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Biomedical subjects

R S Tepper

Publications and source records attributed to R S Tepper.

At least 55 records · Page 3Linked to original sources
PubMed1993

Maturation affects the maximal pulmonary response to methacholine in rabbits.

Maximal bronchoconstriction in normal adults produces only small reductions in pulmonary function; however, in normal infants severe airway obstruction limits testing to low agonist concentrations. In this study, maximal pulmonary response to methacholine was evaluated in 5 immature (1 month old) and 5 mature (6 months old) rabbits. Animals were anesthetized, paralyzed, and mechanically ventilated via a tracheostomy tube. Changes in pulmonary function were assessed from maximal deflation flow volume curves following inhalation of doubling concentrations of methacholine between 0.6 and 320 mg/mL. Following 320 mg/mL methacholine, the immature rabbits had a greater percent decline in forced vital capacity (FVC) than the mature animals (55 +/- 15% vs. 36 +/- 10%; P < 0.05). At 50% FVC, isovolume flows were measurable in the 5 mature rabbits, and 4 of 5 had plateaus in their dose-response curves. At the higher methacholine doses, only 1 of 5 immature animals had measurable isovolume flows because of the decrease in FVC. There was no significant difference between immature and mature animals in the methacholine dose required to decrease baseline flows by 50%. We conclude that in rabbits maturation affects maximal pulmonary response but not the sensitivity to methacholine.

Aging↗
PubMed1993

Airway responsiveness in infants: comparison of inhaled and nasally instilled methacholine.

Airway responsiveness of infants is evaluated during sleep and the infants inhale the bronchial challenge agent via the nasal airway. Since stimulation of the nasal airway may produce bronchoconstriction, it is unclear whether the observed response in the infants results from deposition of the aerosol in the lower airways or from stimulation of nasal receptors. Therefore, in 6 healthy infants we compared the changes in partial expiratory flow-volume (PEFV) curves produced by aerosol inhalation of methacholine and the changes produced by instillation of equivalent doses of methacholine liquid into the nares. Following aerosol, the peak expiratory flow and the flow at functional residual capacity decreased, PEFV curves became concave in shape, and the oxygen saturation (SaO2) decreased. The highest methacholine concentration inhaled by any infant was 1.25 mg/mL. In contrast to aerosol delivery, a maximal methacholine concentration of 10.0 mg/mL was instilled into the nares of all 6 infants without any change in maximal flow at functional respiratory capacity (VmaxFRC) or SaO2. There was a significant decrease in peak flow and flattening of the PEFV curves at higher lung volumes; however, the PEFV curve remained convex in shape at the lower lung volumes. The changes in the PEFV curve following nasal instillation of methacholine are consistent with an increase in nasal resistance and no change in the lower airways. We conclude that the bronchoconstriction observed following inhaled methacholine does not result from stimulation of nasal receptors.

Administration, Inhalation↗
PubMed1993

Longitudinal evaluation of pulmonary function in infants and very young children with cystic fibrosis.

Thirty-two infants with cystic fibrosis (CF) had pulmonary function testing and chest radiographs at the time of diagnosis and on average 1 year later, when they had no acute respiratory symptoms. At diagnosis, 14 of 32 infants had respiratory symptoms (RESP) and 18 did not have respiratory symptoms (NRESP). There were no significant differences in age, weight, or length between the RESP and NRESP groups. At diagnosis, the RESP group had significantly lower forced expiratory flows compared to the NRESP group (41 +/- 32% vs. 98 +/- 48% predicted); however, there were no significant differences in functional residual capacity or chest radiographic scores. Between diagnosis and follow-up, the NRESP group had no significant change in pulmonary function but a decline in chest roentgenographic (CXR) scores (22 +/- 2 to 21 +/- 2). For infants in the RESP group, there were no significant changes in FRC or CXR score. Maximal expiratory flow at functional residual capacity (Vmax FRC) rose from diagnosis to 1 year follow-up (41 +/- 32% to 74 +/- 27% predicted; P < 0.002); however, at follow-up flows for the RESP group remained significantly lower than flows for the NRESP group (74% vs. 113% predicted; P < 0.0005). For the 32 infants with CF, there was significant correlation between percent predicted Vmax FRC at follow-up and at diagnosis (r = 0.47; P < 0.02). Those infants with lower percent predicted flows at diagnosis were more likely to have lower percent predicted flows 1 year later.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗
PubMed1992

Airway responsiveness in infants following bronchiolitis.

