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Hypersensitivity pneumonitis happens when the immune system reacts to something breathed in — most often proteins from birds, or mould growing in damp buildings, hay, humidifiers or hot tubs — and inflames the deepest part of the lung where oxygen crosses into the blood. The main symptoms are breathlessness on exertion and a dry cough, sometimes with feverish episodes hours after an exposure. If the trigger is found and removed early, the lung can recover completely. If the exposure continues for years, the inflammation can turn into permanent scarring, which behaves much more like pulmonary fibrosis. That is why the single most important part of treatment is not a tablet but a piece of detective work: identifying what you are reacting to, and getting away from it.
Definition
Hypersensitivity pneumonitis — historically called extrinsic allergic alveolitis — is an immune-mediated interstitial lung disease caused by repeated inhalation of an antigen to which the person has become sensitised. The reaction takes place in the alveoli and the smallest airways rather than in the larger airways, which is what separates it from asthma. It belongs within the family of interstitial lung diseases, and it is the one member of that family with a potentially removable cause.
Two forms, and why the distinction decides everything
The 2020 international guideline abandoned the old acute/subacute/chronic split in favour of a two-way classification based on whether fibrosis is present on imaging and histology. That change was not cosmetic — it separates a condition that can resolve completely from one that behaves like progressive fibrosis.
| Non-fibrotic | Fibrotic | |
|---|---|---|
| What is happening | Inflammation only | Inflammation plus established scarring |
| Typical story | Symptoms within hours of exposure; better away from it | Months to years of gradually worsening breathlessness |
| Reversibility | Often complete with antigen avoidance | Scarring is permanent; the aim is to stop progression |
| Outlook | Good | Worse; a proportion behave like IPF |
Pathophysiology
Sensitisation, then reaction
The first requirement is repeated exposure to an inhaled organic antigen small enough to reach the alveoli. In a susceptible person the immune system mounts a response — immune complexes and complement in the early phase, and a T-cell–mediated granulomatous response with continued exposure. Only a minority of exposed people become sensitised, which is why one member of a household with the same birds may be ill while the others are not, and why the exposure history has to be taken seriously even when others sharing it are well.
From inflammation to scar
With continued exposure the granulomatous inflammation involving the small airways and alveoli begins to remodel the tissue. Chronic bronchiolar involvement produces air trapping — the mosaic attenuation characteristic on CT — and progressive fibrosis distorts architecture, most typically with an upper- or mid-zone bias that helps distinguish it from IPF. Once fibrosis is established it does not reverse, and a proportion of patients follow a progressive course despite the antigen being removed.1
Co-morbidities
- Pulmonary hypertension — develops in advanced fibrotic disease and worsens breathlessness disproportionately to lung function; see pulmonary hypertension.
- Gastro-oesophageal reflux — common across the fibrotic ILDs and worth treating.
- Smoking-related disease — paradoxically, smoking reduces the risk of developing hypersensitivity pneumonitis but worsens outcome once it is established.
- Deconditioning and muscle weakness — the usual consequence of activity avoidance, and the most treatable contributor to exertional breathlessness.
- Anxiety and low mood — heightened in a disease where the patient is often asked to give up birds, a home, or a job.
- Corticosteroid-related problems — weight gain, hyperglycaemia, bone loss and proximal myopathy where long courses are used.
Prevalence
Hypersensitivity pneumonitis accounts for a meaningful minority of interstitial lung disease presentations, though estimates vary widely because diagnosis depends on how hard the exposure is looked for. Incidence is strongly patterned by exposure: bird keeping and damp indoor environments dominate in domestic cases, while farming, metalworking fluid, and some manufacturing processes dominate occupational ones. A causative antigen is never identified in a substantial proportion of cases — and those patients have a worse prognosis, because the exposure cannot be removed.2
Causes
Hundreds of antigens have been implicated. The common ones in Australian practice:
- Birds — pigeons, budgerigars, cockatiels, parrots, chickens; also feather bedding, quilts and pillows, which are often missed because the patient does not own a bird.
- Mould and damp — water-damaged buildings, air conditioning and humidification systems, spa baths and hot tubs, indoor pools.
- Agricultural — mouldy hay, grain and silage; mushroom compost; animal sheds.
- Occupational and industrial — contaminated metalworking fluid, isocyanates, some woods and resins.
