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.

Revised ISHAM-ABPA working group clinical practice guidelines for diagnosing, classifying and treating allergic bronchopulmonary aspergillosis/mycoses.

BACKGROUND: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics. METHODS: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively. RESULTS: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response. CONCLUSION: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.

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.

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.

Comparison of Protocol-Based Continuous and Intermittent Tube Feeding in Mechanically Ventilated Critically Ill Children - An Open Label Randomized Controlled Trial.

OBJECTIVES: To compare the time taken to reach the target calories and proteins by protocol based "continuous tube feeding (CTF)" and "intermittent tube feeding (ITF)" in critically ill children. METHODS: This trial was conducted in the Pediatric Intensive Care Unit (PICU) of a tertiary care institute. Eligible children were randomized to receive CTF or ITF. Target calories were defined as 70% of calorie amount as per the WHO formula and target protein was defined as 1.5 g/kg as per the American Society of Parenteral and Enteral Nutrition (ASPEN) criteria. The primary outcome was time taken to reach target calories, the secondary outcomes were time taken to reach target protein, incidence of feed intolerance, PICU mortality, duration of ventilation, and outcome on 28th day. RESULTS: Fifty-eight children were randomized; 29 in each group. The baseline characters were comparable. The median (IQR) times for reaching target calories were 1.7 (1.4, 2.5) d and 1.8 (1.4, 4.4) d in the CTF and ITF groups, respectively [Hazards ratio (HR) 0.89 (95% CI 0.5, 1.5); p = 0.69]. For the target protein intake, the median times were comparable in the 2 groups [HR 0.82 (95% CI 0.4-1.5); p = 0.55]. The other outcomes were not significantly different between the groups. CONCLUSIONS: The authors did not observe any difference in the time taken to reach target calories and protein between the two different modes of delivery of enteral nutrition.

Efficacy and Safety of Olanzapine for the Prevention of Chemotherapy-induced Nausea and Vomiting in Children: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Chemotherapy-induced nausea and vomiting (CINV) remain the most distressing event in patients receiving highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). This meta-analysis was conducted to evaluate the efficacy and safety of olanzapine containing regimen in preventing CINV in children on HEC and MEC. We searched PubMed, Embase, and Cochrane central register of controlled trials electronic databases to identify randomized clinical trials that compared 2 groups who either got olanzapine (olanzapine group) or placebo/no olanzapine (control group) for the prevention of CINV in children. The primary outcome was to determine the efficacy of olanzapine (complete response). The secondary outcomes were nausea control, the need for rescue medications, and adverse events of olanzapine. Three randomized clinical trials (n=394 patients) were included in this meta-analysis (olanzapine group, n=194, and placebo/control group, n=200). The pooled analysis of this meta-analysis found that olanzapine had a higher complete response in all phases of emesis in the HEC group and only in the acute phase in HEC/MEC groups compared with the control group. Olanzapine had higher nausea control in all phases of HEC but no nausea control in HEC/MEC. Olanzapine also reduced the need for rescue medications. A significant number of patients in the olanzapine group experienced somnolence (grades 1 and 2), but none of the participants discontinued the study due to side effects. In conclusion, this meta-analysis showed that olanzapine significantly prevented CINV in HEC. There was also a lesser need for rescue medications in the olanzapine group. Somnolence was higher in the olanzapine group, but it was clinically insignificant.

Multiple Electrolytes Solution Versus Saline as Bolus Fluid for Resuscitation in Pediatric Septic Shock: A Multicenter Randomized Clinical Trial.

OBJECTIVE: To determine if initial fluid resuscitation with balanced crystalloid (e.g., multiple electrolytes solution [MES]) or 0.9% saline adversely affects kidney function in children with septic shock. DESIGN: Parallel-group, blinded multicenter trial. SETTING: PICUs of four tertiary care centers in India from 2017 to 2020. PATIENTS: Children up to 15 years of age with septic shock. METHODS: Children were randomized to receive fluid boluses of either MES (PlasmaLyte A) or 0.9% saline at the time of identification of shock. All children were managed as per standard protocols and monitored until discharge/death. The primary outcome was new and/or progressive acute kidney injury (AKI), at any time within the first 7 days of fluid resuscitation. Key secondary outcomes included hyperchloremia, any adverse event (AE), at 24, 48, and 72 hours, and all-cause ICU mortality. INTERVENTIONS: MES solution ( n = 351) versus 0.9% saline ( n = 357) for bolus fluid resuscitation during the first 7 days. MEASUREMENTS AND MAIN RESULTS: The median age was 5 years (interquartile range, 1.3-9); 302 (43%) were girls. The relative risk (RR) for meeting the criteria for new and/or progressive AKI was 0.62 (95% CI, 0.49-0.80; p < 0.001), favoring the MES (21%) versus the saline (33%) group. The proportions of children with hyperchloremia were lower in the MES versus the saline group at 24, 48, and 72 hours. There was no difference in the ICU mortality (33% in the MES vs 34% in the saline group). There was no difference with regard to infusion-related AEs such as fever, thrombophlebitis, or fluid overload between the groups. CONCLUSIONS: Among children presenting with septic shock, fluid resuscitation with MES (balanced crystalloid) as compared with 0.9% saline resulted in a significantly lower incidence of new and/or progressive AKI during the first 7 days of hospitalization.

