Marc Albertini

Distinct epithelial gene expression phenotypes in childhood respiratory allergy.

Epithelial cell contribution to the natural history of childhood allergic respiratory disease remains poorly understood. Our aims were to identify epithelial pathways that are dysregulated in different phenotypes of respiratory allergy. We established gene expression signatures of nasal brushings from children with dust mite-allergic rhinitis, associated or not associated with controlled or uncontrolled asthma. Supervised learning and unsupervised clustering were used to predict the different subgroups of patients and define altered signalling pathways. These profiles were compared with those of primary cultures of human nasal epithelial cells stimulated with either interleukin (IL)-4, IL-13, interferon (IFN)-&agr;, IFN-&bgr; or IFN-&ggr;, or during in vitro differentiation. A supervised method discriminated children with allergic rhinitis from healthy controls (prediction accuracy 91%), based on 61 transcripts, including 21 T-helper cell (Th) type 2-responsive genes. This method was then applied to predict children with controlled or uncontrolled asthma (prediction accuracy 75%), based on 41 transcripts: nine of them, which were down-regulated in uncontrolled asthma, are directly linked to IFN. This group also included GSDML, which is genetically associated with asthma. Our data revealed a Th2-driven epithelial phenotype common to all children with dust mite allergic rhinitis. It highlights the influence of epithelially expressed molecules on the control of asthma, in association with atopy and impaired viral response.

La fibroscopie bronchique chez l’enfant: Expertise des centres français de pneumologie pédiatrique

INTRODUCTION Fibreoptic bronchoscopy (FB) is an important diagnostic examination in paediatric pulmonology. In 2002 the Paediatric Pulmonology and Allergy Club undertook a retrospective study to establish the current status of fibreoptic bronchoscopy among its members. METHODS In 2001 sixty five paediatric pulmonologists carried out an average of 116 examinations (+/- 111) in 35 paediatric centres. FB was performed either in an operating theatre (15 centres), a dedicated bronchoscopy suite (6 centres) or an endoscopy suite shared with gastro-enterologists (7 centres). Other examinations were performed in areas dedicated to, or associated with intensive care. General anaesthesia was routinely used in 18 centres. The others used sedation including an equimolar mixture of oxygen and nitrous oxide in 14 centres. Ten centres performed less than 50 examinations, 12 between 51 and 100, 4 between 101 and 200 and 8 centres more than 200 in the year. Seventy two per cent of the children were less than 6 years old. The washing and disinfection procedures were manual in 20 centres and automatic in 15. RESULTS Three principal indications were reported: persistent wheezing, suspicion of a foreign body and ventilatory difficulties. Cough, desaturation and fever were the most frequently reported side effects. CONCLUSIONS This is the first survey in paediatric pulmonology in France. It shows a wide variation in the practice of fibreoptic bronchoscopy in children.Resume Introduction La fibroscopie bronchique est un examen complementaire cle dans la demarche diagnostique en pneumologie pediatrique. Le Club Pediatrique de Pneumologie et d’Allergologie a realise en 2002 une enquete retrospective permettant d’etablir un etat des lieux de la pratique par les pneumopediatres de la fibroscopie bronchique. Methodes Soixante cinq pneumopediatres ont effectues en moyenne 116 examens (± 111) dans 35 centres pediatriques en 2001. Les fibroscopies ont ete realisees soit dans un bloc operatoire (15 centres), soit un bloc dedie a la fibroscopie (6 centres), soit un site partage avec les gastroenterologues (7 centres). Les autres examens ont ete pratiques dans des locaux pediatriques (salle dediee et/ou unite de soins intensifs). L’anesthesie generale a ete systematique dans 18 centres. Les autres centres ont pratique une sedation consciente, avec utilisation de melange gazeux equimolaire oxygene protoxyde d’azote dans 14 centres. Dix centres ont realise moins de 50 examens, 12 entre 51 et 100, 4 entre 101 et 200 et 8 centres plus de 200 fibroscopies dans l’annee. Soixante douze pour cent des enfants avaient moins de 6 ans. Les procedures de lavage desinfection ont ete « manuelles » dans 20 centres et automatisees dans 15 centres. Resultats Trois indications principales ont ete rapportees : respiration sifflante persistante, suspicion de corps etranger et troubles de ventilation. Parmi les effets indesirables, la toux, la desaturation en oxygene et la fievre ont ete le plus souvent rapportees. Conclusion Cette enquete est une premiere en pneumologie pediatrique en France. Elle montre l’heterogeneite des pratiques en matiere de fibroscopie bronchique chez l’enfant.

