Cryptococcosis is an invasive, opportunistic, fungal infection that predominantly effects the respiratory tract and central nervous system in immunocompromised patients. It is classically associated with defects in cellular immunity such as acquired immunodeficiency syndrome. Here we describe a case of life-threatening laryngitis, endobronchitis and pneumonia due to Cryptococcus neoformans in a teenager with hypogammaglobulinaemia. To the best of our knowledge, no previous cases of laryngeal cryptococcosis have been reported in the paediatric population.
Objective Our objective was to test the hypothesis that in-hospital respiratory viral infections (RVI) would be significantly lower in a cohort of patients with established bronchopulmonary dysplasia in the SARS-CoV-2 era when compared to historical controls. Study Design On April 1, 2020, we implemented a universal infection prevention bundle to minimize the risk of nosocomial SARS-CoV-2 transmission in a dedicated BPD intensive care unit. We performed a retrospective cohort study and included patients with established BPD, as defined by the 2019 Neonatal Research Network criteria, admitted to our center who underwent real-time polymerase-chain-reaction RVI testing between January 1, 2015 and March 31, 2021. We excluded patients re-admitted from home. We compared to number of tests performed, the proportion of positive tests, and the distribution of viral respiratory pathogens in the pre- and post-SARS-CoV-2 eras. Results Among 176 patients included in the sudy, 663 RVI tests were performed and 172 (26%) tests were positive. The median number of tests performed, measured in tests per patient per month, in the SARS-CoV-2 era was not significantly different compared to the pre-SARS-CoV-2 era (0.45 vs 0.34 tests per patient per month, P = 0.07). The proportion of positive RVI tests was significantly lower in the SARS-CoV-2 era when compared to the pre-SARS-CoV-2 era (0.06 vs 0.30, P<0.0001). No patients tested positive for SARS-CoV-2 in the SARS-CoV-2 era. Conclusions Infection prevention measures developed in response to the SARS-CoV-2 pandemic may reduce the risk of RVIs in hospitalized patients with established BPD.
Introduction: The COVID-19 pandemic has accelerated the move towards home spirometry monitoring, including in children. Our aim was to determine whether the remote supervision of spirometry by a physiologist improves the technical quality and failure rate of the manoeuvres. Method: Children with cystic fibrosis who had been provided with NuvoAir home spirometers were randomly allocated to either supervised or unsupervised home spirometry following a detailed training session. Home spirometry was performed every 2 weeks for 12 weeks. Tests were assigned a quality factor (QF) using our laboratory grading system as per ATS/ERS standards, with tests marked from A to D, or Fail. In our laboratory we aim for QF A in all spirometry tests, but report results of QF B or C with a cautionary note. QF A was therefore the primary outcome, and QF A-C the secondary outcome. Results: 61 patients were enrolled; 166 measurements were obtained in the supervised group, and 153 in the unsupervised group. Significantly more measurements achieved QF A in the supervised compared to unsupervised group (89% vs 74%; p= <0.001) whilst proportions reaching grade A-C were similar (99% vs 95%; p=0.1). All significant declines in spirometry results had a clinical rather than technical reason. Family/patient feedback for both arms was very positive. Conclusion: These results suggest that home spirometry in children should ideally be remotely supervised by a physiologist, but acceptable results can be obtained if resources do not allow this, provided that training is delivered and results monitored according to our protocol.
Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been described to partially overlap with Kawasaki disease (KD) with regard to clinical symptoms, but they are unlikely to share the same disease entity. We conducted a systematic review and meta-analysis to characterize the laboratory parameters of MIS-C compared with those of KD and Kawasaki disease shock syndrome (KDSS). Databases were searched for studies on laboratory parameters of MIS-C (hematology, inflammatory markers, cardiac markers and biochemistry) through May 31, 2021. Twelve studies with 3073 participants yielded 969 MIS-C patients. In terms of hematology, MIS-C patients had lower levels of leukocytes, absolute lymphocyte count and platelet count (PLT) than KD patients and had similar absolute neutrophil count (ANC) and hemoglobin (Hb) levels. In terms of inflammatory markers, MIS-C patients had higher levels of C-reactive protein, D-dimer and ferritin than KD patients and had similar levels of procalcitonin and ESR. In terms of cardiac markers, MIS-C patients had higher CPK levels than KD patients. The levels of NT-proBNP, troponin and AST were not significantly different between MIS-C and KD patients. In terms of biochemistry, MIS-C patients had lower levels of albumin, sodium and ALT and higher levels of creatinine than KD patients. In addition, MIS-C patients had lower levels of PLT, Hb and ESR and higher levels of ANC than KDSS patients. Measurement of laboratory parameters might assist clinicians with accurate evaluation of MIS-C and further mechanistic research.
