Increasing ventilator surge capacity in COVID 19 pandemic: design, manufacture and in vitro-in vivo testing in anaesthetized healthy pigs of a rapid prototyped mechanical ventilator.

OBJECTIVE: The advent of new technologies has made it possible to explore alternative ventilator manufacturing to meet the worldwide shortfall for mechanical ventilators especially in pandemics. We describe a method using rapid prototyping technologies to create an electro-mechanical ventilator in a cost effective, timely manner and provide results of testing using an in vitro-in vivo testing model. RESULTS: Rapid prototyping technologies (3D printing and 2D cutting) were used to create a modular ventilator. The artificial manual breathing unit (AMBU) bag connected to wall oxygen source using a flow meter was used as air reservoir. Controlled variables include respiratory rate, tidal volume and inspiratory: expiratory (I:E) ratio. In vitro testing and In vivo testing in the pig model demonstrated comparable mechanical efficiency of the test ventilator to that of standard ventilator but showed the material limits of 3D printed gears. Improved gear design resulted in better ventilator durability whilst reducing manufacturing time (< 2-h). The entire cost of manufacture of ventilator was estimated at 300 Australian dollars. A cost-effective novel rapid prototyped ventilator for use in patients with respiratory failure was developed in < 2-h and was effective in anesthetized, healthy pig model.

Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome.

OBJECTIVE: It has proved that muscle paralysis was more protective for injured lung in severe acute respiratory distress syndrome (ARDS), but the precise mechanism is not clear. The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS. METHODS: Eighteen male Beagles were studied under mechanical ventilation with anesthesia. Severe ARDS was induced by repetitive oleic acid infusion. After lung injury, Beagles were randomly assigned into spontaneous breathing group (BIPAPSB) and abdominal muscle paralysis group (BIPAPAP). All groups were ventilated with BIPAP model for 8h, and the high pressure titrated to reached a tidal volume of 6ml/kg, the low pressure was set at 10 cmH2O, with I:E ratio 1:1, and respiratory rate adjusted to a PaCO2 of 35-60 mmHg. Six Beagles without ventilator support comprised the control group. Respiratory variables, end-expiratory volume (EELV) and gas exchange were assessed during mechanical ventilation. The levels of Interleukin (IL)-6, IL-8 in lung tissue and plasma were measured by qRT-PCR and ELISA respectively. Lung injury scores were determined at end of the experiment. RESULTS: For the comparable ventilator setting, as compared with BIPAPSB group, the BIPAPAP group presented higher EELV (427±47 vs. 366±38 ml) and oxygenation index (293±36 vs. 226±31 mmHg), lower levels of IL-6(216.6±48.0 vs. 297.5±71.2 pg/ml) and IL-8(246.8±78.2 vs. 357.5±69.3 pg/ml) in plasma, and lower express levels of IL-6 mRNA (15.0±3.8 vs. 21.2±3.7) and IL-8 mRNA (18.9±6.8 vs. 29.5±7.9) in lung tissues. In addition, less lung histopathology injury were revealed in the BIPAPAP group (22.5±2.0 vs. 25.2±2.1). CONCLUSION: Abdominal muscle activity during mechanically ventilation is one of the injurious factors in severe ARDS, so abdominal muscle paralysis might be an effective strategy to minimize ventilator-induce lung injury.

Work of Breathing into Snow in the Presence versus Absence of an Artificial Air Pocket Affects Hypoxia and Hypercapnia of a Victim Covered with Avalanche Snow: A Randomized Double Blind Crossover Study.

Presence of an air pocket and its size play an important role in survival of victims buried in the avalanche snow. Even small air pockets facilitate breathing. We hypothesize that the size of the air pocket significantly affects the airflow resistance and work of breathing. The aims of the study are (1) to investigate the effect of the presence of an air pocket on gas exchange and work of breathing in subjects breathing into the simulated avalanche snow and (2) to test whether it is possible to breathe with no air pocket. The prospective interventional double-blinded study involved 12 male volunteers, from which 10 completed the whole protocol. Each volunteer underwent two phases of the experiment in a random order: phase "AP"--breathing into the snow with a one-liter air pocket, and phase "NP"--breathing into the snow with no air pocket. Physiological parameters, fractions of oxygen and carbon dioxide in the airways and work of breathing expressed as pressure-time product were recorded continuously. The main finding of the study is that it is possible to breath in the avalanche snow even with no air pocket (0 L volume), but breathing under this condition is associated with significantly increased work of breathing. The significant differences were initially observed for end-tidal values of the respiratory gases (EtO2 and EtCO2) and peripheral oxygen saturation (SpO2) between AP and NP phases, whereas significant differences in inspiratory fractions occurred much later (for FIO2) or never (for FICO2). The limiting factor in no air pocket conditions is excessive increase in work of breathing that induces increase in metabolism accompanied by higher oxygen consumption and carbon dioxide production. The presence of even a small air pocket reduces significantly the work of breathing.

