Late outcomes of a randomized trial of high-frequency oscillation in neonates. Zivanovic Sanja,Peacock Janet,Alcazar-Paris Mireia,Lo Jessica W,Lunt Alan,Marlow Neil,Calvert Sandy,Greenough Anne The New England journal of medicine BACKGROUND:Results from an observational study involving neonates suggested that high-frequency oscillatory ventilation (HFOV), as compared with conventional ventilation, was associated with superior small-airway function at follow-up. Data from randomized trials are needed to confirm this finding. METHODS:We studied 319 adolescents who had been born before 29 weeks of gestation and had been enrolled in a multicenter, randomized trial that compared HFOV with conventional ventilation immediately after birth. The trial involved 797 neonates, of whom 592 survived to hospital discharge. We compared follow-up data from adolescents who had been randomly assigned to HFOV with follow-up data from those who had been randomly assigned to conventional ventilation, with respect to lung function and respiratory health, health-related quality of life, and functional status, as assessed with the use of questionnaires completed when the participants were 11 to 14 years of age. The primary outcome was forced expiratory flow at 75% of the expired vital capacity (FEF75). RESULTS:The HFOV group had superior results on a test of small-airway function (z score for FEF75, -0.97 with HFOV vs. -1.19 with conventional therapy; adjusted difference, 0.23 [95% confidence interval, 0.02 to 0.45]). There were significant differences in favor of HFOV in several other measures of respiratory function, including forced expiratory volume in 1 second, forced vital capacity, peak expiratory flow, diffusing capacity, and impulse-oscillometric findings. As compared with the conventional-therapy group, the HFOV group had significantly higher ratings from teachers in three of eight school subjects assessed, but there were no other significant differences in functional outcomes. CONCLUSIONS:In a randomized trial involving children who had been born extremely prematurely, those who had undergone HFOV, as compared with those who had received conventional ventilation, had superior lung function at 11 to 14 years of age, with no evidence of poorer functional outcomes. (Funded by the National Institute for Health Research Health Technology Assessment Programme and others.). 10.1056/NEJMoa1309220
    Cardioventilatory Control in Preterm-born Children and the Risk of Obstructive Sleep Apnea. Armoni Domany Keren,Hossain Md Monir,Nava-Guerra Leonardo,Khoo Michael C,McConnell Keith,Carroll John L,Xu Yuanfang,DiFrancesco Mark,Amin Raouf S American journal of respiratory and critical care medicine RATIONALE:The contribution of ventilatory control to the pathogenesis of obstructive sleep apnea (OSA) in preterm-born children is unknown. OBJECTIVES:To characterize phenotypes of ventilatory control that are associated with the presence of OSA in preterm-born children during early childhood. METHODS:Preterm- and term-born children without comorbid conditions were enrolled. They were categorized into an OSA group and a non-OSA group on the basis of polysomnography. MEASUREMENTS AND MAIN RESULTS:Loop gain, controller gain, and plant gain, reflecting ventilatory instability, chemoreceptor sensitivity, and blood gas response to a change in ventilation, respectively, were estimated from spontaneous sighs identified during polysomnography. Cardiorespiratory coupling, a measure of brainstem maturation, was estimated by measuring the interval between inspiration and the preceding electrocardiogram R-wave. Cluster analysis was performed to develop phenotypes based on controller gain, plant gain, cardiorespiratory coupling, and gestational age. The study included 92 children, 63 of whom were born preterm (41% OSA) and 29 of whom were born at term (48% OSA). Three phenotypes of ventilatory control were derived with risks for OSA being 8%, 47%, and 77% in clusters 1, 2, and 3, respectively. There was a stepwise decrease in controller gain and an increase in plant gain from clusters 1 to 3. Children in cluster 1 had significantly higher cardiorespiratory coupling and gestational age than clusters 2 and 3. No difference in loop gain was found between clusters. CONCLUSIONS:The risk for OSA could be stratified according to controller gain, plant gain, cardiorespiratory coupling, and gestational age. These findings could guide personalized care for children at risk for OSA. 10.1164/rccm.201708-1700OC
