Raised Volume Rapid Thoracoabdominal Compression Research Articles

Forced expiratory flows and diffusion capacity in infants born from mothers with pre-eclampsia.

Animal models suggest pre-eclampsia (Pre-E) affects alveolar development, but data from humans are lacking. Assess the impact of Pre-E on airway function, diffusion capacity, and respiratory morbidity in preterm and term infants born from mothers with Pre-E. Infants born from mothers with and without Pre-E were recruited for this study; term and preterm infants were included in both cohorts. Respiratory morbidity in the first 12 months of life was assessed through monthly phone surveys. Raised volume rapid thoracoabdominal compression and measurement of diffusion capacity of the lung to carbon monoxide (DLCO) were performed at 6 months corrected age. There were 146 infants in the Pre-E cohort and 143 in the control cohort. The Pre-E cohort was further divided into nonsevere (N = 41) and severe (N = 105) groups. There was no significant difference in DLCO and DLCO/alveolar volume amongthe three groups. Forced vital capacity was similar amongthe three groups, but the nonsevere Pre-E group had significantly higher forced expiratory flows than the other two groups. After adjusting for multiple covariates including prematurity, the severe Pre-E group had a lower risk for wheezing in the first year of life compared to the other two groups. Pre-E is not associated with reduced DLCO, lower forced expiratory flows, or increased wheezing in the first year of life. These results differ from animal models and highlight the complex relationships between Pre-E and lung function and respiratory morbidity in human infants.

Relationship between lung function and exhaled volatile organic compounds in healthy infants.

ObjectiveThe aim of this study is to assess, for the first time, the relationship between the volatilome and lung function in healthy infants, which may be of help for the early detection of certain respiratory diseases. Lung function tests are crucial in chronic respiratory diseases diagnosis. Moreover, volatile organic compounds (VOCs) analysis in exhaled breath is a noninvasive technique that enables the monitorization of oxidative stress, typical of some forms of airway inflammation.MethodsLung function was studied in 50 healthy infants of 3–8 months of age and the following parameters were obtained: forced vital capacity (FVC), forced expiratory volume at 0.5 s (FEV0.5), forced expiratory flow at 75% of FVC (FEF75), forced expiratory flow at 25%–75% of FVC (FEF25–75), and FEV0.5/FVC. Lung function was measured according to the raised volume rapid thoracoabdominal compression technique. In addition, a targeted analysis of six endogenous VOCs (acetone, isoprene, decane, undecane, tetradecane, and pentadecane) in the exhaled breath of the children was carried out by means of thermal desorption coupled gas chromatography‐single quadrupole mass spectrometry system.ResultsA negatively significant relationship has been observed between levels of acetone, tetradecane, and pentadecane in exhaled breath and several of the lung function parameters. Levels of acetone (feature m/z = 58) were significantly negatively associated with FVC and FVE0.5, levels of tetradecane (feature m/z = 71) with FEV0.5, and levels of pentadecane (feature m/z = 71) with FEV0.5 and FEF25–75.ConclusionThe findings of this study highlight a significant association between VOCs related to oxidative stress and lung function in healthy infants.

Infant spirometry as a predictor of lung function at early childhood in cystic fibrosis patients

BackgroundInfant pulmonary function testing using the raised volume rapid thoracoabdominal compression (RVRTC) technique requires sedation and is time consuming. Many cystic fibrosis (CF) centers do not have access to equipment and the utility of routine testing remains to be determined. We aimed to assess whether RVRTC tests performed during infancy predict spirometry at early school age. MethodsThe RVRTC-based forced expiratory flow measures in infants were compared to the first adequately performed spirometry at school age. All tests were carried out during routine clinic visits and expressed as age related z-scores; only test occasions where patients were considered stable were included in the analysis. Results47 patients had useable infant RVRTC as well as matching school age spirometry data. There was weak correlation between infant FEV0.5 and early school age FEV1 (R = 0.29, p = 0.05). Four infants had significantly low zFEV0.5 (zFEV0.5 < -1.96), of which one of those remained under that limit at childhood. Changes in spirometry between infancy and early childhood were negatively correlated to baseline FEV0.5 (R = 0.61 p<0.001) reflecting that the change was driven by where individuals started off with. There was no difference in clinical characteristics between those improving, those with stable or deteriorating in lung function. ConclusionInfant RVRTC measures were not predictive of pulmonary function in early school age, likely due to the high proportion of measures of forced expiratory flows within the normal range at both time points.

