• HP is a rare disease in children. Incidence figures are not available, but a large respiratory centre might see fewer than one or two children each year.
• It can affect children of any age, including infants, although it most often affects school-aged children.
• HP is caused by a damaging host immune response to tiny (0.5–5 microns in size) inhaled organic particles. The list of potential sources of the organic particles is long, particularly in adults. In children, the most likely sources are bird proteins (especially pigeons) and fungi, particularly Aspergillus species and thermophilic Actinomycetes (from humidifiers and mouldy hay).
• About 50% of individuals exposed to large amounts of these types of organic dust will make an immune response, but only 5–15% will develop disease.
• The nature of the damaging response appears to involve both an immune complex formation (type III hypersensitivity response) and T-cell-mediated responses (type IV hypersensitivity response). It is not an IgE-mediated allergic response.
• Alveolar inflammation results in a diffusion defect that can lead to hypoxaemia.
• The condition can occur in acute, subacute, and chronic forms. The distinction between subacute and chronic is blurred. The major distinction is that, with chronic disease, there is only a partial recovery of lung function and respiratory symptoms when exposure to the cause ceases, whereas, in the subacute form, recovery is complete.
• HP is described in association with some drugs, such as bleomycin and methotrexate, and following radiation to the lungs. The mechanism behind these forms of HP is poorly understood, although peripheral and lung eosinophilia has been described. These conditions usually respond well to a combination of stopping the offending drug and a course of systemic corticosteroids.
The acute form of HP is unusual in children, although cases have been described. The episodes resemble ‘flu-like’ illnesses, coming on 4–6 h after exposure and lasting for 2–5 days. Typical symptoms include:
• dry cough;
• fever (as high as 40°C);
Subacute or chronic HP, the common form of the disease in children, arises from more prolonged contact with smaller amounts of the antigen. Typical symptoms include:
• dry cough;
• exercise intolerance;
• weight loss;
• wheezing episodes.
In acute disease, the child may look unwell, with respiratory distress and inspiratory crackles. In subacute and chronic disease, findings include:
• inspiratory crackles;
• finger clubbing;
• evidence of pulmonary hypertension in long-standing disease (right ventricular (RV) heave, loud P2, enlarged liver).
The differential diagnosis in a previously well child with a history of cough and exercise intolerance lasting for several weeks includes the following.
• Atypical infection:
• Chlamydophila pneumoniae;
• Chlamydia trachomatis (in infants, can be associated with eosinophilia);
• Mycoplasma pneumoniae.
• Immune deficiency, including HIV, either alone or combined with an opportunistic infection (EBV, CMV, PCP).
• Cardiac disease, including cardiomyopathy.
• Pulmonary arterial hypertension, either primary or secondary (including secondary to chronic HP).
• Other forms of ILD.
The diagnosis is not straightforward. There is no simple diagnostic test. Immunological tests indicate exposure but do not indicate that the symptoms a child has are due to a hypersensitivity reaction. Careful investigation and consideration of other causes is usually necessary. Investigation of a child presenting with the symptoms as described will include the following.
• CXR: typically shows diffuse reticulonodular or micronodular infiltrate. However, early in the disease, it is often normal.
• Lung function tests, including DLCO. There is usually evidence of restriction with a decreased DLCO. A mixed pattern, including obstruction, may also be seen. It is usually only possible to measure DLCO in children >8–10 years of age.
• Resting and exercise oxygen saturation. In severe disease, there may be resting hypoxia. In milder disease, desaturation may become apparent only on exercise.
• Blood tests:
• FBC and film: the leucocyte count may be elevated; 10% have eosinophilia;
• Total Igs, including IgE;
• Increased IgG (not IgE) antibodies directed against the suspected antigens. The test used depends on the centre—either precipitation tests (such as Ouchterlony) or enzyme-linked (ELISA) or using radioisotopes (RAST). The term precipitating antibodies refers to the test method, not the activity of the antibodies in vivo;
• HIV test;
• EBV and CMV serology/culture/PCR;
• Serology of Mycoplasma pneumoniae and Chlamydophila pneumoniae.
• ECG and echocardiography.
• Bronchoscopy and BAL. Bronchoscopic appearances are usually normal. BAL should be sent for culture (viral, bacterial, and TB) and cytological analysis. Typically, in HP, there is a marked increase in T lymphocytes, up to 70% of the cells present, about half of which are CD8+ cells (unlike sarcoidosis where the CD4+:CD8+ ratio is around 5:1).
• CT scan: may show nodular opacities with ground-glass attenuation, sometimes with a mosaic pattern. In more advanced disease, there may be prominent interstitial markings, giving a honeycomb appearance.
• Lung biopsy: may be carried out in chronic disease when either the diagnosis is unsuspected or where there is clinical doubt. Typical findings are inflammatory nodules or granulomata containing lymphocytes, plasma cells, and foamy macrophages. Similar cells can be seen within the alveoli and interstitium. In severe disease, there may be changes of interstitial fibrosis and/or obliterative bronchiolitis.
The diagnosis needs to be based on the presence of likely symptoms and signs, combined with the CXR or CT scan appearance, plus a history of exposure and immunological evidence of exposure. If there is intermittent exposure, it may be possible to elicit a history of worsening symptoms during the periods of exposure. The value of specific challenge tests in children has not been tested.
The most important treatment is removal of the causative organic antigen. In most children, this will be sufficient; 1–2 mg/kg/day of prednisolone will speed recovery.
In the vast majority of children, full recovery will occur, with a return to normal lung function and normal chest imaging. Occasionally, the disease is detected late, after irreversible interstitial fibrosis or BO have become established. In these children, there may be progressive hypoxia and pulmonary hypertension. Other immunosuppressant drugs can be tried in this group of children, although evidence of benefit is lacking.