Section 1: Epidemiology and aetiology
Hypersensitivity pneumonitis (HP) is an umbrella term for conditions affecting the lung, characterised by hypersensitivity immune responses to inhaled antigens derived from fungal, bacterial, animal protein or chemical sources.
It is also known as extrinsic allergic alveolitis (EAA), but HP is the preferred term since EAA is misleading both in terms of the pathological process (it is not an allergy) and the site of disease (involving both the distal airways and alveolar spaces).
HP occurs through repeated exposure to a number of aeroallergens (see box below). The most common causes in the UK are farmer's lung (sensitisation to thermophilic actinomycetes) and bird fancier's lung (sensitisation to avian proteins).
The incidence of HP is highly variable and related to exposure risk.
Previous studies have demonstrated a prevalence of 4 per cent of farmer's lung in Scotland1 and 3 per cent in the USA,2 although rates may be lower due to the increased use of silos to store hay.
The prevalence of bird fancier's lung can be as high as 10-20 per cent among pigeon breeders,3 particularly when there is regular exposure to the birds in their lofts.
Intriguingly, numerous studies have demonstrated lower rates of HP in smokers than in non-smokers.
The antigens that cause HP can be classified as coming from microbial (fungal or bacterial), animal or chemical sources.
The most common microbial antigens are derived from thermophilic actinomycetes and fungi, such as Aspergillus spp, which are ubiquitous in soil and decaying vegetables. Antigens associated with HP are smaller than 3micrometre, allowing them to be deposited in distal airways and alveolar spaces.
Classical immunological teaching has classed HP as due to a type III hypersensitivity reaction, involving antigen- antibody complex deposition and complement activation. However, this is an over-simplification as histological specimens demonstrate loose granulomas, indicating cell-mediated (type IV) reactions.
|Types and causes of hypersensitivity pneumonitis|
|Farmer’s lung||Mouldy hay||Saccharospora rectivirgula, Thermophilic actinomycetes|
|Compost lung||Compost||Aspergillus spp, Thermoactinomyces vulgaris|
|Mushroom worker’s lung||Mouldy compost and mushrooms||S rectivirgula, T vulgaris, aspergillus spp|
|Malt worker’s lung||Contaminated barley||Aspergillus clavatus|
|Humidifier lung, air conditioner lung||Contaminated air conditioners and humidifiers||Amoebae, T vulgaris, aspergillus spp, penicillium spp, nematodes|
|Bird fancier’s lung||Budgerigars, pigeons, parrots, chickens, geese||Proteins in avian dropping, feathers and serum|
|Animal handler’s lung||Rats, gerbils||Proteins from pelts, urine|
|Chemical worker’s lung||Polyurethane foams, spray paints, glues||Diisocyanates, trimellitic anhydride|
Section 2: Making the diagnosis
Although HP has been recognised in farming communities for many centuries, it was first described in 1932.4
Classically, symptoms of cough, fever, dyspnoea and myalgias develop four to eight hours after exposure to the relevant antigen in the acute form.
Taking a history is vital to the diagnosis and often patients will volunteer relevant information, for example, symptoms developing hours after cleaning out hay from stables.
Chest examination typically reveals crepitations, but importantly, wheeze is not a feature. In the acute form, symptoms generally resolve spontaneously over several days.
In the subacute and chronic forms of HP, the clinical presentation reflects both the antigen load and frequency of exposure, together with aspects of the host immune response. As would be expected, the chronic form presents more insidiously with dyspnoea and frequently weight loss, without the systemic features of myalgias and fever. The subacute form is intermediate between these two.
Crepitations on auscultation are typical of all forms of HP and hypoxaemia may occur in both acute and chronic disease.
Typically, in acute HP, the chest radiograph may demonstrate subtle soft nodular and interstitial abnormalities, but it may also be normal in up to 20 per cent of cases.
In the subacute form the radiograph is frequently normal, but as the disease spectrum progresses to the chronic form, interstitial changes dominate, reflecting the development of fibrosis. If acute HP is suspected, a high resolution CT scan (HRCT) is helpful diagnostically, demonstrating soft centrilobular nodules, often with areas of ground glass opacities.
In chronic HP, the CT reveals more non-specific fibrotic changes.
