Mechanical Ventilation Drives Inflammation in Severe Viral Bronchiolitis

Introduction

Respiratory insufficiency due to severe respiratory syncytial virus (RSV) infection is the most frequent cause of paediatric intensive care unit admission in infants during the winter season. Previous studies have shown increased levels of inflammatory mediators in airways of mechanically ventilated children compared to spontaneous breathing children with viral bronchiolitis. In this prospective observational multi-center study we aimed to investigate whether this increase was related to disease severity or caused by mechanical ventilation.

Materials and Methods

Nasopharyngeal aspirates were collected <1 hour before intubation and 24 hours later in RSV bronchiolitis patients with respiratory failure (n = 18) and non-ventilated RSV bronchiolitis controls (n = 18). Concentrations of the following cytokines were measured: interleukin (IL)-1α, IL-1β, IL-6, monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-1α.

Results

Baseline cytokine levels were comparable between ventilated and non-ventilated infants. After 24 hours of mechanical ventilation mean cytokine levels, except for MIP-1α, were elevated compared to non-ventilated infected controls: IL-1α (159 versus 4 pg/ml, p<0.01), IL-1β (1068 versus 99 pg/ml, p<0.01), IL-6 (2343 versus 958 pg/ml, p<0.05) and MCP-1 (174 versus 26 pg/ml, p<0.05).

Conclusions

Using pre- and post-intubation observations, this study suggests that endotracheal intubation and subsequent mechanical ventilation cause a robust pulmonary inflammation in infants with RSV bronchiolitis.     

Local interleukin-10 production during respiratory syncytial virus bronchiolitis is associated with post-bronchiolitis wheeze

Background

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants. Following RSV bronchiolitis, 50% of children develop post-bronchiolitis wheeze (PBW). Animal studies have suggested that interleukin (IL)-10 plays a critical role in the pathogenesis of RSV bronchiolitis and subsequent airway hyperresponsiveness. Previously, we showed that ex vivo monocyte IL-10 production is a predictor of PBW. Additionally, heterozygosity of the single-nucleotide polymorphism (SNP) rs1800872 in the IL10 promoter region was associated with protection against RSV bronchiolitis.

Methods

This study aimed to determine the in vivo role of IL-10 in RSV pathogenesis and recurrent wheeze in a new cohort of 235 infants hospitalized for RSV bronchiolitis. IL-10 levels in nasopharyngeal aspirates (NPAs) were measured at the time of hospitalization and the IL10 SNP rs1800872 genotype was determined. Follow-up data were available for 185 children (79%).

Results

Local IL-10 levels during RSV infection turned out to be higher in infants that later developed physician diagnosed PBW as compared to infants without PBW in the first year after RSV infection (958 vs 692 pg/ml, p = 0.02). The IL10 promoter SNP rs1800872 was not associated with IL-10 concentration in NPAs.

Conclusion

The relationship between high local IL-10 levels during the initial RSV infection and physician diagnosed PBW provides further evidence of the importance of the IL-10 response during RSV bronchiolitis.     

Prospective Validation of a Prognostic Model for Respiratory Syncytial Virus Bronchiolitis in Late Preterm Infants: A Multicenter Birth Cohort Study

Objectives

This study aimed to update and validate a prediction rule for respiratory syncytial virus (RSV) hospitalization in preterm infants 33–35 weeks gestational age (WGA).

Study Design

The RISK study consisted of 2 multicenter prospective birth cohorts in 41 hospitals. Risk factors were assessed at birth among healthy preterm infants 33–35 WGA. All hospitalizations for respiratory tract infection were screened for proven RSV infection by immunofluorescence or polymerase chain reaction. Multivariate logistic regression analysis was used to update an existing prediction model in the derivation cohort (n = 1,227). In the validation cohort (n = 1,194), predicted versus actual RSV hospitalization rates were compared to determine validity of the model.

