A document by Daniel Penela-Sánchez. Click on the document to view its contents.

Objectives: Airway clearance therapy (ACT) is an important component of therapy for cystic fibrosis (CF) but is associated with significant treatment burden. Highly effective CFTR modulator therapy (HEMT) has improved pulmonary function for many people with CF(pwCF). We sought to understand changes in attitudes and practices about ACT in the post-HEMT era. Study design: Surveys of CF community members and CF care team members Methodology: Separate surveys were created for the CF community and CF care providers to evaluate attitudes towards ACT and exercise in the post-HEMT era. We solicited answers from pwCF via the CF Foundation’s Community Voice and from CF care providers via CF Foundation listservs. Surveys were available between July 20 and August 3, 2021. Results: Surveys were completed by 153 community members (parents of children and pwCF) and 192 CF care providers. Belief that exercise can substitute partially for ACT was endorsed similarly by community members (59%) and providers (68%) . After starting HEMT, 36% of parents of children and 51% of adults did fewer ACT treatments including 13% who stopped ACT. Adults reported altering their ACT regimen more than parents of children. Half of providers had changed their ACT recommendations for those on HEMT. Fifty-three percent of respondents had discussed changing ACT with their care team (36% of parents, 58% of pwCF). Conclusions: Providers should be aware that ACT management changes may have been undertaken by pwCF who have pulmonary benefits of HEMT. Treatment burden should be considered in co-management decisions regarding ACT and exercise.

Background: Among children with tracheostomies, little is known about how respiratory culture results differ between states with and without acute respiratory infections (ARI), or the overall test performance of respiratory cultures. Objective: To determine the association of respiratory culture organism isolation with diagnosis of ARI in children with tracheostomies, and assess test characteristics of respiratory cultures in the diagnosis of bacterial ARI (bARI). Methods: This single-center, retrospective cohort study included respiratory cultures of children with tracheostomies obtained between 2010-2018. The primary predictor was ARI diagnosis code at the time of culture; the primary outcomes were respiratory culture organism isolation and species identified. Generalized estimating equations were used to assess for association between ARI diagnosis and isolation of any organism while controlling for potential confounders and accounting for within-patient clustering. A multinomial logistic regression equation assessed for association with specific species. Test characteristics were calculated using bARI diagnosis as the reference standard. Results: Among 3,578 respiratory cultures from 533 children (median 4 cultures/child, IQR: 1-9), 25.9% were obtained during ARI and 17.2% had ≥1 organism. Children with ARI diagnosis had higher odds of organism identification (aOR 1.29, 95% CI 1.16–1.44). When controlling for covariates, ARI was associated with isolation of H. influenzae, M. catarrhalis, S. pneumoniae, and S. pyogenes. Test characteristics revealed a 24.3% sensitivity, 85.2% specificity, 36.5% positive predictive value, and 76.3% negative predictive value in screening for bARI. Conclusion: The utility of respiratory culture testing to screen for, diagnose, and direct treatment of ARI in children with tracheostomies is limited.

Rationale: Patients with congenital central hypoventilation syndrome (CCHS) require long-term ventilation to ensure gas exchange and to prevent deleterious consequences for neurocognitive development. Two ventilation modes may be used for these patients depending on their tolerance, one invasive by tracheostomy and the other noninvasive (NIV). For patients who have undergone a tracheostomy, transition to NIV is possible when they meet predefined criteria. Identifying the conditions favorable for weaning from a tracheostomy it critical for the success of the process. Objective: The aim of the study was to share our experience of decannulation in a reference center; we hereby describe the modality of ventilation and its effect on nocturnal gas exchange before and after tracheostomy removal. Methods: Retrospective observational study at Robert Debré Hospital over the past 10 years. The modalities of decannulation and transcutaneous carbon dioxide recordings or polysomnographies before and after decannulation were collected. Results: Sixteen patients underwent decannulation following a specific procedure for transition from invasive to NIV. All decannulations were successful. The median age at decannulation was 12.6 [9.7; 15.0] years. Nocturnal gas exchange was not significantly different before and after decannulation, while expiratory positive airway pressure and inspiratory time increased significantly. An oronasal interface was chosen in two out of three patients. The mean duration of hospital stay for decannulation was 4.0 [3.0; 6.0] days. Conclusion: Our study underlines that decannulation and transition to NIV are achievable in CCHS children using a well-defined procedure. Patient preparation is crucial to the success of the process.

