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(1) Background: Stereological estimations significantly contributed to our understanding of lung anatomy and physiology. Taking stereology fully 3-dimensional facilitates the estimation of novel parameters. (2) Methods: We developed a protocol for the analysis of all airspaces of an entire lung. It includes (i) high-resolution synchrotron radiation-based X-ray tomographic microscopy, (ii) image segmentation using the free machine-learning tool Ilastik and ImageJ, and (iii) calculation of the airspace diameter distribution using a diameter map function. To evaluate the new pipeline, lungs from adult mice with cystic fibrosis (CF)-like lung disease (ßENaC-transgenic mice) or mice with elastase-induced emphysema were compared to healthy controls. (3) Results: We were able to show the distribution of airspace diameters throughout the entire lung, as well as separately for the conducting airways and the gas exchange area. In the pathobiological context, we observed an irregular widening of parenchymal airspaces in mice with CF-like lung disease and elastase-induced emphysema. Comparable results were obtained when analyzing lungs imaged with µCT, sugges-ting that our pipeline is applicable to different kinds of imaging modalities. (4) Conclusions: We conclude that the airspace diameter map is well suited for a detailed analysis of unevenly distri-buted structural alterations in chronic muco-obstructive lung diseases such as cystic fibrosis and COPD.
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Fibrose Cística , Enfisema , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Camundongos , Animais , Fibrose Cística/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Enfisema Pulmonar/diagnóstico por imagem , Elastase PancreáticaRESUMO
BACKGROUND: Interstitial lung diseases (ILD), such as idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP), and chronic obstructive pulmonary disease (COPD) are severe, progressive pulmonary disorders with a poor prognosis. Prompt and accurate diagnosis is important to enable patients to receive appropriate care at the earliest possible stage to delay disease progression and prolong survival. Artificial intelligence-assisted lung auscultation and ultrasound (LUS) could constitute an alternative to conventional, subjective, operator-related methods for the accurate and earlier diagnosis of these diseases. This protocol describes the standardised collection of digitally-acquired lung sounds and LUS images of adult outpatients with IPF, NSIP or COPD and a deep learning diagnostic and severity-stratification approach. METHODS: A total of 120 consecutive patients (≥ 18 years) meeting international criteria for IPF, NSIP or COPD and 40 age-matched controls will be recruited in a Swiss pulmonology outpatient clinic, starting from August 2022. At inclusion, demographic and clinical data will be collected. Lung auscultation will be recorded with a digital stethoscope at 10 thoracic sites in each patient and LUS images using a standard point-of-care device will be acquired at the same sites. A deep learning algorithm (DeepBreath) using convolutional neural networks, long short-term memory models, and transformer architectures will be trained on these audio recordings and LUS images to derive an automated diagnostic tool. The primary outcome is the diagnosis of ILD versus control subjects or COPD. Secondary outcomes are the clinical, functional and radiological characteristics of IPF, NSIP and COPD diagnosis. Quality of life will be measured with dedicated questionnaires. Based on previous work to distinguish normal and pathological lung sounds, we estimate to achieve convergence with an area under the receiver operating characteristic curve of > 80% using 40 patients in each category, yielding a sample size calculation of 80 ILD (40 IPF, 40 NSIP), 40 COPD, and 40 controls. DISCUSSION: This approach has a broad potential to better guide care management by exploring the synergistic value of several point-of-care-tests for the automated detection and differential diagnosis of ILD and COPD and to estimate severity. Trial registration Registration: August 8, 2022. CLINICALTRIALS: gov Identifier: NCT05318599.