Results

RSV hospitalization risk in both cohorts was comparable (5.7% versus 4.9%). In the derivation cohort, a prediction rule to determine probability of RSV hospitalization was developed using 4 predictors: family atopy (OR 1.9; 95%CI, 1.1–3.2), birth period (OR 2.6; 1.6–4.2), breastfeeding (OR 1.7; 1.0–2.7) and siblings or daycare attendance (OR 4.7; 1.7–13.1). The model showed good discrimination (c-statistic 0.703; 0.64–0.76, 0.702 after bootstrapping). External validation showed good discrimination and calibration (c-statistic 0.678; 0.61–0.74).

Conclusions

Our prospectively validated prediction rule identifies infants at increased RSV hospitalization risk, who may benefit from targeted preventive interventions. This prediction rule can facilitate country-specific, cost-effective use of RSV prophylaxis in late preterm infants.     

In Very Young Infants Severity of Acute Bronchiolitis Depends On Carried Viruses

Background

RT amplification reaction has revealed that various single viruses or viral co-infections caused acute bronchiolitis in infants, and RV appeared to have a growing involvement in early respiratory diseases. Because remaining controversial, the objective was to determine prospectively the respective role of RSV, RV, hMPV and co-infections on the severity of acute bronchiolitis in very young infants.

Methods and Principal Findings

209 infants (median age: 2.4 months) were enrolled in a prospective study of infants <1 year old, hospitalized for a first episode of bronchiolitis during the winter epidemic season and with no high risk for severe disease. The severity was assessed by recording SaO₂% at admission, a daily clinical score (scale 0–18), the duration of oxygen supplementation and the length of hospitalization. Viruses were identified in 94.7% by RT amplification reaction: RSV only (45.8%), RV only (7.2%), hMPV only (3.8%), dual RSV/RV (14.3%), and other virus only (2%) or coinfections (9%). RV compared respectively with RSV and dual RSV/RV infection caused a significant less severe disease with a lower clinical score (5[3.2–6] vs. 6[4–8], p = 0.01 and 5.5[5–7], p = 0.04), a shorter time in oxygen supplementation (0[0–1] days vs. 2[0–3] days, p = 0.02 and 2[0–3] days, p = 0.03) and a shorter hospital stay (3[3–4.7] days vs.6 [5–8] days, p = 0.001 and 5[4–6] days, p = 0.04). Conversely, RSV infants had also longer duration of hospitalization in comparison with RSV/RV (p = 0.01) and hMPV (p = 0.04). The multivariate analyses showed that the type of virus carried was independently associated with the duration of hospitalization.

Conclusion

This study underlined the role of RV in early respiratory diseases, as frequently carried by young infants with a first acute bronchiolitis. RSV caused the more severe disease and conversely RV the lesser severity. No additional effect of dual RSV/RV infection was observed on the severity.     

Association of Eosinophilic Inflammation with FKBP51 Expression in Sputum Cells in Asthma

Background

Airway eosinophilia is a predictor of steroid responsiveness in steroid-naïve asthma. However, the relationship between airway eosinophilia and the expression of FK506-binding protein 51 (FKBP51), a glucocorticoid receptor co-chaperone that plays a role in steroid insensitivity in asthma, remains unknown.

Objective

To evaluate the relationship between eosinophilic inflammation and FKBP51 expression in sputum cells in asthma.

Methods

The FKBP51 mRNA levels in sputum cells from steroid-naïve patients with asthma (n = 31) and stable asthmatic patients on inhaled corticosteroid (ICS) (n = 28) were cross-sectionally examined using real-time PCR. Associations between FKBP51 levels and clinical indices were analyzed.

Results

In steroid-naïve patients, the FKBP51 levels were negatively correlated with eosinophil proportions in blood (r = −0.52) and sputum (r = −0.57), and exhaled nitric oxide levels (r = −0.42) (all p<0.05). No such associations were observed in patients on ICS. In steroid-naïve patients, improvement in forced expiratory volume in one second after ICS initiation was correlated with baseline eosinophil proportions in blood (r = 0.74) and sputum (r = 0.76) and negatively correlated with FKBP51 levels (r = −0.73) (all p<0.0001) (n = 20). Lastly, the FKBP51 levels were the lowest in steroid-naïve asthmatic patients, followed by mild to moderate persistent asthmatic patients on ICS, and the highest in severe persistent asthmatic patients on ICS (p<0.0001).

