Medicine › Pulmonary and Respiratory Medicine

Neonatal Respiratory Health Research

Works Count: 134687

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Description

This cluster of papers focuses on neonatal lung development, respiratory morbidity, and the impact of various interventions on outcomes for preterm infants. It covers topics such as bronchopulmonary dysplasia, lung stem cells, surfactant proteins, pulmonary hypertension, and the use of antenatal corticosteroids. The research also delves into neonatal resuscitation, oxygen saturation targeting, and the potential for lung regeneration in this population.

Keywords

Bronchopulmonary Dysplasia; Preterm Infants; Lung Stem Cells; Respiratory Distress Syndrome; Surfactant Proteins; Neonatal Resuscitation; Pulmonary Hypertension; Oxygen Saturation; Antenatal Corticosteroids; Lung Regeneration

Textbook of Neonatal Resuscitation

2021-06-01

John Kattwinkel

The NRP 8th Edition introduces a new educational methodology to better meet the needs of health care professionals who manage the newly born baby. Available for purchase at https://www.aap.org/textbook-of-neonatal-resuscitation-8th-edition-paperback/ (NOTE: … The NRP 8th Edition introduces a new educational methodology to better meet the needs of health care professionals who manage the newly born baby. Available for purchase at https://www.aap.org/textbook-of-neonatal-resuscitation-8th-edition-paperback/ (NOTE: This book features a full text reading experience. Click a chapter title to access content.)

Abnormal Pulmonary Outcomes in Premature Infants: Prediction From Oxygen Requirement in the Neonatal Period

1988-10-01

Andrew Shennan , Michael Dunn , A. Ohlsson +2 more

The follow-up records of 605 infants with birth weights of less than 1,500 g, with data available for 2 years after birth, were examined for evidence of abnormal pulmonary signs … The follow-up records of 605 infants with birth weights of less than 1,500 g, with data available for 2 years after birth, were examined for evidence of abnormal pulmonary signs or symptoms. A total of 119 infants were identified and the neonatal oxygen requirements of these infants were compared with those of 486 infants who had normal pulmonary function. A requirement for oxygen at 28 days of life had a positive predictive value for abnormal pulmonary findings at the time of follow-up of only 38%, whereas 31% of those with normal pulmonary findings at the time of follow-up were still receiving oxygen at this age. The need for oxygen at 28 days was a good predictor of abnormal findings in infants of ≥3O weeks' gestational age at birth but became increasingly less useful as gestational age decreased It was found that, irrespective of gestational age at birth, the ment for additional oxygen at 36 weeks' corrected postnatal gestational age was a better predictor of abnormal outcome, increasing the positive predictive value to 63%. The prediction of a normal outcome remained 90% for infants not receiving oxygen at this corrected gestational age.

The Lung: Scientific Foundations

1991-09-15

Ronald G. Crystal , John B. West

Section Titles I. General Biologic Processes II. Strategies for Understanding the Lung in Health and Disease III. Major Components IV. Integrated Morphology: Growth and Form V. Integrated Physiology and Pathophysiology … Section Titles I. General Biologic Processes II. Strategies for Understanding the Lung in Health and Disease III. Major Components IV. Integrated Morphology: Growth and Form V. Integrated Physiology and Pathophysiology VI. The Fetal, Perinatal, Postnatal, and Aging Lung VII. Lung Injury, Defense and Repair VIII. Special Environments and Interventions

Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures. Protection by positive end-expiratory pressure.

1974-11-01

Hanna Webb , Donald F. Tierney

We used a small animal respirator to ventilate normal, anesthetized rats with room air at peak inspiratory pressures of 14, 30, or 45 cm H2O and no added end-expiratory pressures … We used a small animal respirator to ventilate normal, anesthetized rats with room air at peak inspiratory pressures of 14, 30, or 45 cm H2O and no added end-expiratory pressures (intermittent positive pressure breathing [IPPB] 14/0, high inspiratory positive pressure breathing [HIPPB] 30/0, HIPPB 45/0). Other rats were ventilated with the same high inspiratory pressures but with an added end-expiratory pressure of 10 cm H2O (positive end-expiratory pressure [PEEP] 30/10, PEEP 45/10). Control rats that were not ventilated and the IPPB 14/0 group showed no pathologic lung changes. The HIPPB 30/0 and PEEP 30/10 groups had perivascular edema but no alveolar edema. The HIPPB 45/0 animals had alveolar and perivascular edema, severe hypoxemia, and decreased dynamic compliance and died within one hour. In contrast, the PEEP 45/10 animals had no alveolar edema and survived. We postulate that interstitial perivascular edema develops from ventilation with high inflating pressures by mechanisms of lung interdependen...

Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993-2012

2015-09-08

Barbara J. Stoll , Nellie I. Hansen , Edward F. Bell +7 more

<h3>Importance</h3> Extremely preterm infants contribute disproportionately to neonatal morbidity and mortality. <h3>Objective</h3> To review 20-year trends in maternal/neonatal care, complications, and mortality among extremely preterm infants born at Neonatal Research … <h3>Importance</h3> Extremely preterm infants contribute disproportionately to neonatal morbidity and mortality. <h3>Objective</h3> To review 20-year trends in maternal/neonatal care, complications, and mortality among extremely preterm infants born at Neonatal Research Network centers. <h3>Design, Setting, Participants</h3> Prospective registry of 34 636 infants, 22 to 28 weeks' gestation, birth weight of 401 to 1500 g, and born at 26 network centers between 1993 and 2012. <h3>Exposures</h3> Extremely preterm birth. <h3>Main Outcomes and Measures</h3> Maternal/neonatal care, morbidities, and survival. Major morbidities, reported for infants who survived more than 12 hours, were severe necrotizing enterocolitis, infection, bronchopulmonary dysplasia, severe intracranial hemorrhage, cystic periventricular leukomalacia, and/or severe retinopathy of prematurity. Regression models assessed yearly changes and were adjusted for study center, race/ethnicity, gestational age, birth weight for gestational age, and sex. <h3>Results</h3> Use of antenatal corticosteroids increased from 1993 to 2012 (24% [348 of 1431 infants]) to 87% (1674 of 1919 infants];<i>P</i> < .001), as did cesarean delivery (44% [625 of 1431 births] to 64% [1227 of 1921];<i>P</i> < .001). Delivery room intubation decreased from 80% (1144 of 1433 infants) in 1993 to 65% (1253 of 1922) in 2012 (<i>P</i> < .001). After increasing in the 1990s, postnatal steroid use declined to 8% (141 of 1757 infants) in 2004 (<i>P</i> < .001), with no significant change thereafter. Although most infants were ventilated, continuous positive airway pressure without ventilation increased from 7% (120 of 1666 infants) in 2002 to 11% (190 of 1756 infants) in 2012 (<i>P</i> < .001). Despite no improvement from 1993 to 2004, rates of late-onset sepsis declined between 2005 and 2012 for infants of each gestational age (median, 26 weeks [37% {109 of 296} to 27% {85 of 320}]; adjusted relative risk [RR], 0.93 [95% CI, 0.92-0.94]). Rates of other morbidities declined, but bronchopulmonary dysplasia increased between 2009 and 2012 for infants at 26 to 27 weeks' gestation (26 weeks, 50% [130 of 258] to 55% [164 of 297];<i>P</i> < .001). Survival increased between 2009 and 2012 for infants at 23 weeks' gestation (27% [41 of 152] to 33% [50 of 150]; adjusted RR, 1.09 [95% CI, 1.05-1.14]) and 24 weeks (63% [156 of 248] to 65% [174 of 269]; adjusted RR, 1.05 [95% CI, 1.03-1.07]), with smaller relative increases for infants at 25 and 27 weeks' gestation, and no change for infants at 22, 26, and 28 weeks' gestation. Survival without major morbidity increased approximately 2% per year for infants at 25 to 28 weeks' gestation, with no change for infants at 22 to 24 weeks' gestation. <h3>Conclusions and Relevance</h3> Among extremely preterm infants born at US academic centers over the last 20 years, changes in maternal and infant care practices and modest reductions in several morbidities were observed, although bronchopulmonary dysplasia increased. Survival increased most markedly for infants born at 23 and 24 weeks' gestation and survival without major morbidity increased for infants aged 25 to 28 weeks. These findings may be valuable in counseling families and developing novel interventions. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT00063063.

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The relationship between the spleen colony-forming cell and the haemopoietic stem cell.

1978-01-01

R. Schofield

Several experimental findings that are inconsistent with the view that the spleen colony-forming cell (CFU-S) is the primary haemopoietic stem cell are reviewed. Recovery of CFU-S, both quantitatively and qualitatively, … Several experimental findings that are inconsistent with the view that the spleen colony-forming cell (CFU-S) is the primary haemopoietic stem cell are reviewed. Recovery of CFU-S, both quantitatively and qualitatively, can proceed differently depending upon the cytotoxic agent or regime used to bring about the depletion. The virtual immortality of the stem cell population is at variance with evidence that the CFU-S population has an 'age-structure' which has been invoked by several workers to explain experimental and clinical observations. To account for these inconsistencies, a hypothesis is proposed in which the stem cell is seen in association with other cells which determine its behaviour. It becomes essentially a fixed tissue cell. Its maturation is prevented and, as a result, its continued proliferation as a stem cell is assured. Its progeny, unless they can occupy a similar stem cell 'niche', are first generation colony-forming cells, which proliferate and mature to acquire a high probability of differentiation, i.e., they have an age-structure. Some of the experimental situations reviewed are discussed in relation to the proposed hypothesis.

A CONTROLLED TRIAL OF ANTEPARTUM GLUCOCORTICOID TREATMENT FOR PREVENTION OF THE RESPIRATORY DISTRESS SYNDROME IN PREMATURE INFANTS

1972-10-01

G. C. Liggins , R. Nicole Howie

A controlled trial of betamethasone therapy was carried out in 282 mothers in whom premature delivery threatened or was planned before 37 weeks' gestation, in the hope of reducing the … A controlled trial of betamethasone therapy was carried out in 282 mothers in whom premature delivery threatened or was planned before 37 weeks' gestation, in the hope of reducing the incidence of neonatal respiratory distress syndrome by accelerating functional maturation of the fetal lung. Two hundred and thirteen mothers were in spontaneous premature labor. When necessary, ethanol or salbutamol infusions were used to delay delivery while steroid or placebo therapy was given. Delay for at least 24 hours was achieved in 77% of the mothers. In these unplanned deliveries, early neonatal mortality was 3.2% in the treated group and 15.0% in the controls (p 0.01). There were no deaths with hyaline membrane disease or intraventricular cerebral hemorrhage in infants of mothers who had received betamethasone for at least 24 hours before delivery. The respiratory distress syndrome occurred less often in treated babies (9.0%) than in controls (25.8%, p 0.003), but the difference was confined to babies of under 32 weeks' gestation who had been treated for at least 24 hours before delivery (11.8% of the treated babies compared with 69.6% of the control babies p. 0.02). There may be an increased risk of fetal death in pregnancies complicated by severe hypertensionedema-proteinuria syndromes and treated with betamethasone, but no other hazard of steroid therapy was noted. We conclude that this preliminary evidence justifies further trials, but that further work is needed before any new routine procedure is established.

Epithelial-Mesenchymal Transitions in Development and Disease

2009-11-01

Jean Paul Thiery , Hervé Acloque , Ruby Yun‐Ju Huang +1 more

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Alveolar progenitor and stem cells in lung development, renewal and cancer

2014-02-04

Tushar Desai , Douglas Brownfield , Mark A. Krasnow

Chronic Lung Disease after Premature Birth

2007-11-07

Eugenio Baraldi , Marco Filippone

Bronchopulmonary dysplasia has become the most common chronic lung disease of infancy. This review summarizes the patterns and pathogenesis of chronic lung impairment that may become clinically significant decades after … Bronchopulmonary dysplasia has become the most common chronic lung disease of infancy. This review summarizes the patterns and pathogenesis of chronic lung impairment that may become clinically significant decades after the use of mechanical ventilation and oxygen supplementation in premature newborns.

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Control of Cachectin (Tumor Necrosis Factor) Synthesis: Mechanisms of Endotoxin Resistance

1986-05-23

Bruce Beutler , Nadia Krochin , Ian W. Milsark +2 more

Cachectin (tumor necrosis factor) is a macrophage hormone strongly implicated in the pathogenesis of endotoxin-induced shock. The availability of a DNA probe complementary to the cachectin messenger RNA (mRNA), as … Cachectin (tumor necrosis factor) is a macrophage hormone strongly implicated in the pathogenesis of endotoxin-induced shock. The availability of a DNA probe complementary to the cachectin messenger RNA (mRNA), as well as a specific antibody capable of recognizing the cachectin gene product, has made it possible to analyze the regulation of cachectin gene expression under a variety of conditions. Thioglycollate-elicited peritoneal macrophages obtained from mice contain a pool of cachectin mRNA that is not expressed as protein. When the cells are stimulated with endotoxin, a large quantity of additional cachectin mRNA is produced, and immunoreactive cachectin is secreted. Macrophages from mice of the C3H/HeJ strain do not produce cachectin in response to endotoxin. A dual defect appears to prevent cachectin expression. First, a diminished quantity of cachectin mRNA is expressed in response to low concentrations of endotoxin. Second, a post-transcriptional defect prevents the production of cachectin protein. Macrophages from endotoxin-sensitive mice do not produce cachectin if they are first treated with dexamethasone, apparently for similar reasons. These findings give new insight into the nature of the C3H/HeJ mutation and suggest an important mechanism by which glucocorticoids may act to suppress inflammation.

The EPICure Study: Outcomes to Discharge From Hospital for Infants Born at the Threshold of Viability

2000-10-01

Kate Costeloe , Enid Hennessy , Alan T. Gibson +2 more

Objective. To evaluate the outcome for all infants born before 26 weeks of gestation in the United Kingdom and the Republic of Ireland. This report is of survival and complications … Objective. To evaluate the outcome for all infants born before 26 weeks of gestation in the United Kingdom and the Republic of Ireland. This report is of survival and complications up until discharge from hospital. Methodology. A prospective observational study of all births between March 1, 1995 and December 31, 1995 from 20 to 25 weeks of gestation. Results. A total of 4004 births were recorded, and 811 infants were admitted for intensive care. Overall survival was 39% (n = 314). Male sex, no reported chorioamnionitis, no antenatal steroids, persistent bradycardia at 5 minutes, hypothermia, and high Clinical Risk Index for Babies (CRIB) score were all independently associated with death. Of the survivors, 17% had parenchymal cysts and/or hydrocephalus, 14% received treatment for retinopathy of prematurity (ROP), and 51% needed supplementary oxygen at the expected date of delivery. Failure to administer antenatal steroids and postnatal transfer for intensive care within 24 hours of birth were predictive of major scan abnormality; lower gestation was predictive of severe ROP, while being born to a black mother was protective. Being of lower gestation, male sex, tocolysis, low maternal age, neonatal hypothermia, a high CRIB score, and surfactant therapy were all predictive of oxygen dependency. Intensive care was provided in 137 units, only 8 of which had &gt;5 survivors. There was no difference in survival between institutions when divided into quintiles based on their numbers of extremely preterm births or admissions. Conclusions. This study provides outcome data for this geographically defined cohort; survival and neonatal morbidity are consistent with previous data from the United Kingdom and facilitate comparison with other geographically based data.

The fetal inflammatory response syndrome

1998-07-01

Ricardo Gómez , Roberto Romero , Fabio Ghezzi +3 more

Inflammatory and immune processes in the human lung in health and disease: evaluation by bronchoalveolar lavage.

