Simple pulmonary eosinophilia is a relatively mild illness with a slight fever and cough and usually lasting for less than 2 weeks. It is probably due to a transient allergic reaction in the alveolus. Many allergens have been implicated, including Ascaris lumbricoides, Ankylostoma braziliense and Trichuris trichiura as well as drugs such as paminosalicylic acid, aspirin, penicillin, nitrofurantoin and sulphonamides. Often, no allergen is identified. No treatment is required and the disease is self-limiting. Occasionally, however, the disease becomes more prolonged, with a high fever lasting for over a month. There is usually an eosinophilia in the blood and this condition is called prolonged pulmonary eosinophilia. Similar allergens are thought to be involved, with the addition of Strongyloides stercoralis. In both conditions the chest Xray shows either localized or diffuse opacities. Corticosteroid therapy is indicated, with resolution of the disease over the ensuing weeks.
Asthmatic bronchopulmonary eosinophilia
This is characterized by the presence of asthma, transient fleeting shadows on the chest X-ray, and blood or sputum eosinophilia. By far the commonest cause worldwide is allergy to A. fumigatus (see below), although Candida albicans may be an allergen in a small number of patients. In many, the appropriate allergen has still to be identified. Diseases caused by Aspergillus fumigatus. The various types of lung disease caused by A. fumigatus are illustrated.
The spores of A. fumigatus (5 J-Lm in diameter) are readily inhaled and are present in the atmosphere throughout the year, though they are at their highest concentration in the late autumn. They can be grown from the sputum in up to 15% of patients with chronic lung disease in whom they do not produce disease. They are an important cause of extrinsic asthma in atopic individuals.
Allergic bronchopulmonary aspergillosis
In allergic bronchopulmonary aspergillosis Aspergillus actually grows in the walls of the bronchi and eventually produces proximal bronchiectasis. There are episodes of eosinophilic pneumonia throughout the year, particularly in late autumn and winter. The episodes present with a wheeze, cough, fever and malaise. They are associated with expectoration of firm sputum plugs containing the fungal mycelium, which results in the clearing of the pulmonary infiltrates on the chest X-ray. Occasionally the large mucus plugs obliterate the bronchial lumen, causing collapse of the lung.
Repeated episodes of eosinophilic pneumonia left untreated can result in progressive pulmonary fibrosis that is often seen in the upper zones and can give rise to a similar chest X-ray appearance to that produced by tuberculosis.
The peripheral blood eosinophil count is usually raised, and total levels of IgE are extremely high (both that specific to Aspergillus and non-specific). Skin-prick testing with protein allergens from A. fumigatus gives rise to positive immediate skin tests. Sputum may show eosinophils and mycelia, and precipitating antibodies are usually found in the serum.
Lung function tests show a decrease in lung volumes and gas transfer in more chronic cases but in all cases evidence of reversible airflow limitation can be demonstrated. Treatment for this allergic pneumonia is with prednisolone 30 mg daily, which readily causes clearing of the pulmonary infiltrates. Frequent episodes of the disease can be prevented by long-term treatment with prednisolone, but doses as high as 10-15 mg daily are usually required. Moderately severe asthma itself requires continuous treatment with oral corticosteroids. Inhaled corticosteroids do not influence the occurrence of pulmonary infiltrates but are useful for the asthmatic element of the disease.
Diseasescaused by Aspergillus fumigatus
Aspergilloma and invasive aspergillosis
This is a totally separate disease from allergic bronchopulmonary aspergillosis. It simply represents the growth within previously damaged lung tissue of A. fumigatus, which forms a ball of mycelium within lung cavities. The typical appearance on the chest X-ray is of a round lesion with an air ‘halo’ above it. The continuing antigenic stimulation gives rise to large quantities of precipitating antibody in the serum. The aspergilloma itself causes little trouble, though occasionally massive haemoptysis may occur, requiring resection of the damaged area of lung containing the aspergilloma. Although treatment with antifungal agents, such as amphotericin (250 J.Lgkg” i.v.), has been tested in both allergic bronchopulmonary aspergillosis and aspergilloma, this has had little success, though it remains the only treatment for invasive aspergillosis, when it is often combined with flucytosine (200 mg kg” i.v. daily in four doses).
Tropical pulmonary eosinophilia
This condition presents with cough and wheeze together with fever, lassitude and weight loss. The typical appearance of the chest X-ray is of bilateral hazy mottling that is frequently uniformly distributed in both lung fields. The individual shadows may be as large as 5 mm or may become more confluent, giving the appearance of pneumonia. It is found in many tropical countries, but particularly in the Asian subcontinent, due to an allergic reaction to microfilaria, probably from Wuchereria hancrofti.
