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Glycolipid accumulation in bronchoalveolar space in adult respiratory distress syndrome.

Surfactant lipids in the alveolar space are believed to play an important role in normal respiratory function. Although the surface-active phospholipids have been extensively studied, the possible role of glycolipids in the surfactant remains to be explored. We have studied the glycolipid composition of cell-free bronchoalveolar lavage from healthy subjects and from adult patients with respiratory distress syndrome. Glycolipids were barely detectable in bronchoalveolar lavage from healthy subjects. However, in adult respiratory distress syndrome, the amount of glycolipid relative to phospholipid was increased by more than twenty times. These lipids, identified as lactosylceramide (galactose-glucose-ceramide) and paragloboside (galactose-N-acetylglucosamine-galactose-glucose-ceramide), may prove to be sensitive markers of lung injury. Since the glycolipids decreased the surface activity of surfactant in vitro, their potential role in the pathogenesis of adult respiratory distress syndrome should be considered.

Carbohydrates↗

Failure of association of premature rupture of membranes with respiratory-distress syndrome.

Records on 16,458 consecutive births were examined to determine associations between the respiratory-distress syndrome of the newborn and cesarean section, maternal diabetes, ante-partum hemorrhage, toxemia of pregnancy, low one-minute Apgar scores and prolonged rupture of fetal membranes. Groups of infants were compared by four-week gestational age blocks. One-minute Apgar scores of less than 5 and of less than 8 were associated with a significant ( less than 0.05) increase in the incidence of respiratory-distress syndrome at gestational ages beyond 30 weeks. Cesarean section was associated with a significant increase after 34 weeks of gestation. There was no association between the syndrome and toxemia of pregnancy, ante-partum hemorrhage or prolonged rupture of fetal membranes. These data do not support the hypothesis that there is a lower incidence of the respiratory-distress syndrome in infants born after prolonged rupture of fetal membranes.

Apgar Score↗

Adult respiratory distress syndrome in a previously healthy young male.

Infection with pneumocystis carinii and cytomegalovirus was found in a young male suspected of having miliary tuberculosis. Problems of diagnosis and predisposing factors for these infections in the patient are discussed. The patient's clinical course and management are reviewed. Autopsy findings are presented. Alternative modes of therapy are considered.

Acquired Immunodeficiency Syndrome↗

A two year follow-up of infants with respiratory distress syndrome.

Forty-seven of 74 infants with idiopathic respiratory distress syndrome who had received intensive care in the neonatal period were examined between the ages of 15 and 24 months to assess their progress. All the children (including the premature infants) had caught up with their peers in height, weight and head circumference. Although 11 infants had a history of respiratory problems, only two showed residual lung changes on radiological examination. Only one infant who had frequent apnoeic spells had serious eye problems due to retrolental fibroplasia. A definite neurological deficit was found in one case, in which a congenital infection could not be ruled out.

Child Development↗

Cavitating lung infarction after bland pulmonary thromboembolism in patients with the adult respiratory distress syndrome.

During one year five patients were observed with the adult respiratory distress syndrome who were found at necropsy to have cavitated lung infarcts following bland (non-infected) pulmonary thromboembolism. There were three instances of bronchopleural fistula and in one person a tension pneumothorax was the immediate cause of death. Four of the five patients had severe lung infections. In all patients airway pressure was raised as a result of positive pressure mechanical ventilation. It is postulated that diffuse microvascular injury, bacterial pneumonia, and high airway pressures may be important factors predisposing patients with adult respiratory distress syndrome to develop lung necrosis, cavitation, and bronchopleural fistula after bland pulmonary thromboembolism. This complication may occur more frequently than has been previously recognised.

Adult↗

Amyloid associated with elastin-staining laminar aggregates in the lungs of patients diagnosed with acute respiratory distress syndrome.

