In a piece of research run at the Paediatric Service of the Hospital Universitario Donostia, Dr Paula Corcuera-Elosegui, assistant consultant in Infant Pneumology, has studied the validity of the exhaled nitric oxide measurement as a complementary procedure in diagnosing and monitoring treatment for childhood asthma and overseeing the condition. She not only confirmed the usefulness of the test, she was able to develop a technique to apply it in breast-fed babies.
Asthma is the most frequent chronic disease in childhood. According to Dr Corcuera, “the prevalence of infant asthma in the north of the [Iberian] peninsula is 10%,” and she added: “Despite the advances that have taken place in recent years, this disease continues to have significant consequences for the patients, their families and the healthcare system.”
The doctor defined asthma as a complex disease, “because it manifests itself differently in each child, and the response to treatments also varies in each case.” One of the most well-known tools for diagnosing and assessing the degree of control of the disease is spirometry, which is used to determine lung function. However, spirometry may not be enough, and in recent years an important marker has emerged to complement the information provided by the spirometry test. It is exhaled nitric oxide, and this is in fact the focus of Dr Corcuera’s study.
“All of us mammals exhale this molecule,” explained Dr Corcuera, “and it is known that in asthma and in some other diseases its level may be above normal.” As there were few studies on exhaled nitric oxide in paediatric patients, the Infant Pneumology Unit set up a line of research to assess how useful the exhaled nitric oxide measurement is.
Dr Corcuera highlights certain aspects of the research, which has taken eight years. For example, with breast-fed babies “we use a mask that covers the nose and mouth and that way we collect the nitric oxide they have exhaled in consecutive breaths with tidal volume.” On the other hand, with older children, they carried out the validation of portable analysers that do not require such complex equipment or such specialised personnel.
Although Dr Corcuera admitted that the technique had certain limitations, and therefore always had to be complemented with clinical observation and the spirometry test, they have, however, proven that it is a valid, useful test, not only to help diagnose the disease but also to monitor the patients. “One of the outstanding results is that the determination of exhaled nitric oxide can also be done on breast-fed babies,” stressed Corcuera. “We have seen that the determination using multiple respirations with tidal volume and using a mouth-and-nose mask can be studied irrespective of age.”
Another of the new aspects observed in the study is that exhaled nitric oxide is usually determined proximally; in other words, in the bronchial tubes. Nevertheless, in the study carried out at the Hospital Universitario Donostia, the nitric oxide was also measured distally or on an alveolar level. This slight difference is important, since the results obtained suggest that raised alveolar nitric oxide could be linked to more severe asthma.
“To determine alveolar nitric oxide, we used another technique that determines the nitric oxide in several flows,” specified Corcuera. This technique has been applied to youngsters of between the ages of six and sixteen. “By means of a mathematical model, we do an approximation of alveolar nitric oxide, and it seems that those with a raised level of nitric oxide had had a larger number of crises over the previous month.”
However, the doctor warned that this link was not conclusive, “because the sample was quite small and the group of patients chosen were not ones with more severe asthma either.” That is why she said that she was planning “to go on studying this aspect to obtain clearer results.”
For the moment Dr Corcuera’s thesis (Óxido nítrico exhalado y asma: metodología, interpretación de los resultados y aplicaciones en niños – Exhaled nitric oxide and asthma: methodology, interpretation of the results and applications in children) covers the results and conclusions obtained so far. In addition, there has been significant dissemination of this work in the field of medical research through the publication of four papers in specialised journals.
About the author
Paula Corcuera-Elósegui (Donostia-San Sebastian, 1980) graduated in Medicine obtaining a first-class degree at the Faculty of Medicine and Odontology of the University of the Basque Country (UPV/EHU). She is a consultant in Paediatrics and its specific areas, and since 2008 has been assistant consultant in the Infant Pneumology Unit, Paediatric Service, Hospital Universitario Donostia.
She wrote up her PhD thesis Óxido nítrico exhalado y asma: metodología, interpretación de los resultados y aplicaciones en niños at the UPV/EHU’s Faculty of Medicine, under the supervision of Dr Eduardo González-Pérez-Yarza, Head of the Paediatric Service of the Hospital Universitario Donostia and tenured lecturer in Paediatrics at the UPV/EHU, and Dr Javier Korta-Murua, Head of the Infant Pneumology Section in the same hospital, and assistant lecturer in Paediatrics at the UPV/EHU.
The publications produced as a result:
– Sardón Prado O, Aldasoro Ruiz A, Korta Murua J, Mintegui Aranburu J, Emparanza Knorr JI, Pérez-Yarza EG. Concordancia entre dos dispositivos de medida de óxido nítrico exhalado [Concordance between two devices for measuring exhaled nitric oxide]. An Pediatr (Barc). 2007; 67: 572-577.
– Sardón Prado O, Pérez-Yarza EG, Aldasoro Ruiz A, Korta Murua J, Mintegui Aranburu J, Emparanza Knorr JI. Fracción exhalada de óxido nítrico: validación de la medida con tiempo de espiración de 6 s con dos analizadores diferentes [Exhaled nitric oxide fraction: measurement validation using 6-second exhalation time with two different analysers]. An Pediatr (Barc). 2008; 69: 221-226.
– Sardón-Prado O, Korta-Murua J, Valverde-Molina J, Fernández Paredes JJ, Mintegui J, Corcuera-Elosegui P et al. Association among lung function, exhaled nitric oxide, and the CAN questionnaire to assess asthma control in children. Pediatr Pulmonol. 2010; 45: 434-439.
– Sardón-Prado O, Pérez-Yarza EG, Aldasoro-Ruiz A, Korta-Murua J, Corcuera-Elosegui P, Mintegui-Aramburu J et al. Óxido nítrico exhalado e índice predictivo de asma en menores de dos años [Exhaled nitric oxide and asthma predictive index in two-year-olds]. Arch Bronconeumol. 2011; 47: 234-238.
– Castro-Rodriguez JA, Sardón O, Perez-Yarza EG, Korta J, Aldasoro A, Corcuera P et al. Young infants with recurrent wheezing and positive asthma predictive index have higher levels of exhaled nitric oxide. J Asthma. 2013; 50: 162-165.
University of the Basque Country