Differences in the peak cough flow among stroke patients with and without dysphagia.

Coughing is an important protective mechanism for keeping the airway clear, and adequate voluntary coughing reduces the risk of aspiration in patients with deglutition disorders. The purpose of this study was to compare the peak cough flow (PCF) of stroke patients with and without dysphagia and to identify the physical and respiratory determinants of PCF.Using a spirometer, we measured and compared the PCFs of 10 stroke patients with dysphagia (SPD), 20 stroke patients without dysphagia (SP) and 10 gender and age matched healthy controls (HC) recruited by using a notice at a clinic and in newspapers. The PCF of the SPD (mean ± SD, 160.1 ± 68.7 l/min) was significantly lower than that of the SP and HC (297.2 ± 114.2 l/min and 462.0 ± 84.4 l/min, respectively; one-way ANOVA, Scheffe's test, P < 0.05). The vital capacity (VC) and inspiratory reserve volume (IRV) of the SPD were lower than those of the HC. Stepwise multivariate regression analysis revealed that IRV and ambulation function (Functional Ambulation Categories, FAC) contributed 50% and 17% to the variance of PCF (P < 0.05), respectively. It is suggested that respiratory function, especially IRV, is important for maintaining PCF in SPD.

Effect of hormone replacement on exercise cardiopulmonary reserve and recovery performance in subclinical hypothyroidism.

Subclinical hypothyroidism (SH) patients present cardiopulmonary, vascular and muscle dysfunction, but there is no consensus about the benefits of levothyroxine (L-T4) intervention on cardiopulmonary performance during exercise. The aim of the present study was to investigate the effects of L-T4 on cardiopulmonary exercise reserve and recovery in SH patients. Twenty-three SH women, 44 (40-50) years old, were submitted to two ergospirometry tests, with an interval of 6 months of normalization of thyroid-stimulating hormone (TSH) levels (L-T4 replacement group) or simple observation (TSH = 6.90 µIU/mL; L-T4 = 1.02 ng/dL). Patients with TSH >10 µIU/mL were excluded from the study to assure that they would receive treatment in this later stage of SH. Twenty 30- to 57-year-old women with no thyroid dysfunction (TSH = 1.38 µIU/mL; L-T4 = 1.18 ng/dL) were also evaluated. At baseline, lower values of gas exchange ratio reserve (0.24 vs 0.30; P < 0.05) were found for SH patients. The treated group presented greater variation than the untreated group for pulmonary ventilation reserve (20.45 to 21.60 L/min; median variation = 5.2 vs 25.09 to 22.45 L/min; median variation = -4.75, respectively) and for gas exchange ratio reserve (0.19 to 0.27; median variation = 0.06 vs 0.28 to 0.18; median variation = -0.08, respectively). There were no relevant differences in cardiopulmonary recovery for either group at baseline or after follow-up. In the sample studied, L-T4 replacement improved exercise cardiopulmonary reserve, but no modification was found in recovery performance after exercise during this period of analysis.

Effect of hormone replacement on exercise cardiopulmonary reserve and recovery performance in subclinical hypothyroidism

