Volume history and effect on airway reactivity in infants and adults.

Volume history is an important determinant of airway responsiveness. In healthy adults undergoing airway challenge, deep inspiration (DI) provides bronchodilating and bronchoprotective effects; however, the effectiveness of DI is limited in asthmatic adults. We hypothesized that, when assessed under similar conditions, healthy infants have heightened airway reactivity compared with healthy adults and that the effectiveness of DI is limited in infants. We compared the effect of DI on reactivity by using full (DI) vs. partial (no DI) forced-expiratory maneuvers on 2 days in supine, healthy nonasthmatic infants (21) and adults (10). Reactivity was assessed by methacholine doses that decreased forced expiratory flow after exhalation of 75% forced vital capacity during a full maneuver and maximal expiratory flow at functional residual capacity during a partial maneuver by 30% from baseline. Reactivity in adults increased when DI was absent, whereas infants' reactivity was unchanged. Infants were more reactive than adults in the presence of DI; however, adult and infant reactivity was similar in its absence. Our findings indicate that healthy infants are more reactive than adults and, like asthmatic adults, do not benefit from DI; this difference may be an important characteristic of airway hyperreactivity.

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.

Static compliance of the respiratory system in healthy infants.

We recorded static deflation pressure-volume (PV) curves from near TLC to FRC in 49 healthy, sedated, spontaneously breathing infants of 1 to 104 wk of age. Respiratory activity was transiently inhibited by inflating the respiratory system several times to a volume at an airway pressure of 30 cm H2O (V30). Passive deflation from V30 to FRC was then interrupted by multiple brief occlusions at the airway opening, in order to measure static recoil pressures. The expired volume from V30 to FRC was defined as V30E. Compliance of the respiratory system (Crs) was calculated as the slope of the linear portion of the PV curve from 5 to 15 cm H2O. Crs and V30E increased with increasing body length (p < 0.001). After adjustment for body length, males had greater Crs values than did females (p < 0.01). V30E was smaller in female infants (p < 0.05) and in infants whose mothers smoked during pregnancy (p < 0.04). Specific compliance (Crs/V30E) declined with increasing age (p < 0.01), but there were no differences related to sex or maternal smoking. We conclude that static deflation PV curves can be recorded in the age range from 1 to 104 wk, and that maternal smoking may produce hypoplastic lungs.

Flow limitation in infants assessed by negative expiratory pressure.

Forced expiratory flows by the rapid compression technique are often used to assess airway function in infants; however, it remains unclear as to whether flow limitation (FL) is achieved. Studies in adults have used negative expiratory pressure (NEP) at the airway opening as a noninvasive technique to assess whether FL is achieved. An increase in flow with NEP indicates that FL has not been achieved, whereas no increase in flow with NEP indicates FL has been achieved. In the adult studies, the change in flow was assessed by visual inspection of the flow-volume curve. We evaluated whether NEP could be used to assess FL during forced expiration in infants. In addition, we quantified the change in flow secondary to NEP. We applied -5 cm H(2)O NEP to four infants during forced expiratory maneuvers. The step increase in flow with NEP was always less than 5% at high jacket compression pressures and consistent with FL. For one subject, FL was also confirmed from isovolume pressure flow-curves measured with an esophageal catheter. We conclude that NEP can be used in infants to assess FL during forced expiratory maneuvers by the rapid compression technique.

Forced expiratory flows and volumes in infants. Normative data and lung growth.

Forced expiratory flows (FEF) can be measured in infants from lung volumes initiated near total lung capacity. In order to establish reference values and to evaluate lung growth, we obtained measurements in 155 healthy subjects between 3 and 149 wk of age. Forced vital capacity (FVC) was highly correlated with body length; however, after accounting for length, age was also significant. When subjects were divided at the median age (40 wk) younger compared with older subjects had a significantly larger slope for length (3.7 versus 2.8; p = 0.002). The flow parameters (FEF(50), FEF(75), FEF(85), and FEF(25-75)) were highly correlated with length, and those infants whose mothers smoked had lower flows. For FEF(75), male subjects had lower flows than female subjects. The relationship between FEF and volume was assessed using FEV(0.5)/FVC, which decreased with increasing length. Smaller subjects emptied their lung volume proportionately faster. We conclude that our study provides reference values for this age group and demonstrates that smoke-exposed infants and male subjects have decreased FEF. In addition, our findings indicate that lung volume increases most rapidly during the first year of life and that airways are large relative to lung volume very early in life.

