Readministration of helper-dependent adenoviral vectors to mouse airway mediated via transient immunosuppression.

The efficacy of adenovirus-mediated gene therapy is attenuated by the host immune responses to both vector and transgene products. Even for helper-dependent adenoviral (HD-Ad) vectors, which have all viral-coding sequences deleted, the viral capsid proteins still cause immune reactions. In order to improve the efficiency in transgene expression during HD-Ad vector readministration, we administered cyclophosphamide to transiently modulate the mouse immune system. We delivered a high dose (5 × 10(10) vector particles (vp) per mouse) of empty HD-Ad to the mouse airway to induce an initial immune response. After 4 weeks, the mice were readministered with an HD-Ad vector containing either the reporter gene, LacZ, or the gene for the human cystic fibrosis transmembrane conductance regulator (CFTR) (1.5 × 10(10) vp per mouse). We found that the expression of both transgenes was greatly improved by the administration of cyclophosphamide when compared with the expression in mice without the immunosuppressing drug. We also found that the high dose of the empty HD-Ad vector administered intranasally does not induce an acute systemic immune response, but it does elicit an acute local response of proinflammatory cytokine production. Antibodies against Ad vector, including the neutralizing antibodies, were greatly reduced by the presence of cyclophosphamide in vector readministratiton. Moreover, cyclophosphamide reduced the infiltration of inflammatory cells, including total leukocytes, lymphocytes, CD4+ and CD8+T cells. These results indicate that transient administration of immunosuppressive agent can be used to extend transgene expression as well as attenuating immunogenicity to HD-Ad vectors in airway readministration.

Exercise capacity of children with pediatric lung disease.

BACKGROUND: Pulmonary function of children with cystic fibrosis (CF) and bronchopulmonary dysplasia (BPD) is similar at rest even though the mechanisms of injury differ. We sought to compare the peak exercise responses in children with BPD versus CF while controlling for pulmonary impairment, nutritional status, gender, age, height, and predicted forced expired volume in 1 second (approximately 73% of predicted). METHODS: Nine BPD children and 9 CF children underwent spirometry and a progressive exercise test to maximum on a cycle ergometer. RESULTS: There was no difference between groups in body mass percentile (CF:97 +/- 13%, BPD: 98 +/- 11%), peak power output (Wpeak) (CF:67 +/- 19 W, BPD:73 +/- 28 W), % predicted Wpeak (CF:83 +/- 28%, BPD:88 +/- 15%), peak oxygen uptake (VO2peak, CF: 38 +/- 7 ml/kg/min, BPD: 39 +/-6 ml/kg/min), or % predicted VO2peak (CF:99 +/- 16 %, BPD:96 +/- 27%). CONCLUSIONS: Children with mild pulmonary impairments are able to achieve a near normal peak power output and a normal VO2peak. Neither the aetiology nor the developmental onset of the process appears to be important influences on VO2peak or Wpeak.

4A randomized trial of prolonged prone positioning in children with acute respiratory failure.

STUDY OBJECTIVE: To compare the effect of the prone position (PP) vs supine position (SP) on oxygenation in children with acute respiratory failure (ARF). DESIGN: Prospective, randomized controlled trial. SETTING: A 36-bed pediatric critical-care unit in a tertiary-care, university-based children's hospital. PATIENTS: Ten children (mean [SD] age, 5 +/- 3.6 years) with ARF with a baseline oxygenation index (OI) of 22 +/- 8.5. INTERVENTIONS: Following a period of stabilization in the SP, baseline data were collected and patients were randomized to one of two groups in a two-crossover study design: group 1, supine/prone sequence; group 2, prone/supine sequence. Each position was maintained for 12 h. Lung mechanics and acute response to inhaled nitric oxide were examined in each position. MEASUREMENTS AND MAIN RESULTS: OI was significantly better in the PP compared to the SP over the 12-h period (analysis of variance, p = 0.0016). When patients were prone, a significant improvement in OI was detected (7.9 +/- 5.3; p = 0.002); this improvement occurred early (within 2 h in 9 of 10 patients) and was sustained over the 12-h study period. Static respiratory system compliance and resistance were not significantly affected by the position change. Inhaled nitric oxide had no effect on oxygenation in either position. Urine output increased while prone, resulting in a significantly improved fluid balance (+ 6.6 +/- 15.2 mL/kg/12 h in PP vs + 18.9 +/- 13.6 mL/kg/12 h in SP; p = 0.041). No serious adverse effects were detected in the PP. CONCLUSION: In children with ARF, oxygenation is significantly superior in the PP than in the SP. This improvement occurs early, remains sustained for a 12-h period, and is independent of changes in lung mechanics.

