Pathologic findings of scrub typhus have been characterized by vasculitis of the microvasculature of the involved organ resulting from a direct invasion by Orientia tsutsugamushi. We experienced a case of acute respiratory distress syndrome (ARDS) associated with scrub typhus. The case was proven by eschar and high titer of serum IgM antibody (positive at 1:1280). Open lung biopsy showed diffuse alveolar damage (DAD) in the organizing stage without evidence of vasculitis. Immunofluorescent antibody staining and polymerase chain reaction for O. tsutsugamushi failed to demonstrate the organism in the lung tissue. The patient expired due to progressive respiratory failure despite doxycycline therapy. Immunologic mechanism, without direct invasion of the organism, may participate in the pathogenesis of ARDS associated with scrub typhus.
Acute Disease ; Aged ; Case Report ; Fatal Outcome ; Female ; Human ; Infant, Newborn ; Pulmonary Alveoli/pathology ; Pulmonary Alveoli/injuries ; Respiratory Distress Syndrome/physiopathology ; Respiratory Distress Syndrome/pathology ; Respiratory Distress Syndrome/immunology ; Respiratory Distress Syndrome/complications* ; Scrub Typhus/physiopathology ; Scrub Typhus/pathology ; Scrub Typhus/immunology ; Scrub Typhus/complications* ; Vasculitis

PURPOSE: Neonatal respiratory distress syndrome is caused by the deficiency of lung surfactant in premature babies. For the treatment of RDS at present surfactants such as Surfacten (Tokyo-Tanabe Co., Japan) and Exosurf (Wellcome Co., USA) are used. As awarded the grant from the Ministry of Science and Technology for a model research project of Medium-Technology program, we have modified (supplemented) the bovine lung extracts to get YY-38, for which we have performed physical and biological activities. METHODS: For physical properties, we performed stable microbubble test (SMR) and measured surface tension lowering activity using a pulsating bubble surfactometer. Minimum and maximum surface tensions measured at 1 and 5 minutes gave surface tension-surface area diagrams, from which compressibility at surface tension 10mN/m was also calculated. As to the biological activity, we used premature rabbit fetuses as a model for the study of pressure-lung volume relationship. The lung pathology was examined on the lung tissues subsequently obtained, and aerated area ratios were calculated based on the area measured by an image analyzer. RESULTS: The minimum surface tensions of YY-38 at 1 and 5 minutes for all different concentrations were low at 10mN/m, while the maximum surface tensions ranged from 33.01mN/m to 41.07mN/m. The surface tension-surface area curve showed a definite hysteresis at 1 and 5 minutes for all concentrations, and the surface tension fell below 10mN/m with 20% surface area compression. The compressibilities at surface tension 10mN/m at 5minutes for all concentrations were all below 0.02. In animal experiments, the mean lung volume of premature rabbit fetuses was inflated to 80.9ml/kg at maximum 30cmH2O, while the lung volume was maintained at 38.3mg/kg when the lung was deflated to 5cmH2O. The overall aerated area ratio was 45.4%. CONCLUSIONS: YY-38 formed sufficient amount of stable microbubbles and had a surface tension low enough to maintain alveolar stability and to exhibit a good hysteresis curve. In animal experiments it helped the expansion of premature lungs during inspiratory phase and was effective in the prevention of collapse during expiratory phase.
Animal Experimentation ; Awards and Prizes ; Fetus ; Financing, Organized ; Lung* ; Microbubbles ; Pathology ; Respiratory Distress Syndrome, Newborn ; Surface Tension ; Surface-Active Agents

Neonatal respiratory distress syndrome (RDS) is a disease that is unique to newborn infants. It is caused by a deficiency of pulmonary surfactant (PS), which is usually ready to be activated around the perinatal period. Until RDS was more clearly understood, it was not known why premature infants died from respiratory failure, although pathology revealed hyaline membranes in the alveoli. Surprisingly, the era of PS replacement therapy began only relatively recently. The first clinical trial investigating neonatal RDS was conducted in 1980. Since then, newborn survival has improved dramatically, which has led to significant advances in the field of neonatology. The present comprehensive review addresses PS, from its discovery to the application of artificial PS in newborns with RDS. It also reviews the history of PS in Korea, including its introduction, various commercial products, present and past research, newborn registries, and health insurance issues. Finally, it describes the inception of the Korean Society of Neonatology and future directions of research and treatment.
History of Medicine ; Humans ; Hyalin ; Infant, Newborn ; Infant, Premature ; Insurance, Health ; Korea ; Membranes ; Neonatology ; Pathology ; Pulmonary Surfactants ; Registries ; Respiratory Distress Syndrome, Newborn ; Respiratory Insufficiency

