Passive Respiratory Mechanics Research Articles

Respiratory pressure and split flow data collection device with rapid occlusion attachment

Respiratory model-based methods require datasets containing enough dynamics to ensure model identifiability for development and validation. Rapid expiratory occlusion has been used to identify elastance and resistance within a single breath. Currently accepted practice for rapid expiratory occlusion involves a 100 ms occlusion of the expiratory pathway. This article presents a low-cost modular rapid shutter attachment to enable identification of passive respiratory mechanics. Shuttering faster than 100 ms creates rapid expiratory occlusion without the added dynamics of muscular response to shutter closure, by eliminating perceived expiratory blockage via high shutter speed. The shutter attachment fits onto a non-invasive venturi-based flow meter with separated inspiratory and expiratory pathways, established using one-way valves. Overall, these elements allow comprehensive collection of respiratory pressure and flow datasets with relatively very rapid expiratory occlusion.

Mechanical power in AVM-2 versus conventional ventilation modes in a normal lung model: A bench study

Introduction Recent studies suggested that the energy delivered by the mechanical ventilator to the lungs termed the mechanical power can induce and increase the risks of ventilator induced lung injury. The components of the mechanical power include the variables delivered by the ventilator: tidal volume, respiratory rate, inspiratory flow, airway pressure. Adaptive Ventilator Mode-2 (AVM-2) is a pressure-controlled mode with an optimal targeting scheme based on the inspiratory power equation that adjusts the respiratory rate and tidal volume to achieve a target minute ventilation. This mode conceptually should reduce the mechanical power delivered to the patients and thus reduce the incidence of ventilator induced lung injury. Methodology A bench study using a lung simulator (TTL, Michigan Instruments, Michigan, USA) was conducted. We constructed a passive single compartment normal respiratory mechanics model with compliance of 50 ml/cmH2O, and resistance of 10 cmH2O/L/s, with IBW 70 kg. We compared three different ventilator modes: Adaptive Ventilation Mode-2 (AVM-2), Pressure Regulated Volume Control (PRVC), and Volume Controlled Ventilation (VCV) in four different scenarios: 2 levels of minute ventilation 7 and 10.5 Lit/min (Experiment 1 and 2 respectively), each with 2 different PEEP levels 5 and 10 cmH2O (Experiment A and B respectively) termed Experiments 1A, 1B, 2A, and 2B respectively. The AVM-2 mode automatically selects the optimal tidal volume, and respiratory rate per the dialed percent minute ventilation with an I:E ratio of 1:1. In the PRVC, VCV we selected target tidal volume 6ml/kg/IBW (420 ml), and respiratory rate adjusted to match the minute ventilation for the AVM-2 mode. I:E ratio was kept 1:2 to avoid intrinsic PEEP. The study was conducted using a bellavista™ 1000 e Ventilator (Vyaire Medical, Illinois, USA). The mechanical power delivered by the ventilator for each mode was computed and compared between the three modes in each experiment. Statistical analysis was done using Kruskal-Wallis test to analyze the difference between the three modes, post HOC Tukey test was used to analyze the difference between each mode with the confidence intervals, P < 0.05 was considered statistically significant. Results There were statistically significant differences between all the three modes regarding the ventilator delivered mechanical power. The AVM-2 mode delivered significantly less mechanical power than VCV which in turn was less than PRVC. Experiment 1A: AVM-2 8.76 土 0.05, VCV 9.78 土 0.04, PRVC 10.82 土 0.08, P < 0.001 Experiment 1B: AVM-2 11.27 ± 0.09 VCV 12.81 ± 0.05, PRVC 13.88 ± 0.06, P < 0.001. Experiment 2A: AVM-2 14.76 ± 0.05, VCV 15.79 ± 0.05, PRVC 18.29 ± 0.07, P < 0.001, Experiment 2B: AVM-2 18.76 ± 0.04, VCV 20.56 ± 0.04, PRVC 21.17 土 0.03, P < 0.001. Discussion AVM2 mode delivered less mechanical power compared to two conventional modes using low tidal volume in a normal lung model. This might reduce the incidence of ventilator induced lung injury. Results need to be validated in more clinical studies.

