Lower Respiratory Tract Disease Research Articles

Human Herpesvirus 6B and Lower Respiratory Tract Disease After Hematopoietic Cell Transplantation.

Human herpesvirus 6B (HHV-6B) DNA is frequently detected in bronchoalveolar lavage fluid (BALF) from immunocompromised subjects with lower respiratory tract disease (LRTD). Whether HHV-6B is a pulmonary pathogen is unclear. We tested BALF for HHV-6B DNA using polymerase chain reaction in allogeneic hematopoietic cell transplantation (HCT) recipients who underwent a BAL for evaluation of LRTD from 1992 to 2015. We used multivariable proportional hazards models to evaluate the association of HHV-6B+ BALF with overall mortality, death from respiratory failure, and the effect of anti-HHV-6B antivirals on these outcomes. We used branched-chain RNA in situ hybridization to detect HHV-6 messenger RNA (U41 and U57 transcripts) in lung tissue. We detected HHV-6B+ BALF from 147 of 553 (27%) individuals. Subjects with HHV-6B+ BALF, with or without copathogens, had significantly increased risk of overall mortality (adjusted hazard ratio [aHR], 2.18; 95% CI, 1.41-3.39) and death from respiratory failure (aHR, 2.50; 95% CI, 1.56-4.01) compared with subjects with HHV-6B- BALF. Subjects with HHV-6B+ BALF who received antivirals within 3 days pre-BAL had an approximately 1 log10 lower median HHV-6B BALF viral load, as well as a lower risk of overall mortality (aHR, 0.42; 95% CI, 0.16-1.10), compared with subjects with HHV-6B+ BALF not receiving antivirals. We detected intraparenchymal HHV-6 gene expression by RNA in situ hybridization in lung tissue in all three tested subjects with HHV-6B+ BALF and sufficient tissue RNA preservation. These data provide evidence that HHV-6B detection in BALF is associated with higher mortality in allogeneic hematopoietic cell transplantation recipients with LRTD. Definitive evidence of causation will require a randomized prevention or treatment trial.

Analysis of the prevalence of lower respiratory tract disease among coal dust-exposed workers

Objective To investigate the prevalence and influencing factors of lower respiratory tract disease. Methods The health physical examination data of 4000 coal dust exposed workers who had physical examination in the Institute of Occupational Disease Prevention and Treatment in 2016 were collected and analyzed with SPSS 20.0 software. Results Out of the 4000 coal workers, the Prevalence rate of pulmonary tuberculosis, chronic bronchitis, CWP were 1.00% (40/4000) , 0.63% (25/4000) , 0.43% (17/4000) . 17 coal workers suffered from coal workers. The prevalence of workers both exposed to silicon and coal dust was 1.15% (2/174) , which was higher than that of other the job type. The prevalence of CWP among age groups, length of service and occupational category were found significant difference (P<0.05) , raising with the increase of duration of dust exposure and age increasing (χ2trend=17.171, 5.344, P<0.05) . The prevalence of emphysema and chronic bronchitis between different working years and different ages are all statistically significant (P<0.05) , increasing with duration of dust exposure (χ2trend=9.906, 10.118, P<0.05) . Conclusion The prevalence rate of CWP is not high, and closely related with duration of dust exposure and dust species. The prevalence of lower respiratory tract disease is higher in the tunneling and mining workers and raising with the duration of dust exposure. Key words: Coal worker's pneumoconiosis; Respiratory disease; Prevalence

A systematic review and meta-analyses of the association between 4 mycoplasma species and lower respiratory tract disease in dogs.

