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A Novel Method of Measuring Fractional Exhaled Nitric Oxide in Tracheostomized Ventilator-Dependent Children

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A Novel Method of Measuring Fractional Exhaled Nitric Oxide in Tracheostomized Ventilator-Dependent Children RESPIRATORY CARE Paper in Press. Published on February 28, 2017 as DOI: 10.4187/respcare.04858 A Novel Method of Measuring Fractional Exhaled Nitric Oxide in Tracheostomized Ventilator-Dependent Children Vydehi R Murthy MD, Hugo Escobar MD, Mike Norberg MDiv, Charisse I Lachica MD, Linda L Gratny MD, Ashley K Sherman MA, William E Truog MD, and Winston M Manimtim MD BACKGROUND: The lower airway concentration of fractional exhaled nitric oxide (FENO)is unknown in children with chronic lung disease of infancy who have tracheostomy for long-term mechanical ventilation. We aimed to evaluate an online method of measuring FENO in a cohort of ventilator-dependent children with a tracheostomy and to explore the relationship between the peak FENO concentration (FENO peak) and the degree of respiratory support using the respiratory se- verity score. METHODS: We conducted a prospective cross-sectional study in 31 subjects who were receiving long-term respiratory support through a tracheostomy. We measured the FENO peak and FENO plateau concentration from the tip of the tracheostomy tube using a nitric oxide analyzer in subjects during a quiet state while being mechanically ventilated. We obtained 2 consecutive 2-min duration measurements from each subject. The FENO peak, exhaled NO output (equal to the FENO -peak ؋ minute ventilation), and pulmonary NO excretion (exhaled NO output/weight) were cal culated and correlated with the respiratory severity score. RESULTS: The median FENO peak was 2.69 ppb, and the median FENO plateau was 1.57 ppb. The coefficients of repeatability between the 2 consecutive measurements for FENO peak and FENO plateau were 0.74 and 0.59, respectively. The intraclass coefficient between subjects within the cohort was 0.988 (95% CI 0.975–0.994, P < .001) for FENO peak and 0.991 (95% CI 0.982–0.996, P < .001) for FENO plateau. We found that the FENO peak was directly correlated with minute ventilation, but we did not find a direct relationship between the FENO peak concentration, exhaled NO output, or pulmonary NO excretion and respi- ratory severity score. CONCLUSIONS: FENO peak and plateau concentration can be measured online easily with a high degree of reliability and repeatability in infants and young children with a tracheostomy. FENO peak concentration from the lower airway is low and influenced by minute ventilation in children receiving mechanical ventilation. Key words: tracheostomy; fractional exhaled nitric oxide; chronic lung disease of infancy. [Respir Care 0;0(0):1–•. © 0 Daedalus Enterprises] Introduction cystic fibrosis, primary ciliary dyskinesia, and pulmonary 1,2 arterial hypertension. In patients with asthma, FENO is now used as a biomarker of eosinophilic airway inflam- Fractional exhaled nitric oxide (FENO) has been studied in many pulmonary diseases, including asthma, COPD, mation to diagnose, to monitor response and adherence to anti-inflammatory medications, and to predict upcoming 3 exacerbations. Studies measuring FENO in infants with respiratory distress syndrome, bronchopulmonary dyspla- The authors are affiliated with the Children’s Mercy Hospitals and Clin- ics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri. This work was supported by the Children’s Mercy Center for Infant Pulmonary Disorders and a Children’s Mercy Fellowship Research grant. Supplementary material related to this paper is available at http:// The authors have disclosed no conflicts of interest. www.rcjournal.com. Correspondence: Winston M Manimtim MD, Children’s Mercy Hospitals and Clinics, University of Missouri-Kansas City School of Medicine, 2401 DOI: 10.4187/respcare.04858 Gillham Road, Kansas City, MO 64108. E-mail: [email protected]. RESPIRATORY CARE • ●●VOL ● NO ● 1 Copyright (C) 2017 Daedalus Enterprises ePub ahead of print papers have been peer-reviewed, accepted for publication, copy edited and proofread. However, this version may differ from the final published version in the online and print editions of RESPIRATORY CARE RESPIRATORY CARE Paper in Press. Published on February 28, 2017 as DOI: 10.4187/respcare.04858 MEASURING FENO IN VENTILATOR-DEPENDENT CHILDREN sia (BPD), and chronic lung disease of infancy have yielded 4-8 conflicting results. The reasons for the variations in FENO QUICK LOOK include differences in patient population, timing of mea- Current knowledge surement in relation to the disease process and inhaled In patients with asthma, Fractional exhaled nitric oxide medication administration, use of different interface tech- (F niques, and other measuring conditions such as tidal breath- ENO) is used as a biomarker of eosinophilic