Infant Pulmonary Function Tests in Children with Airway Anomalies and Correlation with Bronchoscopy Findings.

OBJECTIVES: To evaluate the role infant pulmonary function tests (Tidal Breathing Flow Volume Loops, TBFVL) in children with airway anomalies and to correlate the TBFVL so obtained with bronchoscopy findings. METHODS: In this prospective cohort study, we enrolled children aged 0-2 years with airway anomalies and performed TBFVL and bronchoscopy. The primary outcome measure was graphic pattern of TBFVL in laryngomalacia. Secondary outcome measures were types of TBFVL results in various airway anomalies and controls. RESULTS: Out of 53 children enrolled, 28 (52.3%) had laryngomalacia. Pattern 3 (fluttering of inspiratory limb) was commonest TBFVL pattern in laryngomalacia. Among TBFVL parameters, the ratio of inspiratory time to expiratory time (Ti/Te) and tPTEF/tE was significantly high in children with isolated laryngomalacia compared to controls. At six months of follow-up, TBFVL pattern 1 (normal) became the commonest pattern. CONCLUSION: A particular type of airway anomaly may have a characteristic graphic pattern in TBFVL and TBFVL pattern may indicate improvement in airway anomalies in follow-up.

Validation of a Clinical Tool to Predict Neurological Outcomes in Critically Ill Children-A Prospective Observational Study.

OBJECTIVES: To evaluate the performance of the empiric tool by Gupta et al. in predicting neurological outcomes in children admitted to the pediatric intensive care unit (PICU) and to evaluate the association of biomarkers S100B and NSE with neurological outcomes. METHODS: This prospective observational study was conducted in 163 critically ill children aged 2 mo to 17 y admitted to the PICU from June 2020 to July 2021. The authors used the prediction tool developed by Gupta et al.; the tool was applied at admission and at PICU discharge/death. Samples for NSE and S100B were collected at admission and discharge. The performance of the new tool was assessed through discrimination and calibration. Risk factors for "unfavorable outcomes" (decline in PCPC score by > 1) were evaluated by multivariate analysis. RESULTS: The PICU mortality was 28% (n = 45). When the tool developed by Gupta et al. was used at the time of admission, favorable neurological outcomes were predicted for 69% (112) children. The area under the curve for the new tool at admission was 0.72 and at discharge/death it was 0.99, and the calibration was excellent at both time points. Independent factors associated with unfavorable neurological outcomes were higher PCPC scores and organ failure. As the number of samples processed for NSE and S100B was less, statistical analysis was not attempted. CONCLUSIONS: The new tool by Gupta et al. has good discrimination, calibration, sensitivity, and specificity and can be used as a prediction tool. NSE and S100B are promising biomarkers and need further evaluation.

Development and Validation of a Weight Estimation Tool for Acutely Ill Children Who Cannot be Weighed.

OBJECTIVES: To develop and validate weight estimation tools using mid upper arm circumference (MUAC) and body length, and determine accuracy and precision of Broselow tape in children 6 mo to 15 y of age. METHODS: Data of 18,456 children aged 6 mo to 5 y and 1420 children aged 5 to 15 y were used to develop linear regression equations using length and MUAC to estimate weight. These were validated on prospectively enrolled populations of 276 and 312 children, respectively. Accuracy was measured by Bland-Altman bias, median percentage errors, and percentage of predicted weight within 10% of true weight. Broselow tape was tested on the validation population. RESULTS: Gender specific equations were developed which estimated weight within 10% of true weight in 69.9% (64.1-75.2%) and 65.7% (60.1-70.9%) of children aged 6 mo to 5 y, and 5 to 15 y, respectively. Broselow tape predicted weight within 10% of the true weight in 40.5% (34.7-46.6%) and 32.5% (26.7-38.7%) of children aged 6 mo to 5 y and 5 to 15 y, respectively. CONCLUSIONS: The model developed from MUAC and length accurately estimated weight in children aged 6 mo to 15 y, and is potentially useful during emergencies. The Broselow tape frequently overestimated weight in authors' setting.

