Objective(s): To determine the impact of Clostridioides difficile Infection (CDI) among pediatric Cystic Fibrosis (CF) hospitalizations using a large nationally representative pediatric hospital database . Study design: We identified Cystic Fibrosis-related hospitalizations during the years 1997 to 2016 in the Kids’ Inpatient Database [KID] and compared in-hospital mortality, Length of Stay [LOS], and hospital charges among hospitalizations with and without a coexisting diagnosis of C. difficile using logistic regression models for mortality and general linear models with gamma distribution and logarithmic transformation for LOS and hospital charges. We also evaluated temporal trends in the proportion of CF hospitalizations with concomitant CDI using data published triennially Results: We analyzed 21, 616 pediatric CF hospitalizations between the years 1997 to 2016 and found a total of 240 (1.1%) hospitalizations with concurrent CDI diagnosis. Adjusted analyses demonstrated an association of CDI with increased mortality (OR 5.2, 95% 95% CI 2.5-10.7), longer LOS (46.5% increment, 95% CI 36.0-57.1), and higher charges (65.8% increment, 95% CI 53.5-78.1) for all comparisons. The proportion of CF hospitalizations with CDI increased over time from 0.64% in 1997 to 1.73% in 2016 (p<0.001). Conclusion(s): As CDI is associated with excess mortality, LOS, and cost in children hospitalized for CF, efforts to reduce infection rates and aggressive diagnosis and treatment of active infections should be prioritized to improve hospital outcomes among children with CF.
Introduction Children with Down Syndrome (DS) are at high risk of sleep disordered breathing (SDB). We aimed to examine the burden of SDB in infants with DS referred to tertiary sleep center. Methods Infants (≤12 months old) with DS who underwent consecutive polysomnography (PSG) at a single academic sleep center over a 6-year period were included. OSA (obstructive apnea hypopnea index [oAHI]>1/hr), central sleep apnea (central apnea index>5/hr) and the presence of hypoventilation (% time spent with CO2 > 50 mmHg either by end-tidal or transcutaneous> 25% of total sleep time) and hypoxemia (time spent with O2 saturation <88% >5 min) were ascertained. For infants who underwent adenotonsillectomy (AT), we compared the SDB metrics before and after the AT. Results A total of 40 infants were included (Mean age 6.6 months, male 66%). PSGs consisted of diagnostic (n=13) and split night (n=27, 68%) studies. All met criteria for OSA with mean oAHI 34.6 (32.3). Central sleep apnea was present in 11 (27.5%) of infants. A total of 11 (27.5%) had hypoxemia. Hypoventilation was present in 10 (25%) infants. There was a trend of association between hypothyroidism and hypoventilation (OR: 5.5 [0.96-34.4], p=0.056). Among 13 infants who underwent AT and had a follow up PSG, severity of OSA markedly reduced after AT (oAHI difference: 34/hr , p=0.0002). Conclusion This study highlights the high prevalence of SDB in infants with DS and supports early PSG assessment in this patient population.
Vaping associated lung injury (EVALI) has increased in prevalence after first being noted in an outbreak among teenagers in 2019. Vaping involves the use of a heating device to aerosolize a product, typically nicotine or more recently, cannabinoids. Products that contain cannabinoids, such as CBD oil, are being used more as these products are easy to obtain and are typically less expensive. The clinical manifestations of EVALI are widespread and include respiratory symptoms as well as cardiogenic, gastrointestinal, and constitutive symptoms. EVALI rarely presents with hemoptysis as one of the main presenting symptoms, especially in an adolescent. This case will discuss EVALI with associated hemoptysis in a teenager secondary to vaping cannabinoid oil.