Development of Lung Function in Preterm Infants During the First Two Years of Life

IntroductionIt remains unclear if prematurity itself can influence post delivery lung development and particularly, the bronchial size. AimTo assess lung function during the first two years of life in healthy preterm infants and compare the measurements to those obtained in healthy term infants during the same time period. MethodsThis observational longitudinal study assessed lung function in 74 preterm (30+0 to 35+6 weeks’ gestational age) and 76 healthy term control infants who were recruited between 2011 and 2013. Measurements of tidal breathing, passive respiratory mechanics, tidal and raised volume forced expirations (V’maxFRC and FEF25–75, respectively) were undertaken following administration of oral chloral hydrate sedation according to ATS/ERS recommendations at 6- and 18-months corrected age. ResultsLung function measurements were obtained from the preterm infants and full term controls initially at 6 months of age. Preterm infants had lower absolute and adjusted values (for gestational age, postnatal age, sex, body size, and confounding factors) for respiratory compliance and V’maxFRC. At 18 months corrected postnatal age, similar measurements were repeated in 57 preterm infants and 61 term controls. A catch-up in tidal volume, respiratory mechanics parameters, FEV0.5 and forced expiratory flows was seen in preterm infants. ConclusionWhen compared with term controls, the lower forced expiratory flows observed in the healthy preterm group at 6 months was no longer evident at 18 months corrected age, suggesting a catch-up growth of airway function.

Distinct lung function and bronchodilator responses between term and preterm young children with recurrent wheezing

Recurrent or unresolved wheezing is a common complaint in certain young children populations, especially those born preterm. Using infant lung function testing, we aimed to distinguish the differences between term and preterm young children with recurrent wheezing. Children under 2 years of corrected age were enrolled if they had 3 or more wheezing episodes during the enrollment period. Healthy term controls of comparable age were also recruited for reference. Measurements of lung function were made, including tidal breathing, passive respiratory mechanics, and forced tidal and raised-volume expiration. For children with recurrent wheezing, raised-volume forced expiration was repeated after an adequate delivery of bronchodilator nebulization was achieved. In total, 68 young children (40 with recurrent wheezing and 28 healthy controls) were recruited. Among children with recurrent wheezing, 23 preterm children (preterm group), and 17 term children (term group) were enrolled. Compared with healthy controls, both the term and preterm groups had lower lung function as measured by absolute values and z scores. The term group performed worse than the preterm group with regard to forced vital capacity, forced expiratory volume at 0.5s (FEV0.5), and peak expiratory flow. Following bronchodilator nebulization, the term group had significantly higher increases in FEV0.5 and forced mid-expiratory flow than the preterm group. Young children with recurrent wheezing, especially term infants, demonstrated lower lung function than healthy controls. Moreover, the term group evidenced greater responsiveness to bronchodilators than the preterm group. The distinct bronchodilator responses may offer further information to guide the diagnosis and treatment of young children with recurrent wheezing.

Development of an ex vivo preclinical respiratory model of idiopathic pulmonary fibrosis for aerosol regional studies

