Changes in FeNO, d-ROMs, and BH4 by Intravenous L-Arginine in Children and Its Putative Role in Asthma Treatment.

Purpose: Pteridines are metabolites of tetrahydrobiopterin (BH4), being coenzymes for nitric oxide synthase (NOS). No study has clarified the relationship among pteridines and NOS, fractional exhaled nitric oxide (FeNO) generated by pteridines, and reactive oxygen species. In this study, we administered arginine, a precursor of NO, and confirmed changes in the levels of pteridines, FeNO, and reactive oxygen species and their relationship to clarify the pathogenesis of airway inflammation in which oxidative stress is involved, such as bronchial asthma. Patients and Methods: This is a prospective, randomized open-label study. Children, aged 2 to 15 years, who were scheduled for growth hormone stimulation tests and were able to undergo a respiratory function test were recruited. They were randomly divided into two groups: arginine-administered and control groups. In the former, L-arginine hydrochloride was intravenously administered. After administration, the levels of diacron-reactive oxygen metabolites (d-ROMs), serum pteridines, serum amino acids, and fractional exhaled NO (FeNO) were measured. Results: We analyzed 15 children aged 4 to 14 years. In the arginine-administered group, there was an increase in the FeNO level and a decrease in the d-ROMs level, reaching a peak 30 min after administration, compared with the control group. In addition, there was a decrease in the serum biopterin level and an increase in the d-ROMs level, reaching peak 60 min after administration. Conclusion: The administration of L-arginine increased the NO level and decreased the d-ROMs level. Due to this, biopterin may be consumed and decreased, leading to an increase in the d-ROMs level. As a reduction in reactive oxygen species leads to the relief of inflammation, arginine and biopterin may be useful for inhibiting inflammation.

Pediatric allergies in Japan: Coronavirus disease pandemic-related risk factors.

Background: The coronavirus disease 2019 (COVID-19) pandemic impacted various parts of society, including Japanese children with allergies. Objective: This study investigated risk factors for pediatric allergic diseases associated with the state of emergency owing to the COVID-19 pandemic in Japan, including during school closures. Methods: Parents of pediatric patients (0-15 years) with allergies were enrolled and queried regarding the impact of school closure on pediatric allergies compared to that before the COVID-19 pandemic. Results: A valid response was obtained from 2302 parents; 1740 of them had children with food allergies. Approximately 4% (62/1740) of the parents reported accidental food allergen ingestion was increased compared to that before the COVID-19 pandemic. Accidental ingestion during school closures was associated with increased contact with meals containing allergens meant for siblings or other members of the family at home. The exacerbation rate during the pandemic was highest for atopic dermatitis at 13% (127/976), followed by allergic rhinitis at 8% (58/697), and bronchial asthma at 4% (27/757). The main risk factors for worsening atopic dermatitis, allergic rhinitis, and bronchial asthma were contact dermatitis of the mask area (34/120 total comments); home allergens, such as mites, dogs, and cats (15/51 total comments); and seasonal changes (6/25 total comments), respectively. Conclusion: The main factors affecting allergic diseases were likely related to increased time at home, preventive measures against COVID-19, and refraining from doctor visits. Children with allergies were affected by changes in social conditions; however, some factors, such as preventing accidental ingestion and the management of allergens at home, were similar to those before the COVID-19 pandemic. Patients who had received instructions on allergen avoidance at home before the pandemic were able to manage their disease better even when their social conditions changed.

Long-Term Outcomes of End-Flexible-Rigidscopic Transoral Surgery for Pharyngolaryngeal Cancer.

OBJECTIVE: End-flexible-rigidscopic transoral surgery (E-TOS) is a new and minimally invasive transoral surgery for resection of Tis-selected T3 pharyngolaryngeal cancers. We evaluated long-term oncological outcomes and whether postoperative voice and swallowing function were preserved following E-TOS. METHODS: In this retrospective single-center study, 154 patients treated with E-TOS using a curved retractor, flexible-tip rigid endoscope, and thin curved instruments were included. Their survival rate, larynx preservation rate, and disease control rate were estimated using the Kaplan-Meier method. Postoperative voice function was evaluated using both objective and subjective tests. Postoperative swallowing function was assessed using the Hyodo score and the functional outcome swallowing scale. RESULTS: The 3-year and 5-year overall survival, disease-specific survival, disease-free survival, laryngectomy-free survival, local control, and loco-regional control rates post E-TOS were 89.8% and 82.2%, 95.6% and 92.3%, 78.5% and 70.3%, 87.2% and 80.9%, 93.9% and 92.5%, and 87.2% and 85.7%, respectively. Both objective and subjective postoperative voice and swallowing function tests were within normal limits in more than 90% of the patients. CONCLUSION: E-TOS is an effective, safe, low-cost, and minimally invasive transoral surgery for Tis-selected T3 pharyngolaryngeal cancer; it also preserves postoperative voice, larynx, and swallowing function. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1415-1424, 2023.

Usefulness of serum biopterin as a predictive biomarker for childhood asthma control: A prospective cohort study.

BACKGROUND: Pteridines are metabolites of tetrahydrobiopterin, which serves as co-enzyme of nitric oxide synthase. We sought to investigate the usefulness of pteridines as biomarkers for childhood asthma control. METHODS: We conducted a single-center prospective cohort study involving 168 asthmatic children aged 4-17 years who visited the periodical asthma checkup program. Serum neopterin and biopterin levels were measured as pteridines at each visit along with measurement of FeNO, respiratory function tests, nasal eosinophil test, blood eosinophil count, and IgE level. We calculated coefficients for relation between pteridines and asthma control, which was assessed by questionnaires (JPAC: Japanese Pediatric Asthma Control Program). RESULTS: A total of 168 participants aged 10.3 ± 3.39 years (mean ± SD) with asthma were recruited. The participants in this study contained 58 patients (34.5%) of complete-controlled based on JPAC, 132 patients (76.0%) of well-controlled group based on GINA. FeNO and serum neopterin level did not correlate with following period's JPAC scores. In contrast, serum biopterin level significantly correlated with following period's JPAC total score (Coefficients 0.398; 95% CI 0.164 to 0.632; p value 0.001) and frequency of wheezing during exercise (Coefficients 0.272; 95% CI 0.217 to 0.328; p value < 0.001). CONCLUSIONS: We found serum biopterin effected the following period's control status of asthmatic children, thus monitoring biopterin level will be a useful for management of asthma to adjust treatment.