Cystic fibrosis in Europe: improved lung function and longevity - reasons for cautious optimism, but challenges remain.

BACKGROUND: Prognosis and disease severity in cystic fibrosis (CF) are linked to declining lung function. To characterise lung function by the number of adults in countries with different levels of Gross National Income (GNI), data from the European Cystic Fibrosis Society Patient Registry were utilised. METHODS: Annual data including age, forced expiratory volume in 1 s (FEV1), anthropometry, genotype, respiratory cultures and CF-related diabetes (CFRD) were retrieved between 2011 and 2021. All countries were stratified into GNI per capita to reflect differences within Europe. RESULTS: A consistent improvement in FEV1 % pred and survival was observed among the 47 621 people with CF (pwCF), including subjects with chronic Pseudomonas aeruginosa infection, CFRD and/or undernutrition. Mean values of FEV1 % pred changed from 85% to 94.2% for children and from 63.6% to 74.7% for adults. FEV1 % pred further increased among those carrying the F508del mutation in 2021, when elexacaftor/tezacaftor/ivacaftor was available. The number of adult pwCF increased from 13 312 in 2011 to 21 168 in 2021, showing a 60% increase. PwCF living in European lower income countries did not demonstrate a significant annual increase in FEV1 % pred or in the number of adults. CONCLUSION: This pan-European analysis demonstrates a consistent improvement in FEV1 % pred, number of adult pwCF and survival over the last decade only in European higher and middle income countries. Urgent action is needed in the lower income countries where such improvement was not observed. The notable improvement observed in pwCF carrying the F508del mutation emphasises the need to develop treatments for all CF mutations.

Physical activity and quality of life in children with well-controlled asthma.

BACKGROUND: Asthma is the most common disease in childhood. Appropriate management and programs encouraging exercise enable children to enjoy a good quality of life (QoL). OBJECTIVE: To assess the association between lung function, physical activity (PA), and QoL in children with well-controlled asthma. METHODS: Fifty-four children aged 7-14 years attending a Pediatric Asthma Clinic were included. All children underwent spirometry and completed three self-administered validated questionnaires: The Godin Leisure-Time Exercise Questionnaire (GLTEQ), the ACT (Asthma Control Test), and the DISABKIDS for QoL. RESULTS: Mean age of the study population was 11.43(±2.1), BMI, kg/m2 (20.8 ± 3.9), FVCpp (97.1% ±12.4), and FEV1pp (99.7% ±12.43), ACT (23.4 ± 3). The GLTEQ revealed that only 3% of the studied population presented satisfactory activity, while 86% were sedentary. Both FEV1pp, and PA were significantly correlated to the children's QoL ((r2: 0.55, p:0.0001), and (r2:0.45, p:0.003), respectively). CONCLUSIONS: Despite reasonable asthma control, the children exhibited low physical activity levels, which negatively correlated to their QoL. Families of asthmatic children should be educated to highlight the benefits of exercise and increase the PA of their children.

Hellenic registry of patients with home mechanical ventilation (HR-HMV): profiling sleep Apnea-Hypopnea syndrome patients across Greece.

BACKGROUND: Chronic respiratory conditions are a prominent public health issue and thus, building a patient registry might facilitate both policy decision making and improvement of clinical management processes. Hellenic Registry of patients with Home Mechanical Ventilation (HR-HMV) was initiated in 2017 and a web-based platform is used to support patient data collection. Eighteen hospital departments (including sleep labs) across Greece participate in this initiative, focusing on recording data for both children and adult patients supported by mechanical ventilation at home, including patients with Sleep Apnea-Hypopnea Syndrome (SAHS) under Positive Airway Pressure (PAP) therapy. METHODS: The HR-HMV initiative ultimately aims to provide a database for evidence-based care and policy making in this specific domain. To this end, a web information system was developed and data were manually collected by clinics and hospital departments. Legal and privacy issues (such as General Data Protection Rule compliance and technical information security measures) have been considered while designing the web application. Based on the collected data, an exploratory statistical report of SAHS patients in Greece is presented. RESULTS: Eleven out of the eighteen participating clinics and hospital departments have contributed with data by the time of the current study. More than 5000 adult and children patient records have been collected so far, the vast majority of which (i.e., 4900 patients) diagnosed with SAHS. CONCLUSION: The development and maintenance of patient registries is a valuable tool for policy decision making, observational/epidemiological research and beyond (e.g., health technology assessment procedures). However, as all data collection and processing approaches, registries are also related with potential biases. Along these lines, strengths and limitations must be considered when interpreting the collected data, and continuous validation of the collected clinical data per se should be emphasized. Especially for Greece, where the lack of national registries is eminent, we argue that HR-HMV could be a useful tool for the development and the update of related policies regarding the healthcare services for patients with home mechanical ventilation support and SAHS patients, which could be useful for related initiatives at a European level as well.

