Clinical and Genetic Characteristics of COL2A1-Associated Skeletal Dysplasias in 60 Russian Patients: Part I.

The significant variability in the clinical manifestations of COL2A1-associated skeletal dysplasias makes it necessary to conduct a clinical and genetic analysis of individual nosological variants, which will contribute to improving our understanding of the pathogenetic mechanisms and prognosis. We presented the clinical and genetic characteristics of 60 Russian pediatric patients with type II collagenopathies caused by previously described and newly identified variants in the COL2A1 gene. Diagnosis confirmation was carried out by new generation sequencing of the target panel with subsequent validation of the identified variants using automated Sanger sequencing. It has been shown that clinical forms of spondyloepiphyseal dysplasias predominate in childhood, both with more severe clinical manifestations (58%) and with unusual phenotypes of mild forms with normal growth (25%). However, Stickler syndrome, type I was less common (17%). In the COL2A1 gene, 28 novel variants were identified, and a total of 63% of the variants were found in the triple helix region resulted in glycine substitution in Gly-XY repeats, which were identified in patients with clinical manifestations of congenital spondyloepiphyseal dysplasia with varying severity, and were not found in Stickler syndrome, type I and Kniest dysplasia. In the C-propeptide region, five novel variants leading to the development of unusual phenotypes of spondyloepiphyseal dysplasia have been identified.

Neonatal acute liver failure with pulmonary yellow hyaline membrane and kernicterus

Background Neonatal acute liver failure (NALF) is a rare and life-threatening condition. It causes bilirubin to accumulate to a dangerous level in the body, causing permanent damage to vital organs such as the brain and lungs. In many cases, the etiology of NALF remains unknown. Case presentation We described a case of an 8-day-old baby girl who presented with poor oral intake, lethargy, and jaundice. Her clinical condition rapidly deteriorated with progression to multi-organ failure, and despite intensive resuscitation efforts, she expired. At autopsy, the most significant findings were liver necrosis, yellow hyaline membrane deposition in the lungs, and bilirubin deposition in the brain (kernicterus). Conclusions NALF is a rare and potentially fatal condition necessitating prompt recognition and disease-specific treatment approaches. Toxic accumulation of bilirubin in the lungs can lead to hypoxia and precipitate further ischemic injury to the liver.

Recomendaciones para la asistencia respiratoria en el recién nacido (III). Surfactante y óxido nítrico / Recommendations for respiratory support in the newborn (III). Surfactant and nitric oxide

Las recomendaciones incluidas en este documento forman parte de una revisión actualizada de la asistencia respiratoria en el recién nacido. Están estructuradas en 12 módulos y en este trabajo se presenta el módulo 7. El contenido de cada módulo es el resultado del consenso de los miembros del Grupo Respiratorio y Surfactante de la Sociedad Española de Neonatología. Representan una síntesis de los trabajos publicados y de la experiencia clínica de cada uno de los miembros del grupo (AU)

The recommendations included in this document will be part a series of updated reviews of the literature on respiratory support in the newborn infant. These recommendations are structured into twelve modules, and in this work module 7 is presented. Each module is the result of a consensus process including all members of the Surfactant and Respiratory Group of the Spanish Society of Neonatology. They represent a summary of the published papers on each specific topic, and of the clinical experience of each one of the members of the group (AU)

Association between Kniest dysplasia and chondrosarcoma in a child.

Constitutive COL2A1 mutations are associated with a wide variety of clinical manifestations known as type II collagenopathies. Among them is Kniest dysplasia, which is phenotypically variable and includes both skeletal (short trunk and limbs, kyphoscoliosis, prominent joints, and osteoarthritis) and craniofacial characteristics. Kniest dysplasia mutations primarily arise in the triple-helicoidal region of the alpha 1 (II) chain in COL2A1 between exons 12 and 24. Somatic COL2A1 mutations have been identified in chondrosarcoma, a rare cartilage forming neoplasm, with a hypermutability of the gene reported in 37% of cases. However, to the best of our knowledge, there is no reported increase in predisposition to chondrosarcoma in human collagenopathies, and no reported clinical association between these congenital diseases and cartilaginous tumors. In the case study presented here, we report the first description of an association between these two rare diseases involving COL2A1, in a child presenting with Kniest dysplasia and a grade I sphenoethmoidal chondrosarcoma. We also describe a new constitutive mutation in COL2A1.

