Background: Despite the growing awareness of Cystic Fibrosis (CF) in China, few cases have been reported in Henan, which is the most populous province in the country. This study aimed to describe the clinical phenotype and genotype of children with CF in Henan. Methods: We recruited 14 Chinese children with CF who presented to Children’s Hospital affiliated to Zhengzhou University from January 2019 to January 2023. The demographic data, imaging examinations, and laboratory tests of the patients were reviewed to clarify the clinical phenotype. Whole exome sequencing was conducted to identify the genotype. Results: Respiratory diseases were the main clinical manifestation, including recurrent/persistent pneumonia (85.7%), sinusitis (71.4%), bronchiectasis (71.4%). CF-related liver disease (CFLD) and pancreatic insufficiency (PI) were less common (21.4% each). Infant cases had high frequency of pseudo-Bartter Syndrome (80.0%). Chest computed tomography showed bronchiectasis in older children and air trapping in infant cases. The most common pathogens in the airway were Pseudomonas aeruginosa and Staphylococcus aureus (71.4% respectively). Twenty-four different CFTR gene variants were detected, including four novel observations (c.869+3A>T, c.1064C>G[p.Pro355Arg], c.1209+1G>C and c.1925C>G [p.Ser642X]). The most common variant was c.2909G>A (p.Gly970Asp), with a detected rate of 16.7%. Conclusion: Children with CF in Henan had varied clinical phenotypes by age, with respiratory disease being predominant. The most frequent CFTR gene variant was c.2909G>A(p.Gly970Asp). This study is the first and most comprehensive one on the clinical phenotype and genotype of children with CF in Henan, China. We also reported the first CF case of M. abscessus infection in China.
The ancient Greeks took the entertainment of their crowds very seriously and used drama as a way of investigating the world they lived in. The theatrical re-enactment of suffering and grief in front of a large audience was to foster compassion, as well as a cathartic release of emotion that was restorative through a deeply felt interconnection between actors and audience. When our patients encounter tragedy, we are also drawn into their ordeal and experience it first hand. Such it was with Rose.
The respiratory tract antimicrobial defense system is a multilayered defense mechanism that relies upon mucociliary clearance and components of both the innate and adaptive immune systems to protect the lungs from inhaled or aspirated microorganisms. One of these potential pathogens, non-typeable Haemophilus influenzae ( NTHi), adopts several, multifaceted redundant strategies to successfully colonize the lower airways and establish a persistent infection. NTHi can impair mucociliary clearance, express multiple multi-functional adhesins for various cell types within the respiratory tract and evade host defenses by surviving within and between cells, forming biofilms, increasing antigenic drift, secreting proteases and antioxidants, and by host-pathogen cross-talk, impair macrophage and neutrophil function. NTHi is recognized as an important pathogen in several chronic lower respiratory disorders, such as protracted bacterial bronchitis, bronchiectasis, cystic fibrosis and primary ciliary dyskinesia. The persistence of NTHi in human airways, including its capacity to form biofilms, results in chronic infection and inflammation, which can ultimately injure airway wall structures. The complex nature of the molecular pathogenetic mechanisms employed by NTHi is incompletely understood but improved understanding of its pathobiology will be important for developing effective therapies and vaccines, especially given the marked genetic heterogeneity of NTHi and its possession of phase-variable genes. Currently, no vaccine candidates are ready for large phase III clinical trials.
A 5-month-old male baby was brought to the emergency room with a one-day history of respiratory distress, wheezing, vomiting, and high fever. Wheezing had been present since birth but had recently become more frequent and intense, occurring even at rest. The baby was born full-term by cesarean delivery and had a medical history of gallbladder agenesis, secundum atrial septal defect (ASD), and cryptorchidism.
Severe BPD can be associated with clinical and histologic features that are similar to ACD without evidence of FOXF1 genetic disease. Importantly, lung FOXF1 and TMEM100 gene expression is markedly decreased in severe BPD, suggesting that impaired FOXF1 signaling may contribute to abnormal lung growth and refractory pulmonary hypertension in BPD.
