Unusual long survival despite severe lung disease of a child with biallelic loss of function mutations in ABCA-3.

Homozygous or compound heterozygous for frameshift or nonsense mutations in the ATP-binding cassette transporter A3 (ABCA3) is associated with neonatal respiratory failure and death within the first year of life without lung transplantation. We report the case of a newborn baby girl who developed severe respiratory distress soon after birth. She was diagnosed with compound heterozygous frameshift mutation of the ABCA3 gene. Despite extensive treatment (intravenous corticosteroids pulse therapy, oral corticosteroids, azithromycin, and hydroxychloroquine), she developed chronic respiratory failure. As the parents refused cardio-pulmonary transplantation and couldn't resolve to an accompaniment of end of life, a tracheostomy was performed resulting in continuous mechanical ventilation. A neurodevelopmental delay and an overall muscular dystrophy were noted. At the age of 5 years, after 2 episodes of pneumothorax, the patient died from severe respiratory failure. To our knowledge, this was the first case of a child with compound heterozygous frameshift mutation who posed such an ethical dilemma with a patient surviving till the age of five years.

[Pseudomonas aeruginosa in post-piercing perichondritis: Two case reports]. / Chondrite à Pseudomonas aeruginosa après piercing chez l'adolescent : à propos de deux cas.

The frequency of body piercing has increased in France over the past few years, particularly among teenagers. Piercing can be performed at different sites on the body, especially in the cartilage of the ears. We relate two cases of Pseudomonas aeruginosa chondritis. A 10-year retrospective study at the Marseille University Hospital found no additional pediatric cases. These infectious complications can sometimes be necrotizing. It is therefore important to inform the medical staff on the hygiene measures that need to be respected and the patients on the treatment to follow after the piercing as well as the signs to watch for, possibly indicating chondritis. The esthetic consequences depend on early diagnosis.

An update on bacterial brain abscess in immunocompetent patients.

BACKGROUND: A brain abscess is a focal infection of the brain that begins as a localized area of cerebritis. In immunocompetent patients, bacteria are responsible for >95% of brain abscesses, and enter the brain either through contiguous spread following otitis, sinusitis, neurosurgery, or cranial trauma, or through haematogenous dissemination. AIMS: To identify recent advances in the field. SOURCES: We searched Medline and Embase for articles published during years 2012-2016, with the keywords 'brain' and 'abscess'. CONTENT: The triad of headache, fever and focal neurological deficit is complete in ∼20% of patients on admission. Brain imaging with contrast-preferentially magnetic resonance imaging-is the reference standard for diagnosis, and should be followed by stereotactic aspiration of at least one lesion, before the start of any antimicrobials. Efforts should be made for optimal management of brain abscess samples, for reliable microbiological documentation. Empirical treatment should cover oral streptococci (including milleri group), methicillin-susceptible staphylococci, anaerobes and Enterobacteriaceae. As brain abscesses are frequently polymicrobial, de-escalation based on microbiological results is safe only when aspiration samples have been processed optimally, or when primary diagnosis is endocarditis. Otherwise, many experts advocate for anaerobes coverage even with no documentation, given the sub-optimal sensitivity of current techniques. A 6-week combination of third-generation cephalosporin and metronidazole will cure most cases of community-acquired brain abscess in immunocompetent patients. IMPLICATIONS: Significant advances in brain imaging, minimally invasive neurosurgery, molecular biology and antibacterial agents have dramatically improved the prognosis of brain abscess in immunocompetent patients over the last decades.

Aspergillus fumigatus in cystic fibrosis: An update on immune interactions and molecular diagnostics in allergic bronchopulmonary aspergillosis.

A wide spectrum of pathological conditions may result from the interaction of Aspergillus fumigatus and the immune system of its human host. Allergic bronchopulmonary aspergillosis is one of the most severe A. fumigatus-related diseases due to possible evolution toward pleuropulmonary fibrosis and respiratory failure. Allergic bronchopulmonary aspergillosis occurs almost exclusively in cystic fibrosis or asthmatic patients. An estimated 8%-10% of patients with cystic fibrosis experience this condition. The diagnosis of allergic bronchopulmonary aspergillosis relies on criteria first established in 1977. Progress in the understanding of host-pathogen interactions in A. fumigatus and patients with cystic fibrosis and the ongoing validation of novel laboratory tools concur to update and improve the diagnosis of allergic bronchopulmonary aspergillosis.