Ophthalmic and molecular genetic findings in Kniest dysplasia.

PURPOSE: To study the variability of the ophthalmic phenotype in Kniest dysplasia. Kniest dysplasia is an inherited disorder associated with defects in type II collagen and characterised by short-trunked dwarfism, kyphoscoliosis, and enlarged joints with restricted mobility. Other features include marked hand arthropathy, cleft palate, hearing loss, and ocular abnormalities (myopia, abnormal vitreous, and high risk of developing retinal detachment). METHODS: Data from eight unrelated individuals with a clinical and molecular diagnosis of Kniest dysplasia are reported. Clinical assessment included an audiogram and ophthalmological examination in all but one patient who died in the immediate postnatal period. Sanger sequencing of the COL2A1 gene was performed. RESULTS: Six of the seven patients tested were high myopes with one patient being an emmetrope. Bilateral quandratic cataracts and subluxed lenses were noted in one subject. Variable but abnormal vitreous architecture was observed in all seven individuals tested. Six of the seven patients had significant hearing impairment and five of the seven patients exhibited clefting abnormalities. One patient had bilateral retinal detachments in his twenties. Six dominant disease-causing COL2A1 variants were detected. In three cases, testing of parental samples revealed that the disease-causing variant was not present in either parent. CONCLUSION: The ophthalmic features in Kniest dysplasia are very similar to those in other disorders of type II collagen such as Stickler syndrome. It is likely that different type II collagenopathies have a similar level of ocular morbidity and regular ophthalmologic examination is recommended. Kniest dysplasia is associated with heterozygous COL2A1 mutations that are frequently de novo.

High frequency oscillatory ventilation versus conventional ventilation in a newborn piglet model with acute lung injury.

BACKGROUND: High frequency oscillatory ventilation (HFOV) is considered a protective strategy for human lungs. This study was designed to define microscopic structural features of lung injury following HFOV with a high lung volume strategy in newborn piglets with acute lung injury. METHODS: After acute lung injury with saline lavage, newborn piglets were randomly assigned to 5 study groups (6 in each group): control (no mechanical ventilation), conventional mechanical ventilation for 24 hours, conventional ventilation for 48 hours, HFOV for 24 hours, and HFOV for 48 hours. The right upper lung tissue was divided into the gravitation-dependent and gravitation-nondependent regions after the completion of mechanical ventilation. Under light microscopy, the numbers of polymorphonuclear leukocytes (PMNLs), alveolar macrophages, red blood cells, and hyaline membrane/alveolar edema were assessed in all lung tissues. Oxygenation index was continuously monitored. RESULTS: Our results showed that the degree of histopathologic lung damage in the gravitation-dependent region was greater than that in the gravitation-nondependent region. Compared with the control group, PMNLs, red blood cells and hyaline membrane/alveolar edemas were significantly increased and alveolar macrophages were significantly decreased in lung tissues of conventional ventilation and HFOV piglets. In HFOV with high lung volume strategy piglets, lung tissues had significantly fewer PMNLs, red blood cells, and hyaline membrane/alveolar edemas, and oxygenation was improved significantly, compared to those of the conventional ventilation piglets. CONCLUSIONS: Histopathologic lung damage in newborn piglets with lung injury was more severe in the gravitation-dependent region than in the gravitation-nondependent region. HFOV with high lung volume strategy reduced pulmonary PMNL infiltration, hemorrhage, alveolar edema, and hyaline membrane formation with improved oxygenation.

On the pulmonary toxicity of oxygen. 4. The thyroid arena.

