Interstitial Lung Diseases

Indications for Testing

Testing for ILD is appropriate in individuals with symptoms of ILD and:

• Connective tissue or systemic autoimmune rheumatic disease
• Occupational exposure to materials or substances associated with ILD (eg, asbestos)
• A history of smoking
• Exposure to a pneumotoxic medication or treatment
• Known gene variants associated with the risk of developing ILD (see Genetic Testing)

Asymptomatic family members of those with an ILD-associated gene variant may warrant testing and counseling (see Genetic Testing).

Laboratory Testing

Diagnosis

Nonspecific Testing

Nonspecific laboratory tests in the workup of ILDs include CBC, creatinine, calcium, urine (to detect abnormal sediment), liver function, muscle enzyme, and lymphocyte proliferation tests.  Serum markers, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), are useful for the detection of systemic inflammation.  Abnormal results, in the context of other clinical information such as patient history, examination, and imaging, can help narrow the diagnosis to a particular form of ILD.  For example, detection of eosinophilia on a CBC can suggest drug toxicity or eosinophilic pneumonia, whereas normocytic anemia can point to connective tissue disease or chronic disease. 

Biomarkers for Lung-Specific Injury and Inflammation

Additional serum markers, such as surfactant protein D (SP-D) and Krebs von den Lungen-6 (KL-6), may be helpful to assess lung damage in patients with ILD. ^,  SP-D is involved in pulmonary immune response, and serum levels of SP-D serve as a marker of disease activity in ILD.  SP-D levels may also be useful for disease monitoring.  See Monitoring below.

Patients with ILD have higher KL-6 levels compared with patients with other pulmonary illnesses and healthy individuals, and increased KL-6 levels in serum serve as a marker for lung damage.  KL-6 testing is considered to have a role in ILD diagnosis and determination of disease severity, and may be useful for disease monitoring.  See Monitoring below.

Autoimmune Serologic Testing

A full serologic workup to detect antibodies associated with specific connective tissue diseases is recommended in all patients with ILD.  The particular tests are determined in part by clinical presentation and context, but may include the autoantibodies listed in the table below. Use of a panel test that detects a variety of autoantibodies may be the most efficient testing approach.​

Visit the Connective Tissue Disease ARUP Consult topic for additional information about ANA testing (including a comparison of ANA testing methods) in connective tissue/systemic autoimmune rheumatic diseases.

Visit individual ARUP Consult topics for more information about the use of laboratory testing for specific ILD-associated connective tissue diseases:

• Sjögren syndrome
• Systemic sclerosis
• Systemic lupus erythematosus
• Rheumatoid arthritis
• Mixed connective tissue disease
• Systemic vasculitis
• Inflammatory myopathies (eg, polymyositis and dermatomyositis)

Hypersensitivity Pneumonitis Testing (for Exposure-Related Interstitial Lung Disease)

Hypersensitivity pneumonitis, also called extrinsic allergic alveolitis, is one of the subgroups of ILD and typically results from exposure to organic antigens in the environment, such as mold, farming-related antigens, and avian proteins.  In cases of suspected hypersensitivity pneumonitis, testing for antigens such as Aspergillus flavus, Aspergillus fumigatus, Aureobasidium pullulans, Micropolyspora faeni, Saccharomonospora viridis, Thermoactinomyces candidus, Thermoactinomyces vulgaris, and pigeon serum is recommended. See ARUP Lab Tests below for disease-specific tests.

Genetic Testing

Some forms of ILD are associated with genetic conditions such as Hermansky-Pudlak syndrome, and a number of variants have been linked to an increased risk of ILD disorders (eg, chronic beryllium disease and sarcoidosis).  Genetic variants are also risk factors in both sporadic and familial idiopathic pulmonary fibrosis, and have prognostic relevance. 

Genetic testing should be considered in all patients who have ILD and a family history of ILD.  Some investigators recommend that personal and family history be evaluated, in conjunction with biomarkers, to identify families likely to have a genetic diagnosis before proceeding with genetic testing. The detection of a variant associated with a familial form of ILD warrants consideration of genetic testing and counseling in asymptomatic family members who may be at risk. 

Monitoring

Monitoring of ILDs primarily involves lung function testing, evaluation of dyspnea, and imaging.  In addition, both KL-6 and SP-D may be helpful in monitoring patients with an established diagnosis of ILD because both markers increase with disease exacerbation and decrease when treatment results in disease improvement. ^,  These markers may also be useful to identify disease progression.