Rationale: Animal models suggest pre-eclampsia (Pre-E) affects alveolar development, but data from humans are lacking. Objective: Assess the impact of Pre-E on airway function, diffusion capacity, and respiratory morbidity in preterm and term infants born from mothers with Pre-E. Methods: Infants born from mothers with and without Pre-E were recruited for this study; term and preterm infants were included in both cohorts. Respiratory morbidity in the first 12 months of life was assessed through monthly phone surveys. Raised volume rapid thoracoabdominal compression and measurement of diffusion capacity of the lung to carbon monoxide (DLCO)) were performed at 6 months corrected age. Results: There were 146 infants in the Pre-E cohort and 143 in the control cohort. The Pre-E cohort was further divided into non-severe (N=41) and severe (N=105) groups. There was no significant difference in DCLO and DLCO/aveolar volume amongst the three groups. Forced vital capacity was similar amongst the three groups, but the non-severe Pre-E group had significantly higher forced expiratory flows that the other two. After adjusting for multiple covariates including prematurity, the severe Pre-E group had a lower risk for wheezing in the first year of life compared to the other two. Conclusions: Pre-E is not associated with reduced DLCO, lower forced expiratory flows, or increased wheezing in the first year of life. These results differ from animal models and highlight the the complex relationships between Pre-E and lung function and respiratory morbidity in human infants.
Pneumothorax as a sequalae of vaping is a relatively recent complication being described in the literature. Smoking has classically been associated with increased risk of pneumothorax, and emerging evidence is showing that electronic cigarettes (e-cigarettes) likely carry some of the same risks. Since electronic cigarettes increased in popularity, especially among the adolescent population, there has been reported increased incidence of lung injury, including pneumothorax. We present a case of a 15-year-old female with a history of e-cigarette use admitted for recurrent pneumothorax with failure to re-expand requiring surgical intervention.
Introduction: Lower socioeconomic status is associated with significantly poorer outcomes in weight, lung function, and pulmonary exacerbation rates in People with CF (PwCF). Global aim: We aim to reduce health disparities and inequities faced by PwCF by screening for and addressing unmet social needs. Specific aims: We aimed to increase routine Social Determinants of Health (SDoH) screening of eligible PwCF from 0% to 95% and follow-up within two weeks for those PwCF who screened positive and requested assistance from 0% to 95% by December 31, 2021. Methods: The Model for Improvement methodology was employed. A process map and a simplified failure mode effects analysis chart were created for the screening and SDoH follow-up process. Those who screened positive for SDoH and requested assistance, a follow-up contact was made to offer intervention. Intervention: Adult PwCF who had at least one UVA Clinic encounter in 2021 were screened for SDoH. The SDoH screening tool included eight domains: housing, food, transportation, utilities, health-care access, medication access, income/employment and education. Follow-up was completed with all PwCF who screened positive for SDoH. Results: A total of 132 of 142, (93.0%) PwCF eligible for screening completed the SDoH screening. Of the PwCF who completed screening, 56 (42.4%) screened positive for SDoH. A follow-up rate of 100% was achieved in June 2021 and maintained through December 2021. Conclusion: Implementing screening for SDOH and follow-up to mitigate social difficulties in adult PwCF at UVA was successful and could be reproduced at other CF care center.
An eight-year-old girl with cystic fibrosis (CF) developed a left upper lobe collapse failing to resolve with initial conventional antibiotic treatment, mucolytics and intensified physiotherapy. Mycobacterium abscessus was isolated from her sputum. Bronchoscopy revealed thick viscous mucus plugging of the left upper lobe bronchus with complete obliteration. Three bronchoscopies with saline lavage and Dornase alfa, a rhDNase, at the end of each procedure resulted in removal of this mucus plug and the re-inflation of the affected lobe, with clinical and radiological resolution. The use of flexible bronchoscopy as a ‘secondary’ treatment with 0.9% saline lavage and instillation of rhDNase is described sparsely in the literature. This is the first reported successful therapeutic resolution of a lung collapse in a CF patient with Mycobacterium abscessus, with sequential therapeutic bronchoscopies with instillation of Dornase alfa. This should be considered for lobar collapse in CF not responding to the standard therapeutic regime.
