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Biomedical subjects

R S Tepper

Publications and source records attributed to R S Tepper.

At least 37 records · Page 2Linked to original sources
PubMed2000

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.

Adult↗
PubMed1999

Comparison of the shear modulus of mature and immature rabbit lungs.

Maximal airway narrowing during bronchoconstriction is greater in immature than in mature rabbits. At a given transpulmonary pressure (PL), the lung parenchyma surrounding the airway resists local deformation and provides a load that opposes airway smooth muscle shortening. We hypothesized that the force required to produce lung parenchymal deformation, quantified by the shear modulus, is lower in immature rabbit lungs. The shear modulus and the bulk modulus were measured in isolated mature (n = 8; 6 mo) and immature (n = 9; 3 wk) rabbit lungs at PL of 2, 4, 6, 8, and 10 cmH(2)O. The bulk modulus increased with increasing PL for mature and immature lungs; however, there was no significant difference between the groups. The shear modulus was lower for the immature than the mature lungs (P < 0.025), progressively increasing with increasing PL (P < 0.001) for both groups, and there was no difference between the slopes for shear modulus vs. PL for the mature and the immature lungs. The mean value of the shear modulus for mature and immature rabbit lungs at PL = 6 cmH(2)O was 4.5 vs. 3.8 cmH(2)O. We conclude that the shear modulus is less in immature than mature rabbit lungs. This small maturational difference in the shear modulus probably does not account for the greater airway narrowing in the immature lung, unless its effect is coupled with a relatively thicker and more compliant airway wall in the immature animal.

Aging↗
PubMed1999

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.

Aging↗
PubMed1999

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.

Child, Preschool↗
PubMed1999

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.

Cross-Sectional Studies↗
PubMed1998

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.

Forced Expiratory Flow Rates↗
PubMed1997

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.

Anti-Inflammatory Agents↗
PubMed1997

Mechanisms for the mechanical response of airway smooth muscle to length oscillation.

Airway smooth muscle tone in vitro is profoundly affected by oscillations in muscle length, suggesting that the effects of lung volume changes on airway tone result from direct effects of stretch on the airway smooth muscle. We analyzed the effect of length oscillation on active force and length-force hysteresis in canine tracheal smooth muscle at different oscillation rates and amplitudes during contraction with acetylcholine. During the shortening phase of the length oscillation cycle, the active force generated by the smooth muscle decreased markedly below the isometric force but returned to isometric force as the muscle was lengthened. Results indicate that at rates comparable to those during tidal breathing, active shortening and yielding of contractile elements contributes to the modulation of force during length oscillation; however, the depression of force during shortening cannot be accounted for by cross-bridge properties, shortening-induced cross-bridge deactivation, or active relaxation. We conclude that the depression of contractility may be a function of the plasticity of the cellular organization of contractile filaments, which enables contractile element length to be reset in relation to smooth muscle cell length as a result of smooth muscle stretch.

Acetylcholine↗
PubMed1997

Pharmacological modulation of the mechanical response of airway smooth muscle to length oscillation.

Stretch and retraction of the airways caused by changes in lung volume may play an important role in regulating airway reactivity. We studied the effects of different pharmacological stimuli on airway smooth muscle to determine whether the muscle behavior during length oscillation can be modulated pharmacologically and to evaluate the role of different activation mechanisms in determining its behavior during the oscillation. Active force decreased below the static isometric force during the shortening phase of length oscillation, resulting in an overall depression of force during the length oscillation cycle. This pattern of response was unaffected by the contractile stimulus or level of activation, suggesting that it was caused by a mechanism that is independent of the level of activation of cross bridges. The normalized area of the length-force hysteresis loop (hysteresivity) differed depending on the stimulus used for contraction. Effects of different stimuli on hysteresivity were not correlated with their effects on isotonic shortening velocity or isometric force, suggesting that the pharmacological modulation of the behavior of airway smooth muscle during length oscillation at these amplitudes cannot be accounted for by the effects on the cross-bridge cycling rate.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1997

Effect of tidal volume and frequency on airway responsiveness in mechanically ventilated rabbits.

We evaluated the effects of the rate and volume of tidal ventilation on airway resistance (Raw) during intravenous methacholine (MCh) challenge in mechanically ventilated rabbits. Five rabbits were challenged at tidal volumes of 5, 10, and 20 ml/kg at a frequency of 15 breaths/min and also under static conditions (0 ml/kg tidal volume). Four rabbits were subjected to MCh challenge at frequencies of 6 and 30 breaths/min with a tidal volume of 10 ml/kg and also under static conditions. In both groups, the increase in Raw with MCh challenge was significantly greater under static conditions than during tidal ventilation at any frequency or volume. Increases in the volume or frequency of tidal ventilation resulted in significant decreases in Raw in response to MCh. We conclude that tidal breathing suppresses airway responsiveness in rabbits in vivo. The suppression of narrowing in response to MCh increases as the magnitude of the volume or the frequency of the tidal oscillations is increased. Our findings suggest that the effect of lung volume changes on airway responsiveness in vivo is primarily related to the stretch of airway smooth muscle.

