Automated Interpretation of Lung Sounds by Deep Learning in Children With Asthma: Scoping Review and Strengths, Weaknesses, Opportunities, and Threats Analysis.

BACKGROUND: The interpretation of lung sounds plays a crucial role in the appropriate diagnosis and management of pediatric asthma. Applying artificial intelligence (AI) to this task has the potential to better standardize assessment and may even improve its predictive potential. OBJECTIVE: This study aims to objectively review the literature on AI-assisted lung auscultation for pediatric asthma and provide a balanced assessment of its strengths, weaknesses, opportunities, and threats. METHODS: A scoping review on AI-assisted lung sound analysis in children with asthma was conducted across 4 major scientific databases (PubMed, MEDLINE Ovid, Embase, and Web of Science), supplemented by a gray literature search on Google Scholar, to identify relevant studies published from January 1, 2000, until May 23, 2023. The search strategy incorporated a combination of keywords related to AI, pulmonary auscultation, children, and asthma. The quality of eligible studies was assessed using the ChAMAI (Checklist for the Assessment of Medical Artificial Intelligence). RESULTS: The search identified 7 relevant studies out of 82 (9%) to be included through an academic literature search, while 11 of 250 (4.4%) studies from the gray literature search were considered but not included in the subsequent review and quality assessment. All had poor to medium ChAMAI scores, mostly due to the absence of external validation. Identified strengths were improved predictive accuracy of AI to allow for prompt and early diagnosis, personalized management strategies, and remote monitoring capabilities. Weaknesses were the heterogeneity between studies and the lack of standardization in data collection and interpretation. Opportunities were the potential of coordinated surveillance, growing data sets, and new ways of collaboratively learning from distributed data. Threats were both generic for the field of medical AI (loss of interpretability) but also specific to the use case, as clinicians might lose the skill of auscultation. CONCLUSIONS: To achieve the opportunities of automated lung auscultation, there is a need to address weaknesses and threats with large-scale coordinated data collection in globally representative populations and leveraging new approaches to collaborative learning.

[Puff alert: addiction to nicotine products among young people]. / Alerte aux puffs : addiction aux produits nicotiniques chez les jeunes.

Consumption of e-cigarettes (particularly the famous "puffs") and other nicotine products has risen sharply among Swiss teenagers, and now exceeds consumption of traditional cigarettes. Yet these products are harmful to health. Nicotine is highly addictive for young people, and e-cigarette use causes significant respiratory morbidity for both active and passive users. We are just measuring the extent of the toxic effects of these products, given their recent appearance on the market, but the initial scientific evidence is extremely worrisome and calls for a rapid response. Prevention among young people is crucial, and better legislation is urgently needed.

La consommation d'e-cigarettes (notamment des fameuses « puffs ¼) et d'autres produits nicotiniques a fortement augmenté chez les adolescents suisses, dépassant désormais la consommation de cigarettes traditionnelles. Ces produits sont pourtant nocifs pour la santé. La nicotine a un très fort pouvoir addictif chez les jeunes et la consommation d'e-cigarette induit une importante morbidité respiratoire pour les consommateurs actifs mais aussi passifs. Nous mesurons à peine l'étendue des effets toxiques de ces produits vue leur apparition récente sur le marché, mais les premiers éléments scientifiques sont extrêmement préoccupants et appellent à une réaction rapide. La prévention auprès des jeunes est capitale et un meilleur encadrement législatif nécessaire.

[Where we stand with asthma: optimized medical care and biologic therapy for children]. / Le point sur l'asthme en pédiatrie : optimisation de la prise en charge et thérapies biologiques.

Asthma recommendations are in constant evolution. Salbutamol exclusivity as the historical reference treatment for asthma exacerbations is now questioned. In case of light to moderate crisis, budesonide/formoterol, combining an inhaled corticosteroid and a fast acting long lasting beta2 agonist, can now be proposed as first line as needed treatment, for adolescents older than 12 years old. In addition, progress in fundamental research revealed the heterogeneous nature of asthma and allowed for the emergence of new-targeted therapies.

