Differences In Lung Compliance Research Articles

Serum cytokine dysregulation signatures associated with COVID-19 outcomes in high mortality intensive care unit cohorts across pandemic waves and variants

The aim of this study was to characterize the systemic cytokine signature of critically ill COVID-19 patients in a high mortality setting aiming to identify biomarkers of severity, and to explore their associations with viral loads and clinical characteristics. We studied two COVID-19 critically ill patient cohorts from a referral centre located in Central Europe. The cohorts were recruited during the pre-alpha/alpha (November 2020 to April 2021) and delta (end of 2021) period respectively. We determined both the serum and bronchoalveolar SARS-CoV-2 viral load and identified the variant of concern (VoC) involved. Using a cytokine multiplex assay, we quantified systemic cytokine concentrations and analyzed their relationship with clinical findings, routine laboratory workup and pulmonary function data obtained during the ICU stay. Patients who did not survive had a significantly higher systemic and pulmonary viral load. Patients infected with the pre-alpha VoC showed a significantly lower viral load in comparison to those infected with the alpha- and delta-variants. Levels of systemic CTACK, M-CSF and IL-18 were significantly higher in non-survivors in comparison to survivors. CTACK correlated directly with APACHE II scores. We observed differences in lung compliance and the association between cytokine levels and pulmonary function, dependent on the VoC identified. An intra-cytokine analysis revealed a loss of correlation in the non-survival group in comparison to survivors in both cohorts. Critically ill COVID-19 patients exhibited a distinct systemic cytokine profile based on their survival outcomes. CTACK, M-CSF and IL-18 were identified as mortality-associated analytes independently of the VoC involved. The Intra-cytokine correlation analysis suggested the potential role of a dysregulated systemic network of inflammatory mediators in severe COVID-19 mortality.