Conclusions

Lower FKBP51 expression in sputum cells may reflect eosinophilic inflammation and glucocorticoid responsiveness in steroid-naïve asthmatic patients.     

Viral Etiology of Respiratory Tract Infections in Children at the Pediatric Hospital in Ouagadougou (Burkina Faso)

Background

Acute respiratory infections (ARIs) are a major cause of morbidity and mortality in children in Africa. The circulation of viruses classically implicated in ARIs is poorly known in Burkina Faso. The aim of this study was to identify the respiratory viruses present in children admitted to or consulting at the pediatric hospital in Ouagadougou.

Methods

From July 2010 to July 2011, we tested nasal aspirates of 209 children with upper or lower respiratory infection for main respiratory viruses (respiratory syncytial virus (RSV), metapneumovirus, adenovirus, parainfluenza viruses 1, 2 and 3, influenza A, B and C, rhinovirus/enterovirus), by immunofluorescence locally in Ouagadougou, and by PCR in France. Bacteria have also been investigated in 97 samples.

Results

153 children (73.2%) carried at least one virus and 175 viruses were detected. Rhinoviruses/enteroviruses were most frequently detected (rhinovirus n = 88; enterovirus n = 38) and were found to circulate throughout the year. An epidemic of RSV infections (n = 25) was identified in September/October, followed by an epidemic of influenza virus (n = 13), mostly H1N1pdm09. This epidemic occurred during the period of the year in which nighttime temperatures and humidity were at their lowest. Other viruses tested were detected only sporadically. Twenty-two viral co-infections were observed. Bacteria were detected in 29/97 samples with 22 viral/bacterial co-infections.

Conclusions

This study, the first of its type in Burkina Faso, warrants further investigation to confirm the seasonality of RSV infection and to improve local diagnosis of influenza. The long-term objective is to optimize therapeutic management of infected children.     

Elevated Peptides in Lung Lavage Fluid Associated with Bronchiolitis Obliterans Syndrome

Objective

The objective of this discovery-level investigation was to use mass spectrometry to identify low mass compounds in bronchoalveolar lavage fluid from lung transplant recipients that associate with bronchiolitis obliterans syndrome.

Experimental Design

Bronchoalveolar lavage fluid samples from lung transplant recipients were evaluated for small molecules using ESI-TOF mass spectrometry and correlated to the development of bronchiolitis obliterans syndrome. Peptides associated with samples from persons with bronchiolitis obliterans syndrome and controls were identified separately by MS/MS analysis.

Results

The average bronchoalveolar lavage fluid MS spectrum profile of individuals that developed bronchiolitis obliterans syndrome differed greatly compared to controls. Controls demonstrated close inter-sample correlation (R = 0.97+/−0.02, average+/−SD) while bronchiolitis obliterans syndrome showed greater heterogeneity (R = 0.86+/−0.09, average+/−SD). We identified 89 features that were predictive of developing BOS grade 1 and 66 features predictive of developing BOS grade 2 or higher. Fractions from MS analysis were pooled and evaluated for peptide content. Nearly 10-fold more peptides were found in bronchiolitis obliterans syndrome relative to controls. C-terminal residues suggested trypsin-like specificity among controls compared to elastase-type enzymes among those with bronchiolitis obliterans syndrome.

Conclusions

Bronchoalveolar lavage fluid from individuals with bronchiolitis obliterans syndrome has an increase in low mass components detected by mass spectrometry. Many of these features were peptides that likely result from elevated neutrophil elastase activity.     

The Burden of Image Based Emphysema and Bronchiolitis in HIV-Infected Individuals on Antiretroviral Therapy

Background

With the widespread use of anti-retroviral therapy (ART), individuals infected with human immune deficiency virus (HIV) are increasingly experiencing morbidity and mortality from respiratory disorders. However, the prevalence or the risk factors associated with emphysema and bronchiolitis are largely unknown.

Methods

Thoracic computed tomography (CT) scans were performed in 1,446 patients infected with HIV who were on ART and who attended a tertiary care metabolic clinic (average age 48 years and 29% females). Detailed history and physical examination including anthropometric measurements were performed. Complete pulmonary function tests were performed in a subset of these patients (n = 364). No subjects were acutely ill with a respiratory condition at the time of CT scanning.