Background International consensus statements on depression and anxiety in adolescents and adults with CF recommend assessment for comorbid substance misuse. However, at CF centers, the frequency and impact of substance misuse have not been well characterized, and best practices for prevention, identification, and evidence-based treatment have not been routinely implemented. Methods Medical records of 148 adults with CF over 3 years were reviewed to determine the prevalence of substance misuse (alcohol or opiates) and its relationship with clinical variables and healthcare utilization. Independent-sample t-test for continuous outcomes and chi-square test for binary outcomes were used to compare groups with and without substance misuse. Results Substance misuse was documented in 28 (19%) adults with CF, equally distributed between alcohol (n=13) and opiates (n=15). Adults with substance misuse were more likely to be male. The prevalence of diagnosed anxiety and depression did not differ significantly between groups, but those with substance misuse had more severe anxiety (GAD-7: 10.0±6.1 vs. 3.3±4.4; p<0.001) and depressive symptoms (PHQ-9: 10.4±6.5 vs. 4.0±4.8; p<0.001). Adults with substance misuse had higher annual rates of missed outpatient CF visits and inpatient hospitalizations, with hospital admissions of longer mean duration. Conclusions In adults with CF, substance misuse is common and is associated with adverse indicators of emotional and physical health and service utilization, suggesting that systematic approaches to addressing substance misuse in CF clinics should be considered. Prospective, longitudinal study is warranted to elucidate the complex relationships between depression, anxiety, substance misuse, and health outcomes in individuals with CF.
Cystic fibrosis has seen a multitude of therapeutic advances targeting its downstream effects. This has led to a steady increase in survival over the past few decades. The recent development of disease-modifying drugs targeting the underlying CFTR mutation has revolutionized treatment for CF. Despite these advances, individuals with CF who are racial and ethnic minorities, from low socioeconomic status, or female sex have worse clinical outcomes. The inequitable access to CFTR modulators from cost and/or genetic eligibility has the potential to further worsen the existing health disparities seen within the CF community.
Background: eHealth CF-CBT is the first digital mental health intervention for depression/anxiety in adults with cystic fibrosis (awCF); an 8-session therapist-guided internet-delivered program that was developed in English and Dutch with stakeholder input and evaluation indicating high acceptability and usability. Methods: Dutch eHealth CF-CBT was piloted in awCF with mild-moderate symptoms of depression and/or anxiety. Feasibility, usability, acceptability, and preliminary efficacy were assessed, measuring pre-post changes in depression (PHQ-9), anxiety (GAD-7), perceived stress (PSS) and health-related quality of life (CFQ-R). Results: All participants (n=10, 7 female, mean age 29 (range 21-43), mean FEV1 71%pred (range 31-115)) completed all sessions. Patient-rated feasibility, usability and acceptability of eHealth CF-CBT was positive on validated scales, as were qualitative assessments of content and format. GAD-7 improved in 90% of participants; in 50% by ≥ the minimally important difference (MID) of 4 points. PHQ-9 improved in 90%; 40% by ≥ the MID of 5. PSS improved in 80%. CFQ-R improved in the domain Health Perceptions (70%). Conclusions: eHealth CF-CBT demonstrated feasibility, usability, acceptability and promising preliminary efficacy in this pilot trial with Dutch awCF with mild to moderate symptoms of depression and anxiety.
Background: Hispanic people with cystic fibrosis (CF) have decreased life expectancy and earlier acquisition of Pseudomonas aeruginosa compared to non-Hispanic white individuals with CF. Racial and ethnic differences in the airway microbiome of CF may contribute to known health disparity, but have not been studied. The objective was to describe differences in the upper airway microbial community in Hispanic and non-Hispanic white children with CF. Methods: This prospective, observational cohort study of fifty-nine Hispanic and non-Hispanic white children with CF, ages 2-10 years old, was performed at Texas Children’s Hospital (TCH) from February 2019 to January 2020. Oropharyngeal swabs were collected from the cohort during clinic visit. Swab samples underwent sequencing (16S V4 rRNA), diversity analysis, and taxonomic profiling. Key demographic and clinical data were collected from the electronic medical record and the Cystic Fibrosis Foundation Patient Registry (CFFPR). Statistical analysis compared sequencing, demographic, and clinical data. Results: We found no significant difference in Shannon diversity or relative abundance of bacterial phyla between Hispanic and non-Hispanic children with CF. However, a low abundant taxa- “uncultured bacterium” belonging to the order Saccharimonadales was significantly higher in Hispanic children (mean relative abundance=0.13%) compared to the non-Hispanic children (0.03%). Hispanic children had increased incidence of Pseudomonas aeruginosa (p=0.045) compared to non-Hispanic children. Conclusion: We did not find a significant difference in the airway microbial diversity between Hispanic and non-Hispanic white children with CF. However, we found a greater relative abundance of Saccharimonadales and higher incidence of Pseudomonas aeruginosa in Hispanic children with CF.