Idiopathic pulmonary fibrosis is a progressive disease with unsatisfactory systemic treatments. Aerosol drug delivery to the lungs is expected to be an interesting route of administration. However, due to the alterations of lung compliance caused by fibrosis, local delivery remains challenging. This work aimed to develop a practical, relevant and ethically less restricted ex vivo respiratory model of fibrotic lung for regional aerosol deposition studies. This model is composed of an Ear-Nose-Throat replica connected to a sealed enclosure containing an ex vivo porcine respiratory tract, which was modified to mimic the mechanical properties of fibrotic lung parenchyma - i.e. reduced compliance. Passive respiratory mechanics were measured. 81mKr scintigraphies were used to assess the homogeneity of gas-ventilation, while regional aerosol deposition was assessed with 99mTc-DTPA scintigraphies. We validated the procedure to induce modifications of lung parenchyma to obtain aimed variation of compliance. Compared to the healthy model, lung respiratory mechanics were modified to the same extent as IPF-suffering patients. 81mKr gas-ventilation and 99mTc-DTPA regional aerosol deposition showed results comparable to clinical studies, qualitatively. This ex vivo respiratory model could simulate lung fibrosis for aerosol regional deposition studies giving an interesting alternative to animal experiments, accelerating and facilitating preclinical studies before clinical trials.

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.

Reference values for resistance and compliance based on the single occlusion technique in healthy infants from Southeast China.

Respiratory disease is a major cause of morbidity and mortality in infants and has a large impact on health care. The aim of this study was to present the reference values of resistance and compliance by using a single occlusion technique (SOT) in healthy infants in Southeast China. Respiratory compliance (Crs) and respiratory resistance (Rrs) were measured in healthy infants, aged 1-96 weeks, by using SOT in the Children's Hospital of FuDan University (Shanghai, China). For comparison, the infants were grouped by age as follows: 1-24, 25-48, 49-72 and 73-96 weeks. Multiple regression analysis was performed using age, length, weight, and body mass index (BMI) as the independent variables to obtain predictive equations, separated according to sex. We measured 205 healthy infants from birth up to 96 weeks of age (112 boys, 93 girls). Height and weight increased significantly with age. The Rrs declined with length, whereas the Crs increased. The median Rrs was 5.04 kPa/L/sec (range, 3.73-6.82 kPa/L/sec), and the mean Crs was 119.52±60.47 mL/kPa. Regression equations for Rrs and Crs were obtained. We obtained reference values for passive respiratory mechanics by using SOT in healthy infants from Southeast China. These data provide references for assessing the normality of SOT measurements in infants.

Response to bronchodilators in very preterm infants with evolving bronchopulmonary dysplasia.

There are few effective and safe medications to treat very low birth weight (VLBW) infants with evolving BPD. Bronchodilators are often given to patients who have clinical signs of reactive airway disease, but there is not enough information regarding their effectiveness within this population. To quantify the pulmonary function response to bronchodilator therapy in a population of VLBW infants with evolving BPD. This is a retrospective analysis of an ongoing large database of pulmonary function tests (PFTs) in premature infants. We reviewed pre and post bronchodilator PFTs ordered by a physician due to concern for reactive airway disease. Inclusion criteria: BW< 1500 grams; > 14 days of age; admission diagnosis of respiratory distress syndrome; requiring ongoing oxygen, CPAP or ventilator support at the time of PFT. PFTs were done prior to albuterol therapy and repeated 30 minutes after the therapy was given. PFTs included the measurement of passive respiratory mechanics with the single breath occlusion technique, including passive respiratory compliance (Crs), resistance (Rrs) and tidal volume (Vt). 40 VLBW infants (mean gestation of 27.4 weeks; mean birth weight (BW) of 848 grams) were identified as having PFTs. 29 of these patients had a BW of ≤ 1000 grams. Patients were studied at a mean corrected gestational age of 34.9 weeks. 29 of 40 were extubated at the time of the PFT. Of these patients, 21 (52.5%) had a decrease in Rrs of ≥10%. From the other 19 patients, 5 (12.5%) had a decrease of 0 to < 10% in Rrs, 14 (35%) showed no response to therapy. There was no significant difference in Crs between groups.

Respiratory Function in Healthy Taiwanese Infants: Tidal Breathing Analysis, Passive Mechanics, and Tidal Forced Expiration.