La prise en charge de l'asthme est en constante évolution. L'exclusivité du salbutamol, traitement historique de référence des exacerbations aiguës, même légères, est remise en question depuis plusieurs années. En cas de symptômes ou crise légère à modérée, le budésonide/formotérol, combiné de corticostéroïde inhalé et bronchodilatateur (ß2-agoniste) d'action rapide et prolongée, peut dorénavant être proposé en première intention, à la demande, y compris en pédiatrie, notamment à partir de 12 ans. De plus, les progrès en recherche fondamentale ont permis de révéler la nature hétérogène de l'asthme et de faire émerger de nouvelles cibles thérapeutiques. En particulier, les patients asthmatiques peuvent bénéficier de l'entrée des biologiques dans l'arsenal thérapeutique.

Early life exposure to nicotine modifies lung gene response after elastase-induced emphysema.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is among the top 5 causes of mortality in the world and can develop as a consequence of genetic and/or environmental factors. Current efforts are focused on identifying early life insults and how these contribute to COPD development. In line with this, our study focuses on the influence of early life nicotine exposure and its potential impact on (a) lung pulmonary functions, and (b) elastase-induced emphysema in adulthood. METHODS: To address this hypothesis, we developed a model of 2 hits, delivered at different time points: mouse pups were first exposed to nicotine/placebo in utero and during lactation, and then subsequently received elastase/placebo at the age of 11 weeks. The effect of nicotine pretreatment and elastase instillation was assessed by (a) measurement of pulmonary function at post-elastase day (ped) 21, and (b) transcriptomic profiling at ped3 and 21, and complementary protein determination. Statistical significance was determined by 3- and 2-way ANOVA for pulmonary functions, and RNAseq results were analyzed using the R project. RESULTS: We did not observe any impact of nicotine pre- and early post-natal exposure compared to control samples on lung pulmonary functions in adulthood, as measured by FLEXIVENT technology. After elastase instillation, substantial lung damage was detected by x-ray tomography and was accompanied by loss in body weight at ped3 as well as an increase in cell numbers, inflammatory markers in BAL and lung volume at ped21. Lung functions showed a decrease in elastance and an increase in deep inflation volume and pressure volume (pv) loop area in animals with emphysema at ped21. Nicotine had no effect on elastance and deep inflation volume, but did affect the pv loop area in animals with emphysema at ped21. Extensive transcriptomic changes were induced by elastase at ped3 both in the nicotine-pretreated and the control samples, with several pathways common to both groups, such as for cell cycle, DNA adhesion and DNA damage. Nicotine pretreatment affected the number of lymphocytes present in BAL after elastase instillation and some of the complement pathway related proteins, arguing for a slight modification of the immune response, as well as changes related to general body metabolism. The majority of elastase-induced transcriptomic changes detected at ped3 had disappeared at ped21. In addition, transcriptomic profiling singled out a common gene pool that was independently activated by nicotine and elastase. CONCLUSIONS: Our study reports a broad spectrum of transient transcriptomic changes in mouse emphysema and identifies nicotine as influencing the emphysema-associated immune system response.

Simultaneous isolation of endothelial and alveolar epithelial type I and type II cells during mouse lung development in the absence of a transgenic reporter.

Mouse lung developmental maturation and final alveolarization phase begin at birth. During this dynamic process, alveolar cells modify their morphology and anchorage to the extracellular matrix. In particular, alveolar epithelial cell (AEC) type I undergo cytoplasmic flattening and folding to ensure alveoli lining. We developed FACS conditions for simultaneous isolation of alveolar epithelial and endothelial cells in the absence of specific reporters during the early and middle alveolar phase. We evidenced for the first time a pool of extractable epithelial cell populations expressing high levels of podoplanin at postnatal day (pnd)2, and we confirmed by RT-qPCR that these cells are already differentiated but still immature AEC type I. Maturation causes a decrease in isolation yields, reflecting the morphological changes that these cell populations are undergoing. Moreover, we find that major histocompatibility complex II (MHCII), reported as a good marker of AEC type II, is poorly expressed at pnd2 but highly present at pnd8. Combined experiments using LysoTracker and MHCII demonstrate the de novo acquisition of MCHII in AEC type II during lung alveolarization. The lung endothelial populations exhibit FACS signatures from vascular and lymphatic compartments. They can be concomitantly followed throughout alveolar development and were obtained with a noticeable increased yield at the last studied time point (pnd16). Our results provide new insights into early lung alveolar cell isolation feasibility and represent a valuable tool for pure AEC type I preparation as well as further in vitro two- and three-dimensional studies.