Normative Data of Infant Pulmonary Function Testing: A Prospective Birth Cohort Study from India

To develop a normal reference range of Infant pulmonary function test (IPFT) indices for Indian children. Prospective birth cohort study. Division of Pediatric Pulmonology of a tertiary-care institute in India from August 2012 to March 2017. All neonates born at the institute during the study period were screened for eligibility. IPFT at baseline and every 6-month until 36-months of age. Tidal breathing flow-volume loop (TBFVL), Rapid thoracoabdominal compression (RTC), and Raised volume RTC (RVRTC) indices at baseline and follow-up. 310 newborns were enrolled in the cohort; 281 of them (169 male) had completed 36-months of follow-up at the end of the study period. There was no influence of gender on the baseline IPFT indices. Tidal volume per unit body weight (VT/kg) significantly increased from baseline to 36 months of age (P<0.001) while the peak ratio (tPTEF/tE) initially decreased in first 18-months of age (P<0.001), after that returned to the baseline value by 36 months of age. RTC indices did not change significantly from baseline values. In RVRTC, the ratio of forced expiratory volume in 0.5s to forced vital capacity (FEV0.5/FVC) was significantly decreased from baseline to 36 months of age (P=0.002). Normal values for various IPFT indices for TBFVL, RTC, and RVRTC from neonates to the age of 36-month are provided. These data may be used as normative data for healthy neonates and children of Indian origin.

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

To know the effect of caffeine therapy on infant lung function in preterm infants with a gestational age less than 31 weeks. 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. 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. 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.

Raised-Volume Forced Expiratory Flow-Volume Curve in Healthy Taiwanese Infants

The raised-volume rapid thoracoabdominal compression (RVRTC) manoeuvre has been applied to obtain full forced expiratory flow-volume curves in infants. No reference data are available for Asian populations. This study was conducted to establish predictive reference equations for Taiwanese infants. Full-term infants without any chronic disease or major anomaly were enrolled from this cohort study. Full forced expiratory flow-volume curves were acquired using RVRTC manoeuvres through Jaeger’s system. Tidal breath analysis, passive respiratory mechanics, and tidal forced expiratory flow-volume curves were performed and collected at the same measurement. Multiple linear analyses were used to model the variables. We performed 117 tests of RVRTC flow-volume curves in 97 infants. The results revealed that all parameters, except for FEV0.5 /FVC, correlated highly and positively with body length. These parameters correlated significantly with other parameters of passive respiratory mechanics and tidal forced expiratory flow-volume curves. This is the first study to establish equipment-specific reference data of full forced expiration using RVRTC manoeuvres in Asian infants. The results revealed that parameters of RVRTC manoeuvres are moderately related to other parameters of infant lung function. These race-specific reference data can be used to more precisely and efficiently diagnose respiratory diseases in infants of Chinese ethnicity.

Pulmonary Morbidity in Infancy after Exposure to Chorioamnionitis in Late Preterm Infants.

