A Pediatric Case of Neuromyelitis Optica and Pulmonary Inflammatory Myofibroblastic TumorAlyson Win, BS (firstname.lastname@example.org)a : Conceptualization; writing- original draft; writing- review and editing.Jesper Jiang, BS (email@example.com)a:Conceptualization; writing- original draft. John Fitzwater, MD (john.fitzwater@BSWHealth.org)b : writing- review and editing; supervision. Edwin Hernandez Caro, MD (Edwin.Caro@BSWHealth.org)c : writing- review and editing. Amy Cruickshank, DO (Amy.Cruickshank@BSWHealth.org)d : writing- review and editing. Duriel Hardy, MD (Duriel.Hardy@austin.utexas.edu)e : writing- review and editing. Ydamis Estrella Perez, MD (Ydamis.Perez@BSWHealth.org)f : writing- review and editing. Michele Prater, PNP (JMichele.Prater@BSWHealth.org)c: writing- review and editing. Malvika Sagar, MD (Malvika.Sagar@BSWHealth.org)c : Conceptualization; writing- review and editing; supervision.a: Texas A&M Health Science Center School of Medicine, Temple, TXb: Department of Pediatric Surgery, Baylor Scott and White McClane Children’s Medical Center, Temple, TXc: Department of Pediatric Pulmonology, Baylor Scott and White McClane Children’s Medical Center, Temple, TXd: Department of Pediatric Hematology/Oncology, Baylor Scott and White McClane Children’s Medical Center, Temple, TXe: Department of Pediatric Neurology, Dell Children’s Medical Center, Austin, TXf: Department of Pathology, Baylor Scott and White Medical Center, Temple, TX
Pathogenic variants in the Surfactant Protein C gene ( SFTPC) result in fibrotic childhood interstitial lung disease (chILD). We previously reported three children with SFTPC pathogenic variants with respiratory failure who were supported by chronic invasive ventilation via tracheostomy as an alternative to lung transplantation or comfort care [(1)](#ref-0001). We present two children with SFTPC pathogenic variants treated with non-invasive ventilation (NIV) (Figure 1).
We believe that the data in this letter clearly demonstrate that even with CFTR2 expansion to 719 variants, striving to achieve equity of early diagnosis of CF via screening requires states to perform a sweat test in all infants with a high IRT level and one identified CFTR variant. This recommended policy can be debated but sweat testing overload should not be the argued as the barrier and CF specialists need to recognize that CFTR2 may never include all of the very rare, “private” pathogenic variants nor will next generation sequencing cover the structural variants such as deletions and duplications.
Introduction: The European Respiratory Society Oscillometry Taskforce identified that clinical correlates of bronchodilator responses are needed to advance oscillometry in clinical practice. The understanding of bronchodilator-induced oscillometry changes in preterm lung disease is poor. Here we describe a comparison of bronchodilator assessments performed using oscillometry and spirometry in a population born very preterm and explore the relationship between bronchodilator-induced changes in respiratory function and clinical outcomes. Methods: Participants aged 6-23 born ≤32 (N=288; 132 with bronchopulmonary dysplasia) and ≥37 weeks’ gestation (N=76, term-born controls) performed spirometry and oscillometry. A significant bronchodilator response (BDR) to 400mcg salbutamol was classified according to published criteria. Results: A BDR was identified in 30.9% (n=85) of preterm-born individuals via spirometry and/or oscillometry, with poor agreement between spirometry and oscillometry definitions (k=0.26; 95%CI 0.18 to 0.40, p<0.001). Those born preterm with a BDR by oscillometry but not spirometry had increased wheeze (33% vs 11%, p=0.010) and baseline resistance (Rrs 5 z-score mean difference (MD)= 0.86, 95%CI 0.07 to 1.65, p=0.025), but similar spirometry to the group without a BDR (FEV 1 z-score MD= -0.01, 95%CI -0.66 to 0.68, p>0.999). Oscillometry was more feasible than spirometry (95% vs 85% (FEV 1), 69% (FVC), p<0.001), however being born preterm did not affect test feasibility. Conclusion: In the preterm population, oscillometry is a feasible and clinically useful supportive test to assess the airway response to inhaled salbutamol. Changes measured by oscillometry reflect related but distinct physiological changes to that measured by spirometry and thus these tests should not be used interchangeably.
Mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene typically cause severe health complications in multiple organ systems, including the respiratory and gastrointestinal systems. Certain CFTR mutations, however, cause milder clinical phenotypes which may delay confirmatory diagnosis and treatment. Moreover, rare CFTR variants are not studied frequently or approved for genotype specific CFTR modulator therapies, creating further disadvantage. Herein, we describe a personalized medicine approach for a CF patient with three CFTR variants and mild clinical disease to aid in the diagnosis of CF and development of an optimized treatment plan. This strategy relied on the synergistic combination of advanced genetic analyses, patient-derived models of CFTR function and modulation, and personalized clinical care delivery. Whole Exome Sequencing revealed three compound heterozygous CFTR variants: c.2249C>T (p.P750L), c.1408G>A (p.V470M), and c.1251C>A (p.N417K). The CFTR channel function and nature of protein defects for both V470M and N417K mutations are not previously characterized. Patient-derived intestinal organoid models demonstrated residual CFTR channel activity, with improvement in channel function following treatment with the CFTR modulators. / n vitro studies in heterologous model system demonstrated that P750L has the features of Class II CFTR mutations, whereas V470M/N417K exhibited characteristics of Class II, III, and IV mutations, with all three variants responding to the combination modulator therapy of elexacaftor, tezacaftor, and ivacaftor (ETI) and showing functional rescue to near-wild-type CFTR levels. The laboratory data was then utilized to inform patient care, including off-label prescription of ETI. Following 18 months of ETI therapy, significant improvements were noted in key clinical outcomes, including sweat chloride, nutritional parameters, and respiratory and gastrointestinal symptoms. This study demonstrates a personalized medicine approach across clinical and laboratory domains used to care for CF patients with atypical symptoms and/or rare CFTR mutations.
Aim: Pulmonary near-infrared spectroscopy (NIRS) is a new and promising tool for diagnosis of neonatal respiratory diseases (RD). The study aimed to determine the role of pulmonary regional oxygen saturation (pRSO 2) values obtained by NIRS in the early distinction of neonatal pneumonia (NP) from transient tachypnea of the newborn (TTN). Methods: This prospective, observational, double-blind study was conducted in neonatal intensive care unit (NICU) between 2020-2021. Late preterm and term newborns hospitalized in the NICU due to the diagnosis of TTN and NP were included. Cerebral RSO2 and pRSO2 values were measured during the 1 st, 24 th, 48 th and 72 nd hours of hospitalization, using NIRS. Results: Of the eligible 40 infants, 65% (n:26) were diagnosed as TTN and 35% (n:16) as NP. The pRSO 2 values were significantly higher in the TTN group than the NP group for both apexes (75.3±8.7 vs. 69±5.4, p:0,018, respectively) and lateral lung (77.8±6 vs. 72.7±6.2, p:0,016, respectively) in the 1 st hour of hospitalization. There were significant differences in pRSO 2apex and pRSO 2lateral values between the 1 st and 24 th hours of hospitalization and the 24 th and 48 th hours in the NP group (p 2: 0.001 for both). The optimal pRSO 2apex cut-off value was >72% to predict the diagnosis of NP with a sensitivity of 78.6% and a specificity of 69.2%. Conclusion: Pulmonary NIRS may be considered as a feasible and promising diagnostic tool in late preterm and term infants with RD. It may also be helpful for the early differentiation of NP from TTN and the courses of these diseases.
In conclusion, we present this case in order to complement CFTR gene mutations data of Chinese children with cystic fibrosis and improve clinicians' understanding of this disease in China. Besides, with the development of molecular biology technology, gene detection was expected to play an important role in the early diagnosis, early treatment, and prognosis improvement of the disease.