BackgroundThe pathogenic role of mycoplasmas in the lower respiratory tract (LRT) of dogs is debated, because mycoplasmas can be isolated from both healthy and sick dogs.ObjectivesTo critically assess available data from controlled observational studies on the role of 4 mycoplasma species in LRT disease of dogs.DesignSystematic review and meta‐analyses.MethodsSeven electronic databases were searched for relevant publications. Risk of bias was assessed by the Newcastle‐Ottawa Scale. Meta‐analyses, stratified by mycoplasmal species, were performed using a random effects Bayesian model with noninformative priors to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs) for the association between Mycoplasma cynos, Mycoplasma canis, Mycoplasma spumans, and Mycoplasma edwardii and LRT disease in dogs.ResultsFive studies were included from 1201 references identified. All studies dealt with M. cynos, whereas 3 dealt with the other mycoplasma species. A significant association was found between M. cynos and LRT disease (Bayesian OR, 3.60; CI, 1.31‐10.29). Conversely, M. canis, M. spumans, and M. edwardii were not significantly associated with LRT signs (Bayesian OR, 1.06; CI, 0.10‐14.63; Bayesian OR, 3.40; CI, 0.16‐54.27; and Bayesian OR, 1.04; CI, 0.05‐23.54, respectively).Conclusions and Clinical ImportanceResults support a pathogenic role of M. cynos and a commensal role of M. canis and M. edwardii in LRT in dogs. Although the association was not significant based on the CI, the point estimate of the Bayesian OR was relatively high for M. spumans, making its role less clear. Mycoplasma cynos‐specific polymerase chain reaction should be considered on samples from dogs with LRT.

Liver abscess: presentation and an assesment of the outcome with various treatment modalities

Background: Liver abscess is a disease of frequent occurrence which is important in the differential diagnosis of upper abdominal and right lower respiratory tract diseases. Liver abscess are space occupying lesion in liver which has a higher incidence of mortality and morbidity. The aim is to study the clinical presentation and compare the outcomes of various treatment modalities.Methods: A Retrospective Study was conducted over a period of 3 years from November 2016 to October 2019, in tertiary care centre, R. L. Jalappa hospital, Tamaka, Kolar, Karnataka, India. 46 cases of liver abscesses were studied. Complete clinical details about the clinical presentation of the cases, investigative work up and treatment modalities adopted were collected. The associated morbidity and mortality of all patients were reviewed.Results: In our study, the mean age was 49.5 years which included male patients most commonly. Pyogenic liver abscess was more common than amoebic liver abscess. Right lobe of the liver was most commonly involved. The common treatment modality was continuous drainage of the abscess cavity by the percutaneous insertion of a pig tail catheter. Surgical intervention for the rupture was done in one patient.Conclusions: In our experience of managing liver abscess, pyogenic liver abscess involving right lobe of the liver was common with the presentation of upper abdominal pain, high grade fever with chills and tender hepatomegaly. Ultrasound abdomen is very useful investigative tool in diagnosis and also in intervention and in the follow up of the condition and to evaluate progression or resolution.

Overview of Current Therapeutics and Novel Candidates Against Influenza, Respiratory Syncytial Virus, and Middle East Respiratory Syndrome Coronavirus Infections.

Emergence and re-emergence of respiratory virus infections represent a significant threat to global public health, as they occur seasonally and less frequently (such as in the case of influenza virus) as pandemic infections. Some of these viruses have been in the human population for centuries and others had recently emerged as a public health problem. Influenza viruses have been affecting the human population for a long time now; however, their ability to rapidly evolve through antigenic drift and antigenic shift causes the emergence of new strains. A recent example of these events is the avian-origin H7N9 influenza virus outbreak currently undergoing in China. Human H7N9 influenza viruses are resistant to amantadines and some strains are also resistant to neuraminidase inhibitors greatly limiting the options for treatment. Respiratory syncytial virus (RSV) may cause a lower respiratory tract infection characterized by bronchiolitis and pneumonia mainly in children and the elderly. Infection with RSV can cause severe disease and even death, imposing a severe burden for pediatric and geriatric health systems worldwide. Treatment for RSV is mainly supportive since the only approved therapy, a monoclonal antibody, is recommended for prophylactic use in high-risk patients. The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging respiratory virus. The virus was first recognized in 2012 and it is associated with a lower respiratory tract disease that is more severe in patients with comorbidities. No licensed vaccines or antivirals have been yet approved for the treatment of MERS-CoV in humans. It is clear that the discovery and development of novel antivirals that can be used alone or in combination with existing therapies to treat these important respiratory viral infections are critical. In this review, we will describe some of the novel therapeutics currently under development for the treatment of these infections.