Nebulizer choice for inhaled colistin treatment in cystic fibrosis.

STUDY OBJECTIVES: To develop practical ways of nebulizing colistin by determining the rate of drug output, total drug output, and particle-size distribution of two commercially available jet nebulizers, the disposable Hudson 1730 Updraft II (Hudson Respiratory Care; Temecula, CA) and the reusable Pari LC Star breath-enhanced nebulizer (Pari Respiratory Equipment; Midlothian, VA). METHODS: The nebulizers contained colistin, 75 mg, in 4 mL of isotonic solution. Particle-size distribution was measured by helium-neon laser diffraction, allowing calculation of the respirable fraction (RF), the mass of aerosol comprised of droplets < 5 microm. RESULTS: The mean (95% confidence interval [CI]) total rate of output of the Updraft II was 2.6 mg/min (2.0, 3.1; n = 4) with 1.3 mg/min (1.0, 1.5) mg/min within the RF. The rate of output of the LC Star increased in a quadratic relationship to the inspiratory flow, delivering 1.8 mg/min (0.7, 2.0; n = 4) with 1.4 mg/min (1.3, 1.6) within the RF, and 6.2 mg/min (5.6, 6.8) with 5.3 mg/min (4.8, 5.7) within the RF, at 0 L/min and 20 L/min inspiratory flows, respectively. Efficiency, as the rate of expected pulmonary deposition divided by rate of total output, was then calculated. The LC Star estimated 56% (51, 61) efficiency, with pulmonary delivery of 29% (26, 32) of the charge of the nebulizer, compared to the Updraft II at 22% (22, 23) efficiency and expected pulmonary deposition of 10% (10, 10) of the dose. CONCLUSIONS: Colistin can be successfully nebulized with both nebulizers tested. This study provides an estimate of in vivo efficiency and expected pulmonary deposition that may be used in future trials.

Diffusion capacity and oxygen desaturation effects on exercise in patients with cystic fibrosis.

Although a fall in arterial oxygen saturation (SaO2) during exercise has been reported in patients with advanced lung disease due to cystic fibrosis (CF), not every patient with advanced disease desaturates, and pulmonary function tests have not been considered predictive as to which patient will desaturate. This study evaluated oxygen desaturation by ear oximetry during a progressive exercise test in 21 patients with CF and compared it to forced expiratory volume in one second (FEV1), the forced vital capacity (FVC) and the single breath diffusing capacity for carbon monoxide (DCO), all expressed as percent predicted. During exercise, the SaO2 fell less than 0.25 percent per ml of the maximal O2 consumption per kilogram of body weight to values never less than 90 percent in 15 patients (group A), whereas it fell more than this and always to values at the end of exercise of less than 90 percent in six others (group B). The FEV1 ranged from 103 percent predicted to 37 percent for group A compared to 28 to 17 percent in group B, while the range of FEV1/FVC was 87 to 52 percent for group A and 54 to 40 percent for group B. The range of DCO for group A was 129 to 84 percent compared to 64 to 54 percent. In conclusion, this study found that both the FEV1 and the DCO could separate those that had significant desaturation from those that did not and that no patient with a DCO of 80 percent or greater had significant desaturation during exercise.

Histamine challenge test in children using forced oscillation to measure total respiratory resistance.