Air Pressure↗
PubMed1996

Greater airway narrowing in immature than in mature rabbits during methacholine challenge.

It has been demonstrated that methacholine (MCh) challenge produces a greater increase in lung resistance in immature than in mature rabbits (R. S. Tepper, X. Shen, E. Bakan, and S. J. Gunst. J. Appl. Physiol. 79: 1190-1198, 1995). To determine whether this maturational difference in the response to MCh was primarily related to changes in airway resistance (Raw) or changes in tissue resistance, we assessed airway narrowing in 1-, 2-, and 6-mo-old rabbits during intravenous MCh challenge (0.01-5.0 mg/kg). Airway narrowing was determined from measurements of Raw in vivo and from morphometric measurements on lung sections obtained after rapidly freezing the lung after the MCh challenge. The fold increase in Raw was significantly greater for 1- and 2-mo-old animals than for 6-mo-old animals. Similarly, the degree of airway narrowing assessed morphometrically was significantly greater for 1- and 2-mo-old animals than for 6-mo-old animals. The fold increase in Raw was highly correlated with the degree of airway narrowing assessed morphometrically (r2 = 0.82, P < 0.001). We conclude that the maturational difference in the effect of MCh on lung resistance is primarily caused by greater airway narrowing in the immature rabbits.

Airway Resistance↗
PubMed1995

Effect of transpulmonary pressure on airway closure in immature and mature rabbits.

The transpulmonary pressures (Ptp values) at which airway closure occurred during maximal stimulation with methacholine were compared in 10 mature and 9 immature rabbit lungs by using an alveolar capsule technique to assess airway closure. After maximal constriction, airway opening and alveolar capsule pressures were recorded during small volume oscillations as Ptp was lowered from 12 to 4 cmH2O. At each Ptp, the proportion of alveolar capsules indicating airway closure was greater for the immature than for the mature lungs (P < 0.025). At Ptp of 4 cmH2O, only 20% of alveolar capsules indicated airway closure in the mature lungs in contrast to 85% indicating closure in the immature lungs (P < 0.001). The in vitro sensitivity of tracheal smooth muscle to acetylcholine and histamine was greater in tissues from immature than from mature rabbits. We conclude that the more frequent airway closure observed in immature rabbits could reflect maturational differences in the structure of the bronchi or lung parenchyma or differences in the coupling between the parenchyma and the airways.

Acetylcholine↗
PubMed1995

Maximal airway response in mature and immature rabbits during tidal ventilation.

Airway closure during maximal methacholine (MCh) challenge was evaluated using alveolar capsules in eight immature and eight mature anesthetized rabbits in vivo during imposed tidal ventilation. Changes in airway opening and alveolar pressures (delta PA) and pulmonary resistance (RL) were measured during MCh challenge at a positive end-expiratory pressure of 5 cmH2O. In immature rabbits, delta PA remained > 3 cmH2O in all animals, indicating no detectable airway closure. This contrasts to our previous study of isolated immature rabbit lungs under static conditions in which delta PA was < 0.1 cmH2O during maximal MCh challenge, findings consistent with airway closure. Airway closure also did not occur in mature animals during tidal ventilation in vivo; however, the frequency of closure in isolated lungs under static conditions was very low. With increasing MCh, end-expiratory PA increased in immature but not in mature rabbits. RL did not reach a plateau in immature rabbits during MCh, whereas a plateau was reached in mature rabbits. Immature rabbits also had greater increases in RL. These results suggest that tidal ventilation can limit bronchoconstriction in immature rabbits and prevent airway closure during maximal MCh challenge. Tidal ventilation may limit bronchoconstriction by inhibitory effects of stretch on airway smooth muscle contraction and also by causing hyperinflation and thereby increasing transpulmonary pressure.

Aging↗
PubMed1995

Increased maximal pulmonary response to methacholine and airway smooth muscle in immature compared with mature rabbits.

