Examine this patient's chest.
Examine the respiratory system from the back.
· Progressive exertional dyspnoea (90%).
· Chronic cough (74%).
· ArthralgiaJarthritis (19%).
· Obtain a drug history (amiodarone, nitrofurantoin and busulfan).
· Central cyanosis.
· Bilateral, basal, fine, end-inspiratory crackles which disappear or become quieter on leaning forwards. Furthermore, the
crackles do not disappear on coughing (unlike those of pulmonary oedema). The crackles have been called 'Velcro' or
· Tachypnoea (in advanced cases).
Proceed as follows:
· Examine the following:
-Hands (for rheumatoid arthritis, systemic sclerosis).
-Face (for typical rash of SLE, heliotropic rash of dermatomyositis, typical
facies of systemic sclerosis, lupus pernio of sarcoid).
-Mouth (for aphthous ulcers of Crohn's disease, dry mouth of Sj6gren's
· Look for signs of pulmonary hypertension: 'a' wave in the JVP, left parasternal heave and P2.
This patient has bilateral, basal, fine, end-inspiratory crackles (lesion) due to fibrosing alveolitis (aetiology) and is tachypnoeic at rest
In which other conditions is clubbing associated with crackles? · Bronchogenic carcinoma (crackles are localized).
· Bronchiectasis (coarse crackles).
· Asbestosis (history of exposure to asbestos).
Mention possible aetiological factors.
These include metal dust (steel, brass, lead); wood dust (pine); wood smoke and smoking.
Mention other conditions which have similar pulmonary changes.
· Rheumatoid arthritis, SLE, dermatomyositis, chronic active hepatitis, ulcerative colitis, systemic sclerosis.
· Granulomatous disease: sarcoid, TB.
· Chronic pulmonary oedema.
· Lymphangitis carcinomatosa.
· Extrinsic allergic alveolitis: farmer's lung, bird fancier's lung.
What is the pathology in fibrosing alveolitis?
Fibrosing alveolitis is characterized by the presence of connective tissue matrix proteins within the acinar regions of the lung in
association with a variable cellular infiltrate within the alveoli and in the interstitium.
What are the types of interstitial pneumonitis?
Liebow and Carrington (Liebow AA, Carrington CB 1969 The interstitial pneumonias. In: Simon M, Potchen EJ, LeMay M (eds)
Frontiers of Pulmonary Radiology. Grune &Stratton, New York, pp 102-141) initially described five subgroups, depending on
histology, to which there has recently been an addition:
· Classical (usual) interstitial pneumonia (UIP), characterized by thickening of the alveolar interstitium by fibrous tissue and
mononuclear cells; characteristically varying in severity from one focus to another. The mean survival is 2.8-5.6 years. Twelve
per cent respond to steroids and spontaneous improvement does not occur.
· Desquamative interstitial pneumonia (DIP) where there is a marked accumulation of macrophages in the alveolar airspaces
associated with a relatively mild but uniform thickening of the interstitial space caused by mononuclear inflammatory cells. The
mean survival is 12.4-14 years. The response to steroids is 62% and spontaneous improvement is 22%.
· Non-specific interstitial pneumonia (NSIP). The survival is 14 years and thera-peutic response is similar to DIP.
· A diffuse lesion similar to UIP but with superimposed bronchiolitis obliterans.
· Lymphoid interstitial pneumonia (LIP) in which there is marked infiltration of interstitium by lymphocytes that may be
indistinguishable from lymphoma.
· Giant-cell interstitial pneumonia consisting of a mononuclear cell infiltrate in the interstitium associated with large numbers of
multinucleated giant cells.
How would you investigate this patient?
· CXR typically shows bilateral basal reticulonodular shadows which advance upwards as the disease progresses. In advanced
cases there is marked destruction of the parenchyma causing 'honeycombing' (due to groups of closely set ring shadows), and
nodular shadows are not conspicuous. The mediastinum may appear broad as a result of a decrease in lung volume.
· Blood gases: arterial desaturation worsens while upright and improves on recumbency.
There is arterial hypoxaemia and hypocapnia.