This study analyzed the relationship between total respiratory resistance (Rrs) measured by forced oscillation technique and FEV1 during histamine provocation test in 31 children between seven and 17 years of age. Rrs was measured at frequencies between 6 (R6) and 26 Hz (R26). (R6-R26)/R26 was used as an index of frequency dependency of Rrs. A positive histamine test was defined as PC20 less than 8 mg/ml. Seventeen subjects had a positive test, and all of these had increases from baseline of R6 greater than 50 percent and (R6-R26)/R26 greater than 0.45. Of the 14 subjects whose PC20 was greater than 8 mg/ml, only two had changes in R6 and (R6-R26)/R26 of this magnitude. These two subjects had changes in FEV1 of 16 and 18 percent. There was a strong linear relationship between the changes in FEV1 and both R6 and (R6-R26)/R26 from baseline to the final value at the end of the test (r = 0.87 and 0.91 respectively). In conclusion, this study demonstrated that the evaluation of airway reactivity by histamine challenge may be done by forced oscillation technique. It is easy to administer and may allow testing of children unable to perform spirometry.

Sources of error in flow-volume curves. Effect of expired volume measured at the mouth vs that measured in a body plethysmograph.

The popularity of the maximum expiratory flow-volume curve (FVC) is in part due to the effort independence of expiratory flow. Of interest are expiratory flow rates at specific lung volumes, usually 50 and 25 percent of vital capacity (VC); Vmax50 and Vmax25, which make accurate assessment of lung volumes essential. Changes in lung volume during the test are due to both the volume of gas expired and the volume change due to gas compression (Vcomp). In normal subjects, Vcomp is small but may be considerable in those with airflow obstruction. When the FVC is measured in a plethysmograph (FVCp), both expired volume and Vcomp are measured. When the volume of the FVC is derived from gas expired at the mouth (FVCm), Vcomp is not considered and differences in Vmax25 or Vmax50 may occur. The magnitude of these errors was assessed in 30 children and young adults: nine normal subjects, ten with cystic fibrosis (CF) and 11 with asthma. For Vmax50, use of FVCm instead of FVCp resulted in an error of 8 +/- 7 percent (mean +/- 1 SD) in the normal subjects compared to 32 +/- 23 in those with CF (p less than 0.01) and 24 +/- 18 for those with asthma (p less than 0.05). For Vmax25, the errors were similar. These errors were not predictable from FEV1 or RV/TLC but were related to a combination of expiratory effort, the shape of the FVCp, and the absolute volume of gas that was being compressed (p less than 0.0001). These findings suggest that expiratory flows in the FVCm are not effort-independent in the face of significant airflow obstruction and that comparisons of values derived from an FVCp with those from an FVCm may not be valid.

Effect of different inspiratory maneuvers on FEV1 in patients with cystic fibrosis.

The time course of inspiration has been shown to have a significant influence on the subsequent maximal expiratory flows and timed forced expiratory volumes in healthy adults and those with COPD. The purpose of this study was to evaluate the effect of two different inspiratory maneuvers on the spirogram in 15 patients with cystic fibrosis, aged 13 to 35 years, who had mild to moderate airway obstruction. Patients performed a forced expiratory maneuver either after a rapid inspiration without an end-inspiratory pause or after a slow inspiration with a 4-s end-inspiratory pause. Flow-time and volume-time curves were measured by a pneumotachograph. The mean values of FVC, FEV1, and peak expiratory flow were significantly larger by 11%, 13%, and 26%, respectively, after the rapid inspiration without an end-inspiratory pause compared to the slow inspiration with the end-inspiratory pause. This discrepancy probably reflects differences in effective elastic recoil pressure between the two maneuvers. Although the nature of this phenomenon is not fully understood, our results show that for spirometry in patients with cystic fibrosis, the preceding inspiratory maneuver influences the results. An important corollary is that this inspiratory maneuver should be standardized.

A comparison of pulmonary availability between Ventolin (albuterol) nebules and Ventolin (albuterol) Respirator Solution.

The two most common albuterol preparations used for nebulization are: (1) Ventolin (albuterol) respirator solution (Glaxo Canada Inc; Montreal, Canada) of which 2.5 mg (0.5 mL) is diluted with 2 mL of normal saline solution, and (2) the preservative-free, prediluted Ventolin (albuterol) Nebules PF (Glaxo) (2.5 mg/2.5 mL). The two preparations were compared using both a Hudson 1720 "T" up-draft Neb-U-Mist jet nebulizer and a Hudson 1730 "T" up-draft Neb-U-Mist II jet nebulizer (Hudson; Temecula, Calif), which were driven by a compressor (Pulmo-Aide; Devilbiss; Somerset, Pa) and by dry compressed air at 6 and 8 L/min. Particle size distribution was measured with a particle sizer (Malvern 2600; Malvern Instruments; Malvern, UK) and drug output for the nebulizer was calculated from the differences in predrug and postdrug volume and concentration. Drug availability was defined as the amount of drug carried in particles less than 5 microns in diameter. Drug availability was greater with the albuterol respiratory solution, due to the surface activity of the preservative benzalkonium chloride, for both nebulizers but particularly for the 1720. Differences in drug availability between nebulizers exceeded fourfold depending on the preparation, the nebulizer, and the nebulizing flow. These differences could not have been predicted from the manufacturer's specifications. The results suggest that prediction of drug availability must be based on measurements with the specific preparation and the specific nebulizer used.

