Development of alpha-tocopherol acetate nanoparticles: influence of preparative processes.

We studied different methods of preparing alpha-tocopherol acetate (ATA) nanoparticles, which are to be used in targeting the lungs as aerosols in order to prevent cigarette smoke toxicity. Poly-(lactide) nanoparticles were prepared using nanoprecipitation and solvent evaporation techniques, which produced, respectively, too small and too large nanoparticles to be aerosolized. The emulsification-diffusion method produced 2 months stable nanoparticles with a size between (500-700 nm). Increasing ATA concentration (1-7 mg/mL) induced a decrease in the association rate (97-93%) and in the adsorbed ATA rate (7-4.5%), which was associated with variations of Zeta potentials (-27.5 to -24.3 mV) and decrease in polymeric wall thickness and density.

Effects of obesity on respiratory resistance.

To assess the effects of obesity on pulmonary function, 46 healthy subjects exhibiting various degrees of obesity underwent lung function tests. Subjects were divided into three groups according to body mass index (BMI): 13 had minimal obesity (BMI, 25 to 29 kg/m2, group 1); 24 had a BMI in the 30 to 40 range (group 2); and 9 displayed to morbid obesity (BMI > 40, group 3). Respiratory resistance was estimated by the forced random noise oscillation technique and airway resistance was determined by body plethysmography. Lung volumes and expiratory flows were also determined and significant negative correlations with BMI were found. Expiratory flows diminished in proportion to lung volumes, and the ratio of forced expiratory volume in 1 s to forced vital capacity was within normal limits. Although expiratory flows did not suggest bronchial obstruction, both respiratory resistance and airway resistance rose significantly with the level of obesity (p < 0.005 and p < 0.025, respectively), from 3.2 (+/- 0.02) and 3.2 (+/- 0.02) cm H2O.s.L-1, respectively, in group 1, to 5.5 (+/- 0.06) and 5.0 (+/- 0.05), respectively, in group 3. Evaluation of the factors responsible for this increased resistance disclosed a significant linear correlation between airway conductance and functional residual capacity (r = 0.70, p < 10(-4)), but specific airway conductance was found to be independent of the degree of obesity. The difference between respiratory resistance and airway resistance did not widen significantly according to the level of obesity, suggesting that chest wall resistance was not a factor enhancing these resistances. Taken together, these findings suggest that in addition to the elastic load, obese subjects have to overcome increased respiratory resistance resulting from the reduction in lung volumes related to being overweight.

Forced oscillation technique vs spirometry to assess bronchodilatation in patients with asthma and COPD.

The forced oscillation technique (FOT) is a noninvasive test used to characterize the mechanical impedance of the respiratory system. The aim of the study was to compare the changes in respiratory conductance (Grs) measured with FOT to those in FEV1 in 22 patients with asthma and 20 patients with chronic obstructive pulmonary diseases (COPD) after salbutamol inhalation. FEV1 and Grs indexes, computed as the ratio of the difference between postbronchodilator and prebronchodilator values over the predicted value, were used to express reversibility of airway obstruction. After inhalation of salbutamol in cumulative doses up to 1,200 micrograms in ten patients of each group, FEV1 and Grs indexes showed parallel changes, and most of the increase was observed after the first dose of 200 micrograms of salbutamol for the two indexes. In all the 42 patients, we found a linear relationship between the two indexes after inhalation of 200 micrograms of salbutamol (r = 0.7, p < 0.0001). We evaluated FEV1 and Grs indexes in terms of sensitivity and specificity for identifying asthmatics among patients with COPD: using a 10% change as the cut-off value, these indexes proved of similar value (sensitivity, 0.91 and 0.95; specificity, 0.95 and 0.85, respectively). We conclude that the use of FOT can be considered as an alternative to forced expiration for detecting bronchodilatation in asthmatics and patients with COPD.

Combined effects of a mechanical nasal dilator and a topical decongestant on nasal airflow resistance.

