Idiopathic Respiratory Distress Syndrome Research Articles

The potential use of N-acetylcysteine in respiratory conditions

Currently, despite the accumulated experience with the use of N-acetylcysteine (NAC) in scientific and real clinical practice, there are a number of questions about its potential and the future prospects for its use.The aim of this work was to summarize new data on the use of NAC in patients with various conditions, based on publications in domestic and foreign medical journals.Results. The article presents an overview of publications in domestic and foreign medical journals devoted to the use of N-acetylcysteine (NAC) in pulmonology practice. The experience with the use of NAC in chronic bronchitis (CB), chronic obstructive pulmonary disease (COPD), bronchial asthma, community-acquired pneumonia, idiopathic pulmonary fibrosis, postinfectious bronchiectasis, and acute respiratory distress syndrome associated with COVID-19 (COronaVIrus Disease 2019) is summarized. The aspects of dose-dependent clinical effects and long-term administration of NAC in CB and COPD are analyzed. In addition, there are controversial and contradictory data on the possibility of prescribing NAC for idiopathic pulmonary fibrosis.Conclusion. NAC is a drug with a broad spectrum of action. Due to its antioxidant and anti-inflammatory properties, minor side effects compared to other anti-inflammatory drugs even at high doses, and low price, NAC can be prescribed for many respiratory diseases. Although it has been used for more than half a century, interest in both its practical application and clinical research has not waned to this day.

Metabolome-wide association study of flavorant vanillin exposure in bronchial epithelial cells reveals disease-related perturbations in metabolism

Electronic cigarettes (e-cig) are an increasingly popular alternative to traditional smoking but have been in use for too short of a period of time to fully understand health risks. Furthermore, associated health risks are difficult to evaluate because of a large range of flavoring agents and their combinations for use with e-cig. Many flavoring agents are generally regarded as safe but have limited studies for effects on lung. Vanillin, an aromatic aldehyde, is one of the most commonly used flavoring agents in e-cig. Vanillin is electrophilic and can be redox active, with chemical properties expected to interact within biologic systems. Because accumulating lung metabolomics studies have identified metabolic disruptions associated with idiopathic pulmonary fibrosis, asthma and acute respiratory distress syndrome, we used human bronchial epithelial cells (BEAS-2B) with high-resolution metabolomics analysis to determine whether these disease-associated pathways are impacted by vanillin over the range used in e-cig. A metabolome-wide association study showed that vanillin perturbed specific energy, amino acid, antioxidant and sphingolipid pathways previously associated with human disease. Analysis of a small publicly available human dataset showed associations with several of the same pathways. Because vanillin is a common and high-abundance flavorant in e-cig, these results show that vanillin has potential to be mechanistically important in lung diseases and warrants in vivo toxicity testing in the context of e-cig use.

The Roles of MicroRNAs and Extracellular Vesicles in the Pathogeneses of Idiopathic Pulmonary Fibrosis and Acute Respiratory Distress Syndrome.

The lungs are the organs that work for gas exchange. The basic structure of the lungs is an alveolus, which consists of various types of parenchymal cells and bone marrow-derived cells. Therefore, because the lungs consist of various types of cells with various functions, communication among the different types of the cells should play important roles for the homeostasis and response to disease pathogens. In the past decades, researchers have focused on cytokines or adhesion molecules to reveal the intercellular communication for understanding the homeostasis and pathogenesis in the lungs. Recent investigations have revealed that an extracellular vesicle can move among cells for transferring substances including microRNAs in the vesicles as an intercellular messenger. MicroRNAs and extracellular vesicles are therefore attracting increasing attention from both translational and clinical researchers because these emerging intercellular communication tools seem to be useful for further understanding of the disease pathogenesis as well as the biomarkers for diagnosis and prognosis of the diseases including cancer and inflammatory diseases. This review article is an attempt to review studies about microRNAs and extracellular vesicles in terms of their roles in normal conditions and refractory diseases of the lungs such as idiopathic pulmonary fibrosis and acute respiratory distress syndrome including our recent study about pulmonary microvascular endothelial microparticles particles as the biomarker for diagnosis and prognosis of acute respiratory distress syndrome. This review also addresses the possibility of microRNAs and extracellular vesicles as new clinical tools for the diagnosis or treatment for these refractory respiratory diseases.