Gestation and lactation exposure to nicotine induces transient postnatal changes in lung alveolar development.

Harmful consequences of cigarette smoke (CS) exposure during lung development can already manifest in infancy. In particular, early life exposure to nicotine, the main component of CS, was shown to affect lung development in animal models. We aimed to characterize the effect of nicotine on alveoli formation. We analyzed the kinetics of normal alveolar development during the alveolarization phase and then looked at the effect of nicotine in a mouse model of gestational and early life exposure. Immunohistochemical staining revealed that the wave of cell proliferation [i.e., vascular endothelial cells, alveolar epithelial cells (AEC) type II and mesenchymal cell] occurs at postnatal day (pnd) 8 in control and nicotine-exposed lungs. However, FACS analysis of individual epithelial alveolar cells revealed nicotine-induced transient increase of AEC type I proliferation and decrease of vascular endothelial cell proliferation at pnd8. Furthermore, nicotine increased the percentage of endothelial cells at pnd2. Transcriptomic data also showed significant changes in nicotine samples compared with the controls on cell cycle-associated genes at pnd2 but not anymore at pnd16. Accordingly, the expression of survivin, involved in cell cycle regulation, also follows a different kinetics in nicotine lung extracts. These changes resulted in an increased lung size detected by stereology at pnd16 but no longer in adult age, suggesting that nicotine can act on the pace of lung maturation. Taken together, our results indicate that early life nicotine exposure could be harmful to alveolar development independently from other toxicants contained in CS.

Human Deoxyribonuclease (rhDNase) Nebulization as an Alternative Treatment for Refractory Plastic Bronchitis After Fontan Surgery.

We report the case of a 5-year-old boy who developed chronic plastic bronchitis after Fontan surgery for a complex congenital heart disease. During a new admission for acute exacerbation of plastic bronchitis, he started on a mucolytic treatment with inhaled rhDNAse instead of inhaled fibrinolytics because of the potential bleeding risk in a patient on combined coumarin and aspirin treatment. Respiratory symptoms resolved promptly, and the patient was discharged home on rhDNAse treatment. He remained clinically stable on rhDNAse treatment without further hospitalization until definitive treatment with dynamic lymphangiography and percutaneous embolization.

Pulmonary complications after liver transplantation in children: risk factors and impact on early post-operative morbidity.

Liver transplantation (LT) is associated with high post-operative morbidity, despite excellent survival rates. With this retrospective study, we report the incidence of early and late pulmonary complications (PC) after LT, identify modifiable risk factors for PC and analyzed the role of PC in post-operative ventilation duration and hospital length of stay. In a series of 79 children (0-16 years) with LT over a 12 years period, early (<3 months post-LT) and/or late (>3 months post-LT) PC occurred in 68 patients (86%). Sixty-four percent (64%) developed early major complications such as pulmonary edema, atelectasis, or pleural effusion. Atelectasis requiring an intervention (P ≤ .02), pulmonary edema (P ≤ .02), or elevated PELD/MELD scores (P = .05) were associated with an increase in total ventilation duration and length of stay in the ICU. Risk factors for early PC included preoperative hypoxemia (P = .005), low serum albumin at LT admission (P = .003), or early rejection (P = .002). About 20% of patients experienced late PC of which 81% were infections. Risk factor assessment prior to LT may ultimately help reduce early PC thereby possibly minimizing post-operative morbidity and ICU length of stay.

