Role of body mass index in unbalanced (dysanaptic) lung growth of healthy infants.

RATIONALE: Imbalance between forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) (dysanapsis) has been reported in children who are obese. This dysanaptic growth might begin at an early age, although there are no data on children younger than 6 years. OBJETIVES: To assess whether body mass index (BMI) and early weight gain, in healthy infants born at term, plays a significant role in the imbalance between FEV1 and FVC, even in the absence of obesity. METHODS: Lung function was measured by means of raised volume rapid thoracic compression in 69 healthy infants born at term from the Nutrition in Early Life and Asthma cohort. Dysanapsis was defined as zFVC >0.674, zFEV0 .5 ≥-1.645, and FEV0 .5/FVC ≤-1.645. Weight gain (g/day) and growth rate (cm/year) were calculated as the difference between weight and length on the test date and those at birth. To assess the relationship between zBMI and dysanapsis, a receiver operating characteristic curve was performed. Multivariable analysis was carried out by means of linear regressions (one for each lung function index) and by logistic regression for dysanapsis (yes/no). RESULTS: Higher zBMI was associated with risk of dysanapsis (odds ratio: 3.53, [95% confidence interval: 1.30; 9.66]; p = .014): Each additional zBMI unit was associated with ~10 mL higher FVC and with ~3.5% lower FEV0.5/FVC. Weight gain was associated with lower FEV0.5/FVC ratio. CONCLUSION: Dysanaptic development of lung function begins very early in infancy and is related with weight gain and body mass index, even in the absence of obesity.

Pediatric Pulmonology Training in India: Current Status and Future Directions.

Respiratory illnesses are common causes of morbidity and mortality in children. Postgraduates in Pediatrics spent significant time in learning to manage respiratory disorders. Improved survival of preterm neonates, improved diagnosis and survival of chronic respiratory problems, and advances in diagnosis and therapeutics have increased the need for specialists trained in managing these patients. Training programs in Pediatric Pulmonology are evolving over the past few decades. In India, super-specialty training in Pediatric Pulmonology has grown over the past few years. There is a need to modify the training structure used in industrialized countries due to differences in patient population, priorities, and limited available resources and expertise. Formal training courses have been started in a limited number of institutions. There is a large gap between the need for a trained workforce and the available specialists in the limited number of institutions. The Indian Academy of Pediatrics National Respiratory Chapter (IAPNRC) has initiated a fellowship program to bridge the gap. Comprehensive training involving academic and hands-on training may go a long way to improve the care of children with acute and chronic respiratory problems. For sustainable development of the super specialty, there is a need to work towards creating Pediatric Pulmonology service departments in various institutions that may be responsible for comprehensive training and research activities to answer common research questions.

Infant pulmonary function tests in individuals with Down syndrome.

BACKGROUND AND OBJECTIVE: Down syndrome is associated with significant respiratory morbidity. The available pulmonary function testing data in school aged children and adults with Down show evidence of restrictive lung disease. We aimed to evaluated infant pulmonary function tests (iPFTs) in individuals with Down. METHODS: An observational case-control study evaluating iPFTs results from a registry of patients assessed at the Hadassah Hebrew University Medical Center between 2008 and 2018. iPFTs results in Infants with Down were compared to a spirometry control group of infants with normal expiratory airflows, using the Mann-Whitney U and Fisher's exact tests. RESULTS: iPFT data from 66 infants (20 Down and 46 control) were evaluated in the study. Most infants with Down showed abnormalities of an obstructive lung disease with mildly increased lung volumes and significantly decreased expiratory flows, mostly unresponsive to bronchodilators. Airflow limitations were most prominent at low lung volumes (median (IQR); maximal expiratory flow at functional residual capacity, V˙max FRC = 48 (26-78) %predicted in Down Vs. V˙max FRC = 100 (93-114) %predicted in controls, p < 0.001). We further observed an alteration in breathing mechanics with significantly decreased respiratory system compliance and increased airway resistance associated with decreased tidal volumes but similar minute ventilation. CONCLUSION: Our study shows that infants with have a fixed airflow obstruction phenotype. These results add comprehensive data to allow better understanding of the lung disease present early in life of infants with Down syndrome. Further studies are required to improve management of respiratory disease in individuals with Down.