Background Children with chronic lung disease (CLD) of prematurity who require invasive home mechanical ventilation (iHMV) are medically vulnerable and experience high caregiving and healthcare costs. Predictors for duration of iHMV remain unclear, which can make prognostication and decision-making challenging. Methods A retrospective cohort study of children with CLD of prematurity requiring invasive iHMV was conducted from an independent children’s hospital records (2005-2021). The primary outcome was iHMV duration, defined as time from initial discharge home on iHMV until cessation of positive pressure ventilation (day and night). Two new variables were included: corrected tracheostomy age (CTA) (chronological age at discharge minus age at tracheotomy) and level of ventilator support at discharge (minute ventilation per kg per day). Univariable Cox regression was performed with variables of interest compared to iHMV duration. Significant nonlinear factors (P<0.05) were included in the multivariable analysis. Results One-hundred-and-nineteen patients used iHMV primarily for CLD of prematurity. Patient median index hospitalization lasted 12 months (IQR 8.0,14.4). Once home, half of patients were weaned off iHMV by 36.0 months and 90% by 52.2 months. Being Hispanic/Lantix ethnicity (HR 0.14 (95% CI 0.04, 0.53), p<0.01) and having a higher CTA were associated with increased iHMV duration (HR 0.66 (CI 0.43, 0.98), p<0.05). Conclusions Disparity in iHMV duration exists among patients using iHMV after prematurity. Prospective multisite studies that further investigate new analytic variables, such as CTA and level of ventilator support, and address standardization of iHMV care are needed to create more equitable iHMV management strategies.

Background: Cystic fibrosis (CF) is an autosomal recessive disease affecting multiple organ systems, including the liver, leading to cystic fibrosis-related liver disease (CFLD). It was noted that CFLD in Egyptian children with CF is more common than in non-Egyptian people with CF (pwCF). The present study aimed to determine the incidence of CFLD and the potential risk factors for developing CFLD in Egyptian children. The correlation between CFLD and the various genotypes prevalent in Egyptian CF children and the comparison of CFLD in Egyptian and non-Egyptian CF patients will be done. Methods: The current cross-sectional study included 50 CF cases from Ain Sham University’s Pediatric Pulmonology Clinic in Children‘s Hospital, Cairo, Egypt. The sweat chloride test and genetic studies were done at the time of diagnosis. All patients’ caregivers provided informed consent. Additionally, all subjects underwent detailed history taking, laboratory investigations, clinical assessment, and pelviabdominal ultrasound for evaluation of hepatic involvement. Results: Male sex, severe genetic mutation (class I and II), long duration, and early onset of the disease were independent risk factors for CFLD development. In addition, pancreatic insufficiency, as well as meconium ileus history, were predictors of CFLD. Diabetes mellitus and severe lung disease were proven to significantly elevate the risk of CFLD development. Conclusion: CFLD is not uncommon in Egyptian CF patients as one-third of the patients were found to have liver affection. CF patients with multiple risk factors are at increased risk of developing liver disease.