Chorioamnionitis is an important cause of preterm birth, but its impact on postnatal outcomes is understudied. To evaluate whether fetal exposure to inflammation is associated with adverse pulmonary outcomes at 6 to 12 months' chronological age in infants born moderate to late preterm. Infants born between 32 and 36 weeks' gestational age were prospectively recruited (N = 184). Chorioamnionitis was diagnosed by placenta and umbilical cord histology. Select cytokines were measured in samples of cord blood. Validated pulmonary questionnaires were administered (n = 184), and infant pulmonary function testing was performed (n = 69) between 6 and 12 months' chronological age by the raised volume rapid thoracoabdominal compression technique. A total of 25% of participants had chorioamnionitis. Although infant pulmonary function testing variables were lower in infants born preterm compared with historical normative data for term infants, there were no differences between infants with chorioamnionitis (n = 20) and those without (n = 49). Boys and black infants had lower infant pulmonary function testing measurements than girls and white infants, respectively. Chorioamnionitis exposure was associated independently with wheeze (odds ratio [OR], 2.08) and respiratory-related physician visits (OR, 3.18) in the first year of life. Infants exposed to severe chorioamnionitis had increased levels of cord blood IL-6 and greater pulmonary morbidity at age 6 to 12 months than those exposed to mild chorioamnionitis. Elevated IL-6 was associated with significantly more respiratory problems (OR, 3.23). In infants born moderate or late preterm, elevated cord blood IL-6 and exposure to histologically identified chorioamnionitis was associated with respiratory morbidity during infancy without significant changes in infant pulmonary function testing measurements. Black compared with white and boy compared with girl infants had lower infant pulmonary function testing measurements and worse pulmonary outcomes.

Lung function gain in preterm infants with and without bronchopulmonary dysplasia.

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. 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. 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. 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.

New reference ranges for interpreting forced expiratory manoeuvres in infants and implications for clinical interpretation: a multicentre collaboration

The raised volume rapid thoracoabdominal compression (RVRTC) technique is commonly used to obtain full forced expiratory manoeuvres from infants, but reference equations derived from ‘in-house’ equipment have been shown to...

Changes in multiple breath washout measures after raised volume rapid thoracoabdominal compression maneuvers in infants

Multiple breath inert gas washout (MBW) measurements in infants are performed supine and often obtained under sedation and thus are combined with other lung function tests such as raised volume rapid thoracoabdominal compression (RVRTC). In this study, we sought to determine the effects of RVRTC maneuvers on MBW measures. Compared with tests performed prior to RVRTC, MBW measured after RVRTC was associated with a small reduction in functional residual capacity and a more pronounced decrease in cumulative expired volume in both healthy children and children with obstructive lung disease (cystic fibrosis or recurrent wheeze) indicating a more efficient washout after the raised volume maneuvers. Lung Clearance Index (LCI) decreased significantly in infants with respiratory disease (change in LCI of -0.24 units post RVRTC; standard error (SE) ± 0.07 units; P = 0.0004), but not in healthy infants (change in LCI of -0.08 units; SE ± 0.11 units; P = 0.44). As the RVRTC maneuver affects MBW measurements in infants, the timing of testing procedures needs to be standardized in longitudinal studies.

Lung function at 6 and 18 months after preterm birth in relation to severity of bronchopulmonary dysplasia.

Many preterm infants with bronchopulmonary dysplasia (BPD) demonstrate impaired lung function and respiratory symptoms during infancy. The relationships between initial BPD severity, lung function and respiratory morbidity are not fully understood. We aimed to investigate the association between BPD severity and subsequent lung function and whether lung function impairment is related to respiratory morbidity. In this longitudinal cohort study, 55 infants born preterm (23-30 weeks of gestation) with mild or moderate/severe BPD, based on oxygen requirement at 36 gestational weeks, were followed up at 6 and 18 months postnatal age. Respiratory symptoms, such as recurrent or chronic chough and wheeze, were noted and patient records were scrutinized. Lung function was assessed by passive lung mechanics, whole body plethysmography, and tidal and raised volume rapid thoraco-abdominal compression techniques. Results were related to published normative values. Besides residual functional capacity (FRC) and respiratory system compliance (Cso ) assessed at 18 months, all measures of lung function were significantly below normative values. Moderate/severe BPD differed significantly from mild BPD only with respect to reduced Cso . At follow-up at 6 and 18 months, participants with respiratory symptoms showed lower; maximal forced expiratory flow at FRC (V'maxFRC) (P = 0.006, P = 0.001), forced mid-expiratory flows (MEF50 ) (P = 0.006, P = 0.048), and Cso (P = 0.004, P = 0.015) as compared to participants without symptoms. In the present study BPD severity did not predict lung function, but may be associated with impaired alveolarization, indicated by reduced Cso . Respiratory morbidity was associated with reduced airway function and respiratory compliance in infancy after preterm birth.