Symptomatic preterm infants suffer from lung function deficits, regardless of bronchopulmonary dysplasia.

BACKGROUND: The long-term respiratory consequences for children with bronchopulmonary dysplasia (BPD) are well known. However, there is little emphasis on monitoring preterm infants without BPD. Few studies have explored the lung function status of infants with the symptoms of chronic lung disease of prematurity (CLD). OBJECTIVE: To evaluate functional lung deficits in preterm infants with CLD, and to assess the perinatal determinants of diminished lung function. METHODS: In our cross-sectional study, 132 preterm infants with symptomatic CLD underwent infant pulmonary function testing (iPFT) at a median post-term age of 0.9 years. The iPFT included bodypletysmography, compliance measurement, tidal breath analysis, and rapid thoracoabdominal compression. The relationships between the respective z scores of the iPFT parameters and perinatal characteristics, postnatal treatment, and BPD status were investigated. RESULTS: Seventy-three patients (55.3%) were born before the 28th week of gestation, and 92 (69.7%) met the BPD criteria. Functional deficits were detected in 85.8%. The obstructive ventilatory pattern was more prevalent than restrictive (36.3 vs. 12.4%, p < 0.001). Infants with restriction had lower birth weight (BW) and required a longer duration of oxygenotherapy. In a univariate model, the lung function correlated with the duration of invasive mechanical ventilation, gestational week, and BW. In a general linear model, BPD status was not an additional determinant of the iPFT results. CONCLUSION: IPFT may reveal significant functional deficits in preterm infants with CLD even without BPD. The current symptoms and perinatal factors may be more important determinants of functional deficits than the BPD status itself.

Assessment of bronchodilator response by forced oscillation technique in a preterm infant with evolving bronchopulmonary dysplasia: A case report.

Inhaled bronchodilators are often given in preterm infants with evolving or established bronchopulmonary dysplasia. However, it is unclear which patients may benefit from it and when it is the best time to start treatment. The forced oscillation technique (FOT) is a noninvasive method for assessing lung mechanics that proved sensitive to airway obstruction reversibility in children and adults. FOT does not need patient cooperation, which is ideal for infants. Bedside tools for applying FOT in infants during spontaneous breathing and different respiratory support modes are becoming available. This case report illustrates for the first time that FOT has potential value in assessing airway obstruction reversibility in preterm infants, informing which infants may manifest a clinical benefit from the treatment with bronchodilators.

Effect of human milk and other neonatal variables on lung function at three months corrected age.

OBJECTIVE: To evaluate the impact of human milk and different neonatal variables on tidal breathing flow-volume loop (TBFVL) parameters within three months' corrected age (CA) in infants born ≤32 wks or weighing <1500 g. METHODS: We retrospectively studied 121 infants with gestational age (GA) ≤ 32 weeks or birth weight (BW) <1500 gr who had lung function assessment within three months' CA by TBFVL analysis between June 2009 and April 2018. We investigated the impact of GA, gender, being Small for GA (SGA), sepsis, days of mechanical ventilation (MV) and human milk feeding (HMF) on later respiratory function, both in the entire group and according to BW ( ≤1000 g and >1000 g). RESULTS: The mean(SD) z-score for tidal volume (Vt) and time to peak expiratory flow to expiratory time (tPTEF/tE) were respectively -4.3 (2.5) and -0.8 (2.0) for the overall population with no significant differences between infants <1000 g or ≥1000 g. The mean(SD) Vt standardized for body weight was 6.2(2.0) ml/kg. Being female was associated with better Vt/Kg, whereas longer MV or being born SGA were associated with worst tPTEF/tE. For infants with BW < 1000 gr, tPTEF/tE was positively associated with HMF. CONCLUSION: An early TBFVL assessment within three months' CA already reveals lung function alteration in preterm infants. Being female is associated with better Vt/Kg, while longer duration of MV or being born SGA negatively affect tPTEF/tE. The positive association between HMF and better tPTEF/tE in infants with BW <1000 g has emerged, which deserves further investigation.

