Efficacy of high-dose vitamin D in pediatric asthma: a systematic review and meta-analysis

Context: Observational studies have suggested a relationship between vitamin D status and asthma-related respiratory outcomes. The benefit of vitamin D supplementation for pulmonary function, symptoms and exacerbations is not well established. Objective: To systematically review paediatric clinical trials investigating the role of vitamin D on asthma-related respiratory outcomes. Data sources: MEDLINE, EMBASE and CENTRAL were searched until January 2014. No date or language restrictions. Study selection: Clinical trials reporting asthma-related respiratory outcomes following vitamin D administration at a dose equal or greater than 500 IU per day were included and reviewed independently by two authors for full systematic review eligibility. Data extraction: Two reviewers independently extracted and verified pre-defined data fields. Results: We identified five studies that met study eligibility and assessed final data synthesis. The median trial size was 48 participants (range 17–430) and the average daily dose of cholecalciferol ranged from 500 to 2000?IU/day. Overall study methodological quality was high, but some heterogeneity in population and vitamin D dosing regimen was evident. Meta-analysis suggested a statistically significant reduction (RR 0.41, CI 0.27–0.63) in asthma exacerbation with vitamin D therapy. Limitations: Due to variability in outcome selection and missing data, it was not possible to perform meta-analysis for pulmonary function testing and asthma symptom scores. Vitamin D-related adverse events were not considered in four of five papers. Conclusions: Available evidence from this systematic review suggests that high dose vitamin D may prevent asthma exacerbation. This should be confirmed through larger well-designed randomised controlled trials.     

Thai pediatricians' current practice toward childhood asthma

Background: Childhood asthma is a substantial health burden in Thailand. Due to a lack of pediatric respiratory specialists (pediatric pulmonologists and allergists; RS), most Thai children are cared for by general pediatricians (pediatric primary care providers (PCP)). Objectives: We investigated whether current practices of Thai pediatricians complied with asthma guidelines and compared practices (diagnosis and treatments) provided by PCP and RS. Methods: A cross-sectional study was conducted using electronic surveys including four case scenarios of different asthma phenotypes distributed to Thai pediatricians. Asthma diagnosis and management were evaluated for compliance with standard guidelines. The practices of PCP and RS were compared. Results: From 800 surveys distributed, there were 405 respondents (51%). Most respondents (81%) were PCP, who preferred to use clinical diagnosis rather than laboratory investigations to diagnose asthma. For acute asthmatic attacks, 58% of the pediatricians prescribed a systemic corticosteroid. For uncontrolled asthma, 89% of the pediatricians prescribed at least one controller. For exercise-induced bronchospasm, 55% of the pediatricians chose an inhaled bronchodilator, while 38% chose a leukotriene receptor antagonist (LTRA). For virus-induced wheeze, 40% of the respondents chose an LTRA, while 15% chose inhaled corticosteroids (ICS). PCP prescribed more oral bronchodilators (31% vs. 18%, p = 0.02), antibiotics (20% vs. 6%, p < 0.001), and antihistamines (13% vs. 0%, p = 0.02) than RS for the management of an acute asthmatic attack. Conclusions: Most of the Thai pediatricians' practices toward diagnosis and treatment of acute asthmatic attack and uncontrolled asthma conform to the guidelines. PCP prescribed more oral bronchodilators, antibiotics, and antihistamines than RS.     

