Epidemiology of childhood interstitial lung disease in France: the RespiRare cohort.

INTRODUCTION: Interstitial lung disease in children (chILD) are rare and mostly severe lung diseases. Very few epidemiological data are available in limited series of patients. The aim of this study was to assess the prevalence and incidence of chILD in France. METHODS: We performed within the RespiRare network a multicentre retrospective observational study in patients with chILD from 2000 to 2022 and a prospective evaluation of chILD's incidence between February 2022 and 2023. RESULTS: chILD was reported in 790 patients in 42 centres. The estimated 2022 prevalence in France was 44 /million children (95% CI 40.76 to 47.46) and the computed incidence was 4.4 /million children (95% CI 3.44 to 5.56). The median age at diagnosis was 3 months with 16.9% of familial forms. Lung biopsy and genetic analyses were performed in 23.4% and 76.9%, respectively. The most frequent chILD aetiologies in the <2 years group were surfactant metabolism disorders (16.3%) and neuroendocrine cell hyperplasia of infancy (11.8%), and in the 2-18 years group diffuse alveolar haemorrhage (12.2%), connective tissue diseases (11.4%), hypersensitivity pneumonitis (8.8%) and sarcoidosis (8.8%). The management included mainly oxygen therapy (52%), corticosteroid pulses (56%), oral corticosteroids (44%), azithromycin (27.2%), enteral nutrition (26.9%), immunosuppressants (20.3%) and hydroxychloroquine (15.9%). The 5-year survival rate was 57.3% for the patients diagnosed before 2 years and 86% between 2 and 18 years. CONCLUSION: This large and systematic epidemiological study confirms a higher incidence and prevalence of chILD than previously described. In order to develop international studies, efforts are still needed to optimise the case collection and to harmonise diagnostic and management practices.

COBRAPed cohort: Do sensitization patterns differentiate children with severe asthma from those with a milder disease?

BACKGROUND: It is unclear whether sensitization patterns differentiate children with severe recurrent wheeze (SRW)/severe asthma (SA) from those with non-severe recurrent wheeze (NSRW)/non-severe asthma (NSA). Our objective was to determine whether sensitization patterns can discriminate between children from the French COBRAPed cohort with NSRW/NSA and those with SRW/SA. METHODS: IgE to 112 components (c-sIgE) (ImmunoCAP® ISAC) were analyzed in 125 preschools (3-6 years) and 170 school-age children (7-12 years). Supervised analyses and clustering methods were applied to identify patterns of sensitization among children with positive c-sIgE. RESULTS: We observed c-sIgE sensitization in 51% of preschool and 75% of school-age children. Sensitization to house dust mite (HDM) components was more frequent among NSRW than SRW (53% vs. 24%, p < .01). Sensitization to non-specific lipid transfer protein (nsLTP) components was more frequent among SA than NSA (16% vs. 4%, p < .01) and associated with an FEV1/FVC < -1.64 z-score. Among sensitized children, seven clusters with varying patterns were identified. The two broader clusters identified in each age group were characterized by "few sensitizations, mainly to HDM." One cluster (n = 4) with "multiple sensitizations, mainly to grass pollen, HDM, PR-10, and nsLTP" was associated with SA in school-age children. CONCLUSIONS: Although children with wheeze/asthma display frequent occurrences and high levels of sensitization, sensitization patterns did not provide strong signals to discriminate children with severe disease from those with milder disease. These results suggest that the severity of wheeze/asthma may depend on both IgE- and non-IgE-mediated mechanisms.

Post viral bronchiolitis obliterans in children: A rare and potentially devastating disease.

