Relative ability of full and partial forced expiratory maneuvers to identify diminished airway function in infants with cystic fibrosis

The tidal and raised volume rapid thoracoabdominal compression techniques are increasingly used to detect diminished airway function in infancy. The aim of this study was to assess the relative ability of parameters measured by these techniques to identify diminished airway function in infants newly diagnosed with cystic fibrosis (CF) with and without clinical evidence of prior lower respiratory illness. A cross-sectional, prospective study design was used in which maximal flow at functional residual capacity (VmaxFRC) from the tidal technique and FVC, FEV0.5, FEF75, and FEF25-75 from the raised volume technique were measured in 47 infants with CF and 187 healthy infants of similar body size, sex distribution, ethnic group, and exposure to maternal smoking. Multiple linear regression was used to assess group differences and to calculate SD scores for each parameter for the infants with CF. Airway function was also compared with clinical assessments of respiratory status made by pediatric pulmonologists. FEV0.5 was significantly diminished in 13 infants with CF, of whom 4 had been identified by clinicians as having normal respiratory status. Only one infant with CF had a VmaxFRC below the estimated normal range. Airway function is diminished in infants with CF irrespective of prior lower respiratory illness and in those whose respiratory status is considered normal by pediatric pulmonologists. In infants with CF, the raised volume technique identified diminished airway function more frequently than the tidal technique.     

Thoracoabdominal asynchrony and ratio of time to peak tidal expiratory flow over total expiratory time in adolescents with cystic fibrosis.

Thoracoabdominal asynchrony (TAA) and the ratio of time to peak tidal expiratory flow over total expiratory time (TME/TE) have been used to assess airway obstruction in infants and adults. We obtained these measurements using calibrated respiratory inductance plethysmography (RIP) on 15 adolescents and young adults with cystic fibrosis (CF) and varying disease severity. The measurements were then compared to 15 normal age-matched controls. TAA was expressed as a phase angle (phi) calculated from the abdominal (AB) and ribcage (RC) signals acquired from scalar strip chart recordings. Using CODAS (DATAQ Instruments, Akron, OH) software, the analog signals were digitized, and the differentiated sum (AB + RC) signal was used to calculate TME/TE. Forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1) were obtained using RIP in all subjects. Subjects with CF had a significantly higher mean phi than the control subjects (15 degrees vs. 8 degrees, respectively, P = 0.01). In the CF patients the specificity of a high phi as an indicator of abnormality was 80%, while the sensitivity was 65%. There was no correlation in the magnitude of phi and disease severity as assessed by FVC or FEV1. There was no significant difference in TME/TE between the groups. We conclude that RIP-acquired phi, but not TME/TE, is a simple and useful method to detect the presence of airway obstructive disease. We speculate that the sensitivity of this method will increase in younger patients with more compliant chest walls and less air trapping. Longitudinal studies of phi in infants and young children with lung disease could help in assessing disease severity and progression in this population, in whom repeated measures are few and complex.     

Comparison of normal infants and infants with cystic fibrosis using forced expiratory flows breathing air and heliox

SUMMARY. The detection of early airway disease in infants with cystic fibrosis (CF) may lead to earlier intervention and an improved prognosis. We hypothesized that the ratio of maximal expiratory flows while breathing a mixture of helium and oxygen (heliox) and air, referred to as density dependence (DD), would identify early airway disease in infants with CF who have normal lung function. We also hypothesized that these infants with CF might be better differentiated from normal infants when the flows breathing heliox are compared instead of room air flows. We evaluated 10 infants with CF and 21 infants without CF and with normal lung function, defined as a forced vital capacity (FVC) and forced expiratory flows between 25-75% of expired volume (FEF(25-75)) of greater than 70% predicted (z-score > -2.0). Full forced expiratory maneuvers by the rapid thoracic compression technique were obtained while breathing room air and then heliox. Flow at 50% and 75% of expired volume (FEF(50), FEF(75)), FEF(25-75), and FVC were calculated from the flow volume curve with patients and control subjects breathing each gas mixture. The ratio of heliox to air flow at FEF(50) and FEF(75) was calculated (DD(50), DD(75)), and the point where the two flow-volume curves crossed (V(iso) V') was also measured. DD parameters did not distinguish the infants with CF from the infants without CF; length-adjusted FEF(50) breathing air was significantly lower in the infants with CF compared to the infants without CF (P < 0.05). Length-adjusted flows breathing heliox did not distinguish the two groups. We conclude that the lower FEF(50) value may reflect early airway obstruction in healthy infants with CF, and that measurements obtained with the less dense gas mixture did not improve detection of airway disease in this age group.     