Airway responsiveness to inhaled methacholine was assessed in 18 infants, 4 and 10 months old, following bronchiolitis. Pulmonary function was measured from partial expiratory flow-volume curves generated by the rapid compression technique. Sleeping infants inhaled increasing concentrations of methacholine until maximal expiratory flows at functional residual capacity (VmaxFRC) decreased by 30% or 2.5 mg/mL was inhaled. Airway responsiveness was quantitated by: 1) the threshold concentration (log TC) required to decrease VmaxFRC by 2 standard deviations from baseline; 2) the concentration required to decrease VmaxFRC by 30% (log PC30); and 3) the slope of the dose-response curve between TC and PC30 (log SPC30). At both the first and second evaluation, the bronchiolitic infants had lower baseline VmaxFRC (% pred.) than 24 control infants. In addition, the bronchiolitic infants had heightened airway responsiveness compared to controls, demonstrating lower values for logTC and logPC30 and steeper slopes to their dose-response curves (logSPC30). After accounting for the relationship between airway responsiveness and age, the occurrence of bronchiolitis was found to be a significant independent factor 10 months but not 4 months following bronchiolitis. The bronchiolitic infants did not demonstrate the decline in airway responsiveness with increasing age that occurs in normal infants. We conclude that infants exhibit heightened airway responsiveness following bronchiolitis.

Acute Disease↗
PubMed1992

Comparison of helium dilution and nitrogen washout measurements of functional residual capacity in infants and very young children.

In infants and very young children, functional residual capacity (FRC) is the lung volume most frequently measured and gas dilution techniques are most frequently used to measure FRC. We compared measurements of FRC by helium dilution (FRCHe) and nitrogen washout (FRCN2) in a lung model of known volumes (20, 40, 60, 80 mL) in 8 normal infants (NL), 8 infants with acute respiratory illness (ARI), and 7 infants with chronic lung disease (CLD). In the model lung, measurements of FRCHe had a significantly greater coefficient of variation compared to FRCN2 (6.5 vs 1.5%, P less than 0.02), but there was no such difference in the results from all infants combined (6.5 vs 6.2%). In the model lung, the difference between known volumes and the measured values was significantly different from zero only for FRCHe at 20 mL (-4.4 mL, P less than 0.02). For both FRCHe and FRCN2, the slopes of the regression equations were 0.99 and the intercepts not significantly different from zero. We conclude that techniques for measuring FRCHe and FRCN2 yield accurate, reproducible, and comparable results in normal, healthy infants and very young children, and in those with respiratory disease.

Child, Preschool↗
PubMed1992

Oxygen desaturation during sleep in infants and young children with congenital heart disease.

Oxygen saturation (SaO2) during sleep and pulmonary functions were evaluated in 19 infants with congenital heart disease, aged 6 +/- 4 months, and in 11 normal infants, aged 8 +/- 5 months, to determine whether infants with congenital heart disease have more frequent oxygen desaturation during sleep and, if so, its relationship to underlying pulmonary function. Infants with congenital heart disease were classified as acyanotic (n = 11) or cyanotic (n = 8) on the basis of their aortic SaO2 at the time of cardiac catheterization (greater or less than 90% SaO2). Pulmonary function tests included respiratory rate, functional residual capacity, total respiratory system compliance, and maximal flows at functional residual capacity. Significant differences were found in the values for the lowest SaO2 of each 5-minute epoch (SaO2L) averaged during the entire sleep time (normal 94% +/- 2%, acyanotic 90% +/- 3%, and cyanotic 74% +/- 4%; p less than 0.01). The three groups also differed significantly in frequency distributions of percentage of total sleep time with SaO2L less than 90% (SaO2%T) (normal 10% +/- 17%, acyanotic 36% +/- 34%, and cyanotic 97% +/- 4%; p less than 0.05). Compared with the control group, the acyanotic group had a higher respiratory rate (66 +/- 19 breaths/min vs 35 +/- 6 breaths/min; p less than 0.01), a lower tidal volume (65% +/- 29% predicted vs 105% +/- 18% predicted; p less than 0.01), and a lower total respiratory compliance (59% +/- 18% predicted vs 106% +/- 30% predicted; p less than 0.01). A negative correlation existed between SaO2%T and aortic SaO2 (R2 = 0.64; p less than 0.01). We conclude that oxygen desaturation occurs during sleep in infants with congenital heart disease; the presence of desaturation appears to be related to the initial degree of hypoxemia and the presence of abnormal pulmonary function.

Cyanosis↗
PubMed1991

Assessment of airway responsiveness in infants with cystic fibrosis.