Objective: There has been a rise in the prenatal detection of right sided aortic arch (RAA). When associated with a left-sided arterial duct (LD), this forms a vascular ring encircling the trachea. Infants may have symptoms or signs suggestive of trache-oesophageal compression but many are asymptomatic. The objective of this study was to investigate the relationship between symptoms and severity of tracheo-bronchial compression assessed by bronchoscopy. Methods: Retrospective review of all cases of prenatally diagnosed RAA-LD in the absence of associated congenital heart disease at Evelina London Children’s Hospital and Kings College Hospital over a 4-year period between April 2015-2019. Clinical records, fetal echocardiograms and free-breathing flexible bronchoscopy (FB) data were reviewed. Results: 112 cases of isolated RAA-LD were identified of whom 82 cases (73%) underwent FB. FB was performed median age of 11 months (range 1-36 months), no complications occurred. Aberrant left subclavian artery (ALSA) was present in 86% (96/112) and mirror image branching (MIB) in 13% (15/112). 34/112 (30%) reported symptoms during follow up. 36/77 (47%) with ALSA who underwent FB showed moderate-severe compression mostly at distal tracheal and carinal level of whom 38% had parent-reported symptoms. Moderate-severe compression was seen in 3/5 (60%) with MIB mostly at mid tracheal level of whom 3 were symptomatic but only 2 with compression. In total 36% (18/50) of investigated asymptomatic patients showed moderate to severe compression. Respiratory symptoms were poorly predictive of moderate-severe compression (positive predictive value 66%). Conclusion: The absence of symptoms did not exclude significant tracheal compression. The anatomical effect of the vascular ring is underappreciated when symptoms alone are used as a marker of tracheal compression.

To our knowledge, this is the first reported case of successful transbronchial biopsy via RB in a 5-year-old patient. The sample revealed a potential diagnosis, but more importantly, helped rule out an active infectious process and avoided an open lung biopsy which was being planned and would have otherwise been necessary to establish a diagnosis. We believe this technology can be used to increase the diagnostic yield of flexible bronchoscopy, particularly in the immunocompromised population as there is already evidence supporting image-guided bronchoscopy over conventional bronchoscopy in this population [(4)](#ref-0004). A notable limitation to RB is the size of the available bronchoscopes for robotic platforms (4.5 and 3.5 mm OD). In children, this may limit the capacity to sample more peripheral lesions via fine needle aspiration, as more lung tissue (relative to chest size) may be injured. In our case, the catheter tip was never as close to the lesion as it has been described in adults [(2)](#ref-0002). As the field of pediatric interventional pulmonology continues to develop, RB will likely be one of several options available for safe and high-yield diagnostic procedures.

Pulmonary artery sling is a rare childhood vascualr ring that is frequently associated with tracheal stensois. Consequently, neonates may present with a crictal airway obstruction if tehre is long segemt tarcheal stensosi and complete rings. Rapid diagnosis of this cardiac vascular malfomation and extent airway involvement is essentail as longterm outcoem can be excellent follwoing surgicla repair. In this review we focus on airway invetsigation and management for this challenging congential condition.

Introduction: Congenital diaphragmatic hernia (CDH) is known with high mortality rates and significant pulmonary morbidities. The objective of this study was to describe the histopathological findings of necropsy and clinical manifestations in CDH patients to find the clinicopathological correlations. Methods: We reviewed the postmortem findings with associated clinical characteristics retrospectively in 8 CDH cases from 2017 to2022 July. Results: Of the eight cases, one was bilateral congenital eventration diagnosed by autopsy. Severe pulmonary hypertension with a right to left shunting of large patent ductus arteriosus (PDA) obtained from echocardiogram were most common. And the average time of survive was 46 (8-624) h. According to the autopsy reports, the major pathological lung changes were diffuse alveolar damages (congestion and hemorrhage) and hyaline membrane formation. Notably, although the lung volume was significantly reduced, pulmonary structural dysplasia was not observed at all, presented normal lung development (50%); bilateral (25%) or ipsilateral (25%). Lobulated deformities were accompanied in three (37.5%) cases. All patients exhibited large PDA and a patent foramen ovale with increased right ventricle (RV) volume, and the myocardial fibers were slightly congested and swollen. Pulmonary vessels showed mild to moderate arterial media thickening. Lung hypoplasia and diffuse lung damages reduced gas exchange, meanwhile the PDA and PH caused RV failure, contributed a clinical picture of organ dysfunction, which lead to death. Conclusions: Pulmonary structures have certain heterogeneity in CDH. The arteries’ pathological changes are not consistent with clinical diagnosis. And the adverse outcome may should be due to the cardiopulmonary vicious cycle.