Findings

Nearly 50% of the subjects had CT evidence for emphysema, bronchiolitis or both with 13% (n = 195) showing bronchiolitis, 19% (n = 274) showing emphysema and 16% (n = 238) revealing both. These phenotypes were synergistically associated with reduced regular physical activity (p for interaction <.0001). The most significant risk factors for both phenotypes were cigarette smoking, intravenous drug use and peripheral leucocytosis. Together, the area-under-the curve statistics was 0.713 (p = 0.0037) for discriminating those with and without these phenotypes. There were no significant changes in lung volumes or flow rates related to these phenotypes, though the carbon monoxide diffusion capacity was reduced for the emphysema phenotype.

Interpretation

Emphysema and bronchiolitis are extremely common in HIV-infected patients who are treated with ART and can be identified by use of thoracic CT scanning.     

Stunting,Poor Iron Status and Parasite Infection Are Significant Risk Factors for Lower Cognitive Performance in Cambodian School-Aged Children

Background

Nutrition is one of many factors affecting the cognitive development of children. In Cambodia, 55% of children <5 y were anemic and 40% stunted in 2010. Currently, no data exists on the nutritional status of Cambodian school-aged children, or on how malnutrition potentially affects their cognitive development.

Objective

To assess the anthropometric and micronutrient status (iron, vitamin A, zinc, iodine) of Cambodian schoolchildren and their associations with cognitive performance.

Methods

School children aged 6–16 y (n = 2443) from 20 primary schools in Cambodia were recruited. Anthropometry, hemoglobin, serum ferritin, transferrin receptors, retinol-binding protein and zinc concentrations, inflammation status, urinary iodine concentration and parasite infection were measured. Socio-economic data were collected in a sub-group of children (n = 616). Cognitive performance was assessed using Raven’s Colored Progressive Matrices (RCPM) and block design and picture completion, two standardized tests from the Wechsler Intelligence Scale for Children (WISC-III).

Results

The prevalence of anemia, iron, zinc, iodine and vitamin A deficiency were 15.7%; 51.2%, 92.8%, 17.3% and 0.7% respectively. The prevalence of stunting was 40.0%, including 10.9% of severe stunting. Stunted children scored significantly lower than non-stunted children on all tests. In RCPM test, boys with iron-deficiency anemia had lower scores than boys with normal iron status (−1.46, p<0.05). In picture completion test, children with normal iron status tended to score higher than iron-deficient children with anemia (−0.81; p = 0.067) or without anemia (−0.49; p = 0.064). Parasite infection was associated with an increase in risk of scoring below the median value in block design test (OR = 1.62; p<0.05), and with lower scores in other tests, for girls only (both p<0.05).

Conclusion

Poor cognitive performance of Cambodian school-children was multifactorial and significantly associated with long-term (stunting) and current nutritional status indicators (iron status), as well as parasite infection. A life-cycle approach with programs to improve nutrition in early life and at school-age could contribute to optimal cognitive performance.     

Cerebrospinal Fluid Interleukin-6 in Central Nervous System Inflammatory Diseases

Background

Interleukin (IL)-6 is recognised as an important cytokine involved in inflammatory diseases of the central nervous system (CNS).

Objective

To perform a large retrospective study designed to test cerebrospinal fluid (CSF) IL-6 levels in the context of neurological diseases, and evaluate its usefulness as a biomarker to help discriminate multiple sclerosis (MS) from other inflammatory neurological diseases (OIND).

Patients and Methods

We analyzed 374 CSF samples for IL-6 using a quantitative enzyme-linked immunosorbent assay. Groups tested were composed of demyelinating diseases of the CNS (DD, n = 117), including relapsing-remitting MS (RRMS, n = 65), primary progressive MS (PPMS, n = 11), clinically isolated syndrome (CIS, n = 11), optic neuritis (ON, n = 30); idiopathic transverse myelitis (ITM, n = 10); other inflammatory neurological diseases (OIND, n = 35); and non-inflammatory neurological diseases (NIND, n = 212). Differences between groups were analysed using Kruskal−Wallis test and Mann−Whitney U-test.