Lung function tests
Spirometry is usually restrictive (FEV1/FVC ratio >70 per cent and FVC <80 per="" cent="" predicted="" full="" lung="" function="" tests="" confirm="" a="" restrictive="" defect="" with="" reduced="" volumes="" and="" gas="" diffusion="" p="">
In the context of a typical clinical scenario, the finding of precipitating antibodies to a relevant antigen is diagnostic. If bird fancier's lung is suspected, a serum sample will usually be tested against a number of different avian proteins from different bird species.
If farmer's lung is suspected, the immunological diagnosis is more difficult since only a limited number of laboratories test the serum against thermophilic actinomycetes, the proteins responsible for this condition.
When specifically asked for, the samples should be sent to a laboratory with this expertise.
It is important to point out that the development of sensitising antibodies in the absence of clinical symptoms is common and that the antibody tests must be considered in the light of clinical symptoms.
Historically, there was a vogue for performing bronchoalveolar lavage (BAL), which typically demonstrates a lymphocytosis with a decreased CD4/CD8 ratio. Histological samples from transbronchial or open lung biopsy demonstrate non-caseating granulomas, but the findings are non-specific.
In general, BAL and biopsy are rarely indicated except in patients where there is diagnostic uncertainty.
Clinical scoring tools for HP
In an effort to improve the diagnosis of HP, a multi-centre study has examined a clinical prediction rule.5 The presence of the following six factors showed very high sensitivity and specificity for diagnosing HP:
1. Exposure to a known offending antigen.
2. Positive precipitating antibodies.
3. Recurrent episodes of symptoms.
4. Inspiratory crepitations on auscultation.
5. Symptoms occurring four to eight hours after exposure.
6. Weight loss.
Such a scoring system has yet to gain acceptance, although it could be simplified further as the presence or absence of weight loss adds little.
Section 3: Managing the condition
Avoidance of antigen exposure is the most important measure. In the acute form of the disease this is often sufficient to allow complete resolution of symptoms and avoidance of chronic restrictive lung defects.
Usually, if the patient is unwell, particularly if there is evidence of hypoxaemia, corticosteroids should be given. These have been shown to accelerate recovery.6 A dose of 40mg prednisolone for one to three months reducing according to clinical response is reasonable.
Corticosteroids are also given for subacute and chronic forms although the evidence for their long-term benefit is lacking.
Avoidance of the antigen is often difficult. Nevertheless, patients should be warned about the risks of developing chronic debilitating lung disease with continued exposure. Simple techniques, such as keeping hay dry and changing to silage making, can be beneficial in farmers.
Respirators which are tight fitting and well maintained may have a role in those in whom antigen avoidance is not possible, but symptomatic patients undergoing trials of such interventions should be closely monitored.
Section 4: Prognosis
Prognosis is largely determined by continued antigen exposure once sensitisation has occurred. In a study of farmers from Finland who continued working after developing acute or sub-acute HP, 40 per cent developed reduced gas diffusion and radiological abnormalities after five years' follow-up, suggestive of the development of the chronic fibrotic form of HP.7
Fibrosing alveolitis (Photograph: SPL)
The prognosis of bird fancier's lung is less clear. Long-term studies of pigeon breeders indicate that even after developing acute HP, 75 per cent continued to breed the birds, but only a minority developed chronic symptoms or abnormalities in their pulmonary function tests.8
This lack of progression may relate to antigen avoidance through the use of masks, although antibody levels remained high in the breeders.
Deaths are rare in HP and usually associated with the chronic form and the development of severe fibrotic lung disease with hypoxaemic respiratory failure.
Most studies of farmer's and bird fancier's lung indicate that even when there is a confirmed diagnosis of HP, patients continue with their profession or hobby, although there are usually attempts to modify antigen exposure.
It is important that patients remain under follow-up with measurement of gas diffusion (carbon monoxide transfer factor - TLCO) being the most sensitive parameter of declining lung function and the development of chronic disease.
Although wheeze is not a feature of HP in any of its forms, many studies have demonstrated increased rates of asthma developing in farmers, presumably reflecting an alteration of immunoregulation in the lung.
Section 5: Case study
A 46-year-old woman presented with a history of episodic cough and breathlessness. She worked in London, but lived in Sussex in a rural location.