The disease is characterized by a very high eosinophil count in peripheral blood. The filarial complement fixation test is positive in almost every case. The treatment of choice is diethylcarbamazine at a dose of 5 mg kg:” body weight for 10-14 days; this usually produces a good response.
The hypereosinophilic syndrome
This disease is characterized by eosinophilic infiltration in various organs, sometimes associated with an eosinophilic arteritis. The heart muscle is particularly involved, but pulmonary involvement in the form of pleural effusion or interstitial lung disease occurs in about 40% of cases. Typical features are fever, weight loss, recurrent abdominal pain, persistent non-productive cough and congestive cardiac failure. Corticosteroid treatment may be of value
in some cases.
This is a rare disease characterized by foci of necrotizing arteritis that sooner or later affect many organs in the body. The lungs are rarely involved, except in the variant of polyarteritis nodosa known as the Churg-Strauss syndrome.
The upper respiratory tract may be involved, with nasal obstruction and rhinorrhoea. The chest X-ray may show consolidation that is ill-defined and transgresses anatomical boundaries. These shadows may disappear and reappear over periods of 2-12 weeks, and some may represent intra-alveolar haemorrhage or pulmonary infarcts. pANCA is usually negative in the serum. The overall 5- year survival for polyarteritis nodosa is 80% with corti costeroids and immunosuppressive therapy.
Microscopic polyarteritis involves the kidneys and the lungs, resulting in recurrent haemoptysis. pANCA is usually positive in the serum.
The pathology of this condition is dominated by an eosinophilic infiltration and it occurs in patients usually in their fourth decade who have a previous history of rhinitis and asthma. It may simply represent an unusual progression of allergic disease in a subset of predisposed individuals. It is characterized by a high blood eosinophil count, vasculitis of small arteries and veins, and extravascular granulomas. The lungs, peripheral nerves and skin are most often affected and renal failure is much less common than in generalized polyarteritis nodosa. Transient patchy pneumonia-like shadows may occur as in polyarteritis nodosa, but sometimes these can be massive and bilateral. Skin lesions include tender subcutaneous nodules as well as petechial or purpuric lesions. The disease responds well to corticosteroids. pANCA can be positive.
GOODPASTURE’S SYNDROME AND IDIOPATHIC PULMONARY HAEMOSIDEROSIS
The disease often starts with an upper respiratory tract infection followed by cough and intermittent haemoptysis, tiredness and eventually anaemia, though massive bleeding may occur. The chest X-ray shows transient blotchy shadows due to intrapulmonary haemorrhage. These features usually precede the development of an acute glomerulonephritis by several weeks or months. The course of the disease is variable; some spontaneously improve while others proceed to renal failure. The disease usually occurs in individuals over 16 years of age. It is thought to be due to a type II cytotoxic hypersensitivity reaction, the hypothesis being that there may be a shared antigen between a virus and the basement membrane of both kidney and lung. Anti-GBM antibodies are found in the serum and pANCA may be positive. An association with influenza A2 virus has been reported. Treatment is with corticosteroids, but plasmapheresis to remove the antibodies has led to dramatic improvement in some cases.
This is a similar disease to Goodpasture’s syndrome, but the kidneys are less frequently involved. Most cases occur in children under 7 years of age. Characteristically, haemosiderin-containing macrophages are found in the sputum. The child develops a chronic cough and anaemia and the chest X-ray shows diffuse shadows due to intrapulmonary bleeding, and eventually miliary nodulation. There is an association with a sensitivity to cows’ milk, and an appropriate diet is usually tried. The prognosis in general is poor and treatment with corticosteroids or azathioprine is usually given.
PULMONARY FIBROSIS AND HONEYCOMB LUNG
Pulmonary fibrosis is the end result of many diseases of the respiratory tract. It may be:
LOCALIZED, e.g. following unresolved pneumonia.
BILATERAL, e.g. in tuberculosis.
WIDESPREAD, e.g. in cryptogenic fibrosing alveolitis, due to drugs (busulphan, bleomycin and cyclophosphamide) or in industrial lung disease. Sometimes with widespread fibrosis a typical radiological appearance is seen that is known as honeycomb lung. This refers to the presence, often diffusely in both lungs, of cysts between 0.5 and 2 ern in diameter that are thickwalled and do not fill with opaque material on bronchography. The cystic air spaces probably represent dilated and thickened terminal and respiratory bronchioles.