A prospective multicentre study testing the diagnostic accuracy of an automated cough sound centred analytic system for the identification of common respiratory disorders in children

BackgroundThe differential diagnosis of paediatric respiratory conditions is difficult and suboptimal. Existing diagnostic algorithms are associated with significant error rates, resulting in misdiagnoses, inappropriate use of antibiotics and unacceptable morbidity and mortality. Recent advances in acoustic engineering and artificial intelligence have shown promise in the identification of respiratory conditions based on sound analysis, reducing dependence on diagnostic support services and clinical expertise. We present the results of a diagnostic accuracy study for paediatric respiratory disease using an automated cough-sound analyser.MethodsWe recorded cough sounds in typical clinical environments and the first five coughs were used in analyses. Analyses were performed using cough data and up to five-symptom input derived from patient/parent-reported history. Comparison was made between the automated cough analyser diagnoses and consensus clinical diagnoses reached by a panel of paediatricians after review of hospital charts and all available investigations.ResultsA total of 585 subjects aged 29 days to 12 years were included for analysis. The Positive Percent and Negative Percent Agreement values between the automated analyser and the clinical reference were as follows: asthma (97, 91%); pneumonia (87, 85%); lower respiratory tract disease (83, 82%); croup (85, 82%); bronchiolitis (84, 81%). Conclusion: The results indicate that this technology has a role as a high-level diagnostic aid in the assessment of common childhood respiratory disorders.Trial registrationAustralian and New Zealand Clinical Trial Registry (retrospective) - ACTRN12618001521213: 11.09.2018.

Human Herpesvirus 6B and Pulmonary Disease after Hematopoietic Cell Transplantation

Background: Human herpesvirus 6B (HHV-6B) DNA is frequently detected in bronchoalveolar lavage fluid (BALF) from immunocompromised subjects with lower respiratory tract disease (LRTD). Whether HHV-6B is a pulmonary pathogen is unclear. Methods: We tested prospectively stored BALF for HHV-6B DNA using PCR in allogeneic hematopoietic cell transplantation (HCT) recipients who underwent a BAL for evaluation of LRTD from 1992-2015. We used multivariable proportional hazards models to evaluate the association of HHV-6B+ BALF with overall mortality, death from respiratory failure, and the effect of anti-HHV-6B antivirals on these outcomes. We used branched chain RNA in-situ hybridization (RISH) to detect HHV-6 messenger RNA (U41 and U57) in lung tissue. Findings: We detected HHV-6B+ BALF from 147 of 553 (27%) individuals. Subjects with HHV-6B+ BALF, with or without copathogens, had significantly increased risk of overall mortality (adjusted hazard ratio [HR], 2.06; 95% CI, 1.33-3.21) and death from respiratory failure (aHR, 2.26; 95% CI, 1.44-3.56) compared to subjects with HHV-6B- BALF. Subjects with HHV-6B+ BALF who received antivirals within 3 days pre-BAL had an approximately 1 log10 lower median HHV-6B BALF viral load and lower risk of overall mortality compared to subjects with HHV-6B+ BALF not receiving antivirals (aHR, 0.44; 95% CI, 0.17-1.11). We detected intraparenchymal HHV-6 gene expression by RISH in lung tissue in all 3 tested subjects with HHV-6B+ BALF and sufficient tissue RNA preservation. Interpretation: These data provide evidence that HHV-6B is a pulmonary pathogen after allogeneic HCT. Definitive evidence of causation will require a randomized prevention or treatment trial. Funding: National Institutes of Health, the American Society for Blood and Marrow Transplantation, the HHV-6 Foundation. Declaration of Interest: J.A.H. served as a consultant for Chimerix, Nohla Therapeutics, Inc., and Amplyx and has received research support from Chimerix, Shire, and Karius, Inc. outside the submitted work. C.E.F. has received a grant from Gilead Sciences outside of the submitted work. L.C. has received research support from Sanofi and Immune Design and is a co-inventor on several patents associated with the development of an HSV-2 vaccine; he has no conflicts in the area of HHV-6. M.B. received grants and/or personal fees from Chimerix Inc. and Microbiotix outside the submitted work. L.K.V-V, H.X., E.L.C., S.S., T.S-A, M-L.H, K.R.J., F.M.S, D.M.Z., and W.M.L declare no competing interests. Ethical Approval: The study was approved by the FHCRC Institutional Review Board.

