Severe necrotizing tracheobronchitis caused by influenza B and methicillin-resistant Staphylococcus aureus co-infection in an immunocompetent patient.

PURPOSE AND METHOD: Necrotizing tracheobronchitis is a rare clinical entity presented as a necrotic inflammation involving the mainstem trachea and distal bronchi. We reported a case of severe necrotizing tracheobronchitis caused by influenza B and methicillin-resistant Staphylococcus aureus (MRSA) co-infection in an immunocompetent patient. CASE PRESENTATION: We described a 36-year-old man with initial symptoms of cough, rigors, muscle soreness and fever. His status rapidly deteriorated two days later and he was intubated. Bronchoscopy demonstrated severe necrotizing tracheobronchitis, and CT imaging demonstrated multiple patchy and cavitation formation in both lungs. Next-generation sequencing (NGS) and bronchoalveolar lavage fluid (BALF) culture supported the co-infection of influenza B and MRSA. We also found T lymphocyte and NK lymphocyte functions were extremely suppressed during illness exacerbation. The patient was treated with antivirals and antibiotics including vancomycin. Subsequent bronchoscopy and CT scans revealed significant improvement of the airway and pulmonary lesions, and the lymphocyte functions were restored. Finally, this patient was discharged successfully. CONCLUSION: Necrotizing tracheobronchitis should be suspected in patients with rapid deterioration after influenza B infection. The timely diagnosis of co-infection and accurate antibiotics are important to effective treatment.

Vitamin D3 Attenuates Viral-Induced Inflammation and Fibrotic Responses in Bronchial Smooth Muscle Cells.

Toll-like receptor 3 (TLR3) activation by viral infections plays a key role in promoting inflammatory immune responses that contribute to pulmonary fibrosis in chronic inflammatory respiratory diseases. Vitamin D3 has been shown to be beneficial to patients with asthma and chronic obstructive pulmonary disease (COPD) through its anti-inflammatory and anti-fibrotic properties. Smooth muscle cells are one of the major contributors to airway remodeling in asthma and COPD. We therefore aimed to investigate the effect of vitamin D3 treatment on viral-induced TLR3 responses in Bronchial Smooth Muscle Cells (BSMCs) as a mechanism contributing to pulmonary fibrosis in asthma and COPD. Primary BSMCs from patients with asthma (n=4), COPD (n=4), and healthy control subjects (n=6) were treated with polyinosinic: polycytidylic acid (polyI:C), TLR3 agonist in the presence or absence of vitamin D3 (1,25D3). Here we report the mRNA expression and protein levels of pro-inflammatory and pro-fibrotic markers (IL-6, IFN-ß1, CCL2/MCP-1, fibronectin 1 and type I collagen) among BSMCs groups: asthma, COPD, and healthy controls. We show that at the baseline, prior to polyI:C stimulation, asthma and COPD BSMCs presented increased pro-inflammatory and pro-fibrotic state compared to healthy control subjects, as measured by quantitative PCR and immunoassays (ELISA/Flow Cytometry. Ligation of TLR3 by polyI:C in BSMCs was associated with increased TLR3 mRNA expression, and 1,25D3 treatment significantly reduced its expression. In addition, 1,25D3 decreased the expression of IL-6, IFN-ß1, CCL2, FN1 and COL1A1 induced by polyI:C in BSMCs. The regulatory effect of 1,25D3 treatment on polyI:C-stimulated BSMCs was further confirmed at protein levels. Our findings suggest that vitamin D3 attenuates TLR3 agonist-induced inflammatory and fibrotic responses in BSMCs and support the clinical relevance of vitamin D3 supplementation in patients with viral infections having chronic respiratory diseases, such as asthma and COPD.

miR-122 promotes virus-induced lung disease by targeting SOCS1.

