Bronchiolitis In Infants Research Articles

Prise en charge de la bronchiolite aiguë du nourrisson de moins de 1 an : actualisation et consensus médical au sein des hôpitaux universitaires du Grand Ouest (HUGO)

While our European and North American colleagues have recently updated their recommendations, the 2000 Consensus Conference remains the main guideline on management of acute viral bronchiolitis in France. We aimed to establish an updated inter-regional protocol on management of acute viral bronchiolitis in infants. Pediatricians, pediatric pulmonologists, and emergency physicians of the Grand Ouest University Hospitals (France) gathered to analyze the recent data from the literature. Criteria to distinguish childhood asthma from acute viral bronchiolitis were established, then prescriptions of diagnostic tests, antibiotics, and chest physiotherapy were defined and reserved for very limited situations. Similarly, the modalities of oxygen therapy prescription and nutritional support were proposed. Finally, other therapeutics such as nebulized hypertonic saline seem promising, but their place in the treatment of acute bronchiolitis in infants remains unclear. This work has provided new proposals for management of acute viral bronchiolitis and helped standardize practices within the Grand Ouest University Hospitals. This local organization could lay the keystone for working toward guidelines initiated by learned societies at the national level.

Effects of Formalin-Inactivated Respiratory Syncytial Virus (FI-RSV) in the Perinatal Lamb Model of RSV

Respiratory syncytial virus (RSV) is the most frequent cause of bronchiolitis in infants and children worldwide. There are currently no licensed vaccines or effective antivirals. The lack of a vaccine is partly due to increased caution following the aftermath of a failed clinical trial of a formalin-inactivated RSV vaccine (FI-RSV) conducted in the 1960’s that led to enhanced disease, necessitating hospitalization of 80% of vaccine recipients and resulting in two fatalities. Perinatal lamb lungs are similar in size, structure and physiology to those of human infants and are susceptible to human strains of RSV that induce similar lesions as those observed in infected human infants. We sought to determine if perinatal lambs immunized with FI-RSV would develop key features of vaccine-enhanced disease. This was tested in colostrum-deprived lambs immunized at 3–5 days of age with FI-RSV followed two weeks later by RSV infection. The FI-RSV-vaccinated lambs exhibited several key features of RSV vaccine-enhanced disease, including reduced RSV titers in bronchoalveolar lavage fluid and lung, and increased infiltration of peribronchiolar and perivascular lymphocytes compared to lambs either undergoing an acute RSV infection or naïve controls; all features of RSV vaccine-enhanced disease. These results represent a first step proof-of-principle demonstration that the lamb can develop altered responses to RSV following FI-RSV vaccination. The lamb model may be useful for future mechanistic studies as well as the assessment of RSV vaccines designed for infants.

Defective control of vitamin D receptor‐mediated epithelial STAT1 signalling predisposes to severe respiratory syncytial virus bronchiolitis

Respiratory syncytial virus (RSV) infection causes bronchiolitis in infants with seasonal frequency, for which vitamin D deficiency and a well-described polymorphism in the vitamin D receptor (VDR) FokI are important risk factors. Recent studies suggest that vitamin D regulates immune pathways in airway epithelial cells during RSV infection. It is not understood why the VDR FokI polymorphism predisposes to severe RSV bronchiolitis. We investigated how the VDR FokI polymorphism regulates the epithelial response to RSV infection. To this end, we over-expressed the normal and FokI VDR variants in A549 airway epithelial cells. Vitamin D restrained the expression of both NFκB- and STAT1-induced antiviral genes. However, while NFκB control by vitamin D remained intact, both RSV-induced phosphorylation of STAT1 and expression of its downstream targets, IRF1 and IRF7, escaped vitamin D control in FokI epithelial cells. The poor capacity of vitamin D to regulate IRF1 in FokI VDR-expressing cells was recapitulated using blood samples from normal and FokI VDR-genotyped healthy donors. Hence, we provide mechanistic insight that the FokI VDR polymorphism renders STAT1-mediated antiviral immune reactions to RSV infection non-responsive to vitamin D control, resulting in enhanced immunopathology and exacerbated RSV bronchiolitis.