Effects of a Long-Term Wearable Activity Tracker-Based Exercise Intervention on Cardiac Morphology and Function of Patients with Cystic Fibrosis.

Several studies have shown that patients with cystic fibrosis (CF), even at a young age, have pulmonary and cardiac abnormalities. The main complications are cardiac right ventricular (RV) systolic and/or diastolic dysfunction and pulmonary hypertension, which affects their prognosis. Exercise training (ET) is recommended in patients with CF as a therapeutic modality to improve physical fitness and health-related quality of life. However, questions remain regarding its optimal effective and safe dose and its effects on the patients' cardiac function. The study aimed to provide a wearable activity tracker (WAT)-based ET to promote physical activity in CF patients and assess its effects on cardiac morphology and function. Forty-two stable CF individuals (aged 16.8 ± 3.6 years) were randomly assigned to either the intervention (Group A) or the control group (Group B). Group A participated in a 1-year WAT-based ET program three times per week. All patients underwent a 6-min walking test (6-MWT) and an echocardiographic assessment focused mainly on RV anatomy and function at the baseline and the end of the study. RV systolic function was evaluated by measuring the tricuspid annular plane systolic excursion (TAPSE), the systolic tricuspid annular velocity (TVS'), the RV free-wall longitudinal strain (RVFWSL), and the right ventricular four-chamber longitudinal strain (RV4CSL). RV diastolic function was assessed using early (TVE) and late (TVA) diastolic transtricuspid flow velocity and their ratio TVE/A. Pulmonary artery systolic pressure (PASP) was also estimated. In Group A after ET, the 6MWT distance improved by 20.6% (p < 0.05), TVA decreased by 17% (p < 0.05), and TVE/A increased by 13.2% (p < 0.05). Moreover, TAPSE, TVS', RVFWSL, and RV4CSL increased by 8.3% (p < 0.05), 9.0% (p < 0.05), 13.7% (p < 0.05), and 26.7% (p < 0.05), respectively, while PASP decreased by 7.6% (p < 0.05). At the end of the study, there was a significant linear correlation between the number of steps and the PASP (r = −0.727, p < 0.01) as well as the indices of RV systolic function in Group A. In conclusion, WAT is a valuable tool for implementing an effective ET program in CF. Furthermore, ET has a positive effect on RV systolic and diastolic function.

The Exeter Activity Unlimited statement on physical activity and exercise for cystic fibrosis: methodology and results of an international, multidisciplinary, evidence-driven expert consensus.

BACKGROUND: The roles of physical activity (PA) and exercise within the management of cystic fibrosis (CF) are recognised by their inclusion in numerous standards of care and treatment guidelines. However, information is brief, and both PA and exercise as multi-faceted behaviours require extensive stakeholder input when developing and promoting such guidelines. METHOD: On 30th June and 1st July 2021, 39 stakeholders from 11 countries, including researchers, healthcare professionals and patients participated in a virtual conference to agree an evidence-based and informed expert consensus about PA and exercise for people with CF. This consensus presents the agreement across six themes: (i) patient and system centred outcomes, (ii) health benefits, iii) measurement, (iv) prescription, (v) clinical considerations, and (vi) future directions. The consensus was achieved by a stepwise process, involving: (i) written evidence-based synopses; (ii) peer critique of synopses; (iii) oral presentation to consensus group and peer challenge of revised synopses; and (iv) anonymous voting on final proposed synopses for adoption to the consensus statement. RESULTS: The final consensus document includes 24 statements which surpassed the consensus threshold (>80% agreement) out of 30 proposed statements. CONCLUSION: This consensus can be used to support health promotion by relevant stakeholders for people with CF.