Virus-induced respiratory tract infections are a major health burden in childhood, and available treatments are supportive rather than disease modifying. Rhinoviruses (RVs), the cause of approximately 80% of common colds, are detected in nearly half of all infants with bronchiolitis and the majority of children with an asthma exacerbation. Bronchiolitis in early life is a strong risk factor for the development of asthma. Here, we found that RV infection induced the expression of miRNA 122 (miR-122) in mouse lungs and in human airway epithelial cells. In vivo inhibition specifically in the lung reduced neutrophilic inflammation and CXCL2 expression, boosted innate IFN responses, and ameliorated airway hyperreactivity in the absence and in the presence of allergic lung inflammation. Inhibition of miR-122 in the lung increased the levels of suppressor of cytokine signaling 1 (SOCS1), which is an in vitro-validated target of miR-122. Importantly, gene silencing of SOCS1 in vivo completely reversed the protective effects of miR-122 inhibition on RV-induced lung disease. Higher miR-122 expression in nasopharyngeal aspirates was associated with a longer time on oxygen therapy and a higher rate of treatment failure in 87 infants hospitalized with moderately severe bronchiolitis. These results suggest that miR-122 promotes RV-induced lung disease via suppression of its target SOCS1 in vivo. Higher miR-122 expression was associated with worse clinical outcomes, highlighting the potential use of anti-miR-122 oligonucleotides, successfully trialed for treatment of hepatitis C, as potential therapeutics for RV-induced bronchiolitis and asthma exacerbations.

Reducing Antibiotic Prescribing in Primary Care for Respiratory Illness.

BACKGROUND: One-third of outpatient antibiotic prescriptions for pediatric acute respiratory tract infections (ARTIs) are inappropriate. We evaluated a distance learning program's effectiveness for reducing outpatient antibiotic prescribing for ARTI visits. METHODS: In this stepped-wedge clinical trial run from November 2015 to June 2018, we randomly assigned 19 pediatric practices belonging to the Pediatric Research in Office Settings Network or the NorthShore University HealthSystem to 4 wedges. Visits for acute otitis media, bronchitis, pharyngitis, sinusitis, and upper respiratory infection for children 6 months to <11 years old without recent antibiotic use were included. Clinicians received the intervention as 3 program modules containing online tutorials and webinars on evidence-based communication strategies and antibioti c prescribing, booster video vignettes, and individualized antibiotic prescribing feedback reports over 11 months. The primary outcome was overall antibiotic prescribing rates for all ARTI visits. Mixed-effects logistic regression compared prescribing rates during each program module and a postintervention period to a baseline control period. Odds ratios were converted to adjusted rate ratios (aRRs) for interpretability. RESULTS: Among 72 723 ARTI visits by 29 762 patients, intention-to-treat analyses revealed a 7% decrease in the probability of antibiotic prescribing for ARTI overall between the baseline and postintervention periods (aRR 0.93; 95% confidence interval [CI], 0.90-0.96). Second-line antibiotic prescribing decreased for streptococcal pharyngitis (aRR 0.66; 95% CI, 0.50-0.87) and sinusitis (aRR 0.59; 95% CI, 0.44-0.77) but not for acute otitis media (aRR 0.93; 95% CI, 0.83-1.03). Any antibiotic prescribing decreased for viral ARTIs (aRR 0.60; 95% CI, 0.51-0.70). CONCLUSIONS: This program reduced antibiotic prescribing during outpatient ARTI visits; broader dissemination may be beneficial.

A Novel Mucosal Adjuvant System for Immunization against Avian Coronavirus Causing Infectious Bronchitis.

Infectious bronchitis (IB) caused by infectious bronchitis virus (IBV) is currently a major threat to chicken health, with multiple outbreaks being reported in the United States over the past decade. Modified live virus (MLV) vaccines used in the field can persist and provide the genetic material needed for recombination and emergence of novel IBV serotypes. Inactivated and subunit vaccines overcome some of the limitations of MLV with no risk of virulence reversion and emergence of new virulent serotypes. However, these vaccines are weakly immunogenic and poorly protective. There is an urgent need to develop more effective vaccines that can elicit a robust, long-lasting immune response. In this study, we evaluate a novel adjuvant system developed from Quil-A and chitosan (QAC) for the intranasal delivery of nucleic acid immunogens to improve protective efficacy. The QAC adjuvant system forms nanocarriers (<100 nm) that efficiently encapsulate nucleic acid cargo, exhibit sustained release of payload, and can stably transfect cells. Encapsulation of plasmid DNA vaccine expressing IBV nucleocapsid (N) protein by the QAC adjuvant system (pQAC-N) enhanced immunogenicity, as evidenced by robust induction of adaptive humoral and cellular immune responses postvaccination and postchallenge. Birds immunized with pQAC-N showed reduced clinical severity and viral shedding postchallenge on par with protection observed with current commercial vaccines without the associated safety concerns. Presented results indicate that the QAC adjuvant system can offer a safer alternative to the use of live vaccines against avian and other emerging coronaviruses.IMPORTANCE According to 2017 U.S. agriculture statistics, the combined value of production and sales from broilers, eggs, turkeys, and chicks was $42.8 billion. Of this number, broiler sales comprised 67% of the industry value, with the production of >50 billion pounds of chicken meat. The economic success of the poultry industry in the United States hinges on the extensive use of vaccines to control infectious bronchitis virus (IBV) and other poultry pathogens. The majority of vaccines currently licensed for poultry health include both modified live vaccine and inactivated pathogens. Despite their proven efficacy, modified live vaccine constructs take time to produce and could revert to virulence, which limits their safety. The significance of our research stems from the development of a safer and potent alternative mucosal vaccine to replace live vaccines against IBV and other emerging coronaviruses.