Irreversible airway obstruction in adulthood after bronchiolitis in infancy: Evidence from a 30-year follow-up study

Lower respiratory infections in infancy may be associated with lung function deficits in adulthood. Our aim was to evaluate lung function, with a special focus on irreversible airway obstruction, thirty years after bronchiolitis or pneumonia in infancy. In 1981-1982, 83 children under two years of age were hospitalized for bronchiolitis and 44 for pneumonia at Kuopio University Hospital, Finland. In 2010, 47 bronchiolitis patients, 22 pneumonia patients and 138 controls attended the study, including spirometry before (pre-BD) and after bronchodilatation (post-BD). The measured indices were forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), that were presented as % of predicted value (FVC% and FEV1%). FEV1/FVC was presented as both absolute FVC/FEV1-ratio and % of predicted (FEV1/FVC%). Irreversible airway obstruction was defined as post-BD FEV1/FVC% below 88% of predicted (FEV1/FVC% <88%) according to Finnish reference values or FEV1/FVC-ratio below fifth percentile (FEV1/FVC <5th percentile), according to Global Lung Function Initiative reference values. All lung function indices were lower in former bronchiolitis patients and pre- and post-BD FEV1% in pneumonia patients, compared to controls. 21% of bronchiolitis (OR, 95%CI; 5.59, 1.72-18.21) and 9% of pneumonia patients (2.24, 0.34-13.56) had FEV1/FVC% <88% compared to controls (4%). Likewise 7 (15%) of bronchiolitis (7.07, 1.33-37.22) and 1 (5%) of pneumonia patients (1.73, 0.12-24.77) had FEV1/FVC <5th percentile compared to controls 2 (1%). Evidence of reduced lung function was present 30 years after hospitalization for bronchiolitis or pneumonia in infancy. Irreversible airway obstruction after severe bronchiolitis in infancy suggests permanent, structural alterations in airways.

Systematic review and meta-analysis of respiratory syncytial virus infection epidemiology in Latin America.

Respiratory syncytial virus (RSV) is a frequent cause of acute respiratory infection and the most common cause of bronchiolitis in infants. The aim of this systematic review and meta-analysis was to obtain a comprehensive epidemiological picture of the data available on disease burden, surveillance, and use of resources in Latin America. Pooled estimates are useful for cross-country comparisons. Data from published studies reporting patients with probable or confirmed RSV infection in medical databases and gray literature were included from 74 studies selected from the 291 initially identified. When considering all countries, the largest pooled percentage RSV in low respiratory tract infection patients was found in the group between 0 and 11 months old, 41.5% (95% CI 32.0–51.4). In all countries, percentages were increasingly lower as older children were included in the analyses. The pooled percentage of RSV in LRTIs in the elderly people was 12.6 (95% CI 4.2–24.6). The percentage of RSV infection in hospitalized newborns was 40.9% (95% CI 28.28–54.34). The pooled case fatality ratio for RSV infection was 1.74% (95% CI 1.2–2.4) in the first 2 years of life. The average length of stay excluding intensive care unit admissions among children with risk factors for severe disease was 12.8 (95% CI 8.9–16.7) days, whereas it averaged 7.3 (95% CI 6.1/8.5) days in otherwise healthy children.We could conclude that infants in their first year of age were the most vulnerable population. To our knowledge, this is the first systematic review on RSV disease burden and use of health resources in Latin America.

Racemic Adrenaline and Inhalation Strategies in Acute Bronchiolitis: Skjerven HO, Gjengsto Hunderi JO, Brugmann-Pieper SK, et al. N Engl J Med 2013;368:2286–93.