The current system for disclosing financial conflicts of interest (COIs) can be traced back to the “Uniform requirements for manuscripts submitted to medical journals,” published in 1997. Meanwhile, new molecular and genetic therapies are transforming clinical medicine and these therapies have radically altered the financial landscape of drug development. The average price of new drugs has risen sharply, and in niche areas like rare diseases, the cost of new therapies can be stratospheric. Now, even rare or “orphan” diseases are funded by private investment. With high profitability, there is a new pathway for drug development involving unprecedented ties between industry and academia. The potential for COIs has greatly expanded and decisions that were once science-driven have become profit-driven. As a result, the risk that marginally effective, ineffective and even hazardous treatments will make their way to patients has greatly increased. In this editorial, we propose a system built on process-based COIs. This new system would trace the developmental journey of a drug from the lab to patients. All financial ties that institutions and individuals have to the drug would be disclosed at each developmental step. The goal would be to create a healthy skepticism and debate over the studies behind new drugs, restoring a scientific focus to the assessment of drug efficacy. When society’s limited resources are used to pay for drugs whose excessive cost primarily benefits investors and corporations, it derails scientific objectivity, harms patients, and threatens the financial stability of our health care systems.

Addressing the recognised challenges and inequalities in providing high quality health care for rare diseases such as children’s interstitial lung disease (chILD) requires collaboration across institutional, geographical, discipline, and system boundaries. The Children’s Interstitial Lung Disease Respiratory Network of Australia and New Zealand (chILDRANZ) is an example of a clinical network that brings together multidisciplinary health professionals for collaboration, peer learning, and advocacy with the goal of improving the diagnosis and management of this group of rare and ultra-rare conditions. This narrative review explores the multifaceted benefits arising from social learning spaces within rare disease clinical networks by applying the Value Creation Framework. The operation of the chILDRANZ network is used as an example across the framework to highlight how value is generated, realised, and transferred within such collaborative clinical and research networks. The community of clinical practice formed in the chILDRANZ multidisciplinary clinical peer support meetings provides a strong example of social learning that engages with the uncertainty inherent in rare disease diagnosis and management and pays attention to generate new knowledge and best practice to make a difference for children and families living with chILD. This review underscores international calls for further investment in, and support of, collaborative expert clinical networks for rare disease.

Objective: SARS-COV-2 pandemic had a profound impact on acute bronchiolitis epidemiology, especially in RSV diffusion and the burden of disease with implications on the management of prophylaxis and health resources. We aimed to compare clinical and epidemiological characteristics of bronchiolitis before and during the SARS-CoV-2 pandemic.   Methods: We conducted an observational study involving children aged 0-2 years with bronchiolitis admitted to a tertiary children’s hospital during the last 5 years. Demographic, clinical, microbiological, and outcome data were collected. Comparison between pre- and post-pandemic period, RSV positive versus non-RSV patients, and SARS-CoV-2 positive vs negative patients were carried out.    Results: A total of 647 patients admitted for bronchiolitis were included (264 female,40.8%, median age 78 days). Molecular diagnostic tests were performed in 617 patients (95.4%) with RSV detected in 62.5% of patients. SARS-CoV-2 was found in 3.9% of hospitalized bronchiolitis (3.9%). We observed a progressive increase in bronchiolitis admissions and a statistically significant increase over the years in the need for respiratory support. Conversely, this was not true for mechanical ventilation, duration of respiratory support, ICU admission, and length of stay. During the pandemic period children with prematurity increased, although only 1 child had an indication for prophylaxis. Discussion: We confirm the stronger impact of bronchiolitis in the 2021-22 season, which is likely explained by the higher prevalence of RSV and the immunity debt theory. However, our findings were conflicting in terms of worsening clinical severity. The increase of children with prematurity and the inter-seasonal spread of RSV highlight the importance of epidemiological surveillance systems that monitor RSV circulation.

