Bronchial epithelia from adults and children: SARS-CoV-2 spread via syncytia formation and type III interferon infectivity restriction.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections initiate in the bronchi of the upper respiratory tract and are able to disseminate to the lower respiratory tract, where infections can cause an acute respiratory distress syndrome with a high degree of mortality in elderly patients. We used reconstituted primary bronchial epithelia from adult and child donors to follow the SARS-CoV-2 infection dynamics. We show that, in epithelia from adult donors, infections initiate in multiciliated cells and spread within 24 to 48 h throughout the whole epithelia. Syncytia formed of ciliated and basal cells appeared at the apical side of the epithelia within 3 to 4 d and were released into the apical lumen, where they contributed to the transmittable virus dose. A small number of reconstituted epithelia were intrinsically more resistant to virus infection, limiting virus spread to different degrees. This phenotype was more frequent in epithelia derived from children versus adults and correlated with an accelerated release of type III interferon. Treatment of permissive adult epithelia with exogenous type III interferon restricted infection, while type III interferon gene knockout promoted infection. Furthermore, a transcript analysis revealed that the inflammatory response was specifically attenuated in children. Taken together, our findings suggest that apical syncytia formation is an underappreciated source of virus propagation for tissue or environmental dissemination, whereas a robust type III interferon response such as commonly seen in young donors restricted SARS-CoV-2 infection. Thus, the combination of interferon restriction and attenuated inflammatory response in children might explain the epidemiological observation of age-related susceptibility to COVID-19.

Bronchial Remodeling-based Latent Class Analysis Predicts Exacerbations in Severe Preschool Wheezers.

Rationale: Children with preschool wheezing represent a very heterogeneous population with wide variability regarding their clinical, inflammatory, obstructive, and/or remodeling patterns. We hypothesized that assessing bronchial remodeling would help clinicians to better characterize severe preschool wheezers. Objectives: The main objective was to identify bronchial remodeling-based latent classes of severe preschool wheezers. Secondary objectives were to compare cross-sectional and longitudinal clinical and biological data between classes and to assess the safety of bronchoscopy. Methods: This double-center prospective study (NCT02806466) included severe preschool wheezers (1-5 yr old) requiring fiberoptic bronchoscopy. Bronchial remodeling parameters (i.e., epithelial integrity, reticular basement membrane [RBM] thickness, mucus gland, fibrosis and bronchial smooth muscle [BSM] areas, the density of blood vessels, and RBM-BSM distance) were assessed and evaluated by latent class analysis. An independent cohort of severe preschool wheezers (NCT04558671) was used to validate our results. Measurements and Main Results: Fiberoptic bronchoscopy procedures were well tolerated. A two-class model was identified: Class BR1 was characterized by increased RBM thickness, normalized BSM area, the density of blood vessels, decreased mucus gland area, fibrosis, and RBM-BSM distance compared with Class BR2. No significant differences were found between classes in the year before fiberoptic bronchoscopy. By contrast, Class BR1 was associated with a shorter time to first exacerbation and an increased risk of both frequent (3 or more) and severe exacerbations during the year after bronchoscopy in the two cohorts. Conclusions: Assessing bronchial remodeling identified severe preschool wheezers at risk of frequent and severe subsequent exacerbations with a favorable benefit to risk ratio.

Rhinovirus infection of bronchial epithelium induces specific bronchial smooth muscle cell migration of severe asthmatic patients.