Results

CSF IL-6 levels exceeded the positivity cut-off of 10 pg/ml in 18 (51.4%) of the 35 OIND samples, but in only three (3.9%) of the 76 MS samples collected. CSF IL-6 was negative for all NIND samples tested (0/212). IL-6 cut-off of 10 pg/ml offers 96% sensitivity to exclude MS.

Conclusion

CSF IL-6 may help to differentiate MS from its major differential diagnosis group, OIND.     

Effect of High- versus Low-Intensity Supervised Aerobic and Resistance Training on Modifiable Cardiovascular Risk Factors in Type 2 Diabetes; The Italian Diabetes and Exercise Study (IDES)

Background

While current recommendations on exercise type and volume have strong experimental bases, there is no clear evidence from large-sized studies indicating whether increasing training intensity provides additional benefits to subjects with type 2 diabetes.

Objective

To compare the effects of moderate-to-high intensity (HI) versus low-to-moderate intensity (LI) training of equal energy cost, i.e. exercise volume, on modifiable cardiovascular risk factors.

Design

Pre-specified sub-analysis of the Italian Diabetes and Exercise Study (IDES), a randomized multicenter prospective trial comparing a supervised exercise intervention with standard care for 12 months (2005–2006).

Setting

Twenty-two outpatient diabetes clinics across Italy.

Patients

Sedentary patients with type 2 diabetes assigned to twice-a-week supervised progressive aerobic and resistance training plus exercise counseling (n = 303).

Interventions

Subjects were randomized by center to LI (n = 142, 136 completed) or HI (n = 161, 152 completed) progressive aerobic and resistance training, i.e. at 55% or 70% of predicted maximal oxygen consumption and at 60% or 80% of predicted 1-Repetition Maximum, respectively, of equal volume.

Main Outcome Measure(s)

Hemoglobin (Hb) A_1c and other cardiovascular risk factors; 10-year coronary heart disease (CHD) risk scores.

Results

Volume of physical activity, both supervised and non-supervised, was similar in LI and HI participants. Compared with LI training, HI training produced only clinically marginal, though statistically significant, improvements in HbA_1c (mean difference −0.17% [95% confidence interval −0.44,0.10], P = 0.03), triglycerides (−0.12 mmol/l [−0.34,0.10], P = 0.02) and total cholesterol (−0.24 mmol/l [−0.46, −0.01], P = 0.04), but not in other risk factors and CHD risk scores. However, intensity was not an independent predictor of reduction of any of these parameters. Adverse event rate was similar in HI and LI subjects.

Conclusions

Data from the large IDES cohort indicate that, in low-fitness individuals such as sedentary subjects with type 2 diabetes, increasing exercise intensity is not harmful, but does not provide additional benefits on cardiovascular risk factors.

Trial Registration

www.ISRCTN.org ISRCTN-04252749.     

The Incidence and Clinical Burden of Respiratory Syncytial Virus Disease Identified through Hospital Outpatient Presentations in Kenyan Children

Background

There is little information that describe the burden of respiratory syncytial virus (RSV) associated disease in the tropical African outpatient setting.

Methods

We studied a systematic sample of children aged <5 years presenting to a rural district hospital in Kenya with acute respiratory infection (ARI) between May 2002 and April 2004. We collected clinical data and screened nasal wash samples for RSV antigen by immunofluorescence. We used a linked demographic surveillance system to estimate disease incidence.

Results

Among 2143 children tested, 166 (8%) were RSV positive (6% among children with upper respiratory tract infection and 12% among children with lower respiratory tract infection (LRTI). RSV was more likely in LRTI than URTI (p<0.001). 51% of RSV cases were aged 1 year or over. RSV cases represented 3.4% of hospital outpatient presentations. Relative to RSV negative cases, RSV positive cases were more likely to have crackles (RR = 1.63; 95% CI 1.34–1.97), nasal flaring (RR = 2.66; 95% CI 1.40–5.04), in-drawing (RR = 2.24; 95% CI 1.47–3.40), fast breathing for age (RR = 1.34; 95% CI 1.03–1.75) and fever (RR = 1.54; 95% CI 1.33–1.80). The estimated incidence of RSV-ARI and RSV-LRTI, per 100,000 child years, among those aged <5 years was 767 and 283, respectively.