Efficacy and safety of the combination fluticasone propionate plus salmeterol in asthmatic preschoolers: An observational study.

BACKGROUND: Inhaled Corticosteroids (ICS) are the cornerstone of asthma management in pediatric patients. However, in some cases, asthma is not adequately controlled on ICS alone. Long-acting beta2-agonists (LABA) are one of the available additional therapies but their use has rarely been studied among children younger than 5 years. OBJECTIVE: The aim of this observational study was to evaluate the efficacy and safety of the combination of fluticasone propionate and salmeterol (FP/SA) in asthmatic children younger than 5 years of age. METHODS: A retrospective study of 796 children under the age of 5 years (2.87 ± 1.22 years, 64.2% males), who were treated with FP/SA was conducted. Hospitalization rates, frequency of wheezing, exercise induced asthma, nocturnal wheeze and drug-related side-effects were recorded through children's medical records. RESULTS: The children had previously received short-acting ß2-agonists (73%), ICS (17%), montelukast (1%), and ICS with montelukast (2%). Mean duration of therapy with FP/SA was 12.45 ± 9.14 months. After adjusting for age, gender, and duration of treatment, a 89% reduction was recorded in annual hospitalization rates (from 27.13% before treatment to 3.01% after FP/SA therapy, p < 0.001), a 71% reduction in incidence of exercise-induced asthma (36.8% vs. after 10.6%, p < 0.001), a 81% reduction in nocturnal asthma (33.7% vs. after: 6.4%, p < 0.001), as well as in frequency of wheezing (p < 0.01),. No previous treatment carry-on effect was observed. No major drug-related side-effects occurred in the study group. CONCLUSIONS: Combination therapy (FP/SA) is well-tolerated and highly effective in asthmatic children under the age of 5 years.

Two cases of myositis ossificans in children, after prolonged immobilization.

Myossitis ossificans (MO) is a benign disorder characterized by heterotopic bone formation in skeletal muscle. It is divided in three types, fibrodysplasia ossificans progressive (FOP), myositis ossificans circumscripta or traumatica (MOT) and myositis ossificans without a history of trauma (non traumatic or pseudomalignant MO). Myositis ossificans is extremely rare in children younger than 10 years. We present the clinical and radiological findings of two 5-year-old children with pseudomalignant MO due to prolonged immobilization. Plain x-ray films and CT scan with their characteristic findings of mature bone in the periphery of the lesion with smooth contour and well separated from the bone, enabled us to diagnose the lesion. To the best of our knowledge, no such cases have been reported in the literature.

A "real-life" study on height in prepubertal asthmatic children receiving inhaled steroids.

INTRODUCTION: Asthma is the most common chronic respiratory disease in children and inhaled corticosteroids (ICS) constitute the first line of treatment for these patients. However, the potential growth-inhibiting effect of ICS has often been a cause of concern for both caregivers as well as physicians, and there still remains conflict regarding their safety profile. OBJECTIVE: To assess whether the administration of ICS in low or medium doses is associated with height reduction in prepubertal children. METHODS: We performed a retrospective study to examine the association between ICS treatment and growth deceleration in children with mild persistent asthma. The comparison of height measurements every 6 months from 3 to 8 years of age was conducted among three groups of patients: patients not receiving ICS, patients being treated with low dose of ICS and patients being treated with medium dose of ICS (GINA Guidelines 2015). RESULTS: This study included 284 patients (198 male, 86 female) aged 3-8 years; 75 patients were not receiving ICS, 63 patients were on low-dose ICS and 146 patients were on medium-dose ICS. The measured height every 6 months did not differ significantly (p > 0.05) among the three groups while the difference remained stable (p > 0.05), even when we evaluated males and females separately. CONCLUSIONS: In this "real-life" study we found that long-term treatment with ICS in low or medium doses is not associated with height reduction in prepubertal children with asthma.

