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Diffuse, interstitielle Lungenerkrankungen (ILD) des Sauglings- und Kindesalters (chILD) zeigen ein vom Erwachsenenalter deutlich abweichendes Krankheitsspektrum. Die etablierten Klassifikationen trennen dabei zwischen fur das fruhe Kindesalter typischen ILD und ILD ohne spezifischen Bezug zum Kindesalter. Die Einordnung beruht dabei auf einer synoptischen Betrachtung der Befunde von Klinik, Bildgebung, Genetik und Pathologie. Eine Lungenbiopsie wird in der Regel eingesetzt, um eine spezifische chILD-Diagnose bei bislang unklarem Befund zu erheben oder eine rasch progrediente Lungensymptomatik bzw. einen prolongierten Symptomverlauf abzuklaren. Da auch Pathologen auserhalb von Referenzzentren mit padiatrischen Lungenbefunden konfrontiert werden, stellt diese Ubersicht relevante klinische und morphologische Befunde charakteristischer chILD vor.

In premature neonates with a primary surfactant deficiency , there is ARDS and surfactants is the main line of therapy. Now it is well known that the virus is attached to and is replicated within type 11 pneumocytes, the main function of these cells is production of surfactants which decrease surface tension and keep the alveoli patent without collapse. In this condition there is a secondary surfactant deficiency which may play a role in pathogenesis and deterioration of patient clinical condition.So, I suggest that treatment by surfactant therapy either derived from endogenous or exogenous source in severe cases can improve clinical condition, delay or avoid patient ventilation by refilling debilitated surfactants and lavage of bronchial tree, this directly decrease mortality rate.In premature neonates with a primary surfactant deficiency , there is ARDS and surfactants is the main line of therapy. Now it is well known that the virus is attached to and is replicated within type 11 pneumocytes, the main function of these cells is production of surfactants which decrease surface tension and keep the alveoli patent without collapse. In this condition there is a secondary surfactant deficiency which may play a role in pathogenesis and deterioration of patient clinical condition

Background Diaphragm weakness occurs rapidly in adult animals treated with mechanical ventilation (MV), but the effects of MV on the neonatal diaphragm have not been determined. Furthermore, it is unknown whether co-existent lung disease exacerbates ventilator-induced diaphragmatic dysfunction (VIDD). We investigated the impact of MV (mean duration = 7.65 h), either with or without co-existent respiratory failure caused by surfactant deficiency, on the development of VIDD in newborn lambs. Methods Newborn lambs (1–4 days) were assigned to control (CTL, non-ventilated), mechanically ventilated (MV), and MV + experimentally induced surfactant deficiency (MV+SD) groups. Immunoblotting and quantitative PCR assessed inflammatory signaling, the ubiquitin-proteasome system, autophagy, and oxidative stress. Immunostaining for myosin heavy chain (MyHC) isoforms and quantitative morphometry evaluated diaphragm atrophy. Contractile function of the diaphragm was determined in isolated myofibrils ex vivo. Results Equal decreases (25–30%) in myofibrillar force generation were found in MV and MV+SD diaphragms compared to CTL. In comparison to CTL, both MV and MV+SD diaphragms also demonstrated increased STAT3 transcription factor phosphorylation. Ubiquitin-proteasome system (Atrogin1 and MuRF1) transcripts and autophagy indices (Gabarapl1 transcripts and the ratio of LC3B-II/LC3B-I protein) were greater in MV+SD relative to MV alone, but fiber type atrophy was not observed in any group. Protein carbonylation and 4-hydroxynonenal levels (indices of oxidative stress) also did not differ among groups. Conclusions In newborn lambs undergoing controlled MV, there is a rapid onset of diaphragm dysfunction consistent with VIDD. Superimposed lung injury caused by surfactant deficiency did not influence the severity of early diaphragm weakness. Electronic supplementary material The online version of this article (10.1186/s13054-019-2409-6) contains supplementary material, which is available to authorized users.