Clinical markers of asthma and IgE assessed in parents before conception predict asthma and hayfever in the offspring.

BACKGROUND: Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans. OBJECTIVE: We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever. METHODS: The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972-2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions. RESULTS: Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11-22 years with information on parental disease activity both before and after birth. CONCLUSION & CLINICAL RELEVANCE: Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.

[Health care providers' knowledge and abilities to use inhalation devices and spacers]. / Évaluation des connaissances en aérosolthérapie du personnel hospitalier.

INTRODUCTION: Inhaled therapy is the mainstay of asthma treatment due to its local and rapid action. However, its efficiency relies on the teaching of a good inhalation technique by health care providers. We assessed health care providers' knowledge and practical skills in the use of inhalation devices. METHODS: An observational multicenter study was conducted in the pulmonology and paediatric wards in Marseille. The departments' common practices, theoretical knowledge and practical skills were assessed through a questionnaire and a demonstration using a spacer device. RESULTS: Forty health care providers were interviewed (9 attending physicians, 14 residents, 16 nurses and 1 physiotherapist), in 8 different pulmonology and paediatric wards. A total of 42.5% reported previous training in inhalation device technique. When evaluating theoretical knowledge, we found a mean of 54% correct answers. Attending physicians did significantly better than residents and nurses. With regard to practical skills, we found a mean of 1.12 failed steps out of 7. Here again attending physicians did significantly better than residents and nurses. CONCLUSION: Based on the results of our study, we recommend that attending physicians provide training of inhalation technique to nurses and residents, as they did significantly better theoretically and practically.

[Chest X-ray and acute bronchiolitis: Are these indications decreasing?] / Radiographie de thorax et bronchiolite aiguë : des indications en diminution ?

OBJECTIVE: A management protocol for infants hospitalized for acute bronchiolitis, established after the study conducted in our unit in 2012, recommends a chest X-ray when the clinical course is unusual or if a differential diagnosis is suspected. The goal of this study was to evaluate professional practices after the introduction of this new management protocol. STUDY DESIGN: Retrospective descriptive study in two pediatric units from October 2013 to March 2015, including infants (0-23 months) hospitalized for their first episode of acute bronchiolitis without any underlying chronic condition. RESULT: Overall, 599 infants were included (median age, 3.7 months, 54 % boys). Nearly six out of ten (n=355, 59.3 %) had at least one chest radiograph (38.5 % fewer than in 2012). It was abnormal in 96.3 % of cases, revealing distension and/or bronchial wall thickening (56.7 %), focal opacity (23.5 %), or atelectasis (19.5 %). An X-ray was performed out of the recommendations in 42.5 % of cases. The chest X-ray result led to management changes in 52 infants with prescription of antibiotics for pneumonia (86.5 %) and allowed the diagnosis of heart disease in one case (0.2 %). Management of acute bronchiolitis (X-ray and antibiotics) was statistically different between the two pediatric units. DISCUSSION: This protocol led to a significant decrease in the number of chest X-rays. However, many are still performed out of the recommendations, resulting in an increase of antibiotic use for pneumonia. CONCLUSION: The decrease in use of chest X-rays in acute bronchiolitis for hospitalized infants was significant but remains insufficient.

[Infant food diversification. Assessment of practices in relation to French recommendations in pediatricians and pediatric residents in southern France]. / Diversification alimentaire du nourrisson. Évaluation des pratiques en regard des recommandations françaises actuelles chez les pédiatres varois et les internes affectés à la faculté d'Aix-Marseille.