The main causes of honeycomb lung.
Cryptogenic fibrosing alveolitis «(FA)
This relatively rare disorder of unknown aetiology causes diffuse fibrosis throughout the lung fields, usually in late middle age. The cardinal features are progressive breathlessness and cyanosis, which eventually lead to respiratory failure, pulmonary hypertension and cor pulmonale. Gross clubbing occurs in two-thirds of cases and bilateral fine end-inspiratory crackles are heard on auscultation. Rarely, an acute form known as the Hamman-Rich syndrome occurs. The chest X-ray appearance initially is of ground-glass appearance, progressing to obvious small nodular shadows with streaky fibrosis and finally a honeycomb lung.
A number of autoimmune diseases are seen in association with this, condition. For example, chronic active hepatitis occurs in 5-10% of cases. Similar lung changes are also seen in rheumatoid arthritis, systemic sclerosis and Sjogren’s syndrome, often associated with Raynaud’s phenomenon. CFA has also been reported in association with coeliac disease, ulcerative colitis and renal tubular acidosis.
Histologically there are two main features:
1 Cellular infiltration and thickening and fibrosis of the alveolar walls
2 Increased cells within the alveolar space (mainly shed type II pneumocytes and macrophages) The pathogenesis of damage and fibrosis is complex and several factors are involved.
CT SCAN shows characteristic changes.
RESPIRATORY FUNCTION TESTS show a restrictive ventilatory defect-the lung volumes are reduced, the FEV I and FVC ratio is normal to high (with both values being reduced) and gas transfer is reduced. Peak flow rates may be normal.
BLOOD GASES show an arterial hypoxaemia with normal PaC02′
THE ESR is high.
BRONCHOALVEOLAR LAVAGE shows increased numbers of cells (particularly neutrophils).
ANTINUCLEAR FACTOR is positive in one-third of patients.
RHEUMATOID FACTOR is positive in 50% of patients.
IN YOUNGER PATIENTS histological confirmation may be necessary, requiring a transbronchiallung biopsy or even an open lung biopsy to obtain a larger specimen.
The diagnosis of CFA can be made in an elderly person presenting with the above signs and laboratory test results. In younger people the differential diagnosis includes extrinsic allergic alveolitis, bronchiectasis, chronic left heart failure, sarcoidosis, industrial lung disease and lymphangitis carcinoma to sa.
PROGNOSIS AND TREATMENT
The median survival time for patients with CFA is approximately 5 years although mortality is very high with the acute form. Treatment with prednisolone (30 mg daily) is usually prescribed for disabling disease, though its benefit has still to be proved by appropriate controlled trials. Azathioprine or cyclophosphamide may also be used. Supportive treatment includes oxygen therapy. Extrinsic allergic alveolitis In this disease there is a widespread diffuse inflammatory reaction in both the small airways of the lung and alveoli. It is due to the inhalation of a number of different antigens, as illustrated in Table 12.11. By far the commonest of these diseases worldwide is farmer’s lung, which affects up to 1 in 10 of the farming community in poor, wet areas around the world. In Western countries the incidence is almost certainly declining as more mechanized farming procedures are introduced.
Histologically there is an initial infiltration of the small airways and alveolar walls with neutrophils followed by lymphocytes and macrophages, leading to the development of non-caseating granulomas. These comprise multinucleated giant cells, occasionally containing the inhaled antigenic material. The major allergic response to the inhaled antigens is through cellular immunity, though there is evidence in some cases of an additional immediate hypersensitivity reaction involving specific IgE antibody and the deposition of immune complexes. All these mechanisms can attract and activate alveolar macrophages, so that continued antigenic exposure results in the development of pulmonary fibrosis.
Pathogenesis of pulmonary fibrosis.
CT scan showing cryptogenic fibrosing alveolitis.
The typical history is that of the onset of fever, malaise, cough and shortness of breath several hours after exposure to the causative antigen. For example, a farmer forking hay in the morning may only notice symptoms during the late afternoon and evening that resolve by the following morning. On examination the patient may have a fever, tachypnoea and coarse end-inspiratory crackles and wheezes throughout the chest. Cyanosis may be severe even at rest. Continuing exposure leads to a chronic illness characterized by severe weight loss, effort dyspnoea and cough, and the features of fibrosing alveolitis. The chest X-ray shows fluffy nodular shadowing with the subsequent development of streaky shadows, particularly in the upper zones, and, in very advanced cases, honeycomb lung.
Extrinsic allergic bronchiolar alveolitis