Conclusion

The burden of childhood RSV-associated URTI and LRTI presenting to outpatients in this setting is considerable. The clinical features of cases associated with an RSV infection were more severe than cases without an RSV diagnosis.     

Sono-Electro-Magnetic Therapy for Treating Chronic Pelvic Pain Syndrome in Men: A Randomized,Placebo-Controlled,Double-Blind Trial

Objective

To assess the efficacy and safety of sono-electro-magnetic therapy compared to placebo in men with refractory CPPS.

Patients and Methods

In a randomized, placebo-controlled, double-blind single center trial, we assessed the effect of sono-electro-magnetic therapy in men with treatment refractory CPPS. Sixty male patients were randomly assigned to treatment with either sono-electro-magnetic (n = 30) or placebo therapy (n = 30) for 12 weeks. The primary outcome was a change in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) from baseline to 12 weeks.

Results

The 12-week difference between sono-electro-magnetic and placebo therapy in changes of the NIH-CPSI total score was −3.1 points (95% CI −6.8 to 0.6, p = 0.11). In secondary comparisons of NIH-CPSI sub-scores, we found differences between groups most pronounced for the quality-of-life sub-score (difference at 12 weeks −1.6, 95% CI −2.8 to −0.4, p = 0.015). In stratified analyses, the benefit of sono-electro-magnetic therapy appeared more pronounced among patients who had a symptom duration of 12 months or less (difference in NIH-CPSI total score −8.3, 95% CI −14.5 to 2.6) than in patients with a longer symptom duration (−0.8, 95% CI −4.6 to 3.1; p for interaction = 0.023).

Conclusions

Sono-electro-magnetic therapy did not result in a significant improvement of symptoms in the overall cohort of treatment refractory CPPS patients compared to placebo treatment. Subgroup analysis indicates, however, that patients with a symptom-duration of 12 months or less may benefit from sono-electro-magnetic therapy, warranting larger randomized controlled trials in this subpopulation.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00688506","term_id":"NCT00688506"}}NCT00688506     

Iron Status and Helicobacter pylori Infection in Symptomatic Children: An International Multi-Centered Study

Objective

Iron deficiency (ID) and iron deficiency anaemia (IDA) are global major public health problems, particularly in developing countries. Whilst an association between H. pylori infection and ID/IDA has been proposed in the literature, currently there is no consensus. We studied the effects of H. pylori infection on ID/IDA in a cohort of children undergoing upper gastrointestinal endoscopy for upper abdominal pain in two developing and one developed country.

Methods

In total 311 children (mean age 10.7±3.2 years) from Latin America - Belo Horizonte/Brazil (n = 125), Santiago/Chile (n = 105) - and London/UK (n = 81), were studied. Gastric and duodenal biopsies were obtained for evaluation of histology and H. pylori status and blood samples for parameters of ID/IDA.

Results

The prevalence of H. pylori infection was 27.7% being significantly higher (p<0.001) in Latin America (35%) than in UK (7%). Multiple linear regression models revealed H. pylori infection as a significant predictor of low ferritin and haemoglobin concentrations in children from Latin-America. A negative correlation was observed between MCV (r = −0.26; p = 0.01) and MCH (r = −0.27; p = 0.01) values and the degree of antral chronic inflammation, and between MCH and the degree of corpus chronic (r = −0.29, p = 0.008) and active (r = −0.27, p = 0.002) inflammation.

Conclusions

This study demonstrates that H. pylori infection in children influences the serum ferritin and haemoglobin concentrations, markers of early depletion of iron stores and anaemia respectively.     

Polymorphisms in ABC Transporter Genes and Concentrations of Mercury in Newborns – Evidence from Two Mediterranean Birth Cohorts

Background

The genetic background may influence methylmercury (MeHg) metabolism and neurotoxicity. ATP binding cassette (ABC) transporters actively transport various xenobiotics across biological membranes.

Objective

To investigate the role of ABC polymorphisms as modifiers of prenatal exposure to MeHg.