Reduced mortality from lower respiratory tract disease in adult diabetic patients treated with metformin.

Chronic lower respiratory diseases (CLRD) increase the risk of type 2 diabetes, which in turn may worsen lung function. Metformin, a common antidiabetic with anti-inflammatory and antioxidant properties, may improve respiratory outcomes. Therefore, we examined the association of metformin use with the risk of mortality from CLRD. We analysed data from the National Health and Nutrition Examination Survey during 1988-1994 and 1999-2010 for participants aged 40 years or older who had diabetes and were followed up for mortality through 2011. Information on prescription medicine was collected at baseline and CLRD-related mortality during follow-up was defined using the 10th Revision of the International Classification of Diseases (ICD-10). Cox proportional hazards modelling was used to determine the mortality hazard ratio (HR) associated with metformin use, adjusting for relevant covariates. A total of 5266 participants with a median follow-up of 6.1 years were included. The prevalence of metformin use was 31.9% and 1869 participants died during follow-up, including 72 of CLRD. In the adjusted Cox proportional regression analysis, metformin was associated with a decreased risk of CLRD mortality in the overall population (HR: 0.39, 95% CI: 0.15-0.99) and among participants with baseline CLRD (HR: 0.30, 95% CI: 0.10-0.93), after adjusting for age, gender, race/ethnicity, cigarette smoking, body mass index, current asthma and chronic obstructive pulmonary disease (COPD), insulin and other diabetic medications, and glycohaemoglobin level. We found no association between other antidiabetic medications and CLRD mortality. In this sample representative of the U.S. population, metformin was associated with lower CLRD mortality in adults with diabetes.

Лечение заболеваний нижних и верхних дыхательных путей: проблема резистентности и новые подходы в лечении астмы и ХОБЛ (по материалам симпозиума в рамках XIII Национального конгресса терапевтов)

Лечение заболеваний нижних и верхних дыхательных путей: проблема резистентности и новые подходы в лечении астмы и ХОБЛ (по материалам симпозиума в рамках XIII Национального конгресса терапевтов)

Effect of smoking on chronic rhinosinusitis complicated with lower respiratory tract disease

Objective: To study the effect of smoking on chronic rhinosinusitis with lower respiratory tract diseases and underlaying mechanism. Method: The data of 54 patients diagnosed as CRS with lower respiratory disease (Group A) and 60 patients with CRS (Group B) from otolaryngology head and neck surgery in Wuhan Central Hospital and Renmin Hospital of Wuhan University from January 2014 to December 2017 were analyzed, retrospectively. According to the history of smoking, all patients were divided into smoking group (Group C) and non-smoking group (Group D). Nasal secretory microbial cultures were performed. Result: Patients with CRS with lower respiratory disease had higher smoking rate than patients with CRS alone(P<0.05). CRS patients with smoking increased the rate of bacterial infection in lower respiratory and increased the incidence of lower respiratory disease in patients with CRS (P<0.05). Conclusion: Smoking is an important risk factor for CRS complicated with lower respiratory disease.

Transcriptionally Active Lung Microbiome and Its Association with Bacterial Biomass and Host Inflammatory Status.