Elastic properties of the respiratory system in infants with cystic fibrosis

Respiratory system compliance (Crs) in infants with cystic fibrosis (CF) has been reported as decreased or not different compared with healthy control subjects; however, the reported measurements of Crs were "quasi-static" or by the single-breath occlusion technique, with all measurements limited to tidal lung volume, as well as using inspiratory rather than expiratory pressures. We compared the passive elastic properties of the respiratory system of sleeping infants with CF (n = 10) and healthy control subjects (n = 34) by measuring static deflation pressure--volume (PV) curves from a lung volume at 30 cm H(2)O (V(30)) to FRC. There was no significant difference between the groups for Crs, which was measured as the slope between airway relaxation pressures of 5 and 15 cm H(2)O, the linear portion of the deflation PV curve. In addition, when PV curves were normalized to V(30), there were no differences between the infants with CF and healthy control subjects in the fractional volumes at any airway pressure. The infants with CF had significantly lower forced expiratory flows; however, lower flows did not correlate with fractional volumes measured from the PV curve. Our findings indicate that infants with CF have normal elastic properties of the respiratory system.     

Effect of respiratory rate on airway deadspace ventilation during exercise in cystic fibrosis

Gas exchange during exercise in patients with cystic fibrosis (CF) is characterised by an elevated physiological deadspace to tidal volume ratio. While this has been attributed to alveolar ventilation perfusion mismatch, there are other potential causes of the high proportion of wasted ventilation, including factors relating to the volume and the ventilation of the airway deadspace. CF (n = 6, F = 1, FEV1 26-63% pred) and control (n = 6, F = 2) subjects completed steady-state exercise on a cycle ergometer. Gas exchange was measured breath-by-breath and the volume of the airway deadspace (V(Daw)) determined using the equal areas method. Exercise data were interpolated to a CO2 output of 0.7 l/min. V(Daw) was similar in the two groups both at rest and during exercise. However, the airway deadspace ventilation (V(Daw)) (median (inter-quartile range)), patients, 6.8 (5.1-7.1) l/min; controls, 4.9 (3.5-5.6) l/min, P < 0.05) was significantly greater in the CF group due to a greater respiratory frequency. These results indicate that in CF patients, abnormally increased V(Daw) is an important contributor to the total (physiological) deadspace ventilation. Exercise performance in CF might be enhanced by efforts directed at facilitating an increase in exercise tidal volume and therefore the adoption of a more efficient pattern of breathing.     

Evaluation of ventilation maldistribution as an early indicator of lung disease in children with cystic fibrosis.

Many children with cystic fibrosis (CF), receiving modern, aggressive CF care, have normal spirometry results. This study aimed to see if homogeneity of ventilation distribution is impaired early in the course of CF lung disease, and if ventilation inhomogeneity is a more frequent finding than abnormal spirometry in children benefiting from modern CF care. The study compared spirometry findings to two indices of ventilation inhomogeneity (mixing ratio (MR) and lung clearance index (LCI)) from multiple-breath inert gas washout in 43 children with CF, aged 3-18 yrs, and 28 healthy children. In total, 10/43 CF subjects (23%) had reduced forced expiratory volume in one second (FEV1) and 14/34 (41%) showed abnormal maximum expiratory flow at 25% of forced vital capacity (MEF25). In contrast, MR was abnormal in 31/43 (72%) and LCI in 27/43 (63%). MR was abnormal in 22/33 CF subjects with normal FEV1, versus 0/28 controls (p<0.001), and abnormal MR was found in 10/20 CF subjects with normal MEF25, versus 0/22 controls (p<0.001). Nine of the 10 CF subjects with reduced FEV1 and 12/14 with abnormal MEF25 showed abnormal MR. Inert gas washout discloses airway dysfunction in the majority of children with cystic fibrosis with normal lung function judged by spirometry. These findings suggest that multiple-breath inert gas washout is of greater value than spirometry in detecting early cystic fibrosis lung disease.     