Normally developed thyroid function is critical to the transition from fetal to neonatal life with the onset of independent thermoregulation, the most conspicuous of the many ways in which thyroid secretions act throughout the body. A role for thyroid secretions in growth and maturation of the lungs as part of the preparation for the onset of breathing has been recognized for some time but how this contributes to tissue and cell processes and defenses under the duress of respiratory distress has not been well examined. Extensive archival autopsy material was searched for thyroid and adrenal weights, first by gestational age, and then for changes during the first hours after birth as ratios to body weight. After a gestational age of 22 weeks the fetal thyroid and adrenal glands at autopsy in those with hyaline membrane disease are persistently half the size of those in "normal" infants dying with other disorders. When the thyroid is examined shortly after birth it reveals a post natal loss of mass per body weight of similar orders of magnitude which does not occur in the control group. A clinical sample of premature infants with (12) and without (14) hyaline membrane disease was tested for T(4), TSH, TBG, and total serum protein. The results also demonstrate a special subset with lower birth weights at the same gestational age, and lower serum T(4) and total serum protein. Ventilatory distress in newborn rabbits was induced by bilateral cervical vagotomy at 24 h post natal following earlier injection of thyroxine (T(4)) or thyroid stimulating hormone (TSH) and comparisons were made with untreated animals and by dose. Early life thyroidectomy was performed followed by exposure to either air or 100% oxygen. A final experiment in air was vagotomy after thyroidectomy. Composite analysis of these methods indicates that thyroid factors are both operative and important in the newborn animal with ventilatory distress. This work and the archival data indicate those infants destined to develop hyaline membrane disease through respiratory distress are a distinct developmental and clinical subset with the point of departure from otherwise normal development and maturation in the second or early third trimester. This interval is known to be a period of marked variation in the overview indicators of fetal progress through gestational time. The initiating factor or circumstance which then separates this special subset from normal future development is placed by these observations firmly into the period when human fetal TSH dramatically rises 7-fold (17.5-25.5 weeks) followed by a lesser 3 to 4-fold increase in T(4) which is extended into the early third trimester. The earlier part of this interval is characterized by the thyrotrophic action of chorionic gonadotropin (hCG). The possibility that abnormalities in the intrauterine environment secondary to maternal infection play a role within this time frame is indicated by the demonstration that interleukin-2 (IL-2) induces an anterior pituitary release of TSH. Since IL-2 has this property and is not an acute phase cytokine, some form of chronic infection or an immunopathic process seems more likely as a possible active factor in pathogenesis.

Estudio sobre la correlación clínico-patológica en el síndrome de distrés respiratorio agudo secundario / Study on the clinicopathological correlation in the secondary acute respiratory distress syndrome

Objetivo El objetivo principal del estudio es analizar la correlación clínicopatológica en el diagnóstico de síndrome de distrés respiratorio agudo (SDRA) de origen extrapulmonar. Diseño Se trata de un estudio observacional de una serie de casos. Ámbito UCI de 22 camas de un hospital universitario con 450 camas. Pacientes Diecisiete pacientes fallecidos a causa de un SDRA secundario. Intervención Análisis histopatológico sistemático de todos los lóbulos pulmonares de pacientes que fallecieron en nuestra UCI con el diagnóstico clínico de SDRA secundario y en los que se realizó necropsia entre los años 1999 y 2009. A fin de analizar el grado de correlación entre el diagnóstico clínico y el patológico se aplicó el análisis de kappa. Resultados En 17 pacientes con SDRA secundario la necropsia permitió confirmar 2 casos falsos positivos (11%). El valor kappa fue de 0,77, por lo que el análisis de concordancia fue considerado como satisfactorio. Conclusiones Los criterios clínicos para el diagnóstico de SDRA se correlacionan bien con la presencia de daño alveolar agudo en el estudio patológico necrópsico en pacientes con SDRA secundario, aunque pueden detectarse algunos casos falsos positivos (AU)

Objective This study has aimed to study the clinicopathological correlation of patients with secondary acute respiratory distress syndrome (ARDS), specifically having extrapulmonary causes. Setting A 22 beds intensive care unit. Design An observational study of case series. Patients Seventeen patients whose death was caused by acute respiratory distress syndrome were included. Intervention A systematic histopathological study was made of all the pulmonary lobes of patients who died in our ICU with the clinical diagnosis of secondary ARDS, who had undergone an autopsy between 1999 and 2009. The Kappa analysis was used to analyze the grade of correlation between the clinical and the pathological diagnosis. Results The autopsy confirmed to cases of false positive in 17 patients with ARDS (11%). The kappa value was 0.77, so that the concordance analysis was considered to be satisfactory. Conclusions The clinical criteria for ARDS correlate well with acute alveolar damage (AAD) in the autopsy study in patients with secondary ARDS, although some false positive cases can be observed (AU)

Respiratory distress syndrome of the preterm neonate--placenta and necropsy as witnesses.