Lung Function Tests in Infants and Children.

Lung function testing is an essential modality of investigation in children as it provides objective evidence of lung disease/health. With advances in technology, various tests are available that can aid in the diagnosis of lung disease, assess the progression and response to therapy and document the lung development and evolving lung diseases in infants. This narrative review discusses lung function tests in infants and children. Currently, lung function tests can be performed in every age group, from neonates to the elderly. Spirometry and peak expiratory flow rate (PEFR) are the most employed tests in children more than six years of age. Spirometry helps diagnose and monitoring of both obstructive and restrictive diseases. There is a need for expertise to perform and interpret spirometry correctly. The forced oscillation technique (FOT) or impulse oscillometry (IOS) is done with tidal volume breathing and is feasible even in preschool children. Their utility is mainly restricted to asthma in children at present. Lung function tests can be performed in neonates, infants and children using infant pulmonary function test (PFT) equipment, although their availability is limited. Diffusion capacity for carbon monoxide (DLCO) is a valuable tool in restrictive lung diseases. Lung volumes can be assessed by body plethysmography and multiple washout technique. The latter can also assess lung clearance index. It is essential to perform and interpret the lung function test results correctly and correlate them with the clinical condition for optimum treatment and outcome.

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.

Evidence-Based Guidelines for the Management of Allergic Bronchopulmonary Aspergillosis (ABPA) in Children and Adolescents with Asthma.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) frequently complicates asthma. There is urgent need to develop evidence-based guidelines for the management of ABPA in children. The Evidence Based Guideline Development Group (EBGDG) of the Indian Academy of Pediatrics (IAP) National Respiratory Chapter (NRC) addressed this need. METHODS: The EBGDG shortlisted clinical questions relevant to the management of ABPA in asthma. For each question, the EBGDG undertook a systematic, step-wise evidence search for existing guidelines, followed by systematic reviews, followed by primary research studies. The evidence was collated, critically appraised, and synthesized. The EBGDG worked through the Evidence to Decision (EtD) framework, to formulate recommendations, using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Seven clinical questions were prioritized, and the following recommendations formulated. (1) Children with poorly controlled asthma should be investigated for ABPA (conditional recommendation, moderate certainty of evidence). (2) Low dose steroid therapy regimen (0.5 mg/kg/d for the first 2 wk, followed by a progressive tapering) is preferable to higher dose regimens (conditional recommendation, very low certainty of evidence). (3) Oral steroid regimens longer than 16 wk (including tapering), should not be used (conditional recommendation, very low certainty of evidence). (4) Antifungals may or may not be added to steroid therapy as the evidence was neither in favour nor against (conditional recommendation, low certainty of evidence). (5) For clinicians using antifungal agents, the EBGDG recommends against using voriconazole instead of itraconazole (conditional recommendation, very low certainty of evidence). (6) No evidence-based recommendation could be framed for using pulse steroid therapy in preference to conventional steroid therapy. (7) Immunotherapy with biologicals including omalizumab or dupilumab is not recommended (conditional recommendation, very low certainty of evidence). CONCLUSIONS: This evidence-based guideline can be used by healthcare providers in diverse clinical settings.

Post-COVID-19 Sequelae in Children.