Evaluation of Respiratory Viral Pathogens in Acute Asthma Exacerbations during Childhood

Objective. Common upper respiratory tract viruses are the most frequent and important causes of asthma exacerbations in both children and adults. Prospective epidemiologic studies report that up to 80% of childhood exacerbations are associated with viral upper respiratory tract infections. Materials and methods. The study group consisted of 104 children with asthma aged 3–17 years who received treatment for asthma exacerbations in our clinic between September 2009 and 2010. Nasopharyngeal and nasal swabs were obtained from all patients during an acute attack, and from the control group (31 subjects). These specimens were investigated for the presence of viral respiratory pathogens using a real-time multiplex PCR method. The patients were compared for the presence of respiratory pathogens and factors related to the severity of the asthma exacerbation. Results. A pathogenic respiratory virus was detected in 53.8% of patients in the acute exacerbation group. The most commonly encountered viral agent was Rhinovirus (35.6%). Patients who had an acute exacerbation with or without a detectable viral pathogen were compared according to the severity of the exacerbation, the need for systemic steroids, and hospitalization rates. No statistically significant difference was found. Conclusion. Although viral upper respiratory tract infections are the most common cause of asthma exacerbations, the severity level of the exacerbation seems to be independent of whether a respiratory virus has been detected.     

Viral infection in asthma

In bronchial asthma, respiratory virus infection involves several issues: 1) respiratory virus infection in infancy is a risk factor for, and may predispose to, the development of asthma later in life; 2) respiratory virus infection is associated with the acute exacerbation of bronchial asthma; and, 3) glucocorticosteroids (GC) are not adequate for controlling asthma-related symptoms upon respiratory virus infection. Various cells, inflammatory mediators and cytokines participate in the production of airway inflammation upon respiratory virus infection. Bronchial epithelial cells are a site of infection and replication of respiratory virus. They actively participate in the production of airway inflammation: 1) they produce various proinflammatory cytokines, chemokines and mediators; and, 2) they undergo apoptosis, thereby impairing the repair process. It is therefore important to understand the role of bronchial epithelial cells in the pathophysiology of bronchial asthma. In this review, the interaction between viral infection and asthma is discussed to elucidate the role of bronchial epithelial cells in viral infection.     

Viral Infection and Respiratory Exacerbation in Children: Results from a Local German Pediatric Exacerbation Cohort

Respiratory viruses play an important role in asthma exacerbation, and early exposure can be involved in recurrent bronchitis and the development of asthma. The exact mechanism is not fully clarified, and pathogen-to-host interaction studies are warranted to identify biomarkers of exacerbation in the early phase. Only a limited number of international exacerbation cohorts were studied. Here, we have established a local pediatric exacerbation study in Germany consisting of children with asthma or chronic, recurrent bronchitis and analyzed the viriome within the nasopharyngeal swab specimens derived from the entire cohort (n = 141). Interestingly, 41% of exacerbated children had a positive test result for human rhinovirus (HRV)/human enterovirus (HEV), and 14% were positive for respiratory syncytial virus (RSV). HRV was particularly prevalent in asthmatics (56%), wheezers (50%), and atopic (66%) patients. Lymphocytes were decreased in asthmatics and in HRV-infected subjects, and patients allergic to house dust mites were more susceptible to HRV infection. Our study thus confirms HRV infection as a strong ‘biomarker’ of exacerbated asthma. Further longitudinal studies will show the clinical progress of those children with a history of an RSV or HRV infection. Vaccination strategies and novel treatment guidelines against HRV are urgently needed to protect those high-risk children from a serious course of disease.     

Principal findings of systematic reviews of acute asthma treatment in childhood

Objective: The objective of this study is to summarize the principal findings in the literature about acute asthma management in children. Methods: Systematic reviews of randomized clinical trials (SRCTs) with or without meta-analysis in children (1–18 years) admitted to the emergency department (ED) were retrieved using five data bases. Methodological quality was determined using the AMSTAR tool. Results: One hundred and three studies were retrieved. Among those, 28 SRCTs were included: seven SRCTs related to short-acting beta2-agonists (SABA), three to ipratropium bromide (IB), eight to corticosteroids, one to racemic adrenaline, one to leukotriene receptor antagonists (LTRA), four to magnesium sulfate, one to intravenous (IV) SABA, one to IV aminophylline, one to IV ketamine, and one to antibiotics. It was determined that administering SABA by MDI-VHC is superior to using a nebulizer, because it decreases the hospital admission rate, improves the clinical score, results in a shorter time in the ED, and causes fewer adverse effects. Levalbuterol and albuterol were similar. In patients with moderate to severe exacerbations, IB+SABA was superior to SABA, decreasing hospital admission and improving the clinical score. SABA heliox administered by nebulizer decreased exacerbation severity compared to oxygen. Inhaled corticosteroids (ICS), especially administered by nebulizer, showed results similar to oral corticosteroids (OCS) with respect to reducing hospital admission, unscheduled visits, and the requirement of additional systemic corticosteroids. ICS or OCS following ED discharge was similar with regard to relapse. Compared with a placebo, IV magnesium reduced hospital admission and improved lung function. Conclusions: SRCTs are useful for guiding decisions in acute asthma treatment.     