1979-10-01

Gary W. Hunninghake , James E. Gadek , Oichi Kawanami +2 more

New Ballard Score, expanded to include extremely premature infants

1991-09-01

J. Ballard , Jane Khoury , Kathy E. Wedig +3 more

Pulmonary Disease Following Respirator Therapy of Hyaline-Membrane Disease

1967-02-16

William H. Northway , Robert C. Rosan , David Y. Porter

ALTHOUGH hyaline-membrane disease, the respiratory-distress syndrome of the newborn infant, has been the object of increased clinical and research interest in the past ten years, little attention has been paid … ALTHOUGH hyaline-membrane disease, the respiratory-distress syndrome of the newborn infant, has been the object of increased clinical and research interest in the past ten years, little attention has been paid to its possible sequelae.1 , 2 It is stated that most of these infants who survive the first three days of life will recover completely, and by seven to ten days of life will have normal lungs radiographically.3 , 4 Recent experience with critically ill infants at the Stanford Premature Infant Research Center demonstrates that intensive therapy may modify the acute syndrome so as to permit the development of a previously unrecorded abnormality of . . .

Growth in the Neonatal Intensive Care Unit Influences Neurodevelopmental and Growth Outcomes of Extremely Low Birth Weight Infants

2006-04-01

Richard A. Ehrenkranz , Anna M. Dusick , Betty R. Vohr +3 more

OBJECTIVES. The objectives of this study were to assess whether (1) in-hospital growth velocity is predictive of neurodevelopmental and growth outcomes at 18 to 22 months’ corrected age among extremely … OBJECTIVES. The objectives of this study were to assess whether (1) in-hospital growth velocity is predictive of neurodevelopmental and growth outcomes at 18 to 22 months’ corrected age among extremely low birth weight (ELBW) infants and (2) in-hospital growth velocity contributes to these outcomes after controlling for confounding demographic and clinical variables. METHODS. Infants 501 to 1000 g birth weight from a multicenter cohort study were divided into quartiles of in-hospital growth velocity rates. Variables considered for the logistic-regression models included gender, race, gestational age, small for gestational age, mother’s education, severe intraventricular hemorrhage, periventricular leukomalacia, age at regaining birth weight, necrotizing enterocolitis, late-onset infection, bronchopulmonary dysplasia, postnatal steroid therapy for pulmonary disease, and center. RESULTS. Of the 600 discharged infants, 495 (83%) were evaluated at 18 to 22 months’ corrected age. As the rate of weight gain increased between quartile 1 and quartile 4, from 12.0 to 21.2 g/kg per day, the incidence of cerebral palsy, Bayley II Mental Developmental Index (MDI) &lt;70 and Psychomotor Developmental Index (PDI) &lt;70, abnormal neurologic examination, neurodevelopmental impairment, and need for rehospitalization fell significantly. Similar findings were observed as the rate of head circumference growth increased. The in-hospital rate of growth was associated with the likelihood of anthropometric measurements at 18 months’ corrected age below the 10th percentile values of the Centers for Disease Control and Prevention 2000 growth curve. Logistic-regression analyses, controlling for potential demographic or clinical cofounders, and adjusted for center, identified a significant relationship between growth velocity and the likelihood of cerebral palsy, MDI and PDI scores of &lt;70, and neurodevelopmental impairment. CONCLUSIONS. These analyses suggest that growth velocity during an ELBW infant’s NICU hospitalization exerts a significant, and possibly independent, effect on neurodevelopmental and growth outcomes at 18 to 22 months’ corrected age.

Very Low Birth Weight Outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, January 1995 Through December 1996

2001-01-01

James A. Lemons , Charles R. Bauer , William Oh +7 more

Objectives. To determine the mortality and morbidity for infants weighing 401 to 1500 g (very low birth weight [VLBW]) at birth by gestational age, birth weight, and gender. Study Design. … Objectives. To determine the mortality and morbidity for infants weighing 401 to 1500 g (very low birth weight [VLBW]) at birth by gestational age, birth weight, and gender. Study Design. Perinatal data were collected prospectively on an inborn cohort from January 1995 through December 1996 by 14 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network and were compared with the corresponding data from previous reports. Sociodemographic factors, perinatal events, and the neonatal course to 120 days of life, discharge, or death were evaluated. Results. Eighty four percent of 4438 infants weighing 501 to 1500 g at birth survived until discharge to home or to a long-term care facility (compared with 80% in 1991 and 74% in 1988). Survival to discharge was 54% for infants 501 to 750 g at birth, 86% for those 751 to 1000 g, 94% for those 1001 to 1250 g, and 97% for those 1251 to 1500g. The incidence of chronic lung disease (CLD; defined as receiving supplemental oxygen at 36 weeks' postmenstrual age; 23%), proven necrotizing enterocolitis (NEC; 7%), and severe intracranial hemorrhage (ICH; grade III or IV; 11%) remained unchanged between 1991 and 1996. Furthermore, 97% of all VLBW infants and 99% of infants weighing &lt;1000 g at birth had weights less than the 10th percentile at 36 weeks' postmenstrual age. Mortality for 195 infants weighing 401 to 500 g was 89%, with nearly all survivors developing CLD. Mortality in infants weighing 501 to 600 g was 71%; among survivors, 62% had CLD, 35% had severe ICH, and 15% had proven NEC. Conclusions. Survival for infants between 501 and 1500 g at birth continued to improve, particularly for infants weighing &lt;1000 g at birth. This improvement in survival was not associated with an increase in major morbidities, because the incidence of CLD, proven NEC, and severe ICH did not change. However, poor postnatal growth remains a major concern, occurring in 99% of infants weighing &lt;1000 g at birth. Mortality and major morbidity (CLD, severe ICH, and NEC) remain high for the smallest infants, particularly those weighing &lt;600 g at birth.

ACUTE RESPIRATORY DISTRESS IN ADULTS

1967-08-01

D G Ashbaugh , D. Boyd Bigelow , ThomasL. Petty +1 more

Dimethylbiguanide Inhibits Cell Respiration via an Indirect Effect Targeted on the Respiratory Chain Complex I

2000-01-01

Mohamad-Yehia El-Mir , Véronique Nogueira , Éric Fontaine +3 more

We report here a new mitochondrial regulation occurring only in intact cells. We have investigated the effects of dimethylbiguanide on isolated rat hepatocytes, permeabilized hepatocytes, and isolated liver mitochondria. Addition … We report here a new mitochondrial regulation occurring only in intact cells. We have investigated the effects of dimethylbiguanide on isolated rat hepatocytes, permeabilized hepatocytes, and isolated liver mitochondria. Addition of dimethylbiguanide decreased oxygen consumption and mitochondrial membrane potential only in intact cells but not in permeabilized hepatocytes or isolated mitochondria. Permeabilized hepatocytes after dimethylbiguanide exposure and mitochondria isolated from dimethylbiguanide pretreated livers or animals were characterized by a significant inhibition of oxygen consumption with complex I substrates (glutamate and malate) but not with complex II (succinate) or complex IV (<i>N</i>,<i>N</i>,<i>N</i>′,<i>N</i>′-tetramethyl-1,4-phenylenediamine dihydrochloride (TMPD)/ascorbate) substrates. Studies using functionally isolated complex I obtained from mitochondria isolated from dimethylbiguanide-pretreated livers or rats further confirmed that dimethylbiguanide action was located on the respiratory chain complex I. The dimethylbiguanide effect was temperature-dependent, oxygen consumption decreasing by 50, 20, and 0% at 37, 25, and 15 °C, respectively. This effect was not affected by insulin-signaling pathway inhibitors, nitric oxide precursor or inhibitors, oxygen radical scavengers, ceramide synthesis inhibitors, or chelation of intra- or extracellular Ca<sup>2+</sup>. Because it is established that dimethylbiguanide is not metabolized, these results suggest the existence of a new cell-signaling pathway targeted to the respiratory chain complex I with a persistent effect after cessation of the signaling process.

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Mitochondrial transfer from bone-marrow–derived stromal cells to pulmonary alveoli protects against acute lung injury

2012-04-15

Mohammad Naimul Islam , Shonit Das , Memet Emin +7 more

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Type 2 alveolar cells are stem cells in adult lung

2013-06-09

Christina E. Barkauskas , Michael J. Cronce , Craig R. Rackley +6 more

Gas exchange in the lung occurs within alveoli, air-filled sacs composed of type 2 and type 1 epithelial cells (AEC2s and AEC1s), capillaries, and various resident mesenchymal cells. Here, we … Gas exchange in the lung occurs within alveoli, air-filled sacs composed of type 2 and type 1 epithelial cells (AEC2s and AEC1s), capillaries, and various resident mesenchymal cells. Here, we use a combination of in vivo clonal lineage analysis, different injury/repair systems, and in vitro culture of purified cell populations to obtain new information about the contribution of AEC2s to alveolar maintenance and repair. Genetic lineage-tracing experiments showed that surfactant protein C-positive (SFTPC-positive) AEC2s self renew and differentiate over about a year, consistent with the population containing long-term alveolar stem cells. Moreover, if many AEC2s were specifically ablated, high-resolution imaging of intact lungs showed that individual survivors undergo rapid clonal expansion and daughter cell dispersal. Individual lineage-labeled AEC2s placed into 3D culture gave rise to self-renewing "alveolospheres," which contained both AEC2s and cells expressing multiple AEC1 markers, including HOPX, a new marker for AEC1s. Growth and differentiation of the alveolospheres occurred most readily when cocultured with primary PDGFRα⁺ lung stromal cells. This population included lipofibroblasts that normally reside close to AEC2s and may therefore contribute to a stem cell niche in the murine lung. Results suggest that a similar dynamic exists between AEC2s and mesenchymal cells in the human lung.

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Early Pulmonary Inflammation in Infants with Cystic Fibrosis

1995-04-01

Talat Z. Khan , Jeffrey S. Wagener , Thomas Bost +3 more

The mechanisms underlying the initiation of lung disease and early respiratory morbidity in cystic fibrosis (CF) are poorly understood. By identifying infants with CF through a statewide neonatal screening program, … The mechanisms underlying the initiation of lung disease and early respiratory morbidity in cystic fibrosis (CF) are poorly understood. By identifying infants with CF through a statewide neonatal screening program, we investigated whether airway inflammation was present in these infants, with the goal of furthering our understanding of the early events in this lung disease. Bronchoalveolar lavage fluid (BALF) from 16 infants with CF (mean age, 6 mo) and 11 disease control infants (mean age, 12 mo) was examined for the following inflammatory parameters: (1) neutrophil count; (2) activity of free neutrophil elastase; (3) elastase/alpha1- antiprotease inhibitor complexes; and (4) the level of interleukin-8 (IL-8). We also quantified the spontaneous level of expression of IL-8 mRNA transcripts by airway macrophages. Each index of airway inflammation was increased in the BALF of infants with CF as compared with control infants. In addition, both the number of neutrophils and IL-8 levels were increased in infants with CF who had negative cultures (n = 7) for common bacterial CF-related pathogens, as well as for common respiratory viruses and fungi at the time of bronchoalveolar lavage (BAL). These findings suggest that airway inflammation is already present in infants with CF who are as young as 4 wks. Furthermore, although many different cells types (e.g., epithelial cells) may express IL-8, airway macrophages appear to be a source of this chemokine, and may thus play a prominent role in early neutrophil influx into the lung.

SNAP-II and SNAPPE-II: Simplified newborn illness severity and mortality risk scores

2001-01-01

Douglas K. Richardson , J D Corcoran , Gabriel J. Escobar +1 more

A continuous tumor‐cell line from a human lung carcinoma with properties of type II alveolar epithelial cells

1976-01-15

Michael M. Lieber , George J. Todaro , Barry Smith +2 more

The A549 tumor-cell line, initiated from a human alveolar cell carcinoma, has been continuously propagated in vitro for more than 3 years (more than 1,000 cell generations). These cells have … The A549 tumor-cell line, initiated from a human alveolar cell carcinoma, has been continuously propagated in vitro for more than 3 years (more than 1,000 cell generations). These cells have a human karyotype and appear to have been derived from a single parent cell. All A549 cells examined by electron microscopy at both early and late passage levels contain multilamellar cytoplasmic inclusion bodies typical of those found in type II alveolar epithelial cells of the lung. At early and late passage levels, the cells synthesize lecithin with a high percentage of disaturated fatty acids utilizing the cytidine diphosphocholine pathway; such a pattern of phospholipid synthesis is expected for cells believed to be responsible for pulmonary surfactant synthesis. The A549 cell line should permit in vitro analysis of human surfactant synthesis and secretion and possibly provide a source of human surfactant for therapeutic intervention in pulmonary disease states characterized by surfactant deficiency.

Adenovector-mediated gene transfer of active transforming growth factor-beta1 induces prolonged severe fibrosis in rat lung.

1997-08-15

Patricia J. Sime , Xing Zhang , Frank L. Graham +2 more

Transforming growth factor (TGF)-beta1 has been implicated in the pathogenesis of fibrosis based upon its matrix-inducing effects on stromal cells in vitro, and studies demonstrating increased expression of total TGF-beta1 … Transforming growth factor (TGF)-beta1 has been implicated in the pathogenesis of fibrosis based upon its matrix-inducing effects on stromal cells in vitro, and studies demonstrating increased expression of total TGF-beta1 in fibrotic tissues from a variety of organs. The precise role in vivo of this cytokine in both its latent and active forms, however, remains unclear. Using replication-deficient adenovirus vectors to transfer the cDNA of porcine TGF-beta1 to rat lung, we have been able to study the effect of TGF-beta1 protein in the respiratory tract directly. We have demonstrated that transient overexpression of active, but not latent, TGF-beta1 resulted in prolonged and severe interstitial and pleural fibrosis characterized by extensive deposition of the extracellular matrix (ECM) proteins collagen, fibronectin, and elastin, and by emergence of cells with the myofibroblast phenotype. These results illustrate the role of TGF-beta1 and the importance of its activation in the pulmonary fibrotic process, and suggest that targeting active TGF-beta1 and steps involved in TGF-beta1 activation are likely to be valuable antifibrogenic therapeutic strategies. This new and versatile model of pulmonary fibrosis can be used to study such therapies.

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Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq

2014-04-11

Barbara Treutlein , Douglas Brownfield , Angela Ruohao Wu +6 more

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A practical classification of newborn infants by weight and gestational age

1967-08-01

Frederick C. Battaglia , Lula O. Lubchenco

Nasal CPAP or Intubation at Birth for Very Preterm Infants

2008-02-13

Colin J. Morley , Peter G. Davis , Lex W. Doyle +3 more

Bronchopulmonary dysplasia is associated with ventilation and oxygen treatment. This randomized trial investigated whether nasal continuous positive airway pressure (CPAP), rather than intubation and ventilation, shortly after birth would reduce … Bronchopulmonary dysplasia is associated with ventilation and oxygen treatment. This randomized trial investigated whether nasal continuous positive airway pressure (CPAP), rather than intubation and ventilation, shortly after birth would reduce the rate of death or bronchopulmonary dysplasia in very preterm infants.We randomly assigned 610 infants who were born at 25-to-28-weeks' gestation to CPAP or intubation and ventilation at 5 minutes after birth. We assessed outcomes at 28 days of age, at 36 weeks' gestational age, and before discharge.At 36 weeks' gestational age, 33.9% of 307 infants who were assigned to receive CPAP had died or had bronchopulmonary dysplasia, as compared with 38.9% of 303 infants who were assigned to receive intubation (odds ratio favoring CPAP, 0.80; 95% confidence interval [CI], 0.58 to 1.12; P=0.19). At 28 days, there was a lower risk of death or need for oxygen therapy in the CPAP group than in the intubation group (odds ratio, 0.63; 95% CI, 0.46 to 0.88; P=0.006). There was little difference in overall mortality. In the CPAP group, 46% of infants were intubated during the first 5 days, and the use of surfactant was halved. The incidence of pneumothorax was 9% in the CPAP group, as compared with 3% in the intubation group (P<0.001). There were no other serious adverse events. The CPAP group had fewer days of ventilation.In infants born at 25-to-28-weeks' gestation, early nasal CPAP did not significantly reduce the rate of death or bronchopulmonary dysplasia, as compared with intubation. Even though the CPAP group had more incidences of pneumothorax, fewer infants received oxygen at 28 days, and they had fewer days of ventilation. (Australian New Zealand Clinical Trials Registry number, 12606000258550.).

