Alice Hadchouel

Hôpital Universitaire Necker, Lutetia Parisorum, Île-de-France, France

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Publications (19)52.07 Total impact

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    ABSTRACT: Pulmonary alveolar proteinosis (PAP) is very rare in children. Only a few small series have been published, with little information about long-term progression. The objective of our study was to describe the clinical, radiological and pathological features, and the long-term course of PAP in a cohort of 34 children from La Reunion Island.
    Orphanet Journal of Rare Diseases 06/2014; 9(1):85. · 4.32 Impact Factor
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    ABSTRACT: Congenital pulmonary malformations (CPM) are mostly recognized on prenatal ultrasound scans. In a minority of cases, they may impair breathing at birth. The factors predictive of neonatal respiratory distress are not well defined, but an understanding of these factors is essential for decisions concerning the need for the delivery to take place in a tertiary care center. The aim of this study was to identify potential predictors of respiratory distress in neonates with CPM. We selected cases of prenatal diagnosis of hyperechoic and/or cystic lung lesions from RespiRare, the French prospective multicenter registry for liveborn children with rare respiratory diseases (2008-2013). Prenatal parameters were correlated with neonatal respiratory outcome. Data were analyzed for 89 children, 22 (25%) of whom had abnormal breathing at birth. Severe respiratory distress, requiring oxygen supplementation or ventilatory support, was observed in 12 neonates (13%). Respiratory distress at birth was significantly associated with the following prenatal parameters: mediastinal shift (P = .0003), polyhydramnios (P = .05), ascites (P = .0005), maximum prenatal malformation area (P = .001), and maximum congenital pulmonary malformation volume ratio (CVR) (P = .001). Severe respiratory distress, requiring oxygen at birth, was best predicted by polyhydramnios, ascites, or a CVR >0.84. CVR >0.84, polyhydramnios, and ascites increased the risk of respiratory complications at birth in fetuses with CPM, and especially of severe respiratory distress, requiring oxygen supplementation or more intensive intervention. In such situations, the delivery should take place in a tertiary care center.
    PEDIATRICS 04/2014; · 4.47 Impact Factor
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    ABSTRACT: Bronchopulmonary dysplasia (BPD) is the main respiratory sequela of extreme prematurity. Its pathophysiology is complex, involving interactions between host and environment, likely to be significantly influenced by genetic factors. Thus, the clinical presentation and histological lesions have evolved over time, along with the reduction in neonatal injuries, and the care of more immature children. Impaired alveolar growth, however, is a lesion consistently observed in BPD, such that it is a key feature in BPD, and is even the dominant characteristic of the so-called "new" forms of BPD. This review describes the key molecular pathways that are believed to be involved in the genesis of BPD. Much of our understanding is based on animal models, but this is increasingly being enriched by genetic approaches, and long-term respiratory functional studies. Birth Defects Research, 2014. © 2014 Wiley Periodicals, Inc.
    Birth Defects Research Part A Clinical and Molecular Teratology 03/2014; · 2.27 Impact Factor
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    ABSTRACT: Idiopathic eosinophilic pneumonia is extremely rare in children and adults. We present herein the first series describing the specificities of idiopathic chronic (ICEP) and acute (IAEP) eosinophilic pneumonia in children. We retrospectively analyzed all cases of ICEP and IAEP in children that were retrieved from French Reference Centers for rare pediatric lung diseases. Five cases of pediatric ICEP were identified. Corticosteroid or immunosuppressive therapy dramatically improved the outcome in three cases. The remaining two cases had a persistent interstitial pattern with progressive development of cystic airspace lesions. Three cases of IAEP in adolescents were reported, with one requiring four days of extracorporeal membrane oxygenation. ICEP is a rare disease with a polymorphic clinical presentation in children. We identified patients with persistent interstitial patterns progressing to cystic airspace regions, for which the boundaries with idiopathic interstitial pneumonias are difficult to establish. We therefore propose a specific pediatric definition and classification algorithm. IAEP in children remains an inflammatory reaction of the lung to an acute toxic exposure, mainly tobacco, as in adults. International studies are required to comprehensively assess the various clinical forms of the disease as well as the appropriate therapeutic regimens.