Methods

The study population consisted of participants (n = 1651) in two birth cohorts, one in Italy and Greece (PHIME) and the other in Spain (INMA). Women were recruited during pregnancy in Italy and Spain, and during the perinatal period in Greece. Total mercury concentrations were measured in cord blood samples by atomic absorption spectrometry. Maternal fish intake during pregnancy was determined from questionnaires. Polymorphisms (n = 5) in the ABC genes ABCA1, ABCB1, ABCC1 and ABCC2 were analysed in both cohorts.

Results

ABCB1 rs2032582, ABCC1 rs11075290, and ABCC2 rs2273697 modified the associations between maternal fish intake and cord blood mercury concentrations. The overall interaction coefficient between rs2032582 and log2-transformed fish intake was negative for carriers of GT (β = −0.29, 95%CI −0.47, −0.12) and TT (β = −0.49, 95%CI −0.71, −0.26) versus GG, meaning that for a doubling in fish intake of the mothers, children with the rs2032582 GG genotype accumulated 35% more mercury than children with TT. For rs11075290, the interaction coefficient was negative for carriers of TC (β = −0.12, 95%CI −0.33, 0.09), and TT (β = −0.28, 95%CI −0.51, −0.06) versus CC. For rs2273697, the interaction coefficient was positive when combining GA+AA (β = 0.16, 95%CI 0.01, 0.32) versus GG.

Conclusion

The ABC transporters appear to play a role in accumulation of MeHg during early development.     

Cranialization of the Frontal Sinus for Secondary Mucocele Prevention following Open Surgery for Benign Frontal Lesions

Objective

To compare frontal sinus cranialization to obliteration for future prevention of secondary mucocele formation following open surgery for benign lesions of the frontal sinus.

Study Design

Retrospective case series.

Setting

Tertiary academic medical center.

Patients

Sixty-nine patients operated for benign frontal sinus pathology between 1994 and 2011.

Interventions

Open excision of benign frontal sinus pathology followed by either frontal obliteration (n = 41, 59%) or frontal cranialization (n = 28, 41%).

Main Outcome Measures

The prevalence of post-surgical complications and secondary mucocele formation were compiled.

Results

Pathologies included osteoma (n = 34, 49%), mucocele (n = 27, 39%), fibrous dysplasia (n = 6, 9%), and encephalocele (n = 2, 3%). Complications included skin infections (n = 6), postoperative cutaneous fistula (n = 1), telecanthus (n = 4), diplopia (n = 3), nasal deformity (n = 2) and epiphora (n = 1). None of the patients suffered from postoperative CSF leak, meningitis or pneumocephalus. Six patients, all of whom had previously undergone frontal sinus obliteration, required revision surgery due to secondary mucocele formation. Statistical analysis using non-inferiority test reveal that cranialization of the frontal sinus is non-inferior to obliteration for preventing secondary mucocele formation (P<0.0001).

Conclusion

Cranialization of the frontal sinus appears to be a good option for prevention of secondary mucocele development after open excision of benign frontal sinus lesions.     

Gastric Bypass Surgery Is Followed by Lowered Blood Pressure and Increased Diuresis - Long Term Results from the Swedish Obese Subjects (SOS) Study

Objective

To compare two bariatric surgical principles with regard to effects on blood pressure and salt intake.

Background

In most patients bariatric surgery induces a sustained weight loss and a reduced cardiovascular risk profile but the long-term effect on blood pressure is uncertain.

Methods

Cohort study with data from the prospective, controlled Swedish Obese Subjects (SOS) study involving 480 primary health care centres and 25 surgical departments in Sweden. Obese patients treated with non-surgical methods (Controls, n = 1636 and n = 1132 at 2 y and 10 y follow up, respectively) were compared to patients treated with gastric bypass (GBP, n = 245 and n = 277, respectively) or purely restrictive procedures (vertical banded gastroplasty or gastric banding; VBG/B, n = 1534 and n = 1064, respectively).