Hemoptysis is a serious and potentially life-threatening event. Mortality is estimated at 13% for this chief complaint with age, volume of hemoptysis and receipt of blood products as risk factors for mortality. Hemoptysis is mostly seen in those with underlying congenital cardiac conditions or Cystic Fibrosis. We describe a unique case of a previously healthy 10 year old male who presented to the ED by EMS with a moderate volume episode of hemoptysis. He was admitted to the PICU where a sudden episode of massive hemoptysis precipitated by forced respiratory effort occurred during his examination. He decompensated and was emergently brought to the OR for airway evaluation by ENT and pulmonology. A large clot was found in the RML segment with brisk bleeding following removal of the clot. A 5 Fr bronchial blocker was placed to achieve hemostasis. Bronchial artery angiogram by IR demonstrated extravasation of contrast from right bronchial artery to segmental right lower lobe pulmonary artery shunt. He underwent embolization of the right bronchial artery. He was extubated the following day after no recurrent bleeding was confirmed with bronchoscopy. BA-PA fistulas are rare vascular anomalies in which an anastomosis is formed between systemic and pulmonary arteries. They are most commonly acquired, often described as secondary to chronic inflammatory lung diseases. BA-PA fistulas can also be congenital and have been seldom described in the literature. Our case highlights the importance of this rare diagnosis, which must remain on a pediatric pulmonologist’s differential due to the significant associated mortality.
Objective: To determine the potential longer-term effects of maternal antenatal respiratory syncytial virus (RSV) vaccination, we examined the association between cord-blood RSV-neutralizing antibodies (RSV-NA) and RSV infections in the first 2-years of life, RSV-NA at 3-years, and respiratory health to age 5-years. Methods: Two community-based Australian birth cohorts were combined. For children with at least one atopic parent, paired serum RSV-NA levels were compared in cord-blood and at age 3-years. Weekly nasal swabs were collected in one cohort and during acute respiratory infections (ARI) in the other. Wheeze history up to age 5-years and physician-diagnosed asthma at 5-years was collected by parent report. Results: In 264 children, each log10 increase of cord-blood RSV-NA level was associated with 37% decreased risk (adjusted incidence-rate-ratio (aIRR) 0.63; 95% confidence interval (CI): 0.40–1.01) of RSV-ARI and 49% decreased risk (aIRR 0.51; 95%CI: 0.25–1.02) of RSV acute lower respiratory infections (ALRI) at 12–24 months of age. However, higher cord-blood RSV-NA was associated with increased risk of all-cause ALRI (aIRR 1.29; 95%CI: 0.99–1.69), wheeze-associated ALRI (aIRR 1.75; 95%CI: 1.08–2.82) and severe ALRI (aIRR 2.76; 95%CI: 1.63–4.70) at age 6–<12 months. Cord-blood RSV-NA was not associated with RSV-ARI in the first 6-months, RSV-NA levels at 3-years, or wheeze or asthma at 5-years. Conclusions: Higher levels of cord-blood RSV-NA did not protect against RSV infections during the first 6-months-of-life, time-to-first RSV-ARI, or wheeze or asthma in the first 5-years of life. Additional strategies to control RSV-related illness in childhood are needed.