    Expiratory airflow in late adolescence and early adulthood in individuals born very preterm or with very low birthweight compared with controls born at term or with normal birthweight: a meta-analysis of individual participant data. Doyle Lex W,Andersson Sture,Bush Andy,Cheong Jeanie L Y,Clemm Hege,Evensen Kari Anne I,Gough Aisling,Halvorsen Thomas,Hovi Petteri,Kajantie Eero,Lee Katherine J,McGarvey Lorcan,Narang Indra,Näsänen-Gilmore Pieta,Steinshamn Sigurd,Vollsaeter Maria,Vrijlandt Elianne J L E, The Lancet. Respiratory medicine BACKGROUND:Maximal expiratory airflow peaks early in the third decade of life, then gradually declines with age. The pattern of airflow through adulthood for individuals born very preterm (at <32 weeks' gestation) or with very low birthweight (<1501 g) is unknown. We aimed to compare maximal expiratory airflow in these individuals during late adolescence and early adulthood with that of control individuals born with normal birthweight (>2499 g) or at term. METHODS:We did a meta-analysis of individual participant data from cohort studies, mostly from the pre-surfactant era. Studies were identified through the Adults born Preterm International Collaboration and by searching PubMed and Embase (search date May 25, 2016). Studies were eligible if they reported on expiratory flow rates beyond 16 years of age in individuals born very preterm or with very low birthweight, as well as controls born at term or with normal birthweight. Studies with highly selected cohorts (eg, only participants with bronchopulmonary dysplasia) or in which few participants were born very preterm or with very low birthweight were excluded. De-identified individual participant data from each cohort were provided by the holders of the original data to a central site, where all the data were pooled into one data file. Any data inconsistencies were resolved by discussion with the individual sites concerned. Individual participant data on expiratory flow variables (FEV, forced vital capacity [FVC], FEV/FVC ratio, and forced expiratory flow at 25-75% of FVC [FEF]) were converted to Z scores and analysed with use of generalised linear mixed models in a one-step approach. FINDINGS:Of the 381 studies identified, 11 studies, comprising a total of 935 participants born very preterm or with very low birthweight and 722 controls, were eligible and included in the analysis. Mean age at testing was 21 years (SD 3·4; range 16-33). Mean Z scores were close to zero (as expected) in the control group, but were reduced in the very preterm or very low birthweight group for FEV (-0·06 [SD 1·03] vs -0·81 [1·33], mean difference -0·78 [95% CI -0·96 to -0·61], p<0·0001), FVC (-0·15 [0·98] vs -0·38 [1·18], -0·25 [-0·40 to -0·10], p=0·0012), FEV/FVC ratio (0·14 [1·10] vs -0·64 [1·35], -0·74 [-0·85 to -0·64], p<0·0001), and FEF (-0·04 [1·10] vs -0·95 [1·47], -0·88 [-1·12 to -0·65], p<0·0001). Similar patterns were observed when we compared the proportions of individuals with values below the fifth percentile. INTERPRETATION:Individuals born very preterm or with very low birthweight are at risk of not reaching their full airway growth potential in adolescence and early adulthood, suggesting an increased risk of chronic obstructive pulmonary disease in later adulthood. FUNDING:National Health and Medical Research Council (Australia), University of Bergen, Western Norway Regional Authority, National Institute for Health Research (UK), Stichting Astmabestrijding, St Olav's Hospital's Research Fund, Academy of Finland, European Commission, National Institute of Child Health and Human Development (USA), Victorian Government's Operational Infrastructure Support Program. 10.1016/S2213-2600(18)30530-7
    Effect of Sustained Inflations vs Intermittent Positive Pressure Ventilation on Bronchopulmonary Dysplasia or Death Among Extremely Preterm Infants: The SAIL Randomized Clinical Trial. Kirpalani Haresh,Ratcliffe Sarah J,Keszler Martin,Davis Peter G,Foglia Elizabeth E,Te Pas Arjan,Fernando Melissa,Chaudhary Aasma,Localio Russell,van Kaam Anton H,Onland Wes,Owen Louise S,Schmölzer Georg M,Katheria Anup,Hummler Helmut,Lista Gianluca,Abbasi Soraya,Klotz Daniel,Simma Burkhard,Nadkarni Vinay,Poulain Francis R,Donn Steven M,Kim Han-Suk,Park Won Soon,Cadet Claudia,Kong Juin Yee,Smith Alexandra,Guillen Ursula,Liley Helen G,Hopper Andrew O,Tamura Masanori, JAMA Importance:Preterm infants must establish regular respirations at delivery. Sustained inflations may establish lung volume faster than short inflations. Objective:To determine whether a ventilation strategy including sustained inflations, compared with standard intermittent positive pressure ventilation, reduces bronchopulmonary dysplasia (BPD) or death at 36 weeks' postmenstrual age without harm in extremely preterm infants. Design, Setting, and Participants:Unmasked, randomized clinical trial (August 2014 to September 2017, with follow-up to February 15, 2018) conducted in 18 neonatal intensive care units in 9 countries. Preterm infants 23 to 26 weeks' gestational age requiring resuscitation with inadequate respiratory effort or bradycardia were enrolled. Planned enrollment was 600 infants. The trial was stopped