Treatment and evaluation of patients with acute exacerbation of asthma before and during a visit to the ER in Denmark

Background: Acute exacerbation of asthma may be life‐threatening and quite often results in a visit to the emergency room (ER) or admission to a hospital. The aim was to evaluate the treatment and the quality of clinical management of asthma exacerbations, and finally, to identify the factors leading to admission. Material and methods: In a retrospective design, we audited the hospital records of all patients aged 18–40 years admitted to five Danish university hospitals with an acute exacerbation of asthma in 2004. Results: We found records covering 323 asthmatic patients (186 women). Before admission, the mean (standard deviation) duration of the exacerbation was 5.2 (7.5) days. Of those admitted, 14% did not use any medication, 39% used inhaled corticosteroids (ICS) either with a β₂‐agonist or alone, systemic steroids, and 34% used a β₂‐agonist alone. Lung function (peak flow or forced expiratory volume in first second) was measured in 60% on admission, in 58% on discharge and in 47% on both occasions (P < 0.01). Temperature, heart rate and oxygen saturation were measured in 231 of the patients (72%), but the respiratory frequency rate was measured in only 16% of the patients, with some differences between the five hospitals. On discharge, 50% were treated with systemic steroids, and a further 20% had ICS prescribed (P < 0.01, admission vs discharge). In 21% of the cases, inadequate treatment was identified as the most likely reason for their ER visit/admission to a hospital. Conclusions: The assessment and treatment of patients admitted with acute asthma exacerbation was often suboptimal. Under‐treatment with the anti‐asthmatic medication was the main reason for admission. Please cite this paper as: Backer V, Harving H, Søes‐Petersen U, Ulrik CS, Plaschke P and Lange P. Treatment and evaluation of patients with acute exacerbation of asthma before and during a visit to the ER in Denmark. The Clinical Respiratory Journal 2008; 2: 54–59.     

Epidemiological and clinical features of respiratory viral infections in hospitalized children during the circulation of influenza virus A(H1N1) 2009

Please cite this paper as: Zuccotti et al. (2011) Epidemiological and clinical features of respiratory viral infections in hospitalized children during the circulation of influenza virus A(H1N1) 2009. Influenza and Other Respiratory Viruses 5(6), e528–e534. Background Seasonal influenza viruses and respiratory syncytial virus (RSV) are primary causes of acute respiratory tract infections (ARTIs) in children. New respiratory viruses including human metapneumovirus (hMPV), human bocavirus (hBoV), and influenza 2009 A(H1N1) virus have a strong impact on the pediatric population. Objectives To evaluate epidemiological and clinical features of ARTIs in hospitalized children. Methods From December 1, 2008, to December 31, 2009, all children under age fifteen (n = 575) hospitalized for ARTIs were investigated for influenza A (subtype H1N1, H3N2, and 2009 H1N1) and B, RSV A and B, hMPV, and hBoV by PCR. Results Fifty‐one percent of samples were positive for these respiratory viruses. The frequencies of virus detection were RSV 34·1%, hBoV 6·8%, hMPV 5%, seasonal influenza A 5%, and seasonal influenza B 0%. From April 2009, 11·6% of collected samples were influenza 2009 A(H1N1) positive. Respiratory syncytial virus activity peaked in January, hBoV in February, and hMPV in April. Seasonal influenza A was detected only between January and April 2009, while influenza 2009 A(H1N1) peaked in November. Respiratory syncytial virus and hMPV were mainly associated with lower respiratory tract infections (LRTIs) and with necessity of O₂ administration. The 2009 pandemic influenza was more frequently detected in elder children (P < 0·001) and was associated with higher, longer‐lasting fevers compared with other viral infections (P < 0·05). Conclusions All considered viruses were involved in LRTIs. The primary clinical relevance of RSV and a similar involvement of both seasonal influenza and emerging viruses investigated were observed on the pediatric population.     