Background Surfactant is produced by alveolar type 2 cells and secreted into the alveoli to prevent atelectasis. Respiratory Distress Syndrome (RDS) is caused by surfactant deficiency due to immature lungs in premature infants. Congenital surfactant deficiency is a rare condition caused by mutations in specific surfactant proteins, which can present like RDS in term infants. Mutations in ATP-binding cassette subfamily A3 (ABCA3) are the most common causes of genetic surfactant deficiency. ABCA3-associated surfactant deficiency is inherited in an autosomal recessive manner and has been associated with lethal neonatal respiratory failure and childhood interstitial lung disease (ILD). …

Mutations in adenosine triphosphate-binding cassette transporter A3 (ABCA3) (OMIM: 601615) gene constitute the most frequent genetic cause of severe neonatal respiratory distress syndrome (RDS) and interstitial lung disease (ILD) in children. Interstitial lung disease in children and especially in infants, in contrast to adults, is more likely to appear as a result of developmental deficits or is characterized by genetic aberrations of pulmonary surfactant homeostasis not responding to exogenous surfactant administration. The underlying ABCA3 gene mutations are commonly thought, regarding null mutations, to determine the clinical course of the disease while there exist mutation types, especially missense variants, whose effects on surfactant proteins are difficult to predict. In addition, clinical and radiological signs overlap with those of surfactant proteins B and C mutations making diagnosis challenging. We demonstrate a case of a one-term newborn male with lethal respiratory failure caused by homozygous missense ABCA3 gene mutation c.3445G>A (p.Asp1149Asn), which, to our knowledge, was not previously reported as a causative agent of newborn lethal RDS. Therapeutic strategies for patients with ABCA3 gene mutations are not sufficiently evidence-based. Therefore, the description of the clinical course and treatment of the disease in terms of a likely correlation between genotype and phenotype is crucial for the development of the optimal clinical approach for affected individuals.

Dr. Louis Dehner is an internationally renowned surgical pathologist who has published multiple textbooks and has authored or co-authored nearly 400 original articles in the medical literature. While many think of him as a pediatric pathologist, he has contributed to the literature across virtually the entire breadth of surgical pathology, and the lung and pleura is no exception. This review will highlight Dr. Dehner׳s contributions to the pulmonary and pleural pathology literature in the areas of infectious disease, medical lung disease and transplant pathology, and a number of neoplasms of the lung and pleura, with the remainder of this manuscript dedicated to the still evolving story of the pleuropulmonary blastoma as the signature contribution of his long and distinguished career.

Surfactant catheters are used to administer exogenous surfactant as a preventive and therapeutic measure for surfactant deficiency in premature neonates. We describe the case of a retained surfactant catheter in a 700 g premature neonate with associated pneumothorax.

Objective To evaluate surfactant production and function in term neonates with transient tachypnea of the newborn (TTN). Study design Samples of gastric aspirates collected within 30 minutes of birth from 42 term newborns with gestational age ≥37 weeks (21 patients with TTN and 21 control subjects), delivered via elective cesarean delivery, were analyzed with lamellar body count and stable microbubble test. Results Results of lamellar body counts and stable microbubble tests were significantly lower in the TTN group than in control subjects ( P = .004 and .013, respectively). Lamellar body counts were significantly lower in infants with TTN requiring oxygen for ≥24 hours after birth than in infants requiring oxygen for P = .029). When the cutoff point was 48 hours, the stable microbubble count was significantly lower in the group requiring oxygen for ≥48 hours than in the group requiring oxygen for P = .047). Conclusions Term infants with TTN had low lamellar body counts associated with decreased surfactant function, suggesting that prolonged disease is associated with surfactant abnormalities.