Subclinical hypothyroidism (SH) patients present cardiopulmonary, vascular and muscle dysfunction, but there is no consensus about the benefits of levothyroxine (L-T4) intervention on cardiopulmonary performance during exercise. The aim of the present study was to investigate the effects of L-T4 on cardiopulmonary exercise reserve and recovery in SH patients. Twenty-three SH women, 44 (40-50) years old, were submitted to two ergospirometry tests, with an interval of 6 months of normalization of thyroid-stimulating hormone (TSH) levels (L-T4 replacement group) or simple observation (TSH = 6.90 μIU/mL; L-T4 = 1.02 ng/dL). Patients with TSH >10 μIU/mL were excluded from the study to assure that they would receive treatment in this later stage of SH. Twenty 30- to 57-year-old women with no thyroid dysfunction (TSH = 1.38 μIU/mL; L-T4 = 1.18 ng/dL) were also evaluated. At baseline, lower values of gas exchange ratio reserve (0.24 vs 0.30; P < 0.05) were found for SH patients. The treated group presented greater variation than the untreated group for pulmonary ventilation reserve (20.45 to 21.60 L/min; median variation = 5.2 vs 25.09 to 22.45 L/min; median variation = -4.75, respectively) and for gas exchange ratio reserve (0.19 to 0.27; median variation = 0.06 vs 0.28 to 0.18; median variation = -0.08, respectively). There were no relevant differences in cardiopulmonary recovery for either group at baseline or after follow-up. In the sample studied, L-T4 replacement improved exercise cardiopulmonary reserve, but no modification was found in recovery performance after exercise during this period of analysis.

Respiratory muscle strength in pregnancy.

BACKGROUND: Muscle respiratory strength studies during pregnancy are very scarce. The aim of this paper is to describe maximum inspiratory (PImax) and expiratory (PEmax) mean pressure values in women during their first pregnancy and to determine the relationship between the anthropometric, morphologic and physiologic variables of these pressures. METHODS: One hundred and twenty women (120) primigravidas were studied from the 5th to 40th gestational week, ages ranging from 20 to 29 years old, euthrophic and with low risk pregnancies. RESULTS: PImax and PEmax mean values were 88.5 ± 16.52 cmH(2)O and 99.76 ± 18.19 cmH(2)O respectively. There was no association between gestational age and PImax (r = -0.06; p = 0.49) or PEmax (r = -0.11; p = 0.22). There was also no difference between PImax and PEmax during pregnancy trimesters and no correlation between pregnancy age and the pressures in each trimester. Height was the only anthropometric variable indicating a significant PImax (r = 0.20; p = 0.02) association. Fundal uterus height and inter-recti abdominis distance were not associated to respiratory pressure values. PEmax is not associated with the group of predictor variables (p = 0.127) and PImax demonstrated an independent association with height and dyspnea during physical exertion reflected by the following equation: PImax = 0.6 + 57.9 height - 1.68 dyspnea under effort. The present study suggests that inspiratory and expiratory maximum pressure values are not altered during different stages of pregnancy, however longitudinal studies are needed to assess changes over time.

Disfunción autonómica en pacientes con enfermedad pulmonar obstructiva crónica: efectos del entrenamiento sobre la recuperación de la frecuencia cardiaca / Autonomic dysfunction in patients with chronic obstructive pulmonary disease: Effects of training on heart rate recovery

Introducción: La recuperación de la frecuencia cardíaca (RFC) tras un esfuerzo máximo es un índice de función autonómica y se asocia con mayor mortalidad en algunas patologías. El objetivo de este estudio fue evaluar la prevalencia de disfunción autonómica en pacientes con enfermedad pulmonar obstructiva crónica (EPOC) estable y sus eventuales cambios con un programa de rehabilitación pulmonar. Pacientes y métodos: Estudio transversal de 68 pacientes con EPOC en fase estable (edad media: 71 años [DE: 8]), 65 hombres y 3 mujeres, volumen espiratorio forzado en el primer segundo (%) medio: 36,8 (DE: 11,9), incluidos en programa de entrenamiento aeróbico y de fuerza y resistencia (25 sesiones). Se realizó prueba de esfuerzo cardiopulmonar (PECP), prerrehabilitación en todos los pacientes. En un subgrupo de 12 se realizó, además, PECP posrehabilitación. Se evaluó la RFC en valores absolutos y categorizada tras claudicación en la PECP respecto a la frecuencia cardíaca pico (normalidad RFC>12). Resultados: Hubo 52 (76,5%) pacientes con alteración de la RFC (cambios<12lpm en el primer minuto de la recuperación). La RCF no se asoció con la severidad de la EPOC, la gasometría ni los valores de DLCO. En el subgrupo con PECP, el entrenamiento mejoró la RFC en 4 (80%) y la normalizó en 3 (50%). No se observaron complicaciones durante la rehabilitación en ninguno de los pacientes con disfunción autonómica. Conclusiones: La disfunción autonómica es muy prevalente en pacientes con EPOC estable independientemente de la severidad de la enfermedad, y su relevancia ha sido subestimada. La rehabilitación pulmonar es segura en estos pacientes y modifica el grado de esta disfunción autonómica con tendencia beneficiosa. Si la morbilidad y la supervivencia de los pacientes tienen relación con la disfunción autonómica también en nuestro medio merece ser evaluada (AU)