Bacterial colonization dynamics associated with respiratory syncytial virus during early childhood

Respiratory syncytial virus (RSV) is an important cause of early life acute respiratory infections. Potentially pathogenic respiratory bacteria, including Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae are frequently detected during RSV infections and associated with increased illness severity. However, the temporal dynamics of bacterial colonization associated with RSV infection remain unclear. We used weekly nasal swab data from a prospective longitudinal birth cohort in Brisbane, Australia, to investigate bacterial colonization patterns within children aged less than 2 years in the 4‐week period before and after an RSV infection. During 54 RSV infection episodes recorded in 47 children, both S. pneumoniae and M. catarrhalis were detected frequently (in 33 [61.1%] and 26 [48.1%] RSV infections, respectively). In most cases, S. pneumoniae and M. catarrhalis colonization preceded the viral infection, with the nasal load of each increasing during RSV infection. Generally, the dominant serotype of S. pneumoniae remained consistent in the 1 to 2 weeks immediately before and after RSV infection. Little evidence was found to indicate that prior colonization with either bacteria predisposed participants to developing RSV infection during the annual seasonal epidemic. Possible coacquisition events, where the bacteria species was first detected with RSV and not in the preceding 4 weeks, were observed in approximately 20% of RSV/S. pneumoniae and RSV/M. catarrhalis codetections. Taken together our results indicate that RSV generally triggered an outgrowth, rather than a new acquisition, of S. pneumoniae and M. catarrhalis from the resident microbial community.     

Impact of viral infections in children with community‐acquired pneumonia: results of a study of 17 respiratory viruses

Please cite this paper as: Esposito et al. (2012) Impact of viral infections in children with community‐acquired pneumonia: results of a study of 17 respiratory viruses. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2012.00340.x. Background Little is known about the prevalence of viral infections in children with community‐acquired pneumonia (CAP). Objectives To describe the clinical and virological data collected from children with radiographically confirmed CAP in whom 17 respiratory viruses were sought in respiratory secretion samples during the acute phase of the disease. Patients and methods The study involved 592 children with radiographically confirmed CAP whose respiratory secretion samples were tested using the Luminex xTAG Respiratory Virus Panel Fast assay, which simultaneously detects influenza A virus, influenza B virus, respiratory syncytial virus (RSV)‐A and ‐B, parainfluenzavirus‐1, ‐2, ‐3, and ‐4, adenovirus, human metapneumovirus, coronaviruses 229E, NL63, OC43, and HKU1, enterovirus/rhinovirus, and bocavirus. A real‐time PCR assay was used to identify the rhinovirus in the enterovirus/rhinovirus‐positive samples. Results A total of 435 children (73·5%) were positive for at least one virus: the most frequently detected was RSV, which was found in 188 (31·7%), followed by rhinovirus (n = 144, 24·3%), bocavirus (n = 60, 10·1%), influenza viruses (n = 57, 9·6), and hMPV (n = 49, 8·2%). Viral co‐infections were found in 117 children (19·7% of the enrolled children; 26·9% of those with viral infections). Marginal differences were found between the infections owing to a single virus. Co‐infections showed radiographic evidence of alveolar pneumonia significantly more frequently than single infections (OR 1·72, 95% CI 1·05–2·81). Conclusions The findings of this study highlight the importance of respiratory viruses (mainly RSV and rhinovirus) in children with CAP and show the characteristics of both the single infections and co‐infections associated with the disease.     