Acute bronchiolitis in infants frequently leads to hospitalization. Despite the burden of this disease, there is no established consensus on inhalation therapy. This multicenter, randomized, double-blind clinical trial compared inhaled racemic epinephrine with inhaled saline, and on-demand inhalation with fixed-schedule inhalation in infants (< 12 months) with moderate-to-severe acute bronchiolitis. The primary outcome was the length of hospital stay, and secondary outcomes included change in clinical score 30 min after the first inhalation, use of nasogastric tube feeding, oxygen supplementation, and ventilator support. Four hundred four (59.4% male) children with a mean age of 4.2 months were enrolled, on hospital admission, from eight hospitals in Norway from January 2010 to May 2011. Inclusion criteria were clinical signs of bronchiolitis, age < 12 months, and a clinical score of at least 4 on a scale of 0–10. Clinical score was calculated by a pediatrician, composed of the sum of points allotted from 0 (normal) to 2 (severe illness) for the following clinical variables: general condition, skin color, auscultatory findings, respiratory rate, and retractions. Exclusion criteria were presence of serious cardiac, immunologic, neurologic, oncologic, or preceding pulmonary disease; more than one prior episode of obstructive airway disease; coughing for more than 4 weeks; and glucocorticoid therapy in the preceding 4 weeks. Subjects were randomized to receive either inhaled epinephrine or inhaled normal (0.9%) saline on either a fixed (not described) or on-demand treatment schedule, resulting in a total of four study groups. There was no significant difference in any of the primary or secondary outcomes in infants treated with inhaled racemic epinephrine vs. inhaled saline (p > 0.1 for all comparisons). Additionally, history of atopic eczema or wheezing, family history of atopic disease, and sex had no significant influence on treatment response. On-demand inhalation was associated with a significantly shorter estimated length of stay – 47.6 h (95% confidence interval [CI] 30.6–64.6) vs. 61.3 h (95% CI 45.4–77.2, p = 0.01) – as well as less use of oxygen supplementation, less use of ventilator support, and fewer inhalation treatments (12.0 vs. 17.0, p < 0.001) when compared to fixed-schedule treatments. The study medication was discontinued in 83 children (20.5%), however, there was no significant difference in discontinuation rate between subjects in the various groups. In infants with acute bronchiolitis, treatment with inhalation of racemic epinephrine was not associated with shorter hospital stay when compared to treatment with inhaled saline. However, inhalation treatments (regardless of agent) given on demand were superior to those on a fixed schedule, with a reduction of mean length of stay of 13.7 h. On-demand treatment was also associated with a mean five fewer total treatments when compared to fixed scheduling, supporting the goal of “minimal handling,” allowing acutely ill infants to sleep with minimal interruption.

The respiratory syncytial virus (RSV) nonstructural proteins mediate RSV suppression of glucocorticoid receptor transactivation

Respiratory syncytial virus (RSV)-induced bronchiolitis in infants is not responsive to glucocorticoids. We have shown that RSV infection impairs glucocorticoid receptor (GR) function. In this study, we have investigated the mechanism by which RSV impairs GR function. We have shown that RSV repression of GR-induced transactivation is not mediated through a soluble autocrine factor. Knock-down of mitochondrial antiviral signaling protein (MAVS), but not retinoic acid-inducible gene 1 (RIG-I) or myeloid differentiation primary response gene 88 (MyD88), impairs GR-mediated gene activation even in mock-infected cells. Over-expression of the RSV nonstructural protein NS1, but not NS2, impairs glucocorticoid-induced transactivation and viruses deleted in NS1 and/or NS2 are unable to repress glucocorticoid-induction of the known GR regulated gene glucocorticoid-inducible leucine zipper (GILZ). These data suggest that the RSV nonstructural proteins mediate RSV repression of GR-induced transactivation and that inhibition of the nonstructural proteins may be a viable target for therapy against RSV-related disease.