Infant food diversification has undergone a rapid succession of good practice recommendations in France, but there has been no assessment of pediatrician practices on food diversification. OBJECTIVE: To assess the practices of pediatricians in relation to current recommendations of the French Society of Pediatrics on infant food diversification. METHODS: This was an observational study conducted from 1 November 2014 to 31 March 2015. The study population consisted of 97 pediatricians in the Var department and 84 pediatric residents assigned to the University of Aix-Marseille in France. A questionnaire was sent by email or post to determine physician characteristics, food diversification methods in healthy children and those at atopic risk, and how the pediatric consultation was conducted. The expected answers were based on the most recent recommendations of the French Society of Pediatrics published in 2008, updated from 2003. In summary, breastfeeding is recommended up to 6 months. Food diversification can be started between 4 and 6 months in children with no allergy risk. Gluten, honey, legumes and cow's milk are introduced between 4 and 7 months, after 12 months and after 36 months, respectively. In atopic children, food diversification is delayed until after 6 months and the most allergenic foods (nuts, exotic fruits, peanuts, and shellfish) are introduced after the age of 12 months. RESULTS: Eighty-four responses were obtained (51%): 50 pediatricians and 34 pediatric residents. Sixteen items were classified depending on whether or not an update after 2003 existed. Over 80% of the physicians responded as recommended for the recently updated items for the age of introduction of "solid food in healthy children", "gluten", "cow's milk protein hydrolysates", and "the time until introduction of cow's milk in the atopic child". At best, 65% of physicians responded in accordance with recommendations for items without a recent update, age of introduction of "cow's milk", "milk desserts", "animal proteins", "fats", "vegetables", "use of a hypoallergenic infant formula", and "breastfeeding extension with atopic child". Pediatric residents had the same responses as pediatricians. Seventy-two physicians did not consider the allergenic status of the children to delay the introduction of the most allergenic foods. The lack of complete updating the introduction of solid foods schedule could explain the differences between pediatrician practices and recommendations. Moreover, old recommendations on allergenic food eviction are still available. CONCLUSION: Pediatricians and pediatric residents partially applied the current recommendations on the introduction of solid food.

Aspergillus fumigatus components distinguish IgE but not IgG4 profiles between fungal sensitization and allergic broncho-pulmonary aspergillosis.

Aspergillus fumigatus is the causative agent of allergic broncho-pulmonary aspergillosis. Prompt and accurate diagnosis may be difficult to achieve with current clinical and laboratory scores, which do not include immune responses to recombinant A. fumigatus allergens. We measured specific immunoglobulin E and G4 directed to recombinant A. fumigatus allergens in 55 cystic fibrosis patients without allergic broncho-pulmonary aspergillosis but sensitized to A. fumigatus and in nine patients with allergic broncho-pulmonary aspergillosis (two with cystic fibrosis and seven with asthma). IgG4 responses to recombinant A. fumigatus allergens were detected in all patients, but neither prevalence nor levels were different between the two patient groups. On the other hand, both prevalence and levels of IgE responses to Asp f 3, Asp f 4, and Asp f 6 helped distinguish allergic broncho-pulmonary aspergillosis from A. fumigatus sensitization with good negative and positive predictive values.

[Fat overload syndrome]. / Syndrome de surcharge en lipides : un accident iatrogène rare.

We report the case of a 21-month-old child suffering from pulmonary fibrosis, who presented with acute respiratory distress and liver damage, due to an accidental overdose of intravenous lipid emulsion. This poisoning is a rare entity, whose potential severity and almost exclusive iatrogenic effect deserve to be remembered.

[Infant food diversification: Is the information available on the Internet valid?]. / Diversification alimentaire : l'information disponible sur Internet est-elle en accord avec les recommandations des sociétés savantes ?

