Molecular diagnosis of respiratory tract infection in acute exacerbations of chronic obstructive pulmonary disease

Abstract

Acute exacerbations are significant events in the course of chronic obstructive pulmonary disease. Modern diagnostic techniques have revealed an infectious cause for the majority of exacerbations. Common respiratory viruses contribute to 25%-50% of exacerbations. Detection of viral nucleic acids in nasopharyngeal swab or sputum samples has become the preferred method to study viral exacerbations instead of viral cultures and serologic examination. Clinical application of such molecular detection requires additional studies to clarify interpretation of a positive result. Bacteria account for 25%-50% of exacerbations. Studies comparing molecular detection of bacteria in sputum with conventional culture techniques have shown that a substantial proportion of bacteria are not detected by the latter method. However, as with molecular viral detection, clinical application of molecular bacterial diagnosis requires additional studies. Although still faced with several challenges and requiring additional development, it is quite likely that molecular methods will become the preferred methods for determining the etiology of exacerbations of chronic obstructive pulmonary disease.

Figure 1.

Time line from a study clinic patient depicting clinic visits 38–45, which occurred ∼1 month apart. Results of sputum cultures are noted below each clinic visit. “+Hi” indicates culture positive for H. influenzae. “Neg” indicates culture negative for H. influenzae. Identical results of typing by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and pulsed-field gel electrophoresis (PFGE) are shown for the strains isolated at visits 38 and 45. An agarose gel at the right shows the results of PCR of the P2 gene (about 1.2 kb) of the sputum pellets from clinic visits as noted at the top of the gel. Molecular mass markers are noted in kilobases on the right. Reproduced with permission from Murphy TF, Brauer AL, Schiffmacher AT, Sethi S. Persistent colonization by Haemophilus influenzae in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2004;170(3):266–72. ©American Thoracic Society, 2004.