Backup ventilation during neurally adjusted ventilatory assist in preterm infants.

OBJECTIVE: To analyze the proportion of backup ventilation during neurally adjusted ventilatory assist (NAVA) in preterm infants at different postmenstrual ages (PMAs) and to analyze the trends in backup ventilation in relation to clinical deteriorations. METHODS: A prospective observational study was conducted in 18 preterm infants born at a median (range) 27+4 (23+4 -34+4 ) weeks of gestation with a median (range) birth weight of 1,100 (460-2,820) g, who received respiratory support with either invasive or noninvasive NAVA. Data on ventilator settings and respiratory variables were collected daily; the mean values of each 24-h recording were computed for each respiratory variable. For clinical deterioration, ventilator data were reviewed at 6-h intervals for 30 h before the event. RESULTS: A total of 354 patient days were included: 269 and 85 days during invasive and noninvasive NAVA, respectively. The time on backup ventilation (%/min) significantly decreased with increasing PMA during both invasive and noninvasive NAVA. The neural respiratory rate did not change over time. The median time on backup ventilation was less than 15%/min, and the median neural respiratory rate was more than 45 breaths/min for infants above 26+0 weeks PMA during invasive NAVA. The relative backup ventilation significantly increased before the episode of clinical deterioration. CONCLUSION: The proportion of backup ventilation during NAVA showed how the control of breathing matured with increasing PMA. Even the most immature infants triggered most of their breaths by their own respiratory effort. An acute increase in the proportion of backup ventilation anticipated clinical deterioration.

Hyperinflation is associated with increased respiratory rate and is a more sensitive measure of cystic fibrosis lung disease during infancy compared to forced expiratory measures.

BACKGROUND: The goal of this study was to identify clinical features associated with abnormal infant pulmonary function tests (iPFTs), specifically functional residual capacity (FRC), in infants with cystic fibrosis (CF) diagnosed via newborn screen (NBS). We hypothesized that poor nutritional status in the first 6-12 months would be associated with increased FRC at 12-24 months. METHODS: This study utilized a combination of retrospectively and prospectively collected data from ongoing research studies and iPFTs performed for clinical indications. Demographic and clinical features were obtained from the electronic medical record. Forced expiratory flows and volumes were obtained using the raised volume rapid thoracoabdominal technique (RVRTC) and FRC was measured via plethysmography. RESULTS: A total of 45 CF NBS infants had iPFTs performed between 12 and 24 months. Mean forced vital capacity, forced expiratory volume in 0.5 s, and forced expiratory flows were all within normal limits. In contrast, the mean FRC z-score was 2.18 (95% confidence interval [CI] = 1.48, 2.88) and the mean respiratory rate (RR) z-score was 1.42 (95% CI = 0.95, 1.89). There was no significant association between poor nutritional status and abnormal lung function. However, there was a significant association between higher RR and increased FRC, and a RR cutoff of 36 breaths/min resulted in 92% sensitivity to detect hyperinflation with 32% specificity. CONCLUSION: These results suggest that FRC is a more sensitive measure of early CF lung disease than RVRTC measurements and that RR may be a simple, noninvasive clinical marker to identify CF NBS infants with hyperinflation.

Clinical, functional, and computed tomography findings in a cohort of patients with neuroendocrine cell hyperplasia of infancy.