INTRODUCTION: The Internet provides easy access to information on health, but the quality and validity of this information are variable. OBJECTIVES: To evaluate the quality of websites and the information provided on the timing and consequences of food diversification for infants. MATERIALS AND METHODS: We analyzed the websites addressing infant food diversification that appeared on the first two pages of the search engines Google, Yahoo, and Bing. The websites were selected from four different queries. We initially assessed (a) the structure of the websites with two instruments (the Criteria for Assessing the Quality of Health Information on the Internet (HITI) and NetScoring) and (b) the presence of certification (quality label Health on the Net [HON] Code). Secondly, we evaluated the content of the websites concerning the time of introducing five classes of foods (gluten, fat, allergenic foods, solid foods, and animal protein), the duration of breastfeeding, and four potential consequences of food diversification (allergy, nutritional, autoimmune, and cardiovascular). Our repository was based on the most recent recommendations of the French Society of Pediatrics published in 2008. RESULTS: In all, 19 websites were included. Six of 19 websites scored above average on the two instruments (average: 131.26/312 with NetScoring and 46.73/104 with HITI). No correlation was observed between the referencing of websites analyzed and the notes obtained with both instruments. A majority of the websites analyzed were consistent with the recommendation favoring breast milk (100%), the age of introducing meat proteins (74%), and the age of introducing gluten (63%). A majority of the websites disagreed on the age of introducing solid foods (16%). As four consequences, only the risk of allergy (63%) was cited by a majority of the sites. There was a small nonsignificant correlation between the results obtained for the website about introducing solid foods and the results obtained for the websites analyzed with the NetScoring and HITI instruments (Pearson coefficient 41%, p=0.07). CONCLUSION: The websites were in partial agreement with the French recommendations. To date, the pediatrician remains the main actor in guiding parents on food diversification.

[Aspirin hypersensitivity: characteristics and diagnostic approach]. / Intolérance à l'aspirine : caractéristiques et éléments diagnostiques.

INTRODUCTION: In routine medical practice, the diagnosis of aspirin hypersensitivity (AH) remains difficult. No clinical feature or biomarker is available to reliably confirm this diagnosis and oral provocation tests (OPT) are rarely performed. AIM: To compare asthmatics with and without AH. METHOD: The clinical characteristics of 21 asthmatics with and 24 without AH respectively were determined. AH was defined by a positive OPT. A full blood count was done before and 24 hours after the OPT. RESULTS: The medical history was associated with a weak sensitivity (52%) and a good specificity (96%) for assessing the diagnosis of AH. There was a higher prevalence of AH in women, and a higher frequency of allergic rhinitis in AH, but no characteristic was useful to facilitate the diagnosis of AH in asthmatic patients. Our results demonstrate higher values of platelets in AH patients. Following OPT, in AH patients only, a decrease in blood eosinophils and an increase in neutrophils was observed. CONCLUSIONS: These results confirm that the diagnosis of AH is challenging, with the history having only weak sensitivity. The observation that fluctuations in eosinophils and neutrophils occur following OPT in AH patients only warrants further investigations and suggests a rapid pro-inflammatory role for aspirin.

[Chest radiographs in infants hospitalized for acute bronchiolitis: real information or just irradiation?]. / La radiographie de thorax chez le nourrisson hospitalisé pour bronchiolite aiguë : réelle information ou simple irradiation ?

OBJECTIVE: To describe the chest radiographs of infants hospitalized for acute bronchiolitis and to assess whether patient management changed after radiography. STUDY DESIGN: All infants hospitalized in our pediatric unit with a first episode of acute bronchiolitis from October 2010 to March 2012 were included in the study. Infants with chronic disease or transferred from a pediatric intensive care unit were excluded. The following data were collected: sex, age, neonatal history, atopy, tobacco exposure, admission criteria, treatment, laboratory parameters, ultrasonography and its outcome, results of chest radiography on admittance, the reason for a second chest radiograph, change in management as a result of the radiograph. RESULTS: The study comprised 232 infants (median age 2.2 months, boys 56%, positive respiratory syncytial virus 73.4%). Among them, 227 children had a routine chest radiograph revealing distension and/or bronchial wall thickening (n=141, 62.4%), focal opacity (19.9%), or atelectasis (17.7%). This radiograph led to the prescription of antibiotics in six patients (2.6%) and allowed the diagnosis of vascular abnormality to be made in one case (0.4%). Thirty-five patients (15.4%) had a second chest radiograph during their hospitalization owing to oxygen dependency (n=21), respiratory distress (n=11), persistent fever (n=2), or no reason specified (n=1). Pneumonia (n=7) and/or atelectasis (n=15) were then found in 62.9%. Patient management (antibiotics, postural maneuvers) was modified in six patients (17.1%). CONCLUSIONS: Routine chest radiographs contribute only partially to the treatment of infants hospitalized for acute bronchiolitis. However, radiography is useful when the hospitalized child does not improve at the expected rate or if the disease is severe. The indication of chest radiography in infants hospitalized for acute bronchiolitis should be discussed on a case by a case basis.