Female ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Infant, Newborn ; Lung ; metabolism ; pathology ; Macrophage Migration-Inhibitory Factors ; analysis ; genetics ; Male ; Respiratory Distress Syndrome, Adult ; blood ; genetics ; pathology

This study was aimed to provide data on the use of medical resources by preterm infants following discharge from the neonatal intensive care unit (NICU). The cohort included preterm infants (n=2,351) born at 22-32 weeks' gestation who were discharged from the NICUs of 44 Korean hospitals between April 2009 to March 2010. Mean duration of post-discharge follow-up was 425+/-237 days. After discharge from the NICU, 94.5% of total infants visited a pediatric outpatient clinic (11.5+/-9.8 mean visits), 42.9% visited a pediatric clinic for respiratory problems irregularly (4.9+/-6.6 mean visits), and 31.1% utilized emergency center at least once. Among all visits to the emergency center, 24.7% resulted in readmission and 50.8% of those visits were due to respiratory problems. At least one episode of readmission was required by 33.6% (788/2,346) of total infants, and 18.4% (431/2,346) of total infants were readmitted with respiratory problems at least once. Among all infants readmitted for respiratory problems, 16.2% (70/341) were diagnosed with respiratory syncytial virus infection which accounted for 30.3% of viral etiologies confirmed by laboratory testing. Infants born at <30 weeks' gestation had more frequent total readmission and respiratory readmission than those > or =30 weeks' gestation (2+/-1.7 vs. 1.7+/-1.2, P=0.009, 1.8+/-1.2 vs. 1.5+/-1.1, 0.027, respectively). Overall, use of medical resources is common, and respiratory problems are the leading cause of use of medical resources. Total readmissions and respiratory readmissions are more frequent in more immature infants.
Cohort Studies ; Databases, Factual ; Emergency Service, Hospital ; Female ; Follow-Up Studies ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases/*pathology ; Intensive Care Units, Neonatal ; Male ; Patient Readmission ; Republic of Korea ; Respiratory Distress Syndrome, Newborn/*pathology ; Retrospective Studies

We undertook a multi-hospital collective study to evaluate outcomes of neonatal respiratory distress syndrome (RDS) patients treated with pulmonary surfactant (PS) over 17 yr in Korea (Group I; 1990/91, Group II; 1996, Group III; 2002, and Group IV; 2007). There were 60 neonates in Group I (16 hospitals), 1,179 in Group II (64), 1,595 in Group III (62), and 1,921 in Group IV (57). We adopted Bomsel's classification to evaluate initial chest radiographic findings, categorized RDS severities, and classified response types to PS therapy. Almost all cases were treated using a single dose in Groups I and II, but 19.5% received multiple-dose therapy in Group IV. In Group IV, Bomsel's stages III and IV composed 62.9% and initial severities of mild, moderate, and severe RDS were 23.0%, 42.0%, and 35.0%. More infants showed good response in Groups II, III, and IV than in Group I (71.7%, 66.8%, and 69.2% vs. 58.3%). Complications and mortality rate were lower in Group IV than in Groups I, II, and III (mortality rate: 14.3% vs. 40.0%, 30.0%, and 18.7%). We conclude that PS therapy in neonates with RDS had a remarkable impact on improving clinical course and outcomes over 17 yr in Korea.
Birth Weight ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Premature, Diseases/epidemiology/mortality/pathology/*therapy ; Korea/epidemiology ; Longitudinal Studies ; Pregnancy ; Pulmonary Surfactants/*therapeutic use ; Questionnaires ; Radiography, Thoracic ; Respiratory Distress Syndrome, Newborn/epidemiology/mortality/pathology/*therapy ; Treatment Outcome

Newfactan(R) is a domestically developed, bovine lung-derived, semi-synthetic surfactant. The aim of this study was to compare the clinical efficacy of Newfactan(R) with that of Surfacten(R) in the treatment of respiratory distress syndrome (RDS). Newfactan(R) or Surfacten(R) was randomly allocated to 492 newborn infants who were diagnosed as RDS and required surfactant instillation in four participating hospitals. The comparisons were made individually in two subsets of infants by birth weight (<1,500 g group [n=253] and >or=1,500 g group [n=239]). Short-term responses to surfactant and acute complications, such as the total doses of surfactant instilled, response type, extubation rate, ventilator settings, changes in respiratory parameters, air leak, patent ductus arteriosus, pulmonary hemorrhage, and intraventricular hemorrhage, and mortality during the 96 hr after surfactant instillation were measured. Long-term outcome and complications, such as total duration of intubation, bronchopulmonary dysplasia and periventricular leukomalacia, and ultimate mortality were measured. There were no significant differences in demographic and perinatal variables, shortterm responses to surfactant and acute complications, and long-term outcome and complications between Newfactan(R) and Surfacten(R) in both birth weight groups. We concluded that Newfactan(R) was comparable to Surfacten(R) in the clinical efficacy in the treatment of RDS in both birth weight groups.
Comparative Study ; Female ; Humans ; Infant, Newborn ; Lung/drug effects/pathology/physiopathology ; Male ; Pulmonary Surfactants/*therapeutic use ; Research Support, Non-U.S. Gov't ; Respiratory Distress Syndrome, Newborn/*drug therapy/mortality ; Survival Rate ; Time Factors ; Treatment Outcome