The goal of this study was to compare the isolated and combined effects of two treatments being used to reduce nasal airflow resistance (NR): an internal nasal mechanical dilator (Nozovent; Prevancure; Sté Pouret, Paris, France) and a topical decongestant, fenoxazoline hydrochloride (Aturgyl; Synthelabo; Le Plessis-Robinson, France). The study was performed in 17 healthy subjects. NR was estimated by active posterior rhinometry at a 0.5 L/s flow under four conditions: in the basal state, with the internal nasal mechanical dilator, after treatment with fenoxazoline hydrochloride, and with both fenoxazoline hydrochloride and the mechanical dilator. The mean NR (+/- SD) decreased from 1.65+/-0.54 cm H2O/L/s in the basal state to 1.02+/-0.27 cm H2O/L/s with the mechanical dilator (p < 0.001), 1.03+/-0.47 cm H2O/L/s with fenoxazoline hydrochloride (p < 0.001), and 0.48+/-0.15 cm H2O/L/s with both the mechanical dilator and fenoxazoline hydrochloride (p < 0.001). The decreases in NR observed after using either the mechanical dilator (deltaNR(N)) or fenoxazoline hydrochloride (deltaNR(A)) were not significantly different. The decrease in NR observed with both (deltaNR(N + A)) was not significantly different from the sum deltaNR(N) + deltaNR(A): 1.16+/-0.53 cm H2O/L/s vs 1.25+/-0.63 cm H2O/L/s, respectively (p > 0.05). deltaNR(N + A) strongly correlated with deltaNR(N) + deltaNR(A): deltaNR(N + A) = 0.80 (deltaNR(N) + deltaNR(A)) + 0.15 (r = 0.96; p < 0.0001). However, the slope of the regression line of deltaNR(N + A) vs deltaNR(N) + deltaNR(A) was significantly lower than unity (p < 0.003). These results demonstrate that, although not totally additive, the effects of using the mechanical dilator and fenoxazoline hydrochloride are cumulative. Further studies that include patients with nasal obstruction would allow us to better evaluate the benefit of a therapy combining both treatments.

Effects of different mechanical treatments on nasal resistance assessed by rhinometry.

The goal of this study was to compare the effectiveness of three treatments aiming to reduce nasal airflow resistance (NR): an external nasal strip device (Respir+), an internal nasal mechanical dilator (Nozovent), and a topical decongestant (Pernazène). NR was estimated by active posterior rhinometry at both a 0.5 L/s flow (NRF) and a 1 cm H2O pressure (NRP), under four conditions: in the basal state, with Respir+, with Nozovent, and after treatment with Pernazène. The efficacy of each treatment was assessed by the percentage changes in NRF and NRP (%NRF and %NRP, respectively). The study was performed in 15 healthy subjects. The efficacy of the treatments was significantly different, depending on whether it was evaluated by NRF or by NRP (p<0.02), with %NRF and %NRP values, respectively, equal to the following: 88+/-20% and 91+/-14% with Respir+, 58+/-17% and 70+/-13% with Nozovent, and 55+/-29% and 69+/-22% with Pernazène. NRF remained unchanged with Respir+, whereas it significantly decreased with Nozovent and Pernazène (p<0.0001). No significant difference was observed between the effects of the two latter treatments. These results demonstrate that Nozovent, which involves no risk of side effects or drug interactions, is an effective treatment to improve nasal breathing. Nozovent might therefore be recommended as an alternative to topical decongestants, for certain subjects presenting with nasal obstruction.

Abdominal muscle activity in sleep apnea during continuous positive airway pressure titration.