The effect of digoxin on exercise capacity and exercising cardiac function in cystic fibrosis.

The ability of digoxin to increase exercise capacity and stroke volume (SV) during exercise was evaluated in ten patients with cystic fibrosis (CF) ages 12 to 20 years with moderate to severe degrees of airway obstruction but no history of heart failure. A double-blind crossover trial of digoxin versus placebo was carried out. An evaluation of exercise performance was undertaken upon entry into the study, and after each of the one-week periods in which digoxin 0.25 mg/day or placebo was taken. Exercise testing consisted of a progressive exercise test on a cycle ergometer to measure maximum work capacity (Wmax) and a steady state test at 2/3 of the baseline Wmax. During the steady state test, the oxygen consumption and carbon dioxide production were measured and cardiac output (Q) was calculated by the indirect Fick (CO2) method. From Q and heart rate (HR), SV was derived. After digoxin, Wmax was unchanged. On steady state exercise HR was unchanged, but there was a slight but significant fall in Q due to a fall in SV. The decrease in SV was associated with exercising hypoxemia. We conclude that digoxin did not increase exercise capacity or improve exercising cardiac function in patients with moderate to severe airway obstruction due to CF.

A comparison of the availability of tobramycin for inhalation from vented vs unvented nebulizers.

STUDY OBJECTIVE: To compare drug output from a vented nebulizer (Pari LC Jet Plus) with a traditional unvented nebulizer (Hudson 1730 T Up-Draft 11) using aerosolized tobramycin, which is frequently used in the treatment of cystic fibrosis. DESIGN: Six nebulizers of each type were filled with a 4 mL tobramycin (80 mg) solution and were driven by a compressor (Pulmo-Aide). Various inspiratory flows (VI) (0, 5, 10, 15, 20 L/min for the Pari LC Jet Plus and 0, 5, and 10 L/min for the Hudson 1730, all at 40% relative humidity) were directed through each nebulizer. Drug output was measured from changes in weight and concentration (assessed by changes in osmometry) within the nebulizer. Particle size distributions were determined by laser diffraction allowing the calculation of the amount of aerosol output in the respirable range (<5 microm). The nebulizers were first run until end-nebulization to establish total drug output and then for either 4 or 5 min to determine the rate of drug output (mg/min) before intermittent aerosol output. RESULTS: The total drug output without VI for both the unvented and the vented nebulizers was not significantly different, 55 (51, 60) mg for the Hudson 1730 vs 51 (49, 53) mg for the Pari LC Jet Plus (mean [95% confidence limits]). Inspiratory flow had no effect on the unvented Hudson 1730 nebulizer but significantly increased the rate of total drug output and the rate of drug output in the respirable range for the vented Pari LC Jet Plus nebulizer (VI=0, 3.35 [2.84, 3.85] and 1.72 [1.48, 1.96] compared with VI=20, 9.87 [9.03, 10.70] and 6.11 [5.33, 6.88] mg/min). CONCLUSIONS: These findings indicate that the increase in the rate of drug output with VI for the vented nebulizer would result in shorter nebulization times and a relative decrease in drug loss during the expiratory phase.

The choice of jet nebulizer, nebulizing flow, and addition of albuterol affects the output of tobramycin aerosols.

