Prevalence of SARS-CoV-2 positivity in infants with bronchiolitis: a multicentre international study

Background Bronchiolitis is the leading acute respiratory tract infection in infants during the winter season. Since the beginning of the SARS-CoV-2 pandemic, a reduction in the number of bronchiolitis diagnoses has been registered. Objective The present study aimed to describe the incidence and clinical features of bronchiolitis during the 2020-2021 winter season in a large cohort of children in Europe and Israel, and to clarify the role of SARS-CoV-2. Setting, patients, interventions We conducted a multicentre observational cross-sectional study in 23 paediatric emergency departments in Europe and Israel. Clinical and demographic data about all the cases of infants diagnosed with bronchiolitis from 1 October 2020 to 30 April 2021 were collected. For each enrolled patient, diagnostic tests, treatments and outcomes were reported. Main outcome measures The main outcome was the prevalence of SARS-CoV-2-positive bronchiolitis. Results Three hundred and fourteen infants received a diagnosis of bronchiolitis during the study period. Among 535 infants who tested positive for SARS-CoV-2, 16 (3%) had bronchiolitis. Median age, male sex predominance, weight, history of prematurity and presence of comorbidities did not differ between the SARS-CoV-2-positive and SARS-CoV-2-negative groups. Rhinovirus was the most common involved pathogen, while respiratory syncytial virus (RSV) was detected in one case. SARS-CoV-2 bronchiolitis had a mild clinical course, with one patient receiving oxygen supplementation and none requiring paediatric or neonatal intensive care unit admission. Conclusions During the SARS-CoV-2 pandemic, a marked decrease in the number of bronchiolitis diagnoses and the disappearance of the RSV winter epidemic were observed. SARS-CoV-2-related bronchiolitis was rare and mostly displayed a mild clinical course.During the SARS-CoV-2 pandemic, very few infants with SARS-CoV-2 had bronchiolitis and mostly displayed a mild clinical course. Overall there was a marked decrease in bronchiolitis cases, indeed the RSV winter epidemic did not occur

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

Antibiotic Resistance in Patients with Cystic Fibrosis: Past, Present, and Future

Patients with cystic fibrosis (CF) are repeatedly exposed to antibiotics, especially during the pulmonary exacerbations of the disease. However, the available therapeutic strategies are frequently inadequate to eradicate the involved pathogens and most importantly, facilitate the development of antimicrobial resistance (AMR). The evaluation of AMR is demanding; conventional culture-based susceptibility-testing techniques cannot account for the lung microenvironment and/or the adaptive mechanisms developed by the pathogens, such as biofilm formation. Moreover, features linked to modified pharmaco-kinetics and pulmonary parenchyma penetration make the dosing of antibiotics even more challenging. In this review, we present the existing knowledge regarding AMR in CF, we shortly review the existing therapeutic strategies, and we discuss the future directions of antimicrobial stewardship. Due to the increasing difficulty in eradicating strains that develop AMR, the appropriate management should rely on targeting the underlying resistance mechanisms; thus, the interest in novel, molecular-based diagnostic tools, such as metagenomic sequencing and next-generation transcriptomics, has increased exponentially. Moreover, since the development of new antibiotics has a slow pace, the design of effective treatment strategies to eradicate persistent infections represents an urgency that requires consorted work. In this regard, both the management and monitoring of antibiotics usage are obligatory and more relevant than ever

Genomic profiling supports the diagnosis of primary ciliary dyskinesia and reveals novel candidate genes and genetic variants.

Primary ciliary dyskinesia (PCD) is a rare inherited autosomal recessive or X-linked disorder that mainly affects lungs. Dysfunction of respiratory cilia causes symptoms such as chronic rhinosinusitis, coughing, rhinitis, conductive hearing loss and recurrent lung infections with bronchiectasis. It is now well known that pathogenic genetic changes lead to ciliary dysfunction. Here we report usage of clinical-exome based NGS approach in order to reveal underlying genetic causes in cohort of 21 patient with diagnosis of PCD. By detecting 18 (12 novel) potentially pathogenic genetic variants, we established the genetic cause of 11 (9 unrelated) patients. Genetic variants were detected in six PCD disease-causing genes, as well as in SPAG16 and SPAG17 genes, that were not detected in PCD patients so far, but were related to some symptoms of PCD. The most frequently mutated gene in our cohort was DNAH5 (27.77%). Identified variants were in homozygous, compound heterozygous and trans-heterozygous state. For detailed characterization of one novel homozygous genetic variant in DNAI1 gene (c. 947_948insG, p. Thr318TyrfsTer11), RT-qPCR and Western Blot analysis were performed. Molecular diagnostic approach applied in this study enables analysis of 29 PCD disease-causing and related genes. It resulted in mutation detection rate of 50% and enabled discovery of twelve novel mutations and pointed two possible novel PCD candidate genes

CFTR Genotype and Maximal Exercise Capacity in Cystic Fibrosis: A Cross-sectional Study.