Post infectious bronchiolitis obliterans (PIBO) is a rare but severe disease in children. Several respiratory pathogens are incriminated but adenovirus is still the most represented. Risk factors are well described: the male gender, hypoxemia at diagnosis and required mechanical ventilation. No risk factor is linked to the newborn period. The clinical spectrum of PIBO is broad, ranging from asymptomatic patients with fixed airflow obstruction to severe respiratory insufficiency requiring continuous oxygen supplementation. Diagnosis includes a combination of a clinical history, absence of reversible airflow obstructions and ground glass and gas trapping on high resolution computed tomography. PIBO is primarily a neutrophilic pathology of small bronchioles characterized by high levels of pro-inflammatory cytokines leading to tissue remodeling and fibrosis of the small airways. The difficulty is to discriminate between the host's normal response, an exaggerated inflammatory response and the potential iatrogenic consequences of the initial infection treatment, particularly prolonged mechanical ventilation. Damage to the respiratory epithelium with a possible link to viral infections are considered as potential mechanisms of PIBO. No specific management exists. Much remains to be done in this field to clarify the underlying mechanisms, identify biomarkers, and develop clear monitoring pathways and treatment protocols.

Lung Transplantation under a Janus Kinase Inhibitor in Three Patients with SAVI Syndrome.

Stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) is a very rare autoinflammatory disease related to STING1 mutation. SAVI is mainly characterized by fever attacks and skin and respiratory manifestations such as interstitial lung disease or alveolar hemorrhage. Respiratory involvement occurs in 80% of cases and might progress to severe lung fibrosis and require lung transplantation (LT). Three patients with SAVI who underwent LT have been reported to date. Two of the three patients died months or years after LT due to multiple organ failure or sepsis. However, the diagnosis of SAVI was made after LT, thus preventing the use of targeted therapy, such as the Janus kinase 1 and 2 inhibitor (JAK1/2i) ruxolitinib, which might be beneficial for the respiratory status of these patients. We aimed to report our experience in managing three patients who were followed in three large lung transplantation centers in France and who benefited from ruxolitinib before undergoing LT. We describe posttransplant complications that occurred as well as outcomes.

Long-term evolution of neuroendocrine cell hyperplasia of infancy: the FRENCHI findings.

Only few studies report long-term evolution of patients with neuroendocrine cell hyperplasia of infancy (NEHI). We report data from a 54-patient cohort followed up in the French network for rare respiratory diseases (RespiRare). Demographic characteristics and respiratory and nutritional evolution were collected at the time of the patient's last scheduled visit. The mean duration of follow-up was 68 months (5 months to 18 years). Fifteen patients (27.8%) were considered clinically cured. During follow-up, hospitalizations for wheezy exacerbations were reported in 35 patients (55%), and asthma diagnosed in 20 (37%). Chest CT scan improvement was noted in 25/44 (56.8%). Spirometry showed a persistent obstructive syndrome in 8/27 (29.6%). A sleep disorder was rare (2/36, 5.5%). Oxygen weaning occurred in 28 of the 45 patients initially treated (62.2%) and was age-dependent (35.7% under 2 years, 70.5% between 2 and 6 years, and 100% after 7 years). Oxygen duration was linked to a biopsy-proven diagnosis (p = 0.02) and to the use of a nutritional support (p = 0.003). Corticosteroids were largely prescribed at diagnosis, with no evident respiratory or nutritional effect during follow-up. Among 23 patients with an initial failure to thrive, 12 (52.2%) had no weight recovery. Initial enteral feeding (17/54, 31.5%) was stopped at a mean age of 43 months (3 to 120), with no effect on cure and oxygen liberation at the last visit.  Conclusion: Our results show that NEHI has a globally positive, but unequal, improvement over time. Further prospective studies are needed to better clarify the different trajectories of patients with NEHI. What is Known: • Neuroendocrine cell hyperplasia of infancy (NEHI) is an interstitial lung disease whose long-term outcome is considered positive from very few studies including heterogeneous populations. What is New: • The 68-month follow-up of our 54-patient cohort showed respiratory/nutritional symptom persistence in 72.2%, oxygen requiring in 34%, and asthma in 37%. When controlled, radiological or functional improvement was noted in 56.8 and 40.7%. Further prospective studies are needed to better clarify the different trajectories of patients with NEHI.

French national cohort of neuroendocrine cell hyperplasia of infancy (FRENCHI) study: diagnosis and initial management.

