Regulatory T (Treg) cells play a central role in protecting against the development of allergic asthma and interleukin-10 (IL-10) producing T regulatory type 1 (Tr1) cells contribute to the regulation of asthma. Complement regulatory protein CD46 was shown to stimulate the development of IL-10 producing Tr1 cells. Crosslinking of CD46 during CD4+ T cell priming induces production of large amount of IL-10 and granzyme B. These CD46-induced regulatory T cells (Tr1) does not require pre-existing basal expression of FoxP3. Through local IL-10 and granzyme B secretion, such Tr1 cell could control T-cell-mediated inflammation. In asthmatic patients, we found that diminished IL-10, granzyme B, and CCR 4 expression from CD3/CD46-activated Tr1 cells. CD3/CD46-activated Tr1 cells from asthma patients co-cultured with BEAS-2B cells suppressed dermatophagoides pteronyssinus 2 (Der p 2)-induced nuclear factor-κB/p65 by cell contact inhibition. Decreased interaction of CD3/CD46-activated Tr1 and BEAS-2B cells from asthmatics was associated with downregulation of phosphorylation of protein kinase B expression. Decreased interaction between CD46-mediated Tr1 and lung epithelial cells with less IL-10 and granzyme B production may contribute to airway inflammation in allergic asthma. Der p specific immunotherapy enhances the suppressive function of IL-10 in CD46-mediated Tr1 cell from asthmatic patients and suppresses airway inflammation in these patients. Based on these results, it might be possible to design therapeutic strategies to manipulate complement activated Tr1 cells to achieve allergen tolerance and suppress airway inflammation in patients with allergic asthma.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub] [CITATIONS]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

[FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

Background: Pertussis incidence has been increasing despite high early childhood vaccination coverage. Various strategies have been recommended to combat this problem which includes cocooning, booster doses for adolescents and young adults, and more recently maternal intrapartum vaccination. A previous report had highlighted an increase in pertussis in infants. This review was done to evaluate if there has been any change in the prevalence in the subsequent 10 years. Materials and Methods: Retrospective cohort study of admissions for pertussis in patients aged 0–18 years in a single-center tertiary maternal-pediatric hospital in Singapore from January 1, 2008, to October 31, 2017. Results: There were 221 cases identified. The majority were infants <6 months (89%) and of Malay (46%) ethnicity. About 54% were male and 81% were delivered term. Nearly, 69.7% had not received pertussis immunization. 64.2% had exposure to an unwell family member with respiratory symptoms. Cough was the most common presenting complaint (100%). High dependency or intensive care treatment was required in 21 cases (9.5%). Length of stay was significantly longer for infants under 6 months of age compared to those aged 6 months or older (additional 1.63 days, 95% confidence interval 0.57–2.68, P = 0.003). Coinfection was found in 23 cases, associated comorbidities in 22 cases, and both conditions in 3 children. There were 2 deaths and 11 readmissions. Conclusions: Pertussis in young infants in Singapore remains a significant healthcare burden despite current immunization strategies. Routine maternal vaccination to confer passive immunity on the newborn child may be beneficial to address this problem.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]

Background: Bronchoalveolar lavage (BAL) is a useful procedure in the diagnosis and treatment of several respiratory diseases. The right middle lobe or lingula is the preferred location of BAL in diffuse lung disease. The aim of this study was to determine the proper location of BAL in infants and children. Design: This was prospective, observational study at Queen Sirikit National Institute of Child Health between January and December 2017. Materials and Methods: Children, aged 1 month to 15 years, who underwent BAL were enrolled for this study. BAL was performed with the flexible bronchoscope under general anesthesia. The total instilled volume was generally 2–3 ml/kg, divided into 2–6 aliquots. The location of BAL was the most affected area in chest radiography. In diffuse lung disease, BAL was performed in all lobes. The volume and percentage of fluid recovered from various lobes were compared. Statistical Analysis: Statistical analysis was performed using SPSS version 23. The value of P < 0.05 was considered statistically significant. Results: A total of 66 patients with a median age of 1.6 years were enrolled. The total volume recovered was 20% of the instilled volume (interquartile range [IQR] 13.4, 31.8). The volume recovered from the right lung (23%, IQR 13.4, 32.58) was significantly higher than from the left lung (18.9%, IQR 12.5, 30, P = 0.019). There was no significant difference between volume recovered from various lobes. However, there was a trend toward higher volume recovered from the right lower lobe (RLL) (25%, IQR 13.1, 33.75). Conclusions: In infants and children, BAL performed in the right lung and RLL is associated with a higher volume recovered.

[ABSTRACT]  [FULL TEXT]  [PDF]  [Mobile Full text]  [EPub]