Effect of intubation and mechanical ventilation on exhaled nitric oxide in preterm infants with and without bronchopulmonary dysplasia measured at a median postmenstrual age of 49 weeks

BMC Research Notes

Christoph Bührer¹  Hendrik S Fischer¹  Silke Wilitzki¹  Gerd Schmalisch¹ 

[1]Department of Neonatology, Charité University Medicine, Charitéplatz 1, D - 10117 Berlin, Germany

关键词: Neonate;    Lung function test;    Bronchopulmonary dysplasia;    Mechanical ventilation;    Exhaled nitric oxide;    Prematurity;   

Others  :  1132399
DOI  :  10.1186/1756-0500-7-389

 received in 2014-01-24, accepted in 2014-06-19,  发布年份 2014

【 摘 要 】

Background

Exhaled nitric oxide (eNO) is a marker of established airway inflammation in adults and children, but conflicting results have been reported in preterm infants when postnatal eNO is measured during tidal breathing. This study investigated the extent to which intubation and mechanical ventilation (MV) affect eNO and NO production (V’_NO) in preterm infants with and without bronchopulmonary dysplasia (BPD).

Patients and methods

A total of 176 very low birth weight (VLBW) infants (birth weight <1500 g), including 74 (42%) with and 102 (58%) without BPD, were examined at a median postmenstrual age of 49 weeks. Of the 176 infants, 84 (48%) did not require MV, 47 (27%) required MV for <7 days and 45 (26%) required MV for ≥7 days. Exhaled NO and tidal breathing parameters were measured in sleeping infants during tidal breathing, respiratory mechanics were assessed by occlusion tests, and arterialized capillary blood gas was analyzed.

Results

eNO was significantly correlated with tidal breathing parameters, while V’_NO was correlated with growth parameters, including age and body length (p < 0.001 each). Infants who were intubated and received MV for <7 days had significantly lower eNO (p < 0.01) and V’_NO (p < 0.01) than non-ventilated infants. In contrast, eNO and V’_NO did not differ significantly in non-ventilated infants and those receiving MV for ≥7 days. Multivariate analysis showed that independent on the duration of MV eNO (p = 0.003) and V’_NO (p = 0.018) were significantly increased in BPD infants comparable with the effects of intubation and MV on eNO (p = 0.002) and V’_NO (p = 0.017).

Conclusions

Preterm infants with BPD show only weak postnatal increases in eNO and V’_NO, but these changes may be obscured by the distinct influences of breathing pattern and invasive respiratory support. This limits the diagnostic value of postnatal eNO measurements in the follow-up of BPD infants.