    Orphanet Journal of Rare Diseases 02/2014; 9(1):28. · 4.32 Impact Factor
  • Alice Hadchouel, Christophe Delacourt
    Medecine sciences: M/S 10/2013; 29(10):821-3. · 0.56 Impact Factor
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    ABSTRACT: Type I pleuropulmonary blastoma (PPB) and congenital cystic adenomatoid malformation of the lung (CCAM) are cystic lung diseases of childhood. Their clinical and radiological presentations are often similar, and pathologic discrimination remains difficult in many cases. As a consequence, type I PPB and CCAM are frequently confused, leading to delayed adequate management for type I PPB. Recent studies have suggested a role for fibroblast growth factor (FGF) 10 signal pathway in CCAM pathogenesis. The objective of our study was to determine whether FGF10 signaling differs between CCAM and type I PPB. Immunohistochemical studies were performed for expression of FGF10, its receptor FGFR2b, and its inhibitor sonic hedgehog (SHH) in focal type I PPB (n=6), CCAM type I (n=7), CCAM type II (n=7), and control lungs (n=5). FGF10, FGFR2b, and SHH expressions differed markedly between type I PPB and both types of CCAM. Type I and type II CCAM cystic walls expressed FGF10, FGFR2b, and SHH, whereas staining was absent or poor in type I PBB cystic walls. Expression of FGF10, FGFR2b, and SHH did not differ between CCAM cystic walls and control airway walls. These findings show that immunohistochemistry with FGF10, FGFR2b, or SHH could be useful in differentiating CCAM from type I PPB, when a child presents with a focal cystic lung lesion. The absence of strong expression of FGF10, FGFR2b, and/or SHH makes the diagnosis of CCAM very doubtful.
    Orphanet Journal of Rare Diseases 09/2013; 8(1):130. · 4.32 Impact Factor
  • A Hadchouel, C Delacourt
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    ABSTRACT: Bronchopulmonary dysplasia (BPD) is the most common chronic respiratory disease in premature infants. BPD was first described by Northway in 1967 as a chronic respiratory condition that developed in premature infants exposed to mechanical ventilation and high oxygen supplementation. DBP is currently defined by the need for supplemental oxygen at 28 days of life (mild BPD) and at the 36weeks of post-menstrual age (moderate and severe BPD). With the advances of neonatal care, epidemiological characteristics and mechanisms of the disease as well as pathological characteristics and clinical course have profoundly changed within the last two decades, but still no effective curative treatment exists and BPD continue to occur among 10 to 20% of premature infants. Furthermore, BPD is a significant source of respiratory and neuro-cognitive morbidities. Thus, its treatment makes a considerable demand on health services. Regarding its pathophysiological mechanisms, it is now established that BPD is a complex disease combining genetic susceptibility and environmental injuries. The identification of genetic variants involved in BPD is a potential source of innovative development in terms of diagnosis and treatment. Indeed, no curative or effective prophylactic therapeutic exists and BPD treatment is currently symptomatic.
    Revue de Pneumologie Clinique 07/2013; · 0.20 Impact Factor
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    ABSTRACT: The need to systematically remove congenital cystic lung lesions is based on three main arguments. First, cystic malformations are often considered as congenital cystic adenomatoid malformations (CCAM), while other less favorable diagnoses are possible, such as pleuropulmonary blastoma. Only postsurgical pathological analysis allows diagnosis. Second, there are clinical and biological arguments for considering macrocystic lesions as likely to degenerate. The only prevention is surgical removal. Finally, there is no recommendation on how to follow these children, in the absence of removal, causing unnecessary family stress. This seems unjustified, compared to a feasibility of thoracoscopic removal in most cases.
    Paediatric Respiratory Reviews 07/2013; · 2.77 Impact Factor
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    ABSTRACT: Congenital cystic adenomatoid malformations (CCAM) of the lung are the most frequent congenital lung malformations. Their diagnosis is based on histological features. CCAM consist of bronchopulmonary cystic lesions which are classified according to the presence and cysts size. Type I CCAM are composed of large cysts (>2cm) lined by a columnar pseudostratified epithelium. Type II CCAM contain multiple small cystic lesions (<1cm) lined by a flattened cuboidal epithelium. Type III CCAM are more solid and contain immature structures resembling the pseudoglandular stage of lung development. Ultrasonography (US) allows early detection during the second trimester of pregnancy as cystic, and/or hyperechoic fetal lung lesions. Although most CCAM remain asymptomatic, CCAM can cause polyhydramnios or fetal hydrops, respiratory distress at birth, infections and pneumothoraces during infancy, and may give rise to malignancies. Serial US allow detection of complications, and planification of delivery. Complicated forms require an urgent treatment. In fetuses with a macrocystic life-threatening lesion, a thoraco-amniotic shunt can be placed. Microcystic compressive forms may respond to prenatal steroids. Post-natal symptomatic lesions require early surgery. The treatment of asymptomatic forms remains controversial. Some recommend a non-operative approach with a long-term clinical and radiological following, whereas other favour a preventive surgical excision. The origin of CCAM remains unknown. Recent advances suggest a transient and focal abnormality in lung development which may result from an airway obstruction. This article reviews the diagnosis, treatment, and pathophysiology of CCAM.
