Besides routine laboratory blood and urine tests, several specific blood and other tests for respiratory diseases are available (table 1). Investigations of sputum include bacteriological examination, cell differentiation, including eosinophils, and measurement of various inflammatory mediators. Exhaled gases or exhaled breath condensates, such as carbon monoxide and exhaled nitric oxide fraction, are used as markers of inflammatory and other diseases.
Microbiological tests have an essential role in the investigation of infectious respiratory diseases caused by viruses, bacteria, fungi or parasites. They include examination of expectorated (or induced) sputum and of specimens acquired by invasive biopsy techniques (discussed further later). The standard bacteriological techniques of microscopy and culture are often supplemented by molecular biological techniques (PCR) for detecting the DNA (or RNA) of the organism. Testing the susceptibility to antimicrobial agents is clinically very important.
Serological tests for confirming particular infections include identification of the relevant bacteriological or virological antigens and measurement of specific antibodies, in particular the demonstration of a rise in antibody titre. Urinary antigen detection may permit the rapid diagnosis of pneumococcal and Legionella infections.
Respiratory viruses may be cultured from different materials, most easily from nose or throat swabs. Serological tests in general provide only a retrospective assessment; specific immunoglobulin M may be of greater diagnostic value.
The laboratory diagnosis of pulmonary fungal infections is usually based on isolation of the organism from cultures, histological examination and serological tests, but also on direct microscopy after special staining (e.g. Pneumocystis jirovecii ).
Parasitic lung infections may be detected by microscopy of certain materials (e.g. stool, blood), serological tests or histological tests.
|Cystic fibrosis||Specific genetic tests|
|Lung cancer||Tumour marker (e.g. CEA, CYFRA 21-1, NSE, SCC)|
|Malignant mesothelioma||Tumour marker (mesothelin, osteopontin, fibulin)|
|(Latent) tuberculosis infection||Tuberculin skin test, interferon-gamma release assays|
|Unexplained breathlessness||NT-proBNP (increased in heart failure)|
|Sarcoidosis||Angiotensin-converting enzyme (ACE)|
|Extrinsic allergic alveolitis (hypersensitivity pneumonitis)||Specific precipitating antibodies|
|Asthma||Total and specific immunoglobulin E, skin testing with allergens|
|Connective tissue disorders||Immunological tests such as rheumatoid factor|
|Pleural effusion||Total protein, LDH, glucose, cholesterol and others in pleural fluid|
Table 1 – Specific laboratory tests for some respiratory diseases. NT-proBNP: N-terminal pro-brain natriuretic peptide; LDH: lactate dehydrogenase.
Histological and cytological examination
Histology and cytology play a central role in the diagnosis of many malignant and benign respiratory diseases, including infections. Apart from expectorated sputum, which can be examined cytologically, the specimens are acquired using various biopsy techniques (discussed further later) and are sent for histological and/or cytological evaluation.
Conventional histopathological techniques are often supplemented by immunohistochemistry using specific markers for the differentiation of several neoplasms, such as small cell neuroendocrine carcinoma and malignant lymphoma. In addition, results from molecular diagnostic tests may have important therapeutic (‘targeted’ treatment) as well as prognostic implications in certain types of nonsmall cell lung cancers (e.g. if mutations of the epidermal growth factor receptor (EGFR) are present).
Cytopathological examination is used mainly in the diagnosis of malignancies (e.g. malignant effusion). In bronchoalveolar lavage fluid, it may be helpful in the diagnosis of some interstitial lung diseases, such as extrinsic allergic alveolitis (hypersensitivity pneumonitis), eosinophilic pneumonia, alveolar proteinosis or asbestosis.
Ultimately, utopsy examination of the lung may provide important information regarding the underlying disease, but it is rarely performed nowadays.