Pranlukast treatment and the use of respiratory support in infants with respiratory syncytial virus infection.

BACKGROUND: In infants, respiratory syncytial virus (RSV) infection occasionally causes severe symptoms requiring respiratory support; however, supportive care is the primary treatment. This study compared the use of respiratory support among infants with RSV infection treated with or without pranlukast. METHODS: This retrospective cohort study included infants aged <10 months with RSV infection who were admitted to three secondary level hospitals in Japan between 2012 and 2019. The infants were divided into two groups depending on whether they were treated with pranlukast. The primary outcome was the receiving respiratory support (high-flow nasal cannula, nasal continuous positive airway pressure, or ventilator). The secondary outcomes were the length of hospital stay, and the Global Respiratory Severity Score (GRSS) on starting respiratory support or at the time of the worst signs during hospitalization. We performed a propensity score-matched analysis. RESULTS: A total of 492 infants, including 147 propensity score-matched pairs, were included in the analysis. The use of respiratory support was significantly lower in infants treated with pranlukast (3.4% [5/147]) than those treated without pranlukast (11.6% [17/147]; P = 0.01). In the propensity score-matched analysis, pranlukast use was associated with a significantly lower chance of needing respiratory support (odds ratio: 0.27, 95% confidence interval: 0.08-0.79; P = 0.01); however, the length of hospital stay (median: 4 days) and the GRSS (median: 2.804 and 2.869 for infants treated with and without pranlukast, respectively) did not differ significantly between propensity score-matched pairs. CONCLUSIONS: Pranlukast use was associated with a reduced likelihood of requiring respiratory support in infants aged <10 months with RSV infection.

Targeted Use of Prednisolone with Intravenous Immunoglobulin for Kawasaki Disease.

BACKGROUND AND OBJECTIVES: Intravenous immunoglobulin (IVIG) therapy for acute-stage Kawasaki disease (KD) is the first-line treatment for preventing the development of coronary artery aneurysms (CAA). Corticosteroids (prednisolone) and infliximab are often used in patients at a high risk of CAA or those with CAA at diagnosis; however, there are only a few reports of non-responders to corticosteroids as an adjuvant therapy or rescue alternative to IVIG. In this study, we compared the therapeutic effects of primary and secondary prednisolone with IVIG for KD. METHODS: We established the following three protocols: A was a secondary rescue prednisolone protocol; B was no prednisolone and second-line infliximab protocol, and C was the primary prednisolone protocol. The indication for prednisolone administration was based on the following: primary prednisolone administration, Kobayashi score; and secondary administration, Shizuoka score. RESULTS: Four hundred and sixty-nine patients were enrolled in the three protocols. A comparison between primary and secondary prednisolone and IVIG, as the first-line therapy revealed that the number of first non-responders in C group was 7 (8.3%), which was significantly lower than the 50 (20.9%) in A group. There was a significant difference in the first and second non-responders among the three groups, and the number of non-responders in A group was 6 (2.5%), which was significantly lower than the 13 (9.9%) in B group (p < 0.001, by Bonferroni test). The multivariate logistic regression analysis showed that IVIG non-responders among the protocol groups had an adjusted odds ratio of 6.47. Fifteen IVIG non-responders were administered infliximab as a second-line therapy, and of them, 9 (60%) showed therapy resistance. CAA occurred in 21 patients (4.6%). There was no significant difference among each protocol group. CONCLUSIONS: The number of IVIG non-responders in the group with prednisolone administration was lower than that in the group without prednisolone administration. Secondary rescue infliximab therapy for IVIG non-responders resulted in a lower defervescence effect than the secondary rescue IVIG with prednisolone administration. Further prospective randomized studies are needed to identify factors useful for preventing IVIG non-responders and determine the optimal rescue therapy for preventing CAA.

Efficacy of Brazilian Propolis Supplementation for Japanese Lactating Women for Atopic Sensitization and Nonspecific Symptoms in Their Offspring: A Randomized, Double-Blind, Placebo-Controlled Trial.

Propolis is a natural product collected from several plants by honeybees and mixed with beeswax and salivary enzymes. In animal models, propolis suppressed IgE-mediated allergies. However, there is no clinical evidence that propolis prevents human atopic sensitization, to the best of our knowledge. Therefore, a randomized, double-blind, placebo-controlled trial was conducted to assess whether propolis supplementation for lactating women increases or decreases the level of total IgE and antigen-specific IgE in the serum of their offspring (i.e., atopic sensitization) at the time of their first birthday. In addition, whether propolis supplementation improves or worsens nonspecific symptoms (e.g., eczema) in the lactating women and their offspring was also investigated. This trial is registered with UMIN000020794. Eligible pairs of mothers and their offspring (n=80) were randomized to two groups: propolis (n=40) and placebo (n=40). Participants were evaluated every month, and 31 (78%) of the propolis group and 23 (58%) of the placebo group underwent blood tests at the first birthday of the offspring. Total IgE ≥ 10 UA/ml was seen in 26 (84%) infants whose mothers were given propolis, which was not significantly different from the 19 (86%) given placebo (P=0.80). Total IgE as a continuous variable was not significantly different between the propolis and placebo groups (P=0.70). Antigen-specific IgE levels for mites, egg white, cow's milk, and wheat, as both dichotomous and continuous variables, were not significantly different between the two groups. Both in mothers and their offspring, there were no significant differences in the subjective improvements of nonspecific symptoms between the two groups. Except for one mother who had transient and mild nausea, none of the other mothers or their offspring developed severe adverse events during the follow-up period. In conclusion, compared with placebo, Brazilian propolis supplementation did not influence the risk of atopic sensitization in infants and neither did it improve nor worsen nonspecific symptoms in either mothers or their infants.