INTRODUCTION: Neuroendocrine cell hyperplasia of infancy (NEHI) is one of the most common interstitial lung diseases in children. Both the etiology and pathophysiological mechanisms of the disease are still unknown. Prognosis is usually favorable; however, there are significant morbidities during the early years of life. OBJECTIVE: To describe the clinical course, infant pulmonary function tests and computed tomography (CT) findings in a cohort of patients with NEHI in Argentina. METHODS: This is a observational multicenter cohort study of children diagnosed with NEHI between 2011 and 2020. RESULTS: Twenty patients participated in this study. The median age of onset of symptoms was 3 months and the median age at diagnosis was 6 months. The most common clinical presentation was tachypnea, retractions and hypoxemia. The chest CT findings showed central ground glass opacities and air trapping. Infant pulmonary function tests revealed an obstructive pattern in 75% of the cases (10/12). Most patients (75%) required home oxygen therapy for 17 months (interquartile range 12-25). In 85% of them, tachypnea and hypoxemia spontaneously resolved between the second and third years of life. CONCLUSION: In this cohort, the first symptoms appeared during the early months of life. The typical clinical, CT, and functional findings allowed the diagnosis without the need of a lung biopsy. Although most patients required home oxygen therapy, they showed a favorable evolution.

Respiratory syncytial virus seropositivity at birth is associated with adverse neonatal respiratory outcomes.

BACKGROUND: More than 60 years since the discovery of the respiratory syncytial virus (RSV), the effects of prenatal exposure to this virus remain largely unknown. In this investigation, we sought to find evidence of RSV seroconversion in cord blood and explore its clinical implications for the newborn. METHODS: Offspring from 22 pregnant women with a history of viral respiratory infection during the third trimester of pregnancy (respiratory viral illness [RVI] group) and 40 controls were enrolled in this study between 1 September 2016 and 31 March 2019. Cord blood sera were tested for anti-RSV antibodies by indirect fluorescent antibody assay. RSV seropositivity was defined as the presence of anti-RSV immunoglobulin M (IgM) or immunoglobulin A (IgA), in addition to IgG in cord blood serum at ≥1:20 dilution. RESULTS: Anti-RSV IgG was present in all cord blood serum samples from infants born to RVI mothers (95% confidence interval [CI] = 82%-100%), with 16 samples also having elevated titers for either anti-RSV IgA or IgM (73%; 95% CI = 52%-87%). No controls had evidence of anti-RSV antibodies. Eight (50%) seropositive newborns developed at least one respiratory tract finding, including respiratory distress syndrome (N = 8), respiratory failure (N = 3), and pneumonia (N = 1). RSV seropositive newborns also required more days on oxygen, had leukocytosis and elevated C-reactive protein (P = .025, P = .047, and P < .001, respectively). CONCLUSION: This study provides evidence of acute seropositivity against RSV in cord blood of newborns delivered from mothers with a history of upper respiratory tract illness in the third trimester. Cord blood seropositivity for anti-RSV IgA or IgM was associated with adverse clinical and laboratory outcomes in newborns.

Pediatric pulmonology year in review 2019: Physiology.

Pulmonary physiologic assessments are critical for the care and study of pediatric respiratory disease. In 2019, there were numerous contributions to this topic in Pediatric Pulmonology.

Prenatal exposure to VOCs and NOx and lung function in preschoolers.