We compared the responses of cystic fibrosis (CF) (N = 14) and normal (N = 14) infants with inhaled methacholine. Airway function was assessed by forced expiratory flows at functional residual capacity (Vmax FRC) generated by the rapid compression technique, and methacholine responsiveness was quantitated as (1) TC: the threshold concentration to decrease Vmax FRC by 2 SD from baseline; (2) PC50: the provocative concentration to decrease Vmax FRC by 30%; and (3) SPC30; the slope of the dose-response curve between TC and PC30. There were no significant differences in age between CF and normal infants (16 +/- 8 versus 17 +/- 5 months, p greater than 0.3); however, the CF infants were shorter (74 +/- 10 versus 81 +/- 5 cm, p less than 0.05), had lower absolute Vmax FRC (241 +/- 103 versus 374 +/- 113 ml/s, p less than 0.001), and tended to have lower percentage of predicted flow values (87 +/- 13 versus 111 +/- 34%, p less than 0.10). Comparison of the indices of airway responsiveness revealed no difference in logTC; however, the CF infants had smaller, more negative values for logPC30 (-0.76 +/- 0.52 versus -0.22 +/- 0.53, p less than 0.02) and steeper slopes to their dose-response curves (logSPC30, 2.42 +/- 0.45 versus 1.88 +/- 0.74, p less than 0.025). Indices of airway responsiveness correlated significantly with baseline Vmax FRC (% of predicted). After the influence of baseline flow upon airway responsiveness was accounted for by multiple linear regression analysis, there was a tendency for CF infants to be more responsive than control infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchial Provocation Tests↗
PubMed1990

Changes in airway reactivity with age in normal infants and young children.

We have previously demonstrated that normal healthy infants exhibit airway reactivity to inhaled methacholine. The purpose of this study was to evaluate the changes in airway reactivity with age in infants and young children. We tested 24 healthy term subjects 4 to 24 months of age (mean 13 months) with history negative for lower respiratory illnesses and wheezing. Airway function was assessed by maximal expiratory flow at FRC (VmaxFRC), generated by rapid chest compression. After baseline measurements, each subject inhaled increasing concentrations of methacholine (Mch), beginning with 0.075 mg/ml, until VmaxFRC decreased 30% or Mch = 2.5 mg/ml. Sensitivity to Mch was defined as the threshold concentration (TC) required to decrease VmaxFRC 2 SD from control, and the Mch required to decrease VmaxFRC 30% (PC-30). Airway reactivity was defined as the slope between TC and PC-30 (SPC-30). We found significant regressions for TC, PC-30, and log SPC-30 versus age. TC and PC-30 increased with increasing age (r = 0.51, p less than 0.02; r = 0.63, p less than 0.001, respectively), indicating decreasing sensitivity to Mch with increasing age. Log SPC-30 became less steep with increasing age (r = -0.59, p less than 0.01), reflecting decreasing reactivity to Mch with increasing age. Of these infants, 10 had their Mch challenge repeated a mean of 8 months (range 4 to 11.5) following their initial test, with no lower respiratory illnesses in the interim.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1990

Drug use in pregnancy and lactation.

When prescribing drugs for patients who are pregnant or lactating, a clinician needs to ask the following questions: (1) Is pharmacotherapy necessary? (2) What drug can be used that has the lowest potential toxicity according to current knowledge? (3) What pharmacokinetic parameters does the drug follow during pregnancy? (4) What are the major risks inherent to this particular drug treatment? (5) Do the benefits outweight the risks? and (6) How can the risks be minimized by adjusting the drug dosage and duration? It is important to inform the patient of the possible risks and have her participate in making treatment decisions. If possible, the fetus or neonate should be monitored for adverse reactions during the course of treatment, and if any serious problems occur, the medication can be discontinued. Although it is true that no drug is totally without risk when used during pregnancy or lactation, if proper precautions are taken, then treatment can be rendered with minimal risks to both mother and child.

Decision Making↗
PubMed1989

Use of maximal expiratory flows to evaluate central airways obstruction in infants.

Partial expiratory flow-volume (PEFV) curves obtained by the rapid compression technique were employed to assess airway function in three infants with three different lesions of the central airways (vascular ring, congenital tracheal stenosis, subglottic polyp). Preoperatively, all three demonstrated severe flow limitation with a relatively constant forced expiratory flow over the tidal volume range. Postoperatively the PEFV curves changed to a normal convex shape, and the maximal expiratory flows at functional residual capacity (VmaxFRC) returned to normal. The PEFV curve adds to our physiologic assessment of the severity of the central airway obstruction in infants and to the efficacy of our therapeutic intervention.

Airway Obstruction↗
PubMed1988

Infants with cystic fibrosis: pulmonary function at diagnosis.