Old wine in new wineskins. Hamman-Rich syndrome has much in common with severe COVID-19: Do they share any link of pathogenesis or depend on the similar aetiological factor(s)?

For the first time the acute interstitial pneumonitis as a main cause of adult idiopathic respiratory distress syndrome was described in 1933–35 by the American medical scholars Louis Virgil Hamman and Arnold Rice Rich as “acute fibrosing alveolitis” later given the eponymous name Hamman-Rich syndrome. This disease targets the interstitium of the lungs and characterized by fulminant onset, acute respiratory disorder with possibility of respiratory failure, being clinically similar to respiratory distress syndrome with the pathomorphologically revealed diffuse alveolar damage. Hamman-Rich syndrome is characterized by rapid progression from symptoms of common cold such as cough, fever, chills and dyspnea to severe respiratory failure. The syndrome affects apparently healthy individuals and is not associated with any anamnestic chronic lung diseases, smoking habits, neither with patients’ age or sex. The aetiology and pathogenesis of the Hamman-Rich syndrome are not clear yet. The familiar genetic predisposition is of definite meaning, especially related to mutations of surfactant proteins and their metabolism. The possible mechanistic links of this fulminant lung disease involve: NK-cells, auto-aggressive immune activation and certain types of cytokines during their excessive systemic action, so-called cytokine storm (e.g. interleukin-18 and interleukin-2), which play the leading part in the patho-genesis of acute lung cell injury resulting in diffuse non-remitting pneumofibrosis. But all these clinical and pathogenetic features are also common for severe COVID-19. Computed tomography is used for instrumental diagnosis of Hamman-Rich syndrome and also gives the lung images quite similar to that of COVID-19, including ground glass opacity symptoms. The authors hypothesize that the same link(s) of pathogenesis underlie the severe course of COVID-19 and Hamman-Rich syndrome. It is possible that cases of Hamman-Rich syndrome were due to the circulation in populations of a less virulent, unrecognized coronavirus, which interacts with the immune system of genetically susceptible individuals in a way similar to SARS-CoV2. For sure, the identification of the characteristics of the genome of patients with Hamman-Rich syndrome will shed light on the genetic mechanisms that predispose to the severe course of COVID-19 and vice versa — the experience of severe COVID-19 treatment can be applied to the therapy of Hamman-Rich syndrome as well.

121. Neonatal outcome after natural course of preterm IUGR fetuses with abnormal umbilical Doppler flow in combination with preeclampsia

Introduction The natural course of preterm IUGR pregnancies with absent or reversed end diastolic flow (AREDF) in the umbilical artery and preeclampsia has not been investigated so far. Objectives Determine neonatal outcome of preterm IUGR pregnancies with AREDF and preeclampsia after expectant obstetric management. Methods Patients were admitted between 2004 and 2014 in the Erasmus Medical Centre with preterm IUGR. Inclusion criteria: singletons, IUGR, 24–32 weeks, birth weight 500–1250 g. Admission was on clinical grounds and/or because of AREDF. Patients were allocated to the AREDF group or the normal end-diastolic flow (NEDF) group. After expectant management, pregnancies were terminated because of fetal distress or for maternal reasons. Short-term primary outcomes: idiopathic respiratory distress syndrome (IRDS), sepsis, bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage, composite neonatal outcome and perinatal mortality. Long-term primary outcome: cognitive and motor neurodevelopment at two years of age with Bayley III (BSID III). Results 433 women with preterm IUGR were admitted, 184 met the inclusion criteria, 33 were also diagnosed with preeclampsia. AREDF had no adverse effects on perinatal morbidity and mortality. NEDF seemed to increase the risk for IRDS (P = 0.021). Between the two groups, no differences were found on cognitive (P = 0.078) and motor development (P = 0.568). There were no differences in gestational age at delivery. Expectant management had positive effects on sepsis (P = 0.006) and perinatal mortality (P = 0.042). Delivery was postponed between 1 day and 10 weeks. Preeclampsia had no additional adverse effects on the prevalence of perinatal morbidity and mortality (P = 0.402) and cognitive and motor neurodevelopment (P = 0.611 and P = 0.640). Discussion No significant differences in neonatal outcome were found between the AREDF and NEDF group irrespective of co-existing preeclampsia after expectant management. It seems that postponing the delivery reduces perinatal morbidity and mortality. NEDF seemed to increase the risk of IRDS.