Results

At long-term follow-up (median 10 y) GBP was associated with lowered systolic (mean: −5.1 mm Hg) and diastolic pressure (−5.6 mmHg) differing significantly from both VBG/B (−1.5 and −2.1 mmHg, respectively; p<0.001) and Controls (+1.2 and −3.8 mmHg, respectively; p<0.01). Diurnal urinary output was +100 ml (P<0.05) and +170 ml (P<0.001) higher in GBP subjects than in weight-loss matched VBG/B subjects at the 2 y and 10 y follow-ups, respectively. Urinary output was linearly associated with blood pressure only after GBP and these patients consumed approximately 1 g salt per day more at the follow-ups than did VBG/B (P<0.01).

Conclusions

The purely restrictive techniques VBG/B exerted a transient blood pressure lowering effect, whereas gastric bypass was associated with a sustained blood pressure reduction and an increased diuresis. The daily salt consumption was higher after gastric bypass than after restrictive bariatric surgery.     

Can Certain Genotypes Predispose to Poor Asthma Control in Children? A Pharmacogenetic Study of 9 Candidate Genes in Children with Difficult Asthma

Objective

We tested the hypothesis that patients with difficult asthma have an increased frequency of certain genotypes that predispose them to asthma exacerbations and poor asthma control.

Methods

A total of 180 Caucasian children with confirmed asthma diagnosis were selected from two phenotypic groups; difficult (n = 112) versus mild/moderate asthma (n = 68) groups. All patients were screened for 19 polymorphisms in 9 candidate genes to evaluate their association with difficult asthma.

Key Results

The results indicated that LTA4H A-9188>G, TNFα G-308>A and IL-4Rα A1727>G polymorphisms were significantly associated with the development of difficult asthma in paediatric patients (p<0.001, p = 0.019 and p = 0.037, respectively). Haplotype analysis also revealed two haplotypes (ATA haplotype of IL-4Rα A1199>C, IL-4Rα T1570>C and IL-4Rα A1727>G and CA haplotype of TNFα C-863>A and TNFα G-308>A polymorphisms) which were significantly associated with difficult asthma in children (p = 0.04 and p = 0.018, respectively).

Conclusions and Clinical Relevance

The study revealed multiple SNPs and haplotypes in LTA4H, TNFα and IL4-Rα genes which constitute risk factors for the development of difficult asthma in children. Of particular interest is the LTA4H A-9188>G polymorphism which has been reported, for the first time, to have strong association with severe asthma in children. Our results suggest that screening for patients with this genetic marker could help characterise the heterogeneity of responses to leukotriene-modifying medications and, hence, facilitate targeting these therapies to the subset of patients who are most likely to gain benefit.     

Health-Related Quality of Life among Children with Recurrent Respiratory Tract Infections in Xi’an,China

Objective

The aim of this study was to investigate the health-related quality of life (HRQOL) in 2−7-year-old children diagnosed with recurrent respiratory tract infections (RRTIs) and the impact of RRTIs on affected families.

Methods

This was a cross-sectional case-control study evaluating 2−7-year-old children with RRTIs (n = 352), 2−7-year-old healthy children (n = 376), and associated caregivers (parents and/or grandparents). A Chinese version of the PedsQL™ 4.0 Generic Core Scale was used to assess childhood HRQOL, and a Chinese version of the Family Impact Module (FIM) was used to assess the impact of RRTIs on family members. HRQOL scores were compared between children with RRTIs and healthy children. In addition, a multiple step-wise regression with demographic variables of children and their caregivers, family economic status, and caregiver’s HRQOL as independent variables determined factors that influenced HRQOL in children with RRTIs.

Results

Children with RRTIs showed significantly lower physical, emotional, social, and school functioning scores than healthy children (p<0.05). Caregivers for children with RRTIs also scored significantly lower than caregivers for healthy children on physical, emotional, social, cognitive, and communication functioning (p<0.05). Caregivers for RRTIs affected children also reported significantly higher levels of worry. Multivariate analyses showed that children’s age, children’s relation with caregivers, the frequency of respiratory tract infections in the preceding year, caregiver’s educational level, and caregiver’s own HRQOL influenced HRQOL in children with RRTIs.

Conclusions

The current data demonstrated that RRTIs were associated with lower HRQOL in both children and their caregivers and negatively influenced family functioning. In addition, caregivers’ social characteristics also significantly affected HRQOL in children with RRTIs.