婴幼儿哮喘患儿潮气呼吸肺功能改变的特征

目的观察婴幼儿哮喘患儿在发作期与缓解期的潮气呼吸流速——容量曲线测定结果。方法选择婴幼儿哮喘患儿40例，于镇静后进行潮气呼吸流速容量曲线测定（TBFV）。主要参数有：每公斤潮气量（VT／kg）、呼吸频率（RR）、吸气时间（Ti）、呼气时间（Te）、吸呼比（Ti／Te）、达峰时间比（TPTEF／TE）、达峰容积比（VPEF／VE），并对30例哮喘患儿经正规吸入治疗1～3月的缓解期进行复查。观察其改善情况。同时对40例无呼吸道疾病的婴幼儿进行肺功能检测，作为正常对照。结果哮喘组的潮气量与正常对照组无显著差异，其他各指标差异均有显著性（P〈0．01）。哮喘组经1～3月治疗后，复查TPEF／TE，VPEF／VE显著上升，但与对照组仍有显著差异，未能恢复正常水平。结论潮气呼吸肺功能测定能反映出婴幼儿哮喘的病理生理特点，可成为呼吸系统疾病诊断的重要补充。     

Shape of forced expiratory flow-volume curves in infants

An inflatable cuff was used to generate partial forced expiratory flow-volume (FEFV) curves in 36 infants with and without obstructive airway disease. Curves were recorded in each infant over a range of compression pressures as high as and exceeding the pressure required for the maximal partial FEFV curve. The maximal curves were quantitated and compared with passive compliance and conductance of the respiratory system and absolute lung volume measured by whole-body plethysmography. In some infants, the transmission of pressure between cuff and pleural space was determined. Partial FEFV curve shapes generated with a standardized compression pressure calculated from the transmission of pressure data to give an increase in pleural pressure at FRC of 10 cm H2O were compared between infants. For these standardized compressions, infants with convex curves tended to have better respiratory function than did those with concave curves. The combination of a concave curve and flow limitation during tidal expiration was associated with the worst function. Two parameters, the ratio of forced maximal expiratory flow (measured from the maximal partial FEFV curve) to tidal expiratory flow (measured from the expiratory flow-volume curve of tidal breathing) at midtidal volume (Vm1d(forced/tidal] and the minimal compression pressure required to generate maximal expiratory flow at FRC (Pmin), satisfactorily quantified respiratory function without the need for size correction with absolute lung volume. In addition, Vm1d(forced/tidal) provides an index of expiratory flow reserve. We conclude that useful information can be provided from the shape of a partial FEFV curve in an infant, provided that curves are generated by a standardized compression pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventilation inhomogeneity assessed by nitrogen washout and ventilation-perfusion mismatch by capnography in stable and induced airway obstruction

Few studies have been published on gas distribution in the lung during acute and stable airway obstruction in children. Multiple breath nitrogen (N(2)) washout is an established method for assessing ventilation inhomogeneity, while the tidal breathing capnogram may be used as an indicator of ventilation-perfusion (V(')(A)/Q) mismatch. We hypothesized that significant V(')(A)/Q mismatch is not seen in stable airway obstruction unless obstruction is severe, and that stable and induced airway obstruction of similar severity would result in different degrees of V(')(A)/Q mismatch. To test this hypothesis, we performed spirometry measurements of forced expiratory volume in 1 sec (FEV(1)), multiple breath N(2) washout, and tidal breathing capnography in 11 young patients (9-30 years) with cystic fibrosis, 37 asthmatic patients (8-18 years), and 34 healthy subjects (7-20 years). Lung function was measured at rest, after airway obstruction induced by cold dry air hyperventilation or methacholine challenge, and after beta(2)-agonist treatment. V(')(A)/Q mismatch was assessed from the slopes of the phases II and III of the capnogram. We observed a normal capnogram during stable obstruction of moderate severity despite significant ventilation inhomogeneity. In patients with severe stable obstruction and in those with induced airway obstruction significant ventilation inhomogeneity and pathological capnograms were seen. Induced airway obstruction, resulted in a more pathological capnogram than stable obstruction of similar severity. beta(2)-agonist treatment reduced ventilation inhomogeneity, but did not improve the capnogram. Our findings are compatible with the presence of an efficient pulmonary blood flow regulatory mechanism that adequately compensates for chronic ventilation inhomogeneity of moderate severity, but not for severe or sudden airway obstruction.     