BackgroundAlthough infant lung function (ILF) testing is widely practiced in developed Western countries it is not typically performed in Eastern countries, and lung measurements are scarce for Asian infants. Therefore, this study aimed to establish normal reference values for Taiwanese infants.Materials and MethodsFull-term infants without any chronic diseases and major anomalies were enrolled in the Prediction of Allergies in Taiwanese Children (PATCH) cohort study. Detailed medical data, such as body weight and length, birth history, and histories of previous illness and hospitalization were recorded. Lung function measurements such as analysis of tidal breathing, passive respiratory mechanics, and forced tidal expiratory flow-volume curves were obtained through Jaeger Masterscreen BabyBody Paediatrics System. Multiple linear analyses were performed to determine various parameters of the lung function tests.ResultsILF test parameters were collected from 126 infants, and 189 tests were performed. The results revealed that the ratio of time to peak expiratory flow to total expiratory time, the ratio of volume to peak expiratory flow to total expiratory volume, and the ratio of inspiratory time to total respiratory time remained relatively constant despite differences in age. However, body length is the strongest independent variable influencing tidal volume, respiratory rate, resistance, compliance, and maximal expiratory flow at functional residual capacity.ConclusionAccording to our review of relevant literature, this is the first study to establish a reference data of ILF tests in the Asian population. This study provided reference values and regression equations for several variables of lung function measurements in healthy infants aged less than 2 years. With these race-specific reference data, ILF can more precisely and efficiently diagnose respiratory diseases in infants of Chinese ethnicity.

Assessment of early pulmonary function abnormalities in giant omphalocele survivors

PurposeInfants with giant omphalocele (GO) are at increased risk for persistent respiratory insufficiency, yet information regarding the systematic assessment of their lung function is limited. We performed a group of pulmonary function tests (PFTs) including spirometry, fractional lung volume measurements, assessment of bronchodilator responsiveness, and passive respiratory mechanics in GO survivors during infancy and early childhood to evaluate the nature and degree of pulmonary dysfunction. Material and MethodsBetween July 2004 and June 2008, 30 consecutive GO survivors were enrolled in our interdisciplinary follow-up program. Forty-seven percent (14/30) underwent PFT during follow-up evaluation using the raised volume rapid thoracic compression technique to measure forced expiratory flows and bronchodilator responsiveness, body plethysmography to calculate lung volumes, and the single breath occlusion technique to measure passive mechanics of the respiratory system. ResultsThe mean age at PFT assessment was 19.3 ± 19.7 months (range, 1.0-58). Mean forced vital capacity and mean forced expiratory volume in the first 0.5 second were significantly reduced compared with published normative values (P = .03 and P < .01, respectively). Total lung capacity was significantly reduced (P < .001), whereas functional residual capacity, residual volume, and residual volume to total lung capacity ratio were within the normative range (P = .21, P = .34, and P = .48, respectively). Among the 46% who demonstrated significant bronchodilator responsiveness, there were greater increases in the mean percentage changes in flow at 25% to 75% (P = .01), flow at 75% (P < .001), and flow at 85% (P < .001) compared with those participants that did not respond. Specific compliance was reduced, whereas specific conductance increased, compared with published normal results. ConclusionsAbnormalities of pulmonary function in GO survivors include lung volume restriction without airway obstruction, an increased likelihood of airway hyperresponsivness, and reduced respiratory system specific compliance. Early recognition of pulmonary functional impairment in GO survivors could help to develop targeted treatment strategies to reduce the risk of subsequent pulmonary morbidity.