The use of inhaled antibiotics in the treatment of cystic fibrosis has become widespread despite controversy in the literature as to the appropriate dosing regimen and its effectiveness. This study compared two tobramycin (T) preparations (one with and one without the addition of albuterol) using two different jet nebulizers in order to determine if drug output would be affected. Using calibrated flows from a dry compressed gas source of 6 and 8 L/min as well as a specific compressor (Pulmo-Aide), the Hudson 1720 nebulizer was compared with the newer disposable Hudson 1730. The albuterol preparation used in this study was the Ventolin (albuterol) Respirator Solution (VRS). The nebulizers were charged with (1) 2 mL T (80 mg/2 mL) with 0.5 mL VRS (5 mg/mL) and normal saline solution to make the total nebulizer charge of 3 or 4 mL, or (2) 2 mL T and either 1 or 2 mL normal saline solution. A laser diffraction analyzer (Malvern 2600) was used to determine the aerosol particle size distribution. From the distribution, the respirable fraction, which is the fraction of aerosol that could enter and remain in the lungs, was calculated. For all solutions and each particular flow, the Hudson 1730 had a larger respirable fraction of T. The addition of VRS lowered the surface tension of the solution in the nebulizer and resulted in a greater output of T. This effect was most apparent for the 3-mL volume fills of the Hudson 1720. The greatest differences were between the 3-mL nebulizer charges of T using the Hudson 1720 driven by a flow of 6 L/min, which produced 8 mg of T in the respirable fraction, compared with 35 mg produced by the Hudson 1730 driven by a flow of 8 L/min. These results suggest that different nebulizers, different nebulizer solutions, and different techniques of nebulization may result in very different amounts of T aerosol output in the respirable fraction.

Effect of size and disease on estimated deposition of drugs administered using jet nebulization in children with cystic fibrosis.

STUDY OBJECTIVES: To develop a model that quantified the nebulizer output that was inhaled by subjects with cystic fibrosis (CF) in order to predict the amount of drug likely to enter the upper airway contained in particles small enough to be deposited in the lower respiratory tract of individual patients. DESIGN: Forty-three patients (age, 6 to 18 years) with CF, with FEV(1) of 26 to 124% of predicted, breathed through a nebulizer circuit with a pneumotachograph in place at the distal end. Algorithms were developed from the measured flows through the pneumotachograph, allowing partitioning of inspiration into undiluted aerosol and fresh gas. In order to validate the algorithms, argon was added to the nebulizing gas flow and then its concentration was analyzed at the mouth by mass spectrometry. RESULTS: Predictions of the concentration of argon at the mouth were concordant with that measured by mass spectrometry, thus validating the model. Combining data from the model with in vitro nebulizer performance data, predictions for estimates for lung deposition for individuals were possible. Total estimate was independent of patient size or FEV(1). The respiratory duty cycle was 0.44 +/- 0.05 (mean +/- SD) and correlated (r = 0.91, p < 0.001) with estimated deposition and minute ventilation (r = 0.60, p < 0.01). However, when expressed in milligrams per kilogram of body weight, the estimated deposition in smaller children was fourfold higher than in larger children. CONCLUSIONS: If the effect of patient size and pattern of breathing on estimated drug deposition are not considered when prescribing drugs given by nebulization, the result may be overdosing younger children, underdosing older children, or both.

Effects of nutritional status on exercise performance in advanced cystic fibrosis.

Initial evaluation of 22 patients with cystic fibrosis (CF) on entry into a trial of home oxygen therapy was used to elucidate the possible effects of poor nutritional status on exercise performance in CF. The patients had advanced lung disease (mean FEV1, 36 percent predicted) and all had a stable resting PaO2 less than or equal to 65 mm Hg. Nutritional status was determined by calculating weight as a percentage of ideal for height (Wt/Ht) for each subject. Exercise testing consisted of a progressive exercise test on a cycle ergometer to measure maximum work capacity (Wmax), and a steady state test at 50 percent of baseline Wmax. During the steady state test, cardiac output (Q) and stroke volume (SV) were computed by the indirect Fick (CO2) method. Wmax, SV, Q and lung function results are expressed as percent predicted. Mean (+/- SD) Wmax was 58 +/- 15 percent predicted. Wmax correlated with both FEV1 and Wt/Ht, but FEV1 and Wt/Ht were not related. During steady state exercise, 12 of 22 patients had a SV less than 80 percent predicted. SV correlated with Wt/Ht, but not with lung function. Thirteen of the 22 patients had a Wt/Ht less than or equal to 90 percent and were considered malnourished. When compared with the well-nourished patients (Wt/Ht greater than 90%), these malnourished subjects had significantly lower mean values for Wmax%, SV% and Q% predicted, but not for lung function parameters. We conclude that: in patients with CF and advanced lung disease, nutritional status plays a significant role in determining exercise capacity; lower exercise tolerance of malnourished patients is an independent effect, as nutritional status and lung function were not related; and malnourished patients with CF have an altered cardiac performance on exercise testing which is due to a reduced SV rather than an impaired heart rate response.

