The role of monocytes and natural killers' immunophenotypic subsets in bronchial asthma in children.

Objective: Childhood bronchial asthma (BA) is a globally significant chronic disease with major health consequences. Recently, focus on the role of the innate immune system has been highlighted. Therefore, this study explores the role of circulating monocytes and natural killer (NK) clusters in childhood asthma.Methods: This case-control study enrolled 50 children with asthma divided equally into severe and mild groups and 26 healthy children. Flow-cytometry analysis was used to identify circulating blood monocytes and natural killers' subsets. In addition, pulmonary function test (spirometry) for children with asthma was performed.Results: This study showed significant negative correlations between frequency of total circulating, classical, intermediate, and nonclassical monocytes with ratio of forced expiratory volume/forced vital capacity (FEV1/FVC) (r = -0.637, P < 0.001; r = -0.575, P < 0.001; r = -0.657, P < 0.001; r = -0.329, P = 0.004, respectively). Also, there was significant negative correlations between frequency of total NKs and CD56dim CD16+ NK with FEV1/FVC (r = -0.584, P < 0.001) and (r = -0.579, P < 0.001). Significant predictors of childhood asthma severity were frequencies of total monocytes, total NKs, intermediate monocytes, and CD56dimCD16+ NK.Conclusion: Finally, we concluded that the FEV1/FVC is linked to aberrations of monocytes' and natural killers' immunophenotypic subsets in children with asthma. The frequencies of total monocytes and NK are significant predictors of severity of childhood asthma. The frequencies of CD14high CD16+ intermediate monocytes and CD56dim CD16+ NK cells are the best independent predictors of severity in children with asthma.

MicroRNA-146a-5p and microRNA-210-3p Correlate with T Regulatory Cells Frequency and Predict Asthma Severity in Egyptian Pediatric Population.

Background: Severe bronchial asthma (BA) affects 5-10% of children, which imposes socioeconomic burden. Therefore, it is crucial to identify biomarkers for risk stratification in children with BA. T regulatory cells (Tregs) play a balancing role in allergic response regulation. We aimed to investigate the relationship between Treg, miR-210-3p, and miR-146a-5p in relation to asthma phenotypes in search of novel biomarkers of disease severity. Methods: This study included 50 children with BA classified into Group 1 (n = 25) children with mild to moderate asthma and Group 2 (n = 25) children with severe asthma. In addition to 26 control subjects. Flow cytometry was used to detect Tregs. Plasma miR-210-3p and miR-146a levels were determined using quantitative real-time PCR. Patients' FEV1 (Forced Expiratory Volume in the first second) was measured. Results: miR-210-3p level correlated negatively with Treg frequency (r = -0.828, P < 0.001) and FEV1 (r = -0.621, P < 0.001). The level of miR-146a-5p positively correlated positively with Treg% (r = 0.303, P = 0.032). ROC curve analysis revealed that miR-210-3p was the most sensitive biomarker of severity, with the area under curve (AUC) = 0.923, 96% sensitivity, and 60% specificity. According to multivariate analysis, miR-210-3p is an independent risk factor for BA severity [OR =3.119, P = 0.030], while miR-146a-5p is a protective factor [OR =0.811, P = 0.049]. Conclusion: Treg frequency is linked to FEV1, miR-146a-5p and miR-210-3p in childhood BA. Upregulation of miR-210-3p is a sensitive biomarker and an independent risk factor for BA severity in Egyptian children.

Is there a role of viral infection in cystic fibrosis exacerbation in children?

BACKGROUND: Cystic fibrosis (CF) is a degenerative disease distinguished by progressive epithelial secretory gland dysfunction associated with recurrent respiratory tract infections. Despite that bacteria have previously been studied as the main cause of CF airway damage, a strong effect of respiratory viral infections is also now recognized. We aimed to detect the relationship between viral infection and exacerbation in children with cystic fibrosis. METHODS: This is a cross sectional observational study recruiting 60 patients diagnosed as CF following in Cystic Fibrosis Clinic, Children`s Hospital, Cairo University, throughout a period of 7 months. Their age ranged from 6 months to 13 years. Patients had nasal swabs and sputum samples obtained when they developed respiratory exacerbations. Multiplex PCR (polymerase chain reaction) technique was used to detect respiratory viruses from nasal swabs. RESULTS: We detected viruses in 48 patients during exacerbation (80%), the most common virus was rhinovirus in 43.4% of patients, followed by bocavirus in 20%, adenovirus in 13.3%, enterovirus in 10% and human metapneumovirus in 6.7%. Co-infection with double viruses was detected in 10 patients. Bacterial infection was present in 56.7% of patients; the most common organism was Pseudomonas in 20% of patients, followed by Staphylococcus aureus, methicillin resistant Staphylococcus aureus, Klebsiella and Haemophilus influenzae. CRP was positive in 53.3% of patients. There was a significant relationship between sputum positive bacterial culture and each of influenza A virus, enterovirus and human metapneumovirus. CONCLUSIONS: This study demonstrated that exacerbation in cystic fibrosis may be exaggerated by viral infections such as influenza A and enterovirus necessitating hospitalization which shows the important protective role of vaccination. Also, a strong relationship was detected between some viruses such as enterovirus, human metapneumovirus and influenza and between bacterial infection.