New reference equations to improve interpretation of infant lung function

With increasing use of infant pulmonary function tests (IPFTs) in both clinical and research studies, appropriate interpretation of results is essential. To investigate the potential bias associated with "normalising" IPF by expressing results as a ratio of body size and to develop reference ranges for tidal breathing parameters, passive respiratory mechanics (compliance [Crs] and resistance [Rrs]) and plethysmographic functional residual capacity (FRCp ) for white infants during the first 2 years of life. IPFTs were measured using the Jaeger BabyBody system and standardized protocols. Reference equations, adjusted for body size, age, and sex where appropriate, were created using multilevel modeling. The ratio of lung function to body length changes markedly with growth, thereby precluding its use for any outcome. While the ratio of tidal volume and Crs to body weight remained relatively constant with growth, this was not the case for FRCp . Even in healthy infants, a strong inverse relationship was observed between lung function/body weight and weight z-score which could distort interpretation of results in growth-restricted infants with lung disease, such as cystic fibrosis. Reference equations were derived from 153 healthy white infants on 232 test occasions (median age 35.5 weeks [range: 2.6-104.7]). Crown-heel length was the strongest predictor of IPF. When reporting IPF, use of size-corrected ratios should be discouraged, with interpretation instead based on appropriate reference equations. The current equations are applicable to white infants and young children up to 2 years of age, studied using the same commercially available equipment. The extent to which these equations are applicable to infants and young children of other ethnic backgrounds or who are tested with different equipment needs to be established.

Lung function at 10 yr is not impaired by early childhood lower respiratory tract infections

The causal relationship between lower respiratory tract infections (LRIs) in early life and reduced lung function later in childhood is unsettled. Therefore, we assessed whether LRIs the first 2 yr of life influenced lung function development from birth to school age. In the prospective Oslo birth cohort, 'the Environment and Childhood Asthma (ECA) study' lung function was measured at birth in 802 infants by tidal flow volume loops and in 664 infants by passive respiratory mechanics and half yearly questionnaires, including LRI questions, were completed until 2 yr of age. The present study includes 607 children with information about LRIs the first 2 yr of life and successfully forced expiratory flow (FEF) volume measurements at the 10-yr follow-up assessment. At 10 yr of age, FEF at 50% of forced vital capacity (FEF(50)) (mean 95% confidence interval) was reduced in children with at least one bronchiolitis (85.0, 80.6-89.5, p = 0.020) or bronchitis (86.2, 82.6-89.8, p = 0.030) or > or =3 LRIs (83.4, 78.1-88.8, p = 0.017) when compared with no LRIs (90.6, 88.8-92.5) by 2 yr of life. The effects were significant in girls only when stratifying for gender. Among girls with later bronchiolitis compliance of the respiratory system (3.64, 3.17-4.10 vs. 4.18, 3.98-4.37, p = 0.031) and the ratio of time to peak tidal expiratory flow to total expiratory time (t(PTEF)/t(E)) measured at birth was significantly reduced (0. 26, 0.23-0.29 vs. 0.32, 0.30-0.33, p = 0.005) when compared with children with no LRIs. Change in lung function from birth (by t(PTEF)/t(E)) to 10 yr of age was not significantly associated with LRIs the first 2 yr of life, and LRIs by 2 yr of life were not significantly associated with lung function at 10 yr of age in regression analyses including lung function at birth and other possible predictors of lung function at 10 yr. In our study, LRIs during the first 2 yr of life did not impair lung function development from birth until 10 yr of age.

Longitudinal assessment of lung function from infancy to childhood in patients with cystic fibrosis