Effect of analyzer on determination of mixed venous PCO2 and cardiac output during exercise.

Cardiac output (CO) during exercise can be determined noninvasively by using the indirect Fick CO2-rebreathing technique. CO2 measurements for this technique are usually performed with an infrared analyzer (IA) or mass spectrometer (MS). However, IA CO2 measurements are susceptible to underreading in the face of high O2 concentrations because of collision broadening. We compared an IA (Ametek model CD-3A) with a MS (Marquette model MGA-1100) to see the effect this would have on mixed venous PCO2 (PVCO2) and CO measurements. After calibration with room air and a gas mixture of 5% CO2-12% O2-83% N2, both devices were tested with three different gas mixtures of CO2 in O2. For each gas mixture, IA gave lower CO2 values than did the MS (4.1% CO2: IA, 3.85 +/- 0.01% and MS, 4.13 +/- 0.01%; 9.2% CO2: IA, 8.44 +/- 0.07% and MS, 9.19 +/- 0.01%; 13.8% CO2: IA, 12.57 +/- 0.15% and MS, 13.82 +/- 0.01%). Warming and humidifying the gases did not alter the results. The IA gave lower values than did the MS for eight other medical gases in lower concentrations of O2 (40-50%). Equilibrium and exponential rebreathing procedures were performed. Values determined by the IA were > 10% higher than those determined by the MS for both rebreathing methods. We conclude that all IAs must be checked for collision broadening if they are to be used in environments where the concentration of O2 is > 21%. If collision broadening is present, then either a special high O2-CO2 calibration curve must be constructed, or the IA should not be used for both arterial PCO2 and PVCO2 estimates because it may produce erroneously low PVCO2 values, with resultant overestimation of CO.

A very low dead space pneumotachograph for ventilatory measurements in newborns.

In premature and full-term neonates, technical limitations hamper the measurements of pulmonary mechanics. Current commercially available pneumotachographs (PNT) either increase the dead space, causing hyperventilation, or increase resistance, thus altering the mechanics of breathing. We modified a previously described low dead space PNT for infants to increase the linear range and frequency response. The mean resistance of the new PNT was 2.44 cmH2O.1-1.s compared with 2.65 cmH2O.1-1.s for the Fleisch no. 0 PNT. The added dead space over the standard endotracheal connector was 0.6 ml compared with 4.7 ml for the Fleisch PNT. Like the Fleisch PNT, the flow resistance was linear from 0 to 15 l/min. In response to a sinusoidal waveform, the new PNT had a phase angle of 21 degrees at 5 Hz and 50 degrees at 16 Hz compared with 19 degrees and 43 degrees, respectively, for the Fleisch PNT. The change in attenuation for both systems was zero until 20 Hz. In summary, the new PNT is lightweight and provides accuracy and low resistance with a very small dead space.

Measurement of pulmonary mechanics in the newborn lamb: a comparison of three techniques.

Although recent interest in neonatal respiratory mechanics has led to the development of a plethora of techniques for measuring lung compliance and resistance, a critical appraisal of the limitations of these techniques in the newborn has not been performed to date. We evaluated three techniques of measuring respiratory mechanics in the newborn lamb, with the reference method (method 1) being the Mead-Whittenberger technique using flow, volume, and esophageal pressure (Pes) by water-filled catheter, and the other two methods entailing the measurement of mouth pressure (Pm) during airway occlusion (method 2 using end-expiratory occlusion; method 3 using end-inspiratory occlusion). Each technique was evaluated during eupnea and tachypnea in intubated and nonintubated newborn lambs. We found that the use of Pes for the measurement of resistance and compliance gave the most reliable results during both eupnea and tachypnea in both the intubated and nonintubated subjects. The airway occlusion techniques that use Pm to derive resistance and compliance (methods 2 and 3) gave more variable results under all conditions of testing. Method 2 was the least precise method of measurement with a variability of greater than 30% compared with a variation of less than 20% for method 1. For all three methods, it was found that the number of breaths needed for reproducible measurements of mechanics was four to six during eupnea and seven to nine during tachypnea.