Background: Bronchiolitis is a viral respiratory illness most commonly caused by respiratory syncytial virus (RSV). COVID-19 disrupted typical patterns of viral transmission. Our study aimed to compare low value care for bronchiolitis in a tertiary emergency department (ED) in the United States over the previous five years. Methods: This was a descriptive cohort study through a retrospective chart review from 2017-2022 analyzing ED visits for bronchiolitis including disposition, disease severity, chest radiographs, albuterol, and high flow nasal cannula. A year was a 12 month period from March to February. Results: In the three years prior to the pandemic, there were over 2000 ED visits for bronchiolitis per year (3.1% of all ED visits), which decreased to 450 visits for bronchiolitis (1% of all visits) in 2020. Human rhino/enterovirus was the most common virus detected (92%). Admission rates, albuterol use, high flow nasal cannula use, and chest radiographs were all higher during the first year of the pandemic. The summer of 2021 had the highest visits across the 5 study years (2743, 4.0% of all visits) with a return to previous rates of resource utilization. Conclusions: During the early pandemic, measures to halt the spread of COVID-19 also altered the transmission of RSV and emergency visits for bronchiolitis. There was an increase in lower value care while the volume was low and rhinovirus was the dominant virus detected. As restrictions lifted in 2021, there was a large resurgence of RSV in the atypical summer months with a return of previous rates of resource utilization.
Fibroblast growth factor 10 (FGF10) is a signaling molecule with a well-established role for lung branching morphogenesis. Rare heterozygous, deleterious variants in the FGF10 gene are known causes of the lacrimo-auriculo-dento-digital (LADD) syndrome as well as aplasia of lacrimal and salivary glands (ALSG). Previous studies indicate that pathogenic variants in FGF10 can cause lethal human developmental disorders of the lung, but reports on diffuse lung disease caused by pathogenic variants in the FGF10 gene are lacking. We describe four children with postnatal onset of severe diffuse lung disease and heterozygous variants in FGF10, each detected by whole exome or whole genome sequencing. All children presented with postnatal respiratory failure. Two children died within the first 2 days of life, one patient died at age of 12 years and one patient is alive at age of six years, but still symptomatic. One patient presented signs of severe dental caries suggestive for ALSG or LADD-syndrome. Histopathological analysis of lung biopies from the two children with early postpartum demise revealed diffuse developmental disorder representing acinar dysplasia. Sequential biopsies of the child with survival until the age of 12 years revealed alveolar simplification and progressive interstitial fibrosis. Our report extends the phenotype of FGF10-related disorders to diffuse developmental disorders of the lung and early onset lung fibrosis. Therefore, FGF10-related disorder should be considered even without previously described syndromic stigmata in children with postnatal respiratory distress, not only when leading to death in the neonatal period but also in case of persistent respiratory complaints.
with other laboratory and clinical investigations. Early and accurate diagnosis of inherited conditions generally leads to better medical care for patients and their families, with improved knowledge of the natural history of the condition and early intervention. It is therefore essential that equitable access to such testing is established for indigenous and isolated populations, in order to further narrow the health disparity gap. Although supported by funding from a few sources, this study signals a success for the Silent Genomes Project, with one of the cases having been identified by whole genome sequencing within that project, after negative whole exome sequencing. Furthermore the study has potential life-changing clinical consequences and provides starting points for possible interventions for respiratory medicine in the Inuit population. These include increased awareness of the possibility of PCD in patients presenting with neonatal respiratory distress, bronchiectasis or otitis media leading to early intervention; and in conjunction with Inuit organizations and public health officials, targeted analysis of the DNAH11 variant in the population with the possible introduction of newborn screening for PCD.