MANAGEMENT OF PNEUMOTHORAX AND PNEUMOMEDIASTINUM IN COVID-19 PATIENTS WITH ARDS

SESSION TITLE: What Lessons Will We Take From the Pandemic?SESSION TYPE: Rapid Fire Original InvPRESENTED ON: 10/19/2022 11:15 am - 12:15 pmPURPOSE: Since the emergence of COVID-19, many serious complications have arisen especially in the setting of Acute Respiratory Distress Syndrome (ARDS) in the intensive care unit. Historically, ARDS and mechanical ventilation is associated with higher rates of pneumothorax. It has been well described that ARDS is the result of inflammatory lung injury, with increased activation of circulating neutrophils, complement and proinflammatory mediators leading to loss of surfactant, alveolar atelectasis, and fibrin deposition. This leads to a less compliant lung parenchyma, and higher airway pressures, which has been attributed as a risk factor for pneumothorax. The management of pneumothorax varies depending on the etiology of the pneumothorax. In the case of iatrogenic pneumothorax (i.e. mechanical ventilation), tube thoracostomy is generally recommended, however the size of the chest tube inserted remains less clear.METHODS: This is a multi-center retrospective cohort study of 88 hospitalized patients with a diagnosis of COVID-19 and pneumothorax or pneumomediastinum between the dates of 3/11/2020 to 01/26/2021. Patient demographics, comorbidities, laboratory and hemodynamic data were collected as well as ventilator settings, lung mechanics, and clinical patient outcome data including type of intervention and rate of resolution of pneumothorax. Final statistical analysis is pending.RESULTS: Our preliminary results reveal that there was a higher rate of resolution of pneumothorax with a large bore chest tube (LBCT) compared to a small bore chest tube (SBCT). There was no significant difference in lung compliance or tidal volume in cc/kg between the patients with a resolving pneumothorax compared to the patients with a nonresolving pneumothorax. Overall mortality rate among all patients was 70.4%.CONCLUSIONS: Patients with a large bore chest tube placed are more likely to have resolution of pneumothorax compared to small bore chest tube or serial X-ray. Lung compliance and tidal volume were not significantly different between patients that had a resolving pneumothorax compared to nonresolving pneumothorax. It is important to manage a pneumothorax early on to reduce associated morbidity.CLINICAL IMPLICATIONS: The development of pneumothorax in COVID patients with ARDS has significant associated morbidity and mortality. Utilization of a large bore chest tube may result in improved rates of resolution of pneumothorax.DISCLOSURES: No relevant relationships by Nathalie AntoniosNo relevant relationships by Colby BakerNo relevant relationships by Jessica JohnsonNo relevant relationships by Karen Sayad SESSION TITLE: What Lessons Will We Take From the Pandemic? SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Since the emergence of COVID-19, many serious complications have arisen especially in the setting of Acute Respiratory Distress Syndrome (ARDS) in the intensive care unit. Historically, ARDS and mechanical ventilation is associated with higher rates of pneumothorax. It has been well described that ARDS is the result of inflammatory lung injury, with increased activation of circulating neutrophils, complement and proinflammatory mediators leading to loss of surfactant, alveolar atelectasis, and fibrin deposition. This leads to a less compliant lung parenchyma, and higher airway pressures, which has been attributed as a risk factor for pneumothorax. The management of pneumothorax varies depending on the etiology of the pneumothorax. In the case of iatrogenic pneumothorax (i.e. mechanical ventilation), tube thoracostomy is generally recommended, however the size of the chest tube inserted remains less clear. METHODS: This is a multi-center retrospective cohort study of 88 hospitalized patients with a diagnosis of COVID-19 and pneumothorax or pneumomediastinum between the dates of 3/11/2020 to 01/26/2021. Patient demographics, comorbidities, laboratory and hemodynamic data were collected as well as ventilator settings, lung mechanics, and clinical patient outcome data including type of intervention and rate of resolution of pneumothorax. Final statistical analysis is pending. RESULTS: Our preliminary results reveal that there was a higher rate of resolution of pneumothorax with a large bore chest tube (LBCT) compared to a small bore chest tube (SBCT). There was no significant difference in lung compliance or tidal volume in cc/kg between the patients with a resolving pneumothorax compared to the patients with a nonresolving pneumothorax. Overall mortality rate among all patients was 70.4%. CONCLUSIONS: Patients with a large bore chest tube placed are more likely to have resolution of pneumothorax compared to small bore chest tube or serial X-ray. Lung compliance and tidal volume were not significantly different between patients that had a resolving pneumothorax compared to nonresolving pneumothorax. It is important to manage a pneumothorax early on to reduce associated morbidity. CLINICAL IMPLICATIONS: The development of pneumothorax in COVID patients with ARDS has significant associated morbidity and mortality. Utilization of a large bore chest tube may result in improved rates of resolution of pneumothorax. DISCLOSURES: No relevant relationships by Nathalie Antonios No relevant relationships by Colby Baker No relevant relationships by Jessica Johnson No relevant relationships by Karen Sayad

Effects of intraoperative inverse ratio ventilation on postoperative pulmonary function tests in the patients undergoing laparoscopic cholecystectomy: A prospective single blind study.

Background and Aims:Induction of general anaesthesia is associated with development of atelectasis in the lungs, which may further lead to postoperative pulmonary complications. Inverse ratio ventilation (IRV) has shown to improve oxygenation and minimise further lung injury in patients with acute respiratory distress syndrome. We evaluated the safety and effectiveness of IRV on intraoperative respiratory mechanics and postoperative pulmonary function tests (PFTs).Methods:In a prospective, controlled study, 128 consecutive patients with normal preoperative PFTs who underwent elective laparoscopic cholecystectomy were randomised into IRV and conventional ventilation groups. Initially, all patients were ventilated with settings of tidal volume 8 mL/kg, respiratory rate 12/min, inspiratory/expiratory ratio (I: E) = 1:2, positive end expiratory pressure = 0. Once the pneumoperitoneum was created, the conventional group patients were continued to be ventilated with same settings. However, in the IRV group, I: E ratio was changed to 2:1. Peak pressure (Ppeak), Plateau pressure (Pplat) and lung compliance were measured. Haemodynamic parameters and arterial blood gas values were also measured. PFTs were repeated in postoperative period. Statistical tool included Chi-square test.Results:There was no significant difference in PFTs in patients who underwent IRV as compared to conventional ventilation [forced vital capacity (FVC) 2.52 ± 0.13 versus 2.63 ± 0.16, P = 0.28]. The Ppeak (cmH2O) and Pplat (cmH2O) were statistically lower in IRV patients [Ppeak 21.4 ± 3.4 versus 22.4 ± 4.2, P = 0.003] [Pplat 18.7 ± 2.4 versus 19.9.4 ± 3.2, P = 0.008]. There was no significant difference in lung compliance and oxygenation intraoperatively.Conclusion:Intraoperative IRV led to reduced airway pressures; however, it did not prevent deterioration of PFTs in postoperative period.

