01OverviewDefinition, clinical context and the essential points that orientate the chapter.
Hypersensitivity pneumonitis, historically called extrinsic allergic alveolitis, reflects repeated or intense inhalation of antigen capable of reaching distal airways and alveoli. The diagnostic problem is causal attribution. Bird ownership, mould exposure or a positive antibody is common enough to mislead, while hidden sources in bedding, lofts, water damage, farming, woodworking or metalworking may be missed. Diagnosis therefore combines a plausible temporal and biological exposure, compatible HRCT, physiology and sometimes lavage or histology at specialist MDT.
Non-fibrotic disease tends to show inflammatory ground glass, ill-defined centrilobular nodules, mosaic attenuation and air trapping, often with systemic symptoms after exposure. Fibrotic HP shows distortion, traction bronchiectasis and sometimes honeycombing, while lobular air trapping or a three-density pattern can preserve an airway clue. Differentiation from IPF, CTD-ILD and smoking-related disease matters because exposure control and immunomodulation may change outcome.
The practical treatment is elimination or substantial reduction of the responsible antigen without creating avoidable financial or housing harm. Occupational physicians, industrial hygienists, employers and local housing services may be needed. Respiratory specialists decide whether corticosteroid or steroid-sparing therapy is justified, and whether persistent fibrosis meets current criteria for nintedanib. The limited dedicated contemporary UK guidance makes local ILD MDT documentation particularly important.
Key points
- Hypersensitivity pneumonitis is an immune-mediated parenchymal and small-airway response to inhaled antigen in a susceptible person; exposure alone is not disease.
- Use non-fibrotic and fibrotic phenotypes because older acute, subacute and chronic labels overlap and can obscure behaviour.
- Sources include birds, mouldy hay or buildings, compost, metalworking fluids, humidifiers and other aerosolised biological material; the antigen is sometimes never identified.
- Ask where, when and how symptoms change: improvement away from work or home and relapse after return can be more useful than a generic allergy history.
- HRCT may combine ground glass, centrilobular nodules, mosaic attenuation and expiratory air trapping; fibrosis adds reticulation, traction change or honeycombing.
- Serum antigen-specific IgG indicates exposure and immune recognition, not causation, severity or a stand-alone diagnosis.
- Bronchoalveolar lavage lymphocytosis can support non-fibrotic disease but no universal threshold proves or excludes hypersensitivity pneumonitis.
- Avoidance is the central intervention, yet vague advice to 'avoid mould' is ineffective without identifying sources and involving occupational or environmental expertise.
- Corticosteroids may accelerate early improvement in selected inflammatory disease but have uncertain long-term benefit and require specialist, infection-aware decisions.
- Fibrotic disease can continue after exposure removal; monitor behaviour and consider progressive-fibrosis pathways rather than assuming avoidance guarantees stability.
02AetiologyUnderlying causes, associations and risk factors, with why each one matters.
Avian proteins
Bird feathers, droppings and bloom from domestic, occupational or hobby exposure are well-recognised antigens, including indirect household exposure.
Mould and microbial aerosols
Damp buildings, compost, hay, farming, metalworking fluids and contaminated water systems aerosolise fungal or bacterial antigens.
Occupational chemicals
Some low-molecular-weight agents and complex workplace mixtures provoke HP-like immune lung disease, making task-level exposure assessment important.
Host susceptibility
Only a minority of exposed people develop disease, reflecting immune predisposition, exposure intensity and duration, and possible interaction with smoking or infection.
03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.
- 1Repeated antigen inhalation
Small airborne particles reach terminal bronchioles and alveoli during recurrent domestic, hobby or workplace exposure, which helps produce the characteristic physiological impairment.
- 2Immune alveolitis
Antigen-specific immune responses recruit lymphocytes and macrophages, producing bronchiolocentric interstitial inflammation and poorly formed granulomas, which helps produce the characteristic physiological impairment.
- 3Small-airway obstruction
Bronchiolar inflammation and air trapping create mosaic attenuation and uneven ventilation alongside restrictive parenchymal change, which helps produce the characteristic physiological impairment.
- 4Fibrotic remodelling
Continued or self-sustaining injury activates fibroblasts, distorts lung architecture and may progress despite later antigen avoidance.
04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.
Cough, dyspnoea, fever, chills, malaise or chest tightness occur hours after a heavy antigen exposure and improve away from the environment, though timing becomes less clear with continuous exposure.
HRCT shows diffuse or patchy ground glass, poorly defined centrilobular nodules, mosaic attenuation and expiratory air trapping in a compatible exposure setting.
Progressive breathlessness, crackles, restrictive physiology and reticulation or traction change coexist with air trapping, upper or mid-zone involvement, or other exposure-linked clues.
Marked tachypnoea, hypoxaemia, diffuse opacities and systemic illness after exposure can mimic infection or oedema and requires emergency hospital care rather than outpatient antigen testing.
