Exhaled nitric oxide in extreme environments

Exhaled nitric oxide (NO) is a useful marker for lower airway inflammation. Since NO was found to be a component of an exhaled breath in the early 1990´s, the Fractional Exhaled Nitric Oxide (FENO 50) measurement is now well accepted among clinicians as a complementary test in the management of asthma. It is also used to some extent as a marker for other airway diseases, e.g. to map inflammation in the peripheral parts of the airway tree.

The first study in this thesis reports the development of a novel hand-held and highly portable instrument for exhaled NO measurement. It is principally intended for clinical use, but also potentially suitable for use in extreme environments, such as high altitude and spaceflight.

A second study investigated the effects of microgravity on exhaled NO and was based on results from cosmonauts and astronauts stationed on the International Space Station (ISS). It was concluded that the 45 % decrease in exhaled NO levels found in microgravity might be due to an increased backdiffusion of NO in the peripheral airways. The underlying mechanism leading to this increase is likely more homogenous distributions of the lung parenchyma and pulmonary-capillary blood. This would provide a more optimised airway caliber/length ratio which in turn would facilitate the gas diffusion from conducting airways to the alveoli. At the same time, the uptake of NO to the blood is likely to be enhanced due to an increased contact area between alveolar gas and pulmonary-capillary blood in microgravity.

In the third study, two instruments designed to measure exhaled NO were investigated at altitude. Because of decreased gas density and increased gas diffusivity at altitude, they behaved differently with regard to flow control and detector sensitivity. The readings at, for example an altitude of 4000 m, became 60 % too high in one of the instruments. Procedures were recommended for correction of the instrument output, so that it becomes comparable to sea level use. It is also recommended that exhaled NO measurements are quantified as partial pressure of NO (PENO), which would make comparison of readings over a range of altitudes more simple.

In the final study reported in this thesis, exhaled NO was studied in healthy humans at altitude. Measurements were performed at different levels of hypoxia down to an inspired PO2 of 10.7 kPa at simulated high altitude in a hypobaric chamber and were compared to similar levels of hypoxia at sea level. After corrections for the above instrument deviations, the exhaled NO levels at altitude were decreased with up to 33 % at 5000 m. The lowering of PENO could be related to the lower density and the higher binary diffusivity for NO in air at altitude. It is therefore proposed that the decrease was due to an increased backdiffusion of NO with increased uptake in pulmonary-capillary blood. The overall conclusion of the thesis is that changes in the physical environment (gravity, pressure) have profound effects on the measurements of exhaled NO.

List of scientific papers

I. Hemmingsson T, Linnarsson D, Gambert R (2004). Novel hand-held device for exhaled nitric oxide-analysis in research and clinical applications. J Clin Monit Comput. 18(5-6): 379-87
https://pubmed.ncbi.nlm.nih.gov/15957630

II. Karlsson LL, Kerckx Y, Gustafsson LE, Hemmingsson TE, Linnarsson D (2009). Microgravity decreases and hypergravity increases exhaled nitric oxide. J Appl Physiol. 107(5): 1431-7. Epub 2009 Sep 10
https://pubmed.ncbi.nlm.nih.gov/19745185

III. Hemmingsson T, Horn A, Linnarsson D (2009). Measuring exhaled nitric oxide at high altitude. Respir Physiol Neurobiol. 167(3): 292-8. Epub 2009 Jun 11
https://pubmed.ncbi.nlm.nih.gov/19524073

IV. Hemmingsson T, Linnarsson D (2009). Lower exhaled nitric oxide in hypobaric than in normobaric acute hypoxia. Respir Physiol Neurobiol. 169(1): 74-7. Epub 2009 Aug 15
https://pubmed.ncbi.nlm.nih.gov/19686871