STUDY OBJECTIVES: The aim of this study was to investigate whether presence of expiratory abdominal muscle activity (EAMA) in obstructive sleep apnea syndrome (OSAS) patients during nasal continuous positive airway pressure (nCPAP) is due to either nCPAP overprescription or nCPAP underprescription. DESIGN: Airflow, esophageal pressure (Pes), and gastric pressure (Pga) were routinely measured during polysomnography aimed at determining the optimal nCPAP level, and the magnitude of EAMA was evaluated in relation to the nCPAP level and to the conventional indexes of upper-airway obstruction used during nCPAP titration. PATIENTS: The study was performed 12 patients with OSAS. RESULTS: Six patients displayed sustained EAMA, ie, EAMA lasting > 3 min, and characterized by a decrease in abdominal diameter and a paradoxical rise in Pga during expiration. In all six patients, EAMA decreased gradually as nCPAP neared optimal levels, and then disappeared when the optimal nCPAP level was achieved. The decrease in EAMA as nCPAP increased was associated with an increase in minute ventilation, decreases in both inspiratory and expiratory resistance, a decrease in Pes swing, and the normalization of the inspiratory flow contour. CONCLUSIONS: We conclude that the EAMA observed in some OSAS patients might be an indirect marker of upper-airway obstruction, and that the presence of EAMA during nCPAP titration might indicate a suboptimal nCPAP level rather than a deleterious effect of nCPAP.

Combined effects of a nasal dilator and nasal prongs on nasal airflow resistance.

STUDY OBJECTIVES: Nasal prongs (NPs), when used to assess nasal flow, can result in dramatic increases in nasal airflow resistance (NR). The aim of this study was to investigate whether the NP-induced increases in NR could be corrected by the simultaneous use of an internal nasal dilator (ND). DESIGN: NR was estimated by posterior rhinomanometry, in the basal state (NRb), and while breathing with NP (NRp), with ND (NRd), and with both ND and NP (NRd + p). PARTICIPANTS: The study was performed in 15 healthy subjects. MEASUREMENTS AND RESULTS: NR (mean NRb [+/- SEM], 2.5 +/- 0.4 cm H(2)O/L/s) significantly decreased with ND (NRd = 1.4 +/- 0.2 cm H(2)O/L/s; p < 0.001) and significantly increased with NP (NRp = 3.8 +/- 0.8 cm H(2)O/L/s; p < 0.001). A significant logarithmic relationship was found between NRd and NRb (r(2) = 0.95; p < 0.0001), and a significant exponential relationship was found between NRp and NRb (r(2) = 0.99; p < 0.0001). While breathing with both ND and NP, NRd + p was significantly lower than NRb (1.9 +/- 1.4 cm H(2)O/L/s; p < 0.02). CONCLUSIONS: Our results demonstrate that the ND tends to slightly overcorrect the NP-induced increase in NR and suggest that, in view of the possible effects of NPs on upper airway resistance, the combination of both devices might be used for nasal airflow monitoring during nocturnal polysomnography in patients presenting with highly resistive nares.

Effects of nasal prongs on nasal airflow resistance.

STUDY OBJECTIVES: The aim of this study was to investigate whether nasal prongs, which have been proposed to assess nasal flow during sleep, affect nasal airflow resistance (NR). DESIGN: NR was estimated by posterior rhinomanometry at a 0.5 L/s flow, under eight conditions: in the basal state, and with seven different nasal prongs. PARTICIPANTS: The study was performed in 17 healthy supine subjects, 8 of whom had basal NR values within the normal range (< or = 2 cm H(2)O.L(-1).s, group 1), and 9 had increased basal NR values (> 2.5 cm H(2)O.L(-1).s, group 2), because of nare narrowness and/or deviated nasal septum. MEASUREMENTS AND RESULTS: NR increased significantly while breathing with nasal prongs (p < 0.0001 in both groups). The changes in NR (DeltaNR) induced by the different nasal prongs were characterized by large intersubject and intrasubject variability, with a maximum DeltaNR of 24.2 cm H(2)O.L(-1).s. Significant differences were found between the DeltaNR induced by the different nasal prongs (p < 0.001 in group 1, and p < 0.0003 in group 2), and for six of them, DeltaNR was significantly higher in group 1 than in group 2 (p < 0.02). CONCLUSIONS: This study demonstrates that nasal prongs can markedly increase NR in subjects presenting with nare narrowness and/or deviated nasal septum. Further investigations that would include nocturnal polysomnography are still required to evaluate the possible influence of nasal prongs on the diagnosis of obstructive sleep apnea syndrome and its severity.