Computational simulation to assess patient safety of uncompensated COVID-19 two-patient ventilator sharing using the Pulse Physiology Engine.

BackgroundThe COVID-19 pandemic is stretching medical resources internationally, sometimes creating ventilator shortages that complicate clinical and ethical situations. The possibility of needing to ventilate multiple patients with a single ventilator raises patient health and safety concerns in addition to clinical conditions needing treatment. Wherever ventilators are employed, additional tubing and splitting adaptors may be available. Adjustable flow-compensating resistance for differences in lung compliance on individual limbs may not be readily implementable. By exploring a number and range of possible contributing factors using computational simulation without risk of patient harm, this paper attempts to define useful bounds for ventilation parameters when compensatory resistance in limbs of a shared breathing circuit is not possible. This desperate approach to shared ventilation support would be a last resort when alternatives have been exhausted.MethodsA whole-body computational physiology model (using lumped parameters) was used to simulate each patient being ventilated. The primary model of a single patient with a dedicated ventilator was augmented to model two patients sharing a single ventilator. In addition to lung mechanics or estimation of CO2 and pH expected for set ventilation parameters (considerations of lung physiology alone), full physiological simulation provides estimates of additional values for oxyhemoglobin saturation, arterial oxygen tension, and other patient parameters. A range of ventilator settings and patient characteristics were simulated for paired patients.FindingsTo be useful for clinicians, attention has been directed to clinically available parameters. These simulations show patient outcome during multi-patient ventilation is most closely correlated to lung compliance, oxygenation index, oxygen saturation index, and end-tidal carbon dioxide of individual patients. The simulated patient outcome metrics were satisfactory when the lung compliance difference between two patients was less than 12 mL/cmH2O, and the oxygen saturation index difference was less than 2 mmHg.InterpretationIn resource-limited regions of the world, the COVID-19 pandemic will result in equipment shortages. While single-patient ventilation is preferable, if that option is unavailable and ventilator sharing using limbs without flow resistance compensation is the only available alternative, these simulations provide a conceptual framework and guidelines for clinical patient selection.

Intraoperative initiation of a modified ARDSNet protocol increases survival of septic patients with severe acute respiratory distress syndrome

PurposeTo assess the intraoperative initiation and feasibility of a modified NIH-NHLBI ARDS Network Mechanical Ventilation Protocol (mARDSNet protocol) in septic patients with severe ARDS. Materials and methodsThis prospective observational study included consecutive adult septic patients with severe ARDS who underwent emergency abdominal surgery prior to intensive care unit (ICU) admission. The primary outcome was survival to hospital discharge and at 90 days. Secondary outcomes were intraoperative adverse events and ICU length of stay. ResultsSeven patients were included. A statistically significant difference in lung compliance [ε=0.150, F(1.053, 3.158)=31.098, p=0.010] and driving pressure [ε=0.263, F(1.844, 5.532)=7.042, p=0.031] was observed with time, while plateau pressure did not changed significantly during surgery [ε=0.322, F(2.256, 6.769)=1.920, p=0.219]. Also, PEEP values were constantly increased during surgery [ε=0.252, F(1.766, 5.297)=9.994, p=0.017], with the highest values being observed towards to the end of the procedure. No intraoperative adverse events were observed. Mean (±SD) ICU length of stay was 10.43 (±2.64) days, while all patients survived to hospital discharge and at 90 days. ConclusionsThe intraoperative implementation of our mARDSNet protocol is feasible and may increase the survival of septic patients with severe ARDS if initiated prior to ICU admission.