Prevalence of Metabolic Abnormalities and their Association with Asthma Symptom Control in Children.

OBJECTIVES: To determine the prevalence of insulin resistance (IR), dyslipidemia and metabolic syndrome (MS) in children with asthma, aged 10 to 15 y, and to determine if these metabolic abnormalities showed an association with asthma symptom control and lung function. METHODS: A cross-sectional study was conducted at a tertiary centre in north India. Consecutive children with physician diagnosed asthma were enrolled. Asthma symptom control over previous four weeks was assessed as per Global Initiative for Asthma (GINA) recommendations. Fasting plasma glucose, serum insulin and lipid levels were estimated. Homeostasis Model Assessment- Insulin Resistance (HOMA-IR) was used as a marker of IR. Spirometry was performed for assessing lung function. RESULTS: Eighty-three children were enrolled. Median (IQR) age was 12.0 (11.0, 13.5) y and mean (SD) body mass index (BMI) Z score was -0.42 (1.0). Median (IQR) HOMA-IR was 1.65 (1.06, 2.39). Prevalence of IR was 42.3% (95% CI: 31.7-52.9%). Number of children with elevated triglycerides, total cholesterol, and low-density lipoprotein (LDL)-cholesterol was 4 (4.8%), 4 (4.8%) and 5 (6%), respectively. Sixty-seven (80.7%) children had low high-density lipoprotein (HDL)-cholesterol. Only one subject was found to have metabolic syndrome. Presence of IR and elevation in serum insulin and triglycerides were associated with poorer asthma control, independent of BMI. None of the metabolic parameters were associated with lung function, after adjusting for height. CONCLUSIONS: Among children with asthma, aged 10 to 15 y, the prevalence of IR was 42.3% (95% CI: 31.7-52.9%). Elevated serum insulin, triglycerides, and presence of IR were associated with poorer asthma control, after adjusting for BMI.

MDCT and MRI in Bronchiectasis in Older Children and Young Adults - A Non-Inferiority Trial.

OBJECTIVES: To compare and evaluate the usefulness of magnetic resonance imaging (MRI) with computed tomography (CT) in bronchiectasis; to compare MRI and CT scores with pulmonary function tests (PFT) and to evaluate the role of Diffusion-weighted imaging (DWI) in bronchiectasis. METHODS: In this prospective study, 25 patients between 7-21 y of age with a clinical/radiological diagnosis of bronchiectasis underwent MDCT and MRI chest. MRI and CT scoring was performed using modified Bhalla-Helbich's score by two independent radiologists for all parameters. A final consensus score was recorded. The overall image quality of different MRI sequences to identify pathologies was also assessed. Appropriate statistical tests were used for inter-observer agreements, and correlation amongst CT and MRI; as well as CT, MRI and PFT. RESULTS: Strong agreement (ICC 0.80-0.95) between CT and MRI was seen for extent and severity of bronchiectasis, number of bullae, sacculation/abscess, emphysema, collapse/ consolidation, mucus plugging, and mosaic perfusion. Overall CT and MRI scores had perfect concordance (ICC 0.978). Statistically significant (p-value <0.01) intra-observer and inter-observer agreement for all CT and MRI score parameters were seen. A strong negative correlation was seen between total CT and MRI severity scores and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), forced expiratory flow (FEF) 25-75%. DWI MR, with an apparent diffusion coefficient (ADC) cut-off of 1.62 × 10-3 mm3/s had a sensitivity of 70% and specificity of 75% in detecting true mucus plugs. CONCLUSIONS: MRI with DWI can be considered as a radiation-free alternative in the diagnostic algorithm for assessment of lung changes in bronchiectasis, especially in follow-up.

GeneXpert Ultra in Urine Samples for Diagnosis of Extra-Pulmonary Tuberculosis.