airway ing parameters and variable exhalation flow. In 2005, the inflammation to diagnose, to monitor response and ad- American Thoracic Society and the European Respiratory herence to anti-inflammatory medications, and to pre- dict upcoming exacerbations. Studies measuring F Society jointly published recommendations9 for standard- ENO ized procedures for online and offline measurement of in infants with bronchopulmonary dysplasia and chronic exhaled lower respiratory NO and nasal NO. lung disease of infancy have yielded conflicting results. Additionally, the lower airway concentration of FENO is To our knowledge, FENO measurement in tracheos- tomized ventilator-dependent children with chronic lung unknown in children with a tracheostomy. disease of infancy has not been reported in the literature. What this paper contributes to our knowledge A small study in adult subjects with a tracheostomy (N ϭ 5) FENO concentration in ventilator-dependent children found that the baseline FENO was 4 times higher during oral exhalation compared with tracheal exhalation (16 Ϯ 2 with chronic lung disease of infancy who have a tra- ppb vs 4.6 Ϯ 0.8 ppb, P Ͻ .05), suggesting substantial cheostomy was measured easily with a high degree of 10 reliability and repeatability. The FENO concentration contribution from the upper airways. More recently, FENO was also found to be very low when measured from a measured from the tip of the tracheostomy tube was tracheostomy tube in adult subjects (N ϭ 14) after total low. FENO peak concentration from the lower airway laryngectomy (4 ppb, range 1–22) compared with healthy was affected by minute ventilation in ventilator-depen- controls (21 ppb, range 9–41).11 Contamination by nasal dent children with a tracheostomy. nitric oxide greatly affects the FENO level; therefore, it is essential to exclude the upper airways when determining FENO. In this study, we evaluated a novel method of measuring esophageal fistula, congenital cardiac disease, and congen- ital neuromuscular disorders.12 Those infants who remained FENO in a cohort of tracheostomized ventilator-dependent children with chronic lung disease of infancy. Second, we hospitalized were recruited while they were being cared for in the ICU, whereas those infants who were discharged attempted to correlate the FENO concentration with demo- graphic characteristics and degree of mechanical respira- home were recruited during their clinic visit to the infant tory support at the time of measurement by calculating the home ventilator clinic. Our reported rate of BPD is 45% respiratory severity score. We hypothesized that our method for infants with a birthweight of Ͻ1,500 g. The rate of tracheostomy in our patients with severe BPD is higher be- of measuring FENO would be feasible and reliable and that cause of the inherent population selection bias due to the fact the FENO concentration measured from the tip of the tra- cheostomy tube would be low in ventilator-dependent chil- that we are a level IV regional referral hospital where venti- dren with chronic lung disease of infancy. lator-dependent infants are being transferred for evaluation for tracheostomy and chronic home ventilation. To be in- Methods cluded, subjects had to be ventilator-dependent through a tracheostomy tube and clinically stable on a laptop ventilator, Study Design and Subjects LTV series 950 or 1150 (CareFusion, San Diego, California). Those patients whose ventilator dependence was due to ab- We conducted a prospective cross-sectional study from normal control of breathing (eg, central hypoventilation February 1, 2013 to May 31, 2014 and enrolled 31 subjects syndrome, severe post-hypoxic ischemic encephalopa- from a cohort of infants with chronic lung disease of in- thy) or peripheral neuromuscular disorders (eg, spinal fancy who had tracheostomy for long-term mechanical muscular atrophy) were excluded. Additionally, those ventilation. The diagnosis of chronic lung disease of in- infants with a diagnosis of cystic fibrosis or primary fancy was based on the American Thoracic Society defi- ciliary dyskinesia confirmed by genetic testing as doc- nition as a heterogeneous group of respiratory diseases umented in the electronic medical records were also that begin in the neonatal period, which includes BPD in excluded. Eligible infants who had received escalated premature infants and other chronic pulmonary conditions respiratory support within 48 h before FENO measure- in term newborns that result from meconium aspiration, ment as well as those who had received inhaled nitric pneumonia, pulmonary hypoplasia, persistent pulmonary oxide within the previous 48 h were likewise excluded. hypertension, congenital diaphragmatic hernia and tracheo- Our study was approved by the institutional review board 2RESPIRATORY CARE • ●●VOL ● NO ● Copyright (C) 2017 Daedalus Enterprises ePub ahead of print papers
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