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Last updated: 10/24/2023
Years published: 1987, 1989, 1996, 1998, 2005, 2022, 2023
NORD gratefully acknowledges Evans Fernández Pérez, MD, MS, Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, for assistance in the preparation of this report.
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Summary
Hypersensitivity pneumonitis (HP) is a form of lung disease resulting from inhalation to a large variety of organic and, less often, nonorganic antigens. These antigens, frequently found in certain occupational settings, cause a reaction from the immune system (allergic reaction) that causes inflammation in the lungs.
The inflammatory reaction associated with HP occurs in the alveoli, the air sacs inside the lungs that are responsible for breathing and gas exchange. This is different from allergic asthma, as HP occurs in the alveoli, while asthma occurs in the airways or bronchi of the lungs. HP is a complex respiratory syndrome with varying intensity and clinical presentation. HP can occur for a short duration with respiratory symptoms and fever lasting from hours to several weeks after a subsequent exposure. The chronic form arises from long-term exposure to the inciting antigen and may last from weeks to years. Chronic HP can ultimately lead to permanent lung scarring (pulmonary fibrosis) and inadequate oxygen intake (respiratory insufficiency).
The clinical presentation of a patient with HP varies substantially depending on the type, duration and intensity of the inciting antigen exposure and whether they have lung fibrosis. Symptoms of early non-fibrotic HP may arise several hours after the exposure and consist of a flu-like syndrome with malaise, fever and chills. Respiratory symptoms include non-productive cough and difficulty breathing. Symptoms usually resolve within 24-48 hours but may recur upon re-exposure to the antigen. The presentation of fibrotic HP has a more gradual onset with dry cough, exertional breathlessness and fatigue as the most common symptoms.
Symptoms may be episodic or situational in relation to inciting antigen exposure. Patients without lung fibrosis may have a normal physical examination or show inspiratory expiratory wheeze. Patients with fibrotic HP typically have inspiratory Velcro-like crackles on lung auscultation. In advanced cases of lung fibrosis, heart failure and abnormally rounded fingertips (digital clubbing) may occur.
Hundreds of antigen exposure sources have been implicated in causing HP. These causes of HP are frequently named according to the setting in which the patient was exposed (e.g., humidifier lung, farmer’s lung, mushroom picker’s disease, bird fancier lung). HP antigens can be grouped according to three main categories – microbial, animal proteins and chemical sensitizers. These exposures can take place in residential, occupational, avocational or geographic settings.
The development of HP depends not only on the type, intensity and duration of exposure to an inciting antigen but also on individual susceptibility. Only a small proportion of any population of exposed individuals develop HP suggesting an underlying genetic predisposition. Studies investigating genetic susceptibility and HP have been limited, but genes that play a major role in the immune response have been identified as critical factors contributing to HP.
Additionally, depending on individual genetics, variable amounts of signaling molecules used by the immune system (cytokines) during inflammation and genes associated with lung repair and lung scarring may be responsible for HP disease course and varying severity.
External risk factors may modify HP’s development and clinical course. Factors associated with a worse prognosis include unidentified antigen exposure, continuing long-term exposure to the antigen, older age, male sex, cigarette smoke, auscultatory crackles on lung examination, the presence and extent of lung fibrosis on imaging at the time of diagnosis, lower lung function and progressive decrease in lung function from baseline and acute respiratory exacerbation leading to hospitalization.
The prevalence rate for HP in the U.S. is approximately 2 to 3 cases per 100,000 persons. HP is one of the most common diagnoses encountered at interstitial lung disease referral centers worldwide.
Variations in the number of HP cases correlate with age, geography, occupation, season and host risk factors. Farmer’s lung and bird related HP are among the most common forms of HP globally. Farmer’s lung is prevalent during late winter and the early spring cattle feeding period and after the harvest season. In contrast to work-related HP, non-occupational HP cases are not reportable and therefore likely underrepresented in the estimated frequency of HP. HP can occur at any age, with most patients presenting after the fourth decade of life.
HP is classified based on the presence or absence of radiologic or lung tissue fibrosis, antigen exposure likelihood, and the confidence level of imaging and lung tissue findings by a radiologist and pathologist, respectively. Both lung fibrosis and inciting antigen exposure characterization have implications for diagnosis, prognosis and treatment. The diagnosis of HP requires the exclusion of other conditions and a thorough multidisciplinary evaluation. No single test can confidently establish or exclude a diagnosis of HP. Exposure history, clinical manifestations, and radiological and lung tissue biopsy information must be considered before a diagnosis is made.
A consensus diagnostic approach by a multidisciplinary team with expertise in ILD can enhance the accuracy and confidence of diagnosis and help determine whether more invasive diagnostic procedures (e.g., lung biopsy, which is not always necessary) may be needed to support the diagnosis in a patient suspected to have HP.