Rationale The lung clearance index (LCI) is increasingly being used in the clinical surveillance of patients with cystic fibrosis (CF). However, there are limited data on long-term variability and clinically relevant changes in LCI during routine clinical surveillance. Objectives To evaluate long-term variability of LCI and propose a threshold for a clinically relevant change. Methods Children with CF aged 4-18 years performed LCI measurements every three months as part of routine clinical surveillance during 2011-2020 in two centers. The variability of LCI during periods of clinical stability was assessed using mixed-effects models and was used to identify thresholds for clinically relevant changes. Results Repeated LCI measurements of acceptable quality (N= 858) were available in 100 patients with CF. Variability of repeated LCI measurements over time expressed as coefficient of variation (CV%) was 7.4%. The upper limit of normal (ULN) for relative changes in LCI between visits was 19%. Conclusion We report the variability of LCI in children and adolescents with CF during routine clinical surveillance. According to our data, a change in LCI beyond 19% may be considered clinically relevant. These findings will help guide clinical decisions according to LCI changes.
We read with great interest recent research by Anderson et al.1 on how NICU respiratory support affects infant feeding, and by Behnke et al.2 on the potential interference of infant feeding with successful respiratory stabilization of the preterm infant. Since both preclinical and human studies have established that nutrition plays a key role in preterm lung growth and development, a crucial aspect of any research undertaken in the field of neonatal respiratory outcomes should be the breastfeeding history. It is now becoming well established that human milk feeding actively contributes in limiting lung injury among vulnerable neonates.
People with cystic fibrosis (CF) have an amazing outlook with the treatment availability of highly effective modulators. Unfortunately, not all PwCF are eligible for modulators leading to continued pulmonary exacerbations and advanced lung disease. Additionally, optimizing diagnosis and evaluation for CF in the newborn period continues to be an area of focus for research. This review article will work to cover articles published in 2021 with high clinical relevance related to the above topics, however due to the extensive body of research published, this review will not be comprehensive.
A previous study has reported cryptococcal meningoencephalitis in a previously healthy adult affected with H1N1 influenza. Here, we report cryptococcosis occurred in a previously healthy child with H3N2-influenza, which further suggests a potential association between cryptococcosis and influenza viral infection. In this case, a 5-year-old girl presented with fever and cough was admitted to our hospital with positive test for H3N2 influenza and pulmonary infiltration by chest CT scan. After antibiotic regimens, the clinical symptoms were not improved at all. Her bone marrow culture proved Cryptococcus infection. Following treatments with amphotericin B liposome and flucytosine, her body temperature returned to normal. Pulmonary infection was completely absorbed following oral fluconazole treatment for 6 mon.
Introduction: Infants and children diagnosed with BPD have a higher likelihood of recurrent hospitalizations and asthma-like symptoms. Socio-environmental factors that influence frequency and severity of pulmonary symptoms in these children during the pre-school age are poorly under-stood. In this study, we used the Area Deprivation Index (ADI) to evaluate the relationship between the socio-environmental exposures in children with BPD and respiratory outcomes during the first few years of life. Methods: A registry of subjects recruited from outpatient BPD clinics at Johns Hopkins University (n=909) and the Children’s Hospital of Philadelphia (n=125) between January 2008 and October 2021 was used. Subjects were separated into tertiles by ADI scores aggregated to ZIP codes. Care-giver questionnaires were used to assess the frequency of respiratory morbidities and acute care usage for respiratory symptoms. Results: The mean gestational age of subjects was 26.8±2.6 weeks with a mean birthweight of 909±404 grams. The highest tertile (most deprived) of ADI was significantly associated with emer-gency department visits (aOR 1.72; p=0.009), hospital readmissions (aOR 1.66; p=0.030), and activi-ty limitations (aOR 1.55; p=0.048) compared to the lowest tertile. No association was seen with steroid, antibiotic or rescue medication use, trouble breathing, or nighttime symptoms. Conclusion: In this study, children with BPD who lived in neighborhoods of higher deprivation were more likely to be re-hospitalized and have ED visits for respiratory reasons. Identifying socio-environmental factors that contribute to adverse pulmonary outcomes in children with BPD may provide opportunities for earlier interventions to improve long-term pulmonary outcomes.