Early diagnosis of neuroendocrine cell hyperplasia of infancy (NEHI) is crucial as, conversely to the other causes of intersititial lung disease, corticosteroids are not recommended. Diagnosis is historically based on lung biopsy (NEHI), but in current practice, a clinical and radiological approach is more and more preferred (NEHI syndrome). This national study aimed to address diagnosis and initial management of patients followed up for a NEHI pattern in pediatric centers for rare lung diseases (RespiRare, France). Data on neonatal and familial events, symptoms at diagnosis, explorations performed and results, and therapeutic management were collected by questionnaire. Fifty-four children were included (boys 63%). The mean onset of symptoms was 3.8 ± 2.6 months. The most frequent symptoms at diagnosis were tachypnea (100%), retraction (79.6%), crackles (66.7%), and hypoxemia (59.3%). The mean NEHI clinical score, evocative when ≥ 7/10, was 7.9 ± 1.4 (76% with a score ≥ 7). All chest CT-scans showed ground glass opacities evolving at least the middle lobe and the lingula. Lung biopsy was performed in 38.9% of the cases and was typical of NEHI in only 52.4%, even when the clinical presentation was typical. Initial treatments were oxygen (83.6%) and more curiously intravenous pulses of steroids (83.3%) and azithromycin (70.2%). CONCLUSION: This national cohort of patients underlines diagnosis difficulties of NEHI. A composite clinical and radiological score should help clinicians for limiting the use of anti-inflammatory drugs. WHAT IS KNOWN: •Neuroendocrine cell hyperplasia of infancy (NEHI) is an interstitial lung disease whose diagnosis is essential to limit corticosteroids therapy. WHAT IS NEW: •In this national cohort of 54 patients with a NEHI pattern, diagnosis is mainly based on clinical symptoms and chest CT-scan results. The newly proposed clinical score and, when performed, the lung biopsies are faulted in 25 and 50% of the cases, respectively. •Corticosteroids are widely used. Such results plead for a new composite score to formally diagnose NEHI.

Management of primary spontaneous pneumothorax in teenagers: An 11-year study.

AIM: Management of teenagers with primary spontaneous pneumothorax (PSP) is not consensual. We report our experience over an 11-year period. METHODS: For each patient under 20 years hospitalised with PSP from 2008 to 2018, demographic data, smoking habits, clinical presentation, hospitalisation unit, radiological management and its results, therapeutic management (observation, needle aspiration, chest tube drainage and surgery), complications, length of stay, given advice at discharge and recurrence were collected. RESULTS: Seventy patients were included in different paediatric or adult surgery or pulmonology wards (82.9% boys; 16.8 ± 1.7 years; one severe presentation; 18/58 smokers). Chest CT-scan (n = 42/70, 60%) revealed blebs/bullae in 18/39 examinations (46.2%). Treatment consisted of observation (14/70, 20%), needle aspiration (2/70, 2.9%), chest tube (53/70, 75.7%) and video-assisted thoracoscopy surgery (27/70, 38.6%). Half patients with interventional procedure presented complications. A median of 10 chest X-rays was noted during a median stay of 8 days. Advice concerning sport practice, flying, smoking, etc., was variably delivered. PSP recurrence concerned 35/70 patients (50%) without identified predictive factors. CONCLUSION: Compared to recent recommendations of a more conservative approach, chest CT-scan and interventional strategy are overused in our teenagers with PSP. Observation, more or less needle aspiration, should be clearly the first-line treatments.

Neighborhood Disadvantage and Early Respiratory Outcomes in Very Preterm Infants with Bronchopulmonary Dysplasia.

OBJECTIVE: To investigate the impact of neighborhood conditions on respiratory-related hospital admissions in the first year after discharge from the neonatal unit in a population of infants born very preterm with bronchopulmonary dysplasia (BPD). STUDY DESIGN: Very preterm infants (gestational age <33 weeks) who had BPD at 36 weeks postconceptional age and who received follow-up in a French regional medical network were included. Socioeconomic context was estimated using a neighborhood-based Socioeconomic Deprivation Index. Poisson regression analysis was used to identify risk factors associated with rehospitalization. RESULTS: The study included 423 infants with a mean gestational age of 27 ± 2 weeks and mean birth weight of 941 ± 277 g; 51% of the population lived in a disadvantaged area. The hospital admission rate was increased by 8.8% for infants living in affluent areas and by 24% for those living in disadvantaged areas (P <.01) and reached 30% in extremely preterm infants from disadvantaged areas. After adjusting for perinatal characteristics, home oxygen therapy, and season of birth, the respiratory-related hospitalization rate was almost 3-fold higher in infants living in disadvantaged areas, with an adjusted incidence rate ratio of 2.79 (95% CI, 1.29-6.09; P <.01). CONCLUSIONS: Disadvantaged neighborhoods adversely impact early respiratory outcomes in infants born very preterm with BPD. The social context should be considered in routine follow-up care of children born preterm. Further studies investigating the underlying mechanisms are warranted for implementing preventive strategies.