A chest x-ray of someone with HP could be either normal or abnormal, depending on the severity of the condition. The upper lung zone frequently appears to be affected in patients with HP. Chest x-ray may also reveal air trapping, scarring or air-filled sacs of lung tissue (lung cysts). CT chest is more accurate and sensitive than chest x-rays in capturing the variety of different patterns and distribution of abnormalities observed in HP.
The detection of serum antigen-specific antibodies is indicative of previous exposure but is not a confirmation of the presence of HP.
Pulmonary function tests are non-diagnostic but are a reliable tool in quantifying the severity of the underlying lung impairment, in addition to monitoring disease progression and response to therapy.
For further analysis, it may be recommended to obtain a sample of the lung fluids (bronchoalveolar lavage (BAL) fluid) for analysis of white blood cells in the lungs or a biopsy of the lung (transbronchial lung biopsy or a surgical lung biopsy). Patients with more advanced HP (fibrotic HP – lung tissue has been replaced with scar tissue) are generally older (above 65 years old), tend to have lower lung capacity (maximal expiratory volume) and decreased oxygen uptake by the lungs (decrease rate of gas exchange in the alveoli).
All symptoms can usually be resolved in acute cases if they are diagnosed and treated early before permanent changes in the lungs can develop. If permanent lung changes such lung scarring are present at the time of diagnosis, it is possible that the patient may not respond well to treatment.
Management of HP is primarily aimed at antigen identification and avoidance. Antigen avoidance is the only non-pharmacological measure known to improve the clinical course and survival of patients with HP. Referral to and collaboration with an occupational medicine specialist should be considered in suspected occupational cases and multiple exposure sources. Removing the patient from the likely antigen-containing environment should be considered when complete antigen avoidance is impossible, particularly in patients with worsening disease.
If symptoms persist after avoiding exposure, an anti-inflammatory drug such as corticosteroid may be helpful. Other drugs that suppress the immune system may also be used to stabilize the lung disease. It is important to note that while these drugs may alleviate symptoms and improve breathing capacity in HP patients, they do suppress the immune system. As a result, patients may be more susceptible to infections. In patients with advanced HP, some supportive therapies may be prescribed, such as oxygen therapy to increase oxygen uptake by the lungs or drugs that open the airways (bronchodilator).
In patients with progressive fibrotic HP, antifibrotic therapy should be considered.
Other supportive management approaches include pulmonary rehabilitation to improve exercise endurance, capacity and quality of life; smoking cessation; appropriate vaccination to prevent infection; appropriate treatment of other conditions the patient has (e.g., coronary artery disease, sleep apnea, obesity, gastroesophageal reflux disease, pulmonary hypertension); disease education, symptom management (e.g., cough) and palliative care when appropriate. Lung transplant evaluation should be considered for patients with progressive disease despite comprehensive management.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact: www.centerwatch.com
For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLES
Furusawa H, Peljto AL, Walts AD, et al. Common idiopathic pulmonary fibrosis risk variants are associated with hypersensitivity pneumonitis. Thorax. 2022 May;77(5):508-510. doi: 10.1136/thoraxjnl-2021-217693. Epub 2022 Jan 7
Yang SR, Beasley MB, Churg A, Colby TV, Fernández Pérez ER, Lynch D, Müller NL, Travis WD. Diagnosis of Hypersensitivity Pneumonitis: Review and Summary of American College of Chest Physicians Statement. Am J Surg Pathol. 2022 Apr 1;46(4):e71-e93. doi: 10.1097/PAS.0000000000001827. PMID: 34753865
Fernández Pérez ER, Travis WD, Lynch DA, et al. Diagnosis and evaluation of hypersensitivity pneumonitis: CHEST Guideline and Expert Panel Report. Chest. 2021 Aug;160(2):e97-e156. doi: 10.1016/j.chest.2021.03.066
Petnak T, Moua T. Exposure assessment in hypersensitivity pneumonitis: a comprehensive review and proposed screening questionnaire. ERJ Open Res. 2020;6(3):00230-02020. doi:10.1183/23120541.00230-2020
Flaherty KR, Wells AU, Cottin V, el al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med 2019; 381:1718-1727. DOI: 10.1056/NEJMoa1908681
Fernandez Perez ER, Kong AM, Raimundo K, et al. Epidemiology of hypersensitivity pneumonitis among an insured population in the United States: a claims-based cohort analysis. Ann Am Thorac Soc. 2018; 15: 460-469.
Fernandez Perez 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: 1644-1651.
INTERNET
ATS Interstitial Lung Disease Primer: Hypersensitivity Pneumonitis. https://www.thoracic.org/education-center/ild/pdf/2021_ats_hp-ild_web.pdf Accessed Oct 10, 2023.
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