Predictors of early lung function in patients with congenital diaphragmatic hernia

PurposeLong-term pulmonary outcomes of congenital diaphragmatic hernia (CDH) have demonstrated airflow obstruction in later childhood. We examined pulmonary function data to assess what factors predict lung function in the first three years of life in children with CDH. MethodsThis was a retrospective study of patients treated for CDH who underwent infant pulmonary function testing (IPFT) between 2006 and 2012. IPFT was performed using the raised volume rapid thoracoabdominal compression technique and plethysmography. ResultsTwenty-nine neonates with CDH had IPFTs in the first 3years of life. Their mean predicted survival using the CDH Study Group equation was 63%±4%. Fourteen infants (48%) required extracorporeal membrane oxygenation (ECMO). The mean age at IPFT was 85.1±5weeks. Airflow obstruction was the most common abnormality, seen in 14 subjects. 12 subjects had air trapping, and 9 demonstrated restrictive disease. ECMO (p=0.002), days on the ventilator (p=0.028), and days on oxygen (p=0.023) were associated with restrictive lung disease. ConclusionDespite following a group of patients with severe CDH, lung function revealed mild deficits in the first three years of life. Clinical markers of increased severity (ECMO, ventilator days, and prolonged oxygen use) are correlated with reduced lung function.

Exhaled nitric oxide predicts persistence of wheezing, exacerbations, and decline in lung function in wheezy infants and toddlers.

There are limited data assessing the predictive value of fraction of exhaled nitric oxide (FENO ) for persistence of wheezing, exacerbations, or lung function change over time in infants/toddlers with recurrent wheezing. In an ongoing longitudinal cohort of infants and toddlers with recurrent wheezing, we compared predictive values of single-breath FENO (SB-FENO ), tidal-breathing mixed expired FENO (tidal-FENO ), bronchodilator responsiveness (BDR) and the Castro-Rodriquez Asthma Predictive Index (API) for persistence of wheezing, exacerbations and lung function change through age 3years. Enrolment forced expiratory flows and volumes infant pulmonary function tests (iPFTs) were measured in 44 infants/toddlers using the raised volume rapid thoracoabdominal compression method. SB-FENO was measured at 50mL/s, and tidal-FENO was measured during awake tidal breathing. Clinical outcomes were assessed at age 3years in 42 infants. Follow-up iPFTs were completed between ages 2.5-3years in 32 subjects. An enrolment SB-FENO concentration ≥30p.p.b. predicted persistence of wheezing at age 3years with a sensitivity of 77%, a specificity of 94%, and an area under the curve (AUC) of 0.86 (95% CI: 0.74-0.98). The sensitivity, specificity, positive predictive, and negative predictive values of SB-FENO for persistence of wheezing and exacerbations were superior to tidal-FENO , BDR, and the API. SB-FENO ≥30p.p.b. and tidal-FENO ≥7p.p.b. measured at enrolment was associated with a decline in both FEV0.5 and FEF25-75 between enrolment and age 3years. In wheezy infants/toddlers, SB-FENO was superior to tidal-FENO , BDR, and the API in predicting future exacerbations and persistence of wheezing at age 3years. Both SB-FENO and tidal-FENO were associated with lung function decline over time.

A 2-year-old girl with co-inherited cystic fibrosis and sickle cell-β+ thalassemia presenting with recurrent vaso-occlusive events during cystic fibrosis pulmonary exacerbations: a case report