Infant pulmonary function testing (IPFT) has become an important clinical tool for the evaluation of lung function in infants with Cystic Fibrosis (CF); however, it is still unclear whether lung function in infancy is predictive of lung function later in life. We hypothesized that measures of airflow obstruction by IPFT would correlate strongly with lung function by conventional spirometry later in childhood. A retrospective analysis was performed of all CF infants studied with IPFT at the University of Minnesota Children's Hospital between September 1994 and March 2003. A total of 41 patients underwent IPFT and had valid spirometry results available at age 6 or later. IPFT values, such as I:E ratio, respiratory rate, tidal volume, and T(ptef)/T(e), were calculated from tidal breathing loops. Passive respiratory system mechanics, which included C(rs), R(rs), and tau(rs), were measured by the single breath end-inspiratory occlusion technique. Forced expiratory flows, including V(max)FRC, FVC, FEF(50), and FEF(75), were obtained by rapid thoracic compression and included a full vital capacity maneuver by the multiple inflation method. FRC measurements were calculated from data obtained via nitrogen washout in a subset of patients. In addition, information on age at diagnosis and results of oropharyngeal (OP) cultures at diagnosis and on subsequent visits was recorded. Standard spirometry was performed in all patients starting at age 5. The first valid flow-volume loop after age six was selected for analysis. Significant correlations were observed for the R(rs) and the FEF(50) by IPFT and the FEV(1) and the FEF(25-75) by standard spirometry (r > 0.4 and P < 0.03 for all correlations). These correlations were the strongest for those IPFT measurements obtained within 1 month of diagnosis and when R(rs) was expressed as sG(rs). The correlations observed were independent of the effects of age at diagnosis, gender and presence of Pseudomonas in oropharyngeal cultures at the time of diagnosis. Mean R(rs) declined from 0.050 to 0.027 cm H(2)O/ml/sec with treatment (P < 0.0001). There were no other significant associations found between other IPFT values measured and FEV(1) by spirometry. Measures of airflow obstruction on IPFT, specifically R(rs), sG(rs), and FEF(50), were strongly correlated with future lung function. IPFT measurement of R(rs) in addition to forced expiratory flows may help select patients at the greatest risk of early lung function decline. This study supports the use of R(rs) as a surrogate variable to help assess the impact of early therapies in CF.

Reduced Lung Function at Birth and the Risk of Asthma at 10 Years of Age

Håland G, Carlsen KC, Sandvik L, et al. N Engl J Med. 2006;355:1682–1689 PURPOSE OF THE STUDY. To evaluate whether reduced lung function at birth predicts the development of asthma and markers of obstructive airway diseases by 10 years of age. STUDY POPULATION. A prospective cohort of 616 10-year-old Norwegian children from the Environmental and Childhood Asthma (ECA) study who were initially enrolled as healthy term infants and had undergone lung-function testing and passive respiratory mechanics evaluation shortly after birth. METHODS. Lung function at birth was measured by calculating the fraction of time to peak expiratory flow to total expiratory time (tPTEF/tE) on the basis of tidal breathing flow-volume loops. Respiratory mechanics at birth were assessed by calculating respiratory system compliance and resistance during passive maneuvers. Data at the 10-year follow-up were collected during 2 clinical visits including forced expiratory flow-volume loops, methacholine-challenge tests, a treadmill exercise test, and skin-prick testing for common inhalant and food allergens. Parents also completed a validated International Study of Asthma and Allergies in Childhood questionnaire on airway symptoms, asthma-medication use, and previous physician-diagnosed asthma. The follow-up assessments and interviews were blinded with regard to the lung-function measurements at birth. RESULTS. In this cohort, the prevalence of a history of asthma was 20.2%, and prevalence of current asthma was 11.1%. Children with a tPTEF/tE at or below the median at birth were more likely at 10 years of age to have a history of asthma (24.3% vs 16.2%; P = .01), current asthma (14.6% vs 7.5%; P = .005), severe bronchial hyperresponsiveness (9.1% vs 4.9%; P = .05), and inhaled corticosteroid use (5.9% vs 2.4%; P = .02). Children with respiratory system compliance at or below the median were more likely to have a history of asthma (27.4% vs 14.8%; P = .001) and current asthma (15.0% vs 7.7%; P = .009). Decreased lung-function measurements did not consistently correlate with percent predicted forced flow-volume loops and exercise testing. CONCLUSIONS. Reduced lung function at birth may be a risk factor for the development of asthma by 10 years of age. REVIEWER COMMENTS. Other studies to date have shown that infants with reduced lung function have an increased risk for wheezing and asthma in the first few years of life. This study suggests that measuring lung function at birth may be useful in predicting which infants will develop asthma by late childhood. Knowing these risks may allow for directed therapy and prevention.