Extra-pulmonary tuberculosis (EPTB) continues to be difficult to diagnose. Novel biomarkers in biological specimens offer promise. Detection of Mycobacterium tuberculosis (Mtb) DNA in urine could prove useful in diagnosis of EPTB, possibly due to disseminated disease or micro-abscesses reported in kidneys. The current study was designed to detect Mtb DNA in stored urine samples from patients with EPTB. Diagnosis of EPTB was reached using Microbiological Reference Standards (MRS) on samples from the disease site using WHO Recommended Diagnostics (WRD), [smear microscopy, liquid culture (MGIT-960)] and GX (molecular WRD, mWRD) and Comprehensive reference standards [CRS, clinical presentation, microbiological reference standards, radiology, histopathology]. GX-Ultra was performed on urine samples stored in -80oC deep freezer, retrospectively. Of 70 patients, 51 (72.9%) were classified as confirmed TB, 11 (15.7%) unconfirmed TB, and 8 (11.4%) unlikely TB. GX-Ultra in urine samples demonstrated sensitivity of 52.9% and specificity of 57.9% against MRS, and higher sensitivity of 56.5% and specificity of 100% against CRS. The sensitivity and specificity of GX-Ultra in urine was 53.6% and 75% for pus sample subset and 52.2% and 53.3% for fluid sample subset. Urine being non-invasive and easy to collect, detection of Mtb DNA using mWRD in urine samples is promising for diagnosis of EPTB.

A "Cool" extraction technique for difficult pediatric airway foreign bodies: Report of two cases.

Foreign body (FB) aspiration is a potentially life-threatening accident in children. Traditionally, rigid bronchoscopy has been the procedure of choice for FB removal, however it may miss distally lodged FBs. We report two pediatric cases with distal impacted FBs that could not be retrieved by rigid bronchoscopy (RB) and were mobilised using Fogarty balloon followed by flexible bronchoscopic cryoextraction. The advantage of a cryoprobe is lower risk of fragmentation of FB that may occur with forceps. Cryoextraction is particularly advantageous for removing water-containing FBs. In both patients, FB was removed more than 2 weeks following aspiration, leading to the formation of granulation tissue around the FB, which considerably hampered the process. Using a laryngeal mask airway to secure the airway, FB removal by flexible bronchoscopy may be a safe and effective technique in skilled hands, especially for FBs impacted in distal airways with granulation tissue where RB fails.

Transition Care in Cystic Fibrosis.

Cystic fibrosis (CF) is a chronic childhood illness with gradually improving survival and significant burden of disease during adult life. Transition of CF care from pediatric to an adult based multidisciplinary team is a complex process and careful coordination with a transition key worker is necessary for successful transition without adverse outcome. Transition is associated with a key change in CF management with shift from family-centred care to self-reliance and independence on part of the patient. Readiness and skills of self-managed care play central part in successful transition. Resource materials for transition are available online for different countries for improved readiness and smooth transition. Situation is worse in resource-limited settings as facilities of fully functional adult multidisciplinary care for CF is not readily available.

Oral Propranolol Therapy for Infantile Hemangioma: Long-term Follow-up.

ß-blocker therapy is currently the treatment of choice for infantile hemangiomas (IH), albeit with limited data on long-term treatment outcomes. Herein, authors treated 67 IH lesions in 47 patients with oral propranolol at 2 mg/kg/d for a median of 9 mo and followed them up for a median of 48 mo. While no maintenance therapy was required for 18 lesions (26.9%), the rest needed maintenance therapy. Both treatment regimens had comparable efficacy (83.3±23.9% and 92.0±13.8%) but chances of IH recurrence was higher in lesions requiring maintenance therapy. Also, patients treated at ≤5 mo of age had a significantly better response and a lower recurrence rate than patients treated at >5 mo of age (95.0±7.9% vs. 87.0±17.5%, p = 0.05). Authors' experience suggests that longer durations of maintenance therapy offered no added advantage to the overall improvement of IH while treatment initiation at an earlier age showed better improvement and lower recurrence rates.

Expedited diagnosis of pediatric tuberculosis using Truenat MTB-Rif Dx and GeneXpert MTB/RIF.