Topical upper airway anaesthesia with lidocaine increases airway resistance by impairing glottic function.

OBJECTIVE: To assess if two different forms of upper airway topical anaesthesia induce similar changes in airway flow resistance (Rrs). DESIGN: Serial measurements of Rrs before and after topical anaesthesia with acqueous or paste lidocaine. SETTING: Lung function test laboratory. PARTICIPANTS: 9 normal men with documented normal lung function tests. INTERVENTIONS: 2 different session of topical upper airway anaesthesia with 100 mg of liquid 5% lidocaine and 100 mg of 2% lidocaine paste, respectively. MEASUREMENTS AND RESULTS: Rrs was measured by the random noise forced oscillation technique. Fiberoptic upper airway examination was performed in two subjects. Rrs increased on average by 81% after lidocaine spray and by 68% after lidocaine paste (p < 0.005, respectively) with no difference in the magnitude of Rrs increase between the two modes of anaesthesia studied. This increase lasted 13 +/- 3 min (spray) and 12 +/- 3 min (paste), respectively (p = ns). Fiberoptic examination of the two most responders showed inspiratory laryngeal collapse. CONCLUSIONS: Topical upper airway anaesthesia transiently increases Rrs with no specific effects regarding the drug presentation. Laryngeal dysfunction may be one mechanisms involved in Rrs increase following upper airway topical anaesthesia. Such findings may explain some poor respiratory tolerance reported during endoscopy.

Techniques for measuring respiratory mechanics: an analytic approach with a viscoelastic model.

A homogeneous model with stress relaxation that is described by a pure viscoelastic component was recently proposed to describe the mechanical behavior of the respiratory system during mechanical ventilation (Bates et al. J. Appl. Physiol. 67: 2276-2285, 1989). With the use of this model, analytic expressions of the pressure in response to typical volume inputs are developed, and the recently published studies relating to the influence of the ventilatory pattern on respiratory mechanics are reviewed and analyzed. The analytic expression of pressure responses to rapid airway occlusion following constant-flow inflation and to sinusoidal volume oscillations allows prediction of most of the reported results. The theoretical analysis suggests that in normal subjects the observed flow and volume dependencies of respiratory mechanics are, in fact, illustrations of the dependence of the viscoelastic resistance on inspiratory time and respiratory frequency. Thus the homogeneous viscoelastic model appears suitable to describe respiratory system mechanical behavior under mechanical ventilation.

Influence of signal processing on estimation of respiratory impedance.

Respiratory impedance was estimated between 4 and 30 Hz by spectral analysis of the mouth flow and pressure signals measured in spontaneously breathing subjects when applying a pseudorandom pressure excitation at the mouth. The signals were submitted to antialiasing low-pass filtering followed by digital preprocessing before the calculation of spectra by a fast Fourier transform algorithm. The effectiveness of signal preprocessing in eliminating the leakage error due to breathing noise was illustrated in both a mechanical analogue and a patient. Five preprocessing techniques that combined high-pass filtering and windowing were then compared in 32 randomly selected patients by examining the influence of these techniques on 1) the values of impedance at 5, 10, and 20 Hz, and 2) the parameters of linear models fitting the real (Zr) and imaginary (Zi) parts of impedance for coherence values higher than a preset threshold. The impedance values and derived parameters were either the mean of the estimates separately obtained in the three data recordings (PA) or the single estimate obtained from average spectra (SP). Small but significant differences between filtering and windowing, as well as between SP and PA, were evidenced for the Zr, whereas Zi was only slightly sensitive to the type of averaging technique. We conclude that the signal preprocessing and data averaging techniques selected in this study have similar effects on spectral estimation of respiratory impedance.

