MCC/IMS as potential noninvasive technique in the diagnosis of patients with COPD with and without alpha 1-antitrypsin deficiency

Abstract

BackgroundChronic obstructive lung disease (COPD) is characterizedby a not fully reversible and usually progressive airflowlimitation. The disease is associated with an inflammatoryresponse of the lungs to noxious particles, mainly cigarettesmoke but also alpha 1-antitrypsin (AAT) deficiencypredisposes to COPD. The usual clinical practice fordiagnosing COPD is following symptoms, performing lungfunction and the assessment of responses to inhaledpharmacological agents. These tests have been standardizedand are generally considered as informative [1]. The testsare time consuming. Still the quality of the tests isinfluenced by experience and may differ depending wherethe tests are performed. Further, it is suggested that everyCOPD patient is once screened for AAT deficiency(AATD). Alpha 1-antitrypsin deficiency is a co-dominantinherited disorder that is diagnosed by low serum levels,genotyping and phenotyping of AAT.Usually the serum AAT levels are analyzed first. If theserum levels are decreased further procedures like genotyp-ing (with polymerase chain reaction) and phenotyping(isoelectric focusing) are suggested. The costs of thesediagnostic procedures are high [2] and therefore often notcarried out. Thus, there is a need for novel diagnosticmethods that are simple, fast and cost-effective and maybeperformed bedside. Within the past decade, cellular andmolecular techniques have been utilized as options for thediagnosis and monitoring of COPD and AAT deficiency [3].The analysis of exhaled breath (EB) has been used tononinvasively obtain information about inflammatory pro-cesses within the lung. EB contains a complex mixture ofvolatile organic compounds (VOCs), which can be detectedusing gas chromatography–mass spectrometry (GC-MS)[4]. Electronic noses (eNoses) use a concept essentiallydifferent from GC-MS. In addition, they allow the onlinerecognition of complex VOC mixtures via compositenanosensor arrays in combination with learning algorithms[5, 6]. Another approach is the ion mobility spectroscopy(IMS), were about 10 ml human breath will be analyzeddirectly and without any pre-enrichment. Two differenttypes of IMS, such coupled to multi-capillary columns(MCC/IMS) [7–15] and differential mobility spectrometers[16, 17] were used.It is currently assumed that COPD with or without AATdeficiency shows different molecular and cellular character-istics due to the pathophysiological inflammation present inAAT deficiency [18]. Thus, it may be that the VOC profileor smellprint is different in the EB of patients with COPD