Comparison of Mechanical Insufflation-Exsufflation and Endotracheal Suctioning in Mechanically Ventilated Patients: Effects on Respiratory Mechanics, Hemodynamics, and Volume of Secretions.

Context:Cough assist (CA) is a device to improve bronchial hygiene of patients with secretion in the airways and ineffective cough.Aims:To compare the physiological effects and the volume of secretion of mechanical insufflation–exsufflation (CA device) with isolated endotracheal suctioning in mechanically ventilated patients.Settings and Design:Randomized crossover trial.Materials and Methods:The patients were randomly allocated to the first technique, then the following technique was performed in the next day. We collected the variables related to oxygen saturation, hemodynamics (heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure [MAP]), and respiratory mechanics (tidal volume, minute volume, respiratory rate, and lung compliance and resistance), pre- and postimplementation (immediately and after 15 and 30 min), and the aspirated volume of secretion.Statistical Analysis Used:We used two-way analysis of variance followed by the Student–Newman–Keuls t-test to compare the variables at different time points. Student's t-test was used to compare secretion volumes. All data were stored and analyzed in SPSS for Windows Version 19.0. The significance level was set at 5%.Results:Forty-three patients were included in the study. When we compared the results before and after the application of the techniques, we observed no significant difference in lung compliance, pulmonary resistance, MAP, peripheral oxygen saturation, and secretion volume in both groups.Conclusions:The mechanical insufflation–exsufflation does not alter respiratory mechanics and hemodynamic stability, and it does not improve airway clearance in mechanically ventilated patients.

Electrical impedance tomography to evaluate air distribution prior to extubation in very-low-birth-weight infants: a feasibility study

OBJECTIVES:Nasal continuous positive airway pressure is used as a standard of care after extubation in very-low-birth-weight infants. A pressure of 5 cmH2O is usually applied regardless of individual differences in lung compliance. Current methods for evaluation of lung compliance and air distribution in the lungs are thus imprecise for preterm infants. This study used electrical impedance tomography to determine the feasibility of evaluating the positive end-expiratory pressure level associated with a more homogeneous air distribution within the lungs before extubation.METHODS:Ventilation homogeneity was defined by electrical impedance tomography as the ratio of ventilation between dependent and non-dependent lung areas. The best ventilation homogeneity was achieved when this ratio was equal to 1. Just before extubation, decremental expiratory pressure levels were applied (8, 7, 6 and 5 cmH20; 3 minutes each step), and the pressure that determined the best ventilation homogeneity was defined as the best positive end-expiratory pressure.RESULTS:The best positive end-expiratory pressure value was 6.3±1.1 cmH20, and the mean continuous positive airway pressure applied after extubation was 5.2±0.4 cmH20 (p = 0.002). The extubation failure rate was 21.4%. X-Ray and blood gases after extubation were also checked.CONCLUSION:This study demonstrates that electrical impedance tomography can be safely and successfully used in patients ready for extubation to suggest the best ventilation homogeneity, which is influenced by the level of expiratory pressure applied. In this feasibility study, the best lung compliance was found with pressure levels higher than the continuous positive airway pressure levels that are usually applied for routine extubation.

Airflow distribution with manual hyperinflation as assessed through gamma camera imaging: a crossover randomised trial