OBJECTIVETo investigate the association of ATP-binding cassette transporter A3 (ABCA3) gene mutations with severe neonatal respiratory distress syndrome (NRDS) and lung disease in children.

METHODThirty-eight children hospitalized with respiratory disorders in Children's Hospital of Chongqing Medical University from January 2010 to December 2011 were screened. Two mutations (E292V, G1221S) in the ABCA3 gene were identified. Interstitial lung disease (ILD) was present in 10 cases, NRDS was found in 23 and congenital pulmonary dysplasia in 5 cases. There were 24 males and 14 females, with an age range of 1 hour to 15 years. Genomic DNA was prepared from blood samples and sequences were analyzed by polymerase chain reaction (PCR). Clinical feature, imaging characteristics and the results of gene detection were retrospectively analyzed.

RESULTFour cases with ABCA3 gene mutations were found; 2 patients (case 2 and case 4) had the heterozygous mutation of ABCA3 E292V. One was a 3-hour-old girl and another was a 52-day-old boy, 2 patients (case 1 and case 4) had the heterozygous mutation of ABCA3 G1221S. One was a 78-day-old boy and another was a girl, 15 years and one month old. The family history was negative for respiratory disease. Three patients (case 1, 2, 4 ) had NRDS and 2 (case 1, 2) of them were premature. One patient (case 3) had normal growth and development. She was diagnosed clinically as interstitial lung disease (ILD) after admission. The clinical outcomes of 4 cases were various. Case 1 had recurrent wheezing and inhaled corticosteroid was needed. Case 2 died because she failed to wean from mechanical ventilator. Case 3 was discharged with improvement but lost to follow-up. Case 4 grows normally.

CONCLUSIONGenetic variants within ABCA3 may be the genetic causes or background of a contributor to some unexplained refractory NRDS, and chronic lung disease developed in latter childhood. Identification of ABCA3 genetic variants in NRDS infants is important to offer genetic counseling, as well as early prognosis estimation and intervention in pediatric chronic lung disease.

ATP-Binding Cassette Transporters ; genetics ; Adolescent ; Child ; Child, Preschool ; DNA Mutational Analysis ; Exons ; Female ; Heterozygote ; Humans ; Infant ; Infant, Newborn ; Lung ; diagnostic imaging ; pathology ; Lung Diseases, Interstitial ; diagnosis ; genetics ; Male ; Mutation ; genetics ; Radiography ; Respiratory Distress Syndrome, Newborn ; diagnosis ; genetics