Rapid, cost-effective, and sensitive diagnostic assays are essential for global tuberculosis (TB) control, especially in high TB burden, resource-limited settings. The current study was designed to evaluate diagnostic accuracy of Truenat MTB-Rif Dx (MolBio) in children less than 18 years of age, with symptoms suggestive of TB. Gastric aspirate, induced sputum, and broncho-alveolar lavage samples were subjected simultaneously to AFB-smear, GeneXpert MTB/RIF, liquid culture (MGIT-960) and Truenat MTB-Rif Dx. The index-test results were evaluated against microbiological reference standards (MRS). Truenat MTB-Rif Dx had a sensitivity of 57.1%, specificity of 92% against MRS. The sensitivity and specificity of the Truenat MTB-RIF Dx compared with liquid culture was 58.7% and 87.5% while GeneXpert MTB/RIF was 56% and 91.4%. The performance of both GeneXpert MTB/RIF and Truenat MTB-Rif Dx are comparable. Result of our study demonstrates that Truenat MTB-Rif can aid in early and efficient diagnosis of TB in children.

Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis.

BACKGROUND: Suboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line anti-TB drug pharmacokinetics in children and adolescents at a global level. METHODS: We systematically searched MEDLINE, Embase and Web of Science (1990-2021) for pharmacokinetic studies of first-line anti-TB drugs in children and adolescents. Individual patient data were obtained from authors of eligible studies. Summary estimates of total/extrapolated area under the plasma concentration-time curve from 0 to 24 h post-dose (AUC0-24) and peak plasma concentration (C max) were assessed with random-effects models, normalised with current World Health Organization-recommended paediatric doses. Determinants of AUC0-24 and C max were assessed with linear mixed-effects models. RESULTS: Of 55 eligible studies, individual patient data were available for 39 (71%), including 1628 participants from 12 countries. Geometric means of steady-state AUC0-24 were summarised for isoniazid (18.7 (95% CI 15.5-22.6) h·mg·L-1), rifampicin (34.4 (95% CI 29.4-40.3) h·mg·L-1), pyrazinamide (375.0 (95% CI 339.9-413.7) h·mg·L-1) and ethambutol (8.0 (95% CI 6.4-10.0) h·mg·L-1). Our multivariate models indicated that younger age (especially <2 years) and HIV-positive status were associated with lower AUC0-24 for all first-line anti-TB drugs, while severe malnutrition was associated with lower AUC0-24 for isoniazid and pyrazinamide. N-acetyltransferase 2 rapid acetylators had lower isoniazid AUC0-24 and slow acetylators had higher isoniazid AUC0-24 than intermediate acetylators. Determinants of C max were generally similar to those for AUC0-24. CONCLUSIONS: This study provides the most comprehensive estimates of plasma exposures to first-line anti-TB drugs in children and adolescents. Key determinants of drug exposures were identified. These may be relevant for population-specific dose adjustment or individualised therapeutic drug monitoring.

Evaluation of Changes in Quadriceps Femoris Muscle in Critically III Children Using Ultrasonography.

OBJECTIVE: To measure changes in muscle thickness and echogenicity, reflecting muscle bulk and quality, respectively, of quadriceps femoris (QF), in critically ill children. METHODS: This study was done on 58 children aged 1-18 y requiring mechanical ventilation, admitted in a pediatric intensive care unit (PICU) of a tertiary care hospital from January 2018 to June 2019. QF thickness was measured twice in longitudinal plane and twice in transverse plane, and an average of these four measurements was used. Muscle quality was assessed using ImageJ software to determine the mean echogenicity, and was calculated separately for vastus intermedius and rectus femoris. These observations were repeated on day 3 and day 7 of the ICU stay. RESULTS: The median muscle thickness of QF was 1.58 cm, and vastus intermedius and rectus femoris echogenicity was 35.5 and 25.88 units, respectively in the present cohort, with median age of 6 y. Only 36 of the 58 patients underwent day 7 ultrasonography, as the remainder were either extubated or died. There was no significant change in the muscle thickness over 7 d. Rectus femoris echogenicity increased significantly over 7 d by 16.1% (p = 0.03). Baseline vastus intermedius echogenicity was significantly higher in patients who subsequently died during the course of their illness (p = 0.026). CONCLUSION: There was a significant change in rectus femoris echogenicity, but not in QF thickness. Echogenicity rather than muscle thickness may be a more sensitive marker for changes in muscle properties.