Introduction: Heart rate recovery (HRR) after maximal effort is an indicator of autonomic function and is related to mortality in different diseases. This study was aimed to estimate prevalence of autonomic dysfunction in patients with chronic obstructive pulmonary disease (COPD) and assess potential clinical effects of a pulmonary rehabilitation program (PRP). Patients and methods: Transversal study of 68 stable COPD patients (71±8 years; 65 men and 3 women; FEV1 36.8±11.9%) who received a PRP consisting of 5-week general and specific training (25 sessions). Cycle ergometry test (CET) was performed in all patients prior to the PRP. In a subset of 12 patients, CET was performed both previously and after rehabilitation. The primary end point was the prevalence of autonomic dysfunction as assessed by abnormal heart rate recovery in the first minute of recovery following a maximal symptom limited CET, and the potential changes following a normalised PRP. Results: A total of 52 (76.5%) patients showed abnormal HRR (i.e. change from peak exercise to first recovery minute <12bpm). HRR was not associated with the severity of COPD, arterial blood gases or DLCO values. The PRP induced significant changes in exercise capacity which was related to improvement of HRR in 4 (80%) and was normalised in 3 (50%). No complications or adverse effects were observed during rehabilitation. Conclusions Autonomic dysfunction is a highly prevalent impairment in COPD patients, irrespective the severity of the disease as assessed by conventional pulmonary function test. Relevance of autonomic dysfunction has been understimated in COPD. Pulmonary rehabilitation is safe and modifies the degree of autonomic dysfunction with potential benefits. The relatioship of morbidity and mortality with autonomic dysfunction in COPD in our setting remains to be evaluated (AU)

Dynamic hyperinflation during daily activities: does COPD global initiative for chronic obstructive lung disease stage matter?

BACKGROUND: One of the contributors to exercise limitation in COPD is dynamic hyperinflation. Although dynamic hyperinflation appears to occur during several exercise protocols in COPD and seems to increase with increasing disease severity, it is unknown whether dynamic hyperinflation occurs at different severity stages according to the Global initiative for chronic Obstructive Lung Disease (GOLD) in daily life. The present study, therefore, aimed to compare dynamic hyperinflation between COPD GOLD stages II-IV during daily activities. METHODS: Thirty-two clinically stable patients with COPD GOLD II (n = 10), III (n = 12), and IV (n = 10) participated in this study. Respiratory physiology during a daily activity was measured at patients' homes with Oxycon Mobile. Inspiratory capacity maneuvers were performed at rest, at 2-min intervals during the activity, and at the end of the activity. Change in inspiratory capacity is commonly used to reflect change in end-expiratory lung volume (DeltaEELV) and, therefore, dynamic hyperinflation. The combination of static and dynamic hyperinflation was reflected by inspiratory reserve volume (IRV) during the activity. RESULTS: Overall, increase in EELV occurred in GOLD II-IV without significant difference between the groups. There was a tendency for a smaller DeltaEELV in GOLD IV. DeltaEELV was inversely related to static hyperinflation. IRV during the daily activity was related to the level of airflow obstruction. CONCLUSIONS: Dynamic hyperinflation occurs independent of GOLD stage during real-life daily activities. The combination of static and dynamic hyperinflation, however, increases with increasing airflow obstruction.

Performance during constant workrate cycling exercise in women with COPD and hyperinflation.

We aimed to characterize gender differences in exercise endurance, operating lung volumes and symptoms limitation during exercise in patients with COPD. Ninety-three women and 93 men with COPD matched for age and disease severity were evaluated during symptom-limited constant-work rate cycle exercise at 75% of peak capacity. Breathing pattern, inspiratory capacity, dyspnoea and leg discomfort Borg scores were recorded during exercise. Endurance time was shorter in women compared to men. Inspiratory capacity decreased at a similar rate during exercise in women and men (0.71 vs. 0.81 ml x s(- 1) for women and men respectively, p = 0.47) despite lower ventilation at end-exercise in women. At end-exercise, women showed lower inspiratory reserve volume (p < 0.005). Dyspnoea responses during exercise occurred with a steep rise near end-exercise, when inspiratory reserve volume approached a critical value, at 10% of total lung capacity, this onset of dyspnoea acceleration occurred earlier in women (p < 0.0001). At the same relative exercise intensity, women with COPD had lower endurance time than men. Compared to men, women with COPD were disadvantaged during exercise as they reached a critical inspiratory reserve volume earlier, leading to a steep increase in dyspnoea and to exercise termination.