BACKGROUND: Patients with severe asthma show an increase in both exacerbation frequency and bronchial smooth muscle (BSM) mass. Rhinovirus (RV) infection of the bronchial epithelium (BE) is the main trigger of asthma exacerbations. Histological analysis of biopsies shows that a close connection between BE and hypertrophic BSM is a criterion for severity of asthma. OBJECTIVE: We hypothesized that RV infection of BE specifically increases BSM-cell migration from patients with asthma. METHODS: Serum samples, biopsies, or BSM cells were obtained from 86 patients with severe asthma and 31 subjects without asthma. BE cells from subjects without asthma were cultured in an air-liquid interface and exposed to RV-16. Migration of BSM cells was assessed in response to BE supernatant using chemotaxis assays. Chemokine concentrations were analyzed by transcriptomics and ELISAs. Immunocytochemistry, western blotting, and flow cytometry were used to quantify CXCR3 isoform distribution. CXCR3 downstream signaling pathways were assessed by calcium imaging and western blots. RESULTS: BSM cells from patients with severe asthma specifically migrated toward RV-infected BE, whereas those from subjects without asthma did not. This specific migration is driven by BE C-X-C motif chemokine ligand 10, which was increased in vitro in response to RV infection as well as in vivo in serum from exacerbating patients with severe asthma. The mechanism is related to both decreased expression and activation of the CXCR3-B-specific isoform in BSM cells from those with severe asthma. CONCLUSIONS: We have demonstrated a novel mechanism of BSM remodeling in patients with severe asthma following RV exacerbation. This study highlights the C-X-C motif chemokine ligand 10/CXCR3-A axis as a potential therapeutic target in severe asthma.

Mitochondria are involved in bronchial smooth muscle remodeling in severe preschool wheezers.

BACKGROUND: Bronchial remodeling is a key feature of asthma that is already present in preschoolers with wheezing. Moreover, bronchial smooth muscle (BSM) remodeling at preschool age is predictive of asthma at school age. However, the mechanism responsible for BSM remodeling in preschoolers with wheezing remains totally unknown. In contrast, in adult asthma, BSM remodeling has been associated with an increase in BSM cell proliferation related to increased mitochondrial mass and biogenesis triggered by an altered calcium homeostasis. Indeed, BSM cell proliferation was decreased in vitro by the calcium channel blocker gallopamil. OBJECTIVE: Our aim was to investigate the mechanisms involved in BSM cell proliferation in preschoolers with severe wheezing, with special attention to the role of mitochondria and calcium signaling. METHODS: Bronchial tissue samples obtained from 12 preschool controls without wheezing and 10 preschoolers with severe wheezing were used to measure BSM mass and establish primary BSM cell cultures. BSM cell proliferation was assessed by manual counting and flow cytometry, ATP content was assessed by bioluminescence, mitochondrial respiration was assessed by using either the Seahorse or Oroboros technique, mitochondrial mass and biogenesis were assessed by immunoblotting, and calcium response to carbachol was assessed by confocal microscopy. The effect of gallopamil was also evaluated. RESULTS: BSM mass, cell proliferation, ATP content, mitochondrial respiration, mass and biogenesis, and calcium response were all increased in preschoolers with severe wheezing compared with in the controls. Gallopamil significantly decreased BSM mitochondrial biogenesis and mass, as well as cell proliferation. CONCLUSION: Mitochondria are key players in BSM cell proliferation in preschoolers with severe wheezing and could represent a potential target to treat BSM remodeling at an early stage of the disease.

Reduced Intestinal Inflammation With Lumacaftor/Ivacaftor in Adolescents With Cystic Fibrosis.

A chronic intestinal inflammation may occur in patients with cystic fibrosis (CF), while no therapeutic management is proposed. Although Lumacaftor/Ivacaftor is well-known to modulate the defective cystic fibrosis transmembrane conductance regulator (CFTR) protein in lungs, no data are available on the impact of this treatment on CF intestinal disorders. We, therefore, investigated the evolution of intestinal inflammation after initiation of Lumacaftor/Ivacaftor in CF adolescents (median of follow-up: 336 days [IQR: 278;435]). Median fecal calprotectin concentrations decreased significantly after Lumacaftor/Ivacaftor initiation (102 µg/g [IQR: 69-210]) compared with the baseline (713 µg/g (IQR:148-852), P = 0.001). To our knowledge, this study showed for the first time that CF-related intestinal inflammation is improved by Lumacaftor/Ivacaftor treatment.