To analyze clinical characteristics and risk factors of very low birth weight and extremely low birth weight infants with bronchopulmonary dysplasia (BPD). A retrospective epidemiological study was performed in 768 neonates (376 males) with birth weights<1 500 g and gestational age ≤ 34 weeks who survived ≥28 days. Clinical data were obtained from the multi-center clinical database of neonatal intensive care units (NICU) in 19 hospitals of Jiangsu Province between January 1, 2017 and December 31, 2017. These infants were divided into non-BPD group and BPD group according to BPD diagnositic criteria. Clinical features and potential risk factors were compared between groups with Chi-square test or nonparametric test. Risk factors for BPD were analyzed with Logistic regression analysis. Among the total of 768 eligible neonates, 577 without BPD, 191 with BPD (24.9%). Mild, moderate and severe BPD accounted for 73.3% (140/191), 23.6% (45/191) and 3.1% (6/191) of all BPD cases respectively. There were significant differences in the average gestational age (29 (28, 30) 30 (29, 31) weeks) or the average birth weight (1 170 (990, 1 300) 1 300 (1 160, 1 400) g) between BPD group and non-BPD group (-9.959,-7.202, both 0.000). The incidences of BPD in the infants with gestational age of<28 weeks, 28-31 weeks and 32-34 weeks were 51.7% (46/89), 24.8% (139/561), 5.1% (6/118) respectively. The incidences of BPD in infants with birth weigh1 000 g, 1 000- 1 249 g and 1 250-1 500 g were 62.3% (48/77), 25.9% (70/270) and 17.3% (73/421) respectively. Proportion of male (55.5% (106/191) 46.8% (270/577)), rate and length of conventional mechanical ventilation (48.7% (93/191) 14.9% (86/577), 120 (72, 259) 80 (29, 144)h), initial inhaled oxygen concentration and maximum inhaled oxygen concentration (0.35 (0.30, 0.40) 0.30(0.25, 0.40), 0.40 (0.30, 0.50) 0.30 (0.30, 0.40)) and volume of red blood cell transfusion (53(30, 90) .38(28, 55) ml) were higher in BPD group than in non-BPD group (χ(2)=4.350, 91.640, -3.557, -2.848, -3.776, -4.677, all 0.05). Rate of continuous positive airway pressure (12.6%(24/191) 19.4%(112/577)) during neonatal resuscitation in delivery room was lower in BPD group than that in non-BPD group (χ(2)=4.614, 0.032). The incidences of complications in BPD group including severe asphyxia, neonatal respiratory distress syndrome (NRDS), persistent pulmonary hypertension in newborns (PPHN), patent ductus arteriosus, anemia of prematurity, early onset sepsis, clinical sepsis and ventilator associated pneumonia were higher than that in non-BPD group (15.2%(29/191) 4.5% (26/577), 91.1% (174/191) 56.7% (327/577), 2.6% (5/191) 0.2% (1/577), 43.5% (83/191) 34.2% (197/577), 88.0% (168/191) 58.8% (339/577), 15.7% (30/191) 9.9% (57/577), 42.9% (82/191) 18.6% (107/577), 14.1% (27/191) 2.3% (13/577); χ(2)=24.605, 74.993, 9.167, 5.373, 61.866, 4.557, 43.149, 34.315, all 0.05). Multivariate logistic regression analysis showed that NRDS (4.651, 95: 1.860-11.625), clinical sepsis (1.989, 95: 1.067-3.708), ventilator associated pneumonia (3.155, 95: 1.060-9.388), conventional mechanical ventilation (2.298, 95: 1.152-4.586), and volume of red blood cell transfusion (1.013, 95: 1.002-1.024) were risk factors of BPD. BPD is more common in very low birth weight infants of male with gestational age less than 32 weeks. Using CPAP in the delivery room, active treatment of NRDS, preventing nosocomial infection, and reducing invasive ventilation and red blood cell transfusion may decrease the incidence of BPD.
Birth Weight ; Bronchopulmonary Dysplasia ; complications ; epidemiology ; pathology ; Gestational Age ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Infant, Very Low Birth Weight ; Male ; Respiratory Distress Syndrome, Newborn ; Retrospective Studies ; Risk Factors

Conflicting results on the influences of histologic chorioamnionitis (HC) on neonatal morbidities might be partly originated from using different definition of HC. The aim of this study was to determine the relationship between HC and neonatal morbidities using definition of HC that reflects the site and extent of inflammation. This was a retrospective cohort study of 261 very low birth weight (VLBW) infants admitted at a tertiary academic center. Based on the site of inflammation, HC was categorized: any HC; amnionitis; funisitis; amnionitis+funisitis. The extent of inflammation in each site was reflected by sub-defining high grade (HG). The incidences of morbidities in infants with and without HC were compared. The bronchopulmonary dysplasia (BPD) rate was significantly higher in infants with amnionitis and the severe retinopathy of prematurity (ROP) rate was significantly higher in infants with any HC and funisitis. After adjustment for both gestational age and birth weight, the respiratory distress syndrome (RDS) rate was significantly lower in infants with all categories of HC except for HG amnionitis and HG funisitis, which are not associated with lower RDS rate. HG amnionitis was significantly associated with increased BPD rate but the association of HC with severe ROP disappeared. In conclusion, HC is significantly associated with decreased RDS and HG amnionitis with increased BPD while lacking association with other neonatal morbidities in VLBW infants. The association with HC and neonatal morbidities differs by the site and extent of chorioamnionitis.
Adult ; Birth Weight ; Bronchopulmonary Dysplasia/complications/*epidemiology ; Chorioamnionitis/classification/*epidemiology/pathology ; Cohort Studies ; Female ; Gestational Age ; Humans ; Infant, Newborn ; *Infant, Very Low Birth Weight ; Neutrophil Infiltration/immunology ; Placenta/pathology ; Pre-Eclampsia/*epidemiology/pathology ; Pregnancy ; Respiratory Distress Syndrome, Newborn/complications/*epidemiology ; Retinopathy of Prematurity/complications/*epidemiology ; Retrospective Studies ; Tertiary Care Centers