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Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF

2013-09-16

Martin Guilliams , Ismé de Kleer , Sandrine Henri +7 more

Tissue-resident macrophages can develop from circulating adult monocytes or from primitive yolk sac–derived macrophages. The precise ontogeny of alveolar macrophages (AMFs) is unknown. By performing BrdU labeling and parabiosis experiments … Tissue-resident macrophages can develop from circulating adult monocytes or from primitive yolk sac–derived macrophages. The precise ontogeny of alveolar macrophages (AMFs) is unknown. By performing BrdU labeling and parabiosis experiments in adult mice, we found that circulating monocytes contributed minimally to the steady-state AMF pool. Mature AMFs were undetectable before birth and only fully colonized the alveolar space by 3 d after birth. Before birth, F4/80hiCD11blo primitive macrophages and Ly6ChiCD11bhi fetal monocytes sequentially colonized the developing lung around E12.5 and E16.5, respectively. The first signs of AMF differentiation appeared around the saccular stage of lung development (E18.5). Adoptive transfer identified fetal monocytes, and not primitive macrophages, as the main precursors of AMFs. Fetal monocytes transferred to the lung of neonatal mice acquired an AMF phenotype via defined developmental stages over the course of one week, and persisted for at least three months. Early AMF commitment from fetal monocytes was absent in GM-CSF–deficient mice, whereas short-term perinatal intrapulmonary GM-CSF therapy rescued AMF development for weeks, although the resulting AMFs displayed an immature phenotype. This demonstrates that tissue-resident macrophages can also develop from fetal monocytes that adopt a stable phenotype shortly after birth in response to instructive cytokines, and then self-maintain throughout life.

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TGFβ2 knockout mice have multiple developmental defects that are non-overlapping with other TGFβ knockout phenotypes

1997-07-01

Lynn Sanford , Ilona Ormsby , Adriana C. Gittenberger–de Groot +5 more

The growth and differentiation factor transforming growth factor-beta2 (TGFbeta2) is thought to play important roles in multiple developmental processes. Targeted disruption of the TGFbeta2 gene was undertaken to determine its … The growth and differentiation factor transforming growth factor-beta2 (TGFbeta2) is thought to play important roles in multiple developmental processes. Targeted disruption of the TGFbeta2 gene was undertaken to determine its essential role in vivo. TGFbeta2-null mice exhibit perinatal mortality and a wide range of developmental defects for a single gene disruption. These include cardiac, lung, craniofacial, limb, spinal column, eye, inner ear and urogenital defects. The developmental processes most commonly involved in the affected tissues include epithelial-mesenchymal interactions, cell growth, extracellular matrix production and tissue remodeling. In addition, many affected tissues have neural crest-derived components and simulate neural crest deficiencies. There is no phenotypic overlap with TGFbeta1- and TGFbeta3-null mice indicating numerous non-compensated functions between the TGFbeta isoforms.

Neonatal Outcomes of Extremely Preterm Infants From the NICHD Neonatal Research Network

2010-08-24

Barbara J. Stoll , Nellie I. Hansen , Edward F. Bell +7 more

This report presents data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network on care of and morbidity and mortality rates for very … This report presents data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network on care of and morbidity and mortality rates for very low birth weight infants, according to gestational age (GA). Perinatal/neonatal data were collected for 9575 infants of extremely low GA (22-28 weeks) and very low birth weight (401-1500 g) who were born at network centers between January 1, 2003, and December 31, 2007. Rates of survival to discharge increased with increasing GA (6% at 22 weeks and 92% at 28 weeks); 1060 infants died at <or=12 hours, with most early deaths occurring at 22 and 23 weeks (85% and 43%, respectively). Rates of prenatal steroid use (13% and 53%, respectively), cesarean section (7% and 24%, respectively), and delivery room intubation (19% and 68%, respectively) increased markedly between 22 and 23 weeks. Infants at the lowest GAs were at greatest risk for morbidities. Overall, 93% had respiratory distress syndrome, 46% patent ductus arteriosus, 16% severe intraventricular hemorrhage, 11% necrotizing enterocolitis, and 36% late-onset sepsis. The new severity-based definition of bronchopulmonary dysplasia classified more infants as having bronchopulmonary dysplasia than did the traditional definition of supplemental oxygen use at 36 weeks (68%, compared with 42%). More than one-half of infants with extremely low GAs had undetermined retinopathy status at the time of discharge. Center differences in management and outcomes were identified. Although the majority of infants with GAs of >or=24 weeks survive, high rates of morbidity among survivors continue to be observed.

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Identification of Bronchioalveolar Stem Cells in Normal Lung and Lung Cancer

2005-06-01

Carla F. Bender Kim , Erica L. Jackson , Amber Woolfenden +6 more

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Fibroblast Growth Factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung

1997-12-01

Savério Bellusci , Justin C. Grindley , Hisayo Emoto +2 more

ABSTRACT During mouse lung morphogenesis, the distal mesenchyme regulates the growth and branching of adjacent endoderm. We report here that fibroblast growth factor 10 (Fgf10) is expressed dynamically in the … ABSTRACT During mouse lung morphogenesis, the distal mesenchyme regulates the growth and branching of adjacent endoderm. We report here that fibroblast growth factor 10 (Fgf10) is expressed dynamically in the mesenchyme adjacent to the distal buds from the earliest stages of lung development. The temporal and spatial pattern of gene expression suggests that Fgf10 plays a role in directional outgrowth and possibly induction of epithelial buds, and that positive and negative regulators of Fgf10 are produced by the endoderm. In transgenic lungs overexpressing Shh in the endoderm, Fgf10 transcription is reduced, suggesting that high levels of SHH downregulate Fgf10. Addition of FGF10 to embryonic day 11.5 lung tissue (endoderm plus mesenchyme) in Matrigel or collagen gel culture elicits a cyst-like expansion of the endoderm after 24 hours. In Matrigel, but not collagen, this is followed by extensive budding after 48-60 hours. This response involves an increase in the rate of endodermal cell proliferation. The activity of FGF1, FGF7 and FGF10 was also tested directly on isolated endoderm in Matrigel culture. Under these conditions, FGF1 elicits immediate endodermal budding, while FGF7 and FGF10 initially induce expansion of the endoderm. However, within 24 hours, samples treated with FGF10 give rise to multiple buds, while FGF7-treated endoderm never progresses to bud formation, at all concentrations of factor tested. Although exogenous FGF1, FGF7 and FGF10 have overlapping activities in vitro, their in vivo expression patterns are quite distinct in relation to early branching events. We conclude that, during early lung development, localized sources of FGF10 in the mesoderm regulate endoderm proliferation and bud outgrowth.

Validation of the National Institutes of Health Consensus Definition of Bronchopulmonary Dysplasia

2005-12-01

Richard A. Ehrenkranz , Michele C. Walsh , Betty R. Vohr +5 more

Objective. A number of definitions of bronchopulmonary dysplasia (BPD), or chronic lung disease, have been used. A June 2000 National Institute of Child Health and Human Development/National Heart, Lung, and … Objective. A number of definitions of bronchopulmonary dysplasia (BPD), or chronic lung disease, have been used. A June 2000 National Institute of Child Health and Human Development/National Heart, Lung, and Blood Institute Workshop proposed a severity-based definition of BPD for infants &lt;32 weeks’ gestational age (GA). Mild BPD was defined as a need for supplemental oxygen (O2) for ≥28 days but not at 36 weeks’ postmenstrual age (PMA) or discharge, moderate BPD as O2 for ≥28 days plus treatment with &lt;30% O2 at 36 weeks’ PMA, and severe BPD as O2 for ≥28 days plus ≥30% O2 and/or positive pressure at 36 weeks’ PMA. The objective of this study was to determine the predictive validity of the severity-based, consensus definition of BPD. Methods. Data from 4866 infants (birth weight ≤1000 g, GA &lt;32 weeks, alive at 36 weeks’ PMA) who were entered into the National Institute of Child Health and Human Development Neonatal Research Network Very Low Birth weight (VLBW) Infant Registry between January 1, 1995 and December 31, 1999, were linked to data from the Network Extremely Low Birth Weight (ELBW) Follow-up Program, in which surviving ELBW infants have a neurodevelopmental and health assessment at 18 to 22 months’ corrected age. Linked VLBW Registry and Follow-up data were available for 3848 (79%) infants. Selected follow-up outcomes (use of pulmonary medications, rehospitalization for pulmonary causes, receipt of respiratory syncytial virus prophylaxis, and neurodevelopmental abnormalities) were compared among infants who were identified with BPD defined as O2 for 28 days (28 days definition), as O2 at 36 weeks’ PMA (36 weeks’ definition), and with the consensus definition of BPD. Results. A total of 77% of the neonates met the 28-days definition, and 44% met the 36-weeks definition. Using the consensus BPD definition, 77% of the infants had BPD, similar to the cohort identified by the 28-days definition. A total of 46% of the infants met the moderate (30%) or severe (16%) consensus definition criteria, identifying a similar cohort of infants as the 36-weeks definition. Of infants who met the 28-days definition and 36-weeks definition and were seen at follow-up at 18 to 22 months’ corrected age, 40% had been treated with pulmonary medications and 35% had been rehospitalized for pulmonary causes. In contrast, as the severity of BPD identified by the consensus definition worsened, the incidence of those outcomes and of selected adverse neurodevelopmental outcomes increased in the infants who were seen at follow-up. Conclusion. The consensus BPD definition identifies a spectrum of risk for adverse pulmonary and neurodevelopmental outcomes in early infancy more accurately than other definitions.

An overview of mortality and sequelae of preterm birth from infancy to adulthood

2008-01-01

Saroj Saigal , Lex W. Doyle

Caffeine Therapy for Apnea of Prematurity

2006-05-17

Barbara Schmidt , Robin S. Roberts , Peter G. Davis +5 more

Methylxanthines reduce the frequency of apnea of prematurity and the need for mechanical ventilation during the first seven days of therapy. It is uncertain whether methylxanthines have other short- and … Methylxanthines reduce the frequency of apnea of prematurity and the need for mechanical ventilation during the first seven days of therapy. It is uncertain whether methylxanthines have other short- and long-term benefits or risks in infants with very low birth weight.We randomly assigned 2006 infants with birth weights of 500 to 1250 g during the first 10 days of life to receive either caffeine or placebo, until drug therapy for apnea of prematurity was no longer needed. We evaluated the short-term outcomes before the first discharge home.Of 963 infants who were assigned to caffeine and who remained alive at a postmenstrual age of 36 weeks, 350 (36 percent) received supplemental oxygen, as did 447 of the 954 infants (47 percent) assigned to placebo (adjusted odds ratio, 0.63; 95 percent confidence interval, 0.52 to 0.76; P<0.001). Positive airway pressure was discontinued one week earlier in the infants assigned to caffeine (median postmenstrual age, 31.0 weeks; interquartile range, 29.4 to 33.0) than in the infants in the placebo group (median postmenstrual age, 32.0 weeks; interquartile range, 30.3 to 34.0; P<0.001). Caffeine reduced weight gain temporarily. The mean difference in weight gain between the group receiving caffeine and the group receiving placebo was greatest after two weeks (mean difference, -23 g; 95 percent confidence interval, -32 to -13; P<0.001). The rates of death, ultrasonographic signs of brain injury, and necrotizing enterocolitis did not differ significantly between the two groups.Caffeine therapy for apnea of prematurity reduces the rate of bronchopulmonary dysplasia in infants with very low birth weight. (ClinicalTrials.gov number, NCT00182312.).

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Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes

1995-02-01

Larry C. Gilstrap , Robert E. Christensen , William H. Clewell +7 more

The National Institutes of Health Consensus Development Conference on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes brought together specialists in obstetrics, neonatology, pharmacology, epidemiology, and nursing; basic … The National Institutes of Health Consensus Development Conference on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes brought together specialists in obstetrics, neonatology, pharmacology, epidemiology, and nursing; basic scientists in physiology and cellular biology; and the public to address the following questions: (1) For what conditions and purposes are antenatal corticosteroids used, and what is the scientific basis for that use? (2) What are the short-term and long-term benefits of antenatal corticosteroid treatment? (3) What are the short-term and long-term adverse effects for the infant and mother? (4) What is the influence of the type of corticosteroid, dosage, timing and circumstances of administration, and associated therapy on treatment outcome? (5) What are the economic consequences of this treatment? (6) What are the recommendations for use of antenatal corticosteroids? and (7) What research is needed to guide clinical care? Following 1 1/2 days of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared their consensus statement. The consensus panel concluded that antenatal corticosteroid therapy for fetal maturation reduces mortality, respiratory distress syndrome, and intraventricular hemorrhage in preterm infants. These benefits extend to a broad range of gestational ages (24-34 weeks) and are not limited by gender or race. Although the beneficial effects of corticosteroids are greatest more than 24 hours after beginning treatment, treatment less than 24 hours in duration may also improve outcomes. The benefits of antenatal corticosteroids are additive to those derived from surfactant therapy. In the presence of preterm premature rupture of the membranes, antenatal corticosteroid therapy reduces the frequency of respiratory distress syndrome, intraventricular hemorrhage, and neonatal death, although to a lesser extent than with intact membranes. Whether this therapy increases either neonatal or maternal infection is unclear. However, the risk of intraventricular hemorrhage and death from prematurity is greater than the risk from infection. Data from trials with followup of children up to 12 years indicate that antenatal corticosteroid therapy does not adversely affect physical growth or psychomotor development. Antenatal corticosteroid therapy is indicated for women at risk of premature delivery with few exceptions and will result in a substantial decrease in neonatal morbidity and mortality, as well as substantial savings in health care costs. The use of antenatal corticosteroids for fetal maturation is a rare example of a technology that yields substantial cost savings in addition to improving health.

Neurodevelopmental and Functional Outcomes of Extremely Low Birth Weight Infants in the National Institute of Child Health and Human Development Neonatal Research Network, 1993–1994

2000-06-01

Betty R. Vohr , Linda L. Wright , Anna M. Dusick +7 more

Objectives. The purposes of this study were to report the neurodevelopmental, neurosensory, and functional outcomes of 1151 extremely low birth weight (401–1000 g) survivors cared for in the 12 participating … Objectives. The purposes of this study were to report the neurodevelopmental, neurosensory, and functional outcomes of 1151 extremely low birth weight (401–1000 g) survivors cared for in the 12 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network, and to identify medical, social, and environmental factors associated with these outcomes. Study Design. A multicenter cohort study in which surviving extremely low birth weight infants born in 1993 and 1994 underwent neurodevelopmental, neurosensory, and functional assessment at 18 to 22 months' corrected age. Data regarding pregnancy and neonatal outcome were collected prospectively. Socioeconomic status and a detailed interim medical history were obtained at the time of the assessment. Logistic regression models were used to identify maternal and neonatal risk factors for poor neurodevelopmental outcome. Results. Of the 1480 infants alive at 18 months of age, 1151 (78%) were evaluated. Study characteristics included a mean birth weight of 796 ± 135 g, mean gestation (best obstetric dates) 26 ± 2 weeks, and 47% male. Birth weight distributions of infants included 15 infants at 401 to 500 g; 94 at 501 to 600 g; 208 at 601 to 700 g; 237 at 701 to 800 g; 290 at 801 to 900 g; and 307 at 901 to 1000 g. Twenty-five percent of the children had an abnormal neurologic examination, 37% had a Bayley II Mental Developmental Index &lt;70, 29% had a Psychomotor Developmental Index &lt;70, 9% had vision impairment, and 11% had hearing impairment. Neurologic, developmental, neurosensory, and functional morbidities increased with decreasing birth weight. Factors significantly associated with increased neurodevelopmental morbidity included chronic lung disease, grades 3 to 4 intraventricular hemorrhage/periventricular leukomalacia, steroids for chronic lung disease, necrotizing enterocolitis, and male gender. Factors significantly associated with decreased morbidity included increased birth weight, female gender, higher maternal education, and white race. Conclusion. ELBW infants are at significant risk of neurologic abnormalities, developmental delays, and functional delays at 18 to 22 months' corrected age.

Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth

2017-03-21

Devender Roberts , Julie Brown , Nancy Medley +1 more

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Macrophages and Polymorphonuclear Neutrophils in Lung Defense and Injury

1990-02-01

Yves Sibille , Herbert Y. Reynolds

"Macrophages and Polymorphonuclear Neutrophils in Lung Defense and Injury." American Review of Respiratory Disease, 141(2), pp. 471–501 "Macrophages and Polymorphonuclear Neutrophils in Lung Defense and Injury." American Review of Respiratory Disease, 141(2), pp. 471–501

Asthma and Wheezing in the First Six Years of Life

1995-01-19

Fernando D. Martínez , Anne L. Wright , Lynn M. Taussig +3 more

Many young children wheeze during viral respiratory infections, but the pathogenesis of these episodes and their relation to the development of asthma later in life are not well understood. Many young children wheeze during viral respiratory infections, but the pathogenesis of these episodes and their relation to the development of asthma later in life are not well understood.

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Treatment of the Idiopathic Respiratory-Distress Syndrome with Continuous Positive Airway Pressure

1971-06-17

George A. Gregory , Joseph A. Kitterman , Roderic H. Phibbs +2 more

Abstract We applied a continuous positive airway pressure to 20 infants (birth weight 930 to 3800 g) severely ill with the idiopathic respiratory-distress syndrome. They breathed spontaneously. Pressure, up to … Abstract We applied a continuous positive airway pressure to 20 infants (birth weight 930 to 3800 g) severely ill with the idiopathic respiratory-distress syndrome. They breathed spontaneously. Pressure, up to 12 mm of mercury, was delivered through an endotracheal tube to 18 infants and via a pressure chamber around the infant's head to two. Arterial oxygen tension rose in all, permitting us to lower the inspired oxygen an average of 37.5 per cent within 12 hours. Minute ventilation decreased with increased continuous positive airway pressure, but this had little effect on arterial carbon dioxide tension, pH, arterial blood pressure and lung compliance. Sixteen infants survived, including seven of 10 weighing less than 1500 g at birth.

The Contribution of Low Birth Weight to Infant Mortality and Childhood Morbidity

1985-01-10

Marie C. McCormick

The low-birth-weight infant remains at much higher risk of mortality than the infant with normal weight at birth. In the neonatal period, when most infant deaths occur, the proportion of … The low-birth-weight infant remains at much higher risk of mortality than the infant with normal weight at birth. In the neonatal period, when most infant deaths occur, the proportion of low-birth-weight infants, especially those with very low weight, is the major determinant of the magnitude of the mortality rates. Furthermore, differences in low-birth-weight rates account for the higher neonatal mortality rates observed in some groups, particularly those characterized by socioeconomic disadvantages. Much of the recent decline in neonatal mortality can be attributed to increased survival among low-birth-weight infants, apparently as a result of hospital-based services. The application of these services is currently considered cost-effective, although whether this will continue to be true in the future is unclear because of the increased survival of very tiny infants. Although low-birth-weight infants remain at increased risk of both postneonatal mortality and morbidity in infancy and early childhood, the risk is substantially smaller than that of neonatal death. In addition, these adverse later outcomes have not offset the gains achieved in the neonatal period. Nonetheless, the increased survival of high-risk infants raises concern about their future requirements for special medical and educational services and about the stress on their families. Despite increased access to antenatal services, only moderate declines in the proportion of low-birth-weight infants has been observed, and almost no change has occurred in the proportion of those with very low weight at birth. In addition, in many areas of the country the birth-weight-specific neonatal mortality rates are similar for groups at high and low risk of neonatal death. In view of these findings, continuation of the current decline in neonatal mortality and reduction of the mortality differentials between high- and low-risk groups require the identification and more effective implementation of strategies for the prevention of low-weight births.

A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte

2018-07-31

Lindsey W. Plasschaert , Rapolas Žilionis , Rayman Choo-Wing +5 more

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A revised airway epithelial hierarchy includes CFTR-expressing ionocytes

2018-07-31

Daniel T. Montoro , Adam L. Haber , Moshe Biton +7 more

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European Consensus Guidelines on the Management of Respiratory Distress Syndrome – 2019 Update

2019-01-01

David G. Sweet , Virgilio Carnielli , Gorm Greisen +7 more

As management of respiratory distress syndrome (RDS) advances, clinicians must continually revise their current practice. We report the fourth update of "European Guidelines for the Management of RDS" by a … As management of respiratory distress syndrome (RDS) advances, clinicians must continually revise their current practice. We report the fourth update of "European Guidelines for the Management of RDS" by a European panel of experienced neonatologists and an expert perinatal obstetrician based on available literature up to the end of 2018. Optimising outcome for babies with RDS includes prediction of risk of preterm delivery, need for appropriate maternal transfer to a perinatal centre and timely use of antenatal steroids. Delivery room management has become more evidence-based, and protocols for lung protection including initiation of CPAP and titration of oxygen should be implemented immediately after birth. Surfactant replacement therapy is a crucial part of management of RDS, and newer protocols for its use recommend early administration and avoidance of mechanical ventilation. Methods of maintaining babies on non-invasive respiratory support have been further developed and may cause less distress and reduce chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease, although minimising time spent on mechanical ventilation using caffeine and, if necessary, postnatal steroids are also important considerations. Protocols for optimising general care of infants with RDS are also essential with good temperature control, careful fluid and nutritional management, maintenance of perfusion and judicious use of antibiotics all being important determinants of best outcome.

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A Proposal for a New Method of Evaluation of the Newborn Infant.

1953-01-01

Virginia Apgar

Bronchopulmonary Dysplasia

2001-06-01

Alan H. Jobe , Eduardo Bancalari

Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth

2006-07-18

Devender Roberts , Stuart R Dalziel

Background Respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal mortality and disability. Objectives To assess the effects on fetal and … Background Respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal mortality and disability. Objectives To assess the effects on fetal and neonatal morbidity and mortality, on maternal mortality and morbidity, and on the child in later life of administering corticosteroids to the mother before anticipated preterm birth. Search methods We searched the Cochrane Pregnancy and Childbirth Group Trials Register (30 October 2005). We updated this search on 30 April 2010 and added the results to the awaiting assessment section of the review. Selection criteria Randomised controlled comparisons of antenatal corticosteroid administration (betamethasone, dexamethasone, or hydrocortisone) with placebo or with no treatment given to women with a singleton or multiple pregnancy, expected to deliver preterm as a result of either spontaneous preterm labour, preterm prelabour rupture of the membranes or elective preterm delivery. Data collection and analysis Two review authors assessed trial quality and extracted data independently. Main results Twenty‐one studies (3885 women and 4269 infants) are included. Treatment with antenatal corticosteroids does not increase risk to the mother of death, chorioamnionitis or puerperal sepsis. Treatment with antenatal corticosteroids is associated with an overall reduction in neonatal death (relative risk (RR) 0.69, 95% confidence interval (CI) 0.58 to 0.81, 18 studies, 3956 infants), RDS (RR 0.66, 95% CI 0.59 to 0.73, 21 studies, 4038 infants), cerebroventricular haemorrhage (RR 0.54, 95% CI 0.43 to 0.69, 13 studies, 2872 infants), necrotising enterocolitis (RR 0.46, 95% CI 0.29 to 0.74, eight studies, 1675 infants), respiratory support, intensive care admissions (RR 0.80, 95% CI 0.65 to 0.99, two studies, 277 infants) and systemic infections in the first 48 hours of life (RR 0.56, 95% CI 0.38 to 0.85, five studies, 1319 infants). Antenatal corticosteroid use is effective in women with premature rupture of membranes and pregnancy related hypertension syndromes. Authors' conclusions The evidence from this new review supports the continued use of a single course of antenatal corticosteroids to accelerate fetal lung maturation in women at risk of preterm birth. A single course of antenatal corticosteroids should be considered routine for preterm delivery with few exceptions. Further information is required concerning optimal dose to delivery interval, optimal corticosteroid to use, effects in multiple pregnancies, and to confirm the long‐term effects into adulthood. [Note: The 16 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]

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Neurodevelopment Among Infants With Late-Onset Fetal Growth Restriction

2025-06-25

Liqun Sun , Fu‐Tsuen Lee , Natasha Milligan +7 more | JAMA Network Open

Importance Fetal growth restriction (FGR) is associated with adverse neurodevelopmental outcomes. However, the delineation of neurodevelopmental sequela in late-onset FGR has been hampered by challenges in diagnosing late-onset FGR and … Importance Fetal growth restriction (FGR) is associated with adverse neurodevelopmental outcomes. However, the delineation of neurodevelopmental sequela in late-onset FGR has been hampered by challenges in diagnosing late-onset FGR and the confounding influence of prematurity. Objective To characterize neurodevelopmental outcomes in full-term infants exposed to late-onset FGR and to examine the association of FGR with fetal hemodynamics, perinatal brain development, and somatic growth. Design, Setting, and Participants In this single-center cohort study, pregnant persons with fetuses small for gestational age were enrolled between April 1, 2010, and August 31, 2016, and followed up until the infant was 36 months of age. Follow-up was completed November 2019. Data analysis was performed from June to August 2024. Exposures Late-onset FGR diagnosed based on a composite scoring system. Main Outcomes and Measures The primary outcomes were neurodevelopmental outcomes at 4, 8, and 12 months of age assessed by the Alberta Infant Motor Scale (AIMS) and at 18 and 36 months of age assessed by the Bayley Scales of Infant and Toddler Development, Third Edition. Secondary outcomes included fetal hemodynamics and perinatal brain development assessed by magnetic resonance imaging findings and serial somatic growth. Results Among 97 singleton pregnancies (mean [SD] maternal age, 33.5 [3.8] years; 50 [52%] male neonates), 41 neonates (42%) were exposed to late-onset FGR. At 12-month follow-up, motor development was significantly delayed among full-term infants exposed to late-onset FGR compared with neonates appropriate for gestational age (AIMS mean difference, −4.5; 95% CI, −8.6 to −0.3). At all other time points, neurodevelopmental outcomes were similar between the groups. In models adjusted for covariates, gestational age at birth was associated with 18-month cognitive outcomes (coefficient, 4.13 [95% CI, 0.54-7.72]), while the diagnosis of late-onset FGR was not. Preterm infants exposed to FGR exhibited higher fetal combined ventricular output, higher ratio of cerebral to pulmonary blood flow, and lower oxygen saturation compared with full-term infants exposed to FGR and infants with no FGR exposure. In general, neonatal brain maturation and somatic growth by 12 months of age were similar between full-term infants exposed to FGR and those with no exposure. However, head circumference was smaller from birth until the 36-month follow-up in infants exposed to FGR. Conclusions In this cohort study, full-term infants exposed to late-onset FGR exhibited normal neurodevelopmental outcomes by 18 and 36 months of age, and longer gestation was associated with improved outcomes. These findings suggest that early delivery is unlikely to offer neurodevelopmental benefit, and any adverse impact on neurodevelopmental outcomes of late-onset FGR among full-term infants is likely to be modest.

Child and Family Outcomes After PICU Admission: Creation of an Open Access Literature Database Using a Global Team of PICU Specialists Integrated With Machine Learning

2025-06-25

Rebecca E. Hay , David J. Zorko , Katie O’Hearn +7 more | Pediatric Critical Care Medicine

Objectives: As research examining child health outcomes after PICU admission grows, so does the need for the identification and synthesis of a large body of literature. We aimed to create … Objectives: As research examining child health outcomes after PICU admission grows, so does the need for the identification and synthesis of a large body of literature. We aimed to create an open-access scoping repository of literature describing longer-term health outcomes after PICU admission, using a large multinational team (crowdsourcing) and a machine learning (ML) algorithm. Data Sources: We performed a registered scoping review (OSF DOI10.17605/OSF.IO/HE5VB; Registered November 21, 2022) using MEDLINE, Embase, CINAHL, and CENTRAL databases, 2000–2022, with no language restrictions. Study Selection: Observational or interventional studies describing outcomes of children (0–17 yr old) and their families or caregivers measured greater than 2 weeks post-PICU discharge. Titles and abstracts and full texts were initially screened by a large team of PICU healthcare workers and researchers who were recruited as part of an Evidence Hackathon event at the 2022 World Federation of Pediatric Intensive and Critical Care Societies conference. Initial screening results from 5000 citations were used to develop and validate an ML algorithm, after which a hybrid human crowdsourcing and ML approach was used to screen the remaining 11,055 studies. Data Extraction: Not applicable. Data Synthesis: Of 16,055 eligible citations, 1,301 met the criteria at full text for inclusion in the database. The screening was completed in just under 2 months while adhering to the gold standard systematic review methodology. Sensitivity for the hybrid human crowdsourcing and ML was 98%. Conclusions: A collaborative, global PICU team integrated with ML was successful in efficient and accurate large data synthesis, producing a scoping open-access database of studies reporting on post-PICU outcomes. The development of this repository has implications for future reviews, providing opportunities for networking and collaborative engagement in research. The next steps should examine database maintenance, utilization, and dissemination of research findings.

Impact of Tele-Kangaroo Mother Care (KMC) Clinics on the Respiratory Outcomes of Newborns: Correspondence

2025-06-24

Xuehui Cai , Yihang Yang , Z. Zhang | The Indian Journal of Pediatrics

Risk factors for early wheezing in preterm infants: a retrospective cohort study

2025-06-24

Xun Chen , Minjing Yang , Jun Xie +7 more | Frontiers in Pediatrics

Introduction The related factors that cause recurrent wheezing in children are complex, and premature delivery may be one of the reasons. Little is known about early wheezing in preterm infants. … Introduction The related factors that cause recurrent wheezing in children are complex, and premature delivery may be one of the reasons. Little is known about early wheezing in preterm infants. Methods Data sourced from 1,616 children born between 2007 and 2013 from 8 hospitals of Guangxi in China. All children were followed by telephone or questionnaire through the sixth year of life. Children were grouped by characters of age: Group A: gestational age (GA ≤ 32 weeks, Group B: 32 weeks &lt; GA &lt; 37 weeks, Group C: 37 weeks ≤ GA &lt; 42 weeks. Results The incidence and the risk factors of early wheezing in preterm infants were analyzed. The incidence of early wheezing: Group A &gt; Group B &gt; Group C. In Group A, the proportion of small-for-gestational-age (SGA) infant was higher in early wheezing group than in normal group ( P &lt; 0.05). Male ( 95% CI : 1.611–4.601) and family history of allergy ( 95% CI : 1.222–3.411) were the risk factors for early wheezing in Group B. Conclusions Lower gestational age is associated with higher wheezing risk. Preterm infants have higher persistent wheezing incidence than full-term infants. Preterm infants with gestational age &lt;32 weeks have higher transient wheezing incidence than those with gestational age 32–37 weeks or full-term infants. In preterm infants &lt;32 weeks, small for gestational age (SGA) is a potential factor for wheezing. In preterm infants aged 32–37 weeks, male sex, personal allergy history, and family allergy history are potential factors for wheezing, with male sex and family allergy history being significant risk factors.