- Household — humidifiers, unvented dryers, mouldy bathrooms, and less commonly foods or fermentation processes.
The exposure is frequently intermittent or historic, and patients rarely volunteer it because they do not connect a bird kept for years, or a spa used weekly, with breathlessness that came on slowly.
Symptoms
Non-fibrotic presentation
Episodes of cough, breathlessness, chest tightness, fever, chills and aching that begin four to eight hours after an exposure and settle over a day or two — often mistaken for recurrent viral illness. The clue is periodicity: better on holiday, worse back at home or at work.
Fibrotic presentation
Slowly progressive breathlessness on exertion over months to years, a dry cough, fatigue, and sometimes weight loss. There may be no fever, no episodes, and no obvious link to any exposure. Fine crackles are usual on examination and clubbing may be present.
Warning signs
Diagnosis
Why the diagnosis matters
Fibrotic hypersensitivity pneumonitis is frequently misdiagnosed as idiopathic pulmonary fibrosis, and the consequences run both ways: the removable cause is missed, and immunosuppression appropriate to one condition can be harmful in the other. Distinguishing them is one of the more consequential problems in respiratory medicine.
How it is diagnosed
There is no single test. The 2020 guideline builds the diagnosis from four elements weighed together at a multidisciplinary meeting:
- Exposure history — detailed, structured, and repeated. A single question about pets and work is not sufficient; questionnaires improve the yield substantially.
- High-resolution CT — ground-glass, mosaic attenuation and air trapping, with an upper- or mid-zone predominance; the three-density pattern is characteristic.
- Bronchoalveolar lavage lymphocytosis — supports the diagnosis and is one of the few tests that meaningfully shifts probability away from IPF.
- Histology — where non-invasive assessment leaves genuine doubt, showing poorly formed granulomas and bronchiolocentric inflammation.
Serum specific IgG (“precipitins”) confirms exposure, not disease — a positive result in an asymptomatic bird keeper means only that they keep birds. Lung function typically shows a restrictive pattern with reduced gas transfer, though an obstructive or mixed picture occurs with prominent small-airway involvement.3
Management
Antigen avoidance is the treatment
Everything else is secondary. Complete removal from the antigen offers the possibility of full recovery in non-fibrotic disease and is associated with better survival in fibrotic disease. It is also the hardest part, because it can mean rehoming birds kept for decades, remediating or leaving a home, or changing occupation. Partial avoidance — keeping the bird outside, cleaning more often — is generally insufficient. Where the antigen is occupational, workplace assessment and formal exposure control are needed, and the case may be compensable.
Drug treatment
Corticosteroids speed recovery from acute inflammatory disease but have not been shown to change long-term outcome, and are used with more restraint than they once were. In progressive fibrotic disease, steroid-sparing immunosuppression is commonly used, and antifibrotic therapy is an option where the disease meets criteria for progressive pulmonary fibrosis. These are specialist decisions taken in an ILD service.
Non-drug management
Living with hypersensitivity pneumonitis
Losing the exposure
The advice to give up birds, or leave a house, or stop doing a job, is asked of people who did nothing wrong and often feel the diagnosis is being blamed on a hobby they love. It is worth naming that directly. Practical support — help rehoming animals, occupational advice, written documentation for employers or insurers — makes the difference between advice given and advice followed.
Pacing and activity
Breathlessness on exertion drives activity avoidance, which drives deconditioning, which worsens breathlessness. Breaking that loop with structured, progressive exercise is more effective than rest, and safe under supervision even with exertional desaturation.
Monitoring
Regular lung function and symptom review detects progression early. Patients should know which changes warrant contact rather than waiting for the next appointment.
Prognosis
Non-fibrotic disease with a removed antigen has a good outlook, and lung function frequently returns to normal. Fibrotic disease is more serious: survival is better than in IPF overall, but a subgroup with a usual-interstitial-pneumonia-like pattern, or with no identifiable antigen, does considerably worse. The two strongest modifiable determinants are whether the antigen is found and whether exposure genuinely stops.4
Role of the physiotherapist
Assessment
Quantify exertional capacity and desaturation with a six-minute walk test or an equivalent field test rather than resting observations — the resting saturation is frequently normal in someone who desaturates markedly on stairs. Assess breathlessness with a validated scale, screen for anxiety around breathlessness, and take an activity history detailed enough to show what has already been given up.