Fibrosing Interstitial Lung Disease in Children: An HRCT-Based Analysis.

OBJECTIVE: To determine high resolution CT (HRCT) patterns of pulmonary fibrosis (PF) in children; and their etiological correlates. METHODS: This was a retrospective study involving 149 children with diffuse lung disease (DLD). Patterns of involvement were classified based on dominant lung finding as ground glass opacity (GGO) dominant, nodule dominant, cystic lung disease, or PF. Patterns of PF were classified based on distribution and morphology into airway centric fibrosis (ACF), subpleural fibrosis (SPF), progressive massive fibrosis (PMF) and fibrocavitary. A comparison was made between the two dominant groups for apicobasal distribution, associated findings (GGO, nodules, cysts), and pulmonary artery hypertension (PAH). RESULTS: Nineteen patients showed PF on HRCT. ACF was commonest (52.6%), followed by SPF (42.1%). The common etiology was sarcoidosis (30%) in ACF, and connective tissue disorders (CTD) (50%) in SPF. Significant difference was found between ACF and SPF in apicobasal distribution (p = 0.04), presence of nodules (p = 0.03), and cysts (p = 0.02). CONCLUSION: PF may present as an end stage of several childhood lung diseases. PF on imaging has discernible morphological patterns that correlate with underlying etiology.

Imaging Findings in Chronic Granulomatous Disease (CGD).

OBJECTIVES: To describe prevalence of various imaging findings in chronic granulomatous disease (CGD) patients; and find imaging biomarkers for differentiating chest infections caused by different micro-organisms. METHODS: A retrospective study was conducted on 15 patients (49 scans) with proven CGD. Scans which had a correlative microbiological diagnosis for organisms were included in the analysis. The scans were reviewed by 3 radiologists on a predefined proforma, under the lung parenchymal, airway, pleural, mediastinal, and extrathoracic abnormalities. Analysis of various imaging parameters on a semiquantitative scale was performed, followed by a correlation of each imaging findings with causative organisms. RESULT: The mean age of presentation was nearly 7 y, with a male preponderance. Definitive proof of causative organisms was obtained in 22 scans. Bacterial infection was found in 7, fungal in 12, tubercular in 2, and viral in 1 scan. Most prevalent thoracic imaging manifestations included lymphadenopathy (commonest), consolidation, nodules, air trapping, and bronchiectasis. Fungal infections showed necrotic conglomerate lymphadenopathy, cavitating nodules, and multilobar consolidation more frequently than bacterial infections (though not statistically significant). Abscesses and lymphadenopathy were the most common extrathoracic manifestations. CONCLUSION: In patients with CGD, multifocal or multilobar consolidation, mass-like consolidation, cavitating nodules, and conglomerate necrotic lymphadenopathy should alert the radiologist to a possible fungal cause.

Development of algorithm for diagnosis of cystic fibrosis in absence of sweat chloride testing in resource-limited setting.

