Transfluthrin is Associated with High Susceptibility to Asthma in Children with Promoter Variants of Beta Chain of High-Affinity Receptor IgE and Tumour Necrosis Factors-α Genes.

This study investigates the genetic variations in FcεR1ß-109 C/T (rs512555) and TNF-α-308 G/A (rs1800629) genes and examines whether the mosquito repellent transfluthrin (TFT) modifies the risk for asthmatic children. A case-control study was conducted involving 130 asthmatic children and 123 age-sex matched controls. Differential leukocyte counts, IgE, and hs-CRP levels were estimated using a five-part haematology analyzer and Beckman Coulter (AU480), respectively. Genetic variations in FcεR1ß-109 and TNF-α-308 were analysed using restriction fragment length polymorphism. Serum TFT levels were measured using gas chromatography-tandem mass spectrometry. Asthmatic children had significantly increased total leukocyte, neutrophil, lymphocyte, eosinophil, and basophil counts (p < 0.0001), while their monocyte counts were lower compared to controls (p < 0.0001). TFT levels were higher in asthmatic children (1.38 ± 0.91 vs. control 0.69 ± 0.41µg/L, p < 0.0001), which predominantly induced wheezing. Elevated TFT levels were associated with an increased risk of childhood asthma (OR: 3.08, p < 0.0001). Children with the FcεRIß TT (OR: 2.39, p < 0.017) and TNF-α GG genotypes (OR: 7.17, p < 0.0001) were more susceptible to asthma. TFT synergistically enhanced the risk of asthma in both FcεRIß-109 TT (OR: 5.3, p = 0.001) and TNF-α-308 GG (OR: 17.18, p < 0.0001) genotypes. TFT levels were correlated with IgE (r = 0.363; p = 0.006), hs-CRP (r = 0.324; p = 0.049) and eosinophil (r = 0.300; p = 0.038), respectively. IgE and eosinophils were correlated (r = 0.599, p = 0.001) in the FcεRIß TT genotype-carrying asthmatic children. Similarly, neutrophils and hs-CRP were correlated (r = 0.768, p < 0.0001) in asthmatic children with TNF-α GG genotype. The risk of asthma is inherently higher in children with FcεRIß TT and TNF-α GG variants. TFT exposure amplifies the risk of asthma in children among all the subgenotypes of both genes. TFT influences IgE and eosinophil in FcεRIß TT genotype while it influences neutrophils and hs-CRP in TNF-α GG genotypes.

Low Serum Levels of Zinc, Selenium, and Vitamin D3 Are Biomarkers of Airway Inflammation and Poor Asthma Control: A Two-Centre Study.

Background Asthma is a chronic inflammatory disease with its control being affected by underlying oxidative stress. Trace elements, along with vitamin D3, play an important role in immune alterations leading to an imbalance of Th1/Th2 helper cells. However, their role in asthma pathogenesis and control is inconsistent and inconclusive. The objective of our study was to assess levels of serum trace elements like zinc, copper, selenium, iron, magnesium, vitamin D3 levels, IgE, and HsCRP in asthmatic children, compare with healthy controls, and assess their association with the level of asthma control. Methods A cross-sectional study was conducted from 2019 to 2021 enrolling 100 asthmatic children and 75 healthy controls. The level of asthma control was assessed as uncontrolled, partly controlled, and controlled asthma as per GINA Guidelines. Mean and standard deviation were calculated for each element and mean differences between groups were analyzed by student t-test. A p-value of <0.05 was considered significant. Results The mean age was 8.75±2.89 yrs in cases and 9.04±2.79 in controls. A total of 57.6% of cases had atopic comorbidities. The mean serum zinc levels were 51±12.8 mg/dl, which was very low in asthmatic children as compared to 60±18.2mg/dl (p-value 0.0002) in healthy controls. Serum selenium was 13±3 µg/dl in asthmatics vs. 15±4 µg/dl (p-value 0.0002) in healthy controls. Serum copper was 115.2±21.92µg/dl vs. 125.3±31.99µg/dl (p-value 0.015), Serum vitamin D3 levels were 13.07±7.82ng/ml vs. 17.82±14.62 ng/ml(p-value 0.006) in both groups, respectively. SIgE and HsCRP were high in asthmatic children suggestive of eosinophilic inflammation. Serum zinc was 49±5.45 mg/dl in the uncontrolled group, 53±6.1 in the partly controlled, and 58±8.0 in the well-controlled group (p<0.0001). Serum selenium was 10± 3.0 µg/dl in the uncontrolled group vs. 13± 2.0 and 14± 2.0 µg/dl in the partly controlled and well-controlled groups, respectively (p-value <0.0001). Vitamin D3 was significantly low (9.32±5.95ng/dl) in the uncontrolled group vs. 12.99±4.97 and 13.40±5.92 ng/dl(p<0.005) in the partly controlled and well-controlled groups respectively. Vitamin D3 showed a strong positive correlation with zinc (r=0.4,p< 0.0001) and a negative correlation with inflammatory markers like SIgE and HsCRP. Conclusion Children with asthma had low zinc, selenium, and vitamin D3 levels, and were associated with airway inflammation and poor asthma control.