Background Artificial intelligence (AI) is a promising field in the neonatal field. We focused on lung ultrasound (LUS), a useful tool for the neonatologist. Our aim was to train a neural network to create a model able to interpret LUS. Methods Our multicentric, prospective study included newborns with gestational age (GA) ≥ 33+0 weeks with early tachypnea/dyspnea/oxygen requirements. For each baby, three LUS were performed: within 3 hours of life (T0), at 4–6 hours of life (T1) and in the absence of respiratory support (T2). Each scan was processed to extract ROI used to train a neural network to classify it according to the LUS score. We assessed sensitivity, specificity, positive and negative predictive value of the AI model’s scores in predicting the need for respiratory assistance with nasal Continuous Positive Airway Pressure (nCPAP) and for surfactant, compared to the “classical” scores. Results We enrolled 62 newborns (GA=36±2 weeks). In the prediction of the need for CPAP, we found a cut-off of 6 (at T0) and 5 (at T1) for both the classical nLUS and AI score. In the prediction of surfactant therapy we found a cut-off of 9 for both scores at T0, at T1 the nLUS cut-off was 6, while the AI’s one was 5. Classification accuracy was good both at the image and classes level. Conclusions This is, to our knowledge, the first attempt to use an AI model to interpret early neonatal LUS and can be extremely useful for neonatologist in the clinical setting.
Context – The negative effects of socioeconomic, environmental and ethnic inequalities on childhood respiratory diseases are known in the development of persistent asthma and can result in adverse outcomes. However, little is known about the effects of these disparities on pediatric intensive care unit (PICU) outcomes in respiratory diseases. Objective – The purpose of this systematic review is to evaluate the literature on disparities in socioeconomic, environmental and ethnic determinants on PICU outcomes. We hypothesize that these disparities negatively influence the outcomes of children’s respiratory diseases at the PICU. Methods – A literature search (in PubMed, Embase.com and Web of Science Core Collection) was performed up to September 30, 2022. Two authors extracted the data and independently evaluated the risk of bias with appropriate assessment methods. Articles were included if the patients were below 18 years of age (excluding neonatal intensive care unit admissions), they concerned respiratory diseases and incorporated socioeconomic, ethnic or environmental disparities. Results – Of 8746 references reviewed, 15 articles were included; seven articles on the effect of socioeconomic status, five articles on ethnicity, one on the effect of sex and lastly two on environmental factors. All articles but one showed an unfavorable outcome at the PICU. Conclusion – Disparities in socioeconomic (such as a low-income household, public health insurance), ethnic and environmental factors (such as exposure to tobacco smoke and diet) have been assessed as risk factors for the severity of children’s respiratory diseases and can negatively influence the outcomes of these children at the PICU.
Background: Less invasive forms of ventilation have evolved aiming to decrease bronchopulmonary Dysplasia (BPD) morbidity. It is unclear whether changes in ventilation practices have been associated with improvements in respiratory outcomes. Objective: To examine trends of ventilation modes in preterm neonates over the last decade and their impact on BPD. Methods: A retrospective chart review of very low birth weight infants (VLBW) and those born at less than 32 weeks gestation hospitalized during two periods: the years 2012-2013 and 2018-2019. The primary outcome was the prevalence of BPD. Study variables included the mode and duration of ventilation, duration of oxygen need, and perinatal clinical parameters. Results: Four hundred eighty-one infants were enrolled. Between the two study periods, a significant increase was observed in invasive (33% to 47%, p=0.002), and non-invasive ventilation rates (44% to 72%, p<0.001). The average duration of non-invasive ventilation increased significantly (from 9.24 to 14.08 days, p=0.016). The total duration of respiratory support remained unchanged. The overall prevalence of moderate and severe BPD at 36 weeks corrected age remained approximately 40% in preterm infants born at less than 28 weeks gestation. Conclusion: The increasing use of non-invasive ventilation was not accompanied by a reduction in the use of invasive ventilation, nor by a reduced prevalence of BPD. The high prevalence of BPD remains a significant problem in preterm infants born < 28 weeks of age. Other interventions, in addition to less aggressive ventilation, need to be explored.