ObjectivesManual hyperinflation (MHI) has been shown to improve lung compliance, reduce airway resistance, and enhance secretion removal and peak expiratory flow. The aims of this study were to investigate whether there is a difference in airflow distribution through patients’ lungs when using the Laerdal and Mapleson-C circuits at a set level of positive end-expiratory pressure (PEEP), and to establish whether differences in lung compliance and haemodynamic status exist when patients are treated with both these MHI circuits. DesignCrossover randomised controlled trial. SettingAdult multidisciplinary intensive care unit (ICU) at an academic hospital. ParticipantsFifteen adult patients were recruited and served as their own controls. InterventionIn the Nuclear Medicine Department, MHI with PEEP 7.5cmH2O was performed in the supine position (Day 1) with either Laerdal or Mapleson-C circuits, in a random order, while technetium-99m (Tc-99m) aerosol was administered and images were taken with a gamma camera. Changes in heart rate (HR), mean arterial pressure (MAP) and dynamic lung compliance (CD) were documented at baseline, immediately after return to ICU, and 10, 20 and 30minutes after return to ICU. The alternative circuit was used on Day 2. ResultsTc-99m deposition was greater in the right lung field (62% and 63% for Laerdal and Mapleson-C circuits, respectively) than the left lung field (38% and 37%, respectively) for all patients, and least deposition occurred in the left lower segments (6% and 6%, respectively). No differences in Tc-99m deposition in the lungs, HR, MAP or CD were noted between the two MHI circuits. ConclusionAirflow distribution through patients’ lungs was similar when the Laerdal and Mapleson-C MHI circuits were compared using a set level of PEEP in the supine position.

New images, new insights for VILI

prioritization of high-volume vs. low-volume mechanisms of ventilator-induced lung injury (VILI) is an issue that is often discussed and debated in clinical ventilator management. Abundant laboratory studies ([7][1]), as well as several prominent clinical studies ([1][2], [3][3], [14][4], [19][5]),

C-Kit is essential for alveolar maintenance and protection from emphysema-like disease in mice.

Previously, we demonstrated a candidate region for susceptibility to airspace enlargement on mouse chromosome 5. However, the specific candidate genes within this region accounting for emphysema-like changes remain unrecognized. c-Kit is a receptor tyrosine kinase within this candidate gene region that has previously been recognized to contribute to the survival, proliferation, and differentiation of hematopoietic stem cells. Increases in the percentage of cells expressing c-Kit have previously been associated with protection against injury-induced emphysema. Determine whether genetic variants of c-Kit are associated with spontaneous airspace enlargement. Perform single-nucleotide polymorphism association studies in the mouse strains at the extremes of airspace enlargement phenotype for variants in c-Kit tyrosine kinase. Characterize mice bearing functional variants of c-Kit compared with wild-type controls for the development of spontaneous airspace enlargement. Epithelial cell proliferation was measured in culture. Upstream regulatory single-nucleotide polymorphisms in the divergent mouse strains were associated with the lung compliance difference observed between the extreme strains. c-Kit mutant mice (Kit(W-sh)/(W-sh)), when compared with genetic controls, developed altered lung histology, increased total lung capacity, increased residual volume, and increased lung compliance that persist into adulthood. c-Kit inhibition with imatinib attenuated in vitro proliferation of cells expressing epithelial cell adhesion molecule. Our findings indicate that c-Kit sustains and/or maintains normal alveolar architecture in the lungs of mice. In vitro data suggest that c-Kit can regulate epithelial cell clonal expansion. The precise mechanisms that c-Kit contributes to the development of airspace enlargement and increased lung compliance remain unclear and warrants further investigation.

Prophylactic Intratracheal Polymyxin B/Surfactant Prevents Bacterial Growth in Neonatal Escherichia coli Pneumonia of Rabbits

In neonatal pneumonia, the surface activity of pulmonary surfactant is impaired and microorganisms may invade by passing the air-liquid interface. Previously, we have shown that addition of the antimicrobial peptide polymyxin B (PxB) to modified porcine surfactant (pSF) improves resistance to surfactant inactivation in vitro while antimicrobial activity of PxB is maintained. In this study, we investigated pSF/PxB in vivo. Neonatal near-term rabbits were treated with intratracheal pSF and/or PxB. Rabbits treated with only saline served as controls. Animals were ventilated with standardized tidal volumes and received ∼10(7) Escherichia coli intratracheally. Plethysmographic pressure-volume curves were recorded every 30 min. After 240 min, animals were killed, the right lung and left kidney were excised, and bacterial growth was determined. The left lung was used for histologic analysis. Intratracheal administration of PxB ± pSF significantly reduced the growth of E. coli compared with control animals or animals receiving only pSF. This was accompanied by reduction of severe inflammatory tissue destruction and significantly reduced bacterial translocation to the left kidney. Animals receiving pSF + PxB had no difference in lung compliance compared with the pSF- or PxB-treated group. Mixtures of PxB and pulmonary surfactant show antimicrobial effects in neonatal rabbits and prevent systemic spreading of E. coli.