Although there was a significant lag time between the discovery of surfactant and its clinical application, the seminal paper was written by Mary Ellen Avery and Jere Mead in 1959. (1) Treatment of respiratory distress syndrome (hyaline membrane disease) took a giant step forward when surfactant was approved by the United States Food and Drug Administration for use in neonates more than a decade ago. In addition to the original paper by Avery and Mead, we also have permission to reproduce two pieces by Dr. Avery, which tell the story of the discovery of the role of surfactant and its modern application. The first was published in the Ross series, “Landmarks in Perinatology/Neonatology” in February 1977, and the second comes from a presentation that Dr. Avery recently made in Japan, which will be published in the Journal of the Japan Society for Premature and Newborn Medicine . Finally, more details of how this discovery “really happened” are available in another recent review. (2) 1. ↵ Avery ME, Mead J. Surface properties in relation to atelectasis and hyaline membrane disease. Am J Dis Child.1959;97:517–523 [OpenUrl][1][CrossRef][2][PubMed][3] 2. ↵ Avery ME. Surfactant deficiency in hyaline membrane disease: the story of discovery. Am J Respir Crit Care Med.2000;161:1074–1075 [OpenUrl][4][PubMed][5] # Historic Perspective on Surfactant Deficiency {#article-title-2} The following commentary originally appeared in 1977 as one of a series published by Ross Laboratories entitled “Landmarks in Perinatology/Neonatology” and is reproduced with permission of Ross Products Division, Abbott Laboratories, Inc, Columbus, OH. The demonstration of deficient surface-tension-lowering substances in lung extracts of infants who died with hyaline membrane disease was a step in a series of observations that had previously set the stage. Peter Gruenwald, the pathologist, had wondered about the abnormal patterns of aeration in lungs of premature infants and doubted as early as 1947 that hyaline membranes were not responsible for resorption atelectasis. Richard Pattle, the student of foams and anti-foam agents at the Chemical Defense Establishment in England, had discovered the surface-tension-lowering properties of the alveolar lining layer and wondered if a deficiency of it could be responsible for poor aeration … [1]: {openurl}?query=rft.jtitle%253DArchives%2Bof%2BPediatrics%2Band%2BAdolescent%2BMedicine%26rft.stitle%253DArch%2BPediatr%2BAdolesc%2BMed%26rft.issn%253D0002-922X%26rft.aulast%253DAVERY%26rft.auinit1%253DM.%2BE.%26rft.volume%253D97%26rft.issue%253D5_PART_I%26rft.spage%253D517%26rft.epage%253D523%26rft.atitle%253DSurface%2BProperties%2Bin%2BRelation%2Bto%2BAtelectasis%2Band%2BHyaline%2BMembrane%2BDisease%26rft_id%253Dinfo%253Adoi%252F10.1001%252Farchpedi.1959.02070010519001%26rft_id%253Dinfo%253Apmid%252F13649082%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1001/archpedi.1959.02070010519001&link_type=DOI [3]: /lookup/external-ref?access_num=13649082&link_type=MED&atom=%2Fneoreviews%2F3%2F12%2Fe239.atom [4]: {openurl}?query=rft.jtitle%253DAmerican%2BJournal%2Bof%2BRespiratory%2Band%2BCritical%2BCare%2BMedicine%26rft.stitle%253DAm.%2BJ.%2BRespir.%2BCrit.%2BCare%2BMed.%26rft.issn%253D1073-449X%26rft.aulast%253DAVERY%26rft.auinit1%253DM.%2BE.%26rft.volume%253D161%26rft.issue%253D4%26rft.spage%253D1074%26rft.epage%253D1075%26rft.atitle%253DSurfactant%2BDeficiency%2Bin%2BHyaline%2BMembrane%2BDisease%253A%2BThe%2BStory%2Bof%2BDiscovery%26rft_id%253Dinfo%253Apmid%252F10764292%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [5]: /lookup/external-ref?access_num=10764292&link_type=MED&atom=%2Fneoreviews%2F3%2F12%2Fe239.atom

Respiratory distress is a common problem in the neonate, and imaging plays an important part in the initial diagnosis and management of these infants. This chapter discusses the most common medical and surgical conditions of the lung encountered in the newborn, with emphasis on the role of a multi-modal evaluation for surgical planning.