ETI treatment reduces inflammatory markers and positive bacterial cultures on BAL in PwCF. These findings suggest that ETI has a greater impact on chronic infection and inflammation than ivacaftor alone. However, airway inflammation persists in a fraction of treated individuals, indicating an ongoing need to optimize other treatments in a subset of patients.
Introduction Lung biopsy is infrequently utilized in the population of infants with severe bronchopulmonary dysplasia (BPD). Yet, its presentation may overlap with other infant diffuse lung diseases, including those within the spectrum of childhood interstitial lung diseases (chILD). Lung biopsy might differentiate between these entities, or discern those with an extremely poor prognosis. Both might alter the clinical management of a subset of infants diagnosed with BPD. Methods In this tertiary referral center, we drew on a retrospective cohort of 306 preterm infants with severe BPD. Of these, nine underwent lung biopsy between 2012 and 2017. Our aim was to assess the indication of lung biopsy, the prior clinical history, safety of the procedure, and describe the biopsy findings. Finally, we considered management decisions in relation to the biopsy results in these patients. Results The average gestational age and birth weight of the 9 patients were 30±3 (range 27-34) weeks and 1421±571 (range 611-2140) grams. All infants had serial echocardiograms to assess for pulmonary hypertension, genetic testing, and computed tomography angiography (CTA) prior to biopsy. All patients showed moderate to severe alveolar simplification and 8 had some degree of pulmonary interstitial glycogenosis (PIG) ranging from focal to diffuse. Following biopsy, 2 infants with findings of PIG received high dose systemic steroids and 2 separate infants had care redirected. Conclusion In our cohort, lung biopsy was safe and well tolerated. Findings from lung biopsy may aid decision making in selected patients when used as a part of a step-wise diagnostic algorithm.
Introduction: Preterm children with bronchopulmonary dysplasia (BPD) frequently require supplemental oxygen in the outpatient setting. In this study, we sought to determine patient characteristics and demographics associated with need for supplemental oxygen at initial hospital discharge, timing to supplemental oxygen liberation, and associations between level of supplemental oxygen and likelihood of respiratory symptoms and acute care usage in the outpatient setting. Methods: A retrospective analysis of subjects with BPD on supplemental oxygen (O 2) was performed. Subjects were recruited from outpatient clinics at Johns Hopkins University and the Children’s Hospital of Philadelphia between 2008 and 2021. Data were obtained by chart review and caregiver questionnaires. Results: Children with BPD receiving > 1 liter of O 2 were more likely to have severe BPD, pulmonary hypertension and be older at initial hospital discharge. Children discharged on higher levels of supplemental O 2 were slower to wean to room air compared to lower O 2 groups (p<0.001). Additionally, weaning off supplemental O 2 in the outpatient setting was delayed in children with gastrostomy tubes and those prescribed inhaled corticosteroids, on public insurance or with lower estimated household incomes. Level of supplemental O 2 at discharge did not influence outpatient acute care usage or respiratory symptoms. Conclusion: BPD severity and level of supplemental oxygen use at discharge did not correlate with subsequent acute care usage or respiratory symptoms in children with BPD. Weaning of O 2 however was significantly associated with socioeconomic status and respiratory medication use, contributing to the variability in O 2 weaning in the outpatient setting.
Interstitial Lung Disease in childhood (chILD) is rare and no longer solely a childhood issue. Many are surviving into adult life. Therefore, many affected with chILD need to transition from paediatric to adult healthcare services. Transition is a significant life event that has the potential to impact on physical and mental health outcomes and across Europe this is a haphazard process for chILD. This qualitative study explores how young people and parents in the United Kingdom experienced transition from paediatric to adult healthcare services for chILD. Participants (n = 7) were recruited from chILD patient organisations and online communities. We focused on the experience of transition and whether there were any information packs or support provided for the transition. The data was analysed by constructivist grounded theory. The study presents a lived experience of transition with themes of lack of transition preparation and planning, challenges of learning how to adapt to adult services and a changing healthcare scene. Due to the complexity of ChILD, parents discussed their need to remain, in part, as an advocate for the young person. Respondents provided recommendations for how transition could be improved along with tips for young people who are new to the transition process, which include educating oneself about the condition and learning medical terminology, being open if there are issues and reaching out for support.