Human Respiratory Syncytial Virus Memphis 37 Grown in HEp-2 Cells Causes more Severe Disease in Lambs than Virus Grown in Vero Cells

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants and young children. A small percentage of these individuals develop severe and even fatal disease. To better understand the pathogenesis of severe disease and develop therapies unique to the less-developed infant immune system, a model of infant disease is needed. The neonatal lamb pulmonary development and physiology is similar to that of infants, and sheep are susceptible to ovine, bovine, or human strains of RSV. RSV grown in Vero (African green monkey) cells has a truncated attachment G glycoprotein as compared to that grown in HEp-2 cells. We hypothesized that the virus grown in HEp-2 cells would cause more severe clinical symptoms and cause more severe pathology. To confirm the hypothesis, lambs were inoculated simultaneously by two different delivery methods (intranasal and nebulized inoculation) with either Vero-grown or HEp-2-grown RSV Memphis 37 (M37) strain of virus to compare viral infection and disease symptoms. Lambs infected with HEp-2 cell-derived virus by either intranasal or nebulization inoculation had significantly higher levels of viral RNA in lungs as well as greater clinical disease including both gross and histopathologic lesions compared to lambs similarly inoculated with Vero-grown virus. Thus, our results provide convincing in vivo evidence for differences in viral infectivity that corroborate previous in vitro mechanistic studies demonstrating differences in the G glycoprotein expression by RSV grown in Vero cells.

Atomic force microscopic investigation of respiratory syncytial virus infection in HEp‐2 cells

Respiratory syncytial virus (RSV) primarily causes bronchiolitis and pneumonia in infants. In spite of intense research, no safe and effective vaccine has been developed yet. For understanding its pathogenesis and development of anti-RSV drugs/therapeutics, it is indispensable to study the RSV-host interaction. Although, there are limited studies using electron microscopy to elucidate the infection process of RSV, to our knowledge, no study has reported the morphological impact of RSV infection using atomic force microscopy. We report the cytoplasmic and nuclear changes in human epidermoid cell line type 2 using atomic force microscopy. Human epidermoid cell line type 2 cells, grown on cover slips, were infected with RSV and fixed after various time periods, processed and observed for morphological changes using atomic force microscopy. RSV infected cells showed loss of membrane integrity, with degeneration in the cellular content and cytoskeleton. Nuclear membrane was disintegrated and nuclear volume was decreased. The chromatin of the RSV infected cells was condensed, progressing towards degeneration via pyknosis and apoptosis. Membrane protrusions of ~150-200 nm diameter were observed on RSV infected cells after 6 h, suggestive of prospective RSV budding sites. To our knowledge, this is the first study of RSV infection process using atomic force microscopy. Such morphological studies could help explore viral infection process aiding the development of anti-RSV therapies.

Exhaled nitric oxide is related to atopy, but not asthma in adolescents with bronchiolitis in infancy

BackgroundThe fraction of exhaled nitric oxide (FeNO) has been suggested as a non-invasive marker of eosinophilic inflammation in asthma, but lately rather as a biomarker of atopy than of asthma itself. Asthma after bronchiolitis is common up to early adolescence, but the inflammation and pathophysiology may differ from other phenotypes of childhood asthma. We aimed to assess if FeNO was different in children with former hospitalization for bronchiolitis and a control group, and to explore whether the role of FeNO as a marker of asthma, atopy or bronchial hyperresponsiveness (BHR) differed between these two groups of children.MethodsThe study included 108 of 131 children (82%) hospitalized for bronchiolitis in 1997–98, of whom 82 (76%) had tested positive for Respiratory syncytial virus, and 90 age matched controls. The follow-up took place in 2008–2009 at 11 years of age. The children answered an ISAAC questionnaire regarding respiratory symptoms and skin prick tests, spirometry, methacholine provocation test and measurement of FeNO were performed.ResultsAnalysed by ANOVA, FeNO levels did not differ between the post-bronchiolitis and control groups (p = 0.214). By multivariate regression analyses, atopy, height (p < 0.001 for both) and BHR (p = 0.034), but not asthma (p = 0.805) or hospitalization for bronchiolitis (p = 0.359), were associated with FeNO in the post-bronchiolitis and control groups. The associations for atopy and BHR were similar in the post-bronchiolitis and in the control group.ConclusionFeNO did not differ between 11 year old children hospitalized for bronchiolitis and a control group. FeNO was associated with atopy, but not with asthma in both groups.