Children with sickle cell disease (SCD) have an increased risk of sleep disordered breathing (SDB) compared with the general pediatric population. There has been a growing research interest on this field in recent years, yet many questions regarding risk factors and clinical implications of SDB remain unclear. The aim of this review is to provide a concise narrative and systematic synthesis of the available evidence on the epidemiology, clinical presentation, complications and management, of SDB in children with SCD. An electronic search was conducted on studies published from the 1st of January 2000 to the 31st of December 2020 in PubMed/Medline, Scopus and Cochrane databases. All studies focusing on SDB in children with SCD aged from 0 to 20 years were included. Studies were eligible for inclusion if available in the English language. A quantitative synthesis of the included studies was performed. Only studies focusing on specific treatment outcomes were included in a meta-analytic process. A total of 190 papers were initially identified. After screening the title and abstract, 112 articles were evaluated for eligibility. At the end of the selection process, 62 studies were included in the analysis. Sleep-disordered breathing is associated with worse neurological, neurocognitive and cardiological outcomes, whereas the association with frequency or severity of vaso-occlusive pain events and acute chest syndrome was not clarified. Therapeutic interventions like adenotonsillectomy or oxygen supply may result in a significant increase in mean nocturnal oxygen saturation but effective clinical implications remain still unclear.
Miracles, like London buses, just seem to come along. The truth is, there are no miracles, just lots of hard work behind the scenes, minds open to opportunity, serendipity and possibly a little luck. In my time as a paediatric respiratory physician, I have born witness to remarkable advances in treatment that have changed patients' fortunes overnight. Examples of these include artificial surfactant replacement for premature newborns, conjugate haemophilus influenzae type b vaccination, propranolol for infants with subglottic haemangiomas, mandibular distraction for babies with micrognathia, cystic fibrosis transmembrane conductance regulator modulators therapy for patients with cystic fibrosis and antisense oligonucleotide therapy for infants with spinal muscular atrophy. There are lessons to be learned from reflection upon these life transforming treatments, and perhaps it is a good time just to pause and wonder.
Introduction: Although prolonged respiratory symptoms following SARS-CoV-2 infection have been reported in adults, there is a paucity of literature describing post-acute symptoms in pediatric patients following COVID-19. In this study we describe health data and respiratory findings in pediatric patients presenting with complaints of persistent respiratory symptoms following acute COVID-19 infection. Methods: This study included patients referred to Pulmonary Clinic at the Children’s Hospital of Philadelphia between December 2020 and April 2021 (n=29). Inclusion criteria included a history of SARS-CoV-2 RNA positivity or confirmed close household contact. A retrospective chart review was performed and demographic, clinical, imaging, and functional test data were collected. Results: The mean age at presentation to clinic was 13.1 years (range: 4-19 years). Patients had persistent respiratory symptoms ranging from 1.3 to 6.7 months post-acute infection. Persistent dyspnea and/or exertional dyspnea were present in nearly all (96.6%) of the patients at the time of clinic presentation. Other reported chronic symptoms included cough (51.7%) and exercise intolerance (48.3%). Fatigue was reported in 13.7% of subjects. Many subjects were overweight or obese (62.1%) and eleven subjects had a prior history of asthma. Lung function was normal in most patients. The six-minute walk test (6MWT) revealed exercise intolerance and significant tachycardia in two-thirds of children tested. Conclusion: Exertional dyspnea, cough and exercise intolerance were the most common respiratory symptoms in children with post-acute COVID-19 respiratory symptoms seen in an outpatient pulmonary clinic. Lung function, however, was mostly normal, and exertional intolerance was frequently demonstrated using the 6MWT.
Introduction: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is a highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy (HEMT) originally approved in 2019 for use in patients 12 years of age and older with at least one F508del mutation or a mutation in the CFTR gene that is responsive based on in vitro data. This report describes coverage of ELX/TEZ/IVA for CF in children 6 to 11 years of age prior to the recent age expansion by the Food and Drug Administration (FDA). Methods: An email was sent to pharmacists and pharmacy technicians through the CF Foundation LISTSERV and all responses regarding ELX/TEZ/IVA use in children 6 to 11 years of age were collected. Results: A total of 65 children from 15 CF care centers were included in the study. A total of 55 children had early coverage of ELX/TEZ/IVA for an overall approval rate of 84.6%. The median time to approval was 15 days. Lung function and weight outcomes were also positive. Conclusions: Early insurance coverage of ELX/TEZ/IVA for CF in children 6 to 11 years was achieved regardless of insurance type and should be considered an option for patients in need of HEMT therapy.