[Pectus excavatumn and carinatum in children and adolescents : what to say, what to do ?] / Pectus excavatum et carinatum chez l'enfant et l'adolescent : que dire, que faire ?

In children presenting with a pectus excavatum (PE) or pectus carinatum (PC) an underlying syndrome including Marfan's syndrome needs to be excluded. In adolescents, severe chest wall deformities may cause cardiac or respiratory problems but most commonly they have a psychological impact. The conservative treatment is a Vacuum Bell for PE, and a Dynamic Compression System for PC ; they play an increasing role in young patients. These devices need to be worn multiple hours per day for several months for an optimal result. Surgery is usually reserved for adolescents. The Nuss procedure for PE, also known as minimal invasive repair of PE offers excellent results. Sterno-chondro-plasty with stabilisation of the sternum with struts clipped to the ribs offers the same good results for PC. In our opinion, a multidisciplinary approach is preferable.

En présence d'un thorax en entonnoir (pectus excavatum, PE) ou en carène (pectus carinatum, PC), une affection syndromique, dont la maladie de Marfan, doit être recherchée. La déformation, avant tout disgracieuse, peut générer des troubles psychologiques chez l'adolescent, et des désordres cardiorespiratoires dans les formes sévères. Les traitements conservateurs sont très utiles chez le jeune : cloche aspirante pour PE ou corset dynamique de compression pour PC. Ils sont portés quelques heures par jour pendant plusieurs mois selon un « contrat moral ¼ établi avec l'enfant. La chirurgie peut être négociée chez l'adolescent. La technique mini-invasive par thoracoscopie de Nuss offre des résultats satisfaisants dans les PE. Il en est de même des sternochondroplasties fixées par des attelles-agrafes pour les PC. Un avis pluridisciplinaire est utile.

Laser microdissection, proteomics, and multiplex immunohistochemistry: a bumpy ride into the study of paraffin-embedded fetal and pediatric lung tissues.

Background: Knowledge about lung development or lung disease is mainly derived from data extrapolated from mouse models. This has obvious drawbacks in developmental diseases, particularly due to species differences. Our objective is to describe the development of complementary analysis methods that will allow a better understanding of the molecular mechanisms involved in the pathogenesis of rare congenital diseases. Methods: Paraffin-embedded human pediatric and fetal lung samples were laser microdissected to enrich different lung regions, namely, bronchioli or alveoli. These samples were analyzed by data-independent acquisition-based quantitative proteomics, and the lung structures were subsequently compared. To confirm the proteomic data, we employed an optimized Sequential ImmunoPeroxidase Labeling and Erasing (SIMPLE) staining for specific proteins of interest. Results: By quantitative proteomics, we identified typical pulmonary proteins from being differentially expressed in different regions. While the receptor for advanced glycation end products (RAGE) and the surfactant protein C (SFTPC) were downregulated, tubulin beta 4B (TUBB4B) was upregulated in bronchioli, compared to alveoli. In fetal tissues, CD31 was downregulated in fetal bronchioli compared to canaliculi. Moreover, we confirmed their presence using SIMPLE staining. Some expected proteins did not show up in the proteomic data, such as SOX-9, which was only detected by means of immunohistochemistry in the SIMPLE analysis. Conclusion: Our data underline the robustness and applicability of this type of experimental approach, especially for rare paraffin-embedded tissue samples. It also strengthens the importance of these methods for future studies, particularly when considering developmental lung diseases, such as congenital lung anomalies.

DeepBreath-automated detection of respiratory pathology from lung auscultation in 572 pediatric outpatients across 5 countries.