Plastic bronchitis due to adenoviral infection: a case report.

BACKGROUND: Plastic bronchitis (PB) frequently occurs as a serious postoperative complication of the Fontan procedure. The definitive causes of PB are unknown. CASE PRESENTATION: Herein, we report a pediatric case of PB secondary to adenoviral infection. A 4-year-old girl was admitted to the general pediatric ward for cough since 2 weeks and fever since 11 days. Consolidated lesions were noted in the right upper and both lower lung lobes. Extracorporeal membrane oxygenation was performed because the patient's respiratory failure remained unalleviated despite the use of a ventilator. Bronchial dendritic casts were extracted using flexible bronchoscopy, and the patient's breathing improved. Pathological examination of the dendritic cast confirmed the diagnosis of type I PB. The exfoliated cells of sputum and cells from bronchoalveolar lavage fluid were positive for adenoviral antigen. Human adenovirus 7 was detected by next-generation sequencing of the bronchoalveolar lavage fluid. The patient recovered and was discharged 39 days after admission without recurrence of cough or wheezing. CONCLUSIONS: PB due to human adenovirus 7 infection should be considered in children with persistent respiratory failure. Flexible bronchoscopy should be performed early to confirm diagnosis and to remove any airway obstruction.

Necrotizing tracheobronchitis causing airway obstruction complicated by pandemic 2009 H1N1 influenza: A case report.

RATIONALE: Influenza is an infection caused by the influenza virus, and its symptoms are mostly mild and self-limiting. However, influenza can cause severe or fatal complications in high-risk patients. Although tracheobronchitis is one of the common complications of influenza, necrotizing tracheobronchitis is very rare. Herein, we describe a case of necrotizing tracheobronchitis causing airway obstruction complicated by pandemic 2009 H1N1 influenza. PATIENT CONCERNS: A 60-year-old man presented with fever and dyspnea. On arrival at the emergency room (ER), the patient received oxygen 4 L/minute via a nasal prolong owing to mild hypoxemia. And invasive mechanical ventilation was needed 5 hours after arrival at the ER due to progressive hypoxemia. DIAGNOSES: Fiberoptic bronchoscopy was performed owing to bloody secretion in the endotracheal tube and revealed diffuse tracheobronchitis with necrotic and hemorrhagic materials obstructing the trachea and bronchus. The pandemic 2009 H1N1 influenza virus was detected from the bronchial washing sample; no other microorganism was detected. INTERVENTION: He received peramivir plus oseltamivir and broad-spectrum antibiotics. OUTCOMES: The bloody secretion continued. He developed cardiac arrest due to airway obstruction on the 6th day of admission. After cardiac arrest, his condition progressed to multi-organ failure, and the patient died on the 10th day of admission. LESSONS: We suggest that necrotizing tracheobronchitis be considered in patients with influenza who present with unexplained hypoxemia.

Emerging lethal infectious bronchitis coronavirus variants with multiorgan tropism.

Infectious bronchitis virus (IBV) causes respiratory diseases in chickens and poses an economic threat to the poultry industry worldwide. Despite vaccine use, there have been field outbreaks of IBV in Taiwan. This study aimed to characterize the emerging IBV variants circulating in Taiwan. The analysis of the structural protein genes showed that these variants emerged through frequent recombination events among Taiwan strains, China strains, Japan strains and vaccine strains. Cross-neutralization tests revealed that two of the variants exhibited novel serotypes. Clinicopathological assessment showed that two of the variants caused high fatality rates of 67% and 20% in one-day-old SPF chicks, and all the variants possessed multiorgan tropisms, including trachea, proventriculus and urogenital tissues. Furthermore, the commercial live-attenuated Mass-type vaccine conferred poor protection against these variants. This study identified novel genotypes, serotypes and pathotypes of emerging IBV variants circulating in Taiwan. There is an urgent need for effective countermeasures against these variant strains.

