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Competing Interests: Competing interests: None declared.

Preschool wheeze is a public health issue. Disease control can be difficult to obtain in this population, in which no biologic therapy is indicated. We studied the evolution of severe preschool wheezers in real-life and identified the factors leading to no-control. We conducted a retrospective study at our tertiary asthma center. Each child under 3 years of age with severe, uncontrolled preschool wheeze was admitted to a pediatric day hospital for further investigations. We collected the results of clinical, biological and radiological exams, and follow-up data at 1 (Y +1 ), 2 (Y +2 ) and 3 years (Y +3 ). We included 135 patients; 63 (47 %) were still being followed at Y +3 ; 53 % were discontinued due to disease control. The median age at inclusion was 12 months. 29 % of patients followed up still had severe uncontrolled wheezing at Y +3 . Eosinophils greater than 0.23G/L (p = 0.03) and a first case of bronchiolitis before the age of 2 months (p = 0.01) were factors in uncontrolled wheezing at Y 1 . Tobacco exposure was a factor associated with uncontrolled wheezing at Y +2 (p < 0.001). A first case of bronchiolitis before the age of 2 months (p = 0.007), male sex (p < 0.001) and a familial history of atopy (p = 0.05) were factors in uncontrolled disease at Y +3 . We report a real-life study, with a very young population and very severe wheezing. Our therapeutic approach is original, enabling us to study the evolution of "therapeutic pressure" in the early years of this frequent disease, the pathophysiology of which is still poorly understood., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Among the causes of abnormal fetal lung development, active and environmental maternal smoking represents a major potential target in preventive medicine. Prevalence of smoking among women, particularly during pregnancy, varies across the different regions of the world. We reviewed the literature on the repercussions of maternal smoking on the lungs of the fetus and the neonate. One of the main consequences is prematurity, leading to pulmonary bronchodysplasia followed by respiratory infections, which particularly affect young children. In the medium- and long-term, smoking in utero leads to asthma and allergies, and is suspected to be associated with impaired respiratory function in children and teenagers. We also report on the potential effects of e-cigarettes, which represent an emerging threat to children's respiratory health., (Copyright © 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Acute respiratory infections (ARI) are the most common infections in the general population and are mainly caused by respiratory viruses. Detecting several viruses in a respiratory sample is common. To better understand these viral codetections and potential interferences, we tested for the presence of viruses and developed quantitative PCR (Polymerase Chain Reaction) for the viruses most prevalent in coinfections: human rhinovirus (HRV) and respiratory syncytial virus (RSV), and quantified their viral loads according to coinfections and health status, age, cellular abundance and other variables., Materials and Methods: Samples from two different cohorts were analyzed: one included hospitalized infants under 12 months of age with acute bronchiolitis (n=719) and the other primary care patients of all ages with symptoms of ARI (n=685). We performed Multiplex PCR on nasopharyngeal swabs, and quantitative PCR on samples positive for HRV or/and RSV to determine viral loads (VL). Cellular abundance (CA) was also estimated by qPCR targeting the GAPDH gene. Genotyping was performed either directly from first-line molecular panel or by PCR and sequencing for HRV., Results: The risks of viral codetection were 4.1 (IC 95 [1.8; 10.0]) and 93.9 1 (IC 95 [48.7; 190.7]) higher in infants hospitalized for bronchiolitis than in infants in primary care for RSV and HRV respectively (p<0.001). CA was higher in samples positive for multiple viruses than in mono-infected or negative samples (p<0.001), and higher in samples positive for RSV (p<0.001) and HRV (p<0.001) than in negative samples. We found a positive correlation between CA and VL for both RSV and HRV. HRV VL was higher in children than in the elderly (p<0.05), but not RSV VL. HRV VL was higher when detected alone than in samples coinfected with RSV-A and with RSV-B. There was a significant increase of RSV-A VL when codetecting with HRV (p=0.001) and when co-detecting with RSV-B+HRV versus RSV-A+ RSV-B (p=0.02)., Conclusions: Many parameters influence the natural history of respiratory viral infections, and quantifying respiratory viral loads can help disentangle their contributions to viral outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Petat, Corbet, Leterrier, Vabret and Ar Gouilh.)

Introduction: Acute respiratory infections (ARIs) are the most common viral infections encountered in primary care settings. The identification of causal viruses is still not available in routine practice. Although new strategies of prevention are being identified, knowledge of the relationships between respiratory viruses remains limited., Materials and Methods: ECOVIR was a multicentric prospective study in primary care, which took place during two pre-pandemic seasons (2018-2019 and 2019-2020). Patients presenting to their General practitioner (GP) with ARIs were included, without selecting for age or clinical conditions. Viruses were detected on nasal swab samples using a multiplex Polymerase Chain Reaction test focused on 17 viruses [Respiratory Syncytial Virus-A (RSV-A), RSV-B, Rhinovirus/Enterovirus (HRV), human Metapneumovirus (hMPV), Adenovirus (ADV), Coronaviruses (CoV) HKU1, NL63, 229E, OC43, Influenza virus (H1 and H3 subtypes), Influenza virus B, Para-Influenza viruses (PIVs) 1-4, and Bocavirus (BoV)]., Results: Among the 668 analyzed samples, 66% were positive for at least one virus, of which 7.9% were viral codetections. The viral detection was negatively associated with the age of patients. BoV, ADV, and HRV occurred more significantly in younger patients than the other viruses ( p  < 0.05). Codetections were significantly associated with RSV, HRV, BoV, hMPV, and ADV and not associated with influenza viruses, CoV, and PIVs. HRV and influenza viruses were negatively associated with all the viruses. Conversely, a positive association was found between ADV and BoV and between PIVs and BoV., Conclusion: Our study provides additional information on the relationships between respiratory viruses, which remains limited in primary care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Petat, Schuers, Marguet, Humbert, Le Bas, Rabiaza, Corbet, Leterrier, Vabret and Ar Gouilh.)