Effects of depth and chest volume on cardiac function during breath-hold diving.

Cardiac response to breath-hold diving in human beings is primarily characterized by the reduction of both heart rate and stroke volume. By underwater Doppler-echocardiography we observed a "restrictive/constrictive" left ventricular filling pattern compatible with the idea of chest squeeze and heart compression during diving. We hypothesized that underwater re-expansion of the chest would release heart constriction and normalize cardiac function. To this aim, 10 healthy male subjects (age 34.2 +/- 10.4) were evaluated by Doppler-echocardiography during breath-hold immersion at a depth of 10 m, before and after a single maximal inspiration from a SCUBA device. During the same session, all subjects were also studied at surface (full-body immersion) and at 5-m depth in order to better characterize the relationship of echo-Doppler pattern with depth. In comparison to surface immersion, 5-m deep diving was sufficient to reduce cardiac output (P = 0.042) and increase transmitral E-peak velocity (P < 0.001). These changes remained unaltered at a 10-m depth. Chest expansion at 10 m decreased left ventricular end-systolic volume (P = 0.024) and increased left ventricular stroke volume (P = 0.024). In addition, it decreased transmitral E-peak velocity (P = 0.012) and increased deceleration time of E-peak (P = 0.021). In conclusion the diving response, already evident during shallow diving (5 m) did not progress during deeper dives (10 m). The rapid improvement in systolic and diastolic function observed after lung volume expansion is congruous with the idea of a constrictive effect on the heart exerted by chest squeeze.

Lung function reference values in Iranian adolescents.

There is insufficient information about reference values for pulmonary volumes for Iranian populations. A study of lung function parameters was made on 302 non-smoking healthy Iranian students (152 male and 150 female). Lung function measures correlated strongly with height but not with body mass index. There were significant differences between some of the measured parameters and American Thoracic Society reference values for Caucasians (P < 0.05). Of note is the high functional residual capacity (110% higher) and low inspirational capacity (86% lower) in males compared with the reference values.

Normal variability of the peak-to-trough amplitude of isointegral QRST body surface maps.

The peak-to-trough amplitude (sum of absolute values of maximum and minimum) of an isointegral QRST body surface map was shown, according to literary data, to be sensitive to changes in ventricular sympathetic tone. Statistics of this parameter were obtained, with an 80 electrodes array, in 135 healthy subjects of both sexes, aged from 10 to 67 years (37 +/- 16). The QRST amplitudes were smaller in females than in males in average by 28% (P < .0001). They decreased with increasing age (r = -0.237, P < .01). Larger QRST amplitudes went with longer RR intervals (r = .449, P < .0001). In held deep inspiration, the amplitude decreased in 79% and increased in 21% of subjects. The change of the amplitude was related to the inspiratory change of the RR interval (r = .343, P < .0001), but not to the RR interval preceding the deep inspiration. Body mass index and somatometric characteristics of chest configuration did not significantly affect the QRST amplitude. The results may serve as a basis for further studies on the usefulness of the QRST amplitude as another variable reflecting changes of ventricular recovery properties.

Hyperventilation with He-O2 breathing is not decreased by superimposed external resistance.

The purpose of this study was to determine the effect of imposed external resistance on the ventilatory response to He-O(2) breathing during peak exercise. To accomplish this purpose, separate inspiratory and expiratory external resistances were applied to offset for the decrease in intrapulmonary airway resistance with He-O(2) breathing. Seven men and three women (69+/-3 years, mean+/-S.D.) with normal pulmonary function performed graded cycle ergometry to exhaustion breathing room air, He-O(2) (79% He, 21% O(2)), He-O(2) with imposed expiratory resistance, and He-O(2) with imposed inspiratory resistance. Ventilation (VE), lung mechanics, and PET(CO(2)) were measured during each 1 min increment in work rate and were analyzed by one-way ANOVA for repeated measures at rest, ventilatory threshold (VTh), and peak exercise. In response, VE was increased and PET(CO(2)) was decreased at VTh (P<0.01) and peak exercise (P<0.01) whenever breathing He-O(2). Thus, VE was increased during exercise above VTh with He-O(2) breathing regardless of increases in inspiratory or expiratory external resistance. In conclusion, these data suggest that inspiratory resistive unloading is no more important than expiratory resistive unloading to the increase in VE with He-O(2) breathing during heavy and peak exercise.