after enrolling 426 infants, following a prespecified review of adverse outcomes. Interventions:The experimental intervention was up to 2 sustained inflations at maximal peak pressure of 25 cm H2O for 15 seconds using a T-piece and mask (n = 215); standard resuscitation was intermittent positive pressure ventilation (n = 211). Main Outcome and Measures:The primary outcome was the rate of BPD or death at 36 weeks' postmenstrual age. There were 27 prespecified secondary efficacy outcomes and 7 safety outcomes, including death at less than 48 hours. Results:Among 460 infants randomized (mean [SD] gestational age, 25.30 [0.97] weeks; 50.2% female), 426 infants (92.6%) completed the trial. In the sustained inflation group, 137 infants (63.7%) died or survived with BPD vs 125 infants (59.2%) in the standard resuscitation group (adjusted risk difference [aRD], 4.7% [95% CI, -3.8% to 13.1%]; P = .29). Death at less than 48 hours of age occurred in 16 infants (7.4%) in the sustained inflation group vs 3 infants (1.4%) in the standard resuscitation group (aRD, 5.6% [95% CI, 2.1% to 9.1%]; P = .002). Blinded adjudication detected an imbalance of rates of early death possibly attributable to resuscitation (sustained inflation: 11/16; standard resuscitation: 1/3). Of 27 secondary efficacy outcomes assessed by 36 weeks' postmenstrual age, 26 showed no significant difference between groups. Conclusions and Relevance:Among extremely preterm infants requiring resuscitation at birth, a ventilation strategy involving 2 sustained inflations, compared with standard intermittent positive pressure ventilation, did not reduce the risk of BPD or death at 36 weeks' postmenstrual age. These findings do not support the use of ventilation with sustained inflations among extremely preterm infants, although early termination of the trial limits definitive conclusions. Trial Registration:clinicaltrials.gov Identifier: NCT02139800. 10.1001/jama.2019.1660
    Lung function deficits of adults born very preterm and with very low birthweight. Dharmage Shyamali C,Bui Dinh S,Perret Jennifer L,Lodge Caroline J The Lancet. Respiratory medicine 10.1016/S2213-2600(19)30042-6
    Bronchopulmonary dysplasia. Thébaud Bernard,Goss Kara N,Laughon Matthew,Whitsett Jeffrey A,Abman Steven H,Steinhorn Robin H,Aschner Judy L,Davis Peter G,McGrath-Morrow Sharon A,Soll Roger F,Jobe Alan H Nature reviews. Disease primers In the absence of effective interventions to prevent preterm births, improved survival of infants who are born at the biological limits of viability has relied on advances in perinatal care over the past 50 years. Except for extremely preterm infants with suboptimal perinatal care or major antenatal events that cause severe respiratory failure at birth, most extremely preterm infants now survive, but they often develop chronic lung dysfunction termed bronchopulmonary dysplasia (BPD; also known as chronic lung disease). Despite major efforts to minimize injurious but often life-saving postnatal interventions (such as oxygen, mechanical ventilation and corticosteroids), BPD remains the most frequent complication of extreme preterm birth. BPD is now recognized as the result of an aberrant reparative response to both antenatal injury and repetitive postnatal injury to the developing lungs. Consequently, lung development is markedly impaired, which leads to persistent airway and pulmonary vascular disease that can affect adult lung function. Greater insights into the pathobiology of BPD will provide a better understanding of disease mechanisms and lung repair and regeneration, which will enable the discovery of novel therapeutic targets. In parallel, clinical and translational studies that improve the classification of disease phenotypes and enable early identification of at-risk preterm infants should improve trial design and individualized care to enhance outcomes in preterm infants. 10.1038/s41572-019-0127-7
    Physiology and Predictors of Impaired Gas Exchange in Infants with Bronchopulmonary Dysplasia. Svedenkrans Jenny,Stoecklin Benjamin,Jones J Gareth,Doherty Dorota A,Pillow J Jane American journal of respiratory and critical care medicine A sensitive outcome measure for infants with bronchopulmonary dysplasia would facilitate clinical benchmarking and enhance epidemiologic understanding, evaluation of clinical interventions, and outcome prediction. Noninvasive assessment of pulmonary gas exchange in preterm infants with and without bronchopulmonary dysplasia to grade disease severity and to identify determinants of impaired gas exchange. This is a prospective observational study in very preterm infants. Inspired oxygen partial pressure (Pi) was decreased stepwise to achieve oxygen saturation as measured by pulse oximetry (Sp) that decreased from 95% to 86%. Right shift, a/, and right-left shunt were derived from the resulting