A Multiple Cause-of-Death Analysis of Asthma Mortality in the United States, 1990–2001

Objectives. Most analyses of asthma mortality in the United States have relied solely on underlying cause-of-death data, which may underestimate the magnitude of asthma-related mortality. We used multiple cause-of-death data to examine asthma-related mortality trends in the United States. Methods. Data were selected from the United States Multiple Cause-of-Death Files, 1990–2001. Mortality rates and 95% confidence intervals were computed to examine differences in asthma mortality over time and by age, race/ethnicity, and gender. Location of death and seasonal variations in asthma mortality were also assessed, as well as the impact of seasonal respiratory infections. Results. We identified 135,668 asthma-related deaths in the United States over the 12-year period, representing an age-adjusted mortality rate of 4.4 per 100,000. Only 45% of the asthma-related deaths had asthma recorded as the underlying cause. Whites and older adults were less likely to have asthma listed as the underlying cause. Asthma mortality rates mirrored underlying cause trends, increasing slightly between 1990 and 1995, declining between 1996 and 1998, and further declining after International Classification of Disease (ICD)-10 implementation in 1999. Mortality was highest among blacks and the elderly and was higher among females than males. Asthma-related deaths peaked in the winter months and were over four times more likely than non-asthma deaths to have acute upper respiratory infections, influenza, or acute bronchitis listed on the death record. The proportion of asthma-related deaths occurring outside a medical setting increased steadily over the period, from 23.3% in 1990 to 29.4% in 2001. Conclusions. The burden of asthma may be underestimated by relying solely on underlying cause-of-death data. Further research is needed to determine the reasons for the steady increase in out-of-hospital deaths and the continued demographic disparities in mortality.     

Respiratory syncytial virus evaluation among asymptomatic and symptomatic subjects in a university hospital in Sao Paulo,Brazil, in the period of 2009‐2013

Background

The respiratory syncytial virus (RSV) is recognized as an important cause of respiratory tract infections. Immunocompromised patients, healthcare workers (HCWs) and children contacts are at increased risk of acquiring the infection. However, the impact of asymptomatic infection in transmission has not been well studied. Objectives: this study evaluated the frequency and viral load (VL) of RSV in nasal swab samples of individuals with different risk factors for acquiring infection in a university hospital in Sao Paulo, Brazil.

Methods

We included 196 symptomatic children and their 192 asymptomatic caregivers, 70 symptomatic and 95 asymptomatic HCWs, 43 samples from symptomatic HIV‐positive outpatients, and 100 samples of asymptomatic HIV patients in the period of 2009‐2013.

Results

RSV infection was detected in 10.1% (70/696) of samples, 4.4% (17/387) of asymptomatic patients, and 17.1% (53/309) from symptomatic patients. (P < .0001). The VL of symptomatic patients (4.7 log copies/mL) was significantly higher compared to asymptomatic patients (2.3 log copies/mL). RSV detection among asymptomatic caregivers (6.8%; 13/192) was significantly higher compared to other asymptomatic adults, HIV and HCWs (2.0%; 4/195; P = .0252). A close contact with an infected child at home was an important risk to RSV acquisition [OR 22.6 (95% CI 4.8‐106.7)]. Children who possibly transmitted the virus to their asymptomatic contacts had significantly higher viral load than children who probably did not transmit (P < .0001).

Conclusions

According to our results, it is important to know if people circulating inside the hospital have close contact with acute respiratory infected children.     