The interpretation of lung auscultation is highly subjective and relies on non-specific nomenclature. Computer-aided analysis has the potential to better standardize and automate evaluation. We used 35.9 hours of auscultation audio from 572 pediatric outpatients to develop DeepBreath : a deep learning model identifying the audible signatures of acute respiratory illness in children. It comprises a convolutional neural network followed by a logistic regression classifier, aggregating estimates on recordings from eight thoracic sites into a single prediction at the patient-level. Patients were either healthy controls (29%) or had one of three acute respiratory illnesses (71%) including pneumonia, wheezing disorders (bronchitis/asthma), and bronchiolitis). To ensure objective estimates on model generalisability, DeepBreath is trained on patients from two countries (Switzerland, Brazil), and results are reported on an internal 5-fold cross-validation as well as externally validated (extval) on three other countries (Senegal, Cameroon, Morocco). DeepBreath differentiated healthy and pathological breathing with an Area Under the Receiver-Operator Characteristic (AUROC) of 0.93 (standard deviation [SD] ± 0.01 on internal validation). Similarly promising results were obtained for pneumonia (AUROC 0.75 ± 0.10), wheezing disorders (AUROC 0.91 ± 0.03), and bronchiolitis (AUROC 0.94 ± 0.02). Extval AUROCs were 0.89, 0.74, 0.74 and 0.87 respectively. All either matched or were significant improvements on a clinical baseline model using age and respiratory rate. Temporal attention showed clear alignment between model prediction and independently annotated respiratory cycles, providing evidence that DeepBreath extracts physiologically meaningful representations. DeepBreath provides a framework for interpretable deep learning to identify the objective audio signatures of respiratory pathology.

Di-Tyrosine Crosslinking and NOX4 Expression as Oxidative Pathological Markers in the Lungs of Patients with Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a noninflammatory progressive lung disease. Oxidative damage is a hallmark of IPF, but the sources and consequences of oxidant generation in the lungs are unclear. In this study, we addressed the link between the H2O2-generating enzyme NADPH oxidase 4 (NOX4) and di-tyrosine (DT), an oxidative post-translational modification in IPF lungs. We performed immunohistochemical staining for DT and NOX4 in pulmonary tissue from patients with IPF and controls using validated antibodies. In the healthy lung, DT showed little or no staining and NOX4 was mostly present in normal vascular endothelium. On the other hand, both markers were detected in several cell types in the IPF patients, including vascular smooth muscle cells and epithelium (bronchial cells and epithelial cells type II). The link between NOX4 and DT was addressed in human fibroblasts deficient for NOX4 activity (mutation in the CYBA gene). Induction of NOX4 by Transforming growth factor beta 1 (TGFß1) in fibroblasts led to moderate DT staining after the addition of a heme-containing peroxidase in control cells but not in the fibroblasts deficient for NOX4 activity. Our data indicate that DT is a histological marker of IPF and that NOX4 can generate a sufficient amount of H2O2 for DT formation in vitro.

Cardiopulmonary function in adolescent patients with pectus excavatum or carinatum.

BACKGROUND: Pectus excavatum (PE) and pectus carinatum (PC) have generally been considered an aesthetic issue, although there is growing evidence of associated cardiopulmonary function (CPF) impairment, especially in PE patients. The study goal was to determine any correlation between pectus malformations and cardiopulmonary symptoms and function based on systematic assessment of CPF and thoracic measurements, such as Haller Index (HI) and sternal torsion angle (STA). METHODS: Data from 76 adolescent patients with PE (n=30) or PC (n=46) were retrospectively collected referred between January 2015 and April 2018. CPF measurements and thoracic imaging were performed in all patients. HI and STA correction indexes were measured in all patients. FINDINGS: Medical records from 76 patients (PE n=30; PC n=46) were analysed. Patients were predominantly male (>93.3%), and aged between 13 and 14½ old. PE was associated with airway obstruction, with a forced expiratory volume in 1 s value under the lower limit of normal in 13% of cases (p<0.001). Restrictive syndrome was observed in 23% of cases (p<0.001), with a Z score for total lung capacity under the lower limit of normal. In PC, pulmonary function was not affected. All patients showed slightly decreased values of left and right ejection fraction and cardiac index at rest, although values were within normal range. There were no significant correlations between pulmonary and cardiac functions or between low CPF and thoracic measurements. INTERPRETATION: Our results confirm the modest impact of pectus malformations on CPF at rest, without correlation with anamnestic dyspnoea on exertion, nor with chest pain or anatomical measurements. Validation of new correction indexes could be helping characterise these malformations and choose optimal therapeutic management.