Sp versus Pi curve and compared with current disease severity classification. Potential determinants of shift, a/, and shunt were identified using principal components analysis and multiple linear regression. A total of 219 infants with median (interquartile range) gestation of 28 weeks and 0 days (26 weeks and 0 days to 29 weeks and 0 days) had a valid study at 35 weeks and 4 days (34 weeks and 1 day to 39 weeks and 3 days) of postmenstrual age. Shift increased and a/ decreased as severity of bronchopulmonary dysplasia increased. Infants with moderate-severe disease also had increased shunt. Extent of impaired gas exchange overlapped between severity groups. Infants requiring mechanical support but no supplemental oxygen at 36 weeks' postmenstrual age had similar values of shift, a/, and shunt to preterm infants without bronchopulmonary dysplasia. Lower gestation and increased duration of invasive ventilation independently predicted increased shift, decreased a/, and increased shunt. Shift was the most sensitive and specific index of the severity of bronchopulmonary dysplasia. Most infants with bronchopulmonary dysplasia have impaired oxygenation quantified by a simple, sensitive bedside test. Shift of the Sp/Pi curve may be useful for prediction and measurement of preterm infant respiratory outcomes. 10.1164/rccm.201810-2037OC
    Ventilation in Preterm Infants and Lung Function at 8 Years. Kugelman Amir The New England journal of medicine 10.1056/NEJMc1711170
    Can infant lung function predict respiratory morbidity during the first year of life in preterm infants? Proietti Elena,Riedel Thomas,Fuchs Oliver,Pramana Isabelle,Singer Florian,Schmidt Anne,Kuehni Claudia,Latzin Philipp,Frey Urs The European respiratory journal Compared with term-born infants, preterm infants have increased respiratory morbidity in the first year of life. We investigated whether lung function tests performed near term predict subsequent respiratory morbidity during the first year of life and compared this to standard clinical parameters in preterms. The prospective birth cohort included randomly selected preterm infants with and without bronchopulmonary dysplasia. Lung function (tidal breathing and multiple-breath washout) was measured at 44 weeks post-menstrual age during natural sleep. We assessed respiratory morbidity (wheeze, hospitalisation, inhalation and home oxygen therapy) after 1 year using a standardised questionnaire. We first assessed the association between lung function and subsequent respiratory morbidity. Secondly, we compared the predictive power of standard clinical predictors with and without lung function data. In 166 preterm infants, tidal volume, time to peak tidal expiratory flow/expiratory time ratio and respiratory rate were significantly associated with subsequent wheeze. In comparison with standard clinical predictors, lung function did not improve the prediction of later respiratory morbidity in an individual child. Although associated with later wheeze, noninvasive infant lung function shows large physiological variability and does not add to clinically relevant risk prediction for subsequent respiratory morbidity in an individual preterm. 10.1183/09031936.00149213
    [Dynamic observation of pulmonary function by plethysmography in preterm infants with bronchopulmonary dysplasia]. Zhang Jing,Zhang Ling-Ping,Kang Lan,Lei Xiao-Ping,Dong Wen-Bin Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics OBJECTIVE:To study the effect of bronchopulmonary dysplasia (BPD) on lung function in preterm infants. METHODS:According to the presence/absence or the severity of BPD, 72 preterm infants were divided into non-BPD group (n=44), mild BPD group (n=15) and moderate BPD group (n=13). Lung function was assessed by plethysmography on days 7, 14 and 28 after birth. RESULTS:The preterm infants in the three groups had gradual increases in tidal volume per kilogram (TV/kg), functional residual capacity (FRC), ratio of time to peak tidal expiratory flow to total expiratory time (%T-PF) and ratio of volume to peak tidal expiratory flow to total expiratory volume (%V-PF) on days 7, 14 and 28 after birth, while there were gradual reductions in effective airway resistance per kilogram (Reff/kg) and respiratory rate (RR) (P<0.05). Compared with the non-BPD group on days 7, 14 and 28 after birth, the mild and moderate BPD groups had significantly lower TV/kg, FRC, %T-PF, and %V-PF and significantly higher Reff/kg and RR (P<0.05). On day 7 after birth, the moderate BPD group had significantly higher airway resistance, Reff/kg and FRC/kg than the mild BPD group (P<0.05). CONCLUSIONS:There is a certain degree of pulmonary function impairment in preterm infants with BPD. Dynamic monitoring of lung function by plethysmography is useful for assessing lung development in the neonatal period in these infants.