RATIONALE Cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in human skeletal muscle cells. Variations of CFTR dysfunction among patients with CF may present an important determinant of aerobic exercise capacity in CF. Previous studies on the relationship between CFTR genotype and aerobic exercise capacity are scarce and contradictory. OBJECTIVES This study was designed to explore factors influencing aerobic exercise capacity, expressed as peak oxygen consumption (VO2peak) with a specific focus on CFTR genotype in children and adults with CF. METHODS In an international, multicenter cross-sectional study we collected data on CFTR genotype and cardiopulmonary exercise tests (CPET) in patients with CF eight years and older. CFTR mutations were classified into functional classes I-V. RESULTS The final analysis included 726 patients (45% females, age 8 to 61 years, FEV1 16 to 123 % predicted) from 17 CF centers in North America, Europe, Australia and Asia whom all had both valid maximal CPET and complete CFTR genotype data. Overall, patients exhibited exercise intolerance (VO2peak, 77.3±19.1 % predicted), but values were comparable among different CFTR classes. Using linear regression analysis adjusted for relevant confounders, lung function and body mass index, but not CFTR genotype were the main predictors of VO2peak. CONCLUSIONS We conclude that lung disease severity and reduced nutritional status rather than CFTR genotypes are the major determinants of aerobic exercise capacity in patients with CF

Cardiopulmonary Exercise Testing Provides Prognostic Information in Advanced Cystic Fibrosis Lung Disease

Rationale: Cardiopulmonary exercise testing (CPET) provides prognostic information in cystic fibrosis (CF); however, its prognostic value for patients with advanced CF lung disease (ACFLD) is unknown. Objectives: To determine the prognostic value of CPET on the risk of death or lung transplant (LTX) within 2-years. Methods: We retrospectively collected data from 20 CF centers in Asia, Australia, Europe, and North America on patients with a forced expiratory volume in 1s (FEV$_{1}$) ≤40% predicted who performed a cycle ergometer CPET between January 2008 and December 2017. Time to death/LTX was analyzed using mixed Cox proportional hazards regression. Conditional inference trees were modelled to identify subgroups with increased risk of death/LTX. Results: In total, 174 patients (FEV$_{1}$ 30.9±5.8% predicted) were included. Forty-four patients (25.5%) died or underwent LTX. Cox regression analysis adjusted for age, sex and FEV$_{1}$, revealed percent predicted peak oxygen uptake (V ̇O$_{2peak}$) and peak work rate (W$_{peak}$) as significant predictors of death/LTX: adjusted hazard ratios per each additional ten percent predicted were 0.60 (95% confidence interval, 0.43-0.90, P=0.008) and 0.60 (0.48-0.82, P49.2% predicted, P<0.001. Conclusions: CPET provides prognostic information in ACFLD and W$_{peak}$ appears to be a promising marker for LTX referral and candidate selection

Cardiopulmonary exercise testing provides prognostic information in advanced cystic fibrosis lung disease

Rationale: cardiopulmonary exercise testing (CPET) provides prognostic information in cystic fibrosis (CF); however, its prognostic value for patients with advanced CF lung disease (ACFLD) is unknown. Objectives: to determine the prognostic value of CPET on the risk of death or lung transplant (LTX) within 2-years. Methods: we retrospectively collected data from 20 CF centers in Asia, Australia, Europe, and North America on patients with a forced expiratory volume in 1s (FEV1) ≤40% predicted who performed a cycle ergometer CPET between January 2008 and December 2017. Time to death/LTX was analyzed using mixed Cox proportional hazards regression. Conditional inference trees were modelled to identify subgroups with increased risk of death/LTX. Results: In total, 174 patients (FEV1, 30.9% ± 5.8% predicted) were included. Forty-four patients (25.5%) died or underwent LTX. Cox regression analysis adjusted for age, sex, and FEV1 revealed percentage predicted peak oxygen uptake (Vo2peak) and peak work rate (Wpeak) as significant predictors of death/LTX: adjusted hazard ratios per each additional 10% predicted were 0.60 (95% confidence interval, 0.43–0.90; P = 0.008) and 0.60 (0.48–0.82; P &lt; 0.001). Tree-structured regression models, including a set of 11 prognostic factors for survival, identified Wpeak to be most strongly associated with 2-year risk of death/LTX. Probability of death/LTX was 45.2% for those with a Wpeak ⩽ 49.2% predicted versus 10.9% for those with a Wpeak &gt; 49.2% predicted (P &lt; 0.001).Conclusions: CPET provides prognostic information in advanced CF lung disease, and Wpeak appears to be a promising marker for LTX referral and candidate selection