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Aprendizado Profundo , Pneumonias Intersticiais Idiopáticas , Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Doença Pulmonar Obstrutiva Crônica , Adulto , Humanos , Inteligência Artificial , Qualidade de Vida , Sons Respiratórios , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/patologia , Pulmão , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Pneumonias Intersticiais Idiopáticas/diagnóstico , Estudos de Casos e Controles , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/complicações , Ultrassonografia , Auscultação , Protocolos Clínicos , Estudos Observacionais como AssuntoRESUMO
The latest guideline from the American Academy of Pediatrics for the management of bronchiolitis has helped reduce unnecessary interventions and costs. However, data on patients still receiving interventions are missing. In patients with acute bronchiolitis whose management was assessed and compared with current achievable benchmarks of care, we aimed to identify factors associated with nonadherence to guideline recommendations. In this single-centre retrospective study the management of bronchiolitis pre-guideline (Period 1: 2010 to 2012) was compared with two periods post-guideline (Period 2: 2015 to 2016, early post-guideline; and Period 3: 2017 to 2018, late post-guideline) in otherwise healthy infants aged less than 1 year presenting at the Children's University Hospitals of Geneva (Switzerland). Post-guideline, bronchodilators were more frequently administered to older (>6 months; OR 25.8, 95%CI 12.6-52.6), and atopic (OR 3.5, 95%CI 1.5-7.5) children with wheezing (OR 5.4, 95%CI 3.3-8.7). Oral corticosteroids were prescribed more frequently to older (>6 months; OR 5.2, 95%CI 1.4-18.7) infants with wheezing (OR 4.9, 95% CI 1.3-17.8). Antibiotics and chest X-ray were more frequently prescribed to children admitted to the intensive care unit (antibiotics: OR 4.2, 95%CI 1.3-13.5; chest X-ray: OR 19.4, 95%CI 7.4-50.6). Latest prescription rates were all below the achievable benchmarks of care. In summary, following the latest American Academy of Pediatrics guideline, older, atopic children with wheezing and infants admitted to the intensive care unit were more likely to receive nonevidence-based interventions during an episode of bronchiolitis. These patient profiles are generally excluded from bronchiolitis trials, and therefore not specifically covered by the current guideline. Further research should focus on the benefit of bronchiolitis interventions in these particular populations.
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Bronquiolite , Sons Respiratórios , Lactente , Humanos , Criança , Estados Unidos , Estudos Retrospectivos , Fidelidade a Diretrizes , Bronquiolite/tratamento farmacológico , Antibacterianos/uso terapêutico , Broncodilatadores/uso terapêuticoRESUMO
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.
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Regulação da Expressão Gênica , Antígenos de Histocompatibilidade Classe I/genética , Expectativa de Vida , Nicotina/efeitos adversos , Enfisema Pulmonar/genética , RNA/genética , Animais , Líquido da Lavagem Broncoalveolar/citologia , Células Cultivadas , Modelos Animais de Doenças , Antígenos H-2 , Antígenos de Histocompatibilidade Classe I/biossíntese , Camundongos , Camundongos Endogâmicos C57BL , Elastase Pancreática/toxicidade , Enfisema Pulmonar/induzido quimicamente , Enfisema Pulmonar/metabolismoRESUMO
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.
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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.
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Tórax em Funil , Parede Torácica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Volume Expiratório Forçado , Tórax em Funil/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Esterno/diagnóstico por imagem , Parede Torácica/diagnóstico por imagem , Adulto JovemRESUMO
BACKGROUND: Lung auscultation is fundamental to the clinical diagnosis of respiratory disease. However, auscultation is a subjective practice and interpretations vary widely between users. The digitization of auscultation acquisition and interpretation is a particularly promising strategy for diagnosing and monitoring infectious diseases such as Coronavirus-19 disease (COVID-19) where automated analyses could help decentralise care and better inform decision-making in telemedicine. This protocol describes the standardised collection of lung auscultations in COVID-19 triage sites and a deep learning approach to diagnostic and prognostic modelling for future incorporation into an intelligent autonomous stethoscope benchmarked against human expert interpretation. METHODS: A total of 1000 consecutive, patients aged ≥ 16 years and meeting COVID-19 testing criteria will be recruited at screening sites and amongst inpatients of the internal medicine department at the Geneva University Hospitals, starting from October 2020. COVID-19 is diagnosed by RT-PCR on a nasopharyngeal swab and COVID-positive patients are followed up until outcome (i.e., discharge, hospitalisation, intubation and/or death). At inclusion, demographic and clinical data are collected, such as age, sex, medical history, and signs and symptoms of the current episode. Additionally, lung auscultation will be recorded with a digital stethoscope at 6 thoracic sites in each patient. A deep learning algorithm (DeepBreath) using a Convolutional Neural Network (CNN) and Support Vector Machine classifier will be trained on these audio recordings to derive an automated prediction of diagnostic (COVID positive vs negative) and risk stratification categories (mild to severe). The performance of this model will be compared to a human prediction baseline on a random subset of lung sounds, where blinded physicians are asked to classify the audios into the same categories. DISCUSSION: This approach has broad potential to standardise the evaluation of lung auscultation in COVID-19 at various levels of healthcare, especially in the context of decentralised triage and monitoring. TRIAL REGISTRATION: PB_2016-00500, SwissEthics. Registered on 6 April 2020.