Effects of sustained exercise on pulmonary clearance of aerosolized 99mTc-DTPA.

The effects of intensive prolonged exercise on the pulmonary clearance rate of aerosolized 99mTc-labeled diethylenetriaminepentaacetate (99mTc-DTPA) and pulmonary mechanics were studied in seven healthy nonsmoking volunteers. 99mTc-DTPA clearance and pulmonary mechanics (lung volumes and compliance) were assessed before and after 75 min of constant-load exercise performed on a treadmill, corresponding to 75% of maximal O2 uptake. Because both clearance measurements were made in similar conditions of pulmonary blood flow, respiratory rate, and tidal volume, changes in clearance rate can be assumed to represent changes of alveolar epithelial permeability. After exercise, total, apical, and basal clearance were significantly increased (P less than 0.01, 0.05, and 0.05, respectively) and the increases in total clearance and tidal volume observed during exercise were significantly correlated (P less than 0.05). In contrast, no significant change was found in pulmonary mechanics. These results show that prolonged intensive exercise induces an increase in epithelial permeability, which appears to be related to the mechanical effects of sustained increased ventilation. Because no change was evidenced in pulmonary volumes or in lung elasticity, our results suggest that this increase may result from alteration of the intercellular tight junctions rather than from a surfactant deficiency.

Influence of body temperature on histamine-induced bronchoconstriction in guinea pigs.

The effects of body temperature on histamine-induced bronchoconstriction were investigated in anesthetized, paralyzed, and mechanically ventilated guinea pigs. Four groups of guinea pigs were studied with constant body temperatures of 40, 38, 35, and 32 degrees C, respectively. Histamine was infused for 5 min at a rate of 50 ng.kg-1.s-1. Body cooling from 40 to 32 degrees C augmented the bronchomotor responses to histamine, which eventually rose almost fourfold. The enhancement of histamine-induced bronchoconstriction induced by body cooling was not suppressed by pretreating guinea pigs with 5 mg/kg hexamethonium or 5 mg/kg hexamethonium plus 3 mg/kg atropine; neither was the enhancement of histamine-induced bronchoconstriction suppressed in pithed guinea pigs, demonstrating that the autonomic nervous system is not involved in potentiating bronchoconstriction at low body temperatures. These results suggest that, at low body temperatures, increased airway responsiveness to histamine may be because of some direct effect of temperature on bronchial airway smooth muscle.

Respiratory resistance by end-inspiratory occlusion and forced oscillations in intubated patients.

Measurement of respiratory impedance by the forced oscillation technique (FOT) in intubated patients requires corrections for the flow-dependent resistance, inertance, and air compression inside the endotracheal tube (ETT). Recently, we published a method to correct respiratory impedance for the mechanical contribution of the ETT. To validate this correction, we compared the respiratory resistance obtained with this method (Rfo) to the intrinsic (Rmin) and total resistances (RT) measured by the airway-occlusion technique (OCT) in 16 intubated sedated paralyzed ventilated patients. The FOT was applied at functional residual capacity in the 4- to 32-Hz frequency range, whereas the OCT was performed at the end of a normal constant-flow inspiration. Rmin corrected with Rfo measured at 16 and 32 Hz [Rfo(16) = 1.10 x Rmin + 0.10 cmH2O.s.l-1, r = 0.96, P < 0.001; Rfo(32) = 0.93 x Rmin + 0.72 cmH2O.s.l-1, r = 0.97, P < 0.001]. RT corrected with Rfo at 4 Hz [Rfo(4) = 1.11 x RT - 1.48 cmH2O.s.l-1; = 0.92; P < 0.001]. We conclude that the FOT improved by correction for the behavior of the ETT is in good agreement with the OCT in intubated patients.