Validation study of the pediatric allergic rhinitis quality of life questionnaire.

BACKGROUND: The Paediatric Allergic Rhinitis Quality of Life Questionnaire (Ped-AR-QoL) is the first tool developed for the assessment of health-related quality of life (QoL) in Greek children with allergic rhinitis (AR). OBJECTIVE: The aim of the current study was to validate the child and parent forms of the Ped-AR-QoL in children aged 6-14 years-old who suffered from AR and were followed in a pediatric allergy clinic. METHODS: The Ped-AR-QoL, which was completed by 112 children and their parents, was correlated to the generic QoL questionnaire (Disabkids), which is already valid in Greece for children with chronic disorders, as well as with expert opinions on the severity of disease. RESULTS: The Ped-AR-QoL child and parent forms had very good internal consistency (α values of 0.797 and 0.872, respectively), while there was a moderate positive correlation of the disease-specific questionnaire with most of the subscales of the generic questionnaire. There has been a statistically significant association between the Ped-AR-QoL and the expert perception of disease severity. CONCLUSIONS: The Ped-AR-QoL had very good reliability and convergent validity when compared with the generic Disabkids QoL. The significance of the association between the disease-specific questionnaire and the expert opinion is an important finding validating the questionnaire. The Ped-AR-QoL may become a helpful tool which can be used in everyday clinical practice by clinicians and it may also be used for assessing therapeutic interventions in clinical trials.

Factors associated with FEV1 decline in cystic fibrosis: analysis of the ECFS patient registry.

Pulmonary insufficiency is the main cause of death in cystic fibrosis (CF). We analysed forced expiratory volume in 1 s (FEV1) data of 14,732 patients registered in the European Cystic Fibrosis Society Patient Registry (ECFSPR) database in 2007. We used linear and logistic regressions to investigate associations between FEV1 % predicted and clinical outcomes. Body mass index (BMI), chronic infection by Pseudomonas aeruginosa, pancreatic status and CF-related diabetes (CFRD) showed a statistically significant (all p<0.0001) and clinically relevant effect on FEV1 % pred after adjusting for age. Patients with a lower BMI experience a six-fold increased odds ratio (95% CI 5.0-7.3) of having severe lung disease (FEV1 <40% pred) compared to patients with normal BMI. Being chronically infected with P. aeruginosa increases the odds ratio of severe lung disease by 2.4 (95% CI 2.0-2.7), and patients with pancreatic insufficiency experience a 2.0-fold increased odds ratio (95% CI 1.6-2.5) of severe lung disease compared to pancreatic sufficient patients. Patients with CFRD have a 1.8-fold increased odds ratio (95% CI 1.6-2.2) compared to patients not affected. These potential risk factors for pulmonary disease in patients with CF are to some degree preventable or treatable. We emphasise the importance of their early identification through frequent routine tests, the implementation of infection control measures, and a timely initiation of relevant therapies.

Use of cystic fibrosis inhaled medication before and after elexacaftor/tezacaftor/ivacaftor initiation.

Elexacator/tezacaftor/ivacaftor (ETI) has improved cystic fibrosis (CF) outcomes. A reduction in use of maintenance medication after its initiation has been reported. Seventy-one adult people with CF (PwCF) who are followed in three CF centers and completed one year of treatment with ETI were included in this study. Their use of inhaled dornase-α, colistin, tobramycin, aztreonam and levofloxacin during this period was compared with the corresponding use during one year without ETI, using the Medication Possession Ratio (MPR). MPR was significantly decreased after ETI initiation for dornase-α (67±35% vs 48±40%, p<0.001) and for all four inhaled antibiotics together (62±33% vs 41±37%, p<0.001). The findings of this multi-center, retrospective, study suggest that the initiation of ETI significantly leads to decrease in use of standard inhaled medication in PwCF. The significance of this finding in the course of the disease is yet to be investigated by larger prospective clinical trials.