Density dependence of forced expiratory flows in healthy infants and toddlers.

In older children and adults, density dependence (DD) of forced expiratory flow is present over the majority of the full flow-volume curve. In healthy subjects, DD occurs because the pressure drop from peripheral to central airways is primarily dependent on turbulence and convective acceleration rather than laminar resistance; however, an increase in peripheral resistance reduces DD. We measured DD of forced expiratory flow in 22 healthy infants to evaluate whether infants have low DD. Full forced expiratory maneuvers were obtained while the subjects breathed room air and then a mixture of 80% helium-20% oxygen. Flows at 50 and 75% of expired forced vital capacity (FVC) were measured, and the ratio of helium-oxygen to air flow was calculated (DD at 50 and 75% FVC). The mean (range) of DD at 50 and 75% FVC was 1.37 (1.22-1.54) and 1.23 (1.02-1.65), respectively, values similar to those reported in older children and adults. There were no significant relationships between DD and age. Our results suggest that infants, compared with older children and adults, have similar DD, a finding that suggests that infants do not have a greater ratio of peripheral-to-central airway resistance.

Rate constant for forced expiration decreases with lung growth during infancy.

Airway caliber and lung volume (VL) increase many fold between infancy and adulthood; however, these two components of the lung may not increase proportionately during lung growth and development. We evaluated in infants the rate of emptying during forced expiration from near total lung capacity to residual volume. From the flow-volume curves we calculated (1) a rate constant (k) as the change in flow divided by the change in volume between 50% and 75% of expired forced vital capacity (FVC), and (2) the fraction of the FVC expired in 0.5 s (FEV(0.5)/FVC). Seventeen normal healthy infants were evaluated twice; mean ages (ranges) at first and second tests were 30 (5 to 76) and 58 (28 to 98) wk. Analysis of cross-sectional and longitudinal data indicated that the rate of emptying during forced expiration measured by both parameters was greatest in the youngest infants and decreased during infancy. Our findings are consistent with the concept that younger infants have large airways relative to their VL and that VL increases more rapidly than airway caliber early in life.

Forced expiratory maneuvers in very young children. Assessment of flow limitation.

The application of negative expiratory pressure (NEP) to the airway opening during forced expiratory maneuvers has recently been described as a noninvasive method to assess whether flow limitation is achieved in adults. This methodology has great potential for extending the measurement of forced expiratory maneuvers to young children who may not produce maximal efforts as reproducibly as adults. We used NEP to assess flow limitation in 10 children between 3 and 5 yr of age. NEP was well tolerated by all subjects. With the application of NEP, there was not a step increase in flow, a finding consistent with flow limitation for the subjects. In addition to visual inspection, we proposed a method to quantify the change in flow during a short NEP. The flow-volume curves obtained with and without NEP were visually the same, other than the flow transients produced by NEP. The calculated values of FVC and FEF25-75 were not significantly different when measured from flow- volume curves with and without NEP. There was a statistically significant increase in FEV1 with NEP; however, the group mean increase in FEV1 was less than 2%. We conclude that NEP may be a useful technique to determine whether flow limitation has been achieved in young children performing forced expiratory maneuvers.

Effect of continuous positive airway pressure on forced expiratory flows in infants with tracheomalacia.