Blood eosinophil counts during bronchiolitis are related to bronchial hyper‐responsiveness and lung function in early adolescence

To assess whether inflammatory markers measured in urine and blood during acute bronchiolitis in infancy were associated with asthma, lung function, bronchial hyper-responsiveness (BHR) and atopy at 11years of age. We included 105 children hospitalised for bronchiolitis during their first year of life. At hospitalisation, urinary (U-) eosinophil protein X, U-leukotriene E4 , U-prostaglandin 9α, 11β-PGF2 and blood eosinophil counts were measured. Ninety-five children (90%) were available for follow-up at 11years of age. At follow-up, higher blood eosinophil counts obtained during bronchiolitis were observed in the group with asthma than in the group without asthma (median 0.27 versus 0.09×10(9) /L, respectively, p=0.048). By regression analyses, blood eosinophil counts during the acute bronchiolitis were positively associated with BHR (p=0.006) and negatively associated with forced expiratory volume in first second (p=0.025) at 11years of age. None of the other inflammatory markers were associated with asthma, lung function, BHR or atopy at 11years of age. Eosinophil inflammation during bronchiolitis may have a long-term impact on lung function and airway responsiveness. The associations could be related to virus-host interactions during bronchiolitis or to predisposed children.

Respiratory syncytial virus: How, why and what to do

Bronchiolitis is the leading cause of hospitalization of infants and young children worldwide. Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants. Studies conducted using molecular diagnostic assays confirmed that RSV accounts for over 50% of bronchiolitis in young children requiring hospitalization. Those studies demonstrate that it is common to identify RSV in association with a second viral agent but it is yet unclear whether the simultaneous detection of two or even three viruses is associated with increased disease severity. Despite extensive efforts, a vaccine for prevention of RSV infection is not yet available. Palivizumab a humanized monoclonal antibody directed against the F protein of RSV is the only agent licensed to prevent severe RSV disease in high-risk children. Among the new antivirals being developed for treatment of RSV infections, an RNA-interference based agent has demonstrated promising results for treatment of lung transplant recipients with acute RSV infection.

Re: Caiulo VA, Gargani L, Caiulo S, Fisicaro A, Moramarco F, Latini G, Picano E. Lung ultrasound in bronchiolitis: comparison with chest X-ray. Eur J Pediatr. 2011;170: 1427–33

Dear Editor, The comment of Toma [5] to the article by Caiulo et al. [1] appropriately raises serious concerns in their recommendation regarding lung ultrasound in infant's bronchiolitis. We too disagree with Caiulo et al. [1] because the Authors state that from their data “correlation between clinical and lung ultrasound findings and correlation between clinical and CXR findings are demonstrated” [1]. This is not evidence-based; the methods used (no detail on equipment setting, no rationale for the chest x-ray prescription) and the published figure are not demonstrating any straightforward information, no convincing image is provided, and no correlation was performed . How authors [1] can state that their data show that LUS may help to better characterize and stratify the patients for the follow-up of lung abnormalities, with sensitivity not inferior to CXR? No sensitivity analysis is quoted in the study. According to the assertion of the authors [1], diagnosis of bronchiolitis is a clinical one; in our daily practice, chest x-ray may help mainly to exclude other different acute pulmonary disease. Which was the indication for x-rays in these seemingly nonconsecutive patients? Moreover, the statement that the lung ultrasound learning curve is simple and fast compared to other ultrasound applications is not the shared experience of teaching centers, as ours, working at postgraduate level. Lung ultrasound procedure and interpretation are not the easiest component of any US curriculum, since it implies the same level of pitfalls of ultrasound assessment of other organs [2, 3]. Ultrasound procedures are probably among the most useful and specialized skills in clinical ultrasound, requiring imaging quality, sustainability, repeatability, and safety of the procedure [4]. Relying on artifacts, such as B-lines, is not an evidence-based best-practice imaging clue and lacks diagnostic specificity and sensitivity [6]. We warrant that recommendations, included in any article, should be, as always in your Journal, more evidence-based and less conjectural.