Home-spirometry exacerbation profiles in children with cystic fibrosis.

BACKGROUND: Pulmonary exacerbations (PEx) are strong predictors of respiratory disease progression in children with cystic fibrosis (CwCF) and may be associated with persistent decreased lung function after acute management. Telemonitoring devices can be used for early detection and monitoring of PEx, but its utility is debated. RESEARCH QUESTION: Which symptoms and telemonitoring spirometry characterics are related to outcome dynamics following initial PEx management? METHODS: This retrospective study included CwCF followed at Bordeaux University Hospital, France. All severe PEx episodes treated with intravenous (IV) antibiotics (ATB) between 1 January 2017 and 31 December 2021 in CwCF using home telemonitoring were analyzed. Symptoms and home spirometry data were collected 45 days before and up to 60 days after each IV ATB course. We defined three response profiles based on terciles of baseline forced expiratory volume in 1 s (FEV1 ) recovery. RESULTS: A total of 346 IV ATB courses for PEx were administered to 65 CwCF during the study period. The drop in FEV1 became significant 8 days before IV ATB initiation. Forty-one percent of IV ATB courses failed to restore baseline FEV1 . The magnitude of FEV1 drop and a greater delay in the initiation of treatment correlated with a low response level. On the 14th day of the IV treatment, a FEV1 recovery less than 94% of baseline was associated with a nonresponder profile. INTERPRETATION: Home spirometry may facilitate the early recognition of PEx to implement earlier interventions. This study also provides an outcome lung function threshold which identifies low responders to IV ATB.

Adherence, reliability, and variability of home spirometry telemonitoring in cystic fibrosis.

Introduction: Forced spirometry is the gold standard to assess lung function, but its accessibility may be limited. By contrast, home spirometry telemonitoring allows a multi-weekly lung function follow-up but its real-life adherence, reliability, and variability according to age have been poorly studied in patients with CF (PwCF). We aimed to compare real-life adherence, reliability and variability of home spirometry between children, teenagers and adults with CF. Methods: This real-life observational study included PwCF followed for six months in whom lung function (i.e, forced expiratory volume maximum in 1 s (FEV1), forced vital capacity (FVC), forced mid-expiratory flow (FEF) and FEV1/FVC ratio) was monitored by both conventional and home spirometry between July 2015 and December 2021. The adherence, reliability and variability of home spirometry was assessed in all PwCF and compared between children (<12years old), teenagers (12-18 years old) and adults. Results: 174 PwCF were included (74 children, 43 teenagers and 57 adults). Home spirometry was used at least one time per week by 64.1 ± 4.9% PwCF, more frequently in children and teenagers than in adults (79.4 ± 2.9%, 69.2 ± 5.5% and 40.4 ± 11.5% respectively). The reliability to conventional lung function testing was good for all assessed parameters (e.g., FEV1: r = 0.91, p < 0.01) and the variability over the 6 months of observation was low (FEV1 coefficient of variation = 11.5%). For each parameter, reliability was better, and the variability was lower in adults than in teenagers than in children. Conclusion: Home spirometry telemonitoring appears to be a reliable tool for multi-weekly lung function follow-up of PwCF.

Nutritional impact of CFTR modulators in children with cystic fibrosis.