Childhood asthma outcomes during the COVID-19 pandemic: Findings from the PeARL multi-national cohort.

BACKGROUND: The interplay between COVID-19 pandemic and asthma in children is still unclear. We evaluated the impact of COVID-19 pandemic on childhood asthma outcomes. METHODS: The PeARL multinational cohort included 1,054 children with asthma and 505 non-asthmatic children aged between 4 and 18 years from 25 pediatric departments, from 15 countries globally. We compared the frequency of acute respiratory and febrile presentations during the first wave of the COVID-19 pandemic between groups and with data available from the previous year. In children with asthma, we also compared current and historical disease control. RESULTS: During the pandemic, children with asthma experienced fewer upper respiratory tract infections, episodes of pyrexia, emergency visits, hospital admissions, asthma attacks, and hospitalizations due to asthma, in comparison with the preceding year. Sixty-six percent of asthmatic children had improved asthma control while in 33% the improvement exceeded the minimal clinically important difference. Pre-bronchodilatation FEV1 and peak expiratory flow rate were improved during the pandemic. When compared to non-asthmatic controls, children with asthma were not at increased risk of LRTIs, episodes of pyrexia, emergency visits, or hospitalizations during the pandemic. However, an increased risk of URTIs emerged. CONCLUSION: Childhood asthma outcomes, including control, were improved during the first wave of the COVID-19 pandemic, probably because of reduced exposure to asthma triggers and increased treatment adherence. The decreased frequency of acute episodes does not support the notion that childhood asthma may be a risk factor for COVID-19. Furthermore, the potential for improving childhood asthma outcomes through environmental control becomes apparent.

Key role of pediatricians and disease for influenza vaccination in children with high-risk chronic diseases.

Annual influenza vaccination is recommended for children with chronic diseases. Studies on influenza vaccines, following controversies related to the 2009 H1N1 influenza, are scarce in Europe. Our aim was to evaluate the influenza vaccination coverage in such children in a French tertiary hospital. Secondary objectives were the evaluation of the influenza vaccination coverage trend and the identification of factors influencing the vaccination status. A prospective and descriptive study by questionnaire was performed at the end of 2017 in 402 French hospital outpatients with various underlying chronic diseases eligible to the influenza vaccination. The 2016-2017 vaccination coverage was 46.5%. Figures of 75% or greater were only found in patients with cystic fibrosis and sickle cell disease. CART analysis identified vaccination in the previous year, medical recommendation for vaccination, and maternal influenza vaccination as a child's decisive factors for being vaccinated.Conclusion: Influenza vaccination coverage remains insufficient in children receiving hospital follow-up for chronic diseases. Its implementation clearly depends on pediatricians' recommendation to vaccinate and on the type of chronic disease. What is Known: • Despite health policy recommendations, the rate of annual influenza vaccination in children with chronic diseases is low What is New: • Influenza vaccination coverage depends on the type of chronic disease and on the pediatricians' counseling to vaccine.

Drug hypersensitivity in children: a retrospective analysis of 101 pharmacovigilance reports.