BACKGROUND: The heterogeneity of conditions underlying respiratory distress, whether classified clinically as acute lung injury (ALI) or the more severe acute respiratory distress syndrome (ARDS), has hampered efforts to identify and more successfully treat these patients. Examination of postmortem lungs among cases clinically diagnosed as ARDS identified a cohort that showed a consistent morphology at the light and electron microscope levels, and featured pathognomonic structures which we termed elastin-staining laminar structures (ELS). METHODS: Postmortem tissues were stained using the Verhoeff-Van Gieson procedure for elastic fibers, and with Congo red for examination under a polarizing microscope. Similar samples were examined by transmission EM. RESULTS: The pathognomonic ELS presented as ordered molecular aggregates when stained using the Verhoeff-van Gieson technique for elastic fibers. In several postmortem lungs, the ELS also displayed apple-green birefringence after staining with Congo red, suggesting the presence of amyloid. Remarkably, most of the postmortem lungs with ELS exhibited no significant acute inflammatory cellular response such as neutrophilic reaction, and little evidence of widespread edema except for focal intra-alveolar hemorrhage. CONCLUSIONS: Postmortem lungs that exhibit the ELS constitute a morphologically-identifiable subgroup of ARDS cases. The ordered nature of the ELS, as indicated by both elastin and amyloid stains, together with little morphological evidence of inflammation or edema, suggests that this cohort of ARDS may represent another form of conformational disease. If this hypothesis is confirmed, it will require a new approach in the diagnosis and treatment of patients who exhibit this form of acute lung injury.

Journal Article↗

Effects of postnatal aminophylline on the course of respiratory distress syndrome in premature infants.

The effect of postnatally administered aminophylline on the development of respiratory distress syndrome was evaluated in 25 premature infants weighing less than 1,500 gm. By random allocation, 14 infants were treated with aminophylline intravenously, and 11 infants served as controls. In the treated infants, a loading dose of 6 mg/kg of aminophylline was administered on the first day of life, and maintenance dosages of 4 mg/kg/day were given for the next three days. Respiratory distress syndrome developed in seven infants in the treated group and seven infants in the control group. Ten infants in each group required mechanical ventilation. More cases of intraventricular hemorrhage were diagnosed in the control group, but more deaths occurred in the treated group. These findings led to the conclusion that aminophylline administered postnatally did not appreciably modify the course of respiratory distress syndrome.

Aminophylline↗

Antenatal ambroxol treatment does not prevent the respiratory distress syndrome in premature infants.

UNLABELLED: The effectiveness of ambroxol in the prevention of neonatal respiratory distress syndrome and in reducing the need for intermittent mandatory ventilation and oxygen therapy was studied in 88 mothers whose infants was born between 24 and 34 weeks of gestation and who were randomized either for treatment with ambroxol (group A = 42) or served as control (group B = 46). There were no significant differences in the mean gestational age, birth weight or Apgar score between the two groups. We found no significant differences in occurrence of respiratory distress syndrome (55% vs 45%), in support by intermittent mandatory ventilation (71% vs 72%) or oxygen therapy (74% vs 75%) at 12 h of age between groups A and B. CONCLUSION: This study does not suggest the efficacy of antenatal ambroxol treatment both for the prevention of neonatal respiratory distress syndrome and for the reduction of its severity.

Ambroxol↗

Cost of surfactant replacement treatment for severe neonatal respiratory distress syndrome: a randomised controlled trial.

OBJECTIVE: To estimate the cost of treating babies with severe respiratory distress syndrome with natural porcine surfactant. DESIGN: Retrospective controlled survey. SETTING: Regional neonatal intensive care unit, Belfast. PATIENTS: 33 Preterm babies with severe respiratory distress syndrome who were enrolled in a European multicentre trial during 1985-7. 19 Babies were treated with surfactant and 14 served as controls. INTERVENTIONS: Treatment with natural porcine surfactant. MAIN OUTCOME MEASURE: Cost associated with surfactant replacement treatment per extra survivor in the treatment group and cost per quality adjusted life year for each extra survivor. RESULTS: Fifteen (79%) of the 19 treated babies and five (36%) of the 14 control babies survived. On average, the control babies required 20 days in hospital compared with 61 days for the treated babies (or 95 [corrected] days per extra survivor in the treatment group). The cost per extra survivor in the treatment group was pounds 13,720, with the cost per quality adjusted life year estimated at pounds 710. CONCLUSION: These costs compare favourably with those of established forms of treatment in adults. Thus surfactant replacement treatment for severe respiratory distress syndrome is fairly inexpensive and cost effective.

Combined Modality Therapy↗

Respiratory index/pulmonary shunt relationship: quantification of severity and prognosis in the post-traumatic adult respiratory distress syndrome.

