarcoid and IPF) which may be inhaled or systemically taken e.g. some drugs.
- In these cases prevention of further exposure is key. As disease worsens so does gas exchange and ventilation/perfusion so supplemental O2 needed
- End stage young patients may be suitable for transplant but the rest mostly need supportive treatment and some respond to immunosuppression especially those with "ground glass" HRCT appearances
- Vaccination to prevent influenza is advocated. Smoking cessation of course should be suggested.
- If presented with a patient with progressive breathlessness and fine inspiratory crackles and restrictive lung disease be sure to ask about occupational exposure, dusts, pets, drugs and any rheumatological disorders. If all negative then Sarcoid and IPF most likely. Age is useful as Sarcoid hits the 20-40 year old and IPF the 50-60 year old.
Summary of Causes of Lung Fibrosis
- Sarcoidosis - Commonest cause in UK. Chronic disease leads to pulmonary fibrosis
- Idiopathic pulmonary fibrosis (IPF/CFA) - Poorly understood leads to progressive fibrosis and death. A minority may get lung transplant. Finger Clubbing in 50%
- Extrinsic allergic alveolitis Chronic exposure to allergens leads to pulmonary fibrosis
- Asbestosis - Chronic exposure to asbestos fibres leads to pulmonary fibrosis
- Silicosis - Chronic exposure to silica dust leads to pulmonary fibrosis
- Coal workers Pneumoconiosis - Chronic exposure leads to coal dust causes pulmonary fibrosis
- Scleroderma and Systemic sclerosis - those who have the anti centromere antibody are typically spared lung disease. Lung disease can include pulmonary hypertension, chest wall restriction, fibrosing alveolitis or aspiration pneumonia due to oesophageal problems. Steroids and azathioprine
- Rheumatoid arthritis - Similar to IPF with dry cough, progressive dyspnoea and clubbing, bilateral inspiratory basal crackles. UIP type picture. Treat as IPF
- Radiation - induced fibrosis - Given to treat malignancies develops 1-8 months after exposure. Progressive fibrosis over 6-12 months. May be some response to steroids
- Drug induced fibrosis - Diffuse lung fibrosis may be seen with chronic exposure to Nitrofurantoin, Amiodarone, Bleomycin, Methotrexate, Cyclophosphamide, Hydralazine. Progressive fibrosis on CXR and restrictive lung defect. Withdraw drug and consider steroids.
- The distinctive pathological finding is the widespread finding of Non caseating granulomata
- Multisystem disease commoner in Blacks/Indians/Irish Females and presents in those aged 20-40.
- Those with sarcoid have "Cutaneous anergy" which is a lack of a skin reaction to various antigens e.g tuberculin
- Possibly due to a diminished cell mediated immune response to antigens as lymphocytes and circulating T cells are sequestered in lungs
- Increase in B cells in peripheral blood and increased bronchial CD4 cells. Exaggerated Th1 response. Increased interferon gamma and IL-2
- Genetic link HLA associated susceptibility
- Acute disease Lofgren's syndrome with fever, erythema nodosum, Arthralgia, Bilateral hilar lymphadenopathy. Lasts 1-2 years. Good prognosis.
- Chronic disease - worse prognosis - Gradual increasing dyspnoea, Pulmonary fibrosis
- Arthritis is common usually involving feet and hands and large joints may be affected too
- Pulmonary findings are bihilar lymphadenopathy and pulmonary changes
- Skin - Erythema nodosum, Lupus pernio (red/blue nose), Nodules, scar infiltration
- Ophthalmic - anterior uveitis and later posterior uveitis which can cause blindness (Heerfordt's syndrome).
- Cardiac - Heart block, arrhythmias, Restrictive Cardiomyopathy is very rare.
- Salivary glands - Heerfordt's syndrome - Uveitis + Parotids enlarged + VIIth palsy + Fever.
- Renal - Hypercalcaemia and hypercalciuria often quoted by found in less than 10% may cause renal stones
- Neurological - Chronic granulomatous meningitis, Fits, Peripheral/cranial neuropathy
- Endocrine - Hypothalamic lesions - diabetes insipidus
- Haematological - Generalised lymphadenopathy, low peripheral CD4 count
- Liver involvement with granulomas on biopsy and mild deranged LFT's
- Often the patients are female of childbearing age and pregnancy usually improves symptoms.