Lung transplantation for COPD: one lung, two lungs, or none?

The history of lung transplantation began with the first unsuccessful attempt in 1963 to transplant one lung to treat chronic obstructive pulmonary disease (COPD).1 Subsequent attempts and failures led to the widely held belief that unilateral transplantation in COPD was not physiologically possible because of differences in lung compliance and pulmonary-vascular resistance between the transplanted healthy lung and the native emphysematous lung.2 With this physiological principle in mind, Cooper and colleagues in 1986 used a bilateral transplantation in the first successful treatment of COPD.

The effect of positive end expiratory pressure on the respiratory profile during one‐lung ventilation for thoracotomy*

Summary In this randomised controlled trial we examined the effects of four different levels of positive end expiratory pressure (PEEP at 0, 5, 8 or 10 cmH(2)O), added to the dependent lung, on respiratory profile and oxygenation during one lung ventilation. Forty-six patients were recruited to receive one of the randomised PEEP levels during one lung ventilation. We did not find significant differences in lung compliance, intra-operative or postoperative oxygenation amongst the four different groups. However, the physiological deadspace to tidal volume ventilation ratio was significantly lower in the 8 cmH(2)O PEEP group compared with the other levels of PEEP (p < 0.0001). We concluded that the use of PEEP (< or =10 cmH(2)O) during one lung ventilation does not clinically improve lung compliance, intra-operative or postoperative oxygenation despite a statistically significant reduction in the physiological deadspace to tidal volume ratio.

Effect of Modified Ultrafiltration on Pulmonary Function After Cardiopulmonary Bypass

Effect of Modified Ultrafiltration on Pulmonary Function After Cardiopulmonary Bypass

EARLY INFECTIOUS PULMONARY COMPLICATIONS IN AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANT (HSCT) RECIPIENTS

Pulmonary dysfunction is one of the most common manifestations of inflammatory response after cardiopulmonary bypass (CPB). This prospective randomized study was conducted to evaluate the effect of a modified ultrafiltration (MUF) technique on pulmonary function after CPB in children. Forty patients weighing from 5 to 10 kg with congenital heart disease who required CPB for primary biventricular operative repair were prospectively randomized into two groups. The control group received conventional ultrafiltration (CUF) during CPB, and the study group received CUF and MUF. Pulmonary compliance (static and dynamic) and gas exchange capacity of the lung expressed as oxygen index, respiratory index, ventilation index, and alveolar-arterial oxygen pressure difference were measured after intubation (baseline), at the termination of CPB, at the end of MUF, on admission to the ICU, and 6 h postoperatively. There was no significant difference in lung compliance and gas exchange between the two groups before CPB. CPB produced a significant decrease in static and dynamic lung compliance in both groups. In the control group, static and dynamic lung compliance decreased from 1.0 +/- 0.3 to 0.90 +/- 0.3 mL/cm/kg and 0.87 +/- 0.2 to 0.71 +/- 0.1 mL/cm/kg (+/- SE) [p = 0.0002 and p = 0.002, respectively]. In the study group, static and dynamic lung compliance decreased from 1.0 +/- 0.2 to 0.89 +/- 0.03 mL/cm/kg and 0.94 +/- 0.2 to 0.77 +/- 0.1 mL/cm/kg (p = 0.002 and p = 0.002, respectively). There was no significant difference in the decrease in static (p = 0.9) or dynamic lung compliance (p = 0.3) between the two groups. MUF produced a significant immediate improvement in both static lung compliance (0.89 +/- 0.2 to 0.98 +/- 0.2 mL/cm/kg, p = 0.03) and dynamic lung compliance (0.77 +/- 0.1 to 0.93 +/- 0.2 mL/cm/kg, p = 0.007). The same was observed regarding the gas exchange capacity. CPB produced a significant decrease in lung gas exchange capacity, and MUF produced a significant immediate improvement in lung gas exchange capacity. The effect of MUF on lung compliance and gas exchange capacity was not sustained after admission to the ICU nor 6 h later postoperatively. There was no significant difference in the time of extubation between the two groups (12 +/- 3 h and 13 +/- 2 h, p = 0.4), the length of ICU stay, or the total hospital stay postoperatively. The use of MUF after CPB can produce an immediate improvement in lung compliance and gas exchange capacity, which may effectively minimize pulmonary dysfunction postbiventricular repair of congenital heart disease. However, these improvements are not sustained for the first 6 h postoperatively and do not reduce the duration of postoperative intubation, ICU stay, or total hospital stay.