Enterovirus D68-associated respiratory and neurological illness in Spain, 2014-2018.

During 2014, enterovirus D68 (EV-D68) outbreaks were described globally, causing severe respiratory diseases in children and, in some cases, subsequent paralysis. In this study, the type characterization of enterovirus (EV) detected in respiratory illnesses and the epidemiology and clinical association of EV-D68 infections in Spain over a five-year period were described. A total of 546 EV-positive samples from hospitalized patients with respiratory infections were included. EV-D68 was the most frequently detected type (46.6%, 191/410 typed EV). Other EV from species A (25.1%), B (27.8%) and C (0.5%) were also identified. EV-D68 infections were more associated with bronchitis while EV-A/B types were more frequent in upper respiratory illness (p < 0.01). EV-D68 was also detected in patients with neurological symptoms (nine meningitis/meningoencephalitis and eight acute flaccid paralysis cases). Phylogenetic analysis of 3'-VP1 region showed most Spanish EV-D68 sequences from 2014 to 2016 belonged to subclades B2/B3, as other American and European strains circulating during the same period. However, those detected in 2017 and 2018 clustered to the emerged subclade D1. In summary, different EV can cause respiratory infections but EV-D68 was the most prevalent, with several strains circulating in Spain at least since 2014. Association between EV-D68 infection and neurological disease was also described.

Occurrence of infectious bronchitis in layer birds in Plateau state, north central Nigeria.

A flock of 54 wk-old layer birds exhibiting signs of respiratory distress, greenish diarrhea, and drop in egg production was investigated. A marked drop in egg production (55%) was recorded with eggs appearing white and soft-shelled. Mortality was in the range of 1%-2% with post-mortem lesions revealing cloudy air sacs, frothy, and congested lungs. Viral RNA was extracted from pooled tissue samples (trachea, lungs, spleen, and liver) and tested for Avian influenza virus (AIV), Newcastle disease virus (NDV), and infectious bronchitis virus (IBV) by reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, virus isolation was attempted in 9-11 day-old embryonating chicken eggs (ECE). In order to determine the prevalence of IBV serotype(s) in the flock, serum samples were screened by hemagglutination-inhibition (HI) test using IBV antigens and antisera (Arkansas, Connecticut, and Massachusetts). Neither AIV nor NDV but IBV was detected in the tissue samples by RT-PCR. In addition, virus isolate obtained after four serial passages in ECE produced dwarfed, stunted, and hemorrhagic embryos, and the isolate was confirmed by RT-PCR to be IBV. The serum samples were 100% seropositive for three serotypes with HI titres ranging from 5 to 12 Log2. In this study, IBV was confirmed as the causative agent of the observed respiratory distress and drop in egg production. Also, the evidence of co-circulation of multiple IBV serotypes was established, this to the best of our knowledge is the first of such report in Nigeria. We recommend extensive molecular and sero-epidemiology of circulating IBV genotypes and serotypes in Nigeria with the aim of developing better control strategies, including vaccination.

The Infectious Bronchitis Coronavirus Envelope Protein Alters Golgi pH To Protect the Spike Protein and Promote the Release of Infectious Virus.

Coronaviruses (CoVs) assemble by budding into the lumen of the early Golgi complex prior to exocytosis. The small CoV envelope (E) protein plays roles in assembly, virion release, and pathogenesis. CoV E has a single hydrophobic domain (HD), is targeted to Golgi membranes, and has cation channel activity in vitro The E protein from avian infectious bronchitis virus (IBV) has dramatic effects on the secretory system, which require residues in the HD. Mutation of the HD of IBV E in a recombinant virus background results in impaired growth kinetics, impaired release of infectious virions, accumulation of IBV spike (S) protein on the plasma membrane compared to wild-type (WT) IBV-infected cells, and aberrant cleavage of IBV S on virions. We previously reported the formation of two distinct oligomeric pools of IBV E in transfected and infected cells. Disruption of the secretory pathway by IBV E correlates with a form that is likely monomeric, suggesting that the effects on the secretory pathway are independent of E ion channel activity. Here, we present evidence suggesting that the monomeric form of IBV E correlates with an increased Golgi luminal pH. Infection with IBV or expression of IBV E induces neutralization of Golgi pH, promoting a model in which IBV E alters the secretory pathway through interaction with host cell factors, protecting IBV S from premature cleavage and leading to the efficient release of infectious virus from the cells. This is the first demonstration of a coronavirus-induced alteration in the microenvironment of the secretory pathway.IMPORTANCE Coronaviruses are important human pathogens with significant zoonotic potential. Progress has been made toward identifying potential vaccine candidates for highly pathogenic human CoVs, including the use of attenuated viruses that lack the CoV E protein or express E mutants. However, no approved vaccines or antiviral therapeutics exist. Understanding the role of the CoV E protein in virus assembly and release is thus an important prerequisite for potential vaccines as well as in identifying novel antiviral therapeutics.

