Development of novel diagnostic approaches based on pulmonary physiology: applications in acute pulmonary embolism and obstructive sleep apnea

The most important function of the lungs is gas exchange. They are able to do so due to a sophisticated balance between ventilation and perfusion. Examples of diseases with a ventilation / perfusion mismatch are acute pulmonary embolism (PE, i.e. blood clots causing (partial) blockage of the pulmonary arteries) and obstructive sleep apnea (OSA, i.e. repetitive breathing stops during sleep due to collapse of the upper airway). In both cases novel diagnostic tools are warranted. The research presented in this thesis focused on the development of novel diagnostic tools using the consequences of ventilation / perfusion mismatches in PE and OSA. For the exclusion of PE at the emergency department, the usability of volumetric capnography and combined measurement of the transfer factor of the lungs for nitric oxide (TLNO) and carbon monoxide (TLCO) were investigated. There was no difference in TLNO / TLCO ratio between subjects with and without PE whereas a novel volumetric capnography derived parameter showed promising results. External validation however showed that this parameter was indeed significantly decreased in subjects with PE but its diagnostic accuracy was too low to allow its use in clinical practice. To be able to find novel strategies to exclude OSA without the need for laborious and expensive tests (e.g. poly(somno)graphy), the oxygen desaturation index (ODI) and the apnea hypopnea index (AHI) were compared in a large polygraphy database. This showed that an ODI < 5 excludes OSA (defined as an AHI ≥ 5) with high certainty. Subsequently, a strategy using a questionnaire and oximetry to exclude OSA in primary care was prospectively validated. As hypothesized, this strategy (i.e. refer to a sleep center if either the oximetry or the questionnaire is aberrant) enabled reliable exclusion of OSA. Another potential tool for the exclusion of OSA was the measurement of exhaled breath profiles using an electronic nose. Though there was a significant relationship between the exhaled breath profiles and the AHI, the profiles could not be used to reliable classify subjects into OSA or non-OSA.