50 Years Ago in TheJournal ofPediatrics: Acetylcholine in the Treatment of Idiopathic Respiratory Distress Syndrome

50 Years Ago in TheJournal ofPediatrics: Acetylcholine in the Treatment of Idiopathic Respiratory Distress Syndrome

Outcome of neonates with idiopathic respiratory distress syndrome; where do we go wrong?

The AMJ is a peer-reviewed, triannual health journal published by Anuradhapura Clinical Society (ACS).The Journal strives to be a forum for all health professionals to publish original research and review articles in their area of expertise. The AMJ publishes articles in clinical medicine, public health and health promotion. Our priority is given to manuscripts on health related issues which affects the communities living in rural tropical communities. Established as a journal in 2006 as a publication parallel to ACS annual scientific sessions, the journal was relaunched as a proper journal in 2013. Anuradhapura Medical Journal is a member of COPE and is included on DOAJ.Cover Image: Computed tomography perfusion (CTP) brain image of a left-sided ischaemic stroke.The image shows time to peak (TTP) perfusion map of the brain with prolongation of TTP in hypoperfused regions of the left hemisphere identified as patchy areas highlighted in red.Dr. Hemal Senanayake

Acute Interstitial Pneumonia (Hamman-Rich Syndrome) as a Cause of Idiopathic Acute Respiratory Distress Syndrome

Hamman-Rich syndrome, also known as acute interstitial pneumonia, is a rare and fulminant form of idiopathic interstitial lung disease. It should be considered as a cause of idiopathic acute respiratory distress syndrome. Confirmatory diagnosis requires demonstration of diffuse alveolar damage on lung histopathology. The main treatment is supportive care. It is not clear if glucocorticoid therapy is effective in acute interstitial pneumonia. We report the case of a 77-year-old woman without pre-existing lung disease who initially presented with mild upper respiratory tract infection and then progressed to rapid onset of hypoxic respiratory failure similar to acute respiratory distress syndrome with unknown etiology. Despite glucocorticoid therapy, she did not achieve remission and expired after 35 days of hospitalization. The diagnosis of acute interstitial pneumonia was supported by the histopathologic findings on her lung biopsy.

Pulmonary Histopathology in Dalmatians with Familial Acute Respiratory Distress Syndrome (ARDS)

The histopathological changes in the lungs of 12 related Dalmatians with idiopathic acute respiratory distress syndrome (ARDS) are described. Affected dogs had multiple foci of marked atypical hyperplasia and squamous metaplasia of the bronchiolar epithelium, patchy ongoing fibrosis with myofibroblastic metaplasia, smooth muscle hyperplasia and occasional honeycombing of alveolar walls, and hyperplasia of atypical type II pneumocytes. There was an abrupt transition between these proliferative lesions and areas of acute alveolar oedema with hyaline membranes in partially normal lung. Diseased areas were associated with moderate lymphohistiocytic interstitial inflammation. Immunohistochemical labelling for cytokeratin expression indicated that the metaplastic epithelium was of bronchiolar origin and that it extended into peribronchiolar alveolar spaces. Some of the bronchiolar lesions were pre-neoplastic and one adult dog suffered from bronchoalveolar carcinoma. These lesions are compared with the two forms of idiopathic interstitial pneumonia reported as causes of ARDS in man: acute interstitial pneumonia (AIP) and acute exacerbation of idiopathic pulmonary fibrosis (IPF). The observed lesions in the Dalmatians are distinct from the diffuse alveolar damage that characterizes AIP, but show some histological similarities to the usual interstitial pneumonia (UIP) that occurs in IPF with acute exacerbation in man. UIP has not previously been described in the dog.

Echocardiographic evaluation of right ventricle function in premature babies with idiopathic respiratory distress syndrome (IRDS)

Echocardiographic evaluation of right ventricle function in premature babies with idiopathic respiratory distress syndrome (IRDS)

Diesel exhaust particles increase IL-1β-induced human β-defensin expression via NF-κB-mediated pathway in human lung epithelial cells