OBJECTIVE: To develop a diagnostic algorithm for cystic fibrosis (CF) in the setting of unavailability of sweat chloride, based on clinical features and basic laboratory investigations. METHODS: In a prospective observational study, we enrolled children with recurrent/persistent pneumonia with either malabsorption or poor growth, undergoing a sweat chloride test, between January 2019 and December 2020. They were simultaneously evaluated for aquagenic wrinkling of hands, stool fat globules, sputum for bacterial culture, blood gas, and serum electrolytes. Sensitivity and specificity were calculated for parameters having a significant difference between CF and non-CF groups. Scoring systems and algorithms for the diagnosis of CF were developed. RESULTS: Of 134 children enrolled, 46 (34%) had CF. The sensitivity and specificity of various parameters to diagnose CF was: sibling death due to respiratory illness (30.43%, 96.59%), aquagenic wrinkling (76.74%, 47.67%), metabolic alkalosis (17.78%, 94.12%), hyponatremia (28.89%, 89.41%), stool fat globules (38.46%, 81.18%), and presence of Pseudomonas in sputum culture (23.68%, 98.80%). Using coefficients of significant parameters on stepwise logistic regression, the composite score for diagnosis of CF was calculated as: 3X sibling death due to respiratory illness + 1.5X hyponatremia + 1.5X metabolic alkalosis + 1.5X aquagenic wrinkling + 1X stool fat globules + 2.5X presence of Pseudomonas in sputum culture (each of the variables scores 0 or 1 for absence and presence, respectively). The cut-off of ≥2.5 had sensitivity and specificity of 81.82% and 76.83%, respectively. CONCLUSIONS: In resource-limited settings, the proposed diagnostic algorithm can be used for the diagnosis of presumptive CF with fair sensitivity and specificity.

Role of computed tomography angiography in the evaluation of haemoptysis in children: Decoding the abnormal vessels.

Background & objectives: Haemoptysis in children is potentially life-threatening. In most cases, the bleeding arises from the systemic circulation, and in 5-10 per cent of cases, it arises from the pulmonary circulation. The role of computed tomography angiography (CTA) in this setting is important. This study was undertaken (i) to study the role of single-phase split-bolus dual energy contrast-enhanced multidetector row CTA (DECTA) in the evaluation of haemoptysis in children; (ii) to analyze the patterns of abnormal vascular supply in the various aetiologies encountered. Methods: A retrospective study of 86 patients who underwent split bolus DECTA for the evaluation of haemoptysis was performed. Final diagnoses were categorized as normal computed tomography, active tuberculosis (TB), post-infectious sequelae, non-TB active infection, cystic fibrosis (CF), non-CF bronchiectasis, congenital heart disease (CHD), interstitial lung disease, vasculitis, pulmonary thromboembolism and idiopathic pulmonary haemosiderosis. Abnormal bronchial arteries (BAs) and non-bronchial systemic collateral arteries (NBSCs) were assessed for number and site and their correlation with underlying aetiologies. Results: A total of 86 patients (45 males, age from 0.3 to 18 yr, mean 13.88 yr) were included in the study; among these only two patients were less than five years of age. The most common cause of haemoptysis was active infection (n=30), followed by bronchiectasis (n=18), post-infectious sequelae (n=17) and CHD (n=7). One hundred and sixty five abnormal arteries were identified (108 BA and 57 NBSC), and were more marked in bronchiectasis group. Interpretation & conclusions: Active infections and bronchiectasis are the most common causes of haemoptysis in children. While post-infectious sequelae are less common, in patients with haemoptysis, the presence of any abnormal arteries correlates with a more frequent diagnosis of bronchiectasis. NBSCs are more common in post-infectious sequelae and CHD.

Allergic Bronchopulmonary Aspergillosis in Children Presenting as Lung Masses.

Allergic bronchopulmonary aspergillosis (ABPA) is an IgE-mediated hypersensitivity reaction predominantly occurring in patients of asthma and cystic fibrosis. The typical radiological findings in ABPA include central bronchiectasis and fleeting opacities. In this retrospective study, the aim was to describe cases of ABPA in children who had a mass-like lesion in the lung. There were 5 cases of ABPA in children, who presented as mass-like lesions that responded very well to treatment for ABPA. All cases, except 1, had asthma as the underlying disease. There was a delay in the diagnosis of ABPA in all 5 cases. There had been unnecessary invasive investigations in some of these cases before the diagnosis of ABPA was made. To conclude, children with ABPA may present with a mass-like lesion in the lung and high index of suspicion is required to diagnose ABPA timely to prevent its consequences.