AIM: To assess the agreement between clinical diagnosis of hyaline membrane disease (HMD) and lung necropsy pathological findings of deceased neonates. MATERIAL AND METHODS: Review of clinical files and necropsy studies of 40 newborn infants ≤ 37 weeks gestational age. RESULTS: The concordance between clinics and necropsy for the diagnosis of HMD was 43% (n = 17). At the necropsy study of the lungs, 11 cases (28%) of clinically diagnosed HMD were associated to meconium aspiration, pneumonia, or pulmonary hemorrhage; 12 (30%) cases were pneumonia and/or meconium aspiration and pulmonary hemorrhage without hyaline membranes. Of the 17 pneumonias, 15 (88%) were associated to histological chorioamnionitis, RR 3.76 (95%CI: 1.9-4.2) (p < 0.001). CONCLUSIONS: The clinical diagnosis of HMD needs a cautious interpretation, as it may be mistaken, or HMD may occur in association with other pathological situations enhancing a more ominous prognosis.

[Lung morphological changes in premature neonates with hyaline membrane disease due to the use of exogenous surfactants during mechanical ventilation].

A complex of studies was used in 4 groups of premature babies to study lung tissue morphological changes in hyaline membrane disease, by applying exogenous surfactants during mechanical ventilation. Background diseases, pre- and intranatal risk factors, the babies' longevity, and the specific features of lung tissue and forming hyaline membranes were ascertained. Exogenous surfactants were found to have a blocking effect on the formation of hyaline membranes under mechanical ventilation.

The effects of surfactant and antenatal corticosteroid treatment on the pulmonary pathology of preterm infants with respiratory distress syndrome.

The aim of this study was to investigate the effects of antenatal steroid treatment and/or postnatal surfactant replacement therapy on the incidence and extent of selected histopathological findings. Seventy complete autopsies were reviewed, and only lung tissues were examined and graded. Infants were divided into treatment and control groups as follows: group 1: surfactant-treated infants (n=15); group 2: infants whose mothers were given steroid treatment (n=16); group 3: surfactant-treated infants whose mothers were given steroid treatment (n=10). The control group included 29 patients not treated with surfactant and steroid. The overall incidence and severity of hyaline membrane and pulmonary hemorrhage were similar in each treatment group when compared to the control group. However, when the treatment groups were compared with each other, the incidence of severe hyaline membrane was more common in group 1 than in group 3. A significant reduction in severe hyaline membrane was associated with combined surfactant and antenatal steroid therapy. However, the cause for the similar incidence of selected histopathological findings in the treatment groups and the control group may be linked to oxygen toxicity due to insufficient antioxidant capacity in premature infants and barotrauma from mechanical ventilation.

[Hyaline membrane disease in full-term neonates]. / Maladie des membranes hyalines chez le nouveau-né à terme.

OBJECTIVES: Evaluation of the consequences of preplanned delivery near term on the neonatal respiratory distress syndrome and its mechanism of occurrence. PATIENTS AND METHODS: During five years, full-term infants (> or =37 weeks gestational age) admitted in the Institut de Puericulture de Paris, with a well characterized hyaline membrane disease, were included in a retrospective study. RESULTS: During this period, 97 full-term neonates with respiratory distress syndrome were hospitalized in the neonatal intensive care unit. The diagnosis of hyaline membrane disease was made in view of clinical and radiological criteria. The study of mode of delivery has shown a high frequency of pre-planned delivery: 54% caesarean and 24% vaginal delivery. A high-risk of occurrence of hyaline membrane disease was identified around 37 weeks gestational age in the case of preplanned delivery. CONCLUSION: Preplanned delivery near 37 weeks gestational age may increase the risk of occurrence of hyaline membrane disease in full-term neonates.

Decreased neutrophil apoptosis in tracheal fluids of preterm infants at risk of chronic lung disease.