Successful home respiratory polygraphy to investigate sleep-disordered breathing in children.

OBJECTIVE: Sleep-disordered breathing (SDB) in children is common. Interest in sleep tests, such as polygraphy (PG), which can be performed in a non-attended setting, are gaining is increasing. PG has, however, been little studied in children with co-morbidities other than obstructive sleep apnea (OSA), and in particular, if performed in a non-attended setting. We report on the feasibility and interpretability of implementing PGs at home versus in hospital. METHODS: PGs were analyzed according to the setting (hospital or home) and sequence (initial or subsequent) in which they were performed. Non-interpretability was defined as absent or unreliable oxygen saturation by pulse oximetry (SpO2), or airflow and respiratory inductance plethysmography flow trace signals during the time analyzed. RESULTS: We retrospectively analyzed 400 PGs; 332/400 were initial PGs. Indications were: suspected OSA (65%), obesity (13%), craniofacial malformations (5%), neuromuscular disease (4%), and other (13%) which included prematurity. 16% were recorded in hospitals and 84% at home. The mean age was 5.7 ± 5.8 years and 7.3 ± 4.5 years for the hospital and home groups, respectively. Interpretability was similar in both settings (87%). In the 68 subsequent PGs, interpretability was 84% when performed for follow-up and 96% when repeated for non-interpretability. Non-interpretability was predominantly due to a failure of the SpO2 channel. CONCLUSIONS: PG performed at home is both feasible and interpretable for a variety of indications. Non-interpretability was not predictable in association with the setting, anthropometric data, or indication, independently of the sequence (initial or subsequent PG) in which the parameters were analyzed.

A Swiss database and biobank to better understand and manage congenital lung anomalies.

Congenital lung anomalies are a group of rare malformations, often diagnosed during the prenatal period. Guidelines on how to manage these patients are currently under debate, especially with regard to prophylactic surgery in asymptomatic patients, or how to proceed with conservative follow-up. Currently, there is no clear consensus on management strategies. A Swiss congenital lung anomaly national database and biobank was created in 2016 to enable data recording and collection of surgical lung samples in order to help define the most appropriate management strategies. This national observational cohort study represents an important step towards a better understanding of the pathophysiology and clinical course of the diseases included under congenital lung anomalies, especially in the context of a small country like Switzerland.

An unusual radiologic manifestation of hypersensitivity pneumonia.

Hypersensitivity pneumonia is clinically suspected and can be characterized on computed tomography by its pattern of diffuse lung disease, in children, as in adults. However, identifying the diagnosis is not always as simple. We report an organizing pneumonia pattern of hypersensitivity pneumonia that can be seen in adult patients, but has not been reported in the pediatric population.

The role of endothelin-1 in hyperoxia-induced lung injury in mice.

BACKGROUND: As prolonged hyperoxia induces extensive lung tissue damage, we set out to investigate the involvement of endothelin-1 (ET-1) receptors in these adverse changes. METHODS: Experiments were performed on four groups of mice: control animals kept in room air and a group of mice exposed to hyperoxia for 60 h were not subjected to ET-1 receptor blockade, whereas the dual ETA/ETB-receptor blocker tezosantan (TEZ) was administered via an intraperitoneal pump (10 mg/kg/day for 6 days) to other groups of normal and hyperoxic mice. The respiratory system impedance (Zrs) was measured by means of forced oscillations in the anesthetized, paralyzed and mechanically ventilated mice before and after the iv injection of ET-1 (2 microg). Changes in the airway resistance (Raw) and in the tissue damping (G) and elastance (H) of a constant-phase tissue compartment were identified from Zrs by model fitting. RESULTS: The plasma ET-1 level increased in the mice exposed to hyperoxia (3.3 +/- 1.6 pg/ml) relative to those exposed to room air (1.6 +/- 0.3 pg/ml, p < 0.05). TEZ administration prevented the hyperoxia-induced increases in G (13.1 +/- 1.7 vs. 9.6 +/- 0.3 cmH2O/l, p < 0.05) and H (59 +/- 9 vs. 41 +/- 5 cmH2O/l, p < 0.05) and inhibited the lung responses to ET-1. Hyperoxia decreased the reactivity of the airways to ET-1, whereas it elevated the reactivity of the tissues. CONCLUSION: These findings substantiate the involvement of the ET-1 receptors in the physiopathogenesis of hyperoxia-induced lung damage. Dual ET-1 receptor antagonism may well be of value in the prevention of hyperoxia-induced parenchymal damage.