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Auscultação/métodos , Teste para COVID-19/métodos , COVID-19/diagnóstico , Aprendizado Profundo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Estudos de Casos e Controles , Regras de Decisão Clínica , Protocolos Clínicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Medição de Risco , Triagem , Adulto JovemRESUMO
OBJECTIVES: The prevalence of obstructive sleep apnea syndrome (OSAS) in children referred for sleep-disordered breathing reaches up to 59%. We aimed to test the adequacy of a questionnaire compared to home respiratory polygraphy (HRP), in 45 subjects (5-16 years-old), without maxillofacial malformations nor other comorbidities, presenting with symptoms compatible with OSAS. METHODS: All children passed a 12-items questionnaire (Obstructive Airway Child test: OACT) and the HRP. OSAS was classified in severity according to the apnea-hypopnea index (AHI). RESULTS: With HRP, 60% and 15% children were detected to have at least mild (AHI ≥1) and moderate (AHI >5) OSAS, respectively. The sensitivity of the questionnaire to detect mild and moderate OSAS was good (93% and 71%, respectively) but the specificity was very low (11% and 34%). However, an OACT score under 61 showed a very good negative predictive value for moderate and severe OSAS (87%). With the questionnaire, we could have avoided a complementary PSG or HRP in 25/45 (56%) of our subjects as in children with mild OSAS and without comorbidities only clinical observation is usually advised. CONCLUSIONS: The OACT questionnaire has shown to be a good and quick instrument to exclude moderate and severe OSAS in our population of children without maxillofacial malformations. Indeed children scoring under 61 could avoid a constraining and expensive sleep exam. However, if the score is above this cut-off, the performance to recognize OSAS is low and the child's evaluation must be completed by a HRP or PSG.
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Apneia Obstrutiva do Sono , Adolescente , Criança , Pré-Escolar , Humanos , Polissonografia , Sono , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Inquéritos e QuestionáriosRESUMO
Importance: Little is known about the natural course of oxygen desaturation in acute bronchiolitis. Information on risk factors associated with desaturation as well as the time to desaturation in infants with bronchiolitis could help physicians better treat these infants before deciding whether to hospitalize them. Objective: To prospectively determine the frequency of desaturation in infants with bronchiolitis, along with the time to desaturation and risk factors associated with desaturation, and to compare infants who were hospitalized with those discharged home and evaluate risk factors for rehospitalization. Design, Setting, and Participants: This cohort study was conducted during the 2017 to 2018 and 2018 to 2019 respiratory syncytial virus seasons in a tertiary care pediatric emergency department in Switzerland. Included individuals were 239 otherwise-healthy infants aged younger than 1 year, diagnosed with acute bronchiolitis and oxygen saturation of 90% or more on arrival. Data were analyzed from July 2019 to October 2020. Exposures: After receiving triage care, study participants admitted to the emergency department were equipped with a pulse oximeter to continuously record oxygen saturation (Spo2 levels), regardless of subsequent hospitalization or discharge home. Main Outcomes and Measures: The primary outcome was desaturation (ie, Spo2 < 90%) during the first 36 hours. Results: Of 239 infants enrolled, with a median (interquartile range [IQR]) age of 3.9 (1.5-6.5) months, 116 (48.5%) were boys and desaturation occurred in 165 infants (69.0%). Median (IQR) time to desaturation was 3.6 (1.8-9.4) hours. The rate of desaturation was similar between infants hospitalized and those discharged home (137 of 200 infants [68.5%] vs 28 of 39 infants [71.8%]; difference, -3.3%; 95% CI, -18.8% to 12.2%; P = .85). A more severe initial clinical presentation with moderate or severe retractions was the only independent risk factor associated with desaturation (odds ratio, 2.73; 95% CI, 1.49 to 5.02; P = .001). Of 39 infants discharged home, 22 infants (56.4%) experienced major desaturations. However, infants with desaturations, including those with major desaturations, had rates of rehospitalization similar to those of infants without desaturations (8 of 28 infants [28.5%] vs 3 of 11 infants [27.3%]; difference, 1.2%; 95% CI, -29.9% to 32.5; P > .99). Conclusions and Relevance: These findings suggest that rates of desaturation in infants with acute bronchiolitis were high and similar between infants who were hospitalized and those discharged home. A more severe initial clinical presentation was the only risk factor associated with desaturation. However, for infants discharged home, desaturation was not a risk factor associated with rehospitalization.