Our objective was to describe and discuss management of recent cases of drug hypersensitivity in children reported in a pharmacovigilance center. Two pediatric allergy units conducted a collaborative retrospective analysis of 101 adverse drug reactions reported to a regional pharmacovigilance center between January 2016 and July 2019. Time lapse between hypersensitivity reaction onset and allergy consultation varied from 1 month to 12 years. Sixty-two patients (61.4%) presented with immediate reactions, 11 (10.9%) with non-immediate reactions, and 28 (27.7%) had reactions impossible to classify through medical interview. Overall, 92 children (91%) were explored for simultaneously administered drugs. All 113 prick tests were negative, and 2 were uncertain. Among 108 intradermal tests, 2 were positive to penicillin and to an iodinated contrast medium, 105 were negative, and 1 was uncertain. Overall, 129 drug provocation tests were proposed. Nine provocation tests among 80 were positive (11.25%): 6 to penicillin, 1 to sulfonamide antibiotics, and 2 to non-steroidal anti-inflammatory drugs; the remaining 71 were negative. No severe reaction was observed during these tests. Finally, drug allergy was only retained in 11 reported cases (10.9%).Conclusion: These pharmacovigilance reports show the difficulty in defining drug allergy in children only by anamnesis, and that explorations, particularly provocation tests, should take place at a reasonable time lapse after drug hypersensitivity reaction onset. What is Known: • True drug allergy is rarely observed in children. • Absence of full workup leads to falsely labeling children as "allergic." What is New: • Short time lapse between hypersensitivity onset and consultation improves classification of pediatric allergy. • Timely allergy consultations are essential, and tests are useful to confirm or exclude pediatric allergy.

Use of epinephrine in emergency department depends on anaphylaxis severity in children.

Despite multiple recommendations, intramuscular epinephrine is poorly prescribed in emergency department receiving pediatric anaphylaxis. To evaluate the role of severity symptoms on this use, we included all admissions for a diagnosis linked to possible allergy in the two pediatric emergency departments of our institution between January 2010 and December 2015. Selection and analysis were restricted to children under 18 years fulfilling Sampson's criteria for anaphylaxis. We retrospectively ranked these admissions with the Ring and Messmer anaphylaxis severity score and compared the use of epinephrine according to this classification. Among 422,483 admissions, 204 (0.05%) fulfilled the anaphylaxis criteria (170 (83.3%) grade II anaphylaxis, and 34 (16.7%) grade III; mean age 7.9 years). Previous allergy, anaphylaxis, and asthma were found in respectively 60.8%, 36.8%, and 35.1%. Food allergy was the main suspected causal trigger. Epinephrine was used in 32.7% (n = 65/199), before admission (11.4% (n = 23/201)) or in the emergency department (22.2% (n = 45/202)). Epinephrine was more frequently prescribed in grade III than in grade II anaphylaxis (84.8% vs 22.3%, p < 0.001; OR = 19.05 [7.05-54.10]). Upon discharge, epinephrine auto-injectors prescription and allergy referral were rare (31.7% and 44.2%).Conclusion: Pediatricians intuitively adapt their epinephrine use to the severity of the anaphylaxis and contribute to epinephrine underuse in pediatric anaphylaxis. What is known: • Intramuscular epinephrine is the recommended treatment for pediatric anaphylaxis. However, most of the European and North-American studies show a low prescription rate of epinephrine in both prehospital and pediatric emergency department management. • Reasons for such a low prescription rate are unknown. What is new: • This study confirms that intramuscular epinephrine is poorly prescribed in pediatric anaphylaxis (about one case among 10 before admission and one among 5 in pediatric emergency departments). • Despite recommendations, pediatricians intuitively adapt their prescription to the clinical severity of anaphylaxis, with a fourfold increase prescription in grade III compared to grade II anaphylaxis. This medical behavior ascertainment may be in part explained by the delay between the ED admission/management and the anaphylactic episode onset.

Use of high-flow nasal cannula in infants with viral bronchiolitis outside pediatric intensive care units.