Targeted use of prednisolone with the second IVIG dose for refractory Kawasaki disease.

BACKGROUND: Prednisolone (PSL) has been suggested to be useful for the treatment of Kawasaki disease (KD) resistant to i.v. immunoglobulin (IVIG), but much remains to be elucidated regarding its use. METHODS: A total of 1087 subjects were involved in a two-study multicenter prospective investigation of the effects of acute phase therapy on IVIG-resistant KD. Subjects resistant to the first dose of IVIG were classified into high (≥10 mg/dL) and low (<10 mg/dL) serum C-reactive protein (CRP) groups after the first dose of IVIG. RESULTS: In the first study, the efficacy of the second dose of IVIG in the high CRP group was significantly lower than in the low CRP group (47.8% vs 76.8%, P < 0.005). In the second study, PSL was co-administered with the second dose of IVIG to the high CRP patients (intensified regimen). The efficacy of the intensified regimen was similar to that of the second dose of IVIG in the low CRP group (79.4% vs 83.3%). Although the difference in the incidence of persistent coronary artery lesions (CAL) between the high and low CRP groups was significant in the first study (19.6% vs 3.0%, P < 0.005), it was not significant in the second study (8.8% vs 2.4%). CONCLUSIONS: The targeted use of PSL with the second dose of IVIG in KD patients resistant to the first dose of IVIG and who are predicted to be resistant to the second dose of IVIG, appears to be effective.

Increased food allergy and vitamin D: randomized, double-blind, placebo-controlled trial.

BACKGROUND: To elucidate whether maternal vitamin D supplementation during lactation improves infantile eczema and other subsequent allergic disorders, a randomized, double-blind, placebo-controlled trial was performed. METHODS: Mothers (n = 164) of infants with facial eczema at 1 month check-up were randomly assigned to receive vitamin D3 supplements (n = 82; 800 IU/day) or placebo (n = 82) for 6 weeks from May 2009 to January 2011. The primary outcome was infantile eczema quantified on Scoring Atopic Dermatitis (SCORAD) index at 3 month check-up, and the secondary outcomes were atopic dermatitis, food allergy, and wheeze diagnosed by doctors up to 2 years of age. RESULTS: There was no significant difference in SCORAD at 3 month check-up between the two groups. Doctor-diagnosed food allergy was significantly more common up to age 2 years in the vitamin D group (10/39, 25.7%) than in the placebo group (3/40, 7.5%; risk ratio (RR), 3.42; 95% confidence interval [CI]: 1.02-11.77; P = 0.030). Moreover, at least one secondary outcome was also significantly more common in the vitamin D group (17/39, 43.6%) than in the placebo group (7/40, 17.5%; RR, 2.49; 95%CI: 1.16-5.34; P = 0.012). CONCLUSIONS: Vitamin D supplementation may not decrease the severity of infantile eczema at 3 months of age, but may rather increase the risk of later food allergy up to 2 years of age. Because a large number of subjects was lost to follow up, further study is needed to confirm the findings.

Bimodal effects of obesity ratio on disease duration of respiratory syncytial virus infection in children.

BACKGROUND: Morbid obesity may be associated with hospitalization and possibly death from the 2009 pandemic H1N1 infection, suggesting a yet unknown association between obesity and the severity of viral infections. Thus, we examined association between obesity ratios and duration of disease in children with Respiratory Syncytial Virus (RSV) infection. METHODS: A retrospective survey of 243 children admitted for bronchitis, bronchiolitis, pneumonia, and those who tested positive for a RSV test, were observed from a single institute in Japan. Primary outcome was set as the total days of wheezing in both the outpatient clinic and during hospitalization. Secondary outcomes were as follows: 1) total days of fever (37.5°C≤) during hospitalization, and 2) days of drip infusion during hospitalization. RESULTS: When the obesity ratio was 6 and less, days of wheezing showed significant negative association with obesity ratios. In contrast, when the obesity ratio was more than 6, days of wheezing, days of fever during admission and days of drip infusion showed significant positive association with obesity ratios. CONCLUSIONS: These results suggest that disease duration of RSV infection may be prolonged not only in lean but also in obese children.