IntroductionThis is the first published report of a young girl with co-inherited sickle cell-β+ thalassemia and cystic fibrosis. Although a small subset of patients with co-inherited cystic fibrosis and other hemoglobinopathies have been reported, this patient developed early hematologic and pulmonary complications that were more severe than the previous cases. To assess pulmonary co-morbidities, we used infant pulmonary function testing through the raised volume rapid thoracoabdominal compression technique as both an established study of early cystic fibrosis and also as a newer study of mechanism for early sickle cell lung disease. This further serves as the first report of the raised volume rapid thoracoabdominal compression technique to determine raised volume forced expiratory flows and fractional lung volumes in a patient with a hemoglobinopathy.Case presentationA 2-year-old African-American girl with co-inherited cystic fibrosis and sickle cell-β+ thalassemia developed severe hematologic complications (recurrent vaso-occlusive events, hepatic sequestration, and acute chest syndrome) during periods of cystic fibrosis pulmonary exacerbations and weight loss. Because cystic fibrosis and sickle cell-β+ thalassemia both confer distinct patterns of pulmonary disease, infant pulmonary function testing with the raised volume rapid thoracoabdominal compression technique was used to define respiratory pathophysiology and guide treatment options. Infant pulmonary function testing data demonstrated moderate-to-severe lower airways obstruction, moderate air trapping, and no evidence of restrictive lung disease.ConclusionsInfant pulmonary function testing with the raised volume rapid thoracoabdominal compression technique guided therapy in this patient with cystic fibrosis and sickle cell-β+ thalassemia. Although this is an original case report on a unique patient, this case highlights the need to evaluate early respiratory pathophysiology in a broader population of young patients with hemoglobinopathies and screen those at risk for early pulmonary co-morbidities.

Abnormal infant pulmonary function in young children with neuroendocrine cell hyperplasia of infancy

Lung function in children with neuroendocrine cell hyperplasia of infancy (NEHI) and correlations with future clinical outcomes are needed to guide clinical management. To compare results of infant pulmonary function tests (IPFTs) in children with NEHI to disease control (DC) subjects and to correlate NEHI IPFTs with future outcomes. We performed a retrospective, single center study of IPFT in subjects diagnosed by lung biopsy (NEHI) or clinically (NEHI syndrome) and in DC subjects evaluated for cancer or pre-hematopoietic stem cell transplantation (HSCT). Raised volume rapid thoracoabdominal compression (RVRTC) and plethysmography were performed on all infants and evaluated for quality. Standard spirometry measures, room air oxygen saturations (RA O2 sat), and weight percentiles were collected during follow up. Fifty-seven IPFTs were performed in 15 NEHI, 22 NEHI syndrome, and 20 DC subjects. RVRTC and FRC measurements were obtained in 85% or more of subjects in all groups. Significant airflow limitation (FEV0.5 P-value ≤ 0.01) and air trapping (FRC P-value ≤ 0.01) were seen in NEHI and NEHI syndrome subjects compared to DCs. No significant correlations were found between IPFT, oxygen use, RA O2 sat, and weight at the time of the IPFTs. Initial FEV0.5 and FRC z-scores correlated with RA O2 sat (r = 0.60 and -0.49) at short-term follow up (6-12 months). Most measurements of RVRTC correlated with FEV1 (n = 5) measured 4-5 years later (r > 0.50). IPFTs in NEHI subjects are feasible, demonstrate significant obstruction and air trapping, and correlate with future RA O2 sat and FEV1 . IPFTs may provide valuable clinical information when caring for NEHI patients. Pediatr Pulmonol. 2013; 48:1008-1015. © 2012 Wiley Periodicals, Inc.

Nasal versus oronasal raised volume forced expirations in infants—A real physiologic challenge

Raised volume rapid thoracoabdominal compression (RTC) generates forced expiration (FE) in infants typically from an airway opening pressure of 30 cm H(2)O (V(30)). We hypothesized that the higher nasal than pulmonary airway resistance limits forced expiratory flows (FEF(%)) during (nasal) FE(n), which an opened mouth, (oronasal) FE(o), would resolve. Measurements were performed during a brief post-hyperventilation apnea on 12 healthy infants aged 6.9-104 weeks. In two infants, forced expiratory (FEFV) flow volume (FV) curves were generated using a facemask that covered the nose and a closed mouth, then again with a larger mask with the mouth opened. In other infants (n = 10), the mouth closed spontaneously during FE. Oronasal passive expiration from V(30) generated either the inspiratory capacity (IC) or by activating RTC before end-expiration, the slow vital capacity ((j) SVC). Peak flow (PF), FEF(25), FEF(50), FEF(25-75), FEV(0.4), and FEV(0.5) were lower via FE(n) than FE(o) (P < 0.05), but the ratio of expired volume at PF and forced vital capacity (FVC) as percent was higher (P < 0.05). FEF(75), FEF(85), FEF(90), FVC as well as the applied jacket pressures were not different (P > 0.05). FEFV curves generated via FE(o) exhibited higher PF than FV curves of IC (P < 0.05); PF of those produced via FE(n) were not different from FV curves of IC (P > 0.05) but lower than those of (j) SVC (P < 0.05). In conclusion, the higher nasal than pulmonary airways resistance unequivocally affects the FEFV curves by consistently reducing PF and decreases mid-expiratory flows. A monitored slightly opened mouth and a gentle anterior jaw thrust are physiologically integral for raised volume RTC in order to maximize the oral and minimize nasal airways contribution to FE so that flow limitation would be in the pulmonary not nasal airways.