Comparison of the hyperoxic test and the alternate breath test in infants.

Peripheral chemoreceptor function has been tested using either the hyperoxic test (HT), which decreases minute ventilation (V E) by causing physiologic chemodenervation, or the alternate breath test (ABT), which induces V E alternations by delivering rapid hypoxic stimuli through breath-by-breath alternations in fractional inspired O(2) between normoxia (0.21) and hypoxia (0.15). No previous studies have compared ventilatory responses to both tests in the same infants. We hypothesized that the V E decrease during HT would be significantly related to V E alternations during ABT. Eighteen infants (postnatal age 21 +/- 14 d) underwent two 30-s HTs and two ABTs (quiet sleep, face mask, and pneumotachograph; mass spectrometry measurement of inspired and expired O(2) and CO(2) fractions; and breath-by-breath analysis). The tests were done in random order. Decreases in V E and mean inspiratory flow (tidal volume over inspiratory time, VT/TI) during HTs were significantly correlated to their respective percentage coefficients of alternation during ABTs (r = 0.69 and 0.70, respectively, p < 0.01). Principal components analysis showed that the V E and VT/TI decreases during HTs were due chiefly to a fall in VT, whereas V E and VT/TI alternations were ascribable to alternations in both VT and TI. Intraindividual coefficients of variation of V E changes were significantly lower during HTs than during ABTs. We conclude that (1) ventilatory responses to HT and ABT are significantly correlated despite differences in the mechanisms of the V E changes; (2) the better reproducibility of the V E response to HT as compared with ABT may be an advantage in clinical practice.

Periodic variation in inspiratory volume characterizes speech as well as quiet breathing.

Variability in inspired lung volume prior to speech is only partially accounted for by speech-related concerns such as the length and loudness of the planned utterance. Control mechanisms known to influence volume variability in non-speech breathing could potentially account for some of this variability, but only if they operate during speech as well. This investigation was designed to test for the presence of several such mechanisms during reading aloud. Lung volumes were recorded from 5 normal females as they read silently, then aloud. Inspired volumes were correlated with the volumes of the previous and following expirations and with inspiratory duration. Coefficients of variation were calculated for inspiratory volume, duration, and mean flow. Time-series analyses were used to compare periodicity in inspired volume for quiet and speech breathing. Control mechanisms operating during both quiet breathing and reading aloud included slow oscillations in inspired volume and minimized variability in mean flow. Inspired volume prior to speech was weakly but significantly correlated with preceding and following expired volume. It is concluded that some control strategies typical of quiet breathing contribute to volume variability in speech breathing.

Measurement of thoracic gas volume in patients born prematurely: should occlusion be made at end-inspiration or end-expiration?

It has been suggested that in infants born at term thoracic gas volume (TGV) may be more accurately estimated in a plethysmograph if end-inspiratory (TGVl) rather than end-expiratory (TGVE) occlusions are used. The aim of this study was to assess whether the timing of occlusion affected TGV results in patients born very prematurely. Fifteen children with a median gestational age of 28 weeks (range 23-34) and postnatal age of 10 months (range 6-24) were studied. Measurements of TGV and airway resistance (R(aw)) were made in a whole body plethysmograph after sedation with chloral hydrate. End-expiratory and end-inspiratory occlusions were performed randomly in each subject. Overall, TGVl was significantly lower than TGVE (median, TGVl 233 mL; range, 130-498. Median TGVE 250 mL; range, 132-604; P < 0.05; 95% confidence intervals for the difference, 4-50 mL). In 13 infants, TGVl was lower than TGVE; the remaining two patients did not differ significantly from the rest of the group and neither had neonatal chronic lung disease. In only five infants did TGVl lie below the 95% confidence intervals of TGVE, however, two-way analysis of variance with replicated measurements showed a significant difference between TGVE and TGVl (P < 0.05). The median R(aw) was 55 cmH2O/L/s (range, 36-71). A significant positive correlation was found between R(aw) and TGVE-TGVl (r2 = 0.5, P < 0.01). We conclude that in children born very prematurely and with high R(aw) occlusion at end-expiration rather than end-inspiration yields higher TGV results at follow-up.