Meconium ileus (MEC), failure to thrive (FTT), and a combination of FTT and pulmonary symptoms (COMB) are the most frequent symptoms of cystic fibrosis (CF) at the time of diagnosis. The purpose of this study was to compare to normal controls (NC) the pulmonary function of CF infants at the time of diagnosis, when grouped by these symptoms. The measurements of pulmonary function included oxygen saturation (SaO2), functional residual capacity (FRC), mixing index (MI), total respiratory system compliance (Crs), and maximal flow at FRC (VmaxFRC). Compared to NC (n = 33), the MEC group (n = 5) had a higher MI (54 vs. 42%) and no difference in SaO2, Crs or VmaxFRC. There were no significant differences between FTT (n = 8) and NC groups although there was a tendency for Crs to be lower in the FTT group (5.1 vs. 6.8 ml/cm H2O). When compared to all other groups, the COMB group (n = 11) had significantly lower SaO2, MI, Crs, and VmaxFRC. The normal lung function in the MEC group is consistent with the normal anatomy reported in CF infants dying secondary to meconium ileus. Longitudinal evaluation of the infants in this study, following initiation of care as patients with a diagnosis of CF, may allow us to determine whether symptoms at diagnosis remain an important determinant of lung function in infancy.

Cystic Fibrosis↗
PubMed1988

Bronchodilator responsiveness in infants and young children with cystic fibrosis.

Response to the inhaled bronchodilator, metaproterenol, was evaluated in 28 outpatient infants and young children with cystic fibrosis (CF) (mean age, 16 months) and in 22 normal control children (mean age, 13 months). Lung function was assessed from partial expiratory flow volume curves generated by the rapid compression technique and was quantitated by the maximal expiratory flow at functional residual capacity (VmaxFRC). For the normal control group there was no significant change in VmaxFRC after the aerosol of either normal saline or metaproterenol. At baseline, the group of infants with CF had significantly lower values of VmaxFRC than did the normal control infants (202 versus 273 ml/s, p less than 0.05). The CF group demonstrated no significant change from baseline VmaxFRC after the aerosol of normal saline. However, after metaproterenol the CF group had a significant increase (p less than 0.001) in VmaxFRC, which eliminated the difference in VmaxFRC between the CF and normal control groups (267 versus 276 ml/s). We conclude that infants and young children with CF have increased bronchomotor tone and that bronchoconstriction represents a significant component of the airway obstruction present in patients with CF at this age.

Child, Preschool↗
PubMed1987

Airway reactivity in infants: a positive response to methacholine and metaproterenol.

Because the presence of bronchial smooth muscle reactivity in infants remains controversial, airway reactivity was assessed in 10 normal, asymptomatic male infants less than 15 mo of age by measuring the changes that occurred in the maximal expiratory flows at functional residual capacity (VmaxFRC) during a methacholine bronchial challenge test. Sleeping infants inhaled doubling concentrations of methacholine by 2 min of tidal breathing, starting with a concentration of 0.075 mg/ml, and the bronchial challenge was stopped when VmaxFRC decreased by at least 40%. The threshold concentration of methacholine required to produce a decrease in VmaxFRC by 2 SD's of the control value was 0.43 mg/ml (0.11-0.90). By a methacholine concentration of 1.2 mg/ml, all infants decreased VmaxFRC by at least 40% (range 40-75%), and the mean dose required to produce a 40% decrease was 0.72 mg/ml. The airway reactivity was not related to base-line flows. During the methacholine challenge, no infant developed wheezing, but the percent oxygen saturation for the group decreased significantly (P less than 0.05) from 94 to 92%. Following the methacholine, the infants inhaled the bronchodilator metaproterenol, and 10 min later, VmaxFRC returned to base line. This study demonstrates that infants exhibit airway reactivity as evidenced by bronchoconstriction with methacholine and the subsequent bronchodilation with metaproterenol.

Dose-Response Relationship, Drug↗
PubMed1987

Total respiratory system compliance in asymptomatic infants with cystic fibrosis.

Total respiratory system compliance (Crs) was assessed by the weighted spirometer method in 11 asymptomatic infants (mean age, 11.1 months) with cystic fibrosis (CF) who had normal chest radiographs. In addition to Crs, functional residual capacity (FRC), respiratory rate (RR), and mixing index (MI) were measured. There was no significant difference in FRC between normal controls (n = 36) and CF infants (190 +/- 69 versus 186 +/- 63 ml; p less than 0.8), although the CF group had a higher RR (32 +/- 7 versus 37 +/- 7 BPM; p less than 0.05) and a lower MI (45 +/- 7 versus 40 +/- 8%; p less than 0.05), reflecting an abnormal distribution of ventilation. The lower Crs (9.0 +/- 3.4 versus 5.7 +/- 2.8 ml/cm H2O; p less than 0.01) and the lower specific compliance, Crs/FRC (0.049 +/- 0.013 versus 0.029 +/- 0.007 1/cm H2O; p less than 0.0001), in the CF group were the parameters that best distinguished the normal control and CF infants. We conclude that the measurement of Crs represents a noninvasive method for detecting early pulmonary function abnormalities in CF infants.

Cystic Fibrosis↗