Background: Nutritional status is a major prognostic factor for breathing and the survival of patients with cystic fibrosis (CF). Since 2012, the development of CFTR modulators has considerably transformed the outcome of this disease. Indeed, both lung function and body mass index are improved by CFTR modulators, such as Lumacaftor/Ivacaftor. However, few data exist regarding the outcome of nutritional intakes under Lumacaftor/Ivacaftor. Methods: We conducted a prospective single-center study in children with CF treated with Lumacaftor/Ivacaftor to evaluate their nutritional intake before and after treatment. Results: Thirty-four children were included in this study, with a median age of 12.4 years [11.9; 14.7]. There was no significant improvement in weight, height or BMI. Patients' total energy intake was not significantly changed with Lumacaftor/Ivacaftor, while carbohydrate intakes decreased significantly. We found that blood levels of vitamin E and Selenium were significantly increased under Lumacaftor/Ivacaftor, without a significant increase in supplementation. In patients with a BMI Z-score < 0 at treatment initiation, there was a significant improvement in weight and BMI Z-score, while TEI and carbohydrate intakes were significantly lower. Conclusion: We showed that treatment with Lumacaftor/Ivacaftor improved the nutritional status of patients without necessarily being associated with an increase in nutritional intake. Although these data need to be confirmed in larger cohorts, they support the hypothesis that weight gain under modulators is multifactorial, and may be related to a decrease in energy expenditure or an improvement in absorption.

Dietary intake assessment in children with cystic fibrosis using 3-day food diaries: a single-centre study.

Background: Malnutrition is both a feature and major cause of morbidity in cystic fibrosis (CF). Therefore, nutritional management is an essential element of patient care. In 2016, an international guideline for nutritional management in patients with CF was published. In light of these recommendations, the aim of this study was to investigate the dietary intake of children with CF at the University Hospital of Bordeaux. Methods: We conducted a retrospective study at the Paediatric CF Centre of the University Hospital of Bordeaux. Patients aged 2-18 years with CF who completed a 3-day food diary at home between January 2015 and December 2020 were included. Results: A total of 130 patients, with a median age of 11.8 [interquartile range (IQR): 8.3; 13.4] years, were included. The median Z-score for BMI was -0.35 (IQR: -0.9; 0.2) and 20% of the patients had a Z-score for BMI < -1. Recommended total energy intakes were achieved in 53% of the patients, particularly those with nutritional support. Recommended protein intake was met in 28% of the cases, while fat and carbohydrate intakes were met in 54%. Vitamin and micronutrient levels were normal in 80% of the patients, with the exception of vitamin K, which was within the therapeutic range in only 42% of the cases. Conclusion: Recommended nutritional targets are difficult to achieve in patients with CF, and providing nutritional support during follow-up remains a challenge.

European Respiratory Society International Congress 2021: highlights from best-abstract awardees.

This article provides an overview of some of the highlights of the @EuroRespSoc Congress 2021 from the perspective of the best-abstract awardees of the ERS Assemblies @EarlyCareerERS @OrphaLung https://bit.ly/3JCjHYS.

Cellular and molecular mechanisms of NiONPs toxicity on eel hepatocytes HEPA-E1: An illustration of the impact of Ni release from mining activity in New Caledonia.

Anthropic activities such as open pit mining, amplify the natural erosion of metals contained in the soils, particularly in New Caledonia, leading to atmospheric emission of nickel oxide nanoparticles (NiONPs). These particles are produced during extraction end up in aquatic ecosystems through deposition or leaching in the rivers. Despite alarming freshwater Ni concentrations, only few studies have focused on the cellular and molecular mechanisms of NiONPs toxicity on aquatic organisms and particularly on eels. Those fish are known to be sensitive to metal contamination, especially their liver, which is a key organ for lipid metabolism, detoxification and reproduction. The objective of this study was to assess in vitro the cytotoxic effects of NiONPs on Anguilla japonica hepatocytes, HEPA-E1. HEPA-E1 were exposed to NiONPs (0.5-5 µg/cm2) for 4 or 24 h. Several endpoints were studied: (i) viability, (ii) ROS production, SOD activity and selected anti-oxidant genes expression, (iii) inflammation, (iv) calcium signalling, (v) mitochondrial function and (vi) apoptosis. The results evidenced that NiONPs induce a decrease of cell viability and an increase in oxidative stress with a significant superoxide anion production. An increase of mitochondrial calcium concentration and a decrease of mitochondrial membrane potential were observed, leading to apoptosis. These results underline the potential toxic impact of NiONPs on eels living in mining areas. Therefore, eel exposure to NiONPs can affect their migration and reproduction in New Caledonia.