OBJECTIVE: To investigate the hypothesis that preterm infants who are more susceptible to lung damage have decreased neutrophil apoptosis, and to explore its relation to interleukin 10 (IL10) concentration. DESIGN: Prospective cohort design. PATIENTS: One hundred tracheal fluid specimens from 50 week-1 ventilated infants were examined for IL10 (by enzyme linked immunosorbent assay) and neutrophil apoptosis (by light microscopy). RESULTS: Neutrophil apoptosis was absent or less than 0.22% (median 0%) in the 11 infants with chronic lung disease (CLD) (24-31 weeks gestation) during the first 4 days of life. This was significantly lower than that of the 20 preterm infants without CLD (27-31 weeks gestation; median 0.47%, range 0-1.25%) and 19 term infants (median 0.5%, range 0-2.25%). There was an increase in apoptosis in infants with CLD (median 0.44%, p = 0.046) during days 5-7. Few infants without CLD were intubated beyond 4 days. Median apoptosis on days 5-7 was 0.26% and 2.78% for non-CLD preterm and term infants, but differences were not significant. IL10 concentration in tracheal fluid of infants with CLD was less than 5 pg/ml. None of the infants with IL10 greater than 5 pg/ml developed CLD. The range of IL10 concentrations in tracheal fluid from infants without CLD was wide (0-938 pg/ml). There was no apparent correlation between IL10 levels and percentage neutrophil apoptosis in infants without CLD. CONCLUSION: Preterm infants with low levels of IL10 and neutrophil apoptosis may be predisposed to disordered lung repair. Further studies into the method of disposal of senescent neutrophils within preterm lungs are required.

Is the BPD epidemic diminishing?

In a previous study of very low birth weight neonates, < or = 1500 g, admitted to the Vanderbilt University Neonatal Intensive Care Unit (NICU) from 1976-1990, improvements in survival were accompanied by a corresponding increase in the incidence of bronchopulmonary dysplasia (BPD). Since then, certain neonatal and perinatal interventions have been introduced and may influence neonatal outcomes. In this study, we have continued the analysis of the incidence of 3 outcomes: 1) Neonatal death (NEOD), 2) BPD, and 3) NEOD or BPD (NEOD/BPD) for an additional 7 years, 1991-1997. A retrospective study was performed of 3,837 patients with birth weight < or = 1500 g and admitted to the Vanderbilt NICU within 24 hours of birth from 1976 through 1997. The outcomes NEOD, BPD, or NEOD/BPD were modeled by using multiple logistic regression with the following risk factors included as covariates: birth weight, gestational age, Apgar scores at 1 and 5 minutes, gender, race, birth location, diagnosis of hyaline membrane disease, maternal age, maternal diabetes, delivery method, multiple births, duration of ruptured membranes, and biologically relevant interactions among these covariates. To assess time trends in the risk factors and outcomes, patients were divided into time periods (1 = 1976-80, 2 = 1981-85, 3 = 1986-90, 4 = 1991-95, and 5 = 1996-97). For each outcome, only covariates or interactions among covariates found to be significant were retained in the final model. Adjusted odds ratios and 95% confidence intervals were calculated to measure the risk associated with a given time period in comparison to the preceding period. There was a progressive decline in NEOD across all time periods. The previously described increase in BPD from period 1 through period 3 is followed by a decrease in periods 4 and 5. The risk of NEOD/BPD remained fairly constant from period 1 to period 3, but then showed a significant decrease over the two most recent periods. Prior to 1991, the cost of improved survival among very low birth weight infants in this large NICU was an increased incidence of BPD. Since 1991, the risk of BPD has been decreasing even though survival continues to improve. If these findings are also representative of other NICUs, they signify an important reduction in the impact of BPD as one of the costly sequelae of prematurity.

Immunohistochemistry of pulmonary surfactant apoprotein A in forensic autopsy: reassessment in relation to the causes of death.

To reassess the immunohistochemical distribution of pulmonary surfactant apoprotein A (SP-A) in relation to the causes of death, 282 forensic autopsy cases were reviewed. The most intense and dense granular immunostaining of intra-alveolar SP-A was observed in the hyaline membrane syndrome from various traumas, protracted death from drowning, and perinatal aspiration of amniotic fluid. Similar granular staining pattern was found in fatal poisoning by a muscle relaxant and organophosphate pesticides. An evident increase of intra-alveolar granular staining was noted in most fatalities from mechanical asphyxia and drowning, and some cases of fire death. SP-A staining was usually very weak or sparse in alcohol intoxication, poisoning by hypnotics and also carbon monoxide poisoning. These findings suggest that the amount of intra-alveolar granular SP-A staining may be a possible indicator of severity and duration of respiratory distress (agony) from peripheral (non-central nervous system) origin and alveolar damage.

Interleukin-8 expression by fetal and neonatal pulmonary cells in hyaline membrane disease and amniotic infection.