The relationship between the respiratory index (RI = alveolar-arterial oxygen gradient [P(A-a)O2] normalized by PaO2) and the pulmonary shunt (Qsp/Qt) has been examined in 929 studies from 240 critically ill post-traumatic patients. Of these, 88 patients (443 studies) were individuals who developed post-traumatic adult respiratory distress syndrome (ARDS) and 152 were patients (486 studies) who did not develop ARDS. This study demonstrates that the RI to Qsp/Qt [RI/(Qsp/Qt)] relationship was significantly (p less than .0001) increased in patients who developed fatal ARDS compared with those who did not develop ARDS, or with those whose ARDS resolved. Because of the increased oxygen consumption (VO2) in ARDS patients in association with their severe limitations in gas exchange (RI) and increased Qsp/Qt, surviving ARDS patients had a significant increase in the cardiac index which resulted in a higher oxygen delivery to VO2 ratio. ARDS patients showed significant (p less than .0001) evidence of increased pulmonary vascular tone, correlated with the increase in the RI/(Qsp/Qt) relationship. In addition, those patients with high RI/(Qsp/Qt) also had increased right ventricular (RVSW) to left ventricular work (LVSW) ratios which were shown to be a direct function of the rise in RI. This increase in both RVSW/LVSW and RI/(Qsp/Qt) ratios was significantly (p less than .0001) correlated with an increased mortality. Thus, the RI/(Qsp/Qt) relationship, which can be obtained from arterial and mixed venous blood gases and saturations only, can be used to predict the severity of the ARDS process as well as important pulmonary vascular and right ventricular overload consequences.

Hemodynamics↗

Surfactant therapy and nasal continuous positive airway pressure for newborns with respiratory distress syndrome. Danish-Swedish Multicenter Study Group.

BACKGROUND: In southern Scandinavia most babies with respiratory distress syndrome are initially treated with nasal continuous positive airway pressure. We performed a multicenter trial to investigate whether the addition of a single dose of porcine surfactant administered during a short intubation before the occurrence of serious deterioration could reduce the subsequent need for mechanical ventilation. METHODS: We randomly assigned 35 infants with moderate-to-severe respiratory distress syndrome to surfactant therapy (Curosurf, 200 mg per kilogram of body weight) plus nasal continuous positive airway pressure and 33 infants to nasal continuous positive airway pressure alone. The study was not blinded. The indications for mechanical ventilation were a ratio of arterial to alveolar oxygen tension of less than 0.15, severe apneic attacks, or both. RESULTS: Six hours after randomization, when the median age of the babies was 18 hours, the mean ratio of arterial to alveolar oxygen tension was 0.37 in the surfactant-treated babies, as compared with 0.25 in the controls (P < 0.001). The need for subsequent mechanical ventilation was reduced with surfactant therapy (to 43 percent of the surfactant-treated babies as compared with 85 percent of the controls; P = 0.003). When 17 infants with ratios of arterial-to-alveolar oxygen tension of less than 0.15 at randomization were excluded, the need for mechanical ventilation was still significantly reduced in the surfactant-treated group (to 33 percent [9 of 27 babies], as compared with 83 percent [20 of 24 babies] in the control group; (P < 0.001). After 28 days, two of the surfactant-treated babies had died, as compared with five of the control babies. CONCLUSIONS: In babies with moderate-to-severe respiratory distress syndrome treated with nasal continuous positive airway pressure, a single dose of surfactant reduced the need for subsequent mechanical ventilation.

Biological Products↗

Efficacy of Curosurf in a rat model of acute respiratory distress syndrome.

Curosurf, a natural lung surfactant, is considered a potential candidate for improving the treatment of acute respiratory distress syndrome (ARDS). To investigate this in a rat model of early-stage ARDS, Curosurf (62.5, 125 or 250 mg x kg(-1)) was administered by intratracheal bolus at 10 or 24 h following an intratracheal lipopolysaccharide (LPS; 1.6 mg x kg(-1)) challenge. Survival, respiratory frequency (fR), lung wet weight (LWW), total protein and cell differentiation in bronchoalveolar lavage fluid (BALF) were assessed. Curosurf treatment at 10 h after LPS challenge resulted in 100% survival at both 62.5 and 125 mg x kg(-1); at a dose of 250 mg x kg(-1) administered at 10 h after LPS, 1 out of 6 animals died. At a dose of 125 mg x kg(-1) Curosurf administered at 24 h after LPS, 1 out of 6 animals died. In contrast, only 35% of animals survived when not treated with Curosurf. Curosurf treatment resulted in an improved fR and in a significantly decreased LWW, total protein and number of polymorphonuclear cells in BALF. In conclusion, Curosurf treatment improved respiratory frequency and decreased mortality, pulmonary oedema and inflammation. As the decreased mortality was observed in spontaneously breathing nonoxygenated animals, the results cannot be extrapolated to human artificially ventilated acute respiratory distress syndrome patients with the expectation of a decreased mortality. The results suggest, however, that Curosurf may be an important therapeutic measure in early-stage acute respiratory distress syndrome.