Longitudinal measures of lung function in infants with bronchopulmonary dysplasia

We previously demonstrated that infants with a history of bronchopulmonary dysplasia (BPD) exhibit airflow obstruction and air trapping. The purpose of this study was to assess longitudinal changes in pulmonary function in infants with a history of BPD over the first 3 years of life, and the relationship to somatic growth. Spirometry was measured using the raised volume rapid thoracoabdominal compression technique, and lung volumes measured by plethysmography. Eighteen infants (mean gestational age ± SD 27.3 ± 2.2 weeks, birthweight 971 ± 259 g) underwent two lung function studies. Average age at first test was 58.8 weeks. Spirometry demonstrated significant reductions in forced expiratory volume in 0.5 sec (FEV(0.5), 76.0 ± 15.9% predicted, Z-score -2.13 ± 1.69), forced expiratory flow at 75% of expired forced vital capacity (FEF(75), 54.8 ± 31.1%, -3.58 ± 2.73), and FEF(25-75) (67.8 ± 33.3%, -1.79 ± 1.76). Group mean total lung capacity (TLC) was in the low normal range (82.9 ± 13.5% predicted) and residual volume (RV)/TLC was mildly elevated (122.4 ± 38.2% predicted). Repeat testing was performed an average of 32.7 weeks after initial testing. At re-evaluation, group mean lung volumes and flows tracked at or near their previous values; thus, in general, there was a lack of catch-up growth. However, compared to infants with below average or average somatic growth (as represented by g/day), infants with above average growth showed significantly greater improvements in percent predicted FVC, FEV(0.5), TLC, and RV/TLC (all P < 0.05, ANOVA). We conclude that longitudinal measures of pulmonary function in infants and young children with BPD demonstrate significant airflow obstruction and modest restriction, which tends to persist with time. On the other hand, infants with above average somatic growth showed greater lung growth than their peers. Additional studies examining the effects of various nutritional regimens on lung function are warranted.

Multicenter Evaluation of Infant Lung Function Tests as Cystic Fibrosis Clinical Trial Endpoints

The conducting of clinical trials in infants with cystic fibrosis (CF) has been hindered by lack of sensitive outcome measures. To evaluate safety, feasibility, and ability to detect abnormalities in lung function of serial pulmonary function tests (PFTs) in infants with CF. Multicenter observational study using a commercial device, rigorous training, ongoing quality control, and over-reading of data by an independent panel. Raised volume rapid thoracoabdominal compression technique and plethysmography were performed at enrollment and at 6 and 12 months, with an additional 1-month reproducibility visit. A total of 342 procedures were performed in 100 infants with CF at 10 centers. FRC measurements were acceptable at a higher proportion of study visits (89%) than raised volume (72%) or fractional lung volume (68%) measurements. Average Z scores for many parameters differed significantly from historical control values. Mean (95% confidence interval) Z scores were: -0.52 (-0.78 to -0.25) for forced expiratory flow at 75% (FEF₇₅) for FVC; 1.92 (1.39-2.45) for FRC; 1.22 (0.68-1.76) for residual volume; 0.87 (0.60-1.13) for FRC/total lung capacity; and 0.66 (0.27-1.06) for residual volume/total lung capacity. For future multicenter clinical trials using infant PFTs as primary endpoints, minimum detectable treatment effects are presented for several sample sizes. In this 10-center study, key PFT measures were significantly different in infants with CF than in historical control subjects. However, infant PFTs do not yet appear ready as primary efficacy endpoints for multicenter clinical trials, particularly at inexperienced sites, based on acceptability rates, variability, and potentially large sample sizes required to detect reasonable treatment effects.