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Bronquiolite/fisiopatologia , Oximetria/estatística & dados numéricos , Consumo de Oxigênio/fisiologia , Alta do Paciente/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Doença Aguda , Serviço Hospitalar de Emergência , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Fatores de Risco , Suíça , Fatores de TempoRESUMO
This short report describes respiratory indices of polygraphies (PG) performed to investigate several sleep-related disorders of breathing in children. It refers to the work of Michelet et al., Successful home respiratory polygraphy to investigate sleep-disordered breathing in children, Sleep Medicine [1]. Indications for PGs were grouped according to 6 categories: craniofacial malformation, neuromuscular disease, obesity, suspected obstructive sleep apnea (OSA), prematurity, and other. The reported data concern the initial interpretable PGs (Nâ¯=â¯289); initial was defined as performed for the first time in any subject. Non-interpretability was defined as absent or unreliable oxygen saturation by pulse oximetry (SpO2), and/or airflow and respiratory inductance plethysmography (RIP) flow trace signals during time analyzed. Analyzed time is reported. In a subset of patients, transcutaneous carbon dioxide partial pressure (ptcCO2) was also measured. Data may be re-used for comparison in future validating research for PGs in children [2].
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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.
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Células Epiteliais Alveolares/citologia , Células Endoteliais/citologia , Células Epiteliais/citologia , Pulmão/citologia , Alvéolos Pulmonares/citologia , Animais , Diferenciação Celular/fisiologia , Separação Celular/métodos , Células Cultivadas , Camundongos , Camundongos Endogâmicos C57BL , Organogênese/fisiologiaRESUMO
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.
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Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Criança , Pré-Escolar , Humanos , Oximetria , Polissonografia , Estudos Retrospectivos , Síndromes da Apneia do Sono/diagnóstico , Apneia Obstrutiva do Sono/diagnósticoRESUMO
In Switzerland, about 13â â % of pregnant women smoke, giving birth to more than 11'000 infants per year exposed to tobacco in utero. Although this proportion is stable since the 2000's, the users of nicotine with new devices (electronic cigarettes, inhaled heated tobacco, sniffed or chewed tobacco) are increasing. The literature is unanimous about deleterious effects of prenatal exposure to tobacco smoke on the fetus, with multiple short- and long-term consequences. Available data suggest that in utero exposure to e-cigarette could also expose the fetus to a similar profile of adverse effects. In this article, we review briefly the known epidemiological and mechanistic data on the short- and long-term effects of prenatal cigarette smoke and nicotine consumption.
En Suisse, environ 13â % des femmes enceintes fument, donnant naissance à plus de 11â 000 nourrissons par an exposés au tabac in utero. Si cette proportion est stable depuis les années 2000, celle des nouveaux modes de consommation du tabac et de la nicotine (cigarette électronique, inhalation de tabac chauffé, tabac à priser ou à sucer) est en augmentation. La littérature est unanime sur les effets délétères de l'exposition anténatale au tabac sur le fÅtus, avec de multiples conséquences à court et à long terme. Les études disponibles à ce jour suggèrent que l'exposition in utero à l'e-cigarette expose à un profil similaire d'effets secondaires indésirables. Dans cet article, nous revoyons brièvement les données épidémiologiques et mécanistiques connues des effets à court et à long terme de la fumée de tabac et de la nicotine en anténatal.