Pulmonary clearance and lung function: influence of acute tobacco intoxication and of vitamin E.

Cigarette smoking increases the alveolar epithelial permeability to small solutes, as assessed by the pulmonary clearance of aerosolized 99mTc-labeled diethylenetriaminepentaacetate. The involvement of lipid peroxidation in this increased clearance was tested in eight asymptomatic young smokers by investigating the effects of a 3-wk supplementation with oral vitamin E (1,000 IU/day) on pulmonary clearance according to a protocol designed as a single-blind crossover study. Indexes of acute tobacco intoxication (exhaled CO, carboxyhemoglobin, and urinary cotinine) and lung function parameters [including Krogh factor (KCO)] were also studied. Under control conditions, pulmonary clearance was abnormally increased (2.93 +/- 0.78%/min), whereas KCO was in the normal range. Pulmonary clearance correlated strongly with expired CO (P < 0.04), HbCO (P < 0.005), urinary cotinine (P < 0.003), and KCO (P < 0.004). Supplementation with vitamin E, a highly efficient antioxidant, neither decreased the pulmonary clearance nor altered the above correlations. However, the strong correlations observed between pulmonary clearance and indexes of acute tobacco intoxication, which reflect the amount of inhaled smoke and the resultant oxidant stress, do not allow exclusion of the involvement of lipid peroxidation in the pulmonary clearance increase observed in smokers.

Vitamin E does not prevent exercise-induced increase in pulmonary clearance.

It has been observed that sustained exercise results in a prolonged increase in alveolar epithelial permeability, as assessed by the pulmonary clearance rate of aerosolized 99mTc-labeled diethylenetriaminepentaacetate (Lorino et al. J. Appl. Physiol. 67: 2055-2059, 1989). The involvement of lipid peroxidation in this increased permeability was tested in seven nonsmoking volunteers by comparing the exercise-induced increases in pulmonary 99mTc-diethylenetriaminepentaacetate clearance before and after a 3-wk supplementation with oral vitamin E (1,000 IU/day), according to a protocol designed as a single-blind crossover study. The 60-min exercise was performed on a treadmill at a constant load corresponding to 80% of maximal O2 uptake. Administration of vitamin E, a very important antioxidant, did not reduce the exercise-induced increase in lung clearance, suggesting that the exercise-induced increase in lung epithelial permeability does not primarily result from the occurrence of lipid peroxidation in the alveolar membrane. This result thus corroborates the hypothesis of an alteration of the intercellular tight junctions due to the mechanical effects of hyperventilation.

Effects of continuous negative airway pressure on lung volume and respiratory resistance.

This study was designed to determine the responses of lung volume and respiratory resistance (Rrs) to decreasing levels of continuous negative airway pressure (CNAP). Twenty normal subjects were studied in the basal state and under CNAP levels of -5, -10, and -15 hPa. Rrs was measured by the forced oscillation technique (4-32 Hz). End-expiratory lung volume (EELV) and tidal volume (VT) were measured by whole body plethysmography. Rrs was extrapolated to 0 Hz (R(0)) and estimated at 16 Hz (R(16)) by linear regression analysis of Rrs vs. frequency. Specific Rrs, SR(0) and SR(16), were then calculated as R(0) (EELV + VT/2) and R(16) (EELV + VT/2), respectively. EELV significantly decreased, whereas R(0), R(16), SR(0), and SR(16) significantly increased, as the CNAP level decreased (P < 0.0001 for all). At the lowest CNAP level, R(0) and R(16) reached 198 +/- 13 and 175 +/- 9% of their respective basal values. The CNAP-induced increase in R(0) was significantly higher than that in R(16) (P < 0.004). Our results demonstrate that the CNAP-induced increase in Rrs does not result from a direct lung volume effect only and strongly suggest the involvement of other factors affecting both intrathoracic and extrathoracic airway caliber.

Influence of tidal volume on histamine-induced bronchoconstriction in guinea pigs.