Association between gastroesophageal reflux and bronchopulmonary dysplasia in preterm infants: a systematic review and meta-analysis

2025-06-24

Xue Yu , Mingjun Sun , Yu Hu | Frontiers in Nutrition

Objective Gastroesophageal reflux (GER) has emerged as a potential contributor to lung injury. This meta-analysis aimed to evaluate the association between GER and bronchopulmonary dysplasia (BPD) in preterm infants. Methods … Objective Gastroesophageal reflux (GER) has emerged as a potential contributor to lung injury. This meta-analysis aimed to evaluate the association between GER and bronchopulmonary dysplasia (BPD) in preterm infants. Methods A systematic literature search was conducted in PubMed, Embase, Web of Science, and Cochrane Library databases up to Oct 19, 2024. Studies assessing the association between BPD and GER in preterm infants were included. Random-effects models was used to calculate pooled risk ratios (RR) with 95% confidence intervals (CIs). Sensitivity analyses and subgroup analyses were performed to assess the robustness of the findings. Results Seven studies were included in the meta-analysis. The overall analysis revealed a non-significant association between GER and BPD (RR = 1.35, 95% CI = 0.91–2.01), but significant heterogeneity was observed across the studies ( p &lt; 0.001, I 2 = 95.2%). The pooled RR ranged from 1.17 (95% CI = 0.79–1.74) to 1.51 (95% CI = 1.02–2.22) with each study omitted. Funnel plot analysis showed noticeable asymmetry, and Egger’s test confirmed potential publication bias (P &gt; |t| = 0.076). Subgroup analysis revealed that GER diagnosed with clinical therapy or ICD-9 codes was significantly associated with BPD (RR = 1.72, 95% CI = 1.52–1.95 and RR = 2.70, 95% CI = 2.48–2.94, respectively). However, GER diagnosed by pH monitoring did not show a statistically significant association with BPD (RR = 0.86, 95% CI = 0.71–1.05). Conclusion Preterm infants with clinically diagnosed GER may face an elevated risk of developing BPD. GER diagnosed by pH monitoring was not associated with BPD. Systematic Review Registration https://www.crd.york.ac.uk/prospero/ .

Epigenetic Changes Regulating Epithelial–Mesenchymal Plasticity in Human Trophoblast Differentiation

2025-06-24

William E. Ackerman , Maurício Rigo , Sonia C. DaSilva‐Arnold +7 more | Cells

The phenotype of human placental extravillous trophoblast (EVT) at the end of pregnancy reflects both differentiation from villous cytotrophoblast (CTB) and later gestational changes, including loss of proliferative and invasive … The phenotype of human placental extravillous trophoblast (EVT) at the end of pregnancy reflects both differentiation from villous cytotrophoblast (CTB) and later gestational changes, including loss of proliferative and invasive capacity. Invasion abnormalities are central to major obstetric pathologies, including placenta accreta spectrum, early onset preeclampsia, and fetal growth restriction. Characterization of the normal differentiation processes is, thus, essential for the analysis of these pathologies. Our gene expression analysis, employing purified human CTB and EVT cells, demonstrates a mechanism similar to the epithelial–mesenchymal transition (EMT), which underlies CTB–EVT differentiation. In parallel, DNA methylation profiling shows that CTB cells, already hypomethylated relative to non-trophoblast cell lineages, show further genome-wide hypomethylation in the transition to EVT. A small subgroup of genes undergoes gains of methylation (GOM), associated with differential gene expression (DE). Prominent in this GOM-DE group are genes involved in epithelial–mesenchymal plasticity (EMP). An exemplar is the transcription factor RUNX1, for which we demonstrate a functional role in regulating the migratory and invasive capacities of trophoblast cells. This analysis highlights epigenetically regulated genes acting to underpin the epithelial–mesenchymal plasticity characteristic of human trophoblast differentiation. Identification of these elements provides important information for the obstetric disorders in which these processes are dysregulated.

Systematic Review of Respiratory Complications in Pregnant Patients: Evidence and Recommendations

2025-06-23

Fath Elrahman Elrasheed , Yasser Osman , Mayada Farah Obaid +7 more | Journal of Neonatal Surgery

Respiratory complications during pregnancy can significantly affect maternal and fetal health. This systematic review aims to consolidate existing literature on the prevalence, risk factors, and management of respiratory complications in … Respiratory complications during pregnancy can significantly affect maternal and fetal health. This systematic review aims to consolidate existing literature on the prevalence, risk factors, and management of respiratory complications in pregnant patients. We conducted a comprehensive search of multiple databases, including PubMed, Scopus, and Cochrane Library, to identify relevant studies published from 2000 to June 2025. A total of 12 articles were included in the review, providing insights into various respiratory conditions, including asthma, pneumonia, and COVID-19.

Born Too Soon: Care for small and sick newborns, evidence for investment and implementation

2025-06-23

Sarah Murless-Collins , Chinyere Ezeaka , Nahya Salim Masoud +7 more | Reproductive Health

Abstract Progress Over the past decade, the world has made policy progress for newborns including the first global Sustainable Development Goal (SDG) target 3.2 (< 12 neonatal deaths per 1000 … Abstract Progress Over the past decade, the world has made policy progress for newborns including the first global Sustainable Development Goal (SDG) target 3.2 (< 12 neonatal deaths per 1000 live births) and the Every Newborn Action Plan (ENAP). However, gaps remain for investment and action, especially for babies born too soon, too small, or who become sick. An estimated 20–30 million newborns have life-threatening conditions requiring hospital care each year. Annually, approximately 2.3 million newborns die during the neonatal period, the majority being preterm. A further 1 million newborn survivors are estimated to have long-term disabilities. Programmatic priorities To achieve SDG 3.2 by 2030, we need to accelerate four-fold. The shift to 80% of births in health facilities creates opportunities for impact, for both maternal and newborn care. Increased coverage and quality of high-impact newborn interventions is urgently needed to reach SDG targets. Most neonatal deaths and disabilities are preventable through an evidence-based package for small and sick newborn care (SSNC), with greatest impact seen in preterm babies—particularly through respiratory support and kangaroo mother care—while placing families at the centre of care. SSNC scale-up requires addressing ten core components, defined by WHO/UNICEF, based on a health systems approach: political commitment and leadership; financing; human resources; appropriate infrastructure; equipment and commodities; robust data systems and use of data for action; referral systems; linkage with high-quality maternal care; family and community involvement; and post-discharge follow-up. Specific focus is required for fragile conflict settings, accounting for 25% global births but 39% global newborn deaths. Pivots More ambitious investment in high-quality, family-centred care for vulnerable newborns can give a high return of between US$ 9−12 for every US$ 1 invested. Accelerating implementation requires diverse stakeholders, including political leaders, bureaucratic and technical leadership in country, professional societies, civil society, the private sector and importantly from families and communities. Cross-country collaboration and strengthening capacities of low- and middle-income countries to address gaps in newborn care are essential for innovations to reach high-burden, conflict-affected, and marginalised populations. Integrating newborn care follow-up into wider child and family care systems is crucial to ensure newborns not only survive but also thrive.

Impact of cessation of caffeine citrate therapy on intermittent hypoxemia patterns among preterm infants born before 34 weeks

2025-06-23

Peter Kipkurui Mashep , Roseline Ochieng , Jesse Coleman +7 more | Frontiers in Pediatrics

Introduction Intermittent hypoxemia (IH) is defined as oxygen saturation (SpO 2 ) drop ≥5% from the baseline (set at 90 s preceding the event) to a level less than 90% … Introduction Intermittent hypoxemia (IH) is defined as oxygen saturation (SpO 2 ) drop ≥5% from the baseline (set at 90 s preceding the event) to a level less than 90% lasting for ≥5 s. Caffeine citrate, the standard of care for apnea of prematurity, reduces IH events. IH contributes to both short and long-term adverse neurologic outcomes. Standard patient monitors cannot detect IH events due to long averaging times. Objective Describe change in patterns of IH events in preterms &lt;34 weeks before and after cessation of caffeine citrate and factors associated. Methods Interrupted time series study design. Data was collected from 1 December 2022 to 30 June 2023. MASIMO RAD-G oximeter was used, and analysis done using Trace software V3028 output was desaturation frequency, duration, and time. Data exported, stored, and analyzed using Excel 2016. Change in slope compared visually in two time periods interrupted at 34 weeks and objective statistical analysis done using the Student- T -test, CI 95% with p -value &lt;0.05 considered significant. Results 49 patients medical records available for secondary analysis. Frequency of IH events increased from 7.94 to 40.94 events/hour (5-fold). IH events of durations lasting between 0 and 10 s, and &gt;20 s decreased by 12.3% and 6.8%, respectively, while those lasting 10–20 s increased by 17%. The mildly severe IH events decreased by nearly half, 46.9% (78.4% to 31.5%), while both the moderately severe and severe IH events increased by 17.4% (18.5%–35.9%), and 26% (6.7% to 32.7%) respectively. The time spent in hypoxemia increased by 2.3 h/week/patient, while the cumulative time in hypoxemia increased by 1.6 h/patient. Preterms exposure to ACS (antenatal corticosteroids) was associated with decrease in IH events. Conclusion Caffeine citrate cessation leads to worsening of IH events with increased frequency, duration, severity and cumulative time spent in hypoxemia. Exposure to ACS was associated with decrease in IH events. Recommendation Caffeine citrate therapy use beyond 34 weeks is likely to be beneficial especially in the context of LMIC where antenatal steroid is not always administered, and monitoring of preterm babies is suboptimal. Safe cessation of caffeine therapy requires monitoring to detect IH events.

Modeling CF Patient-Specific Responses to CFTR Modulators Using Human Induced Pluripotent Stem Cells

2025-06-23

Kayshani R. Kanagarajah , Ming Jia Michael Wu , Timothy T.-Y. Lam +7 more | American Journal of Respiratory and Critical Care Medicine

Sub-optimal oxygen blending and saturation monitoring despite widespread continuous positive airway pressure use: A survey of select sub-Saharan hospitals

2025-06-23

Jennifer Harling , Lloyd Tooke | Tropical Doctor

Respiratory support for neonates is key for reducing mortality; however, the capabilities of countries in sub-Saharan Africa (SSA) are not exactly known. Our aim was to assess the availability of … Respiratory support for neonates is key for reducing mortality; however, the capabilities of countries in sub-Saharan Africa (SSA) are not exactly known. Our aim was to assess the availability of respiratory support systems and medications for neonates in a sample of hospitals in SSA. A survey was conducted among neonatal providers attending an annual neonatal conference in Tanzania. One response per healthcare facility was invited. A total of 47 institutions completed the survey. Continuous positive airway pressure (CPAP) was used in almost all (96.6%) tertiary hospitals and in 88.9% of frontline hospitals. Continuous oxygen saturation monitoring is available in less than 50% of healthcare facilities; the ability to blend oxygen for all infants is available in 22% of facilities. Although the availability of CPAP is high, this sample may not be representative of all hospitals. Monitoring oxygen saturation and the ability to blend oxygen are suboptimal.

A multimodal imaging approach for imaging the metabolic changes resulting from bronchopulmonary dysplasia

2025-06-22

Brittney Gorman , Zhi Li , Gail Deutsch +7 more | bioRxiv (Cold Spring Harbor Laboratory)

Abstract Lung tissue is composed of various functional units, each essential for maintaining the intricate functions of the lung. Disruptions in the molecular and cellular mechanisms in the lung can … Abstract Lung tissue is composed of various functional units, each essential for maintaining the intricate functions of the lung. Disruptions in the molecular and cellular mechanisms in the lung can cause tissue fibrosis, inflammation, and severe breathing difficulties, which are common in conditions such as bronchopulmonary dysplasia (BPD). BPD’s molecular changes are not well understood, which hinders effective diagnosis and treatment. Here, we present a new multimodal imaging workflow for detailed molecular and metabolic characterization of tissues at multiple spatial scales. We applied a combined imaging approach using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and ultrafast focused light-based imaging & photonics platform (U-FLIP) that included two-photon fluorescence (TPF), second harmonic generation (SHG), and stimulated Raman scattering (SRS). We also developed a hierarchical multimodal registration network (HiMReg) for the precise co-registration of each modality. This approach revealed previously unknown metabolic changes in distinct functional tissue units affected by BPD, including altered lipid distributions, reduced optical redox states, and specific collagen remodeling in bronchioles. Our findings evidenced alterations in lipid composition and metabolism of BPD-affected alveoli compared to healthy tissue, providing novel insights into disease pathophysiology. Our findings elucidate the intricate spatial and molecular complexity of BPD, building on prior research that did not provide the spatial resolution necessary to capture the nuances of metabolic alterations. This multimodal approach offers exceptional insights into disease exploration and could transform the way we study spatially heterogeneous conditions. By providing detailed maps of the metabolic shifts occurring in distinct tissue microanatomical features, the methods developed here could enable the discovery of new therapeutic avenues, making it highly attractive for the field of biomedical research.

The role of exogenous surfactant in the treatment of respiratory viral infections

2025-06-22

S. Yu. Chikina | Meditsinskiy sovet = Medical Council

Pulmonary surfactant is a complex substance with high surface activity that prevents alveoli collapse at the end of expiration and, therefore, stabilizes the lung volume and the gas exchange. These … Pulmonary surfactant is a complex substance with high surface activity that prevents alveoli collapse at the end of expiration and, therefore, stabilizes the lung volume and the gas exchange. These properties of surfactant opened the way for its investigation in the respiratory distress syndrome of newborn and the acute respiratory distress syndrome (ARDS) in adults including patients with severe virus-associated and bacterial pneumonias. This paper is a review of published laboratory data and clinical findings on the efficacy of surfactant in adults. Several authors demonstrated that exogenous surfactant could improve mortality in patients with ARDS, reduce the need in mechanical ventilation and a length of hospitalization in general. Most clinical trials of surfactant were related to the novel coronavirus infection COVID-19, but several papers included patient with severe pneumonia associated with influenza or respiratory syncytial virus. Moreover, surfactant could be useful for better delivery of pharmacological agents, including antibiotics, in the distal airways and the lung tissue in patients with bacterial pneumonia. Unfortunately, current findings are scarce to certainly detecting a role of exogenous surfactant in the management of such patients. Further studies of clinical efficacy of exogenous surfactant in severe lung injury are required.

The dynamics of respiratory changes on the background of inhalation treatment with tauractant in patients in the post-covid period

2025-06-22

О. О. Воронкова , N. S. Nikolaeva , G. B. Abdullaeva +3 more | Meditsinskiy sovet = Medical Council

Introduction. Pulmonary surfactant is a key component of the respiratory system that ensures the stability of the alveoli by reducing surface tension, preventing collapse of the respiratory tract and protecting … Introduction. Pulmonary surfactant is a key component of the respiratory system that ensures the stability of the alveoli by reducing surface tension, preventing collapse of the respiratory tract and protecting against infections. Its dysfunction is observed in severe respiratory diseases, including COVID-19, ARDS, pneumonia, COPD and bronchial asthma. Of particular interest is the inhalation use of exogenous forms of surfactant not only in acute COVID-19, but also in the post-covid period. Aim. The aim of the study is to evaluate the effectiveness of a course of inhalation of tauractant emulsion (Surfactant-BL) through a nebulizer in patients with COVID-associated pneumonia with persistent ventilation disorders after 3 months of therapy in the post-covid period. Materials and methods: The study included 60 patients with COVID-associated pneumonia with confirmed violations of lung ventilation and pronounced residual changes in lung tissue, who were randomly divided into 2 groups – the main group (n = 30) and the comparison group (n = 30). The main group, in addition to the standard therapy for post-covid syndrome, received a course of inhalation with Surfactant-BL twice a day for 7 days. All patients underwent a comprehensive study of respiratory function (spirography, bodyplethysmography and diffusion test) at the stage of inclusion in the study and after 3 months. Results. In the main group, significant positive dynamics in FEV1, FEV1/FVC, FRC, and TLC were revealed, while the diffusion capacity DLCO of the lungs did not significantly change. Conclusion. In this study, the effectiveness of the use of an exogenous surfactant in the post-pregnancy period was demonstrated. It is advisable to continue conducting studies using more numerous groups of patients to determine clear criteria for the use of inhaled surfactant therapy in the post-covid period.