Asthma deaths were rare in children but attention should be paid to those with a severe exacerbation (requiring systemic steroids, an ED visit or hospitalization) in the past year, more than three beta-agonist refills in a year and poor adherence to controller medication.

Right and left ventricular dysfunction are commonly encountered in pulmonary disorders. Pulmonary hypertension exerts pressure load on the right ventricle, subsequent RV-LV interactions through shared septum, pericardium and blood supply lead to LV dysfunction. The early detection and treatment of pulmonary hypertension is crucial to improve outcomes of pulmonary disorders. New advanced echocardiographic techniques such as pulmonary artery circumferential strain and pulmonary artery blood speckle tracking might help in replacing invasive hemodynamics, for early detection of pulmonary vasculopathy in pulmonary disorders.

Backround: Mechanical ventilation is associated with mortality/morbidities in preterm infants. Nearly a third of these infants fail extubation and this may increase morbidities. Objective: To evaluate the association of symptomatic patent ductus arteriosus with failure of extubation among preterm infants. Methods: This was a retrospective study on preterm infants (birth weight <1,250 grams and gestational age ≥23weeks) born between January 2009 and December 2016, who were mechanically ventilated and extubated within the first 60 days of age. Results: 360 infants were evaluated, of these, 26% failed and 74% succeeded the initial extubation attempt. On adjusted analysis, symptomatic ductus was associated with an increased risk of extubation failure. Conclusion(s): Presence of symptomatic patent ductus arteriosus was associated with extubation failure. Further investigations are needed to establish whether screening for presence of ductus and treatment of the same, prior to extubation among these infants, improves chances of successful extubation and cardiorespiratory outcomes.

Background: Uniformity and compliance with clinical practice guidelines (CPGs) for use of palivizumab in preventing severe RSV infection in Australian high-risk infants remain unclear. Methods: An online survey was conducted across the Australian and New Zealand Neonatal Network (ANZNN) to determine clinical practices around palivizumab. A literature search was also performed to identify and compare national and international guidelines. Results: Sixty-five of 422 ANZNN members completed the survey. Respondents included 61 senior medical staff of consultants/staff specialists (78%) and four nursing staff (6%). Infants most likely to be recommended palivizumab included preterm infants born <29 weeks gestational age (GA) (30%), children with chronic lung diseases (CLD) born <32 weeks GA (40%), and with hemodynamically significant heart disease (35%). Many respondents (53%) stated that CPGs for palivizumab were developed locally. Twenty guidelines (10 international and 10 domestic) were obtained in total; 16(80%) recommended palivizumab use in preterm infants, 16(80%) recommended use in infants with CLD, 17(85%) congenital heart disease (CHD) and six (30%) bronchopulmonary dysplasia (BPD). Eight (40%) guidelines provided specific recommendations for immunocompromised infants. Canada, Western Australia, and American Academy of Paediatrics provided recommendations for Indigenous children. Frequency and dosage of palivizumab was universal across all CPGs. None of the international guidelines obtained were from low- or middle-income countries. Conclusions: Standardisation of CPGs may improve clinical decision making around use of palivizumab in high-risk infants.

Objectives: Intralobar pulmonary sequestration (ILS) is rare and its optimal clinical management remains ambiguous. This study aimed to introduce our ten-year experience in clinical management of ILS. And the application of our novel surgical method, thoracoscopic anatomical lesion resection (TALR) on ILS was introduced. Materials and Methods: Patients with ILS who received treatment between December 2010 and December 2020 were included in this study, retrospectively. A binary logistic regression model was used to assess risk factors for preoperative symptoms. Intraoperative and postoperative outcomes were compared between the thoracoscopic lobectomy and lung-sparing surgery groups. Results: A total of 112 patients were included in this study. Age and maximum cyst diameter were risk factors for preoperative symptoms. Lung-sparing surgery proved to be safe and feasible with no residual lesions. Conclusions: The overall prognosis of early thoracoscopic surgery for ILS was good. Lung-sparing surgery, especially TALR could be used as a first-line surgery for ILS. It may resolve the long-standing controversy over whether surgery for asymptomatic patients with ILS.