Recently, her daughter had become interested in horse riding and the mother had been taking her to and from the stables. Over the preceding two months she had developed a dry cough and become breathless in the evening at the weekends.
This had become particularly noticeable after she had been involved with 'mucking out' the stables when she had also developed flu-like symptoms.
Although she had previously been completely well during the week at work, she had begun to notice increased breathlessness and was struggling to complete the three flights of stairs to her office. She suspected that the horses or stables may be implicated in her symptoms and mentioned this to the GP.
On examination, the GP noticed fine bibasal crepitiations on chest auscultation but there were no other findings. Suspecting farmer's lung from the history, a chest X-ray was ordered. The patient was referred to the local respiratory medicine department and advised to avoid contact with the stables.
She was seen at the local hospital two months later by which time her symptoms had significantly, but not completely, resolved. The chest X-ray was normal, but the consultant also noticed basal crepitations and requested an HRCT scan of the chest and sent blood for precipitating antibodies to thermophilic actinomycetes and aspergillus.
Spirometry was within the normal range, but full lung function demonstrated a reduced gas diffusion with a TLCO of 65 per cent predicted but a capacity corrected for alveolar ventilation (KCO) of 98 per cent predicted.
The CT revealed soft centrilobular nodules typical for HP without evidence of fibrosis. The patient was started on prednisolone at a dose of 40mg and a further appointment booked for one month. The blood test revealed negative precipitating antibodies for aspergillus, but tests for thermophilic actinomycetes were not available.
On follow-up the patient's symptoms entirely resolved and her gas diffusion normalised. Her steroids were tapered down and she was discharged from clinic with the advice to avoid contact with hay in the future.
Section 6: Evidence base
Unfortunately, the evidence base for the management of HP is weak.
- Lacasse Y, Selman M, Costabell U, et al. Clinical diagnosis of hypersensitivity pneumonitis. Am J Resp Crit Care Med 2003; 168: 952-8
This paper represents a useful attempt to create a helpful diagnostic algorithm with evaluation of a large cohort.
- Bourke SJ, Dalphin JC, Boyd G, et al. Hypersensitivity pneumonitis: current concepts. Eur Resp J 2001; 18 (supp 32): 81s-92s
This is a good overview of the subject from a clinical and pathological perspective.
The current British Thoracic Society (BTS) guidelines for the management of interstitial lung disease (2008) base their recommendations for HP on case-control or cohort studies, case reports, case series or expert opinions, with no meta-analyses, RCTs or high quality systematic reviews available.
The guidelines' recommendations are:
- The diagnosis of HP requires a high index of suspicion and in difficult cases an integrated multidisciplinary approach is essential.
- Avoidance of the causative antigen, when identified, is the most important and effective aspect of management.
- Corticosteroids may have a role in treating severe or progressive disease.
This topic is covered in the GP curriculum in statement 15.8 Respiratory Problems
- BTS interstitial lung disease guidelines - patient information.
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1. Grant IWB, Blyth W, Wardrop VE, et al. Prevalence of farmer's lung in Scotland: a pilot study. BMJ 1972; i:530.
2. Madsen D, Klock LE, Wenzel FJ, et al. The prevalence of farmer's lung in an agricultural population. Am Rev Resp Dis 1976; 113: 171-4.
3. Christensen LT, Schmidt CD, Robbins L. Pigeon breeder's disease: a prevalence study and review. Clin Exp Allergy 1975; 5: 417.
4. Campbell JM. Acute symptoms following work with hay. BMJ 1932; ii: 1143-4.
5. Lacasse Y, Selman M, Costabell U, et al. Clinical diagnosis of hypersensitivity pneumonitis. Am J Resp Crit Care Med 2003; 168: 952-8.
6. Kokkarinen JL, Tukiainen HO, Terho EO. Effect of corticosteroid treatment on the recovery of pulmonary function in farmer's lung. Am Rev Respir Dis 1992; 145: 3-5.
7. Monkare S, Haahtela T. Farmer's lunga 5 year follow-up of 86 patients. Clin Exp Allergy 1987; 17(2): 143-51.
8. Bourke SJ, Banham SW, Carter R, et al. Longitudinal course of extrinsic allergic alveolitis in pigeon breeders. Thorax 1989; 44(5): 415-8.
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