Coronavirus disease 19 (COVID-19), caused by the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), has been implicated in having post-COVID-19 sequelae in both adults and children. There is a lack of good data on the prevalence and risk factors for post-COVID-19 sequelae in children. The authors aimed to review the current literature on post-COVID sequelae. The prevalence of post-COVID sequelae in children is highly variable among studies, with an average of 25%. The sequelae may affect many organ systems, though mood symptoms, fatigue, cough, dyspnea, and sleep problems are common. In many studies, it is difficult to establish a causal association due to the lack of a control group. Furthermore, it is difficult to differentiate whether the neuropsychiatric symptoms in children after COVID-19 are due to infection or a result of lockdowns and social restrictions imposed by the pandemic. Children with COVID-19 should be followed by a multidisciplinary team and screened for symptoms, followed by focused laboratory evaluations as needed. There is no specific treatment for the sequelae. Only symptomatic and supportive treatment is required in most cases. More research is necessary to standardize the definitions of sequelae, establish a causal association, assess various treatment options, and the effects of different virus variants, and finally, see the impact of vaccination on the sequelae.

A Randomized Controlled Trial of Norepinephrine Plus Dobutamine Versus Epinephrine As First-Line Vasoactive Agents in Children With Fluid Refractory Cold Septic Shock.

Our objective was to compare norepinephrine plus dobutamine versus epinephrine as the first-line agent in children with fluid refractory cold septic shock. DESIGN: Open-label randomized controlled study. SETTING: A single-center PICU from North India. PATIENTS: Children 2 months to less than 18 years old with fluid refractory cold septic shock. INTERVENTIONS: In the intervention group, norepinephrine and dobutamine were started and in the control group, epinephrine was started as the first-line vasoactive agent. The primary outcome was the proportion attaining shock resolution (attaining all the therapeutic endpoints) at 1 hour of therapy. MEASUREMENTS AND MAIN RESULTS: We enrolled 67 children: 34 in the norepinephrine plus dobutamine group (intervention) and 33 in the epinephrine group (control). There was no difference in shock resolution at 1 hour (17.6% vs 9%; risk ratio [RR], 2.0; 95% CI, 0.54-7.35; p = 0.25), 6 hours (76.4% vs 54.5%; RR, 1.69; 95% CI, 0.92-3.13; p = 0.06), and 24 hours between the intervention and control groups, respectively. Children in the norepinephrine plus dobutamine group attained shock resolution earlier (measured from starting of vasoactive agents to attaining all the therapeutic endpoints) (hazard ratio, 1.84 [1.1-3.08]). The difference in 28-day mortality was not significant (23.5% vs 39.3% in the intervention and control groups, respectively [RR, 0.59; 95% CI, 0.28-1.25]). CONCLUSIONS: In children with fluid refractory cold septic shock, with use of norepinephrine plus dobutamine as first-line agents, the difference in the proportion of children attaining shock resolution at 1 hour between the groups was inconclusive. However, the time to shock resolution was earlier in the norepinephrine plus dobutamine group. Also, fewer children in the intervention group were refractory to treatment. Further studies powered to detect (or exclude) an important difference would be required to test this intervention.

Impulse oscillometry (IOS) for detection of exercise induced bronchoconstriction in children with asthma ages 6-15 years.

OBJECTIVES: To determine the discriminatory value of various impulse oscillometry (IOS) parameters, and to find the cutoff value of the appropriate parameter for identifying exercise-induced bronchoconstriction (EIB) in children with asthma. METHODS: This cross-sectional study was conducted in India from October 2016 to March 2018 in children with asthma who were 6-15 years of age. One hundred and five children were enrolled and subjected to pre-exercise IOS and spirometry followed by free running treadmill test as an exercise challenge. All children could achieve minute ventilation >17.5-21 times of FEV1 during the exercise challenge test. Then, IOS and spirometry were performed at 10 ± 2, 20 ± 2, and 30 ± 2 min post-exercise challenge. EIB was defined as reduction of FEV1 ≥10% within 30 min of exercise. For purposes of analysis, the children were grouped into two categories: "EIB Present" or "EIB Absent". RESULTS: The prevalence of EIB in our study was 20.95% (n = 22). ΔR5max percentage within 30 min post-exercise (AUC 0.74; 95% CI: 0.64, 0.84) had the best discriminating capacity among all IOS parameters for identifying EIB. A cutoff value of 14.1% increase in R5 within 30 min post-exercise was obtained for detection of EIB (sensitivity-95.45%, specificity-50.6%, PPV-33.87% and NPV-97.67%). CONCLUSIONS: A percentage change in R5 with a cutoff value of 14.1% increase post-exercise had the best discriminatory capacity among all IOS parameters for detection of EIB in children with asthma. However, low positive predictive value (PPV) with high negative predictive value (NPV) made this cutoff value more apt to rule out EIB.