Direct measurement of static chest wall compliance in animal and human neonates.

The measurement of pulmonary mechanics has been developed extensively for adults, and these techniques have been applied directly to neonates and infants. However, the compliant chest wall of the infant frequently predisposes to chest wall distortion, especially when there is a low dynamic lung compliance (CL,dyn). We describe a technique of directly measuring the static chest wall compliance (Cw,st), developed initially in the newborn lamb and subsequently applied to the premature neonate with chest wall distortion. The mean CL,dyn in seven intubated newborn lambs in normoxia was 2.45 +/- 0.41 ml.cmH2O-1.kg-1, whereas Cw,st was 11.81 +/- 0.25 ml.cmH2O-1.kg-1. These values did not change significantly in seven animals breathing through a tight-fitting face mask or with hypercapnia-induced tachypnea. For the eight premature infants the mean CL,dyn was 1.35 +/- 0.36 ml.cmH2O-1.kg-1, whereas the mean Cw,st was 3.16 +/- 1.01 ml.cmH2O-1.kg-1. This study shows that, under relaxed conditions when measurements of static compliance are performed, the chest wall is more compliant than the lung. The measurement of Cw,st may thus be used to determine the contribution of the respiratory musculature in stabilizing the chest wall.

Liquid-filled esophageal catheter for measuring pleural pressure in preterm neonates.

The precise measurement of esophageal pressure (Pes) as a reflection of pleural pressure (Ppl) is crucial to the measurement of lung mechanics in the newborn. The fidelity of Pes as a measurement of Ppl is determined by the occlusion test in which, during respiratory efforts against an occlusion at the airway opening, changes in pressure (delta Pao) (Pao is assumed to be equal to alveolar pressure) are shown to be equal to changes in Pes (delta Pes). Eight intubated premature infants (640-3,700 g) with chest wall distortion were studied using a water-filled catheter system to measure Pes. During the occlusion test, all patients had a finite region of the esophagus where delta Pes equaled delta Pao, which corresponded to points in the esophagus above the cardia but below the carina. In conclusion, even in the presence of chest wall distortion, a liquid-filled catheter with the tip between the cardia and carina can provide an accurate measurement of Ppl, even in the very small premature infant with chest wall distortion.

Maternal anthropometry and idiopathic preterm labor.

OBJECTIVE: To assess the etiologic role of maternal short stature, low pre-pregnancy body mass index (BMI), and low rate of gestational weight gain in idiopathic preterm labor. METHODS: We carried out a three-center case-control study of 555 women with idiopathic onset of preterm labor (before 37 completed weeks), including two overlapping (ie, nonmutually exclusive) subsamples: cases with early preterm labor (before 34 completed weeks) and cases with recurrent preterm labor (before 37 completed weeks plus a history of prior preterm delivery or second-trimester miscarriage). Controls were matched to cases by race and smoking history. All subjects responded in person to questions about height, pre-pregnancy weight, gestational weight gain, and obstetric and sociodemographic histories. RESULTS: Maternal height, pre-pregnancy weight, and gestational weight gain demonstrated excellent test-retest reliability, with intra-class correlation coefficients of 0.97, 0.99, and 0.91, respectively. Based on matched analyses, women with a height of 157.5 cm or less had an increased risk of idiopathic preterm labor (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.25-2.74), as did those with a pre-pregnancy BMI less than 19.8 kg/m2 (OR 1.63, 95% CI 1.09-2.44) or a gestational weight gain rate less than 0.27 kg/week (OR 1.74, 95% CI 1.16-2.62). Conditional logistic regression models containing all three anthropometric variables and controlling for parity, marital status, language, age, and education yielded virtually identical point estimates and CIs. CONCLUSION: Maternal short stature, low pre-pregnancy BMI, and low rate of gestational weight gain may lead to shortened gestation by increasing the risk of idiopathic preterm labor.