Early myocardial functional abnormalities in primary dyslipidemia: clinical and echocardiographic observations in young children from a highly consanguineous population.

BACKGROUND: Dyslipidemia is a major health problem among children and adolescents worldwide due to its significant association with cardiovascular disease. Primary dyslipidemias are commonly familial syndromes that can be completely asymptomatic. PURPOSE: Apart from the risk of coronary artery disease (CAD), limited data are currently available on the direct effects of dyslipidemia on myocardial function in children. METHODS: We recruited 25 children with primary dyslipidemia (14 with isolated hypercholesterolemia, 4 with isolated hypertriglyceridemia, and 7 with combined dyslipidemia). Relevant clinical manifestations and laboratory and radiological investigations were evaluated. Pulsed-wave Doppler and tissue Doppler imaging echocardiography were performed for all recruited patients and the results were compared with those of 15 age- and sex-matched healthy children. RESULTS: The median age of the dyslipidemic children was 8 years (range, 1.5-16 years). A family history was documented in 13 cases (52%), while 18 (72%) had consanguineous parents. None of the dyslipidemic children had a personal history or clinical manifestations of CAD. In contrast, echocardiographic findings differed in several diastolic function parameters of both right and left ventricles in dyslipidemic children compared to controls. Based on normalized z scores, aortic valve narrowing was detected in 7 patients (28%), while narrowing of the aortic sinus (sinus of Valsalva) was detected in 15 patients (60%). CONCLUSION: Different types of primary dyslipidemia produce functional myocardial abnormalities early in childhood. Biochemical and echocardiographic screening of high-risk children is advised to minimize the incidence of serious cardiovascular complications.

The hidden impact of different Blastocystis genotypes on C-3 and IgE serum levels: a matter of debate in asthmatic Egyptian children.

Blastocystis hominis is highly prevalent with respiratory allergies among Egyptian children. Yet, little is known about the possible immunological relationship. Aims of this study were to measure complement-3 (C-3), total and specific IgE to intestinal allergens in patients' serum regarding the identified B. hominis genotypes. In a cross-sectional study, three hundred children (150 asthmatics and 150 non asthmatics) participated in the study from both sexes, mean age 7.5 ± SD (3-4) years after a questionnaire administration. PCR-based genotyping of B. hominis selective in vitro cultivation was performed. C-3, total and specific IgE were all measured in patients' serum utilizing ELISA. Blastocystosis was detected in 100 out of 300 children, 65 (43.3%) out of 150 asthmatics and 35 (23.3%) out of 150 non-asthmatics. Vacuolar forms were the most prevalent in both direct wet mount and stool cultures. Forty (61.5%) out 65 asthmatics and 5 (14.2%) out of 35 non-asthmatics were ≥ 5 organisms/HPF. Sex and irritable bowel disease were statistically insignificant (p value < 0.05). Urticaria was coincided in 15.4% of asthmatics and 8.6% of non-asthmatics. Of 100 cases of blastocystosis, eighty-four were genotype-3 and sixteen were genotype-4. Out of these, 55 cases of genotype-3 and 6 cases of genotype-4 were asthmatics. Positive C-3 serum levels were in 46 (54.81%) of genotype-3 and 2 (12.5%) of genotype-4. High total IgE levels in 30 (35.7%) out of 84 cases of genotype-3 and 4 (25%) out of 16 cases of genotype-4. Positive specific IgE was in 25 (29.8%) of genotype-3 and 3 (18.75%) of genotype-4. Genotype-3 was of higher infection intensity (p value = 0.0001). In conclusion, B. hominis possess a hidden allergy triggering impact that can be obscured by simultaneous high (total and specific) IgE levels towards specific common intestinal allergens. Blastocystosis induces allergy by increasing C-3 serum levels in a genotype-dependent manner being higher in genotype-3. Virulence of genotype-3 seems to stand beyond increased parasite intensity and wide absorption of intestinal allergens that indirectly elevate IgE serum levels.

A novel primer set for improved direct gene sequencing of human bocavirus genotype-1 from clinical samples.

Human bocavirus genotype (HBoV-1) is a parvovirus associated with respiratory tract infections in children with different degrees of severity. The current study intended to improve the direct gene sequencing of the HBoV-1 using a newly developed primer set. Screening the presence of human bocavirus infection among in-patients children suffering from lower respiratory tract infections was another aim of the current study. Nasopharyngeal swab samples from in-patients children suffering from lower respiratory tract infections were examined. The real-time polymerase chain reaction was used for the initial screening as a highly sensitive method to detect the HBoV. Genotyping of real-time positive samples was attempted by direct sequencing of PCR amplicons using NP, VP1/2 and the newly developed VP/NC primers. HBoV-1 was present in 56.8% of the examined children. The newly developed primer set successfully amplified all real-time PCR positive samples, however, the other primer pairs did not reliably detect real-time PCR positive samples. The gene sequences of the detected HBoV-1 showed conserved sequences to each other with a low rate of discrepancies. The high rate of infection and the similarity between the detected strains strongly suggest nosocomial infections.