· Pulmonary function tests: in the early stages lung volumes may be normal, but there is arterial desaturation following exercise.
Typically there is a restrictive defect with reduction of both the gas transfer factor and gas transfer coefficient.
· High ESR; raised immunoglobulins; raised antinuclear factor; rheumatoid factor
· Bronchial lavage: a large number of lymphocytes indicates a good response to steroids and a good prognosis. A large number
of neutrophils and eosinophils indi-cates a poor prognosis (5-year survival rate of 60% for steroid responders versus 25% for
non-responders). The patients are more likely to respond to cyclophos-phamide if the number of neutrophils is increased (Am
Rev Respir Dis 1987; 135: 26).
· Lung biopsy: in early stages there is mononuclear cell infiltration in the alveolar walls, progressing to interstitial fibrosis - known
as usual interstitial pneumonitis (UIP); in later stages fibrotic contraction of the lung, honeycombing, bronchial dilatation and
cysts are seen. DIP - alveolar macrophages with little mononuclear infiltration or fibrosis - has a better prognosis than UIP as it
responds to steroids.
· MRI is useful in determining disease activity without ionizing radiation but it is
an expensive method.
· High-resolution CT (HRCT) is useful to assess the pattern and extent of disease. Patients with a predominantly ground-glass
appearance are treated whereas those with a predominantly reticular appearance undergo technetium diethylenetriamine
penta-acetate scanning (DPTA) to assess the probability of deterioration. HRCT may avoid the need for biopsy, especially if
there is predominantly reticular shadowing. It acts as a guide for ideal biopsy site.
· Technetium-99m diethylenetriamine penta-acetate (DPTA) scanning in non-smokers is of value in identifying which patients are
more likely to deteriorate. Therapy can be postponed when there is slow clearance, whereas those with fast clearance should
receive treatment (Eur Respir J 1993; 6: 797-802).
Mention prognostic factors.
Short duration of disease, young age of patient at onset, female, predominantly ground-glass shadowing on CXR and presence of
little fibrosis on lung biopsies are good prognostic factors.
How would you manage this patient?
· All patients should receive a course of steroids (unless there are contraindi-cations): prednisolone 40 mg per day for 6 weeks.
Monitor symptoms, CXR, lung function tests. If response is good, continue; if no response then taper over 1 week.
· Steroid non-responders may benefit from a course of cyclophosphamide. Occasionally, patients who are unresponsive to
prednisolone and cyclo-phosphamide will respond to prednisolone and azathioprine.
· Identify the underlying cause and manage accordingly.
What is the prognosis?
The 5-year overall survival rate is 50%, 65% in steroid responders and 25% in steroid non-responders.
What are the causes of death in such patients?
· Respiratory failure or cor pulmonale precipitated by chest infection.
* Ten-fold increase in bronchogenic carcinoma compared with normal controls.
What is the role for lung transplantation?
Single-lung transplantation is now an established and effective form of treatment for certain individuals. Current survival rate at 1
year is approximately 60% (N Engl J Med 1986; 314:1140-45).
What do you know about the Hamman-Rich syndrome?
The Hamman-Rich syndrome is a rapidly progressive and fatal variant of interstitial lung disease described by Hamman and
Rich (Bull Johns Hopkins Hosps 1944; 74: 177).
Mention indications for transbronchial and open lung biopsy.
· Transbronchial: sarcoidosis, tuberculosis, berylliosis, lymphangitis carcinomatosa, extrinsic allergic alveolitis.
· Open lung biopsy: fibrosing alveolitis, rheumatological disease, pulmonary vasculitis, lymphangioleiomyomatosis, Langerhans
L.V. Hamman (1877-1946), physician, and A.R. Rich (1893-1968), pathologist, worked at the Johns Hopkins Hospitals, Baltimore (Hamman L, Rich AR 1944 Acute diffuse
interstitial fibrosis of the lungs. Bull Johns Hopkins Hosps 1944; 74' 177).
Dame Margaret Turner-Warwick, contemporary chest physician, was the first woman President of the Royal College of the Physicians of London; her chief interest is
fibrotic lung disease.