BACKGROUND: Several studies have shown that exposure to air pollutants affects lung growth and development and can result in poor respiratory health in early life. METHODS: We included a subsample of 772 Mexican preschoolers whose mothers participated in a Prenatal Omega-3 fatty acid Supplements, GRowth, And Development birth cohort study with the aim to evaluate the impact of prenatal exposure to volatile organic compounds and nitrogen oxides on lung function measured by oscillation tests. The preschoolers were followed until 5 years of age. Anthropometric measurements and forced oscillation tests were performed at 36, 48, and 60 months of age. Information on sociodemographic and health characteristics was obtained during follow up. Prenatal exposure to volatile organic compounds and nitrogen oxides was evaluated using a land use regression models and the association between them was tested using a lineal regression and longitudinal linear mixed effect models adjusting for potential confounders. RESULTS: Overall, the mean (standard deviation) of the measurements of respiratory system resistance and respiratory system reactance at 6, 8, and 10 Hz during the follow-up period was 11.3 (2.4), 11.1 (2.4), 10.3 (2.2) and -5.2 (1.6), -4.8 (1.7), and -4.6 hPa s L-1 (1.6), respectively. We found a significantly positive association between respiratory resistance (ßRrs6 = 0.011; 95%CI: 0.001, 0.023) (P < .05) and prenatal exposure to nitrogen dioxide and a marginally negatively association between respiratory reactance (ßXrs6 = -11.40 95%CI: -25.26, 1.17 and ßXrs8 = -11.91 95%CI: -26.51, 1.43) (P = .07) and prenatal exposure to xylene. CONCLUSION: Prenatal exposure to air pollutants was significantly associated with the alteration of lung function measured by oscillation tests in these preschool children.

Therapy at 30 days of life predicts lung function at 6 to 12 months in infants with congenital diaphragmatic hernia.

INTRODUCTION: Congenital diaphragmatic hernia (CDH) is associated with variable degrees of lung hypoplasia. Pulmonary support at 30 days postnatal age was found to be the strongest predictor of inpatient mortality and morbidity among CDH infants and was also associated with higher pulmonary morbidity at 1 and 5 years. It is not known, however, if there is a relationship between the need for medical therapy at 30 days of life and subsequent abnormalities in lung function as reflected in infant pulmonary function test (iPFT) measurements. OBJECTIVE: We hypothesized that CDH infants who require more intensive therapy at 30 days would have more abnormal iPFT values at the time of their first infant pulmonary function study, reflecting the more severe spectrum of lung hypoplasia. METHODS: A single-institution chart review of all CDH survivors who were enrolled in a Pulmonary Hypoplasia Program (PHP) through July 2019, and treated from 2002 to 2019 was performed. All infants were divided into groups based on their need for noninvasive (supplemental oxygen, high flow therapy, noninvasive mechanical ventilation) or invasive (mechanical ventilation, extracorporeal membrane oxygenation) respiratory assistance, bronchodilators, diuretic use, and pulmonary hypertension (PH) therapy (inhaled and/or systemic drugs) at 30 days. Descriptive and statistical analyses were performed between groups comparing subsequent lung function measurements. RESULTS: A total of 382 infants (median gestational age [GA] 38.4 [interquartile range (IQR) = 37.1-39] weeks, 41.8% female, 70.9% Caucasian) with CDH were enrolled in the PHP through July 2019, and 118 infants underwent iPFT. The median age of the first iPFT was 6.6 (IQR = 5.3-11.7) months. Those requiring any pulmonary support at 30 days had a higher functional residual capacity (FRC) (z) (P = .03), residual volume (RV) (z) (P = .008), ratio of RV to total lung capacity (RV/TLC) (z) (P = .0001), and ratio of FRC to TLC (FRC/TLC) (z) (P = .001); a lower forced expiratory volume at 0.5 seconds (FEV0.5) (z) (P = .03) and a lower respiratory system compliance (Crs) (P = .01) than those who did not require any support. Similarly, those requiring diuretics and/or PH therapy at 30 days had higher fractional lung volumes, lower forced expiratory flows and Crs than infants who did not require such support (P < .05). CONCLUSIONS: Infants requiring any pulmonary support, diuretics and/or PH therapy at 30 postnatal days have lower forced expiratory flows and higher fractional lung volumes, suggesting a greater degree of lung hypoplasia. Our study suggests that the continued need for PH, diuretic or pulmonary support therapy at 30 days can be used as additional risk-stratification measurements for evaluation of infants with CDH.

Association between thoracic musculoskeletal abnormalities and lung function in preterm infants.