Survey Shows Limited Adoption of the Avoidance of Mechanical Ventilation in Japan: A Cross‐Sectional Study

2025-06-21

Takashi Shima , Takeshi Kusuda , Nobuhiko Kan +3 more | Acta Paediatrica

ABSTRACT Aim To investigate Japanese perspectives on the avoidance of mechanical ventilation strategy for extremely preterm infants. Methods A web‐based questionnaire was sent to the perinatal centres enrolled in the … ABSTRACT Aim To investigate Japanese perspectives on the avoidance of mechanical ventilation strategy for extremely preterm infants. Methods A web‐based questionnaire was sent to the perinatal centres enrolled in the Japanese Neonatologist Association and the Japanese Society of Perinatal and Neonatal Circulatory Management. The enrollment window was between the 21st of July and the 31st of December 2021. Results This survey covered 59% of the general perinatal centres in Japan. The study revealed that 64% of respondents would not attempt early continuous positive airway pressure strategy for extremely preterm infants. Intubation–surfactant–extubation and less‐invasive surfactant administration were used in 58% and 11% of the institutes, respectively. Technical unfamiliarity, insufficient evidence, lack of videolaryngoscopy and concerns about potential complications hindered the implementation of less‐invasive surfactant administration. Conclusions Early continuous positive airway pressure strategy was uncommon for extremely preterm infants. Intubation–surfactant–extubation was five times more popular than less‐invasive surfactant administration. Lack of training, evidence, videolaryngoscopy and assurance were the key limiting factors for the uptake of less‐invasive surfactant administration across Japan.

Epigenetic effects of endogenous and exogenous glucocorticosteroids during pregnancy on the offspring: a systematic-narrative review

2025-06-21

Fotini Kanouta , Τheodoros Karampitsakos , Eleni Memi +3 more | HORMONES

Correction: Prevention of nasal injury in preterm infants during positive pressure ventilation: a systematic review of interface and dressing selection

2025-06-21

Tingting Gong , Jiali Yu , Hua Yang +3 more | BMC Pediatrics

Reconsidering milrinone as a primary treatment for neonatal pulmonary hypertension: an alternative to inhaled nitric oxide in resource-limited Asian settings

2025-06-21

Ashir Ahtsham , Nabeel Ahmad | International Journal of Scientific Reports

Neonatal pulmonary hypertension is a commonly encountered condition with underlying low systemic blood pressure and reduced cardiac output secondary to right ventricular overload and myocardial dysfunction. Research indicates a high … Neonatal pulmonary hypertension is a commonly encountered condition with underlying low systemic blood pressure and reduced cardiac output secondary to right ventricular overload and myocardial dysfunction. Research indicates a high incidence of this condition, occurring in 0.5 to 7 neonates per 1000 live births, with a mortality rate of 4-33%, underscoring the need for early diagnosis and effective management.

Management dilemma in choosing evolving treatments in neutropenic septic shock

2025-06-21

H. David Humes , Kera E. Luckritz , Stephen M. Gorga +4 more | Pediatric Nephrology

Abstract How does a physician decide to use a recently FDA-approved life-saving device in a desperately ill child in which little prior clinical experience is available? This report presents a … Abstract How does a physician decide to use a recently FDA-approved life-saving device in a desperately ill child in which little prior clinical experience is available? This report presents a pediatric patient with neutropenic septic shock and multiorgan failure (MOF) with a 95% chance of death and the availability of a therapeutic device with a completely new approach to treat sepsis. This device, called the selective cytopheretic device (SCD), is a first-in-class autologous immune cell directed therapy. The SCD, when integrated into an extracorporeal blood circuit, has been shown to bind activated neutrophils and monocytes. With a simple pharmacologic maneuver within the device, the bound cells in real time are immunomodulated from a highly pro-inflammatory state to a less inflammatory phenotype. These transformed cells are then released back into the systemic circulation thereby tempering the systemic hyperinflammatory disorder. Since this cell directed therapy focuses on neutrophils, the processing of these cells in a neutropenic state may be a substantive risk resulting in further immunosuppression. On the other hand, the immunomodulation of the circulating neutrophils and monocytes, although sparse, may be beneficial to disrupt the dysregulated inflammatory state responsible for ongoing tissue damage and organ dysfunction. Prior clinical SCD trials excluded patients with neutropenia so that no prior clinical experience was available to make a difficult decision. This report presents the way the medical team approached these issues and made a therapeutic plan that resulted in a positive clinical outcome for the patient.

Impact of implementing nasal high flow therapy on body growth in preterm infants

2025-06-21

Rosemarie de Ridder , Trixie A. Katz , Anton H. van Kaam +7 more | Neonatology

Introduction: The objective of this study was to determine the impact of nasal high flow (nHF) implementation on lung growth at six months corrected age (CA) in preterm infants. Methods: … Introduction: The objective of this study was to determine the impact of nasal high flow (nHF) implementation on lung growth at six months corrected age (CA) in preterm infants. Methods: This single-center retrospective cohort study included preterm infants born <30 weeks gestation' and surviving to six months CA at the neonatal intensive care unit of the Amsterdam University Medical Centers. In the nCPAP cohort (2009-2012), continuous distending pressure (CDP) was applied solely with nasal continuous positive airway pressure support. In the nHF cohort (2015-2018) nCPAP was used and followed by nHF therapy to deliver CDP. Bodyweight and length at six months CA were used as a proxy for lung growth. We also assessed the impact on respiratory management and neonatal morbidity. Multivariate analysis was performed after multiple imputation, using a linear regression adjusting for confounding variables. Results: Of the 598 eligible infants, 313 infants were included in the nCPAP cohort, and 285 infants in the nHF cohort. The analyses showed no differences between the nCPAP and nHF cohort in body weight (7.29 vs 7.31 kilogram, 95%CI -0.14-0.20, p=0.71), and length (66.6 vs 66.8 centimeters (95%CI -0.30- 0.81, p=0.26) at six months CA. No differences in moderate/severe bronchopulmonary dysplasia (BPD) were reported, but nHF implementation was associated with longer CDP duration, a trend towards more days on supplemental oxygen, and shift from moderate to severe BPD. Conclusions: Implementation of nHF did not impact body growth, which is associated with lung growth, at six months CA in preterm infants born <30 weeks.

Routine 36‐week scan: prediction of prolonged neonatal intensive care unit admission

2025-06-21

Anastasija Arechvo , Eleftheria Demertzidou , S. Adjahou +5 more | Ultrasound in Obstetrics and Gynecology

ABSTRACT Objectives To examine the contribution of maternal demographic characteristics and elements of medical history to the prediction of prolonged (> 2 days) neonatal intensive care unit (NICU) admission for … ABSTRACT Objectives To examine the contribution of maternal demographic characteristics and elements of medical history to the prediction of prolonged (> 2 days) neonatal intensive care unit (NICU) admission for high‐dependency or intensive care, and to investigate the added value to such prediction of the findings from the 36‐week ultrasound scan and data from labor and delivery. Methods We included 107 762 women with a singleton pregnancy who had undergone a routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation. Assessment included medical history, estimated fetal weight (EFW), and Doppler measurements of uterine artery (UtA) pulsatility index (PI), umbilical artery (UA) PI and fetal middle cerebral artery (MCA) PI. Multivariable logistic regression was used to evaluate the independent contributions to prolonged NICU admission of maternal factors (demographic and pregnancy characteristics), findings from the 36‐week scan, and data from labor and delivery. Detection rates (DRs) and areas under the receiver‐operating‐characteristics curve (AUCs) for prolonged NICU admission were compared. Results Overall, 946 (0.88%) neonates required prolonged NICU admission. The maternal factors that significantly contributed to prediction of prolonged NICU admission were body mass index, social deprivation, conception via in‐vitro fertilization, chronic hypertension, Type‐1 diabetes mellitus, pre‐eclampsia and gestational diabetes mellitus. Screening by maternal factors provided a DR of 20.7% at a false‐positive rate (FPR) of 10% (AUC, 0.606 (95% CI, 0.587–0.625)). Significant predictors from the 36‐week scan included deepest vertical pocket of amniotic fluid < 2 cm and ≥ 8 cm, UA‐PI >95 th percentile and MCA‐PI < 5 th percentile. Screening by a combination of maternal factors and 36‐week scan findings improved the DR at a 10% FPR to 27.5% (AUC, 0.637 (95% CI, 0.618–0.656)). When maternal factors, 36‐week scan findings, and data from labor and delivery (lower gestational age at delivery, delivery by Cesarean section and birth weight < 10 th and > 90 th percentile) were included in the model, the DR at a 10% FPR improved to 39.1% (AUC, 0.709 (95% CI, 0.690–0.728)). When this combined model was restricted to prediction of prolonged NICU admission for indications that excluded those affected by intrapartum events, the DR at a 10% FPR was 57.2% (AUC, 0.790 (95% CI, 0.764–0.815)). Conclusions Maternal factors (particularly social deprivation), 36‐week scan findings, and data from labor and delivery each make an independent contribution to the risk of prolonged NICU admission at term. Nevertheless, more than 40% of these admissions are not predictable prior to labor and birth. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Center-specific variation in outcomes for extremely premature, extremely low birth weight neonates

2025-06-20

Sai Manasa Kalyanam , Jordan R. Kuiper , Theodore J. Iwashyna +4 more | Frontiers in Pediatrics

The survival rate of neonates born with extremely low birth weight (&lt;1,000 g) and extremely preterm (&lt;29 gestational age) has significantly improved with advances in neonatal care. Despite such advances, … The survival rate of neonates born with extremely low birth weight (&lt;1,000 g) and extremely preterm (&lt;29 gestational age) has significantly improved with advances in neonatal care. Despite such advances, outcomes vary widely across neonatal intensive care units due to differences in care practices and patient population. In this study, we examined 1,627 extremely low birth weight and extremely preterm infants admitted to three NICUs across the United States between 2013 and 2023. We evaluated survival and severe intraventricular hemorrhage (SIVH) using statistical models that were adjusted for maternal and neonatal characteristics. Significant differences in outcomes were observed between the centers. These differences were associated with variations in care practices, including resuscitation decisions for the infants. Despite these differences, all centers achieved survival without SIVH for a substantial number of infants, annually. These findings emphasize the need for evidence-based practice-sharing and improvements to ensure better and more consistent care.

Correction: An FGFR-p53 developmental signaling axis drives salivary cancer progression

2025-06-20

Adele M. Musicant , Julia Billington , Jeffrey S. Damrauer +7 more | Oncogene

Short-Term Effects over Time of Endotracheal Suctioning on Very Low Birth Weight Premature Infants with RDS

2025-06-20

Ernestas Viršilas , Arūnas Valiulis , Arūnas Liubšys | Children

Background: Respiratory distress syndrome (RDS) is a frequent cause of invasive respiratory support. Our study aims to assess end-expiratory lung impedance (EELZ) and DeltaZ changes post-suction using electrical impedance tomography. … Background: Respiratory distress syndrome (RDS) is a frequent cause of invasive respiratory support. Our study aims to assess end-expiratory lung impedance (EELZ) and DeltaZ changes post-suction using electrical impedance tomography. Methods: Very low birth weight infants with gestational ages less than 32 weeks under conventional mechanical ventilation with an open endotracheal suction system were included in this study. Data was evaluated at four time periods: immediately after the completion of suctioning and at 1, 5 and 10 min marks post-suction. Results: Sixteen patients participated in this study, during which a total of 31 suctioning events were recorded. There were no significant hypoxemic events during the analyzed timeframe. Over a 10 min period following suction, there was a consistent change in EELZ and DeltaZ, with EELZ decreasing and DeltaZ increasing accordingly (p < 0.001). Conclusions: Our study demonstrated that EELZ and DeltaZ changes persist even 10 min after suctioning using an open endotracheal suction system.

Targeted Pre-Conditioning and Cell Transplantation in the Murine Lower Respiratory Tract

2025-06-20

Anat Kohn , Michael J. Herriges , Pratyay Basak +4 more | American Journal of Respiratory Cell and Molecular Biology

Transplantation of airway basal stem cells could achieve a durable cure for genetic diseases of the airway, such as cystic fibrosis and primary ciliary dyskinesia. Recent work demonstrated the potential … Transplantation of airway basal stem cells could achieve a durable cure for genetic diseases of the airway, such as cystic fibrosis and primary ciliary dyskinesia. Recent work demonstrated the potential of primary- and pluripotent stem cell (PSC)-derived basal cells to efficiently engraft into the mouse trachea after injury. However, there are many hurdles to overcome in translating these approaches to humans including developing safe and efficient methods for delivery in larger animal models. We propose a model which targets preconditioning and cell-delivery to intrapulmonary airways utilizing a micro-bronchoscope for delivery. The detergent polidocanol was adapted for distal lung pre-conditioning, inducing intrapulmonary airway epithelial denudation by 5 and 24-hours post-delivery. While initial re-epithelialization of airways occurred later than tracheas, complete repair was observed within 7-days. Both PSC-derived and primary basal cells delivered via micro-bronchoscope post-polidocanol injury engrafted in tracheas and intrapulmonary airways, respectively. Transplanted cells differentiated into ciliated and secretory lineages while maintaining a population of basal cells. These findings demonstrate the utility of bronchoscopically targeted pre-conditioning and cell delivery to the conducting intra-pulmonary airways. Thus providing an important framework for pre-clinical translation of approaches for engineered airway epithelial regeneration.

Caffeine and preterm infants: multiorgan effects and therapeutic creep: scope to optimise dose and timing

2025-06-20

Michael O’Shea , Louise Butler , S. Holohan +7 more | Pediatric Research

Abstract Caffeine is a methylxanthine used for nearly 50 years in the treatment of apnoea of prematurity (AOP). Caffeine citrate is effective in the treatment of AOP using standard dosing … Abstract Caffeine is a methylxanthine used for nearly 50 years in the treatment of apnoea of prematurity (AOP). Caffeine citrate is effective in the treatment of AOP using standard dosing (loading dose 20 mg/kg, maintenance 5–10 mg/kg/day) and is associated with long-term neurological benefits and other improved organ outcomes as well as immunomodulatory effects. Therapeutic creep has been noted in the use of caffeine in preterm infants differing from the criteria in randomised controlled trials. A Cochrane review showed insufficient evidence to support prophylactic use of caffeine citrate in preterm neonates to prevent AOP, although it is still recommended in many national and local guidelines. Concerns about adverse reactions exist with high-dose caffeine regimens with one high-dose trial reporting statistically significant increases in abnormal neurological outcomes compared with standard doses (80 mg/kg compared to 20 mg/kg). International clinical guidelines vary from clinical trials regarding timing, dose, and duration of caffeine therapy. Further clinical research could help to understand optimal doses for different indications, such as peri-extubation, early postnatal use while ventilated, multiorgan and psychoactive effects, and long-term neurodevelopmental outcomes. This review describes the mechanism and multiorgan effects of caffeine highlighting areas of therapeutic creep and uncertainty requiring further research, such as comparative effectiveness trials. Impact Caffeine citrate is indicated for the management of apnoea of prematurity. Therapeutic creep is evident in international guidelines for the use of caffeine citrate in preterm infants. Caffeine has multiorgan effects involving renal, respiratory, and inflammatory responses, which, by optimising dosing and timing, may improve outcomes. Optimising indications, dose, and timing of caffeine citrate in preterm infants in further large-scale trials is warranted and may have other multiorgan benefits.