Cold air provocation of airway hyperreactivity in patients with cystic fibrosis

Thirty-four patients with cystic fibrosis (CF) were assessed for baseline pulmonary functions before, and 5 and 15 minutes after cold air challenge (CACh). Most of the patients had no change in forced expiratory volume in 1 second (FEV1) and maximum expiratory flow at 25% vital capacity (Vmax25%VC) post-CACh. Five patients responded with reduced FEV1 and 13 with reduced Vmax25%VC. However, paradoxical increases were noted in 10 patients for FEV1 and in 5 for Vmax25%VC. Paradoxical responses were most frequent in patients with severe lung disease. The explanation for this variability may lie in the varying degrees of airway instability and volume of airway contribution (VAC) to early flows, resulting from the damage caused by chronic infection. Conventional challenges may be useless in determining the true incidence of bronchial hyperreactivity in patients with CF.     

喘息婴幼儿潮气肺功能、呼出气一氧化氮及过敏原研究

目的:研究喘息婴幼儿潮气肺功能和呼出气一氧化氮(FeNO)的变化,着重探讨过敏体质在其中的潜在作用。方法:纳入成都市妇女儿童中心医院呼吸科2018年2月至2019年1月收治的急性下呼吸道感染婴幼儿285例,回顾性分析患儿的一般资料,喘息的危险因素,喘息与潮气肺功能及FeNO的关系,并通过亚组分析探究过敏因素在其中的作用...     

Effect of breathing pattern during inhalation challenge on the shape and position of the dose-response curve

To examine the effect of breathing pattern on the dose-response curve, 4 mild asthmatic and 9 normal subjects inhaled increasing concentrations of methacholine (0.03-256 mg/ml) using a quiet tidal breathing pattern or tidal breathing with a forced expiratory phase. The provocative concentration of methacholine causing a 20% decrease in the forced expired volume in 1 s (PC20FEV1) or a 200% increase in pulmonary resistance (PC 200RL) was determined. In addition, the maximal change in FEV1 and RL and the slopes of the dose-response curves were measured. The forced expiratory pattern caused an increase in the central/peripheral deposition ratio of a [99m]technetium-labeled aerosol (n = 3). There were no differences in mean tidal volume, minute ventilation, inspiratory flow rates, or baseline FEV1 or RL between the quiet breathing or forced expiration studies, although mean expiratory flows were increased in the latter (p less than 0.001). PC20FEV1 and PC200 RL decreased (p less than 0.001) but the maximal change in FEV1 and RL was unchanged in the forced expiration studies. Forced expiration during inhalation challenge did not alter the slope of FEV1 or RL dose-response curves. These results suggest that the sensitivity (PC20, PC200) and maximal response of in vivo dose-response curves may be affected independently by factors such as aerosol deposition.     

Comparison of two standardized methods of methacholine inhalation challenge in young adults.

In the European Community Respiratory Health Study (ECRHS), airway responsiveness to methacholine was determined using the Mefar dosimeter protocol. Elsewhere, the 2-min tidal breathing method has become the preferred standardized method. The relationship between measurements of responsiveness by these two methods is not well established. This study measured airway responsiveness to methacholine by dosimeter and tidal breathing methods in 47 healthy asthmatic subjects aged 20-44 yrs. Tests were performed within 1 week and in random order. Baseline forced expiratory volume in one second (FEV1) varied by <10% between tests in 42/47 subjects. There was a close association between responsiveness determined by the two methods. A provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) value of < or =8.0 mg x mL(-1) (tidal method) used to categorize airway hyperresponsiveness agreed most closely with a provocative dose of methacholine causing a 20% fall in FEV1 (PD20) value of < or =0.5 mg (dosimeter method) (kappa statistic 0.78). Each doubling or halving of PC20 to define a level of hyperresponsiveness agreed closely with a doubling or halving of PD20. Assessment of airway responsiveness as provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second by the Mefar dosimeter protocol gave a close and predictable relationship with provocative concentration of methacholine causing a 20% fall in expiratory volume in one second assessed using the tidal breathing method. Airway hyperresponsiveness as determined by the accepted criterion of provocative concentration of methacholine causing a 20% fall in expiratory volume in one second < or =8 mg x mL(-1) was best correlated with provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second <0.5 mg by Mefar dosimeter.     