The diagnosis of primary ciliary dyskinesia (PCD) is made through a combination of clinical features supported by a panel of diagnostic tests. Our cases highlight the similarities in the clinical presentation of patients with the specific immunodeficiency activated phosphatidylinositol 3-kinase delta syndrome 1 (APDS1 or PIK3CD) and PCD. We highlight the importance of repeating nasal nitric oxide testing (nNO) when PCD has not been confirmed by genetic or ciliary electron micrograph (EM) analysis in the setting of an expanded suppurative lung disease differential that includes considerations for immunodeficiency as well as PCD.
Pediatric Pulmonology , LetterElevated serum TARC/CCL17 levels are associated with childhood interstitial lung disease in patients with SFTPC gene mutationYuto Otsubo MD1; Yuji Fujita MD1; Yusuke Ando MD, PhD1; George Imataka MD, PhD1; Shigemi Yoshihara MD, PhD11Department of Pediatrics, Dokkyo Medical University, 880, Kitakobayashi, Mibu, Shimotsuga, Tochigi, 321-0207, JapanCorresponding author:Yuto OtsuboDepartment of Pediatrics, Dokkyo Medical University, 880, Kitakobayashi, Mibu, Shimotsuga, Tochigi, 321-0293, JapanTel: +81-0282-86-1111Fax: +81-0282-86-7152E-mail: [email protected]:Childhood interstitial lung disease; TARC/CCL17; SFTPCRunning head:Childhood ILD and increased TARC/CCL17 levelTo the Editor,Childhood interstitial lung disease (ILD) is a serious and often life-threatening disease that causes interstitial lung lesion formation during childhood. Several causative genes of childhood ILD, such asSFTPC , SFTPB , and ABCA3 , have been identified in some children. The pathogenesis of ILD caused by SFTPC mutations may include the accumulation of surfactant protein C (SP-C) in vesicles, inhibition of pulmonary surfactant reuptake, and decreased secretion of SP-C, but this remains to be confirmed.1Thymus and activation-regulated chemokine/C-C motif chemokine ligand 17 (TARC/CCL17) is a known disease marker of atopic dermatitis. Recently, an association between idiopathic pulmonary fibrosis, a representative disease with pulmonary interstitial lesions, and TARC/CCL17 has been reported,2 but none between childhood ILD and TARC/CCL17.Here we report our experience of a case of childhood ILD in which the patient had an SFTPC mutation and an elevated TARC/CCL17 level at disease onset that decreased as the patient improved with treatment. TARC/CCL17 may be involved in the pathogenesis of ILD in children withSFTPC mutation, which is different from the pathogenesis of atopic dermatitis.An otherwise healthy 15-month-old girl was admitted to our hospital with fever, difficulty breathing, and poor oral intake. Nine days prior to the visit, nasal discharge and cough appeared and gradually worsened; subsequently, poor oral intake appeared. No fine crackles were noted. The patient required supplemental oxygen and was admitted to the hospital. She had no history of respiratory impairment at birth, but she had a family history of ILD in her maternal grandmother. Informed consent was obtained from the patient’s guardians for the publication of this case report.Laboratory tests showed a white blood cell count of 941 × 109/L, neutrophil count of 58%, C-reactive protein level of 0.01 mg/dL, lactate dehydrogenase level of 929 IU/L, Krebs von den Lungen-6 (KL-6) level of 909 U/mL (normal range < 500 U/mL), surfactant protein A level of 2770 ng/mL (normal <43.8 ng/mL), and surfactant protein D level of 319 ng/mL (normal <43 ng/mL), which were suspicious findings for ILD (Table 1). ß-D-glucan level was 7.9 pg/mL (normal <20 pg/mL) and cytomegalovirus antibodies were negative for both IgG and IgM. Chest radiography showed bilateral frosted shadows (Fig. 1), and a chest computed tomography scan showed bilateral diffuse frosted shadows (Fig. 2), leading to ILD diagnosis.Although prednisolone was started on the 2nd day of admission, the patient’s respiratory status did not sufficiently improve, and oxygen supplementation was required. Therefore, methylprednisolone (30 mg/kg/day) was administered twice for 3 consecutive days on days 13-15 and 19-21; however, the respiratory status remained poor. Hydroxychloroquine (10 mg/kg/day) was then started on day 21, and azithromycin (10 mg/kg/day) three times a week was started on day 56, following which the respiratory status gradually improved. On drinking cold water, the patient often coughed and sometimes vomited. When the water was warmed from 4°C to approximately 20°C, coughing and cough-induced vomiting drastically decreased. On day 66 