Neonatal Bronchial Hyperresponsiveness Precedes Acute Severe Viral Bronchiolitis in Infants

BL Chawes, P Poorisrisak, SL Johnston, H Bisgaard. J Allergy Clin Immunol. 2012;130(2):354–361, e3 To determine if host factors in neonates expressed as bronchial hyperresponsiveness precede later development of acute severe bronchiolitis. Previous studies showed that abnormal neonatal pulmonary function was associated with asthma by age 7 years. This study was nested in the Copenhagen Prospective Studies on Asthma in Childhood, a prospective study of a birth cohort of 411 neonates born to mothers with a history of asthma. Infants were enrolled at 1 month of age. Exclusion criteria included symptoms of lower …

Marked induction of matrix metalloproteinase‐10 by respiratory syncytial virus infection in human nasal epithelial cells

Respiratory syncytial virus (RSV) is an important pathogen of bronchiolitis, asthma, and severe lower respiratory tract disease in infants and young children. Matrix metalloproteinases (MMPs) play key roles in viral infection, inflammation and remodeling of the airway. However, the roles and regulation of MMPs in human nasal epithelial cells (HNECs) after RSV infection remain unclear. To investigate the regulation of MMP induced after RSV infection in HNECs, an RSV-infected model of HNECs in vitro was used. It was found that mRNA of MMP-10 was markedly increased in HNECs after RSV infection, together with induction of mRNAs of MMP-1, -7, -9, and -19. The amount of MMP-10 released from HNECs was also increased in a time-dependent manner after RSV infection as was that of chemokine RANTES. The upregulation of MMP-10 in HNECs after RSV infection was prevented by inhibitors of NF-κB and pan-PKC with inhibition of RSV replication, whereas it was prevented by inhibitors of JAK/STAT, MAPK, and EGF receptors without inhibition of RSV replication. In lung tissue of an infant with severe RSV infection in which a few RSV antibody-positive macrophages were observed, MMP-10 was expressed at the apical side of the bronchial epithelial cells and alveolar epithelial cells. In conclusion, MMP-10 induced by RSV infection in HNECs is regulated via distinct signal transduction pathways with or without relation to RSV replication. MMP-10 may play an important role in the pathogenesis of RSV diseases and it has the potential to be a novel marker and therapeutic target for RSV infection.

Viral Etiologies of Infant Bronchiolitis, Croup and Upper Respiratory Illness During 4 Consecutive Years

Prospective data on viral etiology and clinical characteristics of bronchiolitis and upper respiratory illness (URI) in infants are limited. This prospective cohort enrolled previously healthy term infants during inpatient or outpatient visits for acute URI or bronchiolitis during September to May 2004 to 2008. Illness severity was determined using an ordinal bronchiolitis severity score. Common respiratory viruses were identified by real-time reverse-transcriptase polymerase chain reaction. Of 648 infants, 67% were enrolled during inpatient visits and 33% during outpatient visits. Seventy percent had bronchiolitis, 3% croup and 27% URI. Among infants with bronchiolitis, 76% had respiratory syncytial virus (RSV), 18% human rhinovirus (HRV), 10% influenza, 2% coronavirus, 3% human metapneumovirus and 1% parainfluenza virus. Among infants with croup, 39% had HRV, 28% parainfluenza virus, 28% RSV, 11% influenza, 6% coronavirus and none human metapneumovirus. Among infants with URI, 46% had HRV, 14% RSV, 12% influenza, 7% coronavirus, 6% parainfluenza virus and 4% human metapneumovirus. Individual viruses exhibited distinct seasonal, demographic and clinical expression. The most common infections among infants seeking care in unscheduled medical visits for URI or bronchiolitis were RSV and HRV. Demographic differences were observed between patients with different viruses, suggesting that host and viral factors play a role in phenotypic expression of viral illness.