ESPEN-ESPGHAN-ECFS guideline on nutrition care for cystic fibrosis.

BACKGROUND: Nutritional status is paramount in Cystic Fibrosis (CF) and is directly correlated with morbidity and mortality. The first ESPEN-ESPGHAN-ECFS guidelines on nutrition care for infants, children, and adults with CF were published in 2016. An update to these guidelines is presented. METHODS: The study was developed by an international multidisciplinary working group in accordance with officially accepted standards. Literature since 2016 was reviewed, PICO questions were discussed and the GRADE system was utilized. Statements were discussed and submitted for on-line voting by the Working Group and by all ESPEN members. RESULTS: The Working Group updated the nutritional guidelines including assessment and management at all ages. Supplementation of vitamins and pancreatic enzymes remains largely the same. There are expanded chapters on pregnancy, CF-related liver disease, and CF-related diabetes, bone disease, nutritional and mineral supplements, and probiotics. There are new chapters on nutrition with highly effective modulator therapies and nutrition after organ transplantation.

Drug-resistant tuberculosis in two children in Greece: report of the first extensively drug-resistant case.

Extensively drug-resistant (XDR) tuberculosis (TB) represents a serious and growing problem in both endemic and non-endemic countries. We describe a 2.5-year-old girl with XDR-pulmonary TB and an 18-month-old boy with pre-XDR-central nervous system TB. Patients received individualized treatment with second-line anti-TB agents based on genotypic and phenotypic drug susceptibility testing results. Both children achieved culture conversion 3 months and 1 month after treatment initiation, respectively. The child with XDR-pulmonary TB showed evidence of cure while treatment adverse events were managed without treatment interruption. The child with pre-XDR-central nervous system TB after 6-month hospitalization with multiple infectious complications had a dismal end due to hepatic insufficiency possibly related to anti-TB treatment. This is the first report of children with pre-XDR and XDR TB in Greece, emphasizing the public health dimensions and management complexity of XDR TB.

The role of rigid laryngo-tracheo-bronchoscopy in children with obstructive sleep apnoea: a case series of 65 children.

OBJECTIVE: To assess the role of laryngo-tracheo-bronchoscopy in children with obstructive sleep apnoea by identifying airway abnormalities at surgery, that occur separately or in addition to adenotonsillar hypertrophy, and examining the correlation with respiratory parameters. METHODS: A retrospective study was conducted of children with obstructive sleep apnoea who underwent laryngo-tracheo-bronchoscopy intra-operatively, performed by a single ENT surgeon from February 2016 to July 2019. Pre- and post-operative minimum oxygen saturation, apnoea-hypopnoea index, and oxygen desaturation index were recorded. RESULTS: Sixty-five children were identified; 34 were aged less than three years and 31 were aged three years or more. 77 per cent and 13 per cent respectively had an airway abnormality; the t-test showed a significantly higher mean oxygen desaturation index and lower mean minimum oxygen saturation pre-operatively compared to children without an airway abnormality. CONCLUSION: An update of the surgical pathway for children aged less than three years with obstructive sleep apnoea is required to include laryngo-tracheo-bronchoscopy intra-operatively. A t-test analysis of the pre-operative respiratory parameters suggests that airway abnormalities contribute to obstructive sleep apnoea severity.

Mannitol Challenge to Assess Therapy Response in Asthmatic Children: An Interventional Cohort Study.