Continuous positive airway pressure (CPAP) is used to minimize airway collapse in infants with tracheomalacia. Forced expiratory flows (FEFs) at functional residual capacity (FRC) increase with increasing CPAP in infants with tracheomalacia, and it has been suggested that CPAP prevents airway collapse by "stenting" the airway open. Since FEF is greater at higher than at lower lung volumes, we evaluated whether the increase in flow measured at FRC (V FRC) with CPAP could be explained by the increase in FRC with CPAP. We measured full FEF-volume curves at CPAP levels of 0, 4, and 8 cm H2O in six infants with tracheomalacia and five healthy control infants. In both groups of infants, FVC did not change with CPAP; however, inspiratory capacity (IC) decreased and thus FRC increased with increasing CPAP. FEFs at FRC increased with increasing levels of CPAP; however, the FEFs at 50% and 75% of expired volume were not different for the three levels of CPAP for both groups of infants. Our finding that FEFs measured at the same lung volumes did not differ for the different levels of CPAP indicates that CPAP affects forced flows primarily by increasing lung volume.

Lower respiratory illness in infants and young children with cystic fibrosis: evaluation of treatment with intravenous hydrocortisone.

The purpose of our study was to assess the effect on pulmonary function of adding intravenous hydrocortisone to the standard treatment of infants with cystic fibrosis (CF) hospitalized for lower respiratory illnesses (LRI). Twenty CF infants were randomized and received 10 days of hydrocortisone (10 mg/kg/day) or placebo in addition to standard treatment with intravenous antibiotics, chest physiotherapy, and an aerosolized beta-agonist with cromolyn. Functional residual capacity (FRC) and forced expiratory flows (V'mak,FRC) were measured on admission, on Day 10 of hospitalization, and as outpatients 1-2 months following hospital discharge. Pulmonary function values were adjusted for differences in body length and expressed as Z-scores. Upon admission flows were decreased, and FRC was increased in both groups; there were no differences between the groups. The change in pulmonary function from admission to Day 10 of hospitalization was not different for the two groups. From admission to outpatient follow-up after hospitalization, there was a significant increase in flows for the steroid group, but not for the placebo group. In addition, the direction of change in FRC was significantly different for the two groups; the steroid group had a small decrease in FRC, while the placebo group had a small increase in FRC. These findings suggest that the addition of intravenous hydrocortisone to the standard treatment of CF infants hospitalized for a LRI may produce a greater or a more sustained improvement in lung function following hospitalization.

Flow limitation in normal infants: a new method for forced expiratory maneuvers from raised lung volumes.

Forced expiratory maneuvers generated by rapid thoracic compression have been used to assess airway function in infants. It remains unclear whether flow limitation can be achieved in healthy infants because low pressure transmission across the chest wall and inspiratory effort may limit the maximum transpulmonary pressure developed during the maneuver. We have found that several rapid inflations to a lung volume set at an airway pressure of 30 cmH2O (V80) briefly inhibit respiratory effort and allow forced expiration to proceed from V80 to residual volume. We used a water-filled esophageal catheter to measure isovolume pressure-flow curves in seven healthy infants (3-88 mo). Forced vital capacity (FVC) was defined as the volume between V80 and residual volume. Pressure transmission between the compression jacket and the esophagus decreased with decreasing lung volume and averaged 60 and 37% at 50 and 75% of expired FVC, respectively. Subjects demonstrated plateaus in their isovolume pressure-flow curves at 50% of expired FVC and lower lung volumes. We conclude that this new methodology enables forced expiratory maneuvers to achieve flow limitation in healthy infants over at least the lower portion of their lung volume.

Improved survival of ventilated neonates with modern intensive care.

The records of 909 infants who required mechanical ventilation over a 42-month period were reviewed; 68.3% of the infants survived. The highest survival rate was in infants with persistent fetal circulation and hyaline membrane disease, and the lowest in infants with congenital anomalies and miscellaneous diseases. The survival rate for each year of the 3 1/2-year study increased from the previous year. There was also a dramatic increase in the survival rate in infants with a birth weight greater than 1,250 gm.

Use and abuse of oxygen in the newborn.

Hypoxia must be prevented in the newborn. It causes atelectasis, acidosis and pulmonary vasoconstriction, which leads to further hypoxia and, ultimately, brain damage. On the other hand, retrolental fibroplasia and bronchopulmonary dysplasia may result from too-vigorous use of oxygen therapy. Frequent blood gas measurements are required. Administered oxygen must be humidified and heated, and the oxygen concentration must be monitored with each delivery system. It is not enough to know the oxygen flow rate; an oxygen analyzer is essential.