Competing Interests: Competing interests: None declared.

Acute respiratory infections (ARIs) need to be better understood and treated, as they are critical to public health, especially during crises such as the SARS-CoV2 pandemic. These are the most abundant infections in the general population and are seen primarily in primary care by general practitioners (GPs). Many different viruses are involved, according to epidemic variations. Viral co-detections account for a significant proportion of ARIs in hospital cohorts. The objective of the ECOVIR cohort was to study viral co-detections by setting up a biobank of respiratory tract samples from patients consulting their general practitioner for ARI symptoms. We report here on the course of the study: the design, the conduct, and the difficulties encountered. ECOVIR (Etude des CO-detections VIrales dans les prélèvements Respiratoires) was a prospective, multicenter cohort conducted in France during two epidemic seasons (2018-2019 and 2019-2020). We recruited GPs. Each GP investigator (GPI) saw patients weekly for examination, clinical data collection, and nasopharyngeal swabbing. Each sample was sent to the virology unit for biobanking and molecular analysis. Clinical and sociodemographic data were collected 7 days after inclusion. ECOVIR involved 36 GPIs. Patients with symptoms of an ARI were included ( n = 685). The median number of inclusions was 16 patients per GPI over both seasons (IC 25-75% [4.75; 27]). Patients aged 18 to 64 years were the most numerous (57%), followed by children (30%), and the elderly (13% over 65 years). This age distribution emphasizes the young adult and middle-aged population. Residents participated in the project and called patients on day 7 to obtain clinical and sociodemographic data. Our study triggered the creation of an original network, which plans to establish a functional link between research and primary health care. Primary care is unfortunately poorly represented in research protocols, particularly in respiratory infections, even though it is a cornerstone of our French health care system, as demonstrated every day in this period of crisis., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Over two years (2012-2014), 719 nasopharyngeal samples were collected from 6-week- to 12-month-old infants presenting at the emergency department with moderate to severe acute bronchiolitis. Viral testing was performed, and we found that 98% of samples were positive, including 90% for respiratory syncytial virus, 34% for human rhino virus, and 55% for viral co-detections, with a predominance of RSV/HRV co-infections (30%). Interestingly, we found that the risk of being infected by HRV is higher in the absence of RSV, suggesting interferences or exclusion mechanisms between these two viruses. Conversely, coronavirus infection had no impact on the likelihood of co-infection involving HRV and RSV. Bronchiolitis is the leading cause of hospitalizations in infants before 12 months of age, and many questions about its role in later chronic respiratory diseases (asthma and chronic obstructive pulmonary disease) exist. The role of virus detection and the burden of viral codetections need to be further explored, in order to understand the physiopathology of chronic respiratory diseases, a major public health issue.

In cystic fibrosis (CF), Pseudomonas aeruginosa ( Pa ) colonizes the lungs, leading to chronic inflammation of the bronchial epithelium. ChaC glutathione-specific γ-glutamylcyclotransferase 1 ( CHAC1 ) mRNA is differentially expressed in primary human airway epithelial cells from bronchi (hAECBs) from patients with CF and healthy patients at baseline and upon infection with Pa . CHAC1 degrades glutathione and is associated with ER stress and apoptosis pathways. In this study, we examined the roles of CHAC1 in the inflammatory response and apoptosis in lung epithelial cells. First, we confirmed by reverse transcription quantitative polymerase chain reaction that CHAC1 mRNA was overexpressed in hAECBs from patients without CF compared with the expression in hAECBs from patients with CF upon Pa (PAK strain) infection. Moreover, the Pa virulence factors LPS and flagellin were shown to induce CHAC1 expression in cells from patients without CF. Using NCI-H292 lung epithelial cells, we found that LPS-induced CHAC1 mRNA expression was PERK-independent and involved ATF4. Additionally, using CHAC1 small interfering RNA, we showed that reduced CHAC1 expression in the context of LPS and flagellin stimulation was associated with modulation of inflammatory markers and alteration of NF-κB signaling. Finally, we showed that Pa was not able to induce apoptosis in NCI-H292 cells. Our results suggest that CHAC1 is involved in the regulation of inflammation in bronchial cells during Pa infection and may explain the excessive inflammation present in the respiratory tracts of patients with CF.