Bronchial provocation tests, such as the mannitol challenge, can be performed to identify and quantify the severity of bronchial hyperresponsiveness in asthmatic patients. Studies of the mannitol challenge as a monitoring tool in asthmatic children are limited. Our primary aim was to compare the bronchial hyperresponsiveness to mannitol in treatment-naive asthmatic children between baseline and three months after receiving the indicated asthma prophylaxis. Twenty-three asthmatic patients aged 4-16 years were analyzed in this prospective cohort study. All subjects underwent the mannitol challenge at baseline and after three months of treatment with budesonide ± formoterol. The difference in the provocative dose of mannitol to induce a 15% drop in FEV1 (PD15) between baseline and follow-up, as well as its association with the presence of exercise-induced or nocturnal asthma symptoms, were evaluated. The PD15 value increased significantly post-treatment (228.5 mg [4.50-458.15]; p = 0.04). Independently of the evaluation time point, the PD15 values were significantly lower in the presence of nocturnal asthma symptoms (490 mg [122-635] vs. 635 mg [635-635]; p = 0.03), whereas there was no association between the PD15 value and the presence of exercise-induced asthma (p = 0.73). These results suggest that bronchial hyperresponsiveness to mannitol may be a potential monitoring tool in the pediatric asthmatic population, reflecting therapy response in children receiving prophylactic treatment.

Disease severity of people with cystic fibrosis carrying residual function mutations: Data from the ECFS Patient Registry.

RATIONAL: People with cystic fibrosis carrying residual function (RF) mutations are considered to have a mild disease course. This may influence caregivers and patients on how intensive the treatments should be. OBJECTIVES: Characterize disease severity of patients carrying RF mutations, using the European CF Society Patient Registry (ECFSPR) data. METHODS: Demographic, clinical characteristics, lung function and death probability of patients carrying at least one RF mutation were analyzed and compared to patients homozygous to minimal function mutations (MF). MAIN RESULTS: Of the 44,594 eligible patients (median age 19.5 years, IQR 10-29.8), 6,636 (14.6%) carried RF mutations, and 37,958 (85.1%) MF mutations. Patients carrying RF mutations were older, diagnosed at a later age, had lower sweat chloride at diagnosis and better FEV1pp at each age group. However, their FEV1pp declined with age and rates of chronic Pseudomonas aeruginosa increased with age. A significant number of patients with RF had FEV1pp similar to patients with MF at each age group. 4.5% of RF patients were treated with oxygen and 2.61% had a lung transplant. With increasing age, 26.6% of RF patients were treated with pancreatic enzymes associated with a more severe lung disease. RF patients had shortened life spans, with mortality starting around the age of 20 years. CONCLUSIONS: Patients carrying an RF mutations experience a decline of pulmonary function with age, leading to life-shortening. Standard of care therapies and augmenting CFTR function may improve their survival and quality of life.

Low-frequency oscillometry indices to assess ventilation inhomogeneity in CF patients.

BACKGROUND: The utility of the forced oscillations technique (FOT) in cystic fibrosis (CF) remains uncertain. The aim of this study was to explore the ability of lower-frequency FOT indices, alone and after adjustment for the lung volume, to assess the extent of ventilation inhomogeneity in CF patients with varying disease severity. METHODS: Forty-five children, adolescents, and adults with CF (age 6.9-27 years) underwent spirometry, FOT, and nitrogen multiple-breath washout (N2-MBW) measurements. The respiratory resistance and reactance at 5 Hz (Rrs5 and Xrs5, respectively) were recorded, and a novel FOT index, the specific respiratory conductance (sGrs), was computed as the reciprocal of Rrs5 divided by the functional residual capacity. RESULTS: The sGrs correlated well with the lung clearance index (LCI) (Spearman's r: -.797), whereas the correlation of Rrs5 and Xrs5 with the LCI, albeit significant, was weaker (r: .643 and -.631, respectively). The sGrs emerged as the most robust predictor of LCI regardless of the severity of lung disease, as reflected by patients' age and lung function measurements. Most importantly, the relationship between sGrs and LCI remained unaffected by lung hyperinflation, as opposed to that of the LCI with the spirometric and standard FOT indices. CONCLUSIONS: In CF patients, the FOT indices at 5 Hz and the novel, volume-adjusted parameter sGrs, reflect the extent of lung involvement and the underlying ventilation inhomogeneity in a way comparable to N2-MBW. Future research should explore the role of lower-frequency FOT in assessing the severity and monitoring the progression of CF lung disease.