- Tuberculosis - check smear for open TB and tuberculin testing
- Lymphoma - do HRCT and Lung cancer with localised spread
- The ESR and inflammatory markers are elevated with active disease.
- Raised serum ACE - non specific
- Raised 1,25(OH)2 D3 level (due to granulomata). Elevated (Blood and urine) Calcium in only 10%
- Tuberculin tests are usually negative
- Bronchoscopy - Cobble stoning of mucosa
- Bronchoalveolar lavage shows an increased CD4:CD8 T cell ratio
- Trans bronchial biopsy is useful in selected cases - Non-caseating granulomata on biopsy
- Kveim test - historical test - intradermal injection of splenic extract from a sarcoid patient and look for resultant granulomata
- Exclude open (smear positive) TB before formal lung function tests or risks contaminating the equipment
- Reduced transfer factor, Restrictive (small lung) PFT's and reduced DLCO
- ECG ? conduction abnormalities
- Echocardiogram - restrictive cardiomyopathy
- High resolution CT can show the extend of the fibrosis - ground glass appearance suggests active disease which may be steroid responsive
- Gallium-67 scan: The ?panda? sign (localization in the lacrimal and salivary glands, giving a ?panda? appearance to the face) is suggestive of sarcoidosis
- Staging is really all based on the CXR findings (BHL
= Bihilar lymphadenopathy)
- Stage 0 - CXR normal
- Stage 1 - BHL alone 80% resolve
- Stage 2 - BHL + pulmonary infiltrate 50% resolve
- Stage 3 - Pulmonary infiltrate with no BHL 25% resolve.
- Stage 4 - Advanced fibrosis with evidence of honey-combing, hilar retraction, bullae, cysts, and Emphysema
- Poor prognostic indicators
- Age > 40, Afro-Caribbean, Continuous symptoms over 6 months
- Lupus pernio, Involvement of over 3 organs
- No treatment is needed for simple BHL except NSAID's as analgesia for joint involvement
- Prednisolone 30 mg od for 6 weeks and then a reducing dose are given in some cases for 1-2 years.
- Indications for steroids
- Progressive lung disease
- Posterior uveitis
- Cardiac sarcoid
- Severe skin disease
- Muscle or bone disease
- Significant hypercalcaemia
- Topical steroids for uveitis and some skin lesions
- Methotrexate, Azathioprine, Pulsed cyclophosphamide for severe steroid resistant disease
- Chloroquine is used in skin and progressive lung disease
- Lung transplantation in severe cases
- Inhalation of beryllium causes a clinical picture very similar to sarcoidosis
- Beryllium is a rare metal that has many applications because of its light weight, tensile strength, high melting point (1500°C)
- Exposure is seen in machinists and manufacture of fluorescent lamps
- Those with HLA DPB1(Glu69) are more prone to chronic disease
- Acute exposure to beryllium leads to berylliosis with an acute alveolitis with breathlessness, cyanosis and inspiratory crepitations and pulmonary oedema picture on CXR
- Chronic exposure leads to a hypersensitivity response with a sarcoidosis like picture which can also affect close contacts e.g. wives
- Disease may progress over months and years
- Macular skin lesions seen.
- CXR - fine reticulonodular shadowing for chronic disease
- Pulmonary oedema picture for acute alveolitis.
- Biopsy shows a non caseating granulomatous reaction Histologically indistinguishable from sarcoidosis
- Pulmonary function testing - restrictive lung defect.
- Reduced transfer factor
- HRCT chest shows honeycomb lung and ground glass shadowing
- Acute disease - steroids can improve lung function
- Avoid further exposure and consider steroids in chronic exposure and disease
- Complications include Hypercalcaemia (seen with granulomata) and Pneumothorax
Idiopathic Pulmonary fibrosis (CFA)
- This is a diffuse Parenchymal lung disease of unknown
- Progressive fibrosis of alveoli and interstitium forming in later stages a honeycomb lung.
- There is a more aggressive form called Hamman-Rich syndrome.
- Generally poorly understood and the condition seems to strike at random
- In some cases cigarette smoking may play a role or exposure to wood or metal dust
- Commoner in women, age usually over 50
- There is an associated increased risk of lung cancer
- Types - Pathology/HRCT/Prognosis
- Usual interstitial pneumonia - proliferating fibroblasts. Inflammation minimal (Commonest and poor prognosis)
- Desquamative - Pigmented macrophages in alveolar airspace. HRCT ground glass appearance. Smokers. Better prognosis than UIP
- Acute - Hamman Rich syndrome pathology. Interstitium shows hyaline membranes and oedema (like ARDS). Later fibrosis. Better prognosis
- Progressive breathlessness, weight loss, fatigue
- Finger clubbing is seen with time in half the patients.