Similar symptoms among co-workers or improvement during holidays suggests a shared aerosol, commonly metalworking fluid, agricultural material or contaminated process, and warrants occupational-health escalation.
Worsening symptoms, serial FVC or TLCO decline and increasing radiological fibrosis despite credible avoidance indicate a high-risk phenotype requiring specialist re-evaluation.
05InvestigationsWhat to request, why it matters and how to interpret it.
Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.
- 01
Exposure questionnaire and timelineFirst step - Why
- Identify a biologically plausible inhaled antigen and temporal relationship.
- Interpretation and limitations
- Record exact birds, bedding, feed, damp, visible mould, water systems, hot tubs, work tasks, fluids, dust controls and personal protective equipment. Improvement away supports but does not prove causality.
- 02
HRCT with expiratory imaging - Why
- Identify combined parenchymal and small-airway abnormalities.
- Interpretation and limitations
- Centrilobular nodules, mosaic attenuation, air trapping and a three-density pattern support HP. Fibrosis may resemble UIP; distribution and exposure data must be integrated by an experienced thoracic radiologist.
- 03
Pulmonary function and exercise testing - Why
- Quantify impairment, desaturation and future trajectory.
- Interpretation and limitations
- Restriction and reduced TLCO are common, but obstruction or mixed physiology can reflect bronchiolar involvement. Serial change is more useful for prognosis than the initial pattern alone.
- 04
Serum antigen-specific IgG - Why
- Provide evidence of exposure to selected antigens.
- Interpretation and limitations
- A positive result means sensitisation or contact, not disease; a negative result may reflect the wrong antigen panel or assay limitations. Never use it as a binary diagnostic test.
- 05
Bronchoalveolar lavage differential - Why
- Support an inflammatory HP diagnosis and sample for infection.
- Interpretation and limitations
- Lymphocytosis increases diagnostic confidence in a compatible case but varies with smoking, timing, fibrosis and laboratory practice. Microbiology is essential when immunosuppression or acute illness is relevant.
- 06
Histopathology in selected cases - Why
- Resolve consequential uncertainty after non-invasive assessment.
- Interpretation and limitations
- Airway-centred inflammation, poorly formed granulomas and bridging fibrosis may support HP, but sampling is imperfect. MDT must balance potential diagnostic gain against biopsy morbidity and exacerbation risk.
- 07
Workplace or environmental assessment - Why
- Confirm and control a source that history alone cannot characterise.
- Interpretation and limitations
- Occupational-health or hygiene review examines process aerosols, ventilation, maintenance and co-worker illness. Environmental sampling is useful only when expertly designed and clinically linked.
06Differential diagnosisRealistic alternatives and the features that help distinguish them.
Idiopathic pulmonary fibrosis
Basal subpleural fibrosis without credible antigen exposure or prominent air trapping favours IPF, although advanced fibrotic HP can closely resemble UIP.
Connective-tissue-disease ILD
Raynaud phenomenon, inflammatory joints, muscle or skin disease and phenotype-linked serology support systemic autoimmunity, while chronology and directed testing distinguish the competing explanation.
Sarcoidosis
Well-formed granulomas, symmetrical hilar adenopathy and characteristic extrapulmonary disease favour sarcoidosis over bronchiolocentric exposure disease, and corroborating objective findings prevent an incorrect diagnostic label.
Infection
Fever and ground-glass or nodular change may reflect viral, mycobacterial or fungal infection, especially before immunosuppressive treatment.
Drug-induced pneumonitis
A medicine timeline may explain the same radiological patterns even when environmental antibodies or exposures are present coincidentally.
07ManagementImmediate care, first-line treatment, alternatives and escalation.
01Exposure diagnosisTurn a possible contact into a causal assessmentFirst stepClinical or HRCT features raise hypersensitivity pneumonitis.+
- 1Use a structured home, occupational and hobby history to map antigen contact against symptom onset, weekends, holidays, moves and process changes.
- 2Obtain protocolled HRCT, complete physiology and cause-directed tests; use antigen-specific IgG as exposure support, not as diagnostic proof.
- 3Discuss confidence at an ILD MDT and decide whether lavage or tissue would materially distinguish HP from IPF, CTD-ILD, sarcoidosis or infection.
- 4Record the suspected antigen, uncertainty and an achievable control plan, including the teams responsible for workplace or housing action.
02Immediate controlReduce antigen exposure safelyA credible home, hobby or occupational source is identified.+
- 1For severe acute disease, remove the person from exposure and arrange emergency assessment; respiratory support takes priority over detailed source testing.
- 2For ongoing contact, stop the implicated hobby or process where feasible and obtain occupational or environmental advice on engineering controls, remediation and respiratory protection.
- 3Avoid recommending irreversible employment or housing decisions on a weak single test; communicate clinical evidence and involve appropriate workplace services.
- 4Reassess symptoms and physiology after intervention, recognising that improvement supports causation but fibrotic disease may not recover.