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.

Early Atopic Sensitization to House-Dust Mite in Children with Recurrent Wheeze-A Cross-Sectional Study.

OBJECTIVES: To determine sensitization to house-dust mite (HDM) antigen in under-five children with recurrent wheeze, compare it with nonwheezers, and assess atopic comorbidities in them. METHODS: A cross-sectional study was done in the Pediatric department of a teaching hospital in North India, in 190 children aged 1-5 y. Out of these, 127 had recurrent wheeze (RW), and 63 had no wheeze (NW). Sensitivity was done by skin prick test (SPT) for two dust mites antigens: Dermatophagoide farinae and Dermatophagoide pteronyssinus antigens. In addition, atopic comorbidities like atopic dermatitis and allergic rhinitis were assessed. RESULTS: Mean age of the study population was 34.52 ± 20.50 mo. SPT positivity for either of the dust mites was 97 (76.4%) in RW and 13 (20.6%) in NW which was significant (p < 0.001, aOR = 12.27). HDM species sensitization for D. pteronyssinus was 55.1% vs. 15.9% (p < 0.001 aOR = 7.81) and D. farinae was 39.4% vs. 9.5% (p < 0.001, aOR = 5.45) in groups, respectively. Mean wheal size in RW Group was also significantly higher than NW group for D. pteronyssinus (2.39 ± 1.44 vs. 0.52 ± 1.19 mm, median (IQR) 3 (1-3), p < 0.001), D. farinae (1.80 ± 1.39 vs. 0.32 ± 1.00 mm, median (IQR) 2 (0-3), p < 0.001). Allergic rhinitis was present in 55 (43.3%) vs. 7 (11.1%) (p < 0.001), atopic dermatitis in 28 (22%) vs. 2 (3.2%) (p = 0.001) in group 1 and 2, respectively. All children with allergic rhinitis had HDM sensitization in both groups. CONCLUSION: This study showed early sensitization to HDM in children with recurrent wheeze. Atopic comorbidities were also present in them.

Rare Cases of Filarial Chyluria in Children.

Background: Lymphatic filariasis leading to the passage of white urine or chyle is a rare manifestation in children. Filarial parasite infiltration leading to abnormal lymphatic-urinary communication occurs with prolonged infection. The incubation period ranges from 5 to 20 yrs., thus relatively infrequent in the pediatric age group. Index of suspicion should be high when a child presents with the passage of white urine because the subclinical manifestation of filarial infection is difficult to recognize. Moreover, more pathognomonic clinical manifestations such as lymphoedema or hydrocoele are present in adulthood. It should also be differentiated from non-parasitic causes like nephrotic syndrome, urates and phosphates in urine, and congenital lymphatic-urinary communication. Case Presentation: We report two pediatric cases with the intermittent passage of milky white urine since one year. Institutional ethical committee approved the study. In both patients, urine triglycerides were high, and the presence of positive filarial antigen test confirmed the diagnosis. Medical management showed remission of symptoms. Our cases highlight the rare presentation of LF in children and the use of point of care diagnostic tests, management, and outcome in them. Conclusion: LF is a rare condition in children, and the index of suspicion should be high for early management.