Fatal, Fulminant Herpetic Tracheobronchitis following Cardiac Surgery.

Nosocomial infection is a feared complication after any surgical procedure. Respiratory tract microbial colonization and development of ventilator-associated tracheobronchitis and/or pneumonia are unfortunate sequelae in mechanically ventilated patients, commonly caused by bacteria; viral etiology is seldom anticipated. We present a fatal case of fulminant herpetic tracheobronchitis in a 33-month-old patient following cardiac surgery. We intend to highlight the fact that herpetic viral etiology should be considered in post-operative respiratory infections.

Human T-Lymphotropic Virus type 1c subtype proviral loads, chronic lung disease and survival in a prospective cohort of Indigenous Australians.

BACKGROUND: The Human T-Lymphotropic Virus type 1c subtype (HTLV-1c) is highly endemic to central Australia where the most frequent complication of HTLV-1 infection in Indigenous Australians is bronchiectasis. We carried out a prospective study to quantify the prognosis of HTLV-1c infection and chronic lung disease and the risk of death according to the HTLV-1c proviral load (pVL). METHODOLOGY/PRINCIPAL FINDINGS: 840 Indigenous adults (discharge diagnosis of bronchiectasis, 154) were recruited to a hospital-based prospective cohort. Baseline HTLV-1c pVL were determined and the results of chest computed tomography and clinical details reviewed. The odds of an association between HTLV-1 infection and bronchiectasis or bronchitis/bronchiolitis were calculated, and the impact of HTLV-1c pVL on the risk of death was measured. Radiologically defined bronchiectasis and bronchitis/bronchiolitis were significantly more common among HTLV-1-infected subjects (adjusted odds ratio = 2.9; 95% CI, 2.0, 4.3). Median HTLV-1c pVL for subjects with airways inflammation was 16-fold higher than that of asymptomatic subjects. There were 151 deaths during 2,140 person-years of follow-up (maximum follow-up 8.13 years). Mortality rates were higher among subjects with HTLV-1c pVL ≥1000 copies per 105 peripheral blood leukocytes (log-rank χ2 (2df) = 6.63, p = 0.036) compared to those with lower HTLV-1c pVL or uninfected subjects. Excess mortality was largely due to bronchiectasis-related deaths (adjusted HR 4.31; 95% CI, 1.78, 10.42 versus uninfected). CONCLUSION/SIGNIFICANCE: Higher HTLV-1c pVL was strongly associated with radiologically defined airways inflammation and with death due to complications of bronchiectasis. An increased risk of death due to an HTLV-1 associated inflammatory disease has not been demonstrated previously. Our findings indicate that mortality associated with HTLV-1c infection may be higher than has been previously appreciated. Further prospective studies are needed to determine whether these results can be generalized to other HTLV-1 endemic areas.

Clinical characteristics of influenza virus-induced lower respiratory infection during the 2015 to 2016 season.

BACKGROUND: Influenza A(H1N1)pdm09 virus infections often manifest severe respiratory symptoms, particularly in patients with a past history of allergic disease. Most of these findings were reported during the 2009 pandemic. The purpose of this study was to detail the clinical characteristics of influenza virus-induced lower respiratory infection (LRI) during the A(H1N1)pdm09-predominant 2015-2016 season. METHODS: We retrospectively reviewed the clinical characteristics of influenza-induced LRI cases in children admitted to a tertiary children's hospital. Molecular diagnostic evaluation was performed on samples obtained from the most severe cases. RESULTS: We identified 66 patients with influenza-associated hospitalization and included 21 patients with influenza virus-induced LRI for analyses. Twelve patients (57%) were admitted to the pediatric intensive care unit, seven (33%) required mechanical ventilation, and three (14%) required extracorporeal membrane oxygenation. Plastic bronchitis (PB) was identified in six patients (29%), among whom a past medical history of asthma or food allergy were noted in all six patients. A past history of allergic disease was more common among patients with, than among those without, PB (p = 0.009). A(H1N1)pdm09 was detected from all the PB cases, and phylogenetic analyses of the hemagglutinin and neuraminidase genes demonstrated that this virus belonged to subclades 6B.1 and 6B.2. In the six PB cases, we found one patient with H275Y mutation in neuraminidase. CONCLUSION: Allergic disease was a risk factor for developing PB due to influenza A(H1N1)pdm09 infection during the 2015-16 season.

