What is Pneumonitis?

Pneumonitis is an inflammatory respiratory condition caused by acute or chronic exposure to irritating antigens in the environment. Because of the rarity of the condition, pneumonitis is often misdiagnosed. Additionally, the lack of medical research and clinical guidance on how to manage the condition has resulted in a few effective treatment options.

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Pneumonitis, also referred to as hypersensitivity pneumonitis, is a rare immune-related inflammatory respiratory syndrome that occurs in response to environmental and/or occupational antigens. The inflammatory condition is the most common interstitial lung disease and occurs more often in women and people older than 65 years of age.

While the exact prevalence rate of hypersensitivity pneumonitis is unknown, research has indicated that the 1-year prevalence rate ranges from 1.67 to 2.71 per 100,000 persons to 11.2 per 100,000 people aged ≥65 years in the United States alone.

Pneumonitis: Causes, Signs, and Symptoms

A secondary delayed reaction to repeated and long-term exposure to organic dust of vegetable or animal origin is the main cause of pneumonitis. Chemicals are rarely the trigger factor of hypersensitivity pneumonitis.

The individual becomes sensitized and hyperresponsive to these substances, resulting in inflammation of the alveoli, terminal bronchiole, and alveolar interstitium. People most at risk of this condition include those who work outdoors, including farmers or breeders, where exposure to these substances is common.

In addition to environmental antigens, reports in the literature have indicated that pneumonitis may occur in patients with cancer after treatment with immune checkpoint inhibitors, namely PD-1, PD-L1, and CTLA-4 inhibitors.

The severity of symptoms, clinical presentation, and prognosis can vary greatly between patients, as these factors of the disease can depend on the duration of exposures as well as specific characteristics of the antigen. The acute form of hypersensitivity pneumonitis occurs within hours or days of exposure to the antigen and is associated with symptoms such as fever, dyspnea, cough, malaise, and asthenia. These symptoms persist for about a week following exposure to the causative agent.

High-resolution computed tomography (CT) scans may show diffuse or patchy bilateral ground-glass opacities and possibly poorly defined small centrilobular nodules. Primary findings of pneumonitis on expiratory phases studies may also include signs of air trapping

Subacute pneumonitis is a result of longer exposure to the antigen. Symptoms will include productive cough, asthenia, and dyspnea. This form is generally difficult to differentiate from the acute form.

In contrast, continuous exposure to a causative pathogen leads to chronic pneumonitis. This leads to constant inflammation and, over time, possibly irreversible pulmonary fibrosis. Chronic pneumonitis forms over several months or years and includes symptoms such as progressive dyspnea corresponding with wheezing and repeated episodes of low-grade fever.

Diagnosis of Pneumonitis

Appropriate treatment of pneumonitis relies on a timely diagnosis, which is challenging as many cases of hypersensitivity pneumonitis is either unrecognized or initially misdiagnosed as idiopathic interstitial lung disease or respiratory infection.

Misdiagnosis is primarily attributable to the relatively low prevalence of the disease in the population and the subsequent lack of knowledge about the condition in the medical field.

Additionally, the variability of the disease increases the risk of underdiagnoses and misdiagnoses. Patients with comorbidities that increase the risk of respiratory problems may also complicate the appropriate diagnosis of pneumonitis.

A correct diagnosis of pneumonitis relies on a careful review of the patient’s medical history and a full interview to identify relevant occupational and environmental triggers. Since the mainstay of treatment for pneumonitis is complete avoidance of the triggering antigen, clinicians may wish to identify the suspected causative agent by analyzing specific precipitating antibodies in the serum.

For patients who have developed pneumonitis as an immune-related adverse event following checkpoint inhibitor therapy, clinicians may wish to perform pulmonary function testing, thoracic CT imaging, as well as bronchoscopy with bronchoalveolar lavage to rule out the possibility of infection.

Treatment of Pneumonitis

Treatment guidance for pneumonitis is currently unavailable. While avoidance of the antigen is the most necessary step in treating hypersensitivity pneumonitis, absolute removal from the patient’s environment may not be possible.

If complete avoidance of the antigen is not possible because it would result in a dramatic change in the patient’s lifestyle and/or occupation, corticosteroids may be prescribed. These medications can relieve acute symptoms but likely do not have any effect against the disease over the long term. Additionally, the evidence to support corticosteroid therapy for pneumonitis is weak.

Oral prednisone therapy between 40 mg and 60 mg for a few days to 2 weeks could be prescribed for acute pneumonitis, whereas treatment may be needed for 4 to 8 weeks in patients with subacute or chronic forms of the disease. Other research suggests immunosuppressants may be helpful.

Future Directions

Further research is needed on pneumonitis, including an investigation into its prevalence, diagnosis, and prognosis. Researchers have called for wider panels of immunoglobulin G for diagnosis as well as increased utilization of multidisciplinary care for the management of patients with pneumonitis.

References:

• Riario Sforza GG, Marinou A. Hypersensitivity pneumonitis: a complex lung disease. Clin Mol Allergy. 2017;15:6. doi:10.1186/s12948-017-0062-7
• Jain A, Shannon VR, Sheshadri A. Immune-related adverse events: Pneumonitis. Adv Exp Med Biol. 2018;995:131-149. doi:10.1007/978-3-030-02505-2_6
• Leone PM, Richeldi L. Current diagnosis and management of hypersensitivity pneumonitis. Tuberc Respir Dis (Seoul). 2020;83(2):122-131. doi:10.4046/trd.2020.0012
• Fernández Pérez 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(4):460-469. doi:10.1513/AnnalsATS.201704-288OC