Immediate contact urticaria caused by hydrolysed wheat proteins in a child via maternal skin contact sensitization.

Conflicts of interest: The authors have declared no conflicts. device (Stallergenes , Antony, France), and commercially prepared extracts (Stallergenes ), moisturizing cream (Yves Rocher , La Gacilly, France) and its 26 components provided by the manufacturer (Yves Rocher ). Control tests for prick tests were performed with histamine (positive control) and normal saline (negative control). Wheal diameters were measured 15 min after the skin test was applied, and were reported as mean wheal diameter. A prick test wheal diameter at least 3 mm larger than the negative control was considered to be positive. Multiple sensitization to mustard (6 mm), pistachios (23 mm), cashew (15 mm), chestnut (6 mm) and pine nuts (6 mm) was found. A positive response was observed with the moisturizing cream (11 mm), and positive responses were also observed with the macadamia nuts (6 mm) and the commercial hydrolysed wheat protein (4 mm), which were listed in the cream’s composition. Secondary prick tests with 26 components of the cream confirmed the responsibility of hydrolysed wheat

Evaluation of impulse oscillometry during bronchial challenge testing in children.

The impulse oscillation system (IOS) allows easy measurement of respiratory system impedance (Zrs). The aim of this retrospective study was to evaluate the accuracy of IOS parameters obtained during methacholine challenge by comparison with “the gold standard” forced expiratory volume in the first second (FEV1).

Relationship between impulse oscillometry and spirometric indices in cystic fibrosis children

Background: The aim of our retrospective study was to determine the relationship between impulse oscillometry (IOS) data and spirometric tests in cystic fibrosis (CF) children.

Eosinophilic pneumonias in children: A review of the epidemiology, diagnosis, and treatment.

Pediatric eosinophilic pneumonias (EPs) are characterized by a significant infiltration of the alveolar spaces and lung interstitium by eosinophils, with conservation of the lung structure. In developed countries, EPs constitute exceptional entities in pediatric care. Clinical symptoms may be transient (Löffler syndrome), acute (<1 month and mostly <7 days), or chronic (>1 month). Diagnosis relies on demonstration of alveolar eosinophilia on bronchoalveolar lavage, whether or not associated with blood eosinophilia. EPs are a heterogeneous group of disorders divided into: (i) secondary forms (seen mainly in parasitic infections, allergic bronchopulmonary aspergillosis, and drug reactions); and (ii) primary forms (eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome, idiopathic chronic eosinophilic pneumonia, and idiopathic acute eosinophilic pneumonia). Despite their rarity, the etiological approach to EP must be well‐defined as some causes can be rapidly life‐threatening without initiation of the proper treatment. This approach (i) eliminates secondary forms, with comprehensive history taking and minimal biological assessment, (ii) is oriented in primary forms by the acute or chronic setting, and the existence of extrapulmonary symptoms. Treatment of primary forms has traditionally relied on corticosteroids, usually with a dramatic response. Specific treatments or the adjunction of corticosteroid‐sparing treatment or immunosuppressors are currently being evaluated in order to improve the prognosis and the side effects associated with corticosteroid treatment in a pediatric setting. Pediatr Pulmonol. 2016;51:203–216.