Risk factors for forced expiratory volume in 1 s decline in European patients with cystic fibrosis: data from the European Cystic Fibrosis Society Patient Registry.

Aim: To examine the trajectory of forced expiratory volume in 1 s (FEV1) using data from the European Cystic Fibrosis Society patient registry (ECFPR) collected from 2008 to 2016, i.e. the era before highly effective modulator therapy (HEMT). We evaluated risk factors for FEV1 decline. Methods: The study population included patients with a confirmed diagnosis of cystic fibrosis recorded in the ECFPR (2008-2016). The evolution of FEV1 % predicted (%FEV1) with age, and the yearly change in %FEV1 were evaluated. Risk factors considered were cystic fibrosis transmembrane conductance regulator (-CFTR) mutation class, gender, age at diagnosis, neonatal screening, meconium ileus, sweat chloride concentration at diagnosis and country's income level. Results: We used 199 604 FEV1 recordings from 38 734 patients. The fastest decline was seen during puberty and in patients diagnosed before the age of 10 years. Males had a higher %FEV1, but a higher yearly %FEV1 loss between the ages of 15 and 25 years. We showed stabilisation and even improvement in %FEV1 over age in adults with a class III CFTR mutation, but a steady decline in patients homozygous for F508del or with both mutations of classes I/II. A faster decline in %FEV1 was found in patients from low-income countries compared to a similar %FEV1 evolution in patients from middle- and high-income countries. Conclusions: These longitudinal FEV1 data reflect the reality of cystic fibrosis across Europe in the era pre-HEMT, and can serve as baseline for comparison with the post-HEMT era. The similar evolution in middle- and high-income countries underlines opportunities for low-income countries.

SARS-CoV-2-related bronchiolitis: a multicentre international study.

BACKGROUND: Bronchiolitis is the main acute lower respiratory tract infection in infants. Data regarding SARS-CoV-2-related bronchiolitis are limited. OBJECTIVE: To describe the main clinical characteristics of infants with SARS-CoV-2-related bronchiolitis in comparison with infants with bronchiolitis associated with other viruses. SETTING, PATIENTS, INTERVENTIONS: A multicentre retrospective study was conducted in 22 paediatric emergency departments (PED) in Europe and Israel. Infants diagnosed with bronchiolitis, who had a test for SARS-CoV-2 and were kept in clinical observation in the PED or admitted to hospital from 1 May 2021 to 28 February 2022 were considered eligible for participation. Demographic and clinical data, diagnostic tests, treatments and outcomes were collected. MAIN OUTCOME MEASURES: The main outcome was the need for respiratory support in infants testing positive for SARS-CoV-2 compared with infants testing negative. RESULTS: 2004 infants with bronchiolitis were enrolled. Of these, 95 (4.7%) tested positive for SARS-CoV-2. Median age, gender, weight, history of prematurity and presence of comorbidities did not differ between the SARS-CoV-2-positive and SARS-CoV-2-negative infants. Human metapneumovirus and respiratory syncytial virus were the viruses most frequently detected in the group of infants negative for SARS-CoV-2.Infants testing positive for SARS-CoV-2 received oxygen supplementation less frequently compared with SARS-CoV-2-negative patients, 37 (39%) vs 1076 (56.4%), p=0.001, OR 0.49 (95% CI 0.32 to 0.75). They received less ventilatory support: 12 (12.6%) high flow nasal cannulae vs 468 (24.5%), p=0.01; 1 (1.0%) continuous positive airway pressure vs 125 (6.6%), p=0.03, OR 0.48 (95% CI 0.27 to 0.85). CONCLUSIONS: SARS-CoV-2 rarely causes bronchiolitis in infants. SARS-CoV-2-related bronchiolitis mostly has a mild clinical course.