High-flow nasal cannula (HFNC) is frequently used in infants with acute viral bronchiolitis outside pediatric intensive care units (PICU). A structured questionnaire was sent out to pediatricians of all public French hospitals with pediatric emergency and/or general pediatric departments on their use of HFNC outside PICU (department using HFNC, number of available devices, monitoring, criteria for initiating or stopping HFNC, and personal comments on HFNC). Of the 166 eligible hospitals, 135 answered (96 general and 39 university hospitals; 81.3%), for a total of 217 answering pediatricians. Seventy-two hospitals (53.3%) used HFNC in acute bronchiolitis outside PICU, particularly, general hospitals (59.4% vs 38.5%), and mostly in pediatric general departments (75%). Continuous patient monitoring with a cardiorespiratory monitor was usual (n = 58, 80%). Nursing staff was responsible for 2.7 children on HFNC and checked vital signs 8.6 times per day. Criteria for HFNC initiation and withdrawal were not standardized. Pediatricians had a positive opinion of HFNC and were willing to extend its use to other diseases.Conclusion: Use of HFNC outside PICU in infants with acute bronchiolitis is now usual, but urgently requires guidelines. What is Known: • Acute viral bronchiolitis treatment is only supportive • High-flow nasal cannula (HFNC) is a respiratory support accumulating convincing clinical evidence in bronchiolitis • This latter treatment is usually proposed in pediatric intensive care unit (PICU) What is New: • HFNC are increasingly used outside PICU in bronchiolitis, particularly, in general hospitals and in pediatric general departments • Pediatricians are enthusiastic about this device, but validated criteria for initiation and withdrawal are lacking • Guidelines for the use of HFNC outside PICU are urgently required.

Biallelic Mutations of Methionyl-tRNA Synthetase Cause a Specific Type of Pulmonary Alveolar Proteinosis Prevalent on Réunion Island.

Methionyl-tRNA synthetase (MARS) catalyzes the ligation of methionine to tRNA and is critical for protein biosynthesis. We identified biallelic missense mutations in MARS in a specific form of pediatric pulmonary alveolar proteinosis (PAP), a severe lung disorder that is prevalent on the island of Réunion and the molecular basis of which is unresolved. Mutations were found in 26 individuals from Réunion and nearby islands and in two families from other countries. Functional consequences of the mutated alleles were assessed by growth of wild-type and mutant strains and methionine-incorporation assays in yeast. Enzyme activity was attenuated in a liquid medium without methionine but could be restored by methionine supplementation. In summary, identification of a founder mutation in MARS led to the molecular definition of a specific type of PAP and will enable carrier screening in the affected community and possibly open new treatment opportunities.

Vibrating-mesh nebulizer maintenance by CF patients: Results from a French survey.

PURPOSE OF THE STUDY: Vibrating-mesh nebulizers are widely used at home for cystic fibrosis (CF) treatment, with a therapeutic efficiency closely linked to the mesh performance. This national study looks at the maintenance at home by CF patients and their families of the mesh of the eFlow®rapid nebulizer. Ninety-two patients from 34 French CF centers, treated at home with inhaled drugs delivered with a vibrating-mesh nebulizer, answered to a phone standardized questionnaire specifying the different techniques of maintenance of the nebulizer. PRINCIPAL RESULTS: Patients were aged from 2 to 68 years (58.7% of children). They inhaled a mean of 1.8 nebulizations per day. Maintenance was assumed by patients in 36% of the cases. All steps of the theoretical maintenance of a nebulizer were respected in 66% of the cases. The mesh was not cleaned in 45.6%, not disinfected or not thermically disinfected in 32.5%, and not rinsed after chemical disinfection in 45.5% of the case. Only 49% of the patients knew the role of the MeshCare® system in the mesh maintenance, and only 39% had already used it when the nebulization duration reached 10 min. CONCLUSIONS: Efforts about education, particularly for the maintenance of the mesh, are needed for CF patients using a vibrating-mesh nebulizer at home.

Air pollution and children's asthma-related emergency hospital visits in southeastern France.