INTRODUCTION: In view of the difficulties and risks of performing lung function tests in infants and the hypothesis that children with abnormal pulmonary test may exhibit thoracic musculoskeletal alterations. OBJECTIVES: This study aimed to determine the frequency of abnormal lung function and their relationship. MATERIALS AND METHODS: This was a cross-sectional study with children from 6 to 12 months of corrected age, born at a gestational age of <37 weeks and with a birthweight ≤1500 g, who were subjected to a lung function test and photogrammetry--an objective and non-invasive procedure. To verify the association between the thoracic musculoskeletal abnormalities and measure changes in lung function, univariate linear regression was used. The level of statistical significance was setted at P < 0.05. RESULTS: Of the 38 infants, 12 (31.6%) exhibited abnormal lung function, including 9 (23.7%) with obstructive function and 3 (7.9%) with restrictive function. A significant association was noted between forced expiratory volume at 0.5 second <-2 z score and the acromion/xiphoid process/acromion angle (ß = 4.935); forced vital capacity <-2 z score and the angle of the manubrium/left acromion/trapezium (ß = 0.033) and forced expiratory volume at 0.5 second and forced vital capacity ratio <-2 z score and the inframammillary point/xiphoid process/inframammillary point angle (ß = 0.043). CONCLUSION: Preterm infants with very low birthweight presented a high frequency of abnormal lung function, particularly obstructive type and thoracic musculoskeletal abnormalities were associated with changes in lung function.

Impact of early caffeine therapy in preterm newborns on infant lung function.

OBJECTIVE: To know the effect of caffeine therapy on infant lung function in preterm infants with a gestational age less than 31 weeks. MATERIAL AND METHODS: Forced vital capacity (FVC), forced expiratory volume at 0.5 seconds (FEV0.5 ), and forced expiratory flows were measured by raised volume rapid thoracoabdominal compression technique; functional residual capacity was measured by plethysmography (FRCpleth ). Compliance of the respiratory system was measured by a single interruption technique (Crs). The Student t test was used to compare lung function measurements between the two groups: treated versus nontreated with caffeine. A multivariate analysis was carried out considering each and every lung function parameter (z-score) as the dependent variable; and gender, gestational age, birth weight (z-score), corrected age, invasive mechanical ventilation (yes/no), and bronchopulmonary dysplasia (BPD) diagnosis (yes/no) as independent ones. Additionally, stratified analyses by BPD diagnosis were performed. RESULTS: The multivariate analysis showed significant higher z-scores of FVC and FEV0.5 in preterm infants treated with caffeine (P = .004 and P = .024, respectively). This result only being significant in the group of non-BPD infants (P = .021 and P = .042), after stratifying by BPD diagnosis. Differences were not found in z-scores of FEV0.5/FVC, FEF75, FEF25-75, FRCpleth, nor Crs. CONCLUSION: Lung function (FVC and FEV0.5 ) is improved in infants born under 31 weeks of gestation when treated with caffeine. This improvement is driven by the group of infants who did not suffer from BPD. Overall, our results show that there is an early beneficial effect of caffeine treatment in infant lung function.

A novel method for infant multiple breath washout: First report in clinical practice.

BACKGROUND: Lung clearance index (LCI), measured using multiple breath inert gas washout (MBW) is a potentially useful test in infants with respiratory disease, particularly cystic fibrosis (CF). Clinical use is limited however by the need for specialist staff and equipment. We have previously described a novel method for infant MBW suitable for use outside of specialist laboratories. This study describes its performance in vivo in infants with CF and healthy controls, including a limited comparison with the respiratory mass spectrometer. METHODS: Children aged less than 2 years with CF and controls underwent MBW testing on a single occasion. The practical applicability of the system was determined by the number of successful duplicate tests and within-subject repeatability. RESULTS: Twenty-five children (seven with CF, 18 healthy controls, all sedated with chloral hydrate) attempted MBW. Twenty patients (seven with CF) successfully underwent duplicate testing (80% success rate). Mean within-subject coefficient of variation for functional residual capacity (FRC) was 7.2% and for LCI 5.9%. Comparison of LCI with the mass spectrometer was limited but gave very similar values for LCI and FRC in those patients who underwent technically adequate tests with both methods. CONCLUSIONS: We have described a new MBW method that is feasible and reproducible in sedated infants. Results fall within the expected range, and well within accuracy limits set by international guidelines. This could provide a more accessible alternative to previously described systems for infant MBW, and overcomes many of the technical challenges inherent in conventional MBW.