03Treatment and follow-upManage inflammation and progressive fibrosisDisease remains clinically important after exposure intervention or fibrosis is progressing.+
- 1AlternativeConfirm avoidance quality and exclude infection or an alternative diagnosis before attributing persistent ground glass or decline to active immune disease.
- 2Discuss specialist corticosteroid or steroid-sparing treatment when inflammatory disease is substantial, documenting the uncertain long-term evidence and monitoring burden.
- 3If fibrotic progression persists, return to MDT for NICE-approved nintedanib eligibility, rehabilitation, oxygen assessment and transplant consideration where appropriate.
- 4Provide vaccination, smoking cessation, symptom support and a clear urgent plan for new hypoxaemia or fever during immunosuppression.
Key medicines and prescribing safety2 treatments · regimens, roles and cautions+
Prednisolone for selected inflammatory HP
No universal UK regimen exists; an ILD specialist chooses a time-limited daily induction and response-guided taper according to severity, infection evaluation and the current local protocol.It cannot replace source removal and its long-term disease-modifying benefit is uncertain. Screen for infection and monitor glucose, blood pressure, mood, bone and ocular effects; prolonged courses require steroid-protection planning.
Nintedanib for eligible progressive fibrosis
Specialist initiation is normally 150 mg orally twice daily around twelve hours apart with food, with 100 mg twice daily, interruption or cessation for intolerance according to the SmPC.This does not remove antigen or treat inflammatory episodes. Check liver function, diarrhoea and weight, bleeding and arterial-event risk, gastrointestinal perforation risk, interactions and pregnancy precautions under specialist supervision.
08ComplicationsImportant consequences, why they occur and why they matter clinically.
Progressive pulmonary fibrosis
Persistent matrix deposition causes irreversible restriction, impaired gas transfer, exertional desaturation and respiratory failure, and potentially prolonging treatment and functional recovery.
Acute hypoxaemic deterioration
Heavy re-exposure or an inflammatory flare can cause rapid diffuse pneumonitis, while infection and embolism require parallel assessment because each changes the urgent management pathway.
Pulmonary hypertension
Fibrotic vascular loss and chronic hypoxia raise pulmonary resistance and strain the right ventricle, and potentially prolonging treatment and functional recovery.
Occupational and social disruption
Effective avoidance may require major changes to work, housing, hobbies or relationships, with financial and psychological consequences.
Treatment-related infection
Immunosuppressive therapy increases infection risk and may obscure the distinction between relapse and an opportunistic pathogen.
09Monitoring and follow-upTreatment response, safety checks and longer-term review.
- Review symptoms in relation to location and work schedule, documenting whether the suspected exposure has actually changed and whether co-workers remain affected.
- Repeat FVC, TLCO and resting oxygenation at specialist intervals determined by inflammatory activity, fibrosis and recent trajectory.
- Use comparable exertional testing to detect functional decline and to assess rehabilitation or ambulatory oxygen needs.
- Reconsider HRCT when physiology worsens, looking for increasing fibrosis, infection, malignancy, embolism or another explanation rather than scanning to a fixed calendar.
- For corticosteroid or steroid-sparing therapy, monitor infection, metabolic and laboratory toxicity using the precise local medicine protocol.
- For occupational disease, document workplace controls and coordinate follow-up with occupational health; clinical review alone cannot verify exposure removal.
10Special situationsVariants, exceptions and circumstances that change the usual approach.
Sensitisation is not disease
Many exposed people have antigen-specific IgG without HP. Conversely, a patient may have convincing disease despite a negative panel that did not contain the relevant antigen.
Air trapping may preserve the clue
Once fibrosis resembles UIP, lobular expiratory air trapping or a three-density pattern can retain evidence of the bronchiolar immune process.
Exposure is often indirect
Feather bedding, contaminated ventilation or clothing brought home from work can matter even when the patient reports no obvious birds, farming or mould.
Removal can test causality imperfectly
Improvement away from exposure supports the diagnosis, but corticosteroids, seasonal antigen change and the natural course can confound that observation.
Work advice has consequences
Accurate documentation and occupational expertise protect health while avoiding unsupported advice that could cause loss of income or undermine a future compensation assessment.
11Common pitfallsFrequent interpretation and management errors.
- 01
Diagnosing HP from a positive bird or mould IgG result without compatible disease and exposure timing.
- 02
Asking only about current job title and missing hobbies, feather bedding, water damage or historical high-intensity exposure.
- 03
Prescribing corticosteroids while leaving the antigen source unchanged and poorly characterised.
- 04
Assuming established fibrotic HP will improve completely after avoidance and failing to monitor progression.
- 05
Interpreting mosaic attenuation as uniquely diagnostic when vascular and other small-airway diseases can produce it.
- 06
Recommending permanent job loss from uncertain evidence without occupational-health and ILD multidisciplinary input.