Vibration Based Detection for the Monitoring of Neonatal bCPAP Respiratory Support to Minimize Duration of Disconnections

2025-06-20

Kaitlyn Calabresi , Meera Bhat , Lingling Kong +7 more | Journal of Medical Devices

Abstract Bubble continuous positive airway pressure (bCPAP) is a minimally invasive respiratory support for neonates experiencing respiratory distress syndrome (RDS). It exerts continuous, oscillatory air pressure to encourage lung function … Abstract Bubble continuous positive airway pressure (bCPAP) is a minimally invasive respiratory support for neonates experiencing respiratory distress syndrome (RDS). It exerts continuous, oscillatory air pressure to encourage lung function and development. Neonates? movement may cause disconnections at the nasal interface. These disconnections are characterized by the cessation of bubbling at the bCPAP respiratory circuit output and frequently go unnoticed until hypoxia develops. Common Neonatal Intensive Care Unit (NICU) bCPAP systems lack a built-in alarm or accessory device to monitor for disconnections. As a result, nursing personnel must exercise extreme caution utilizing current bCPAP procedure. If a neonate is disconnected, it may go unnoticed for 4 hours or more, depending on nurse availability and rounding schedules. To solve this issue, we propose a novel vibration-based detection apparatus to augment existing bCPAP systems that immediately alert clinicians on the cessation of bubbling in the bCPAP water canister. Our independent monitoring system can assure staff that neonates will not develop hypoxia-related complications due to bCPAP failure. Preliminary benchtop testing with a model bCPAP system indicates that the monitor is effective in detecting bubbling cessation under simulated bCPAP operation conditions, in the pressure range of 5 to 10 cmH2O. The monitor detected disconnections in an average of 4.22 seconds across all setting trials, minimizing the time to intervention. While this study was limited to benchtop testing, our initial findings indicate that an accessory bubbling monitor allows for early detection of bCPAP disconnections with future utility in the NICU.

Protocol for establishing genetically engineered murine lung organoids mimicking cell plasticity and regeneration

2025-06-20

Bong-Jun Kim , Jae‐Il Park | STAR Protocols

Predictive models for intrapartum maternal fever: Development and validation of pre-analgesia and labor process indicators

2025-06-20

Bo Liu , Ling Liang , Dayuan Wei +6 more | Medicine

Combined spinal-epidural anesthesia is effective for labor pain relief but is associated with increased rates of intrapartum maternal fever, which can negatively impact maternal and neonatal outcomes. This study aimed … Combined spinal-epidural anesthesia is effective for labor pain relief but is associated with increased rates of intrapartum maternal fever, which can negatively impact maternal and neonatal outcomes. This study aimed to develop and validate 2 predictive models: one to assess the risk of fever before labor analgesia (model B) and another to evaluate the risk of fever throughout the labor process (model W). This retrospective case-control study was conducted at Chengdu Jinjiang District Maternal & Child Health Hospital, including 2783 parturients who received labor analgesia between January 2021 and March 2022. Stepwise logistic regression was used to identify clinical predictive indicators, followed by multivariate logistic regression to determine intrapartum fever predictors. Model performance was assessed using the Hosmer-Lemeshow test and areas under the receiver operating characteristic curves (AUROCs). A total of 2276 patients were included in the development cohort and 507 in the validation cohort. Optimal predictors for model B included primiparity, neutrophil count, anemia, estimated fetal weight, body surface area, and cervical dilation before analgesia. For model W, predictors included height, primiparity, anemia, neutrophil count, estimated fetal weight, total duration of labor, and time from rupture of membranes to delivery. AUROCs for models B and W were 0.698 and 0.740, respectively; external validation showed AUROCs of 0.703 and 0.797. In conclusion, model B effectively predicts fever risk before labor analgesia, though its predictive efficiency is lower than model W, which better predicts fever risk after analgesia. The combination of these 2 models will aid in the early identification and management of high-risk parturients, thereby reducing the incidence of intrapartum fever and improving maternal and neonatal outcomes.

Tailoring Anesthesia for Whole Lung Lavage: Experiences from a Case Series

2025-06-20

Aakanksha Chawla , Chetan Mehra , Balaji Pallapotu | Indian Journal of Critical Care Case Report

Effect of implementing a clinical practice guideline for prophylactic indomethacin on reduction of severe IVH in extremely preterm infants

2025-06-19

Enikő Szakmár , Sasha Harrison , Hoda El-Shibiny +2 more | Journal of Neonatal-Perinatal Medicine

Background Prophylactic indomethacin in preterm infants has been associated with reduction of severe intraventricular hemorrhage (SIVH) but no improvement in neurodevelopmental outcome. Since January 2016, Brigham and Women’s Hospital has … Background Prophylactic indomethacin in preterm infants has been associated with reduction of severe intraventricular hemorrhage (SIVH) but no improvement in neurodevelopmental outcome. Since January 2016, Brigham and Women’s Hospital has implemented a clinical practice guideline (CPG) for prophylactic indomethacin to prevent SIVH. Our aim was to compare the predicted and observed rate of SIVH before and after CPG implementation. Second, to evaluate the association between indomethacin and development of SIVH. Methods This retrospective cohort study included infants born between 23 and 28 weeks of gestation. Variables were compared between before (pre-group) and after the CPG implementation (post-group). Risk categories for SIVH were defined as the following based on a validated model: low <15%, moderate ≥15% to <25%, and high risk ≥25%. Multivariate logistic regression model was applied to evaluate the association between SIVH and the administration of indomethacin. Results Infants in the post-group ( n = 325) presented with lower Apgar scores, higher rate of necrotizing enterocolitis, abdominal surgery, and mortality comparing to pre-group ( n = 424). The use of indomethacin for any reason was 44% in pre-group and 62% in post-group ( p < 0.001). There was no significant difference in the predicted and observed rate of SIVH between the 2 groups in any risk categories. There was no association between the use of indomethacin and development of SIVH in multivariate regression models. Conclusion The implementation of CPG for prophylactic indomethacin was not associated with reduction in the incidence of SIVH and no association was found between the use of indomethacin and development of SIVH.

Ciliated Epithelial Cell Differentiation at Air-Liquid Interface and RSV infection using Animal-Free Media and Substrates

2025-06-19

Machaela Palor , Elizabeth K. Haughey , Jenny Herbert +5 more | ERJ Open Research

Animal-derived components in cell culture, such as foetal bovine serum (FBS) and extracellular matrix proteins (ECM), pose ethical concerns and contribute to variability in experimental outcomes. This study explores the … Animal-derived components in cell culture, such as foetal bovine serum (FBS) and extracellular matrix proteins (ECM), pose ethical concerns and contribute to variability in experimental outcomes. This study explores the use of animal-free cell culture media and substrates to support the growth and differentiation of primary human bronchial epithelial cells (BECs), as well as their infection by respiratory syncytial virus (RSV). We evaluated the performance of jellyfish collagen 0 and recombinant ECM proteins as alternatives to traditional mammalian substrates. Additionally, we assessed the use of animal-free media and human serum (HS) in viral propagation using HEp2 cells. Results demonstrate that the use of animal-free medium and matrix proteins and human serum can support primary epithelial cell growth and differentiation, with high-levels of ciliation and barrier integrity. RSV propagation in animal-free medium produced an increase in viral titres, indicating the potential of these systems for anti-viral research. Transitioning to include more animal-free medium and substrates for primary cell culture and viral propagation will help improve the ethical standing of research and offer more human-relevant models for studying viral diseases in the future.

Metabolic acidosis as a risk factor for bronchopulmonary dysplasia in preterm infants born between 23 + 0 and 31 + 6 weeks of gestation: a retrospective case-control study

2025-06-19

Taehoon Shin , E. J. Lee , Howard Choi +1 more | Frontiers in Pediatrics

Background Metabolic acidosis is a common condition in preterm infants; however, its independent role in the development of bronchopulmonary dysplasia (BPD) remains unclear. In this study, we examined the association … Background Metabolic acidosis is a common condition in preterm infants; however, its independent role in the development of bronchopulmonary dysplasia (BPD) remains unclear. In this study, we examined the association between metabolic acidosis and the occurrence of moderate/severe BPD or mortality in preterm infants born between 23 + 0 and 31 + 6 weeks of gestation. Methods We retrospectively reviewed the medical records of 254 preterm infants (&lt;32 weeks gestation) admitted between January 2017 and December 2024. The primary outcome was moderate/severe BPD or mortality before 36 weeks of postmenstrual age. Blood gas parameters, including pH, base excess, bicarbonate, and lactate, were analyzed daily during the first 14 days of life. Inverse probability of treatment weighting (IPTW) was applied to adjust for confounders such as gestational age, fluid balance, respiratory support, and patent ductus arteriosus (PDA) status. Results After excluding infants with missing data ( n = 88), 168 infants were included, of whom 55 developed moderate/severe BPD or died. Following IPTW adjustment, metabolic acidosis on day 6 of life (DOL 6) was significantly associated with moderate/severe BPD or mortality (OR: 1.369, 95% CI: 1.085–1.727). Differences in cumulative fluid intake were statistically significant during the first week (7.365% vs. 23.478%, p = 0.022) and became more pronounced in the second week after IPTW adjustment (8.206% vs. 22.888%, p = 0.024). Conclusion Metabolic acidosis on DOL 6 was associated with an increased risk of moderate/severe BPD or mortality, suggesting its potential role as a modifiable risk factor. While excessive fluid intake has been linked to BPD, our findings highlight the complexity of fluid management in preterm infants. Further research is needed to determine whether correcting metabolic acidosis could improve respiratory outcomes.

Development and Validation of an HPLC‐RI Method for the Simultaneous Determination of DPPC, Palmitic Acid, and Cholesterol in Bovine Pulmonary Surfactant

2025-06-19

Mahsa Aghaei , Mahjoobeh Ehsani , Malihe Keramati | Biomedical Chromatography

ABSTRACT This study aimed to develop and validate an HPLC‐RI method for the simultaneous determination of dipalmitoylphosphatidylcholine (DPPC), palmitic acid, and cholesterol in bovine pulmonary surfactant, a critical treatment for … ABSTRACT This study aimed to develop and validate an HPLC‐RI method for the simultaneous determination of dipalmitoylphosphatidylcholine (DPPC), palmitic acid, and cholesterol in bovine pulmonary surfactant, a critical treatment for infants suffering from Respiratory Distress Syndrome (RDS). The Iranian surfactant, Beraksurf, was used as the sample. A simple extraction procedure involving methanol dissolution and protein precipitation was employed, followed by HPLC analysis. The method underwent comprehensive validation for various parameters, including system suitability, repeatability (intra‐assay precision), intermediate precision, linearity, accuracy, limit of detection (LOD), limit of quantification (LOQ), and robustness. The results demonstrated excellent system suitability. Repeatability and intermediate precision were confirmed with low %RSD values, while linearity was established with correlation coefficients ( R 2 ) exceeding 0.99 for all analytes. The method exhibited high accuracy, with recoveries ranging from 97% to 100%, and low LOD and LOQ values, indicating its sensitivity. Robustness testing revealed that minor variations in method parameters did not significantly impact results. This validated RP‐HPLC‐RID method provides a reliable and efficient approach for the analysis of key surfactant components, contributing to improved quality control in surfactant preparations and enhancing therapeutic strategies for managing RDS in infants.

Schichterfüllungsquoten in der Pflege und Überlebenschancen sehr kleiner Frühgeborener – Datenanalyse der Perinatalzentren Level 1 in Deutschland 2019–2023

2025-06-18

Claudia Roll , Kerstin Liersch-Baumann , Christoph Bührer | Zeitschrift für Geburtshilfe und Neonatologie

Zusammenfassung Ein höheres Pflege-Patienten-Verhältnis geht mit geringerer Mortalität und Morbidität einher. Der Gemeinsame Bundesausschuss macht für Neugeborenen-Intensivstationen schichtgenaue Vorgaben zum Pflegepersonalschlüssel. Besteht ein Zusammenhang zwischen Erfüllungsquoten und Ergebnisqualität? Die für … Zusammenfassung Ein höheres Pflege-Patienten-Verhältnis geht mit geringerer Mortalität und Morbidität einher. Der Gemeinsame Bundesausschuss macht für Neugeborenen-Intensivstationen schichtgenaue Vorgaben zum Pflegepersonalschlüssel. Besteht ein Zusammenhang zwischen Erfüllungsquoten und Ergebnisqualität? Die für 2019-2023 veröffentlichten Schichterfüllungsquoten der Perinatalzentren Level I (n=163) wurden mit dem relativen Überleben und Überleben ohne schwere Erkrankung von Frühgeborenen<1500 g (Gestationsalter 240/7–316/7 Wochen) verglichen Es bestand keine Korrelation zwischen Erfüllungsquoten und Überleben (Rs=0,008, p=0,918) oder Überleben ohne schwere Erkrankung (Rs=–0,050, p=0,529). Kliniken mit Erfüllungsquoten ≤ 95% (n=82) hatten gegenüber solchen mit>95% (n=81) höhere Fallzahlen Frühgeborener<1500 g (Median [Interquartilbereich] 53 [37–77] vs 41 [33–53], p=0,001) und höhere risikoadjustierte Fallzahlen (56 [35–77] vs 42 [30–58], p=0,002), unterschieden sich aber nicht bezüglich relativer Überlebensraten (1,00 [0,99–1,01] vs 1,00 [0,99-1,01], p=0,722) oder Überleben ohne schwere Erkrankung (1,00 [0,97–1,03] vs 0,99 [0,97–1,02], p=0,346). Keine signifikanten Unterschiede ergaben sich beim Vergleich mit anderen Grenzwerten oder beim Vergleich der untersten mit der obersten Quartile. Für die Schichterfüllungsquoten fand sich kein Zusammenhang mit der an Überleben und Überleben ohne schwere Erkrankung gemessenen Ergebnisqualität kleiner Frühgeborener.

Incidence and predictors of mortality among preterm neonates admitted to the neonatal intensive care unit of Wallaga University Comprehensive Specialized Hospital, Nekemte Town, East Wallaga, Oromia, Ethiopia: a retrospective cohort study

2025-06-18

Mubarek Abera , Fikadu Enkosa , Emiru Merdassa | Research Square (Research Square)

<title>Abstract</title> BACKGROUND Preterm birth affects 1 in 10 babies globally, with disproportionately high mortality in low-income settings. Sub-Saharan Africa bears a significant burden due to limited healthcare access. Despite the … <title>Abstract</title> BACKGROUND Preterm birth affects 1 in 10 babies globally, with disproportionately high mortality in low-income settings. Sub-Saharan Africa bears a significant burden due to limited healthcare access. Despite the availability of modifiable risk factors and cost-effective interventions, data on incidence of mortality of preterm neonates in the study area is lacking. OBJECTIVE To assess incidence and predictors of mortality among preterm neonates admitted to the neonatal intensive care unit of Wallaga University Comprehensive Specialized Hospital, Nekemte Town, Oromia, Ethiopia, from July 1, 2022, to June 30, 2024. METHODS An institution-based retrospective cohort study was conducted among 264 preterm neonates admitted to the NICU within the study period and study subjects were selected using systematic random sampling technique. Data were collected using a structured checklist, entered via EpiData version 4.6, and subsequently analyzed using STATA version 14.0. Kaplan-Meier and log-rank tests were used to compare survival probability and assess statistically significance difference between groups. The Cox proportional hazards model assumption was checked. A bivariable Cox regression analysis was fitted and those variable with p < 0.2 were included in the multivariable analysis. Finally, statistical significance was declared at a p-value < 0.05. RESULTS Of 259 preterm neonates, 42 died during follow up time, with incidence proportion of 16%. The median survival time was 28 days (IQR: 22–30), with 2,737 neonate-days of follow-up. The overall incidence rate of mortality was 15.3 per 1,000 neonate-days (95% CI: 11.3–20.7). Significant predictors of mortality included were lack of ANC follow-up (AHR: 2.27, 95% CI: 1.13–4.57), antenatal steroid use (AHR: 0.44, 95% CI: 0.21–0.92), home delivery (AHR: 7.74, 95% CI: 1.99–30.03), and presence of hypothermia (AHR: 4.11; 95% CI: 1.55–10.85). CONCLUSION AND RECOMMENDATION: The study identified key clinical and maternal predictors associated with preterm neonatal mortality. Targeted interventions focusing on antenatal care, delivery practices, steroid administration, and thermal regulation are essential.