Acute respiratory distress syndrome (ARDS) is a disabling and potentially lethal syndrome requiring prompt recognition and urgent interventions to prevent morbidity and mortality. Although constipation is not generally recognized as a cause for ARDS or usually listed within the differential diagnosis, there have been case reports describing such an association[2,3]. We present the case of a patient with history of intermittent constipation presenting with progressive abdominal pain and an acute abdomen that required emergent surgical fecal decompaction. This was followed by hypoxemic respiratory distress leading to respiratory failure in the setting of severe constipation and aspirated feculent material. To our knowledge, this is the first published case report describing aspirated feculent material in a child with respiratory failure due to ARDS.
Background: Premature infants who cannot achieve full oral feeds may need a gastrostomy tube (GT) to be discharged from the neonatal intensive care unit (NICU). We previously developed a model to predict which infants born <30 weeks (w) gestational age (GA) will require a GT before discharge. Here we report the detailed respiratory variable data to describe the general respiratory course for infants in the NICU <30w GA at birth and the association between different levels of respiratory support with postmenstrual age (PMA) at the time of first oral feeding attempt (PMAff), including later need for GT for discharge. Methods: Retrospective chart review of 391 NICU admissions comprising test (2015-2016) and validation (2017-2018) cohorts. Data, including respiratory support, were collected on 204 infants, 41 GT and 163 non-GT, in the test cohort, and 187 infants, 37 GT and 150 non-GT, in the validation cohort. Results: Respiratory data were significantly different between GT and non-GT infants. Infants who required GT for discharge were on significantly higher respiratory support at 30 days of age, 32w PMA, and 36w PMA. Respiratory parameters were highly correlated with PMAff. Conclusion: Respiratory status predicts PMAff, which was the variable in our previously described model that was most predictive of failure to achieve full oral feeing. These data provide a catalyst to develop strategies for improving oral feeding outcome for infants requiring prolonged respiratory support in the NICU.
Nutritional deficiencies such as iron, vitamin B12 and folate are recognized as etiologies for several cytopenias; although copper’s role in multiple metabolic enzymes is well-established, copper deficiency is often overlooked as a contributing entity. Frequently diagnosis is delayed, patients may undergo bone marrow investigations with findings overlapping a myelodysplastic process, which can lead to further testing and treatment considerations including hematopoietic stem cell transplant referral. We present a case of a young boy with cystic fibrosis with biliary dysplasia corrected with hepato-portoenterostomy and distal intestinal obstruction syndrome resulting in jejunal resection, with severe anemia and thrombocytopenia requiring transfusion support. Initial evaluation had been unremarkable, ongoing pancytopenia prompted bone marrow studies, which revealed vacuolated granulocytic and erythroid precursors and ring sideroblasts, suggestive of copper deficiency. Serum copper and ceruloplasmin were consistent with severe deficiency, attributed to insufficient absorption intestinal resection, chronic parenteral nutrition and prior zinc supplementation. Following enteral copper supplementation, anemia, leukopenia and thrombocytopenia significantly improved, however upon cessation, counts again worsened and has since been maintained on daily copper supplementation without further transfusion needs. Our experience exemplifies the importance of early consideration for copper deficiency in children with cytopenias, especially within context of intestinal malabsorption or inadequate nutritional intake which often occurs in children with cystic fibrosis.
Background Silent aspirations are frequent in children with neurological impairment. They dramatically increase the risk for acute and chronic respiratory insufficiencies leading to high morbidity and mortality. Laryngeal sensitivity deficits have been linked to aspirations in adults and are a suspected cause for dysphagia in children. In a similar neurological circuit as swallowing, laryngeal receptors trigger coughing as a protective airway reflex. The aim of this study was to examine the association between reduced laryngeal sensitivity, aspiration and coughing in neurologically impaired children. Design and Methods In a retrospective study, 110 children with suspected dysphagia who received a clinical evaluation of swallowing and a flexible endoscopic evaluation of swallowing (FEES) between 2013 and 2019 in the children’s university clinic Düsseldorf were analyzed. Laryngeal sensitivity was tested by the endoscopic touch method. Fifty-four patients (49.1%) had neurological impairments, 56 patients (5.9%) had no or other comorbidities and served as a control cohort. Associations were computed using χ2-test. Results Children with neurological impairment suffered from laryngeal sensory deficit significantly more often and seemed to cough less frequently than children with no or other comorbidities. Reduced laryngeal sensitivity could not be correlated to less coughing. Coughing acted as a predictor of aspiration only in the neurologically impaired group of children with reduced laryngeal sensitivity. Conclusion Reduced laryngeal sensitivity is a potential cause of silent aspirations in children with neurological impairment. However, reduced laryngeal sensitivity did not lead to significantly less coughing which might be due to a lack of discrimination between different levels of sensitivity deficits by the endoscopic touch.