    Chorioamnionitis and subsequent lung function in preterm infants. Jones Marcus H,Corso Andréa L,Tepper Robert S,Edelweiss Maria I A,Friedrich Luciana,Pitrez Paulo M C,Stein Renato T PloS one OBJECTIVE:To explore the relationship between prematurity, gender and chorioamnionitis as determinants of early life lung function in premature infants. METHODS:Placenta and membranes were collected from preterm deliveries (<37 weeks gestational age) and evaluated for histological chorioamnionitis (HCA). Patients were followed and lung function was performed in the first year of life by Raised Volume-Rapid Thoracic Compression Technique. RESULTS:Ninety-five infants (43 males) born prematurely (median gestational age 34.2 weeks) were recruited. HCA was detected in 66 (69%) of the placentas, and of these 55(58%) were scored HCA Grade 1, and 11(12%) HCA Grade 2. Infants exposed to HCA Grade 1 and Grade 2, when compared to those not exposed, presented significantly lower gestational ages, higher prevalence of RDS, clinical early-onset sepsis, and the use of supplemental oxygen more than 28 days. Infants exposed to HCA also had significantly lower maximal flows. There was a significant negative trend for z-scores of lung function in relation to levels of HCA; infants had lower maximal expiratory flows with increasing level of HCA. (p = 0.012 for FEF50, p = 0.014 for FEF25-75 and p = 0.32 for FEV0.5). Two-way ANOVA adjusted for length and gestational age indicated a significant interaction between sex and HCA in determining expiratory flows (p<0.01 for FEF50, FEF25-75 and p<0.05 for FEV0.5). Post-hoc comparisons revealed that female preterm infants exposed to HCA Grade 1 and Grade 2 had significant lower lung function than those not exposed, and this effect was not observed among males. CONCLUSIONS:Our findings show a sex-specific negative effect of prenatal inflammation on lung function of female preterm infants. This study confirms and expands knowledge upon the known association between chorioamnionitis and early life chronic lung disease. 10.1371/journal.pone.0081193
    Lung function gain in preterm infants with and without bronchopulmonary dysplasia. Sanchez-Solis Manuel,Perez-Fernandez Virginia,Bosch-Gimenez Vicente,Quesada Juan J,Garcia-Marcos Luis Pediatric pulmonology OBJECTIVES:The aim of our study was to determine whether the development of lung function, during the first 2 years of life, is different in preterm infants who suffered or did not suffer from Bronchopulmonary dysplasia (BPD). We also assessed the role of nutritional status and growth in that development. METHODS:Lung function tests were performed in 71 preterm infants at two time points: 6 months of corrected age and 1 year after. FVC, FEV0.5, FEF75 , and FEF25-75 were obtained from maximal expiratory volume curves by means of the raised volume rapid thoraco-abdominal compression technique. RESULTS:When comparing lung function measurements, we found that FVC (P = 0.033) FEV0.5 (P = 0.044), FEF75 (P = 0.014), and FEF25-75 (P = 0.036) were significantly lower in BPD infants. We did not find any catch-up of lung function during the study time, in neither the whole group of children nor within the BPD or non-BPD groups. The increase in lung function was directly proportional to the increase in weight and length. The multivariate analysis showed that the increase in z-score of FVC (P = 0.043), FEV0.5 (P = 0.015), and FEF75 (P = 0.042), was related with the height velocity during the study period. CONCLUSIONS:Infants who suffered from BPD have lower lung function (FVC, FEV0.5 , FEF75 , and FEF25-75 ), than those non-BPD, at two different time points 1 year apart. During the study period, there was no lung function catch-up in either BPD or non-BPD infants. The increase in length is closely associated to the increase in lung function. Pediatr Pulmonol. 2016; 51:936-942. © 2016 Wiley Periodicals, Inc. 10.1002/ppul.23393