Nebulised hypertonic saline solution for acute bronchiolitis in infants

Airway oedema and mucus plugging are the predominant pathological features in infants with acute viral bronchiolitis. Nebulised hypertonic saline solution may reduce these pathological changes and decrease airway obstruction. To assess the effects of nebulised hypertonic (≥ 3%) saline solution in infants with acute viral bronchiolitis. We searched CENTRAL 2013, Issue 4, OLDMEDLINE (1951 to 1965), MEDLINE (1966 to April week 4, 2013), EMBASE (1974 to May 2013), LILACS (1985 to May 2013) and Web of Science (1955 to May 2013). Randomised controlled trials (RCTs) and quasi-RCTs using nebulised hypertonic saline alone or in conjunction with bronchodilators as an active intervention and nebulised 0.9% saline as a comparator in infants up to 24 months of age with acute bronchiolitis. Two review authors independently performed study selection, data extraction and assessment of risk of bias in included studies. We conducted meta-analyses using the Cochrane statistical package RevMan 5.2. We used the random-effects model for meta-analyses. We used mean difference (MD) and risk ratio (RR) as effect size metrics. We included 11 trials involving 1090 infants with mild to moderate acute viral bronchiolitis (500 inpatients, five trials; 65 outpatients, one trial; and 525 emergency department patients, four trials). All but one of the included trials were of high quality with a low risk of bias. A total of 560 patients received hypertonic saline (3% saline n = 503; 5% saline n = 57). Patients treated with nebulised 3% saline had a significantly shorter mean length of hospital stay compared to those treated with nebulised 0.9% saline (MD -1.15 days, 95% confidence interval (CI) -1.49 to -0.82, P < 0.00001). The hypertonic saline group also had a significantly lower post-inhalation clinical score than the 0.9% saline group in the first three days of treatment (day 1: MD -0.88, 95% CI -1.36 to -0.39, P = 0.0004; day 2: MD -1.32, 95% CI -2.00 to -0.64, P = 0.001; day 3: MD -1.51, 95% CI -1.88 to -1.14, P < 0.00001). The effects of improving clinical score were observed in both outpatients and inpatients. Four emergency department-based trials did not show any significant short-term effects (30 to 120 minutes) of up to three doses of nebulised 3% saline in improving clinical score and oxygen saturation. No significant adverse events related to hypertonic saline inhalation were reported. Current evidence suggests nebulised 3% saline may significantly reduce the length of hospital stay among infants hospitalised with non-severe acute viral bronchiolitis and improve the clinical severity score in both outpatient and inpatient populations.

Editorial Commentary: Respiratory Syncytial Virus: A Global Pathogen in an Aging World

Respiratory syncytial virus (RSV) was identified in 1957 as a cause of infant bronchiolitis and is now recognized as the major cause of hospitalizations for respiratory infection in young children [1]. Shortly after its discovery, mild illness in adults with RSV reinfection was observed and since the 1980s evidence has been slowly mounting that the burden of adult RSV disease is substantial [2, 3]. Groups at highest risk for severe infection include the elderly, persons with chronic cardiopulmonary diseases, and those with immunosuppression [4, 5]. Despite the currently available epidemiologic data, RSV infection is rarely considered by internists evaluating patients with respiratory illness in their offices or in the hospital. In addition, health agencies and industry remain uncertain as to whether adult RSV disease warrants programs to develop therapeutics and vaccines. The reason for the adult RSV “identity crisis” is in large part because physicians rarely make a specific viral diagnosis in an individual patient and thus, they are unable to personalize the disease. Insensitive pointof-care diagnostics, the lack of a distinct clinical syndrome, and a broad epidemic curve that overlaps with influenza and other respiratory viruses all contribute to this lack of recognition of the problem. The development of new sensitive molecular diagnostics have dramatically altered epidemiologic research involving respiratory viruses, and recent studies now provide a more accurate picture of the burden of RSV disease [6, 7]. Yet, here too, the global community cannot personalize the problem to their own region or countries as most studies to date are from Europe and North America. Unless a disease is demonstrated in one’s own backyard, there is a natural tendency to ignore or minimize the problem. In this issue of Clinical Infectious Diseases, Lee and colleagues [8] present data from a large, 3-year study of adults hospitalized with respiratory illness in Hong Kong, China. In this study, the clinical and radiologic features of 607 adults with confirmed RSV infection are compared and contrasted to patients with seasonal influenza infection. The findings clearly demonstrate significant morbidity and mortality in older persons associated with RSV infection, which is comparable to influenza. RSV accounted for 6%–9% of respiratory illnesses during seasonal peaks; 72% of those admitted with RSV had lower respiratory tract complications, 11% required ventilatory support, and 9% died within 30 days. Similar to previous reports, infected patients were elderly (mean age, 75 years), and most had underlying medical conditions with chronic lung disease reported in 36%. Of note, although substantial proportions of both RSV and influenza patients had underlyin g medical conditions, RSV patients had significantly more lung disease and major systemic comorbidities. This observation may reflect the very large sample size of the current study allowing detection of more subtle differences in patient groups than previous reports. Importantly, there was no significant difference in the overall outcomes of survival and duration of hospitalization of RSV- and influenza-infected patients. Although a number of the observations