BackgroundHuman β-defensin (hBD)-2, antimicrobial peptide primarily induced in epithelial cells, is a key factor in the innate immune response of the respiratory tract. Several studies showed increased defensin levels in both inflammatory lung diseases, such as cystic fibrosis, diffuse panbronchiolitis, idiopathic pulmonary fibrosis and acute respiratory distress syndrome, and infectious diseases. Recently, epidemiologic studies have demonstrated acute and serious adverse effects of particulate air pollution on respiratory health, especially in people with pre-existing inflammatory lung disease. To elucidate the effect of diesel exhaust particles (DEP) on pulmonary innate immune response, we investigated the hBD-2 and interleukin-8 (IL-8) expression to DEP exposure in interleukin-1 beta (IL-1β)-stimulated A549 cells.ResultsIL-1β markedly up-regulated the hBD-2 promoter activity, and the subsequent DEP exposure increased dose-dependently the expression of hBD-2 and inflammatory cytokine IL-8 at the transcriptional level. In addition, DEP further induced the NF-κB activation in IL-1β-stimulated A549 cells more rapidly than in unstimulated control cells, which was showed by nuclear translocation of p65 NF-κB and degradation of IκB-α. The experiment using two NF-κB inhibitors, PDTC and MG132, confirmed that this increase of hBD-2 expression following DEP exposure was regulated through NF-κB-mediated pathway.ConclusionThese results demonstrated that DEP exposure increases the expression of antimicrobial peptide and inflammatory cytokine at the transcriptional level in IL-1β-primed A549 epithelial cells and suggested that the increase is mediated at least partially through NF-κB activation. Therefore, DEP exposure may contribute to enhance the airway-responsiveness especially on the patients suffering from chronic respiratory disease.

Troponin I as a Biomarker of Cardiac Injury in Neonates with Idiopathic Respiratory Distress

Troponin I (TnI), an inhibitory protein complex located on the actin filament of cardiac muscle, has become a specific marker of myocardial damage. Troponin has been studied in a wide range of clinical settings. However, many questions are still unanswered, especially in preterm neonates with the most common pathology at birth, such as idiopathic respiratory distress syndrome (IRDS). The aim of this study was to establish a reference range for cardiac TnI for healthy preterm infants and serum levels in sick preterm infants with IRDS. Echocardiography was performed and TnI serum levels were measured at a median age of 62 hours of life in three groups of healthy preterm infants (n = 10), and ventilated infants with moderate (n = 15) and severe IRDS (n = 15). Ventilated infants with idiopathic moderate IRDS had significantly different cardiac parameters (R/L ejection fraction, R/L stroke volume, R/L cardiac output; p < 0.05) and significantly higher cardiac TnI levels than healthy infants (0.037 versus 0.01 microg/mL; p < 0.05). Furthermore, infants with severe IRDS had higher TnI concentrations than infants with moderate IRDS (0.26 versus 0.037 microg/mL; p < 0.05). The results of this study show that increased TnI serum levels in sick preterm infants with IRDS are explained by myocardial injury or dysfunction due to impaired arterial oxygenation or reduction in cardiac output during treatment with mechanical ventilation. These results suggest that cardiac TnI may be a useful, specific marker for myocardial damage in preterm neonates with IRDS.

Clearance of Fluid From Airspaces of Newborns and Infants

After completing this article, readers should be able to: 1. Describe fetal lung fluid secretion, its application on lung development, and its reabsorption immediately after birth. 2. List the primary cellular mechanism responsible for lung fluid absorption. 3. Describe clinical conditions in newborns and infants associated with impaired sodium transport. 4. Describe how sodium transport can be influenced by fetal lung maturity. When the airspaces of the lungs are filled with fluid, normal gas exchange cannot take place, and there is marked respiratory distress and the need for intensive care. This occurs in only two situations: failure to clear fetal lung liquid at birth and leakage of fluid from the vasculature filling the alveoli (alveolar pulmonary edema). Fluid that is secreted into the fetal airspaces to enable normal lung development must be absorbed at the time of birth for a normal transition from fetal to postnatal life. Failure to do so can lead to two well-known clinical syndromes: transient tachypnea of the newborn (TTN) and when there is coexistent relative surfactant deficiency, neonatal respiratory distress syndrome (nRDS). Pulmonary edema can be caused postnatally by many disorders; those that occur frequently during the neonatal period are patent ductus arteriosus or structural congenital heart disease with marked left-to-right shunting. It is not only biologically reasonable to assume that clearance of such airspace fluid would be beneficial to the patient, but studies in adults suffering from pulmonary edema have shown that the lung’s ability to clear such fluid correlates with survival. In this article, we review how the epithelium of the lung uses the active transport of sodium (Na+), followed by chloride (Cl−) and water, from the apical to basolateral side of the alveolar lining cells to clear fluid and how the underlying mechanisms for active Na+ transport are influenced by the degree of …