NiONPs-induced alteration in calcium signaling and mitochondrial function in pulmonary artery endothelial cells involves oxidative stress and TRPV4 channels disruption.

In New Caledonia, anthropic activities, such as mining, increase the natural erosion of soils in nickel mines, which in turn, releases nickel oxide nanoparticles (NiONPs) into the atmosphere. Pulmonary vascular endothelial cells represent one of the primary targets for inhaled nanoparticles. The objective of this in vitro study was to assess the cytotoxic effects of NiONPs on human pulmonary artery endothelial cells (HPAEC). Special attention will be given to the level of oxidative stress and calcium signaling, which are involved in the physiopathology of cardiovascular diseases. HPAEC were exposed to NiONPs (0.5-150 µg/cm2) for 4 or 24 h. The following different endpoints were studied: (i) ROS production using CM-H2DCF-DA probe, electron spin resonance, and MitoSOX probe; the SOD activity was also measured (ii) calcium signaling with Fluo4-AM, Rhod-2, and Fluo4-FF probes; (iii) inflammation by IL-6 production and secretion and, (iv) mitochondrial dysfunction and apoptosis with TMRM and MitoTracker probes, and AnnexinV/PI. Our results have evidenced that NiONPs induced oxidative stress in HPAEC. This was demonstrated by an increase in ROS production and a decrease in SOD activity, the two mechanisms seem to trigger a pro-inflammatory response with IL-6 secretion. In addition, NiONPs exposure altered calcium homeostasis inducing an increased cytosolic calcium concentration ([Ca2+]i) that was significantly reduced by the extracellular calcium chelator EGTA and the TRPV4 inhibitor HC-067047. Interestingly, exposure to NiONPs also altered TRPV4 activity. Finally, HPAEC exposure to NiONPs increased intracellular levels of both ROS and calcium ([Ca2+]m) in mitochondria, leading to mitochondrial dysfunction and HPAEC apoptosis.

The lower respiratory airway wall in children in health and disease.

Alone or in association with other lung or thorax component disorders, the airway wall (AWW) remains one of the most frequently involved elements in paediatric lung diseases. A myriad of AWW disorders will present with similar symptomatology. It is thus important for the clinician to reappraise the normal development and structure of the AWW to better understand the underlying disease patterns. We herein provide an overview of the structure of the AWW and a description of its development from the fetal period to adulthood. We also detail the most common AWW changes observed in several acute and chronic respiratory disorders as well as after cigarette smoke or chronic pollution exposure. We then describe the relationship between the AWW structure and lung function. In addition, we present the different ways of investigating the AWW structure, from biopsies and histological analyses to the most recent noninvasive airway (AW) imaging techniques. Understanding the pathophysiological processes involved in an individual patient will lead to the judicious choice of nonspecific or specific personalised treatments, in order to prevent irreversible AW damage.

Respiratory rehabilitation for Covid-19 related persistent dyspnoea: A one-year experience.