    Revue de Pneumologie Clinique 07/2013; · 0.20 Impact Factor
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    ABSTRACT: OBJECTIVE: To describe lung manifestations in MPO-ANCA associated vasculitides in children. METHODS: We retrospectively reviewed the medical records of patients with MPO-ANCA associated vasculitis, who were followed in two pediatric nephrology departments from January 2000 to December 2010. RESULTS: Twelve patients were identified with MPO-ANCA over the study period. Their median age (IQR) at diagnosis was 10.5 (6.3-12.0) years, and their median duration of follow-up was 4.8 (1.2-7.5) years. Only five of them had pulmonary involvement with diffuse alveolar hemorrhage. Lung involvement was inaugural for four of five children. One child with severe chronic respiratory disease and renal failure died after 6 years of disease progression. Pulmonary function tests were available for 10 children. They were within normal ranges in four of five patients without clinical lung manifestations, and no significant impairment was observed in children with pulmonary complications. CONCLUSIONS: Diffuse alveolar hemorrhage complicates 40% of cases of MPO-ANCA associated vasculitides in children with renal involvement. After an acute potentially severe phase, a complete recovery without significant functional impairment was observed in four of five affected children. Pediatr Pulmonol. © 2013 Wiley Periodicals, Inc.
    Pediatric Pulmonology 03/2013; · 2.38 Impact Factor
  • A. Hadchouel, C. Delacourt
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    ABSTRACT: Bronchopulmonary dysplasia (BPD) is the most common chronic respiratory disease in premature infants. BPD was first described by Northway in 1967 as a chronic respiratory condition that developed in premature infants exposed to mechanical ventilation and high oxygen supplementation. DBP is currently defined by the need for supplemental oxygen at 28 days of life (mild BPD) and at the 36 weeks of post-menstrual age (moderate and severe BPD). With the advances of neonatal care, epidemiological characteristics and mechanisms of the disease as well as pathological characteristics and clinical course have profoundly changed within the last two decades, but still no effective curative treatment exists and BPD continue to occur among 10 to 20% of premature infants. Furthermore, BPD is a significant source of respiratory and neuro-cognitive morbidities. Thus, its treatment makes a considerable demand on health services. Regarding its pathophysiological mechanisms, it is now established that BPD is a complex disease combining genetic susceptibility and environmental injuries. The identification of genetic variants involved in BPD is a potential source of innovative development in terms of diagnosis and treatment. Indeed, no curative or effective prophylactic therapeutic exists and BPD treatment is currently symptomatic.
    Revue de Pneumologie Clinique 01/2013; 69(4):207–216. · 0.20 Impact Factor
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    ABSTRACT: Congenital cystic adenomatoid malformations (CCAM) of the lung are the most frequent congenital lung malformations. Their diagnosis is based on histological features. CCAM consist of bronchopulmonary cystic lesions which are classified according to the presence and cysts size. Type I CCAM are composed of large cysts (> 2 cm) lined by a columnar pseudostratified epithelium. Type II CCAM contain multiple small cystic lesions (< 1 cm) lined by a flattened cuboidal epithelium. Type III CCAM are more solid and contain immature structures resembling the pseudoglandular stage of lung development. Ultrasonography (US) allows early detection during the second trimester of pregnancy as cystic, and/or hyperechoic fetal lung lesions. Although most CCAM remain asymptomatic, CCAM can cause polyhydramnios or fetal hydrops, respiratory distress at birth, infections and pneumothoraces during infancy, and may give rise to malignancies. Serial US allow detection of complications, and planification of delivery. Complicated forms require an urgent treatment. In fetuses with a macrocystic life-threatening lesion, a thoraco-amniotic shunt can be placed. Microcystic compressive forms may respond to prenatal steroids. Post-natal symptomatic lesions require early surgery. The treatment of asymptomatic forms remains controversial. Some recommend a non-operative approach with a long-term clinical and radiological following, whereas other favour a preventive surgical excision. The origin of CCAM remains unknown. Recent advances suggest a transient and focal abnormality in lung development which may result from an airway obstruction. This article reviews the diagnosis, treatment, and pathophysiology of CCAM.