Sensitivity of bronchial responsiveness measurements in young infants

OBJECTIVES: There is limited evidence on the preferred methods for evaluating lung function in infancy. The objective of this study was to compare sensitivity and repeatability of indexes of lung function in young infants during induced airway obstruction. METHODS: The study population consisted of 402 infants (median age, 6 weeks). Forced flow-volume measurements were obtained by the raised volume rapid thoracoabdominal compression technique and were compared with indexes of tidal breathing, measurements of transcutaneous oxygen (Ptco(2)), and auscultation during methacholine challenge testing. RESULTS: Ptco(2) was the most sensitive parameter to detect increasing airway obstruction during methacholine challenge, followed by forced expiratory volume at 0.5 s (FEV(0.5)). Both were superior to other indexes of forced spirometry as well as tidal breathing indexes and auscultation. Coefficients of variations for Ptco(2) and FEV(0.5) were 4% and 7%, respectively. CONCLUSIONS: Ptco(2) and FEV(0.5) are the most sensitive parameters for measurement of bronchial responsiveness in young infants. Measurements of baseline lung function should preferably be made using FEV(0.5.) Measurements of bronchial responsiveness are best assessed using Ptco(2), which may be performed in nonsedated infants and improve feasibility of future studies on lung function in infancy.     

Tidal expiratory flow limitation and chronic dyspnoea in patients with cystic fibrosis.

Cystic fibrosis (CF) eventually leads to hyperinflation linked to tidal expiratory flow limitation (FL) and ventilatory failure. Presence of FL was assessed at rest in 22 seated children and adults with CF (forced expiratory volume in one second (FEV1) range: 16-92% predicted), using both the negative expiratory pressure (NEP) technique and the "conventional" method based on comparison of tidal and maximal expiratory flow/volume curves. In addition, chronic dyspnoea was scored with the modified Medical Research Council (MRC) scale. Measurements were made before and 15 min after inhalation of salbutamol. With NEP, FL was present in only three malnourished patients, who had the lowest FEV1 values (16-27% pred) and claimed very severe dyspnoea (MRC score 5). By contrast, an additional seven patients were classified as FL with the conventional method. Six of these patients had little or no dyspnoea (MRC scores 0-1). Salbutamol administration had no effect on the extent of FL, and the concomitant decrease in functional residual capacity (FRC) was too small to play any clinically significant role. This study concluded that in seated patients with cystic fibrosis, expiratory flow limitation is absent at rest, unless the forced expiratory volume in one second is <30% predicted. If present, expiratory flow limitation is associated with severe chronic dyspnoea. The conventional method for assessing expiratory flow limitation is not reliable and bronchodilator administration has little effect on expiratory flow limitation.     

Breathing pattern affects respiratory heat loss but not bronchoconstrictor response in asthma

To determine whether changes in breathing pattern alone affect respiratory heat loss (RHL) and the constrictor response to cold dry gas hyperpnea in asthmatic subjects, we performed the following 2 part study: first we measured RHL in 8 asthmatic and 8 normal subjects during controlled eucapnic hyperpnea while they breathed at inspiratory to expiratory ratios (I/E) of 1:3, 3:1, and 2:2, and we recorded postchallenge forced expiratory volume in 1 sec (FEV1) in the asthmatic group; we then performed the same measurements in 8 asthmatic and 8 normal subjects at fixed target minute ventilation (VE) for tidal volumes of 0.2 X Forced vital capacity (FVC), 0.4 X FVC, and 0.6 X FVC by varying the target respiratory rate appropriately. Our results show that (1) increasing I/E ratio or tidal volume-frequency ratio (VT/f) at fixed VE produced small but statistically significant increases (p less than 0.05) in overall heat loss per unit volume of respired gas (RHL/VE) in both asthmatic and nonasthmatic subjects of 1-4 cal/L; (2) changes in breathing pattern alone did not affect bronchoconstrictor response as assessed by lack of change in slopes and intercepts of % delta FEV1 vs. RHL dose-response curves; and (3) the increase in RHL per unit volume of respired gas resulting from increasing VT/f ratios during cold gas hyperpnea was significantly greater in asthmatic than in nonasthmatic subjects. We conclude that changes in breathing pattern may affect overall RHL measured at the mouth, although the maximum effect of such changes in both asthmatic and nonasthmatic subjects is small (10-15%); that such changes do not significantly alter airway constrictor response in asthmatic persons; and (3) that the effects of changing breathing pattern on RHL may be more pronounced in asthmatic than nonasthmatic subjects, which suggests that the asthmatic group may be less able to adapt to factors that alter the magnitude and site of RHL.     

Noninvasive ventilation in cystic fibrosis patients with acute or chronic respiratory failure.