- Progressive hypoxia and eventually pulmonary hypertension with Cor pulmonale.
- Exclude features suggesting alternative diagnoses e.g joint disease may suggest rheumatoid
- Hamman Rich syndrome - onset over weeks. Tiredness, malaise, arthralgia, inspiratory crackles
- The CXR is often diagnostic and shows fibrosis by the time symptoms lead to assessment
- Spirometry will confirm a restrictive (small lungs) defect.
- Additional lung function tests will show reduced diffusing capacity for carbon monoxide (DLco)
- ABG's show hypoxemia (Type 1 RF) which is often exaggerated or elicited by exercise with low arterial CO2 levels.
- Some will have positive Rheumatoid factor or ANA.
- HRCT scanning is useful to confirm the diagnosis and extent of fibrosis and can help look for those who may be more responsive to therapy
- Usual interstitial pneumonia (UIP) where there is progressive fibrosis and honeycomb lung formation is poorly steroid responsive
- Desquamative interstitial pneumonia (DIP) The CT shows 'ground glass appearance' and is more steroid responsive
- Hamman Rich syndrome responds to steroids and supportive management.
- Difficult and treatment for UIP disappointing, Prognosis for DIP is better
- Look particularly for those with evidence of DIP on HRCT and Biopsy
- Immunosuppression - Prednisolone, Azathioprine, Cyclophosphamide have all been used with varying results
- Supplemental oxygen needed as the disease progresses
- Single Lung transplantation considered in selected groups. Many die waiting.
- Progressively treatment is supportive and palliative and life expectancy only 2-3 years.
Clinical examination reveals the classical fine inspiratory 'Velcro' crackles
Extrinsic allergic alveolitis/Hypersensitivity Pneumonitis
- Progressive restrictive fibrosis after months/years exposure to organic antigens
- Antigen exposure leads to an acute inflammatory reaction in bronchioles and alveoli
- It is not an acute allergic reaction as seen with Asthma
- There are circulating IgG antibodies to the antigens
- The lung may show non caseating granuloma and bronchiolitis.
- Always take an accurate home and occupational history looking for sources of inhaled antigens
- Disease and causative antigen
- Farmer's lung : Saccharopolyspora rectivergula found in Mouldy hay or grain or silage
- Pigeon fancier's lung : Avian droppings and feathers and serum from Pigeons, Parakeets, Budgies, Chickens, Turkeys
- Humidifier's lung : Thermoactinomyces vulgaris - Contaminated water systems - reservoirs or forced air systems
- Bagossis : Thermoactinomyces vulgaris Mouldy sugar cane
- Malt worker's lung : Aspergillus fumigatus, Aspergillus clavatus in Mouldy barley
- Animal handler's lung : Rats and gerbils Urine, serum, pelts, proteins
- Acute form - fevers, chills, chest tightness, breathless, malaise, cough and pyrexia several hours after exposure. Weekend improvement of work exposure.
- Chronic - progressive insidious dyspnoea, weight loss, cor pulmonale, cyanosis if severe, Mid to late inspiratory crackles in upper lobes
- Typically no wheeze and no bronchospasm.
- Bloods - raised neutrophils (not eosinophils), raised CRP
- CXR - Mid zonal opacities and nodules, reticulonodular interstitial infiltration, fibrotic changes
- RFT - Restrictive lung defect with reduced FEV and FVC and TLCO (diffusion capacity)
- ABG - hypoxia may be found
- Serum IgG antibodies to the offending antigen in the serum parallel exposure
- HRCT chest ? progressive fibrosis, nodules, ground glass changes
- The main treatment is avoidance of the precipitant antigen. Change in work, hobby. Special breathing apparatus.
- Prednisolone 40-60 mg reducing dose over time may be used if treatment required
Occupational lung disease
Coal Worker's Pneumoconiosis
- Accumulation of coal dust in the lungs and the result of the lung's response to it is seen where there is a coal industry and workers inhale coal dust.