Standardized endotracheal tube and intravascular access placement in infants born at 22-23 weeks gestation

2025-06-18

Nima Naseh , Linda Wallström , Richard Sindelar +1 more | Pediatric Research

The Effect of Systemic Inflammation on Newborns: The Prognostic Value of the Aggregate Systemic Inflammation Index (AISI) and Systemic Inflammatory Response Index (SIRI)

2025-06-17

Samet Kırat | Diagnostics

Objective: This study aimed to investigate the prognostic value of two novel systemic inflammatory indices-the Aggregate Systemic Inflammation Index (AISI) and the Systemic Inflammatory Response Index (SIRI)-in predicting preterm delivery … Objective: This study aimed to investigate the prognostic value of two novel systemic inflammatory indices-the Aggregate Systemic Inflammation Index (AISI) and the Systemic Inflammatory Response Index (SIRI)-in predicting preterm delivery and associated neonatal outcomes. Methods: A retrospective, descriptive, cross-sectional study was conducted using the electronic health records of 1056 pregnant women admitted to a tertiary university hospital between 2020 and 2025. Pregnancies were classified into preterm (n = 528) and term (n = 528) groups. Demographic, obstetric, neonatal, and laboratory data were analyzed. Results: The AISI and SIRI values in the first trimester and at admission were significantly higher in the preterm delivery group than in the term delivery group (p < 0.001). Elevated AISI and SIRI levels correlated with lower 1st- and 5th-minute APGAR scores (p < 0.001) and higher neonatal intensive care unit (NICU) admission rates (35.8% vs. 4.5%; p < 0.001). The AISI cut-offs were 399.2 for preterm delivery (59.7% sensitivity, 59.8% specificity), 558.8 for NICU admission (79.3% sensitivity, 79.2% specificity), 694.0 for RDS (87.8% sensitivity, 87.8% specificity), 602.1 for sepsis (79.6% sensitivity, 79.2% specificity), and 753.8 for congenital pneumonia (81.6% sensitivity, 81.9% specificity). The SIRI cut-offs were 1.7 for preterm delivery (59.1% sensitivity, 58.9% specificity), 2.4 for NICU admission (81.7% sensitivity, 81.6% specificity), 3.1 for RDS (89.0% sensitivity, 89.5% specificity), 3.0 for sepsis (85.8% sensitivity, 85.7% specificity), and 3.4 for congenital pneumonia (85.7% sensitivity, 83.8% specificity). Conclusions: The AISI and SIRI showed significant predictive utility for neonatal morbidity in preterm delivery. The use of these markers in clinical practice may improve neonatal outcomes by enhancing the early diagnosis and management of high-risk pregnancies.

A novel potassium channel opener for spontaneous preterm birth prevention: Bringing the concepts together.

2025-06-17

Amr A. Awd , Adel Aly Elboghdady , Mahmoud Mohammed Mohammed Metwally +7 more | PubMed

Its goal is to evaluate nicorandil, a potassium channel opener, for tocolysis in premature labor patients in a tertiary care facility. We evaluated 100 pregnant women who were given nicorandil … Its goal is to evaluate nicorandil, a potassium channel opener, for tocolysis in premature labor patients in a tertiary care facility. We evaluated 100 pregnant women who were given nicorandil (study group n= 50 cases) and nifedipine (control group n= 50 cases) for tocolysis in established preterm labour between 24 and 33+6 weeks of gestation. The effectiveness of tocolysis in extending pregnancy for more than 48 hours and 7 days, adverse effects on the mother and fetus, and admission to the neonatal critical care unit were compared across the groups. The number of births at 24 0/7- 33 6/7 weeks did not differ significantly between the two groups when pregnancy was prolonged for more than 48 hours or 7 days (P > 0.05). Negative effects on the mother and fetus were lower in the nicorandil group (< P 0.05), although both groups' rates of newborn ICU hospitalization were comparable (P > 0.05). Nicorandil has the benefit of having less harmful effects on the mother and fetus than nifedipine in situations of established preterm labor for inhibiting labor.

Inflammatory signatures and immunomodulation in neonates: a pilot study.

2025-06-17

Lucia Leonardi , Valentina Pennetta , Rossella Laitano +7 more | PubMed

The precise diagnosis of inflammatory responses is essential for managing infectious diseases. Dysregulated inflammatory responses can lead to death and high morbidity in some subjects due to sensitive age, genetic … The precise diagnosis of inflammatory responses is essential for managing infectious diseases. Dysregulated inflammatory responses can lead to death and high morbidity in some subjects due to sensitive age, genetic predisposition, or other comorbidities. More specifically, dysregulated immunological development in newborns has been investigated to elucidate inflammatory regulation in prone populations, as being the first step to future immunomodulatory therapeutic interventions. Indeed, compared to adults, neonates display both an immature immune response to microorganisms, due to a diminished Th1 response and an immature compensatory anti-inflammatory response. In this exploratory study, we aimed to characterize inflammatory signatures in i) preterm newborns, ii) full-term newborns, iii) full-term newborns exposed in-utero to Cytomegalovirus (CMV) infections, and iv) healthy adults as a further control group. Our investigation used a whole-blood approach to quantify the basal and the Toll-like receptors (TLRs)-induced cytokine responses. Samples from cord blood and peripheral blood (of healthy adults) were stimulated or not with ligands for TLR1/2, TLR4, and TLR7/8 to elicit cytokine production. We found that after TLR7/8 stimulation the blood of full-term newborns showed higher concentrations of IL-6 and TNF-α compared to the other groups. Moreover TLR7/8 ligand, compared to other TLR ligands, potentiated pro-inflammatory responses according to the presence of IL-6, TNF-α and CXCL8 in adults, while in preterm new-borns we disclosed TNF-α α elevation. In preterm newborns, we also observed increased TLR1/2-induced IL-10 concentration suggestive of modifications in the immunosuppressive and inflammatory state. Our pilot results strongly encourage further investigations comparing age groups and different immunomodulatory agents further promoting the discussion that TLR7/8 ligands could be suitable vaccine adjuvant candidates for newborns. At the same time, IL-10-associated immunomodulation (monoclonal antibody anti-IL-10, anti-IL-10 receptors, or anti-TLR1/2) might be a future therapeutic option for cases of overwhelming neonatal inflammatory diseases.

Effectiveness of nurses’ training about mechanical ventilation weaning on neonatal outcomes

2025-06-17

Mohammed F Alharbi , Salwa Ali Marzouk , Nojoud Alrashidi +7 more | BMC Nursing

Abstract Introduction Prematurity is a significant global health challenge. Premature infants frequently need invasive mechanical ventilation until their lungs are fully developed. Due to the possible complications of ventilation, nurses … Abstract Introduction Prematurity is a significant global health challenge. Premature infants frequently need invasive mechanical ventilation until their lungs are fully developed. Due to the possible complications of ventilation, nurses in the neonatal intensive care unit (NICU) must deliver specialized care to achieve the best outcomes for these infants. Objective This study aimed to explore the effectiveness of nurses’ training in mechanical ventilation weaning on neonatal outcomes. Method A quasi-experimental non-equivalent group design was used with purposive sampling of 70 nurses and 64 newborn infants on invasive mechanical ventilation. The infants were divided into two groups: 32 weaned by trained nurses (study group) and 32 weaned by standard methods (control group). Data was collected using a structured questionnaire about the nurses and neonates. A well-designed training program, including theoretical and practical components, was conducted for the nurses to ensure proper weaning of neonates from mechanical ventilation. Results The study group demonstrated a significant reduction in the use of surfactant replacement therapy post-extubation compared to the control group ( p = 0.003). Additionally, infants in the study group experienced a statistically significant decrease in NICU hospitalization duration, total weaning time, and total ventilation period compared to the control group ( p = 0.003, 0.0001, and 0.0001, respectively). Complications were markedly lower in the study group, with two-thirds of infants experiencing no complications, compared to 15.6% in the control group ( p = 0.001). Moreover, re-intubation rates were significantly reduced in the study group compared to the control group ( p = 0.1026). Conclusion These results highlight the effectiveness of the intervention in improving clinical outcomes for neonates, including reduced treatment needs, shorter hospital stays, and fewer complications. Clinical trial number Not applicable.

Long-Term Maternal Exposure to Triclosan Provokes Pulmonary Fibrosis in Mouse Offspring

2025-06-17

Jing Liu , Mingzhu Guo , Wenqing Li +2 more | Environment & Health

Comparative analysis on the efficacy of antenatal corticosteroids in preterm newborns in a Kazakhstani Tertiary Care Hospital setting

2025-06-16

Saltanat Sairankyzy , Ingkar Kinayatova , Diana Amangeldi +5 more | World Journal of Clinical Pediatrics

BACKGROUND For over half a century, the administration of maternal corticosteroids before anticipated preterm birth has been regarded as a cornerstone intervention for enhancing neonatal outcomes, particularly in preventing respiratory … BACKGROUND For over half a century, the administration of maternal corticosteroids before anticipated preterm birth has been regarded as a cornerstone intervention for enhancing neonatal outcomes, particularly in preventing respiratory distress syndrome. Ongoing research on antenatal corticosteroids (ACS) is continuously refining the evidence regarding their efficacy and potential side effects, which may alter the application of this treatment. Recent findings indicate that in resource-limited settings, the effectiveness of ACS is contingent upon meeting specific conditions, including providing adequate medical support for preterm newborns. Future studies are expected to concentrate on developing evidence-based strategies to safely enhance ACS utilization in low- and middle-income countries. AIM To analyze the clinical effectiveness of antenatal corticosteroids in improving outcomes for preterm newborns in a tertiary care hospital setting in Kazakhstan, following current World Health Organization guidelines. METHODS This study employs a comparative retrospective cohort design to analyze single-center clinical data collected from January 2022 to February 2024. A total of 152 medical records of preterm newborns with gestational ages between 24 and 34 weeks were reviewed, focusing on the completeness of the ACS received. Quantitative variables are presented as means with standard deviations, while frequency analysis of qualitative indicators was performed using Pearson's χ 2 test (χ ²) and Fisher's exact test. If statistical significance was identified, pairwise comparisons between the three observation groups were conducted using the Bonferroni correction. RESULTS The obtained data indicate that the complete implementation of antenatal steroid prophylaxis (ASP) improves neonatal outcomes, particularly by reducing the frequency of birth asphyxia (P = 0.002), the need for primary resuscitation (P = 0.002), the use of nasal continuous positive airway pressure (P = 0.022), and the need for surfactant replacement therapy (P = 0.038) compared to groups with incomplete or no ASP. Furthermore, complete ASP contributed to a decrease in morbidity among preterm newborns (e.g. , respiratory distress syndrome, intrauterine pneumonia, cerebral ischemia, bronchopulmonary dysplasia, etc. ), improved Apgar scores, and reduced the need for re-intubation and the frequency of mechanical ventilation. However, it was associated with an increased incidence of uterine atony in postpartum women (P = 0.0095). CONCLUSION In a tertiary hospital setting, the implementation of ACS therapy for pregnancies between 24 and 34 weeks of gestation at high risk for preterm birth significantly reduces the incidence of neonatal complications and related interventions. This, in turn, contributes to better outcomes for this cohort of children. However, the impact of ACS on maternal outcomes requires further thorough investigation.

Longitudinal changes in cardiopulmonary outcomes of adults born extremely prematurely: United Kingdom Oscillation Study

2025-06-16

Allan Jenkinson , Christopher Harris , Mona Bafadhel +3 more | Pediatric Research

Abstract Background During puberty, lung function of individuals born extremely prematurely can deteriorate putting them at risk of early chronic obstructive pulmonary disease (COPD). We hypothesise that young adults exposed … Abstract Background During puberty, lung function of individuals born extremely prematurely can deteriorate putting them at risk of early chronic obstructive pulmonary disease (COPD). We hypothesise that young adults exposed to postnatal corticosteroids will have poorer lung and cardiac function, higher pulmonary artery pressures and poorer exercise tolerance compared to preterm born adults not exposed to postnatal steroids and term born adults. We further hypothesise lung function differences may be demonstrated depending on mode of ventilation at birth (high frequency oscillatory or conventional ventilation) in preterm born adults. Methods A prospective study of participants (aged 24-28) from the United Kingdom Oscillation Study (UKOS) and term born controls. Assessments will involve comprehensive lung function, cardiac ultrasound, exercise assessments, inflammatory cell and biomarker profiling and airway microbiome assessment. The primary outcome is the ratio of forced expiratory volume in 1 s/forced vital capacity (FEV 1 /FVC); to detect a significant difference we will recruit 150 individuals. Statistical analysis will involve mixed effect models with adjustment for imbalances and sensitivity analysis. Discussion The results may identify adults born extremely preterm at increased risk of COPD and pulmonary hypertension (PH) who might benefit from interventions to delay the onset of COPD and cardiovascular complications such as PH. Impact Adults born extremely prematurely in the modern era of neonatal care are an emerging population whose long-term outcomes have infrequently been reported. This study will describe their cardiac and lung function, pulmonary artery pressures, exercise capacity and immunobiological profile. We aim to identify risk factors for worse outcomes such as early chronic obstructive pulmonary disease onset and pulmonary hypertension. The results will identify those who might benefit from multi-disciplinary follow-up to ensure interventions are employed to delay the onset of COPD and manage longer term cardiovascular problems.

The role of T-helper and T regulatory cells in driving neutrophilic and eosinophilic inflammation in bronchiectasis

2025-06-16

Evangelia Fouka , Anders Lindén , Apostolos Bossios | Frontiers in Immunology

Bronchiectasis is a chronic airway disease characterized by dysbiosis, persistent inflammation, and permanent structural airway damage. Neutrophilic inflammation is a key pathogenic feature, as indicated by enhanced neutrophil-derived proteases and … Bronchiectasis is a chronic airway disease characterized by dysbiosis, persistent inflammation, and permanent structural airway damage. Neutrophilic inflammation is a key pathogenic feature, as indicated by enhanced neutrophil-derived proteases and formation of neutrophil extracellular traps (NETs), associated with poor prognosis. However, recent studies have identified an eosinophilic endotype in up to 30% of patients, characterized by higher levels of type 2 (T2) cytokines and fractional exhaled nitric oxide (FeNO). The role of T helper (Th) cells in the dysregulated inflammatory environment of bronchiectasis remains unclear. Evidence suggests that persistent bacterial infection can skew adaptive immunity from Th1 toward Th2 response, while the airway microbiome-IL-17 axis is also a critical regulator of chronic inflammation. T regulatory (Treg) cells have been shown to play a protective role against excessive chronic inflammation by modulating the function of several types of effector cells, including the Th17 subset. However, the capacity of this subset to delay or prevent disease progression remains to be determined Microbial dysbiosis, with loss of diversity and increased quantity of bacterial pathogens, may also be important for disease progression, and emerging evidence indicates that distinct inflammatory endotypes associate with specific microbiota alterations, especially in severe disease. In this review, we provide an overview of the immune cells and cytokine signaling that are involved in the pathogenesis of bronchiectasis. Additionally, we present the main endotypes of bronchiectasis and explore the relationships between the type of inflammation and alterations in microbiota, as well as the potential benefits of targeting specific pathophysiological mechanisms for the management of bronchiectasis. This review also examines how bacterial infection can shift adaptive immunity from Th1 toward Th2 responses, the role of the airway microbiome-IL-17 axis in chronic inflammation and the potential protective role of Treg cells against excessive inflammation. Novel therapeutic strategies are highlighted, with focus on targeting specific cytokine signaling pathways and restoring Th17/Treg balance These developments underscore a shift toward precision medicine in bronchiectasis, emphasizing the importance of identifying specific inflammatory endotypes to tailor treatment strategies effectively.