Lung function development in the first 2 yr of life is independent of allergic diseases by 2 yr

The aim of the study was to assess if lung function at birth predicts lung function at 2 yr and secondly, if lung function development was influenced by the common phenotypes of recurrent bronchial obstruction (rBO) or atopic eczema (AE) by 2 yr. Lung function was assessed at birth (n = 802) and at 2 yr within the prospective birth cohort study 'the Environment and Childhood Asthma Study' in Oslo. The 135 children with lung function measured at birth by tidal flow volume (TFV) loops and passive respiratory mechanics, who were included in a nested case-control study were reinvestigated at 2 yr with clinical examination, TFV loops (n = 90) (mean age 26.6 (3.7 s.d.) months), skin prick test and parental interview. Children were categorized into quartiles (lower, middle two, upper) according to time to peak tidal expiratory flow/total expiratory time (t(PTEF)/t(E)) at birth as well as clinical phenotype based on the presence of rBO and/or AE (ever) by 2 yr. The observed reduction in mean t(PTEF)/t(E) from birth to 2 yr within the quartiles, were not significantly different after controlling for 'regression to the mean'. t(PTEF)/t(E) at birth correlated significantly with t(PTEF)/t(E) at 2 yr, (r = 0.475, p < 0.001). Children with both rBO and AE by 2 yr had significantly lower t(PTEF)/t(E) at 2 yr (p = 0.002) and at birth (p = 0.027), compared with children with no rBO or AE. Clinical phenotype at 2 yr did not influence the change in t(PTEF)/t(E) from birth to 2 yr. This study demonstrates a clear tracking of lung function from birth, not influenced by rBO or AE by 2 yr.

Reduced Lung Function at Birth and the Risk of Asthma at 10 Years of Age

Reduced lung function in early infancy has been associated with later obstructive airway diseases. We assessed whether reduced lung function shortly after birth predicts asthma 10 years later. We conducted a prospective birth cohort study of healthy infants in which we measured lung function shortly after birth with the use of tidal breathing flow-volume loops (the fraction of expiratory time to peak tidal expiratory flow to total expiratory time [t(PTEF)/t(E)]) in 802 infants and passive respiratory mechanics, including respiratory-system compliance, in 664 infants. At 10 years of age, 616 children (77%) were reassessed by measuring lung function, exercise-induced bronchoconstriction, and bronchial hyperresponsiveness (by means of a methacholine challenge) and by conducting a structured interview to determine whether there was a history of asthma or current asthma. As compared with children whose t(PTEF)/t(E) shortly after birth was above the median, children whose t(PTEF)/t(E) was at or below the median were more likely at 10 years of age to have a history of asthma (24.3% vs. 16.2%, P=0.01), to have current asthma (14.6% vs. 7.5%, P=0.005), and to have severe bronchial hyperresponsiveness, defined as a methacholine dose of less than 1.0 micromol causing a 20% fall in the forced expiratory volume in 1 second (FEV1) (9.1% vs. 4.9%, P=0.05). As compared with children whose respiratory-system compliance was above the median, children with respiratory compliance at or below the median more often had a history of asthma (27.4% vs. 14.8%; P=0.001) and current asthma (15.0% vs. 7.7%, P=0.009), although this measure was not associated with later measurements of lung function. At 10 years of age, t(PTEF)/t(E) at birth correlated weakly with the maximal midexpiratory flow rate (r=0.10, P=0.01) but not with FEV1 or forced vital capacity. Reduced lung function at birth is associated with an increased risk of asthma by 10 years of age.