- Risk of the disease corresponds to the length and level of exposure
- Smoking and CWP have additive damaging effects on the lungs
- It can be seen in approximately 10% of miners after 20 years exposure
- Coal Worker's Pneumoconiosis and Rheumatoid arthritis cause Caplan's syndrome
- Severe forms include Progressive massive fibrosis which can only be palliated
- Patients have progressive breathlessness
- Some progress to respiratory failure
- CXR shows Nodules > 1cm tend to affect upper lung and can progress to fibrosis
- A condition called progressive massive fibrosis can occur with opacities > 2 cm
- There is interstitial fibrosis
- Avoid coal dust inhalation and the important of smoking cessation cannot be stressed highly enough
- CWP is an occupational disease and the patient may be due compensation
- In the UK the Coroner should be informed if the patient dies as Industrial diseases are notifiable
- Treatment of PMF is simply supportive.
Byssinosis / Bagossis
- Byssinosis is an allergic reaction to an organic dust
- Bagossis is a similar allergy to mouldy sugar cane
- Similar Symptoms are seen with flax, hemp and jute.
- These are similar to Asthma with wheeze symptoms improve following initial re exposure.
- The Monday afternoon back at work with exposure is classically when it worsens and then improves greatly by the end of the week despite ongoing exposure.
- In early mild disease the Symptoms do not recur on the following days
- Smoking makes it much worse and must be stopped and otherwise treat as for asthma with bronchodilators
- Reduction of antigen exposure
- Antihistamines have also been shown to maintain FEV
Asbestos related lung disease
- Asbestos is a naturally occurring silicate with remarkable insulating properties and so was used in boiler making, to lag pipes, ship building from the 1940's but throughout the world was used in buildings and heat resistant paints and brake pads etc.
- It still continues to be used in the developing world but was banned in UK/USA in 1970's.
- Types of Asbestos - Chrysolite - White is most common and least fibrogenic, Crocidolite (blue), Amosite (Brown)
- Most importantly smoking and asbestos exposure increase greatly the risk of bronchogenic carcinoma but not mesothelioma.
- Complications of asbestos exposure take decades to present - peak manifestations of asbestos are predicted around 2012.
- Asbestos bodies are markers of exposure seen in sputum.
- Pleural plaques are seen in 50% of those exposed and only suggest asbestos exposure and of themselves mean little else and appear on CXR like candle wax drippings appearance
- Pleural thickening may cause a restrictive defect and increased dyspnoea.
- Pleural Mesothelioma is a progressive and aggressive tumour that can encase the lung
- Patients with mesothelioma classically present with a dull ache and breathlessness and chest pain
- There is no effective treatment and prognosis is poor
- Can be seen even with relatively low-level exposure
- The tumour can seed along needle sites for pleurocentesis.
- Peritoneal mesothelioma is also seen and is a rapid relentlessly lethal tumour.
- Bronchial carcinoma usually adenocarcinoma but also squamous cell carcinoma are associated with asbestos exposure
- Smoking is additive and must be strongly discouraged wherever there is asbestos exposure in the past.
- Asbestosis - A sign of heavy asbestos exposure, Usually mild and takes 20-30 years to occur
- Increasing dyspnoea, finger clubbing and end inspiratory crackles.
- Radiology CXR - pleural changes and plaques, Fibrosis and effusion may suggest pleural disease
- HRCT - can better show parenchymal and pleural disease
- Pronounced pleural thickening causes a restrictive defect on pulmonary function tests.
- Bronchoscopy to look for tumours where CXR/CT suspicious
- Avoidance of further asbestos exposure
- Smoking cessation is paramount to prevent the combined increased risk of bronchogenic carcinoma
- Mesothelioma is poorly responsive to most treatments and prognosis is poor
- Palliation in most cases
- Patients may be able to claim compensation
- Asbestos related and all industrial related deaths are reportable to the coroner
- Exposure to silica (SiO2) is seen in many industries and occupations such as stone cutting, glass and cement manufacturing, quarrying.
- Disease is dose related to exposure levels and time
- Silica exposure and silicosis are risk factors for lung cancer and TB infection
- The disease may be chronically progressive over years or decades with progressive dyspnoea
- Short term high level exposure can result in an acute silicosis. Progressive massive fibrosis (PMF) may occur.
- Eventually respiratory failure, pulmonary hypertension develop and cor pulmonale.
- CXR Eggshell calcification of the hilar lymph nodes is characteristic with reticulonodular shadowing.
- Whole lung lavage may be useful in some cases of acute silicosis
- Advanced cases of Chronic silicosis may need lung transplantation
- Prevention is the key.