of hospitalization, the patient was discharged with home-based oxygen. Respiratory status, oxygenation, and laboratory data for ILD markers such as KL-6 gradually improved (Table 1).Genetic analysis of SFTPB , SFTPC , ABCA3 ,CSF2RA , and CSF2RB showed SFTPC mutation and p.I73T (c.218T>C), and the ILD was determined to be caused by theSFTPC mutation.Additional examination revealed elevated TARC/CCL17 level at 10,270 pg/mL (normal <998 pg/mL), but IgE (24.2 IU/mL; normal <173 IU/mL) and IL-4 (2.7 pg/mL; normal <6 pg/mL) levels were not elevated in the early stages of treatment. TARC/CCL17 level decreased to 2,122 pg/mL on day 131 after the admission. Granulocyte-macrophage colony-stimulating factor (GM-CSF) level was measured twice on days 11 and 83, and on both, the GM-CSF level was under 5 pg/mL without significant elevation. Anti-GM-CSF antibody (0.3 U/mL; normal <1.7 U/mL) was negative.It has been hypothesized that many of these effector cell populations are recruited by TARC/CCL17 and act profibrogenically, but the details remain largely unknown.3) SFTPC mutations increase the number of abnormal alveolar type 2 epithelial cells (AT2) due to impaired metabolism of SP-C. A knock-in mouse model capable of regulating the expression of an isoleucine-to-threonine substitution at codon 73 (p.I73T) in SFTPC, at the same site as in the present case, showed persistently elevated TARC/CCL17 level in the bronchoalveolar lavage fluid (BALF). Furthermore, the same study also reported that TARC/CCL17 is specifically released by AT2.3 In ILD caused by SFTPC mutations, its pathogenesis involves AT2 hyperplasia. The decrease in TARC/CCL17 level in our patient suggests that either AT2 itself or TARC/CCL17 production from AT2 itself decreased with treatment. In this case, we report, for the first time, elevated serum TARC/CCL17 level in a patient with SFTPC mutation, which decreased with treatment.Our patient showed no symptoms of atopic dermatitis, and she had no skin condition, and no elevation of IgE and IL-4 levels. In the SFTPC p.I73T mouse model mentioned above, no significant level of IL-4 or IL-13 was detected in BALF, and no involvement of the Th2 response was observed.This high TARC/CCL17 level was not considered to be a result of the GM-CSF cascade. TARC/CCL17 is released from macrophages as a product of the GM-CSF cascade.4) GM-CSF is also known to be produced by AT2.5) However, in this case, serum GM-CSF levels were normal and not elevated, both at the beginning of treatment and after improvement.The limitation of this case is that bronchoalveolar lavage was not performed; therefore, the evaluation was based on serum level rather than local lung findings.This case suggests that TARC/CCL17 is involved in ILD pathogenesis. Further elucidation of the chemokine and receptor signaling cascade may lead to the targeting of some stages for therapy, which may be an important issue for future medical treatment. Therefore, elucidation of this pathogenesis is desirable.References1) Beers MF, Mulugeta S. Surfactant protein C biosynthesis and its emerging role in conformational lung disease. Annu Rev Physiol 2005;67:663-696.2) Sivakumar P, Ammar R, Thompson JR, Luo Y, Streltsov D, Porteous M, McCoubrey C, Ill EC, Beers MF, Jarai G, et al. Integrated plasma proteomics and lung transcriptomics reveal novel biomarkers in idiopathic pulmonary fibrosis. Respir Res 2021;22;273:1-13.3) Nureki SI, Tomer Y, Venosa A, Katzen J, Russo SJ, Jamil S, Barrett M, Nguyen V, Kopp M, Mulugeta S, et al. Expression of mutant Sftpc in murine alveolar epithelia drives spontaneous lung fibrosis. J Clin Invest 2018;128:4008-4024.4) Hamilton JA. GM-CSF-dependent inflammatory pathways. Front Immunol 2019;10;2055:1-8.5) Woo YD, Jeong D, Chung DH. Development and functions of alveolar macrophages. Mol Cells 2021;44:292-300.Conflicts of interest:The authors disclose no conflicts.Contributors:YO cared for the patient, conceived the concept of the case report, and drafted the initial manuscript. YF, YA, GI, and SY critically reviewed the manuscript for intellectual content. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work. All authors have read and approved the final manuscript.Acknowledgment:We would like to thank Editage (www.editage.com) for English language editing.We thank Dr. Goro Koinuma, Division of Pulmonology, National Center for Child Health and Development, Tokyo, Japan, for his invaluable expert opinion regarding the diagnosis and treatment of the patients.Sources of funding:No funding was obtained for this study.