Elevated lung volumes in neonates with bronchopulmonary dysplasia measured via MRI.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic lung disease of prematurity defined by requirement for respiratory support at 36 weeks postmenstrual age (PMA), but structural sequelae like lung hyperinflation are often not quantified. Quiet-breathing, nonsedated magnetic resonance imaging (MRI) allows tomographic quantification of lung volumes and densities. We hypothesized that functional residual capacity (FRC) and intrapleural volume (IV) are increased in BPD and correlate with qualitative radiological scoring of hyperinflation. METHODS: Ultrashort echo time (UTE) MRI of 17 neonates (acquired at ~39 weeks PMA) were reconstructed at end-expiration and end-inspiration via the time course of the k0 point in k-space. Images were segmented to determine total lung, tidal, parenchymal tissue, and vascular tissue volumes. FRC was calculated by subtracting parenchymal and vascular tissue volumes from IV. Respiratory rate (RR) was calculated via the UTE respiratory waveform, yielding estimates of minute ventilation when combined with tidal volumes (TVs). Two radiologists scored hyperinflation on the MR images. RESULTS: IV at FRC increased in BPD: for control, mild, and severe (patients the median volumes were 32.8, 33.5, and 50.9 mL/kg, respectively. TV (medians: 2.21, 3.64, and 4.84 mL/kg) and minute ventilation (medians: 493, 750, and 991 mL/min) increased with increasing severity of BPD (despite decreasing RR, medians: 75.6, 63.0, and 56.1 breaths/min). FRC increased with increasing severity of BPD (39.3, 38.3, and 56.0 mL, respectively). Findings were consistent with increased hyperinflation scored by radiologists. CONCLUSIONS: This study demonstrates that UTE MRI can quantify hyperinflation in neonatal BPD and that lung volumes significantly increase with disease severity.

Pulmonary Function Testing in Pediatric Pneumonia Patients With Wheezing Younger Than 3 Years of Age.

Background. Wheezing symptoms are one of the risk factors in young pneumonia patients that often leads to asthma development. Infant pulmonary function test (iPFT) is potentially a useful tool to help identify and manage these high-risk pneumonia patients. Methods. To examine whether patients with wheezing symptoms are more likely to have poorer pulmonary function and treatment outcomes, and also to explore the clinical benefit of iPFT in young pneumonia patients, we conducted a retrospective analysis of 1005 pneumonia inpatients <3 years of age who had undergone iPFT testing in 2016 at Liuzhou Maternity and Child Healthcare Hospital in Guang-Xi, China. Results. We identified from the hospital database 505 pneumonia patients who presented with wheezing and 500 without wheezing. Univariate analysis showed that wheezing symptoms, viral infection, age <1 year, female gender, and prematurity were significantly associated with poorer iPFT results. After adjusting for confounders, patients with wheezing showed significantly poorer pulmonary function. Patients with wheezing had longer length of stay (7.9 ± 3.9 days vs 6.5 ± 2.6 days; P < .001) and lower percent with no residual clinical symptoms at discharge (58% vs 98%; P < .001) when compared with those of non-wheezing patients. In addition, 81% of patients with viral infection as compared with 43% of patients with nonviral infection presented with wheezing symptoms (P < .001). Conclusion. Wheezing symptoms were associated with poorer iPFT measures and treatment outcomes for pneumonia inpatients <3 years of age. Patients with wheezing had poorer treatment outcomes. iPFT can be useful in assessing and monitoring young patients with high risk of developing asthma or chronic lung disease later in life.