The effects of tidal volume amplitude on bronchopulmonary reactivity were investigated in three groups of 14 anesthetized paralyzed mechanically ventilated guinea pigs. Animals of group 1 served as control; in animals of group 2, both the sympathetic and parasympathetic nervous systems were blocked; in animals of group 3, only the parasympathetic system was blocked. In each group, the animals were randomly divided into two subgroups characterized by their ventilatory pattern: rate of 60/min with a 6-ml/kg tidal volume or rate of 40/min with a 9-ml/kg tidal volume. Bronchopulmonary reactivity to infused histamine was assessed by the respiratory compliance and conductance values measured during bronchoconstriction and expressed as a percentage of the corresponding basal values. In group 1 the animals ventilated with a 9-ml/kg tidal volume were found significantly less reactive than those ventilated with a 6-ml/kg tidal volume. This difference was abolished in groups 2 and 3. These results demonstrate that the effects of increased tidal volume on bronchopulmonary reactivity are vagally mediated and suggest that the decrease observed in histamine-induced bronchoconstriction is mainly due to reflex effects evoked by stretch receptor stimulation.

Heavy snoring with upper airway resistance syndrome may induce intrinsic positive end-expiratory pressure.

We studied eight heavy snorers with upper airway resistance syndrome to investigate potential effects of sleep on expiratory airway and lung resistance, intrinsic positive end-expiratory pressure, hyperinflation, and elastic inspiratory work of breathing (WOB). Wakefulness and non-rapid-eye-movement sleep with high- and with low-resistance inspiratory effort (H-RIE and L-RIE, respectively) were compared. No differences in breathing pattern were seen across the three conditions. In contrast, we found increases in expiratory airway and lung resistance during H-RIE compared with L-RIE and wakefulness (56 +/- 24, 16 +/- 4, and 11 +/- 4 cmH2O . 1(-1) . s, respectively), with attendant increases in intrinsic positive end-expiratory pressure (5.4 +/- 1.8, 1.4 +/- 0.5, and 1.3 +/- 1.3 cmH2O, respectively) and elastic WOB (6.1 +/- 2.2, 3.7 +/- 1.2, and 3.4 +/- 0.7 J/min, respectively). The increase in WOB during H-RIE is partly caused by the effects of dynamic pulmonary hyperinflation produced by the increased expiratory resistance. Contrary to the Starling model, a multiple-element compliance model that takes into account the heterogeneity of the pharynx may explain flow limitation during expiration.

Inspiratory work of breathing in ventilated preterm infants.

In ventilated newborns, part of the inspiratory work of breathing (WOB) may be due to the inspiratory efforts preceding inspiratory ventilator flow. This study was designed to quantify the contribution of these efforts to WOB. WOB was evaluated in six intubated preterm infants ventilated by the Dräger Babylog 8000. The ventilatory modes studied were intermittent mandatory ventilation (IMV), continuous positive airway pressure (CPAP), and assist-control ventilation at 10 (ACV10) and 15 (ACV15) cmH2O peak pressure. Mouth flow (V) and esophageal pressure (Pe) were recorded, and WOB was estimate from the area delineated by the esophageal pressure-volume curve, where volume is the time integral of V. Calculation of WOB started either at the onset of the infant's inspiratory flow (WOBi), or at the beginning of the infant's inspiratory muscle efforts, detected on Pe and confirmed on the V tracing (WOBm). WOBm was found to be significantly higher than WOBi under all ventilatory conditions studied. The difference in work of breathing (delta W) between WOBm and WOBi did not depend on the type of ventilatory mode. When delta W was related to WOBm, it amounted to about 30% of WOBm in IMV and CPAP, and 60% in ACV (P < 0.05, ACV15 vs. IMV). These results suggest that, in preterm infants connected to a ventilator, inspiratory efforts preceding flow inspiration might account for a large fraction of the inspiratory work of breathing.