    Revue de Pneumologie Clinique 01/2013; 69(4):190–197. · 0.20 Impact Factor
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    ABSTRACT: Intrathoracic congenital malformations may be associated with long-term pulmonary morbidity. This certainly is the case for congenital diaphragmatic hernia, esophageal atresia and cardiac and aortic arch abnormalities. These conditions have variable degrees of impaired development of both the airways and lung vasculature, with a postnatal impact on lung function and bronchial reactivity. Pulmonary complications are themselves frequently associated to non-pulmonary morbidities, including gastrointestinal and orthopaedic complications. These are best recognized in a structured multidisciplinary follow-up clinic so that they can be actively managed.
    Seminars in Fetal and Neonatal Medicine 04/2012; 17(2):105-11. · 3.51 Impact Factor
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    ABSTRACT: Bronchopulmonary dysplasia is the most common chronic respiratory disease in premature infants. Genetic factors might contribute to bronchopulmonary dysplasia susceptibility. To identify genetic variants involved in bronchopulmonary dysplasia through a genome-wide association study. We prospectively evaluated 418 premature neonates (gestational age <28 wk), of whom 22% developed bronchopulmonary dysplasia. Two discovery series were created, using a DNA pooling strategy in neonates from white and African ancestry. Polymorphisms associated with the disease were confirmed in an independent replication population. Genes were then explored by fine mapping and associations were replicated in an external Finnish population of 213 neonates. Validated genes expression patterns were studied in rat lung, after air or hyperoxia exposure. SPOCK2 gene was identified by both discovery series. The most significant polymorphism (rs1245560; P = 1.66 × 10(-7)) was confirmed by individual genotyping, and in the replication population (P = 0.002). Fine mapping confirmed the association of rs1245560 with bronchopulmonary dysplasia in both white and African populations with adjusted odds ratios of 2.96 (95% confidence interval [CI], 1.37-6.40) and 4.87 (95% CI, 1.88-12.63), respectively. In white neonates, rs1049269 was also associated with the disease (odds ratio, 3.21; 95% CI, 1.51-6.82). These associations were replicated in the Finnish population. In newborn rat lungs, SPOCK2 mRNA levels markedly increased during the alveolar stage of lung development. After rat exposure to hyperoxia, SPOCK2 expression increased relative to air-exposed controls. We identified SPOCK2 as a new possible candidate susceptibility gene for bronchopulmonary dysplasia. Its lung expression pattern points toward a potential role in alveolarization.
    American Journal of Respiratory and Critical Care Medicine 08/2011; 184(10):1164-70. · 11.04 Impact Factor
  • A Hadchouel, A Benachi, C Delacourt
    Ultrasound in Obstetrics and Gynecology 05/2011; 38(1):119; author reply 119-20. · 3.56 Impact Factor
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    ABSTRACT: A decrease in the volume of congenital pulmonary malformations (CPM) can be observed on prenatal ultrasonography, but the underlying mechanism for this phenomenon is unknown. Our objective was to identify factors associated with the prenatal reduction in size of cystic and/or hyperechoic lung lesions. This was a retrospective study of cases with a prenatal diagnosis of hyperechoic and/or cystic lung lesion. The extent of reduction in lesion size was calculated from ultrasound measurements. Clinical, ultrasound, radiological and histological data were tested for their relationship with prenatal CPM reduction. In a 4-year period, 36 patients were referred with a cystic and/or hyperechoic fetal lung lesion diagnosed at a mean gestational age of 23.4 weeks. The lesions were cystic in 16 cases (44%), hyperechoic in 12 (33%) and both in eight (22%). The malformation was no longer visible before birth (apparent disappearance) in nine cases (25%), shrank by 18-90% in 15 (42%) and did not reduce in 12 (33%). Findings on postnatal computed tomography were always abnormal. Isolated hyperechoic lesions were significantly more likely to shrink in utero. The mean reductions were 79%, 35% and 19%, for isolated hyperechoic, cystic and mixed lesions, respectively (P=0.001). Only 8% of hyperechoic lesions demonstrated no volume reduction, as compared to 50% and 42% of cystic and mixed lesions, respectively (P=0.03). Greater gestational age at birth was also associated with a decrease in the incidence of malformations (P=0.02). In cases that underwent surgery, hyperechoic lesions were linked to a variety of pathological diagnoses, whereas cystic lesions were all described histologically as congenital cystic adenomatoid malformations. Prenatal size reduction of fetal lung malformations is associated with isolated hyperechogenicity and greater gestational age at birth. This might result from the resumption of normal lung development after local disruption of lung growth.