    Assessing Initial Response to High-Frequency Jet Ventilation in Premature Infants With Hypercapnic Respiratory Failure. Wheeler Craig R,Smallwood Craig D,O'Donnell Iris,Gagner Daniel,Sola-Visner Martha C Respiratory care BACKGROUND:High-frequency jet ventilation (HFJV) has been used in conjunction with conventional ventilation for infants with respiratory failure. We sought to identify parameters that were associated with successful application of HFJV in patients with hypercapnic respiratory failure. METHODS:A single-center, retrospective review of infants who received HFJV was conducted. Subjects were enrolled if birthweight was ≤2,000 g and capillary P was ≥55 mm Hg. Ventilator parameters and physiologic data were recorded at 1 h before HFJV initiation and at hours 1, 4, and 6 following conversion. Subjects were classified as responders if capillary P was reduced by ≥10% after 1 h of HFJV. Data included peak inspiratory pressure, PEEP, capillary P , and oxygen saturation index (equal to mean airway pressure × F × 100/S ). Because the data were not normally distributed, they are reported as median (interquartile range), and the Mann-Whitney test was used to assess differences in continuous data between groups. Categorical data were analyzed using a chi-square and Fisher exact test. RESULTS:Thirty-four premature infants ( = 24 male) were studied. Twenty-five subjects were classified as responders and demonstrated a significant reduction of capillary P and F and increased pH within the first hour. The non-responders demonstrated a higher conventional ventilation peak inspiratory pressure (25 cm HO vs 19 cm HO, = .005) and had a greater postmenstrual age (30 weeks vs 26.5 weeks, = .01). This group had a higher oxygen saturation index (7.25 vs 3.36, = .03) and F requirements (0.6 vs 0.35, = .038) at 4 h. CONCLUSIONS:We identified that lower postmenstrual age, improvements in capillary P and pH at 1 h, and a reduction of F were associated with good response to HFJV. These data may help to identify patients who are likely to benefit from HFJV in the neonatal intensive care unit. 10.4187/respcare.05264
    Pulmonary function in former very low birth weight preterm infants in the first year of life. Gonçalves Daniela de Melo Miranda,Wandalsen Gustavo Falbo,Scavacini Ana Sílvia,Lanza Fernanda Cordoba,Goulart Ana Lucia,Solé Dirceu,Dos Santos Amélia Miyashiro Nunes Respiratory medicine BACKGROUND:Pulmonary function in former preterm infants may be compromised during childhood. OBJECTIVES:To assess pulmonary function in very-low-birth-weight preterm infants at 6-12 months of corrected age and analyze the factors associated with abnormal pulmonary function. METHODS:Cross-sectional study with preterm infants at 6-12 months of corrected age with birth weight <1500 g. Children with malformations or affected by neuromuscular and respiratory diseases were excluded. Forced expiratory flows were assessed using the chest compression technique, and volumes were measured by total body plethysmography. Pulmonary function parameters in preterm infants were compared to a control group of same-aged children born at term. RESULTS:We studied 51 preterm and 37 infants born at term. Preterm infants had: gestational age at birth (30.0 ± 2.5 weeks), birth weight (1179 ± 247 g), 27.5% had bronchopulmonary dysplasia, and 45% received mechanical ventilation. Preterm infants had lower median z-scores in comparison to term infants for the following parameters (p < 0.05): FVC (-0.3 vs. 0.7), FEV (-0.5 vs. 0.9), FEV/FVC (-0.6 vs. -0.5), FEF (-0.4 vs. 0.9), FEF (-0.3 vs. 0.8), FEF (-0.1 vs. 0.6) and FEF (-0.5 vs. 1.1). No term child had abnormal lung function, compared to 39.2% of preterm infants (p = 0.001). Factors associated with abnormal pulmonary function were lower gestational age at birth, small for gestational age, need for mechanical ventilation and presence of recurrent wheezing. CONCLUSIONS:Preterms had a high prevalence of abnormal pulmonary function and lower pulmonary function in comparison to term infants. Prematurity, intrauterine growth restriction, respiratory support and recurrent wheezing were associated with abnormal pulmonary function. 10.1016/j.rmed.2018.02.004
    Encouraging pulmonary outcome for surviving, neurologically intact, extremely premature infants in the postsurfactant era. Kaplan Eytan,Bar-Yishay Ephraim,Prais Dario,Klinger Gil,Mei-Zahav Meir,Mussaffi Huda,Steuer Guy,Hananya Shai,Matyashuk Yelena,Gabarra Nassrin,Sirota Lea,Blau Hannah Chest OBJECTIVE:The aim of this study was to determine the long-term pulmonary outcome of extreme prematurity at a single tertiary-care center from 1997 to 2001 in the postsurfactant era. METHODS:We assessed symptoms, exhaled nitric oxide, spirometry, methacholine challenge (provocative concentration of methacholine required to decrease FEV₁ by 20% [PC(20)]), lung volumes, diffusion, and cardiopulmonary exercise tolerance. RESULTS:Of 279 infants born, 192 survived to