Passive respiratory mechanics measured during natural sleep in healthy term neonates and infants up to 8 weeks of life

The single occlusion technique (SOT) is a simple and noninvasive technique for measurement of passive respiratory mechanics in infants. Reference values based on measurements of a large population of healthy infants performed outside specialized research laboratories are lacking. The aim of this study was to present reference values for passive respiratory mechanics based on a large population of healthy term neonates and infants measured during natural sleep in routine care. As part of the ongoing Wheezing Illnesses Study Leidsche Rijn (WHISTLER), the compliance (C(rs)) and resistance (R(rs)) of the respiratory system were measured in 450 healthy unsedated neonates and infants with a mean age of 4.6 +/- 1.3 weeks. Multivariable regression analysis, with gestational age, age at measurement, body size, sex, and ethnicity as possible predictors, was carried out to estimate prediction equations for mean C(rs) and R(rs) values. Technically acceptable lung function measurements could be performed in 328 (73%) neonates and infants. Median C(rs) was 39.5 (range 14.8-79.1) ml/kPa and median R(rs) was 7.4 (range 3.8-19.5) kPa/L/sec. The following regression equations for C(rs) and R(rs) were obtained: ln C(rs) = 1.677 + 1.3 x 10(-4) x birth weight (g) + 0.030 x birth length (cm) and ln R(rs) = 2.496-3.1 x 10(-6) x birth length(3) (cm(3)) - 0.114 x sex. We provided reference values for passive respiratory mechanics using the SOT in a large population of healthy term neonates and infants measured during natural sleep. These data provide a frame of reference for assessing the normality of SOT measurements performed in routine care.

Feasibility and Variability of Neonatal and Infant Lung Function Measurement Using the Single Occlusion Technique

For possible use as a predictor of wheezing illnesses in routine care, we evaluated the feasibility and variability of measurement of passive respiratory mechanics in a large, open population of healthy neonates and infants. As part of the ongoing Wheezing Illnesses Study Leidsche Rijn, respiratory compliance (Crs), respiratory resistance (Rrs), and time constant (taurs) were measured during natural sleep in 450 healthy term neonates and infants using the single-occlusion technique (SOT). Interobserver and intraobserver variability of data sampling and the subsequent selection and analysis of occlusions as well as intra-measurement variability were examined. Technically acceptable lung function measurements could be performed in 328 infants (73%). Low intraobserver and interobserver variability was found for both data sampling (intraclass correlation coefficient [ICC] > or = 0.87) and for selection and analysis of occlusions (ICC > or = 0.99). Intra-measurement variability was low, with a mean intra-measurement coefficients of variation for Crs, Rrs, and taurs of 8.5%, 10.4%, and 15.4%, respectively. Averaging three or more occlusions resulted in stable values of Crs, Rrs, and taurs. Results of this study indicate that feasibility and variability of lung function testing using the SOT is acceptable for use in large populations of healthy neonates and infants in routine care.

Assessment of the Single-Occlusion Technique for Measurements of Respiratory Mechanics and Respiratory Drive in Healthy Term Neonates Using a Commercially Available Computerized Pulmonary Function Testing System

In this study, a critical assessment of the single-occlusion technique as a means of measuring passive respiratory mechanics and respiratory drive (P0.1) was performed in nonintubated spontaneously breathing healthy term neonates using commercially available computerized equipment (PEDS system). In general, we found that quality parameters only partially conformed to the international established standards for measuring passive respiratory mechanics. There was a failure rate of technically acceptable occlusions of about 50% for respiratory mechanics measurements and 20% for P0.1 measurements. Intersubject variability of the data was between 10 and 40%. After studying different lengths of occlusion times (Tocc; 0.2, 0.3, 0.4 and 0.5 s), it was found that acceptable occlusions for passive respiratory mechanics were obtained only if the expiratory Tocc exceeded 0.2 s. Increasing the Tocc had no effect on the absolute values of respiratory mechanics but showed a significant trend towards more technically acceptable occlusions. We speculate that a Tocc of at least 0.4 s may be a prerequisite for obtaining reliable results for respiratory mechanics in healthy term neonates.

Two administration methods for inhaled salbutamol in intubated patients

Aims: To compare serum concentrations and effects on respiratory mechanics and haemodynamics of salbutamol administered by small volume nebuliser (SVN) and metered dose inhaler (MDI) plus spacer. Methods: Blinded, randomised,...