    Ultrasound in Obstetrics and Gynecology 12/2010; 38(1):88-93. · 3.56 Impact Factor
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    ABSTRACT: Alveolarization requires coordinated extracellular matrix remodeling, a process in which matrix metalloproteinases (MMPs) play an important role. We postulated that polymorphisms in MMP genes might affect MMP function in preterm lungs and thus influence the risk of bronchopulmonary dysplasia (BPD). Two hundred and eighty-four consecutive neonates with a gestational age of <28 weeks were included in this prospective study. Forty-five neonates developed BPD. Nine single-nucleotide polymorphisms (SNPs) were sought in the MMP2, MMP14 and MMP16 genes. After adjustment for birth weight and ethnic origin, the TT genotype of MMP16 C/T (rs2664352) and the GG genotype of MMP16 A/G (rs2664349) were found to protect from BPD. These genotypes were also associated with a smaller active fraction of MMP2 and with a 3-fold-lower MMP16 protein level in tracheal aspirates collected within 3 days after birth. Further evaluation of MMP16 expression during the course of normal human and rat lung development showed relatively low expression during the canalicular and saccular stages and a clear increase in both mRNA and protein levels during the alveolar stage. In two newborn rat models of arrested alveolarization the lung MMP16 mRNA level was less than 50% of normal. MMP16 may be involved in the development of lung alveoli. MMP16 polymorphisms appear to influence not only the pulmonary expression and function of MMP16 but also the risk of BPD in premature infants.
    PLoS ONE 02/2008; 3(9):e3188. · 3.73 Impact Factor
  • A Hadchouel, F Madhi, C Delacourt
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    ABSTRACT: Despite occurring commonly in children bronchiolitis can also be the presenting feature of other disorders particularly congenital malformations and immunological diseases. We report a rare and severe cause of bronchiolitis: major histocompatibility (MHC) class II deficiency, an autosomal recessive disease. CASE REPORT: An eight month old infant was admitted with hypoxic bronchiolitis. An immunodeficiency disease was suspected based on lingering symptoms associated with poor weight gain. Microbiologic tests revealed an infection with Pneumocystis carinii and immunologic investigations allowed us to make the diagnosis of MHC class II deficiency. DISCUSSION: The lack of MHC class II expression results in a severe defect in both humoral and cellular immune responses to foreign antigens. It is characterised by recurrent bronchopulmonary infections and chronic diarrhoea. The clinical onset occurs within the first months of life. Prognosis is very poor when bone marrow transplantation cannot be performed.
    Revue des Maladies Respiratoires 12/2006; 23(5 Pt 1):467-70. · 0.50 Impact Factor
  • A. Hadchouel, F. Madhi, C. Delacourt
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    ABSTRACT: Despite occurring commonly in children bronchiolitis can also be the presenting feature of other disorders particularly congenital malformations and immunological diseases. We report a rare and severe cause of bronchiolitis: major histocompatibility (MHC) class II deficiency, an autosomal recessive disease. Case report An eight month old infant was admitted with hypoxic bronchiolitis. An immunodeficiency disease was suspected based on lingering symptoms associated with poor weight gain. Microbiologic tests revealed an infection with Pneumocystis carinii and immunologic investigations allowed us to make the diagnosis of MHC class II deficiency. Discussion The lack of MHC class II expression results in a severe defect in both humoral and cellular immune responses to foreign antigens. It is characterised by recurrent bronchopulmonary infections and chronic diarrhoea. The clinical onset occurs within the first months of life. Prognosis is very poor when bone marrow transplantation cannot be performed.
    Revue Des Maladies Respiratoires - REV MAL RESPIR. 01/2006; 23(5):467-470.

Publication Stats

44 Citations
52.07 Total Impact Points

Institutions

  • 2013
    • Hôpital Universitaire Necker
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • Université Paris-Sud 11
      Orsay, Île-de-France, France
    • Université René Descartes - Paris 5
      Lutetia Parisorum, Île-de-France, France
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2008
    • Unité Inserm U1077
      Caen, Lower Normandy, France