discharge, and 79 of these developed bronchopulmonary dysplasia (BPD) (65 mild, 12 moderate, two severe). We studied a subgroup of 53 neurologically intact preterm subjects aged 10 ± 1.5 years (28 with BPD [born, 26.2 ± 1.4 weeks; birth weight, 821 ± 164 g] and 25 without BPD [born, 27.2 ± 1 weeks; birth weight, 1,050 ± 181 g]) and compared them with 23 term control subjects. Of the BPD cases, 21 were mild, seven were moderate, and none was severe; 77.4% of subjects received antenatal steroids, and 83% received postnatal surfactant. Sixty percent of the preterm subjects wheezed at age < 2 years compared with 13% of the control subjects (P < .001), but only 13% wheezed in the past year compared with 0% of control subjects (not significant). For preterm and control subjects, respectively (mean ± SD), FEV₁ % predicted was 85% ± 10% and 94% ± 10% (P < .001), with limited reversibility; residual volume/total lung capacity was 29.3% ± 5.5% and 25% ± 8% (P < .05); diffusing capacity/alveolar volume was 89.6% ± 9.2% and 97% ± 10% (P < .005); and PC(20) was 6.5 ± 5.8 mg/mL and 11.7 ± 5.5 mg/mL (P < .001). PC(20) was < 4 mg/mL in 49% of preterm subjects despite normal exhaled nitric oxide. Most measurements were similar in premature subjects with and without BPD. Peak oxygen consumption and breathing reserve were normal, but % predicted maximal load (measured in Watts) was 69% ± 15% for subjects with BPD compared with 88% ± 23% for subjects without and 86% ± 20% for control subjects (P < .01). CONCLUSIONS:Pulmonary outcome was encouraging at mid-childhood for neurologically intact survivors in the postsurfactant era. Despite mechanical ventilation and oxygen therapy, most had no or mild BPD. Changes found probably reflect the hypoplastic lungs of prematurity. 10.1378/chest.11-1562
    Lung Function and Relevant Clinical Factors in Very Low Birth Weight Preterm Infants with Chronic Lung Disease: An Observational Study. Chen I-Ling,Chen Hsiu-Lin Canadian respiratory journal Background:Chronic lung disease (CLD), most commonly seen in premature infants who required mechanical ventilation, is associated with functional consequences on lungs and respiratory morbidity. This study aimed to evaluate the lung function of premature infants before discharge and their relevant factors related to the lung function. Methods:Very low birth weight (VLBW) preterm infants, who required respiratory support soon after birth and were admitted to a hospital in Taiwan, were enrolled. Infants with a need for supplemental oxygen or positive-pressure ventilation support at the postmenstrual age (PMA) of 36 weeks were diagnosed with CLD. Lung function was examined once using EXHALYZER® D before infants were ready for discharge. Results:Forty-five VLBW preterm infants received the lung function test before discharge, 27 of whom were diagnosed with CLD. The gestational age (=0.001) and birth weight ( < 0.001) were smaller in the CLD group than in the no-CLD group. Furthermore, infants with CLD required a longer duration of respiratory support ( < 0.001). The postnatal age and PMA were higher and body size was bigger in infants with CLD on lung function measurement. However, lung function was comparable between the groups. The functional residual capacity and tidal volume were associated with body size upon measuring lung function among all VLBW premature infants. FRC was positively correlated with the body length on measuring lung function in those with CLD. Conclusion:In our study, we showed FRC was positively related to the PMA and body length and tidal volume was positively correlated with the body weight and length on lung function measurement in VLBW preterm infants before discharge. Moreover, FRC was positively correlated with the body length on measuring lung function in those with CLD. The lung volume, ventilation, and respiratory mechanics on discharge were comparable between CLD and no-CLD groups. 10.1155/2019/5824180