BACKGROUND: Growing consideration is emerging regarding the burden of persisting sequelae after SARS-CoV-2 infection. Out-patients exhibiting long Covid may benefit from ambulatory rehabilitation which is, to date, poorly documented. METHODS: A longitudinal follow-up over a one-year period was conducted in two ambulatory rehabilitation structures in order to describe the characteristics of real-life patients referred with Covid-19 sequelae and their evolution over the course of rehabilitation. RESULTS: 39 consecutive patients were included from April 1st, 2020 to April 1st, 2021. Patients were middle-aged (48 ± 15yr), without comorbidities, and mostly mild to moderate SARS-CoV-2 infection (25(64%) not requiring hospitalisation). Rehabilitation referral was considered with a median delay of 73[34-178] days after disease onset. Most prevalent symptoms were dyspnoea (n = 35(90%)) and fatigue (n = 30(77%)). Hyperventilation syndrome was highly frequent (n = 12(34%)). 29(74%) patients presented with prolonged functional sequelae, which was associated with younger age (43 ± 14 vs. 50 ± 10yr; p = 0.002), greater prevalence of hyperventilation syndrome (n = 12(41%) vs. 0(0%); p = 0.255) and poorer quality of life (VQ-11; 31 ± 10 vs. 23 ± 9; p = 0.030). Over the course of rehabilitation, exertional dyspnoea, 6-min walking distance, 3-min sit-to-stand test, hyperventilation syndrome prevalence and quality of life significantly improved. CONCLUSION: Hyperventilation is frequent in long Covid and may explain persistent dyspnoea as well as altered quality of life. Our data support screening of hyperventilation syndrome and functional impairment in mild Covid-19 out-patients as both of these components may improve with ambulatory rehabilitation.

Long-Term Outcomes in Real Life of Lumacaftor-Ivacaftor Treatment in Adolescents With Cystic Fibrosis.

Background: The combination of the CFTR corrector lumacaftor (LUM) and potentiator ivacaftor (IVA) has been labeled in France since 2015 for F508del homozygote cystic fibrosis (CF) patients over 12 years. In this real-life study, we aimed (i) to compare the changes in lung function, clinical (e.g., body mass index and pulmonary exacerbations) and radiological parameters, and in sweat chloride concentration before and after initiation of LUM/IVA treatment; (ii) to identify factors associated with response to treatment; and (iii) to assess the tolerance to treatment. Materials and Methods: In this tri-center, non-interventional, and observational cohort study, children (12-18 years old) were assessed prospectively during the 2 years of therapy, and retrospectively during the 2 years preceding treatment. Data collected and analyzed for the study were exclusively extracted from the medical electronic system records of the patients. Results: Forty adolescents aged 12.0-17.4 years at LUM/IVA initiation were included. The lung function decreased significantly during and prior to treatment and increased after LUM/IVA initiation, becoming significant after 2 years of treatment. LUM/IVA significantly improved the BMI Z-score and sweat chloride concentration. By contrast, there was no significant change in exacerbation rates, antibiotic use, or CT scan scores. Age at LUM/IVA initiation was lower in good responders and associated with greater ppFEV1 change during the 2 years of treatment. LUM/IVA was well-tolerated. Conclusion: In F508del homozygote adolescents, real-life long-term LUM/IVA improved the ppFEV1 trajectory, particularly in the youngest patients, nutritional status, and sweat chloride concentration but not exacerbation rates or radiological scores. LUM/IVA was generally well-tolerated and safe.

Nursery Assistants' Performance and Knowledge on Cardiopulmonary Resuscitation: Impact of Simulation-Based Training.