Comprehensive integrated spirometry using raised volume passive and forced expirations and multiple-breath nitrogen washout in infants.

With the rapid somatic growth and development in infants, simultaneous accurate measurements of lung volume and airway function are essential. Raised volume rapid thoracoabdominal compression (RTC) is widely used to generate forced expiration from an airway opening pressure of 30 cmH(2)O (V(30)). The (dynamic) functional residual capacity (FRC(dyn)) remains the lung volume most routinely measured. The aim of this study was to develop comprehensive integrated spirometry that included all subdivisions of lung volume at V(30) or total lung capacity (TLC(30)). Measurements were performed on 17 healthy infants aged 8.6-119.7 weeks. A commercial system for multiple-breath nitrogen washout (MBNW) to measure lung volumes and a custom made system to perform RTC were used in unison. A refined automated raised volume RTC and the following two novel single maneuvers with dual volume measurements were performed from V(30) during a brief post-hyperventilation apneic pause: (1) the passive expiratory flow was integrated to produce the inspiratory capacity (IC) and the static (passive) FRC (FRC(st)) was estimated by initiating MBNW after end-passive expiration; (2) RTC was initiated late during passive expiration, flow was integrated to produce the slow vital capacity ((j)SVC) and the residual volume (RV) was measured by initiating MBNW after end-expiration while the jacket (j) was inflated. Intrasubject FRC(dyn) and FRC(st) measurements overlapped (p=0.6420) but neither did with the RV (p<0.0001). Means (95% confidence interval) of FRC(dyn), IC, FRC(st), (j)SVC, RV, forced vital capacity and tidal volume were 21.2 (19.7-22.7), 36.7 (33.0-40.4), 21.2 (19.6-22.8), 40.7 (37.2-44.2), 18.1 (16.6-19.7), 40.7 (37.1-44.2) and 10.2 (9.6-10.7)ml/kg, respectively. Static lung volumes and capacities at V(30) and variables from the best forced expiratory flow-volume curve were dependent on age, body length and weight. In conclusion, we developed a comprehensive physiologically integrated approach for in-depth investigation of lung function at V(30) in infants.

Association of lower airway inflammation with physiologic findings in young children with cystic fibrosis

The relationship between lower airway markers of inflammation and infection with physiologic findings is poorly understood in young children with cystic fibrosis (CF). The goal of this study was to evaluate the association of bronchoalveolar lavage fluid (BALF) markers of infection and inflammation, including mediators linked to airway remodeling, to infant lung function values in young children with CF undergoing clinically indicated bronchoscopy. Plethysmography and the raised volume rapid thoracoabdominal compression (RVRTC) technique were performed in 16 sedated infants and young children with CF prior to bronchoscopy. BALF was collected and analyzed for pathogen density, cell count, % neutrophils, transforming growth factor beta 1 (TGF-beta(1)), matrix metalloproteinases (MMP), and interleukin-8 (IL-8). There was a significant direct correlation between functional residual capacity (FRC), the ratio of residual volume to total lung capacity (RV/TLC) and FRC/TLC with % neutrophils (P < 0.05). Forced expiratory flows were inversely correlated to % neutrophils (P < 0.01). Lung function parameters did not differentiate those with and without lower airway infection; however, pathogen density directly correlated with FRC and inversely correlated with flows (P < 0.05). In a subset of the population, MMP-2 directly correlated with RV/TLC and inversely correlated with flows (P < 0.05) and TGF-beta(1) directly correlated with FRC (P < 0.05). Results from this study suggest that lower airway inflammation as well as mediators linked to airway remodeling play an active role in pulmonary deterioration in CF infants and young children undergoing clinically indicated bronchoscopy.