【 授权许可】

   
2014 Schmalisch et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Jobe AH, Bancalari E: Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001, 163:1723-1729.
• [2]Fakhoury KF, Sellers C, Smith EO, Rama JA, Fan LL: Serial measurements of lung function in a cohort of young children with bronchopulmonary dysplasia. Pediatrics 2010, 125:e1441-e1447.
• [3]Robin B, Kim YJ, Huth J, Klocksieben J, Torres M, Tepper RS, Castile RG, Solway J, Hershenson MB, Goldstein-Filbrun A: Pulmonary function in bronchopulmonary dysplasia. Pediatr Pulmonol 2004, 37:236-242.
• [4]Vrijlandt EJ, Boezen HM, Gerritsen J, Stremmelaar EF, Duiverman EJ: Respiratory health in prematurely born preschool children with and without bronchopulmonary dysplasia. J Pediatr 2007, 150:256-261.
• [5]Gappa M, Stocks J, Merkus P: Lung growth and development after preterm birth: further evidence. Am J Respir Crit Care Med 2003, 168:399.
• [6]Hoo AF, Dezateux C, Henschen M, Costeloe K, Stocks J: Development of airway function in infancy after preterm delivery. J Pediatr 2002, 141:652-658.
• [7]Kotecha SJ, Edwards MO, Watkins WJ, Henderson AJ, Paranjothy S, Dunstan FD, Kotecha S: Effect of preterm birth on later FEV1: a systematic review and meta-analysis. Thorax 2013, 68:760-766.
• [8]Schmalisch G, Wilitzki S, Roehr CC, Proquitte H, Bührer C: Differential effects of immaturity and neonatal lung disease on the lung function of very low birth weight infants at 48–52 postconceptional weeks. Pediatr Pulmonol 2013, 48:1214-1223.
• [9]Pelkonen AS, Hakulinen AL, Turpeinen M: Bronchial lability and responsiveness in school children born very preterm. Am J Respir Crit Care Med 1997, 156:1178-1184.
• [10]Smyth JA, Tabachnik E, Duncan WJ, Reilly BJ, Levison H: Pulmonary function and bronchial hyperreactivity in long-term survivors of bronchopulmonary dysplasia. Pediatrics 1981, 68:336-340.
• [11]Gabriele C, Jaddoe VW, van Mastrigt E, Arends LR, Hofman A, Moll HA, de Jongste JC: Exhaled nitric oxide and the risk of wheezing in infancy: the generation R study. Eur Respir J 2012, 39:567-572.
• [12]May C, Williams O, Milner AD, Peacock J, Rafferty GF, Hannam S, Greenough A: Relation of exhaled nitric oxide levels to development of bronchopulmonary dysplasia. Arch Dis Child Fetal Neonatal Ed 2009, 94:F205-F209.
• [13]Leipala JA, Williams O, Sreekumar S, Cheeseman P, Rafferty GF, Hannam S, Milner A, Greenough A: Exhaled nitric oxide levels in infants with chronic lung disease. Eur J Pediatr 2004, 163:555-558.
• [14]Gabriele C, Nieuwhof EM, Van Der Wiel EC, Hofhuis W, Moll HA, Merkus PJ, de Jongste JC: Exhaled nitric oxide differentiates airway diseases in the first two years of life. Pediatr Res 2006, 60:461-465.
• [15]Roiha HL, Kuehni CE, Zanolari M, Zwahlen M, Baldwin DN, Casaulta C, Nelle M, Frey U: Alterations of exhaled nitric oxide in pre-term infants with chronic lung disease. Eur Respir J 2007, 29:251-258.
• [16]Filippone M, Bonetto G, Corradi M, Frigo AC, Baraldi E: Evidence of unexpected oxidative stress in airways of adolescents born very pre-term. Eur Respir J 2012, 40:1253-1259.
• [17]Cazzato S, Ridolfi L, Bernardi F, Faldella G, Bertelli L: Lung function outcome at school age in very low birth weight children. Pediatr Pulmonol 2012, 48:830-837.
• [18]Mieskonen ST, Malmberg LP, Kari MA, Pelkonen AS, Turpeinen MT, Hallman NM, Sovijarvi AR: Exhaled nitric oxide at school age in prematurely born infants with neonatal chronic lung disease. Pediatr Pulmonol 2002, 33:347-355.
• [19]Baraldi E, Bonetto G, Zacchello F, Filippone M: Low exhaled nitric oxide in school-age children with bronchopulmonary dysplasia and airflow limitation. Am J Respir Crit Care Med 2005, 171:68-72.
• [20]Manna A, Caffarelli C, Varini M, Povesi DC, Montella S, Maglione M, Sperli F, Santamaria F: Clinical application of exhaled nitric oxide measurement in pediatric lung diseases. Ital J Pediatr 2012, 38:74.
• [21]Chang CC, Liu TY, Hua YM, Lee CM, Yuh YS: Endogenous nitric oxide in the nasal airways of healthy term newborn infants in Taiwan. Pediatr Neonatol 2008, 49:166-170.
• [22]Sahin G, Klimek L, Mullol J, Hormann K, Walther LE, Pfaar O: Nitric oxide: a promising methodological approach in airway diseases. Int Arch Allergy Immunol 2011, 156:352-361.