The experience of using noninvasive ventilation (NIV) in 113 adult cystic fibrosis (CF) patients with chronic respiratory failure, during episodes of acute deterioration in respiratory function is reported. The patients aged 15-44 yrs were divided into three groups. Group A consisted of 65 patients (median forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) 0.7/1.4 L) who were on a lung transplant waiting list. Group B consisted of 25 patients (median FEV1/FVC 0.7/1.4 L) who were being evaluated for lung transplantation. Group C consisted of 23 patients (median FEV1/FVC 0.6/1.2 L) who were not being considered for lung transplantation. The mean duration of NIV support for groups A, B and C was 61 (range: 1-600) days, 53 (1-279) days and 45 (0.5-379) days respectively. Twenty-three patients in group A subsequently received lung transplantation and 12 of these patients had a median survival of 39 months postsurgery. Thirty-nine patients died and three awaited transplantation. Five patients in group B received a transplant four of whom survived; thirteen patients died and seven awaited transplantation. Twenty patients in group C died. Noninvasive ventilation improved hypoxia but failed to correct hypercapnia in these cystic fibrosis patients. Noninvasive ventilation is useful in the treatment of acute episodes of respiratory failure in cystic fibrosis patients with end-stage lung disease who have been accepted, or are being evaluated, for lung transplantation. For these patients, there is a possibility of prolonging life if they are successfully treated for their acute episode of respiratory failure until transplantation. In this group, treatment is not merely prolonging the process of dying.     

The association between birthweight, sex, and airway function in infants of nonsmoking mothers.

The risk of respiratory illness and death is increased in infants of low birthweight for gestational age, but the underlying physiologic mechanisms remain unclear. We examined the hypothesis that airway function is diminished in infants of low birthweight for gestational age, independent of exposure to maternal smoking. Respiratory function was measured using partial and raised volume forced expiratory maneuvers in 103 infants (> 35 wk gestation; 56 boys) not exposed pre- or postnatally to maternal smoking who, according to birthweight, were either small (SGA; n = 38) or appropriate (AGA; n = 65) for gestational age. At testing, SGA infants were of similar postnatal age (mean [SD]: SGA 6.8 [2.4] wk, AGA 5.9 [2.3] wk), but remained shorter and lighter than AGA infants. In univariate analyses, FVC, forced expired volume in 0.4 s (FEV(0.4)), and FEF(75) were significantly diminished in SGA compared with AGA infants (mean [95% CI of difference]: FVC: 127 versus 143 ml [-29, -2]; FEV(0.4): 112 versus 125 ml [-24, -2]; and FEF(75): 173 versus 203 ml s(-1) [-57, -3], respectively), but these differences were no longer significant after allowing for sex and body size. Furthermore, FEF(75) was on average 35 ml s(-1) lower in boys than girls (95% CI: -61, -8). We conclude that diminished airway function in SGA infants shortly after birth appears to be primarily mediated through impaired somatic growth.     

Exploring the relationship between forced maximal flow at functional residual capacity and parameters of forced expiration from raised lung volume in healthy infants

The raised volume rapid thoraco-abdominal compression technique (RVRTC) is being increasingly used to assess airway function in infants, but as yet no consensus exists regarding the equipment, methods, or analysis of recorded data. The aim of this study was to explore the relationship between maximal flow at functional residual capacity (V'(maxFRC)) and parameters derived from raised lung volumes, and to address analytical aspects of the latter technique in an attempt to assist with future standardization initiatives. Forced vital capacity (FVC) from lung volume raised to 3 kPa, timed forced expiratory volumes (FEV(t)), and forced expiratory flow parameters at different percentages of expired FVC (FEF(%)) were measured in 98 healthy infants (1-69 weeks of age). V'(maxFRC) using the tidal rapid thoraco-abdominal compression (RTC) technique was also measured. The within-subject relationships and within-subject variability of the various parameters were assessed.Duration of forced expiration was < 0.5 sec in 5 infants, meaning that FEV(0.3) and FEV(0.4) were the only timed volume parameters that could be calculated in all infants during the first months of life, and even when it could be calculated, FEV(0.5) approached FVC in many of these infants. It is recommended that FEV(0.4) be routinely reported in infants less than 3 months of age. Contrary to previous reports, within subject variability of V'(maxFRC) was less than that of FEF(75) (mean CV = 6.3% and 8.9%, respectively).A more standardized protocol when analyzing data from the RVRTC would facilitate comparisons of results between centers in the future.