Subtype-specific Clinical Presentation, Medical Treatment and Family Impact of Influenza in Children 1-5 Years of Age Treated in Outpatient Practices in Germany During Three Postpandemic Years, 2013-2015.

BACKGROUND: Limited data on the influenza burden in pediatric outpatients are available, especially regarding direct comparison of the cocirculating (sub)types A(H1N1)pdm09, A(H3N2) and B. METHODS: Children 1-5 years of age, unvaccinated against influenza and presenting with febrile acute respiratory infections (ARIs), were enrolled in 33 pediatric practices in Germany from 2013 to 2015 (January-May). Influenza was confirmed by multiplex polymerase chain reaction from pharyngeal swabs and (sub)typed. RESULTS: In 805 children with ARI, influenza was the most frequently detected respiratory virus (n = 305; 37.9%). Of 217 influenza patients included, 122 (56.2%) were infected with A(H3N2), 56 (25.8%) with A(H1N1)pdm09 and 39 (18.0%) with B. Median age was 3.7 years [interquartile range (IQR), 2.1-4.8]; 11% had underlying conditions. Median fever duration was 4 days (IQR, 3-5), and the disease duration was 9 days (IQR, 7-12). Most frequent diagnoses were pharyngitis (26%), bronchitis (18%) and acute otitis media (10%). Children received mainly antipyretics (86%) and adrenergic nasal drops/spray (53%); 9% received antibiotics and 3% oseltamivir. Thirty-six percent required at least 1 additional practice visit; 1% was hospitalized. Median absences from childcare were 5 days (IQR, 3-7); parents lost 4 workdays (IQR, 2-6). Symptoms, severity and impact on the family were largely unrelated to (sub)type. However, patients with A(H1N1)pdm09 had fewer underlying conditions (P = 0.017), whereas patients with B more often had pharyngitis (P = 0.022), acute otitis media (P = 0.012) and stenosing laryngotracheitis (P = 0.007). CONCLUSIONS: Influenza was the most frequently detected viral pathogen in outpatient children with febrile, mostly uncomplicated ARI. In this setting, clinical manifestations and severity were similar across the (sub)types prevalent during the postpandemic seasons.

Up-regulation of serum periostin and squamous cell carcinoma antigen levels in infants with acute bronchitis due to respiratory syncytial virus.

BACKGROUND: Periostin and squamous cell carcinoma antigen (SCCA) are involved in the pathogenesis of asthma. Acute bronchitis due to respiratory syncytial virus (RSV) infection during infancy exhibits an asthma-like pathogenesis, suggesting that it may be associated with the subsequent development of asthma. However, the mechanism by which RSV infection leads to development of asthma has not yet been fully elucidated. METHODS: Infants younger than 36 months were enrolled and classified into three groups. Group I included patients hospitalized with RSV-induced bronchitis. These patients were further stratified into two sub-groups according to whether the criteria for the modified Asthma Predictive Index (mAPI) had been met: Group I consisted of mAPI (+) and mAPI (-) patients; Group II included patients with food allergy as a positive control group; and Group III included children with no allergy as a negative control group. Serum periostin and SCCA levels were measured in the groups. This study was registered as a clinical trial (UMIN000012339). RESULTS: We enrolled 14 subjects in Group I mAPI (+), 22 in Group I mAPI (-), 18 in Group II, and 18 in Group III. In Group I, the serum periostin and SCCA levels were significantly higher during the acute phase compared with the recovery phase. However, no significant differences were found between Group I mAPI (+) and mAPI (-). CONCLUSIONS: The serum periostin and SCCA levels increased during acute RSV bronchitis. Both periostin and SCCA may play a role in the pathogenesis of acute bronchitis due to RSV.