Idiopathic eosinophilic pneumonia in children: the French experience

BackgroundIdiopathic 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.MethodsWe retrospectively analyzed all cases of ICEP and IAEP in children that were retrieved from French Reference Centers for rare pediatric lung diseases.ResultsFive 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.ConclusionICEP 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.

Symptomatic accessory cardiac bronchus in an infant

A 13-month-old infant was referred for evaluation of a severe, therapy-resistant asthma. He presented with daily wheezing, recurrent acute exacerbations, chronic dry-to-wet cough and failure to thrive. His mother had severe allergic asthma with recent admission to the intensive care unit. Initial chest X-rays were normal and skin prick tests were negative. It was decided to undertake a comprehensive work-up to exclude differential diagnoses. Paediatric radiologists initially interpreted the chest CT scan as normal. Bronchoscopic examination revealed an accessory cardiac bronchus (ACB) originating from the medial wall of the intermediate bronchus and filled with purulent secretions (108 Haemophilus influenzae and 108 Moraxella catarrhalis on bronchoalveolar lavage). The lesion was observed on re-examination of the CT scan (figure 1A, B) and demonstrated using three-dimensional (3D) virtual bronchoscopy and surface-rendered reconstructions (figure …

Chronic eosinophilic pneumonia with persistent decreased diffusing capacity for carbon monoxide

We report a 15-year-old girl presenting with dry cough, exertional dyspnoea, weight loss, fever and night sweats for over 1 month. Blood tests revealed hypereosinophilia, high IgE and antinuclear antibodies levels. Chest x-rays showed bilateral peripheral infiltrates mostly in the right upper lobe which was confirmed by a chest CT. Bronchoalveolar lavage showed hypercellularity with 28% of eosinophils. Idiopathic chronic eosinophilic pneumonia was confirmed after exclusion of other causes of eosinophilic pneumonia and systemic disease. The patient responded dramatically to oral corticosteroids. Oral corticotherapy was stopped after 4 months. At 8 months of follow-up, diffusing capacity for carbon monoxide (DLCO) remained moderately low (58%) with persistent mild exertional dyspnoea. Cardiopulmonary exercise testing showed muscular peripheral limitation. Even if in our patient, mild exertional dyspnoea can be partly correlated to peripheral deconditioning, DLCO should be systematically evaluated to determine follow-up studies standards, to correlate with subclinical disease, relapse risk and to codify therapeutic options.

Pulmonary Function in HIV-1 Vertically Infected Children

Background: Despite reports of an increasing incidence of asthma in HIV-infected children, exploration of pulmonary function by spirometry has never been reported in this population in the HAART era. Objective: The aim of this study was to determine the prevalence of spirometric abnormalities in HIV-1 infected children. We conducted a cross-sectional study of pulmonary function tests (PFT) in HIV-1 vertically infected children. Methods: Spirometric values were measured in 17 HIV-1 chronically infected children and compared to matched healthy children. In HIV-1 infected children, the correlations between PFT and the determination of the single breath carbon monoxide diffusing capacity of the lung (TL CO ) and immunological and virological values were assessed. Results: Overall, 11 of the 17 PFT were normal. Four showed mild distal obstruction. Two were considered restrictive. When compared with matched healthy children, the only difference was the FEV1/FVC ratio that was significantly lower in the patients’ group (91.9% of predicted value versus 97.1%, p<0.0001). We found a positive correlation between TL CO and the CD4/CD8 T-cell ratio (p=0.012) and viral load (p=0.05). We observed that FEF 25-75 values increased with age and weight in healthy children (p= 0.006 and p=0.007 respectively), but not in infected patients. Conclusions: Our results showed that chronic HIV-1 infection and/or continuous HAART exposure induce a specific response of the pulmonary immune system which may compromise its function with time. If confirmed, it may justify a careful follow-up of pulmonary function in vertically infected children