IL-8, a chemokine with striking neutrophil-activating properties, is important in the pathogenesis of various disorders of the adult lung. Little is known about its production and possible role in fetal and neonatal lung disorders. We therefore examined IL-8 expression by immunohistochemistry in lung tissue from neonates with hyaline membrane disease, from fetuses with amniotic infection, and from a fetal control group with noninflammatory diseases. In the majority of cases with hyaline membrane disease, intense IL-8 immunoreaction was seen in fetal and neonatal neutrophils and in almost half of these cases, in epithelial cells of the terminal airways as well as in the connective tissue cell compartment. In contrast, in the amniotic infection group, strong IL-8 immunostaining was almost exclusively seen in maternal aspirated neutrophils. Little or no IL-8 signal was seen in the control cases in all cell types examined. Also, no IL-8 production by fetal lung cells was detected in fetuses <18 wk of gestation. The marked presence of IL-8 in all cell types of the lung in hyaline membrane disease cases indicates a role for IL-8 in the pathobiology of hyaline membrane disease possibly similar to that in adult respiratory distress syndrome. It further suggests that the cytokine network of the fetal lung is already well developed by the second trimester of pregnancy.

A rat model of acute respiratory distress syndrome (ARDS) Part 2, influence of lavage volume, lavage repetition, and therapeutic treatment with rSP-C surfactant.

UNLABELLED: The influence of lavage volume, and lavage repetition with physiological saline solution (groups 1-3: 3x4, 4x4, 5x4, groups 7-9: 3x8, 5x8, 7x8, mL per animal) was studied in a rat lung lavage model of the acute respiratory distress syndrome (ARDS). Anesthetized and tracheotomized rats (12 rats/group) were pressure-controlled ventilated with 100% oxygen at a respiratory rate of 30 breaths/min, inspiration: expiration ratio of 1:2, peak inspiratory pressure of 28 cm H2O at positive end-expiratory pressure of 8 cm H2O during the whole experimental period. To investigate the influence of therapeutic treatment, a recombinant surfactant protein C (rSP-C) containing surfactant was used. Therefore, rats which received a lavage of 4x4 mL per animal (groups 4 to 6) or 7x8 mL per animal (groups 10-12) were treated intratracheally with surfactant doses of 12.5, 25, or 100 mg phospholipids (PL) per kg body weight (bw). In all groups, partial arterial oxygen pressures (PaO2, mm Hg) and partial arterial carbon dioxide pressures (PaCO2, mm Hg) were determined 30 min before, directly after, and 5, 30, 60, 90, 120, 150, 180, and 210 min after the last lavage. Additionally, animals were euthanized 210 min after the last lavage for semiquantitative histopathological grading of coded lung slides. Grading was performed with respect to the severity of hyaline membrane formation (HM), margination and infiltration of polymorphonuclear neutrophil leukocytes (PMNL) into the lung alveoli and interstitial and intraalveolar edema (E). The intrapulmonary distribution of intratracheally applied rSP-C was estimated in selected lung slides stained with polyclonal anti-rSP-C antibody and was compared to unlavaged control rats and unlavaged rats which received 100 mg/kg bw rSP-C. The repetitive lavage depleted the lung from its natural surfactant resources leading to a pathophysiological cascade similar to that of the acute respiratory distress syndrome. PaO2 levels and HM formation showed a lavage-induced decrease. Both changes were significantly dependent on the repetition and volume of the lavage; however, the parameters PMNL and E did not show such a dependence. Treatment with rSP-C surfactant significantly improved oxygenation and reduced HM-formation in a dose-dependent manner independent from the lavage volume. All doses of rSP-C surfactant showed no clear influence on the parameters PMNL and E independently from the lavage volume. In lavaged rat lungs (ARDS-model), the exogenously applied rSP-C was distributed homogeneously along the alveolar lining. Unlavaged rats that received a similar dose of rSP-C showed a marked inhomogeneous extracellular distribution, mainly associated with larger bronchi, while the type II pneumocytes were stained positively in unlavaged control and unlavaged rSP-C treated rats. CONCLUSION: This model mimics very closely the wide spectrum of the clinical situation of human acute lung injury (ALI) because the variation of lavage volume and repetition lead to reproducible different severity grades and states of ALI. The significant reduction of pathognomic changes due to treatment with rSP-C surfactant showed that this is a useful model to estimate the influence of therapeutic concepts in ALI and ARDS.