    The Effect of Extended Continuous Positive Airway Pressure on Changes in Lung Volumes in Stable Premature Infants: A Randomized Controlled Trial. Lam Ryan,Schilling Diane,Scottoline Brian,Platteau Astrid,Niederhausen Meike,Lund Kelli C,Schelonka Robert L,MacDonald Kelvin D,McEvoy Cindy T The Journal of pediatrics OBJECTIVE:To compare changes in lung volumes, as measured by functional residual capacity (FRC), through to discharge in stable infants randomized to 2 weeks of extended continuous positive airway pressure CPAP (eCPAP) vs CPAP discontinuation (dCPAP). STUDY DESIGN:Infants born at ≤32 weeks of gestation requiring ≥24 hours of CPAP were randomized to 2 weeks of eCPAP vs dCPAP when meeting CPAP stability criteria. FRC was measured with the nitrogen washout technique. Infants were stratified by gestational age (<28 and ≥ 28 weeks) and twin gestation. A linear mixed-effects model was used to evaluate the change in FRC between the 2 groups. Data were analyzed blinded to treatment group allocation. RESULTS:Fifty infants were randomized with 6 excluded, for a total of 44 infants. Baseline characteristics were similar in the 2 groups. The infants randomized to eCPAP vs dCPAP had a greater increase in FRC from randomization through 2 weeks (12.6 mL vs 6.4 mL; adjusted 95% CI, 0.78-13.47; P = .03) and from randomization through discharge (27.2 mL vs 17.1 mL; adjusted 95% CI, 2.61-17.59; P = .01). CONCLUSIONS:Premature infants randomized to eCPAP had a significantly greater increase in FRC through discharge compared with those randomized to dCPAP. An increased change in FRC may lead to improved respiratory health. TRIAL REGISTRATION:ClinicalTrials.gov: NCT02249143. 10.1016/j.jpeds.2019.07.074
    Lung parenchymal development in premature infants without bronchopulmonary dysplasia. Assaf Santiago J,Chang Daniel V,Tiller Christina J,Kisling Jeffrey A,Case Jamie,Mund Julie A,Slaven James E,Yu Zhangsheng,Ahlfeld Shawn K,Poindexter Brenda,Haneline Laura S,Ingram David A,Tepper Robert S Pediatric pulmonology RATIONALE:While infants who are born extremely premature and develop bronchopulmonary dysplasia (BPD) have impaired alveolar development and decreased pulmonary diffusion (DLCO), it remains unclear whether infants born less premature and do not develop BPD, healthy premature (HP), have impaired parenchymal development. In addition, there is increasing evidence that pro-angiogenic cells are important for vascular development; however, there is little information on the relationship of pro-angiogenic cells to lung growth and development in infants. OBJECTIVE:and Methods Determine among healthy premature (HP) and fullterm (FT) infants, whether DLCO and alveolar volume (VA) are related to gestational age at birth (GA), respiratory support during the neonatal period (mechanical ventilation [MV], supplemental oxygen [O2], continuous positive airway pressure [CPAP]), and pro-angiogenic circulating hematopoietic stem/progenitor cells (CHSPCs). We measured DLCO, VA, and CHSPCs in infants between 3-33 months corrected-ages; HP (mean GA = 31.7 wks; N = 48,) and FT (mean GA = 39.3 wks; N =88). RESULT:DLCO was significantly higher in HP than FT subjects, while there was no difference in VA , after adjusting for body length, gender, and race. DLCO and VA were not associated with GA, MV and O2; however, higher values were associated with higher CHSPCs, as well as treatment with CPAP. CONCLUSION:Our findings suggest that in the absence of extreme premature birth, as well as BPD, prematurity per se, does not impair lung parenchymal development. 10.1002/ppul.23134
    Assessment of pulmonary function in a follow-up of premature infants: our experience. Ciuffini F,Marijke O,Lavizzari A,Ghirardi B,Musumeci S,Dusi E,Colnaghi M,Mosca F La Pediatria medica e chirurgica : Medical and surgical pediatrics Respiratory diseases are a major cause of morbidity in neonates, especially preterm infants; a long term complication of prematurity such as bronchopulmonary dysplasia (BPD) is particularly relevant today. The exact role of the Pulmonary Function Test (PFT) in this area is not yet well defined; the PFT in newborns and infants - in contrast to what happens in uncooperative children and adults - are routinely used only in a few centers. The assessment of pulmonary function in newborns and infants, however, is nowadays possible with the same reliability that in cooperative patients with the possibility to extend the assessment of polmonary function from bench to bed. The assessment of pulmonary function must be carried out with non invasive and safe methods, at the bedside, with the possibility of continuous monitoring and providing adequate calculation and management of data. The ability to assess lung function helps to define the mechanisms of respiratory failure, improving the treatment and its effects and is therefore a useful tool in the follow-up of newborn and infant with pulmonary disease. 10.4081/pmc.2014.6