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Sistemas Eletrônicos de Liberação de Nicotina , Exposição Materna/efeitos adversos , Nicotina/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Fumar/efeitos adversos , Produtos do Tabaco/efeitos adversos , Feminino , Humanos , Gravidez , SuíçaRESUMO
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.
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Lactação/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Exposição Materna/efeitos adversos , Nicotina/efeitos adversos , Gravidez/efeitos dos fármacos , Alvéolos Pulmonares/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Ciclo Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
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.
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Bases de Dados Factuais , Pneumopatias/congênito , Pneumopatias/fisiopatologia , Diagnóstico Pré-Natal , Adolescente , Bancos de Espécimes Biológicos , Criança , Pré-Escolar , Estudos de Coortes , Humanos , Lactente , Recém-Nascido , Pneumopatias/terapia , Doenças Raras , SuíçaRESUMO
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.
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INTRODUCTION: Rigid bronchoscopy was traditionally performed in the management of foreign-body aspiration (FBA). More recently, since development of a less invasive method, flexible bronchoscopy has been proposed in some centers for the management of FBA. For the past few years, we have applied a decisional algorithm, privileging flexible bronchoscopy for diagnosis and, in some cases, for extraction of foreign body (FB). Our aims are first to analyze our current management of FBA and second to examine the bronchoscopic findings and complications. MATERIALS AND METHODS: Retrospective medical chart review of all patients with clinical suspicion of FBA who underwent bronchoscopy (flexible and/or rigid) from 2009 through 2014. RESULTS: An FB was found in 23 (33%) of the 70 patients included in the study (45 boys, 25 girls; median age: 21.5 months). Diagnosis of FBA was made on first intention in 22/23 (96%) and extraction was performed in 7/23 (30%) by flexible bronchoscopy. Rigid bronchoscopy was necessary for the extraction of the 16/23 (70%) remaining FBs. The rigid procedure was performed as first intention in only two (3%) patients, and one of the two was negative. Among the clinical signs of FBA, none were > 90% specific except for apnea (100%), but which was poorly sensitive (22%). Seven clinical and radiologic signs were found to be significantly different between FB+ and FB- groups: sudden choking, cyanosis, apnea, decreased breath sounds, atelectasis, mediastinal shift, and air trapping. Conversely, when none of these symptoms or signs and no clear history of sudden choking were present (in 15/70 patients), no FB was found. No life-threatening complications or death were observed. CONCLUSION: Our current management of FBA allows us to avoid almost all negative rigid bronchoscopies. In addition, we identified some symptoms and clinical and radiologic signs whose absence was highly predictive of negative bronchoscopy. We propose a novel algorithm for management of FBA that will help decrease the number of negative bronchoscopies.
Assuntos
Algoritmos , Broncoscopia/métodos , Tomada de Decisão Clínica/métodos , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/terapia , Aspiração Respiratória/diagnóstico por imagem , Aspiração Respiratória/terapia , Pré-Escolar , Serviço Hospitalar de Emergência , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosAssuntos
Pediatria , Especialidades Cirúrgicas , Criança , Humanos , Equipe de Assistência ao PacienteRESUMO
Idiopathic pulmonary fibrosis (IPF) is a severe progressive and irreversible lung disease. Novel antifibrotic drugs that slow disease progression are now available. However, many issues regarding patient management remain unanswered, such as the choice between available drugs, their use in particular subgroups and clinical situations, time of treatment onset, termination, combination or switch, or nonpharmacologic management. To guide Swiss respiratory physicians in this evolving field still characterized by numerous areas of uncertainty, the Swiss Working Group for interstitial and rare lung diseases of the Swiss Respiratory Society provides a position paper on the diagnosis and treatment of IPF.