Background: Child cardiac arrest is rare, but more frequent among infants, requiring immediate cardiopulmonary resuscitation (CPR). Many studies have reported that simulation-based training (SBT) increased CPR performance of healthcare providers. However, the CPR performance of laypeople using basic life support remains poorly known. The aim of this study was to assess nursery assistants' (non-healthcare providers) CPR performance and knowledge, before and after SBT. Methods: The study was carried out from January to June 2018 in the city of Poitiers, France. Two teaching sessions (T1 and T2) and two evaluation sessions (E1 and E2) were performed. Performance in infant CPR on a manikin at E1 and E2 were videotaped and assessed automatically with Resusci Baby QCPR® and a SimPad PLUS SkillReporter (QCPR Global Score and skills) and by an observer using an original CPR performance checklist (MCPR Global-Score and skills). Nursery assistant's CPR knowledge was assessed by a questionnaire at the beginning and the end of the session T1, E1, and E2. Results: Twenty-Seven nursery assistants over 30 contacted were included. There was an improvement between E1 and E2 in QCPR Global-Score (E1: 42.4 ± 23.6 vs. E2: 55.1 ± 23.7%, p = 0.032), MCPR Global-Score (E1: 50.0+11.9 vs. E2: 72.3+8.5%; p < 0.001) and theoretical knowledge with score (over 45) of 16.9+5.4 before T1 and 35.2+2.7 after E2, respectively (p < 0.001). The improvement mainly concerned QCPR and MCPR compression steps scores. MCPR Global-Score was strongly correlated to QCPR Global-Score (r = 0.61; p < 0.01) and predictive to CPR quality determined by QCPR Global-Score (AUC = 0.77; p < 0.01) with a high sensitivity and negative predictive values. Moreover, these improvements were maintained 2 months after training with no difference between scores obtained by the three groups 15, 30, or 60 days after simulation-based training session T2. Conclusion: SBT could significantly improve knowledge and skills in infant CPR management by nursery assistants especially for chest compression. CPR performance checklist appeared as an interesting tool to assess CPR performance quality.

The Gut-Lung Axis in Health and Respiratory Diseases: A Place for Inter-Organ and Inter-Kingdom Crosstalks.

The gut and lungs are anatomically distinct, but potential anatomic communications and complex pathways involving their respective microbiota have reinforced the existence of a gut-lung axis (GLA). Compared to the better-studied gut microbiota, the lung microbiota, only considered in recent years, represents a more discreet part of the whole microbiota associated to human hosts. While the vast majority of studies focused on the bacterial component of the microbiota in healthy and pathological conditions, recent works have highlighted the contribution of fungal and viral kingdoms at both digestive and respiratory levels. Moreover, growing evidence indicates the key role of inter-kingdom crosstalks in maintaining host homeostasis and in disease evolution. In fact, the recently emerged GLA concept involves host-microbe as well as microbe-microbe interactions, based both on localized and long-reaching effects. GLA can shape immune responses and interfere with the course of respiratory diseases. In this review, we aim to analyze how the lung and gut microbiota influence each other and may impact on respiratory diseases. Due to the limited knowledge on the human virobiota, we focused on gut and lung bacteriobiota and mycobiota, with a specific attention on inter-kingdom microbial crosstalks which are able to shape local or long-reached host responses within the GLA.

Increased Fecal Calprotectin Is Associated with Worse Gastrointestinal Symptoms and Quality of Life Scores in Children with Cystic Fibrosis.

In cystic fibrosis (CF), cystic fibrosis transmembrane regulator (CFTR) dysfunction leads to digestive disorders that promote intestinal inflammation and dysbiosis enhancing gastrointestinal symptoms. In pancreatic insufficiency CF patients, both intestinal inflammation and dysbiosis, are associated with an increase in the fecal calprotectin (FC) level. However, associations between the FC level, gastrointestinal symptoms, and quality of life (QoL) remain poorly studied. We aimed to assess such associations in pancreatic insufficiency CF children. The FC level was measured in pancreatic insufficiency CF children's stool samples. Children and their parents completed two questionnaires: The Gastrointestinal Symptoms Scales 3.0-PedsQLTM and the Quality of Life Pediatric Inventory 4.0-PedsQLTM. Lower scores indicated worse symptomatology or QoL. Thirty-seven CF children were included. A FC level above 250 µg/g was associated with worse gastrointestinal symptoms and QoL scores. The FC level was inversely correlated with several gastrointestinal scores assessed by children (i.e., Total, "Heart Burn Reflux", "Nausea and Vomiting", and "Gas and Bloating"). Several QoL scores were correlated with gastrointestinal scores. The FC level was weakly associated with clinical parameters. Some gastrointestinal and QoL scores were related to disease severity associated parameters. In CF, the FC level, biomarker previously related to intestinal inflammation and dysbiosis, was associated with worse digestive symptoms and QoL scores.