We compared the effect of maturation upon the maximal pulmonary response to inhaled methacholine in rabbits and also assessed whether there was an age-related difference in the quantity of airway smooth muscle. In sedated, paralyzed, and mechanically ventilated rabbits, pulmonary resistance was measured following increasing doses of aerosolized methacholine (0.5 to 256 mg/ml). The six mature rabbits (6 mo) demonstrated a plateau in their dose-response curves whereas only three of six immature animals (1 mo) had a plateau. The immature compared with the mature animals had a greater maximal increase in pulmonary resistance (950% versus 380%). The lungs were examined by light microscopy to determine morphometrically the area of smooth muscle (ASM) in the airway walls. ASM was normalized for airway size by dividing by the ideal airway area. The normalized ASM was different for the two age groups and the immature animals' airways had more smooth muscle. The relationship between airway size and ASM was similar for the two age groups with smaller airways having proportionately more smooth muscle. The differences with age in ASM area were primarily due to the immature animals having a greater number of airways of small size. There was not a significant relationship between the maximal percent increase in pulmonary resistance and the normalized ASM. We conclude that inhaled methacholine produces a greater maximal increase in the pulmonary resistance of immature than mature rabbits and that this difference is unlikely to be caused by a proportionately greater quantity of ASM in the immature than the mature rabbit airways.

Aging↗
PubMed1994

Bronchodilator responsiveness in infants with bronchiolitis.

We evaluated 34 infants with bronchiolitis, (17 of both genders; mean age, 4.6 mos; ranges, 0.7-14.5 mos). The 20 inpatients were significantly younger than the 14 outpatients (2.6 vs. 8.2 months, P < 0.05), and more females were inpatients. Forced expiratory flows at functional residual capacity (VmaxFRC) were obtained at baseline, after aerosolized normal saline (NS), and metaproterenol (0.025 mL/kg in 2 mL NS). Flows were expressed as Z-scores, the difference between the measured and predicted flows, divided by the standard deviation for the predicted value. At baseline, outpatients were more obstructed than inpatients (-1.64 vs. -0.95, P < 0.05), infants > 2 months old were more obstructed than infants < or = 2 months old (-1.54 vs. -0.80, P < 0.05), and males more than females (-1.45 vs. -1.02, P < 0.05). Following NS the whole group had a small but significant decrease in Z-scores (-1.23 to -1.31, P < 0.05). Following metaproterenol, the younger infants had significantly (P < 0.05) higher Z-scores compared to baseline and NS (-0.80 vs. -0.86 vs. -0.59). However, no significant changes occurred in older infants. Females also had an increased flow after metaproterenol and were less obstructed than after NS (-1.11 vs. -0.86, P < 0.015). In males no increased flows occurred after metaproterenol (-1.45 vs. -1.48). Bronchodilator responsiveness did not relate to severity of airway obstruction, history of family asthma, allergy, or passive smoke exposure. We conclude that inhaled metaproterenol improves airway function in a subgroup of infants with bronchiolitis, but the subgroup could not clearly be identified because age and gender were confounding factors.

Aerosols↗
PubMed1994

Heightened airway responsiveness in normal female children compared with adults.

Studies have suggested that airway responsiveness declines with maturation; however, studies comparing infants, children, and adults are confounded by differences in size as well as maturation. Therefore, to determine whether maturation has a significant affect on airway responsiveness, we compared normal female children (n = 9; mean age = 13.6 yr) and adults (n = 7; mean age = 42.4 yr) who were matched for body size. Bronchial challenge tests were performed with increasing methacholine concentrations to a maximum of 30 mg/ml. At baseline, there were no significant differences between the two groups in lung volumes (TGV, RV, TLC) or flow-volume curves (FEV1, average forced expiratory flow rate between 25% and 75% of the vital capacity [FEF25-75], FVC). All subjects but one adolescent completed the challenge (30 mg/ml). The children had a greater percentage decline from baseline in FEV1 than the adults (17 versus 7%, p < 0.03). The percentage decline in FEF25-75 was greater for the children than for the adults, but the difference was not statistically significant (35 versus 20%, p < 0.10). Compared with the children, the adults more often demonstrated a plateau in their dose-response curves for FEV1 (22 versus 86%) and for FEF25-75 (33 versus 100%). We conclude that normal female children have a greater airway responsiveness to inhaled methacholine than do adults, and that this difference is not related to baseline lung size, airway caliber, or delivered methacholine dose.

Adolescent↗
PubMed1993

Forced expiratory flows and lung volumes in normal infants.

Forced expiratory flows at functional residual capacity (VmaxFRC) by the rapid compression technique and functional residual capacity (FRC) by the helium dilution technique were assessed in 112 normal infants with a mean age of 10.7 months (range, 1.0-31.0). In predicting FRC, log transformation was appropriate and body length was the best predicator. For VmaxFRC, age was a better predictor than length, and logarithmic transformation was not required. In(FRC) = -5.465 + 2.49 x In(length) SD = 0.178; r2 = 0.83 VmaxFRC = -397 + 9.36 x (age) SD = 88; r2 = 0.52 There were no gender differences for FRC or VmaxFRC; however, male infants exposed to passive cigarette smoke tended to have lower flows than male infants not exposed (P < 0.07). This study establishes normative values for VmaxFRC and FRC in infants between 1 and 31 months of age, and suggests that passive cigarette smoke exposure has an adverse effect upon forced expiratory flows in male infants.

Age Factors↗