The pulmonary surfactant system is uniquely positioned to meet the physical and environmental challenges associated with the transition to air breathing at birth. Its maturation is under complex multifactorial control that ensures the system is mature in late gestation in readiness for birth. Surfactant dysfunction through preterm birth or genetic causes may lead to respiratory distress syndrome (RDS). The use of antenatal glucocorticoids and neonatal administration of exogenous surfactant has been remarkably successful in the treatment of RDS. However, resistance to therapy has uncovered a genetic basis to many cases of acute neonatal RDS. Identification of gene defects relating to surfactant has provided a specific cause to many previously classified idiopathic interstitial lung diseases during neonatal life, early childhood, or adulthood. These discoveries have led to the search for genetic markers of RDS risk and new therapeutic targets of interstitial lung disease, including the development of gene therapy strategies.

For predicting the risk of respiratory distress syndrome (RDS), lung surfactant in amniotic fluid can be assessed by observation of stable microbubbles (2 was defined as cutoff value of the MT. A specificity of 90% and a sensitivity of 52% was obtained with this cutoff value. A much lower rate of false negative results (sensitivity 91%) was noted after surface tension measurement of TA. The sensitivity of the MT (52%) does not encourage the use of the MT on TA.

A rapid test determining surfactant deficiency or dysfunction might help in controlling therapy of respiratory distress syndrome (RDS). Forty tracheal aspirate samples (TA) from 40 newborns with RDS (group 1) and 46 pharyngeal from 46 newborns without RDS (reference group) were analyzed by surface tension measurement with the pulsating bubble surfactometer. Five surface tension parameters were compared. Marked differences between both groups could be noted for the parameters: minimum surface tension (gamma min) and stability index (S), while maximum surface tension (gamma max), surface tension after a 10-second adsorption period and hysteresis area did not have striking differences. The parameters gamma min and S have the highest diagnostic value for determining surfactant deficiency or dysfunction. For a rapid test it is sufficient to compare gamma min with reference values, because S is calculated from gamma min and gamma max.

Pediatric radiologists are frequently called upon to render interpretations of chest radiographs performed on premature infants with chronic respiratory problems. After the acute phase of surfactant deficiency (respiratory distress syndrome), infants with persistent respiratory problems are loosely categorized by clinicians as evolving toward a broad, rather vague entity called bronchopulmonary dysplasia (BPD) or chronic lung disease (CLD). This review aims to update the radiologist on how the characteristics of the disease have shifted and how management, diagnosis and pathology have changed since the disorder was first described more than 40 years ago. The radiologist armed with this information might be better prepared to provide insightful reporting and address the needs of the neonatologist.

Inherited disorders of pulmonary surfactant-associated proteins are rare but provide important insights into unique mechanisms of surfactant dysfunction. Recessive loss-of-function mutations in the surfactant protein-B and the ATP-binding cassette family member A3 (ABCA3) genes present as lethal surfactant deficiency in the newborn, whereas other recessive mutations in ABCA3 and dominant mutations in the surfactant protein-C gene result in interstitial lung disease in older infants and children. The molecular basis and the genetic and tissue-based approaches to the evaluation of children suspected of having one of these disorders are discussed.

We would like to report a series of four newborns in an extended family who have had spontaneous pneumothorax soon after birth without any obvious cause (fig 1). There is no history of pneumothorax in anyone else in the family. Figure 1 Genetic map showing the positions of the neonates with spontaneous pneumothorax in the extended family. A female infant was born in good condition at term by emergency caesarian section after a normal pregnancy. She had a spontaneous right sided tension pneumothorax within a few minutes of birth. The pneumothorax was drained. There was no evidence of surfactant deficiency on any of the initial chest radiographs. After discharge she went on to have three other …