Exercise training
Rehabilitation is the core intervention. Prescribe on symptoms with oxygen support where indicated, expect and plan for desaturation on effort, and use interval formats where continuous work cannot be sustained. Include resistance training — peripheral muscle weakness and steroid myopathy both contribute, and both respond.
Breathlessness management
Pacing, positioning, the handheld fan, and breathing control give patients something to do in the moment. Techniques aimed at reducing air trapping have less to offer here than in COPD, and effort is better spent on exercise capacity and on the cognitive and behavioural side of breathlessness. See managing breathlessness.
Exposure detective work
Physiotherapists see patients repeatedly, at length, and often in more relaxed circumstances than a clinic appointment allows. A history that surfaces the feather quilt, the spa, or the mould in the laundry — and gets fed back to the treating team — can change the entire course of the disease. It is the highest-value contribution a therapist can make in this condition.
Part 1 · References
- Raghu G, Remy-Jardin M, Ryerson CJ, et al. Diagnosis of hypersensitivity pneumonitis in adults: an official ATS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med 2020;202(3):e36–e69.
- Fernández Pérez ER, Travis WD, Lynch DA, et al. Diagnosis and evaluation of hypersensitivity pneumonitis: CHEST guideline and expert panel report. Chest 2021;160(2):e97–e156.
- Vasakova M, Morell F, Walsh S, Leslie K, Raghu G. Hypersensitivity pneumonitis: perspectives in diagnosis and management. Am J Respir Crit Care Med 2017;196(6):680–689.
- Salisbury ML, Gu T, Murray S, et al. Hypersensitivity pneumonitis: radiologic phenotypes are associated with distinct survival time and pulmonary function trajectory. Chest 2019;155(4):699–711.
References are numbered in citation order (Vancouver/BMJ style) and were current at the time of writing. Guidelines are living documents — verify against the latest version before clinical use.
Supervised exercise, breathing technique and self-management education are the mainstay of cardiorespiratory physiotherapy for this condition.
Clinical evidence
Part 1 covers the same condition without the technical detail. What follows is the evidence base behind it, written for clinicians — the literature, the reasoning and the gaps.
For clinicians: this summary supports clinical reasoning and is not a protocol. Check current guidelines and local policy before applying it, and read it alongside the key references and guidelines directory.
Framing. Two shifts define current practice. The first is diagnostic: the 2020 guideline reclassified the disease on the presence of fibrosis rather than on symptom duration, because imaging phenotype predicts survival and chronicity does not.1 The second is therapeutic: fibrotic hypersensitivity pneumonitis is now recognised as a leading cause of progressive pulmonary fibrosis, which brings antifibrotic therapy into a disease previously managed with immunosuppression alone.2 Both changes sharpen the same clinical problem — separating this condition from IPF, in which immunosuppression is harmful.
Treatment evidence
- Antigen avoidance has the strongest outcome signal and no randomised evidence. Cohort data consistently show better survival where a causative antigen is identified and exposure ceases; failure to identify an antigen is an independent predictor of mortality. No trial has randomised avoidance, and none will — but the effect size in observational data exceeds anything achieved pharmacologically.3
- Corticosteroids accelerate recovery without changing long-term outcome. The evidence rests largely on a small randomised trial in farmer's lung showing faster early improvement in gas transfer with prednisolone but no difference at five years, and on observational series. Prolonged steroid use in fibrotic disease is not supported.4
- Steroid-sparing immunosuppression (mycophenolate, azathioprine) is widely used on the basis of retrospective series showing improved or stabilised gas transfer. There is no placebo-controlled trial, and the PANTHER-IPF experience — harm from immunosuppression in a UIP-pattern fibrotic ILD — is a standing caution wherever the phenotype overlaps with IPF.2
- Antifibrotics in the progressive fibrotic phenotype. INBUILD randomised patients with progressive fibrosing ILDs other than IPF — hypersensitivity pneumonitis was the largest single diagnosis in the cohort — and showed nintedanib slowed FVC decline consistently across subgroups. This is the strongest randomised evidence in the condition, though it applies only to those meeting progression criteria.5
- Pulmonary rehabilitation improves exercise capacity, breathlessness and quality of life in fibrotic ILD, with benefits that attenuate over months without maintenance. Trial populations are mixed-ILD rather than hypersensitivity-pneumonitis-specific, and gains are smaller and less durable than in COPD, particularly where gas transfer is severely reduced.6
- Ambulatory oxygen improves exertional endurance and breathlessness in ILD with exercise-induced desaturation; the AmbOx crossover trial showed improved quality of life over two weeks. Long-term survival benefit is unestablished.7
Clinical reasoning
- The diagnosis is a multidisciplinary probability, not a test result. The guideline explicitly frames confidence levels across exposure, HRCT, BAL and histology. A single positive element — particularly serum specific IgG — does not make the diagnosis, and precipitins in an asymptomatic bird keeper mean only exposure.