[Physiopathology of aspirin intolerant asthma]. / Physiopathologie de l'asthme avec intolérance à l'aspirine. Concepts classiques et nouvelles voies métaboliques d'intérêt.

Aspirin-exacerbated respiratory disease (AERD) refers to the development of bronchoconstriction in individuals with asthma following the ingestion of aspirin. AERD affects up to 20 % of adults with asthma. At present, no reliable in vitro test is available to confirm the diagnosis. The confirmation of the diagnosis of AERD therefore depends on the response to challenge testing with aspirin. The pathogenesis of AERD is linked to abnormalities in arachidonic acid metabolism. Prior to exposure to aspirin, respiratory mucosal inflammation is the result of a cell infiltration, an overproduction of leukotrienes, prostaglandins D2, 5-oxo-eicosatetraenoic acid and an underproduction of lipoxins. After aspirin ingestion, patients with AERD synthesize excessive amounts of cysteinyl leukotrienes and prostaglandin metabolites involved in bronchoconstriction. New hypotheses concerning AERD pathogenesis have been added to the initial cyclooxygenase theory. These propose that AERD may be linked to the complement system, adenosine metabolism or angiotensin converting enzyme gene and IgE receptor gene polymorphisms.

[Asthmatic exacerbations: specific features in children]. / Exacerbations asthmatiques: spécificités pédiatriques (en dehors du traitement).

Asthma concerns more than 10% of 10-year-old children. Despite the similarities between adult and childhood asthma, the pediatric population presents some specific characteristics, notably in relation to exacerbations. Asthma in the newborn infant is a specific entity, the definition of which has recently been officially recognized. In exacerbations, the most important trigger factors are respiratory virus infections, the strain having prognostic importance. The indoor and outdoor environments are risk factors, particularly high levels of atmospheric pollution. Nutrients seem to play a prognostic role through vitamin D or food allergy. Measurement of exhaled nitric oxide and examination of induced sputum may help in diagnosis and adjustment of treatment but these tools are not yet effective as predictive factors in asthma exacerbations. Prevention, early management and continued education of children and their families remain the best methods to improve asthma control.

Geographical, urban/rural and socioeconomic variations in nonmelanoma skin cancer incidence: a population-based study in Ireland.

BACKGROUND: Nonmelanoma skin cancer (NMSC) is the most common cancer in white populations worldwide. International comparisons in incidence are limited because few registries collect comprehensive population-based data. OBJECTIVES: We describe spatial, urban/rural and socioeconomic variations in NMSC incidence in Ireland, overall and for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) separately. Methods NMSC cases (n=47 347) diagnosed during 1994-2003 were extracted from the National Cancer Registry. Each case was allocated to a small area (electoral district, ED) based on address at diagnosis. Standardized incidence ratios (SIRs) were calculated and smoothed using a Bayesian conditional autoregressive model. Associations between disease and census-derived area-based socioeconomic factors (unemployment, employment type, early school leavers, deprivation category, population density) were investigated using negative binomial regression. RESULTS: The spatial and socioeconomic distributions differed by subtype, suggesting aetiological differences. For BCC, areas of higher risk were concentrated around the main cities, with small patches on the south and west coast. Higher risks for SCC were seen in the north-east, on the south, mid and north-west coast. BCC risk in males and females, and SCC in males, was significantly higher in those living in the least deprived areas. Risk of BCC and SCC in females was higher in the most densely populated areas. CONCLUSIONS: We observed striking geographical variation in NMSC incidence, which cannot be satisfactorily explained on the basis of known risk factors. Differences by deprivation category and population density may reflect better access to cancer surveillance or care, as well as differences in risk factor exposure.