• [23]Anonymous: ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med 2005, 171:912-930.
• [24]Bohlin K, Jonsson B, Gustafsson AS, Blennow M: Continuous positive airway pressure and surfactant. Neonatology 2008, 93:309-315.
• [25]Hall GL, Reinmann B, Wildhaber JH, Frey U: Tidal exhaled nitric oxide in healthy, unsedated newborn infants with prenatal tobacco exposure. J Appl Physiol 2002, 92:59-66.
• [26]Latzin P, Kuehni CE, Baldwin DN, Roiha HL, Casaulta C, Frey U: Elevated exhaled nitric oxide in newborns of atopic mothers precedes respiratory symptoms. Am J Respir Crit Care Med 2006, 174:1292-1298.
• [27]Nguyen TT, Hoo AF, Lum S, Wade A, Thia LP, Stocks J: New reference equations to improve interpretation of infant lung function. Pediatr Pulmonol 2012, 48:370-380.
• [28]Voigt M, Schneider KT, Jährig K: Analysis of a 1992 birth sample in Germany. 1: new percentile values of the body weight of newborn infants. Geburtshilfe Frauenheilkd 1996, 56:550-558.
• [29]Fuchs O, Latzin P, Thamrin C, Stern G, Frischknecht P, Singer F, Kieninger E, Proietti E, Riedel T, Frey U: Normative data for lung function and exhaled nitric oxide in unsedated healthy infants. Eur Respir J 2010, 37:1208-1216.
• [30]Williams O, Dimitriou G, Hannam S, Rafferty GF, Greenough A: Lung function and exhaled nitric oxide levels in infants developing chronic lung disease. Pediatr Pulmonol 2007, 42:107-113.
• [31]Karadag B, James AJ, Gultekin E, Wilson NM, Bush A: Nasal and lower airway level of nitric oxide in children with primary ciliary dyskinesia. Eur Respir J 1999, 13:1402-1405.
• [32]Corbelli R, Hammer J: Measurement of nasal nitric oxide. Paediatr Respir Rev 2007, 8:269-272.
• [33]Ricciardolo FL, Silvestri M, Pistorio A, Strozzi MM, Tosca MA, Bellodi SC, Battistini E, Gardella C, Rossi GA: Determinants of exhaled nitric oxide levels (FeNO) in childhood atopic asthma: evidence for neonatal respiratory distress as a factor associated with low FeNO levels. J Asthma 2010, 47:810-816.
• [34]Speer CP: Inflammation and bronchopulmonary dysplasia: a continuing story. Semin Fetal Neonatal Med 2006, 11:354-362.
• [35]Frey U, Kuehni C, Roiha H, Cernelc M, Reinmann B, Wildhaber JH, Hall GL: Maternal atopic disease modifies effects of prenatal risk factors on exhaled nitric oxide in infants. Am J Respir Crit Care Med 2004, 170:260-265.
• [36]Latzin P, Frey U: Environmental exposure in relation to exhaled nitric oxide in newborns: is it all about timing? Eur Respir J 2008, 32:252-254.
• [37]Eckel SP, Berhane K, Salam MT, Rappaport EB, Linn WS, Bastain TM, Zhang Y, Lurmann F, Avol EL, Gilliland FD: Residential traffic-related pollution exposures and exhaled nitric oxide in the children’s health study. Environ Health Perspect 2011, 119:1472-1477.
• [38]Baraldi E, de Jongste JC: Measurement of exhaled nitric oxide in children, 2001. Eur Respir J 2002, 20:223-237.
• [39]Proquitte H, Krause S, Rüdiger M, Wauer RR, Schmalisch G: Current limitations of volumetric capnography in surfactant-depleted small lungs. Pediatr Crit Care Med 2004, 5:75-80.
• [40]Schmalisch G, Al-Gaaf S, Proquitte H, Roehr CC: Effect of endotracheal tube leak on capnographic measurements in a ventilated neonatal lung model. Physiol Meas 2012, 33:1-11.
• [41]Latzin P, Roth S, Thamrin C, Hutten GJ, Pramana I, Kuehni CE, Casaulta C, Nelle M, Riedel T, Frey U: Lung volume, breathing pattern and ventilation inhomogeneity in preterm and term infants. PLoS One 2009, 4:e4635.
• [42]Schmalisch G, Wilitzki S, Wauer RR: Differences in tidal breathing between infants with chronic lung diseases and healthy controls. BMC Pediatr 2005, 5:36.
• [43]Lum S, Hoo AF, Hulskamp G, Wade A, Stocks J: Potential misinterpretation of infant lung function unless prospective healthy controls are studied. Pediatr Pulmonol 2010, 45:906-913.
• [44]Fawke J, Lum S, Kirkby J, Hennessy E, Marlow N, Rowell V, Thomas S, Stocks J: Lung function and respiratory symptoms at 11 years in children born extremely preterm: the EPICure study. Am J Respir Crit Care Med 2010, 182:237-245.
• [45]Lum S, Kirkby J, Welsh L, Marlow N, Hennessy E, Stocks J: Nature and severity of lung function abnormalities in extremely pre-term children at 11 years of age. Eur Respir J 2011, 37:1199-1207.