Idiopathic respiratory distress syndrome

Idiopathic respiratory distress syndrome

Neonatal Care for Premature Infants

Perinatal intensive centers deal with preterm infants of the region. Therefore, the rate of preterm deliveries at the Department of Obstetrics and Gynecology, Medical University of Pécs was high in 1997, about the double of the national rate (18.7%). Among prematures the rate of very low birth weight (VLBW) infants (less than 1500 g) was about 40%, moreover, the rate of extremely low birth weight infants (less than 1000 g) was 39% within the latter group. Related to the new regulation concerning preterm delivery the number of immature infants (weighing less than 750 g) with poor outcome increased. The most characteristic disease of preterm infants is the idiopathic respiratory distress syndrome (IRDS). This could be prevented by maternal steroid treatment, a therapy accepted worldwide, however, not so common in Hungary. Direct fetal steroid therapy may be applied also in selected cases. In the treatment of IRDS surfactant products made a breakthrough. Several factors (maternal tocolytic and fluid therapy, Cesarean section) influence the cardiopulmonary adaptation which may be monitored with impedance cardiography. Late hyponatremia and metabolic acidosis may develop in 1/3 of VLBW infants. Besides the fluid therapy the introduction of enteral feeding must be planned carefully and examination of gastric emptying with ultrasound is useful. The development of osteopenia may be prevented by passive exercise of the preterm infant. Anemia is common and human recombinant erythropoietin is available for treatment. Screening of vision, hearing, and neurodevelopmental follow up are integral parts of neonatal care. As a result of the above mentioned preventive and therapeutic interventions neonatal mortality has decreased significantly in Hungary in the past decades.

Pneumopathies interstitielles diffuses idiopathiques: Classification de Consensus International Multidisciplinaire de l’American Thoracic Society et de l’European Respiratory Society, principales entités anatomo-cliniques, et conduite du diagnostic

The classification of the idiopathic interstitial pneumonias includes seven clinico-pathologic entities. The diagnosis is based on a multidisciplinary approach, integrating the clinical evaluation, the high-resolution computerised tomography, and the pathological pattern. A definitive diagnosis of idiopathic pulmonary fibrosis relies on the association of a suggestive clinico-radiological profile and a pathological pattern of usual interstitial pneumonia. Nonspecific interstitial pneumonia is a recently described clinico-pathologic entity, with a better prognosis than that of idiopathic pulmonary fibrosis. Cryptogenic organising pneumonia has been included in the group of idiopathic interstitial pneumonias because of its idiopathic and multifocal characteristics, although it does not predominate in the lung interstitium. Desquamative interstitial pneumonia and respiratory bronchiolitis with interstitial lung disease are rare entities with predominance in young smoking adults. Lymphoid interstitial pneumonia, usually encountered in the context of Sjögren's syndrome, is very rare in its idiopathic form. Acute interstitial pneumonia is responsible for idiopathic acute respiratory distress syndrome. The current classification of idiopathic interstitial pneumonias better defines the diagnostic criterias of each clinico-pathologic entity, and is expected to facilitate clinical research. This classification has clinical implications, with prognostic and therapeutic significance.

In vitro inhibition of human neutrophil histotoxicity by ambroxol: evidence for a multistep mechanism

Neutrophils are major culprits for the protease/antiprotease imbalance during various lung diseases, that is, chronic obstructive pulmonary disease, cystic fibrosis, idiopathic pulmonary fibrosis and adult respiratory distress syndrome. Thus, these cells are presently considered an ideal target for the pharmacologic control of tissue injury during these diseases. This study was planned in order to investigate if ambroxol and its precursor bromhexine are actually capable of preventing alpha-1-antitrypsin (A1AT) inactivation by stimulated neutrophils and possibly to look into the mechanisms underlying this event. Ambroxol inhibited the production of superoxide anion by activated neutrophils, whereas bromhexine had no inhibitory effect. Ambroxol decreased the production of hypochlorous acid (HOCl) from activated neutrophils with high efficiency, whereas bromhexine had a modest activity. Ambroxol and bromhexine were capable of limiting the chlorination of monochlorodimedon by HOCl, displaying the capacity of directly scavenging the oxidant. Ambroxol decreased the release of elastase and myeloperoxidase from activated neutrophils, whereas bromhexine was ineffective. Ambroxol prevented the A1AT inactivation by neutrophils, whereas bromhexine was completely ineffective. Among drugs currently available for in vivo use in humans, ambroxol is unique by virtue of its ability to prevent neutrophil-mediated A1AT inactivation via inhibition of HOCl production as well as HOCl scavenging. Also taking into account its capacity for curbing elastase release, the drug displays the potential to lessen the burden of oxidants/proteases and to increase the antiprotease shield at the site of inflammation. Thus, ambroxol appears to be a good candidate for raising attempts to develop new therapeutic histoprotective approaches to inflammatory bronchopulmonary diseases.