Increased asthma risk and impaired quality of life after bronchiolitis or pneumonia in infancy

Recent studies have revealed that adulthood asthma has its origin in early childhood. The aim of the present study was to evaluate the prevalence of asthma and respiratory health-related quality of life in adults 30 years after hospitalization for bronchiolitis or pneumonia in infancy. Patients who were hospitalized for bronchiolitis or pneumonia at age under 24 months in 1981-1982 have been followed in repeated visits. In 2010, 48 of the 83 former patients with bronchiolitis (57.8%), 22 of the 44 former patients with pneumonia (50.0%), and 138 matched controls participated in the clinical study at the age of 28-31 years. The participants completed a structured questionnaire on respiratory symptoms, the Saint George's Respiratory Questionnaire (SGRQ), and underwent 2-week peak expiratory flow (PEF) monitoring. Asthma was defined as doctor-diagnosed and self-reported asthma based on doctor-prescribed medication for asthma, the presence of asthma-presumptive symptoms, and the results of home PEF monitoring. Both doctor-diagnosed asthma (31.3% vs. 10.9% adjusted P = 0.002) and self-reported asthma (35.4% vs. 14.5% 0.003), as well as repeated on-demand use of bronchodilators (35.4% vs. 14.5% 0.002), and regular use of inhaled corticosteroids (20.8% vs. 8.7% 0.023) were more common in former bronchiolitis patients than in controls. Former bronchiolitis and pneumonia patients had higher total SGRQ scores than controls. The median scores were 5.4 (IQ(25-75) 0.0-14.7, P < 0.001) in bronchiolitis group, 4.9 (1.3-14.8, 0.012) in pneumonia group compared to controls 1.5 (0.0-6.0). Hospitalization for bronchiolitis in infancy is associated with an increased risk of asthma, and an increased use of asthma medication in adulthood at the age of 28-31 years. Impaired respiratory health-related quality of life in adulthood as measured by the SGRQ is present after bronchiolitis and pneumonia in infancy.

Poly I:C and respiratory syncytial virus (RSV) inhibit glucocorticoid receptor (GR)-mediated transactivation in lung epithelial, but not monocytic, cell lines

Respiratory syncytial virus (RSV)-induced bronchiolitis in infants is not responsive to glucocorticoids. We have recently shown that RSV infection of lung epithelial cells impairs glucocorticoid receptor (GR) function. In this current study, we have shown that the viral mimic poly I:C also represses GR-mediated gene activation in lung epithelial cells, suggesting that this might be a common phenomenon of other viral infections. However, we also show that neither RSV infection nor poly I:C affect GR-mediated gene activation in the monocytic cell line THP-1, suggesting that these effects on GR function may be cell-type specific.