IFN-γ Attenuates Eosinophilic Inflammation but Is Not Essential for Protection against RSV-Enhanced Asthmatic Comorbidity in Adult Mice

The susceptibility to respiratory syncytial virus (RSV) infection in early life has been associated with a deficient T-helper cell type 1 (Th1) response. Conversely, healthy adults generally do not exhibit severe illness from RSV infection. In the current study, we investigated whether Th1 cytokine IFN-γ is essential for protection against RSV and RSV-associated comorbidities in adult mice. We found that, distinct from influenza virus, prior RSV infection does not induce significant IFN-γ production and susceptibility to secondary Streptococcus pneumoniae infection in adult wild-type (WT) mice. In ovalbumin (OVA)-induced asthmatic mice, RSV super-infection increases airway neutrophil recruitment and inflammatory lung damage but has no significant effect on OVA-induced eosinophilia. Compared with WT controls, RSV infection of asthmatic Ifng^−/− mice results in increased airway eosinophil accumulation. However, a comparable increase in eosinophilia was detected in house dust mite (HDM)-induced asthmatic Ifng^−/− mice in the absence of RSV infection. Furthermore, neither WT nor Ifng^−/− mice exhibit apparent eosinophil infiltration during RSV infection alone. Together, these findings indicate that, despite its critical role in limiting eosinophilic inflammation during asthma, IFN-γ is not essential for protection against RSV-induced exacerbation of asthmatic inflammation in adult mice.     

Retrospective comparison of respiratory syncytial virus and metapneumovirus clinical presentation in hospitalized children

Respiratory syncytial virus (RSV) and Human metapneumovirus (hMPV), members of Pneumoviridae family are common causes of acute respiratory tract infections (ARTI) among children. Study material includes routine nasopharyngeal samples obtained during 8-year period for hMPV and one single season for RSV in children hospitalized for ARTI between 0 and 15 years at the Center Hospitalier Universitaire (CHU) Saint Pierre in Brussels. Positive samples for RSV or hMPV identified by viral culture, lateral flow chromatography test for RSV or direct fluorescent assay for hMPV were selected retrospectively. Characteristics of children hospitalized for RSV or hMPV infections were compared. Children hospitalized for RSV infection were significantly younger and requiring more respiratory support, longer hospital stay and transfers in Pediatric intensive Care Units than those hospitalized for hMPV infection. Pneumonia diagnostic and antibiotics therapies were more significantly associated with hMPV infections. In conclusion, despite their genetic similarities, RSV, and hMPV present epidemiological and clinical differences in pediatric infections. Our results should be confirmed prospectively.     

Depression symptoms and quality of life among individuals with aspirin-exacerbated respiratory disease

Objective: Patients with aspirin-exacerbated respiratory disease (AERD) have high disease burden due to the severity of asthma and sinonasal symptoms. There is limited research on the psychological well-being and subjective experiences of patients with AERD. This study examined levels of depression symptoms, asthma-related quality of life and asthma control among AERD patients. Methods: Thirty-two adults with AERD and 39 patients without AERD (asthma-only) were recruited from outpatient asthma/allergy clinics. The sample was largely comprised of ethnic minority, inner-city patients who ranged in age from 19 to 84?years old. Participants completed the Beck Depression Inventory (BDI), the Mini Asthma Quality of Life Questionnaire (Mini AQLQ), a self-report rating of asthma severity and spirometry testing. Asthma control and severity were determined following national guidelines. Results: AERD patients reported lower levels of depression symptoms (p?=?0.049), better overall asthma-related quality of life (p?<?0.001), and perceived their asthma to be less severe (p?=?0.01) compared to asthma-only patients. However, clinician ratings of asthma severity were more severe for AERD than asthma-only patients (p?=?0.006). No significant differences were found between the groups on asthma controller medications or oral corticosteroid bursts for asthma. Conclusions: AERD patients may be resilient given their low levels of depression symptoms and positive views of asthma-related impairment despite higher clinician-rated asthma severity. The adult onset nature of asthma in AERD might be a protective factor on mental health. Future studies should explore mechanisms linking AERD and positive psychological health outcomes and subjective perception of asthma.