In a randomized trial in 102 preterm newborns with respiratory distress syndrome (RDS) it has been shown that early Ambroxol treatment (30 mg kg(-1) over the first 5 days) significantly reduces the incidence of RDS-associated complications [bronchopulmonary dysplasia (BPD), intraventricular haemorrhage, post-natal acquired pneumonia]. The aim of the present analysis was to investigate the effect of Ambroxol treatment on lung function in newborns who developed BPD. Respiratory function testing (RFT) was performed immediately after extubation and at day 28. Tidal volume (VT) and respiratory frequency (f) were measured during tidal breathing using the deadspace free flow-through technique. The lung mechanic parameter VT/maxPes was determined by measuring the maximal oesophageal pressure changes, maxPes, with a catheter tip pressure transducer. In the placebo group 36/50 infants were extubated within the first 28 days of life and 13/36 (36%) developed BPD. In the Ambroxol group 44/52 were extubated and 9/44 (20%) developed BPD. After extubation, RFT showed (i) no statistically significant difference in the ventilatory parameters of either treatment group, (ii) improved (P

Pulmonary surfactant is a complex of surface-active lipids mixed with specific proteins. Two of these, SP-B and SP-C, are essential for adsorption of surfactant lipids to the air-liquid interfaces of the lungs and, hence, are also essential for alveolar stability and effective gas exchange. Surfactant substitutes must contain at least one of these proteins (or analogues of them) to be optimally effective when administered into the airways of babies with surfactant deficiency or dysfunction. This review describes how an increased understanding of the properties of surfactant proteins has led to the development of improved synthetic surfactants with the potential to treat a wide range of respiratory disorders.

Cesarean sections performed without antecedent labor are associated with a higher risk of respiratory distress than those performed after the onset of labor, despite the fact that they may have been done at full term (at least 37 weeks of gestation).1 This respiratory distress is usually transient tachypnea of the newborn, which is generally milder in both severity and duration than respiratory distress syndrome due to hyaline membrane disease in premature babies. Unlike hyaline membrane disease, which results from a surfactant deficiency, transient tachypnea of the newborn results from delayed clearance of fetal alveolar fluid. The volume of fetal alveolar . . .

The neonatal respiratory distress syndrome (RDS), which occurs almost exclusively in premature infants, is a disease caused by a surfactant deficiency. The chances of surviving the disease have markedly improved in the last decade. With the introduction of the L/S ratio, which is now an established method, it has been possible for the first time to predict RDS reliably. Widespread application of this method is limited due to the fact that it is relatively staff- and time-consuming.

Pulmonary surfactant replacement has previously been shown to be effective in the human neonatal respiratory distress syndrome. The value of surfactant replacement in models of acute lung injury other than quantitative surfactant deficiency states is, however, uncertain. In this study an acute lung injury model using rats with chronic indwelling arterial catheters, injured with N-nitroso-N-methylurethane (NNNMU), has been developed. The NNNMU injury was found to produce hypoxia, increased mortality, an alveolitis, and alterations in the pulmonary surfactant system. Alterations of surfactant obtained by bronchoalveolar lavage included a reduction in the phospholipid-to-protein ratio, reduced surface activity, and alterations in the relative percentages of the individual phospholipids compared with controls. Treatment of the NNNMU-injured rats with instilled exogenous surfactant (Survanta) improved oxygenation; reduced mortality to control values; and returned the surfactant phospholipid-to-protein ratio, surface activity, and, with the exception of phosphatidylglycerol, the relative percentages of individual surfactant phospholipids to control values.

There are many functional and pathologic similarities between the adult respiratory distress syndrome (ARDS) and the respiratory distress syndrome (RDS) of premature newborn infants, including a lack of surfactant in the alveolar spaces and airways [1, 2]. In ARDS, however, surfactant deficiency is a complication of lung injury rather than, as in neonatal RDS, a primary etiologic factor.

Efficient ventilation relieves pulmonary vasospasm in persistent fetal circulation (PFC). Evidence on surfactant deficiency