Huiyong Hu1#, Xiaoping Jing2#, Xiuhua Duan3, Leiping Zhou4, Yunfeng Xu1*1 Department of the Ultrasonography, Shanghai Children’s Hospital, Shanghai Jiao Tong University, school of medicine, Shanghai 200040, China;2 Department of Traditional Chinese Medicine, Shanghai Children’s Hospital, Shanghai Jiao Tong University, school of medicine, Shanghai 200040, China;3 Department of Radiology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, school of medicine, Shanghai 200040, China;4 Department of Radiology, International Peace Maternity & Child Health Hospital of China welfare institute, Shanghai Jiao Tong University, school of medicine, Shanghai 200030, China;# These authors contributed equally to this work.* Corresponding author: Yunfeng Xu, Department of the Ultrasonography, Shanghai Children’s Hospital, Shanghai Jiao Tong University, school of medicine;Address: 1400 West Beijing Road, Shanghai, China Lane 24 Zip Code 200040;Phone: 18917128478E-mail: xuyunfeng65@163. com (F X).During a prenatal ultrasonography examination late in the second trimester, a fetus was found to have a right diaphragmatic hernia (Figure S1). Multidepartment dynamic monitoring was instituted, and the fetus was later successfully delivered by cesarean section after fetal distress became evident. After intubation, the infant was stabilized and transferred to the Department of Neonatology at our hospital.The enhanced computed tomography of the chest and stomach displayed multiple air-filled intestinal shadows in the right chest cavity, the widest being about 20.0 mm. The right lung, mediastinum, and heart were compressed and displaced, and most of the lung tissue in the right lung was consolidated. Atelectasis is evident in the irregular enhancement shadow at the right upper abdomen, about 43.5 × 32.0 mm in size. The boundary between some sections and the posterior margin of the right lobe of the liver was unclear, but the blood supply (hepatic artery and portal vein branches) was visible (Figure). Blood gases, routine bloodwork, liver and kidney function, and myocardial enzymes were essentially normal.At 40 + 4 weeks, with the infant under total anesthesia, hernia repair was performed. The liver and intestines in the thoracic cavity were brought back into the abdominal cavity; the tissues around the hernia ring in the diaphragm were carefully dissociated; and patch repair and suturing were performed (Figures S2–S4). After the operation, the infant’s vital signs were stable and their condition remained good during follow-up.Congenital diaphragmatic hernia (CDH) is a potentially fatal birth defect[1-3]. In China today, all pregnant women undergo ultrasonography to uncover pregnancy- related conditions. A “green channel” – that is, a multidepartment collaborative for the emergency treatment of perioperative pulmonary hypertension, pulmonary dysplasia, and other complications in newborns with CDH – has been established, helping to assure the best prognosis for those infants.
Introduction: This study aimed to determine if a respiratory therapist (RT)-driven high flow nasal cannula (HFNC) protocol could decrease duration of HFNC use, pediatric intensive care unit (PICU) and hospital length of stay (LOS), and duration of continuous albuterol use in pediatric patients with critical asthma. Methods: This was a quality improvement project performed at a quaternary academic PICU. Patients admitted to the PICU between 2 and 18 years of age with a diagnosis of asthma requiring continuous albuterol and HFNC were included. Implementation of a RT-driven HFNC protocol [Plan-Do-Study-Act (PDSA) 1] occurred in October 2017. Additional interventions included weaning continuous albuterol and HFNC simultaneously (PDSA 2; March 2019), adjusting HFNC wean rate (PDSA 3; July 2020), and a HFNC holiday (PDSA 4; October 2021). HFNC duration was the primary outcome. Secondary outcomes included LOS data and continuous albuterol duration. Noninvasive ventilation (NIV), invasive mechanical ventilation (IMV), and 7-day PICU and hospital readmission rates were balancing measures. Results: 410 patients were included. Patient demographics and adjunct therapy use did not differ among the groups. HFNC duration decreased from 26.8 to 18.1 hours, both PICU and hospital LOS were decreased (41 to 31.8 hours, and 86.5 to 68 hours respectively) after PDSA 2. These outcomes remained stable during PDSA 3 and 4. Continuous albuterol duration and NIV use remained stable, while IMV use decreased throughout the study. Conclusions: An RT-driven HFNC protocol led to an improvement in clinical outcomes for pediatric patients with critical asthma without an increase in adverse events.