A Case of Acute Interstitial Pneumonia with Invasive Pulmonary Aspergillosis

Acute interstitial pneumonia (AIP) is a rare fulminant form of lung injury that presents acutely; usually in a previously healthy individual. It corresponds to a subset of cases of idiopathic adult respiratory distress syndrome (ARDS). Invasive pulmonary aspergillosis is a disease occuring predominantly with defects in immunity such as hematologic malignancy, influenza infection, postchemotherapy, long-term corticosteroid treatment. Invasive aspergillosis has worse prognosis and most cases are diagnosed at postmortem autopsies. We experienced a case of acute interstitial pneumonia with an invasive aspergillosis during corticosteroid treatment. Acute interstitial pneumonia with invasive aspergillosis was diagnosed by an open lung biopsy using thoracoscopy, showing fungal hyphae with sepsis and an acute angle branching invasion of the lung tissue and blood vessels. The patient was treated with IV amphotericin-B, but died due to septic shock.

Role of defensins in inflammatory lung disease

The human airways are protected from invading micro-organisms by the highly efficient innate immune system. Antimicrobial peptides that are produced by inflammatory cells and airway epithelial cells are key elements in this innate immune system. A major subgroup of the antimicrobial peptides is the family of defensins - small non-enzymatic and cationic peptides. Besides their extensively studied role in antimicrobial defense, recent studies have demonstrated that defensins are also able to modulate inflammatory responses, to stimulate adaptive immunity and contribute to tissue repair. In line with these observations, increased defensin levels were observed in inflammatory lung diseases, such as cystic fibrosis (CF), diffuse panbroncheolitis (DPB), idiopathic pulmonary fibrosis (IPF) and acute respiratory distress syndrome (ARDS), and in infectious diseases. In the past decade much has been learnt about the activity of defensins and there is abundant evidence for their presence in human inflammatory lung disease. Future studies are required to elucidate their role in the pathogenesis of these diseases.

Reduction of oscillatory pressure along the endotracheal tube is indicative for maximal respiratory compliance during high‐frequency oscillatory ventilation: A mathematical model study

We hypothesized that during high-frequency oscillatory ventilation (HFOV), a reduction of peak-to-peak oscillatory pressure along the endotracheal tube is maximal when respiratory system compliance is maximal. We made a mathematical model of the endotracheal tube and the respiratory system of a neonate suffering from idiopathic respiratory distress syndrome (IRDS). The model consisted of linear viscous and inertive elements, a non-linear endotracheal tube resistance, and a non-linear compliance allowing for alveolar recruitment and overdistention. Respiratory compliance was maximal at the transition between maximal recruitment and minimal overdistention. A new variable, the oscillatory pressure ratio (OPR), was defined as the ratio between peak-to-peak oscillatory pressures at the distal end and the proximal opening of the endotracheal tube, respectively. The respiratory variables of four patients were fed into the model, and the relationship between respiratory system compliance and OPR was determined. OPR decreased as compliance increased, except for very low compliances below where 0.08 mL. cm H2O(-1), and OPR increased with increasing compliance. The relationship between mean airway pressure P(aw) and OPR revealed that the minimal OPR (range, 0.37-0.78) and maximal respiratory compliance coincided at the same P(aw). However, the relationship did depend on oscillation frequency, applied oscillatory pressure, and endotracheal tube resistance, parameters that may change during clinical application of HFOV. When 81 permutations of nominal and extreme respiratory variables were used in the model, the minimum OPR (0.60 +/- 0.23) and maximum compliance coincided in all cases. These model experiments support our hypothesis. The results indicate that the OPR may be a useful index to optimize lung expansion, where lung recruitment is maximal and overdistention minimal. In vivo tests will be needed to reveal the feasibility and reliability of such an index for biomedical and clinical application.