Presence of tracheal bronchus in children undergoing flexible bronchoscopy.

BACKGROUND AND OBJECTIVES: Tracheal bronchus (TB) is a rare congenital malformation of the lung tree with a bronchus originating from the trachea. Only a small number of publications have analyzed the frequency and diagnostic procedure of TB in children, based on a restricted sample of patients. In the present study, we analyze and discuss new aspects of prevalence, clinical presentation and associated malformations of TB based on a large pediatric cohort. METHODS: Data from 5970 children having a flexible bronchoscopy for investigation of respiratory symptoms were selected. We analyzed the anaesthesic management, the presence of associated malformations, and all tracheobronchial anomalies observed during the endoscopic procedure. RESULTS: Fifty-seven cases of tracheal bronchus were identified (0.9%). In the majority of them, tracheal bronchus was a fortuitous discovery without clear clinical relevance. Statistical analysis revealed that the majority of TB originated from the middle and lower one third of the trachea (56%). 61.5% of patients had associated anomalies such as syndromic association (21%), cardiac malformations (19.2%) or tracheal stenosis (14%). Only 38.5% of children had no associated anomalies. CONCLUSIONS: Tracheal bronchus is a rare morphological anomaly of the tracheobronchial tree. Most often TB is associated with other birth defects such as another tracheo-bronchial tree malformation, vascular abnormality, congenital heart malformation or in the context of a syndromic pattern. A relationship between respiratory symptoms and the presence of TB is very rare and selective treatment is infrequent.

Pulmonary hypoplasia associated with congenital heart diseases: a fetal study.

BACKGROUND: Abnormalities of the fetal pulmonary vasculature may affect lung morphogenesis. Postnatal studies have suggested that pulmonary hypoplasia (PH) may be associated with congenital heart diseases (CHDs). OBJECTIVE: To determine the prevalence of PH associated with CHDs, and to evaluate whether CHDs with right outflow obstruction were associated with the highest risk of lung growth impairment. METHODS: Between January 2006 and December 2010, fetuses with CHD obtained following the termination of pregnancies due to fetal abnormalities were examined in a prospective manner for the detection of heart and lung defects. CHDs were classified into five pathophysiological groups. Lung weight (LW), body weight (BW), and LW/BW ratio were analyzed for each case. The expression of CD31 and VEGF in the lung was evaluated by immunohistochemistry. RESULTS: Fetuses with CHDs and right outflow obstruction had significantly lower LW for a given BW, and significantly lower LW/BW ratios for a given gestational age. When defining PH as a fetal LW/BW ratio <0.015 before 28 weeks, and <0.012 after 28 weeks, PH was detected in 15 of the 119 fetuses analyzed (13%). It was significantly associated with CHD with right outflow obstruction, independently of chromosomal abnormalities and associated extracardiac abnormalities (p<0.03). Right outflow obstruction was detected in 60% of the fetuses with CHD and PH, but in only 32% of those with CHD but no PH. In fetuses with right outflow obstruction, no difference was observed between those with PH and those without PH, in terms of the ratio of pulmonary artery diameter to aortic diameter, lung CD31 expression, or lung VEGF expression. CONCLUSION: CHDs with right outflow obstruction are a significant risk factor for prenatally acquired PH. The occurrence of fetal PH is not correlated with abnormalities of the pulmonary vasculature, suggesting the involvement of perfusion-independent mechanisms.