Clinical care in cystic fibrosis (CF) has continued to advance over the last several years, particularly with the widespread eligibility and use of highly effective modulator therapy. Awareness of the multisystem concerns that face persons with CF (PwCF) has also continued to be recognized as an important aspect of the burden of the disease. This review will cover a broad array of topics, from diagnosis to multisystem effects related to mental health, endocrine, palliative care, reproductive health, otolaryngology, and cardiac issues. Additionally, an understanding of worldwide care delivery will be reviewed, demonstrating variation in outcomes based on resources and populations served, ranging from the advances in care in the United States (US) to the challenges of disease recognition and diagnosis in low-and-middle-income countries (LMIC). This review is the third in a three-part CF Year in Review 2020 series, focusing on the multi-system effects of CF. Part one focused on the literature related to CFTR (cystic fibrosis transmembrane conductance regulator protein) modulators, while part two focused on pulmonary outcomes, radiographic and physiologic assessments, as well as infection and inflammation. Part three has been split into two individual parts, Part 3A presented here, and Part 3B related to CF specific nutrition and gastrointestinal publications will also be published this year. This review focuses on articles from Pediatric Pulmonology but also includes articles published in 2020 from other journals that are of particular interest to clinicians.
The multisystemic manifestations of cystic fibrosis (CF) involve all parts of the gastrointestinal (GI) system, including the pancreas, intestine and liver. As providers who care for people with CF (PwCF), knowledge of the manifestations, treatment and research related to nutrition and GI disease is important. This review is last installment of the CF Year in Review 2020 series, focusing on the multisystem effects of CF. Part one focused on the literature related to CFTR (cystic fibrosis transmembrane conductance regulator protein) modulators, while part two focused on pulmonary outcomes, radiographic and physiologic assessments, as well as infection and inflammation. Part three was split into Part 3A, focusing on the multisystem impact of CF, and this review, Part 3B, focusing on nutritional, gastrointestinal and hepatobiliary articles. Articles were chosen from Pediatric Pulmonology but also include articles published in 2020 from other journals that are of particular interest to clinicians.
Background: The marked heterogeneity in CF disease complicates selection of those most likely to benefit from existing or emergent treatments. Objective: We aimed to predict progression of bronchiectasis in preschool children with CF. Methods: Using data collected up to three years of age, in the Australian Respiratory Early Surveillance Team for CF (AREST CF) cohort study, clinical information, chest computed tomography (CT) scores and biomarkers from bronchoalveolar lavage were assessed in a multivariable linear regression model as predictors for CT bronchiectasis at age 5-6. Results: Follow-up at 5-6 years was available in 171 children. Bronchiectasis prevalence at 5-6 was 134/171 (78%) and median bronchiectasis score 3 (range 0-12). The internally validated multivariate model retained eight independent predictors accounting for 37% (Adjusted R2) of the variance in bronchiectasis score. The strongest predictors of future bronchiectasis were: pancreatic insufficiency, repeated intravenous treatment courses, recurrent lower respiratory infections in the first 3 years of life and lower airway inflammation. Dichotomizing the resulting prediction score at a bronchiectasis score of above the median resulted in a diagnostic odds ratio of 13 (95% CI 6.3-27) with a positive and negative predictive values of 80% (95%CI 72%-86%) and 77% (95% CI 69%-83%) respectively. Conclusion: Early assessment of bronchiectasis risk in children with CF is feasible with reasonable precision at a group level, which can assist in high-risk patient selection for interventional trials. The unexplained variability in disease progression at individual patient level remains high, limiting the use of this model as a clinical prediction tool.