6 month old child presented with complaints of recurrent respiratory infection, tachypnea and decreased air entry on right side . Xray chest AP view (Fig(#fig-cap-0001)) showed opaque right hemithorax with ipsilateral mediastinal shift and compensatory hyperinflation of left lung. Further evaluation with CECT thorax (Fig (#fig-cap-0002)) showed hypoplastic right lung with collapse consolidation and right sided mediastinal shift. Bifurcation of trachea was not seen with trachea continuing as left main bronchus with normal segmental division. Right bronchus appears to be arising from lower part of esophagus, precise communication was not demonstrated (Fig (#fig-cap-0003)). Conventional contrast (non ionic) esophagogram was performed and free flow of contrast was seen from lower third of esophagus to the right main bronchus (Fig (#fig-cap-0004)) confirming the diagnosis of Congenital bronchopulmonary foregut malformation (CBPFM)
Background: Small air filled peripheral subpleural cysts are a well described feature of pulmonary anatomy at computerised tomographic (CAT) scan in children with Trisomy 21, yet only anecdotally described in association with other pathologies. The significance of these cysts is unknown. Objective: To investigate and explore the pathogenesis of these subpleural cysts in children. Materials and Methods: A retrospective review of 16 cases with subpleural cysts diagnosed on CT chest was performed. The distribution, location and ancillary CT findings were recorded. Hospital charts were reviewed for clinical details, especially cardiac abnormalities, pulmonary artery hypertension (PAH) and genetic associations. Histopathological and clinical correlative data were recorded. Results: 11/16 children (69%) were found to have an underlying chromosomal or genetic abnormality, six of whom had Trisomy 21. The remaining 5/16 cases (21%) had miscellaneous disorders without an identifiable genetic basis. The most common co-morbidities were cardiac abnormalities (81%) and PAH (62.5%). Regardless of their underlying etiologies, the cysts were present bilaterally in most cases (14/16, 88%). We observed both the postnatal development and the progression of cysts in our cohort . On long term follow-up, there were five deaths (31%) and six cases (38%) requiring maintenance oxygen therapy due to chronic hypoxia. Two cases (12.5%) became completely asymptomatic after correction of their underlying abnormalities. Conclusion: Subpleural cysts are not exclusive to Trisomy 21 and may be seen in other inherited or acquired causes, likely due to altered alveolar growth. We suspect these cysts are a sign of an underlying developmental disorder with variable clinical effect, especially in children with congenital cardiac disease.
Introduction Viral infections are associated with pulmonary exacerbations in children with Cystic Fibrosis (cwCF), but after 3 years of SARS-CoV-2 pandemic, whether cwCF are at higher risk of developing COVID-19 or its adverse consequences remains controversial. Methods We conducted an observational, multicenter, cross-sectional study of cwCF infected by SARS-CoV-2 between March 2020 and June 2022, (1 st to 6 th COVID-19 pandemic waves) in Spain. The study aimed to describe patients’ basal characteristics, SARS-CoV-2 clinical manifestations and outcomes, and whether there were differences across the pandemic waves. Results During study time, 351 SARS-CoV2 infections were reported among 341 cwCF. Median age was 8.5 years (range 0-17) and 51% were female. Cases were unevenly distributed across the pandemic, with most cases (82%) clustered between November 2021 and June 2022 (6 th wave, also known as Omicron Wave due to the higher prevalence of this strain in that period in Spain). Most cwCF were asymptomatic (24.8%) or presented with mild Covid-19 symptoms (72.9%). Among symptomatic, most prevalent symptoms were fever (62%) and increased cough (53%). No multisystem inflammatory syndrome (MIS-C), persisting symptoms, long-term sequelae or deaths were reported. Conclusions Spanish current data indicate that cwCF do not experience higher risks of SARS-CoV-2 infection nor worse health outcomes or sequelae. Changes in patients’ basal characteristics, clinical courses and outcomes were detected across waves. While the pandemic continues, and new SARS-CoV-2 variants are being identified, a worldwide monitoring of COVID-19 in pediatric CF patients is needed.
Objective: To evaluate the frequency and burden of disease of SARS-CoV-2 and other respiratory viruses in children under the age of 2 months. Methods: A retrospective, cross-sectional, single-center study was conducted between March 2021, and February 2022. All children under the age of 2 months and tested for SARS-CoV-2 were included. The frequency of SARS-CoV-2, of other respiratory viruses and the burden of disease caused by SARS-CoV-2 and other respiratory viruses were evaluated. Results: 727 children with an RT-PCR test for SARS-CoV-2 were included (mean age: 0.9 months (±0.6); boys: 57%); 514 (71%) in the emergency room and 213 (29%) in hospital. Among them, 62 (8.5%) had a positive RT-PCR test for SARS-CoV-2, more often in the Omicron period (23%) than in the Alpha period (4%). Of the 565 (78%) with a multiplex RT-PCR test for other viruses, 325 (58%) were positive. Children with a positive SARS-CoV-2 were less likely to have required respiratory support (p=.001), enteral nutrition (p=.03), or intensive care admission (p=.01) and had a shorter hospital stay than children with other respiratory viruses (5d vs. 7d, p=.007). Conclusion: In this young population of children, SARS-CoV-2 infection was less frequent and less severe than other viral respiratory infections.