Oral Vitamin C (500 mg/d) to Pregnant Smokers Improves Infant Airway Function at 3 Months (VCSIP). A Randomized Trial.

Rationale: We reported a randomized trial demonstrating daily supplemental vitamin C to pregnant smokers significantly improved newborn pulmonary function tests. The current study tests these results in a new cohort using infant pulmonary function tests. Objectives: To determine if infants of pregnant smokers randomized to daily supplemental vitamin C would have improved forced expiratory flows (FEFs) at 3 months of age compared with those randomized to placebo, and to investigate the association of the α5 nicotinic acetylcholine receptor. Methods: A randomized, double-blind, placebo-controlled trial was conducted at three centers. Two hundred fifty-one pregnant smokers were randomized at 13-23 weeks of gestation: 125 randomized to vitamin C (500 mg/d) and 126 to placebo. Measurements and Main Results: The primary outcome was FEF75 at 3 months of age performed with the raised volume rapid thoracic compression technique (Jaeger/Viasys). FEF50 and FEF25-75 obtained from the same expiratory curves were prespecified secondary outcomes. The infants of pregnant smokers randomized to vitamin C (n = 113) had the following FEFs at 3 months of age compared with those randomized to placebo (n = 109) as measured by FEF75 (200.7 vs. 188.7 ml/s; adjusted 95% confidence interval [CI] for difference, -3.33 to 35.64; P = 0.10), FEF50 (436.7 vs. 408.5 ml/s; adjusted 95% CI for difference, 6.10-61.30; P = 0.02), and FEF25-75 (387.4 vs. 365.8 ml/s; adjusted 95% CI for difference, 0.92-55.34; P = 0.04). Infant FEFs seemed to be negatively associated with the maternal risk alleles for the α5 nicotinic acetylcholine receptor (rs16969968). Conclusions: Although the primary outcome of FEF75 was not improved after vitamin C supplementation to pregnant smokers, the predetermined secondary outcomes FEF50 and FEF25-75 were significantly improved. These results extend our previous findings and demonstrate improved airway function (FEF50 and FEF25-75) at 3 months of age in infants after vitamin C supplementation to pregnant smokers. Clinical trial registered with www.clinicaltrials.gov (NCT01723696).

Reference equations for the interpretation of forced expiratory and plethysmographic measurements in infants.

BACKGROUND: Pulmonary function testing is commonly performed for diagnosis and clinical management of respiratory diseases. It is important to use appropriate reference equations from healthy subjects for interpretation of data from infants with lung disease. This study aimed to determine if published reference equations were similar to forced flow measures and plethysmographic infant pulmonary function testing data collected in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. METHODS: Reference equations for five pulmonary function variables (FEV0.5 , FVC, FEF25-75 , FEV0.5 /FVC ratio and plethysmography (FRCpleth )) were developed using data from the nSpire system. New reference equations developed using healthy data from the CHILD Study were compared to previously published reference equations for forced flow and plethysmographic measures. RESULTS: The current analysis included 131 infants (on 181 test occasions) with forced flow measures and 161 infants (on 246 test occasions) with plethysmography measures, aged 3-24 months. Age and length were major determinants of both forced flow and plethysmography measures. In addition, ethnicity (Caucasian vs non-Caucasian) was significantly associated with FEV0.5 /FVC and FEF25-75 measures. We found that the published reference equations based on custom-built equipment or commercially available systems provided poor fit to our current pulmonary function testing data, resulting in placing a large proportion of our healthy population outside the normal ranges. CONCLUSIONS: Our current data support the need for population and device specific reference data for infant pulmonary function studies. By deriving new equipment-specific reference equations for our healthy population, we provide normative data to other centers utilizing this equipment.