Background: Children should be weaned from the ventilator once their clinical condition improves. Extubation failure is associated with poorer clinical outcomes in children. Predictive indicators of successful extubation are needed. This study aims to evaluate the predictive value of ultrasonographic diaphragm imaging could help predict weaning success. Methods: In this prospective, observational study conducted between March and December 2021, children between 1 month and 10 years of age who were mechanically ventilated for more than 48 hours were included. Diaphragm ultrasound (DUS) examinations were performed at the end of 2-hour extubation readiness test (ERT). The end-inspiratory thickness, end-expiratory thickness, diaphragmatic thickening fraction, diaphragmatic excursion, inspiratory slope and expiratory slope were evaluated. Results: Twenty-four (60%) patients were successfully extubated, while 16 (40%) required invasive or non-invasive mechanical ventilation support which were classified as failed extubation group. Three of the sixteen patients in the failed extubation group required re-intubation. Diaphragm thickening fraction was significantly greater in the successful weaning group (55,05 ± 23,75% vs. 30,9 ± 10,38%) (p<0,001). Diaphragm excursion was significantly greater in the SW group (14 ± 4,4 mm vs 11,05 ± 3,25 mm) (p<0,001). DTF and DE were found to have a sensitivity and specificity of 91.67 %, 87.50 %, and 83.33 %, 81.25 %, respectively. Conclusion: Diaphragm ultrasound is a feasible and promising tool to guide physicians during weaning from IMV. Among all DUS measurements, the DE and DTF indexes showed better performance in extubation failure than other diaphragmatic parameters.
Background Children with tracheostomies are at an increased risk of bacterial respiratory tract infections. Infections caused by multidrug-resistant organisms (MDROs) are more difficult to treat and can result in severe complications. We investigated the risk factors and sequelae of MDRO positivity in tracheostomy and chronic ventilator-dependent children. Methods We performed a retrospective chart review of 75 tracheostomy and chronic ventilator-dependent children at St. Louis Children’s Hospital. Data on demographics, respiratory cultures, hospitalizations, emergency department (ED) visits, and antibiotic usage were collected. We determined the frequency of MDRO positivity and compared the number of hospitalizations, number of ED visits, and antibiotic usage in patients with and without MDRO-positive cultures. Patient clinical variables were analyzed before and after MDRO acquisition. Results We found 75.7% (56/74) of our participants had an MDRO-positive culture, with methicillin-resistant Staphylococcus aureus (MRSA, n=36, 64%) and Pseudomonas aeruginosa (n=8, 14%) being the most commonly detected organisms. Patients with MDRO-positive cultures had a greater number of annual non-pulmonary admissions [OR=1.99, 95% CI (1.21-3.29), P= 0.008], inpatient antibiotic courses [OR=1.27, 95% CI (1.07-1.50), P=0.006], total antibiotic courses [OR=1.26, 95% CI (1.08-1.48), P= 0.004], and chronic antibiotic use [OR=2.31, 95% CI (1.12-4.74), P=0.03] compared to MDRO-negative participants. Patients that acquired MDROs during the study period subsequently required increased outpatient antibiotics [P= 0.006] but did not have increased pulmonary admissions or ED visits. Conclusion Frequent antibiotic usage and hospitalizations increase the risk of MDRO acquisition in children with tracheostomies and ventilator-dependence. Further antibiotic stewardship may help prevent resistant infections in technology-dependent children.