- BAL lymphocytosis is the most useful discriminator against IPF among the non-invasive tests, and is under-used. A markedly raised lymphocyte fraction substantially lowers the probability of IPF and can spare a biopsy.
- Exposure history yield depends entirely on how it is taken. Structured questionnaires materially outperform open questioning. Feather bedding, spa baths, water damage and intermittent occupational exposure are the routinely missed categories — and the patient will not volunteer them, because they do not consider them relevant.
- Zonal distribution and air trapping are the imaging discriminators. Upper- or mid-zone predominance with mosaic attenuation and three-density sign points away from IPF; basal, subpleural, honeycomb-predominant disease with none of these features points toward it — and toward avoiding immunosuppression.
- Treat exertional desaturation, not resting saturation. Resting oximetry is frequently normal in patients who desaturate substantially on a walk test. Assess on effort or the oxygen need is missed.
- Physiotherapy prescription: interval training where continuous work cannot be sustained, resistance work for steroid myopathy and disuse, and oxygen during training where it enables a higher work rate. Air-trapping-focused techniques transferred from COPD have little rationale here.
- The clinician who takes the fullest exposure history is often not the physician. Repeated, longer, less formal contact makes physiotherapy a realistic route to the missed antigen — but only if the finding is fed back to the ILD service.
Evidence gaps
- No randomised evidence supports any immunosuppressive regimen in fibrotic disease, and the appropriate strategy in UIP-like phenotypes is unresolved given the PANTHER signal of harm.
- What constitutes adequate antigen avoidance is undefined — complete removal versus mitigation has never been compared, and remediation standards for domestic mould exposure are not evidence-based.
- A causative antigen is unidentified in a substantial minority; no systematic approach has been shown to improve the identification rate, and questionnaire performance varies by region and exposure profile.
- Rehabilitation trials are conducted in mixed ILD cohorts. Optimal intensity, the role of oxygen during training, and how to maintain gains beyond a supervised programme are all untested in this population.
- Whether antifibrotic therapy benefits fibrotic hypersensitivity pneumonitis that has not yet met progression criteria is unknown, and the interaction between antifibrotics and immunosuppression is unstudied.
References for the clinical evidence summary
- Raghu G, Remy-Jardin M, Ryerson CJ, et al. Diagnosis of hypersensitivity pneumonitis in adults: an official ATS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med 2020;202(3):e36–e69.
- Raghu G, Remy-Jardin M, Richeldi L, et al. Idiopathic pulmonary fibrosis (an update) and progressive pulmonary fibrosis in adults: an official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med 2022;205(9):e18–e47.
- Fernández Pérez ER, Swigris JJ, Forssen AV, et al. Identifying an inciting antigen is associated with improved survival in patients with chronic hypersensitivity pneumonitis. Chest 2013;144(5):1644–1651.
- Kokkarinen JI, Tukiainen HO, Terho EO. Effect of corticosteroid treatment on the recovery of pulmonary function in farmer's lung. Am Rev Respir Dis 1992;145(1):3–5.
- Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in progressive fibrosing interstitial lung diseases (INBUILD). N Engl J Med 2019;381(18):1718–1727.
- Dowman L, Hill CJ, May A, Holland AE. Pulmonary rehabilitation for interstitial lung disease. Cochrane Database Syst Rev 2021;(2):CD006322.
- Visca D, Mori L, Tsipouri V, et al. Effect of ambulatory oxygen on quality of life for patients with fibrotic lung disease (AmbOx). Lancet Respir Med 2018;6(10):759–770.
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