Children's asthma is multifactorial. Environmental factors like air pollution exposure, meteorological conditions, allergens, and viral infections are strongly implicated. However, place of residence has rarely been investigated in connection with these factors. The primary aim of our study was to measure the impact of particulate matter (PM), assessed close to the children's homes, on asthma-related pediatric emergency hospital visits within the Bouches-du-Rhône area in 2013. In a nested case-control study on 3- to 18-year-old children, each control was randomly matched on the emergency room visit day, regardless of hospital. Each asthmatic child was compared to 15 controls. PM10 and PM2.5, meteorological conditions, pollens, and viral data were linked to ZIP code and analyzed by purpose of emergency visit. A total of 68,897 visits were recorded in children, 1182 concerning asthma. Short-term exposure to PM10 measured near children's homes was associated with excess risk of asthma emergency visits (adjusted odds ratio 1.02 (95% CI 1.01-1.04; p = 0.02)). Male gender, young age, and temperature were other risk factors. Conversely, wind speed was a protective factor. CONCLUSION: PM10 and certain meteorological conditions near children's homes increased the risk of emergency asthma-related hospital visits in 3- to 18-year-old children in Bouches-du-Rhône. What is Known: • A relationship between short-term exposure to air pollution and increase in emergency room visits or hospital admissions as a result of increased pollution levels has already been demonstrated. What is New: • This study confirms these results but took into account confounding factors (viral data, pollens, and meteorological conditions) and is based on estimated pollution levels assessed close to the children's homes, rather than those recorded at the hospital. • The study area, the Mediterranean, is favorable to creation of secondary pollutants in these sunny and dry seasons.

Early Halt of a Randomized Controlled Study with 3% Hypertonic Saline in Acute Bronchiolitis.

BACKGROUND: Albeit not recommended because of contradictory results, nebulized 3% hypertonic saline is widely used for treating acute viral bronchiolitis. Whether clinical differences may be attributed to the type of nebulizer used has never been studied. OBJECTIVES: By modifying the amount of salt deposited into the airways, the nebulizer characteristics might influence clinical response. METHODS: A prospective, randomized, controlled trial included infants hospitalized in a French university hospital for a first episode of bronchiolitis. Each child received 6 nebulizations of 3% hypertonic saline during 48 h delivered with 1 of the 3 following nebulizers: 2 jet nebulizers delivering large or small particles, with a low aerosol output, and 1 mesh nebulizer delivering small particles, with a high aerosol output. The primary endpoint was the difference in the Wang score at 48 h. RESULTS: Only 61 children of 168 were recruited before stopping this study because of severe adverse events (n = 4) or parental requests for discontinuation due to discomfort to their child during nebulization (n = 2). One minor adverse event was noted in 91.8% (n = 56/61) of children. A high aerosol output induced 75% of the severe adverse events; it was significantly associated with the nebulization-induced cough between 24 and 48 h (p = 0.036). Decreases in Wang scores were not significantly different between the groups at 48 h, 9 recoveries out of 10 being obtained with small particles. CONCLUSION: No beneficial effects and possibly severe adverse events are observed with 3% hypertonic saline in the treatment of bronchiolitis.

Aspergillus tubingensis: a major filamentous fungus found in the airways of patients with lung disease.

The black Aspergillus group comprises A. niger and 18 other species, which are morphologically indistinguishable. Among this species subset, A. tubingensis, described in less than 30 human cases before 2014, is primarily isolated from ear, nose, and throat samples. Recently, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has emerged as a powerful technique to identify microbes in diagnostic settings. We applied this method to identify 1,720 filamentous fungi routinely isolated from clinical samples our laboratory over a two-year study period. Accordingly, we found 85 isolates of A. niger, 58 of A. tubingensis, and six other black Aspergillus (4 A. carbonarius and 2 A. japonicus). A. tubingensis was the fifth most frequent mold isolated in our mycology laboratory, primarily isolated from respiratory samples (40/58 isolates). In this study, we mainly aimed to describe the clinical pattern of Aspergillus tubingensisWe analyzed the clinical features of the patients in whom A. tubingensis had been isolated from 40 respiratory samples. Thirty patients suffered from cystic fibrosis, chronic obstructive pulmonary disease or other types of chronic respiratory failure. Strikingly, 20 patients were experiencing respiratory acute exacerbation at the time the sample was collected. Antifungal susceptibility testing of 36 A. tubingensis isolates showed lower amphotericin B MICs (P < 10(-4)) and higher itraconazole and voriconazole MICs (P < 10(-4) and P = .0331, respectively) compared with 36 A. niger isolates. Further studies are required to better establish the role that this fungus plays in human diseases, especially in the context of cystic fibrosis and chronic pulmonary diseases.