Analysis of Variance↗

A calculator program for determining indices of neonatal respiratory distress syndrome severity.

The potential for treating and preventing neonatal respiratory distress syndrome (RDS) with exogenous surfactant has created renewed interest in quantitative measures and derived scores that can be used to assess disease severity. Many different indices of RDS severity have been suggested. They are useful as outcome measures in clinical trials and may assist in the early identification of infants at risk for severe complications. In this article, a program for the Hewlett-Packard 41CV programmable calculator is presented that calculates indices of RDS severity based on ventilator settings and arterial blood gas values.

Carbon Dioxide↗

Designing clinical trials in acute lung injury/acute respiratory distress syndrome.

PURPOSE OF REVIEW: To review the implications of recent literature for clinical trial design in acute lung injury/acute respiratory distress syndrome (ARDS). RECENT FINDINGS: Refinement of acute lung injury/acute respiratory distress syndrome diagnostic criteria and study enrollment criteria, greater efforts to define usual care appropriately, and balancing of efficacy and effectiveness design principles will be key components of future trials. SUMMARY: Clinical trial design in acute lung injury/acute respiratory distress syndrome faces many challenges. Although we have learned much from past trials, persistent design dilemmas must be addressed for future trials.

Clinical Trials as Topic↗

Plurality-dependent risk of respiratory distress syndrome among very-low-birth-weight infants and antepartum corticosteroid treatment.

OBJECTIVE: The purpose of this study was to determine the effect of antenatal corticosteroids on the incidence of respiratory distress syndrome in singleton infants and multiple infants who weigh <1500 g and are delivered at 24 to 32 weeks of gestation. STUDY DESIGN: The incidence of respiratory distress syndrome was established in 4754 singleton infants, 2460 twin infants, and 906 triplet infants. RESULTS: The incidence of respiratory distress syndrome ranged from 58.2% among singleton infants who received a complete course of antenatal corticosteroid to 81.5% in triplets without any treatment. Complete treatment significantly reduced the incidence of respiratory distress syndrome, compared with partial or no treatment (odds ratio, 0.2-0.6). The adjusted risk for respiratory distress syndrome among infants who received a complete course of antenatal corticosteroids compared with singleton infants increased with plurality (odds ratio, 1.4 and 1.8 for twins and triplets, respectively). CONCLUSION: The effect of corticosteroids decreased with increasing plurality. Irrespective of plurality, a complete course of antenatal corticosteroids significantly reduced the incidence of respiratory distress syndrome, whereas partial treatment had the same effect as no treatment.

Adrenal Cortex Hormones↗

[Respiratory distress syndrome in premature births].

The paper reports the results of a study of respiratory distress syndrome in premature birth, one of the most common and important forms of respiratory disorders affecting neonates during the first days of life. One hundred and fifty-six premature births from 1 January 1986 to 30 June 1988 were included in the study. From an analysis of results it emerges that there is a lower incidence of respiratory distress syndrome in both vaginal deliveries and cases treated with Ambroxol.

Ambroxol↗

Acute respiratory distress syndrome and pneumonia: a comprehensive review of clinical data.

Acute respiratory distress syndrome (ARDS) and pneumonia are closely correlated in the critically ill patient. Whereas ARDS is often complicated by nosocomial pneumonia, pulmonary infection is also the most frequent single cause of ARDS. The prevalence of pneumonia during the course of ARDS seems to be particularly high, but whether persons with ARDS are more susceptible to pneumonia or simply have more risk factors remains unknown because of methodological limitations. Recent research suggests that host factors have a major bearing on the development of ARDS. To date, sepsis seems to be the principal link between pneumonia and ARDS. However, prospective observational data on this supposed sequence are not available. The individual role of specific pathogens for the development of ARDS is difficult to assess, because prospective studies are missing. Respiratory viruses have received particular attention, but this review suggests that infections with coronavirus and avian influenza virus (H5N1) are associated with a high incidence of ARDS.

Animals↗