© 2002 American Thoracic Society
Ups and Downs of Nitric Oxide in Chesty ChildrenInstitute of Pulmonology, Hadassah University Hospital, Jerusalem, Israel Correspondence and requests for reprints should be addressed to Prof. Simon Godfrey, M.D., Institute of Pulmonology, Hadassah University Hospital, POB 12000, Jerusalem, Israel. E-mail: sgodfrey{at}netvision.net.il In 1772, Joseph Priestley first described the brown, pungent gas, nitric oxide (NO), which, in recent times, has been shown to be elevated in that very common chronic disease of childhood, bronchial asthma. We pediatricians have other good reasons to be interested in this gas because its level in expired air is surprisingly low in two other ‘pediatric’ diseases: cystic fibrosis and primary ciliary dyskinesia. Moreover, NO may be involved in defense against infection in the airway, which is a major problem in these diseases. The number of articles published about NO and asthma has increased exponentially since the original studies in adults by Alving and coworkers in 1992 (1), and of these about one third are related to children. There have been several ‘State of the Art’ publications about NO and asthma in recent years, of which one was devoted entirely to childhood asthma (2). Now, the conclusions of a joint task force of the American Thoracic Society and the European Respiratory Society on the measurement of exhaled NO in children, held during 2001, have been published in the European Respiratory Journal (3). Why should we need a task force to study the measurement of exhaled NO (eNO) in children? The beauty and appeal of the measurement of eNO in adults and older children is that it is safe, easy, quick, and provides immediate answers about airway inflammation. All of these are ideal characteristics of a test for use in children, but is it possible to use it in children and are the results of clinical value? In the introduction to the task force report (3), the authors state that there is need for practical recommendations for the measurement of NO in children who cannot actively cooperate with the measurement. This is clearly of major importance because the gold standard of a single long exhalation at constant flow rate against a resistance used in adults and older children is rarely practical in the very young; however, it is just in the very young that we are most interested, because the important pediatric lung diseases for which measurement of eNO is relevant begin in early childhood. The report (3) addresses the problems of measurement of eNO at different ages in childhood. For older children, the standard single breath on-line (immediate analysis) or off-line (delayed analysis) methods of exhalation against an expiratory resistance with a controlled flow rate are clearly the best. In children aged 4 to 8 years, Baraldi and coworkers (4) found that 51% were unable to perform the standard test, chiefly because of inability or unwillingness to cooperate in the rather complicated maneuver required. This agrees with the study by Vilozni and coworkers (5) in which 62% of children aged 3 to 6 years were able to perform spirometry after training with the use of computer games. For children in this age range, Baraldi and coworkers (4) modified the standard single exhalation technique by employing a simple device with which the operator manually controlled expiratory flow. Of obvious appeal for infants and young children is the measurement of eNO during unrestricted tidal breathing, but this is problematic, chiefly because of contamination by NO from the nose and the variation in flow rate. Buchvald and Bisgaard (6) used a simple manual technique to control expiratory flow during tidal breathing in children aged 2 to 5 years to measure eNO. In infants in the first two years of life, measurements are particularly difficult, both because active cooperation is very difficult to obtain and because infants are nose breathers who will not normally tolerate nasal occlusion. Even so, two studies have shown that reasonably reproducible results could be obtained during tidal breathing with or without nasal occlusion (7, 8). Admittedly, we have found it very difficult to get consistent eNO results from infants during tidal breathing. A more complex but potentially more standardized technique was used in a study by Wildhaber and coworkers (9) in which eNO was measured during controlled forced expiratory flow from elevated lung volume in sedated infants. The importance of these studies is that they hint for the first time that there may be clear functional differences between infants with acute viral-induced wheeze and those with recurrent wheezing. In first time wheezers eNO was not elevated; but in recurrent wheezers it was elevated, and in this group it was reduced by corticosteroids. The task force (3) believes that the measurement of eNO in children should be useful for the diagnosis of asthma, to exclude or reduce the likelihood of a diagnosis of cystic fibrosis or primary ciliary dyskinesia, and possibly for monitoring asthma therapy. In older children, as in adults, eNO can be used to screen symptomatic patients for asthma. Of particular importance in childhood is the finding of a normal or low eNO in a symptomatic child who is not receiving corticosteroids. This makes the diagnosis of asthma unlikely and should prompt us to consider cystic fibrosis or primary ciliary dyskinesia as alternative diagnoses. In preschool children in whom eNO measurement is not easy and often impossible, there are other methods that are practical and diagnostic of asthma, such as the auscultatory method of performing a bronchial challenge (PCwheeze) with inhaled adenosine 5'-monophosphate (10). Measurements of eNO in the very young infant are not yet practical on a large scale but clearly of considerable importance. Since the task force completed its report, Hall and coworkers (11) described a very promising on-line tidal breathing technique for measuring eNO in infants with an intrasubject coefficient of variation of approximately 10%. As far as monitoring asthma is concerned, eNO levels track symptoms reasonably well, but in a pediatric study designed to determine whether eNO levels could predict an exacerbation during withdrawal of corticosteroids (12), the sensitivity and specificity of the test was very low, making it highly unreliable. Perhaps the most useful application of measuring eNO is as a measure of compliance—in most children with asthma, a markedly elevated eNO is not compatible with taking corticosteroids properly. FOOTNOTES This Occasional Essay is a commentary on an ERS/ATS Statement on exhaled nitric oxide in children published in the European Respiratory Journal. This statement may also be accessed at: http://www.thoracic.org/adobe/statements/NO1-15.pdf Received in original form July 1, 2002; accepted in final form July 3, 2002 REFERENCES
This article has been cited by other articles:
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