Incidence and prediction of bronchopulmonary dysplasia in a cohort of premature infants.

A prospective study on the incidence of bronchopulmonary dysplasia (BPD) in premature infants is reported. A cohort of premature infants with gestational ages < or = 32 weeks, treated during 1989, was followed for one year. Of a total study population of 117 infants, 23 (19.6%) developed BPD, defined as oxygen dependence at 28 postnatal days. However, only 15 infants (12.8%) needed supplementary oxygen at the age of 36 gestational weeks and 5 infants (4.2%) needed supplementary oxygen periodically at one year of age. BPD was found to account for a significant part of both the total and late mortality in the cohort. Measurements of pulmonary mechanics were performed at 3 +/- 1 and 12(13) +/- 1 days of life in a subgroup of 26 infants with RDS who required assisted ventilation for 4 days or longer. No significant difference in lung compliance or resistance could be found during the first examination between infants who later developed BPD and infants with RDS only. At the second examination, infants who later developed BPD had significantly lower lung compliance (0.48 +/- 0.23 ml/cmH2O) than infants in the RDS group (1.50 +/- 0.72 ml/cmH2O) (p < 0.001). Measurements of pulmonary mechanics could be of importance for early prediction of infants at risk of BPD.

Platelet-activating factor antagonists decrease lung protein leak in preterm ventilated rabbits

The preterm ventilated lung is characterized by an increased protein leak from the pulmonary vascular spaces into the air spaces, which interferes with lung function and plays a role in neonatal respiratory distress syndrome. To investigate the role of platelet-activating factor in this process, platelet-activating factor antagonists were given to preterm ventilated rabbits. New Zealand White rabbits were delivered on day 28 of 31 days' gestation. Each rabbit pup received saline solution or one of two platelet-activating factor antagonists and were ventilated for 30 minutes with measurement of compliance, surfactant pool size, and protein leak into and out of the lung. Statistical analysis was performed with analysis of variance followed by Student-Newman-Keuls correction for multiple comparisons. There were no differences in lung compliance, surfactant pool size, or protein leak out of the air spaces among any of the groups. Treatment with the platelet-activating factor antagonists decreased the protein leak into the air spaces by greater than 50% and into the lung as a whole by 40% (p less than 0.01). Platelet-activating factor plays a role in the protein leak seen in the preterm lung, which contributes to neonatal respiratory distress syndrome.

Pulmonary mechanics in premature infants one month after treatment with synthetic surfactant

During the double-blind, multicenter trials of the synthetic surfactant Exosurf Neonatal, we measured pulmonary mechanics at 28 days of age in 30 surfactant- or placebo-treated infants. In the 20 surfactant-treated and 10 air-treated infants studied, there were no differences in lung compliance or resistance at 28 days of age. These observations suggest that improvements in pulmonary function reported early in the neonatal course after the administration of exogenous surfactant are not detectable at 28 days of age.

Interdependence of regional expiratory flow.

Flows from different lung regions interact at the junctions of the bronchial tree, and flow from each region depends on the driving pressures for other regions. At each junction, flow from the region with the higher driving pressure is favored. As a result there is a limit on the difference in alveolar pressures that can develop during expiratory flow from a lung with regional differences in lung compliance and airway resistance. The limiting pressure difference is smaller for lower flow. A nonuniform lung therefore empties more uniformly if it empties slowly, and maximum flow at low lung volume may be greater than it would be at the same lung volume during a maximal expiratory vital capacity maneuver.