Alteration of the lung microbiome has been observed in several respiratory tract diseases. However, most previous studies were based on 16S ribosomal RNA and shotgun metagenome sequencing; the viability and functional activity of the microbiome, as well as its interaction with host immune systems, have not been well studied. To characterize the active lung microbiome and its associations with host immune response and clinical features, we applied metatranscriptome sequencing to bronchoalveolar lavage fluid (BALF) samples from 25 patients with chronic obstructive pulmonary disease (COPD) and from nine control cases without known pulmonary disease. Community structure analyses revealed three distinct microbial compositions, which were significantly correlated with bacterial biomass, human Th17 immune response, and COPD exacerbation frequency. Specifically, samples with transcriptionally active Streptococcus, Rothia, or Pseudomonas had bacterial loads 16 times higher than samples enriched for Escherichia and Ralstonia. These high-bacterial-load samples also tended to undergo a stronger Th17 immune response. Furthermore, an increased proportion of lymphocytes was found in samples with active Pseudomonas. In addition, COPD patients with active Streptococcus or Rothia infections tended to have lower rates of exacerbations than patients with active Pseudomonas and patients with lower bacterial biomass. Our results support the idea of a stratified structure of the active lung microbiome and a significant host-microbe interaction. We speculate that diverse lung microbiomes exist in the population and that their presence and activities could either influence or reflect different aspects of lung health. IMPORTANCE Recent studies of the microbiome proposed that resident microbes play a beneficial role in maintaining human health. Although lower respiratory tract disease is a leading cause of sickness and mortality, how the lung microbiome interacts with human health remains largely unknown. Here we assessed the association between the lung microbiome and host gene expression, cytokine concentration, and over 20 clinical features. Intriguingly, we found a stratified structure of the active lung microbiome which was significantly associated with bacterial biomass, lymphocyte proportion, human Th17 immune response, and COPD exacerbation frequency. These observations suggest that the microbiome plays a significant role in lung homeostasis. Not only microbial composition but also active functional elements and host immunity characteristics differed among different individuals. Such diversity may partially account for the variation in susceptibility to particular diseases.

Case presentation: persistent adenovirus B3 infections associated with bronchiolitis obliterans treated with cidofovir in a child with mosaic tetrasomy 9p

BackgroundAdenoviruses (AdV) are non-enveloped, double-stranded DNA viruses with multiple serotypes, which cause a variety of end-organ disease in both immunocompetent and immunocompromised individuals. Some adenoviruses can become latent in the mucosa-associated lymphoid tissue (e.g. adenoids and tonsils), with the potential to reactivate sporadically, leading to upper or lower respiratory tract infection and disease. Bronchiolitis Obliterans (BO) is a rare chronic lung disorder which usually follows a severe insult to the respiratory tract. In children, it is a complication of severe infections (as post-infectious BO), typically manifesting after a severe respiratory infection, in previously healthy pre-school children. Symptoms and signs of air trapping (hyperinflated chest, expiratory wheeze) with persistent oxygen requirement are characteristic. The presence of the unusual mosaic tetrasomy 9p genotype in this case, despite standard cidofovir therapy for persistent or chronic adenovirus infection, may have impacted on the child’s long-term clinical outcomes.Case presentationWe present a case of persistent AdV B3 infection in a 14-month old boy with mosaic tetrasomy 9p, which persisted for 10 weeks, resulting in radiologically-confirmed BO, requiring cidofovir to control the persistent AdV B3 infection and standard therapy with pulsed steroids. We argue that in the presence of the mosaic tetrasomy 9p, earlier antiviral therapy may have decreased the severity of BO, as this mutation is known to be associated with some degree of immune dysregulation.ConclusionsAdenovirus infections are common in children and may persist as latent infections, with subsequent reactivations during loss of immune control, related to systemic illness arising from other causes. In chronic, reactivated AdV infection with pneumonia, BO is a recognised complication. However, in this case, with the presence of the mosaic tetrasomy 9p mutation, earlier antiviral therapy may have reduced such longer term complications, due to the immune dysregulatory nature of this mutation.

CLINICAL AND EPIDEMIOLOGICAL CHARACTERISTICS OF RESPIRATORY SYNCYTIAL VIRUS INFECTION IN CHILDREN THE FIRST YEAR OF LIFE

The purpose was to study the clinical and epidemiological features of respiratory syncytial virus infection in hospitalized children the first year of life with lower respiratory tract diseases in different regions of the Russian Federation (Russia) during the 2015–2016 epidemic season.Materials and methods: in the original study data of a multicentre observational study conducted on the basis of children’s hospitals in St. Petersburg, Arkhangelsk, Kazan, and Saratov are presented. Etiology of acute respiratory viral infections were confirmed by examination of smears from the posterior pharyngeal wall by polymerase chain reaction. The study sample included 991 child’s first year of life with lesions of the lower respiratory tract.Results. In the etiological structure of the surveyed children in the season of 2015-2016, RSVI ranged from 14% to 46,2%, an average of 33%. RSVI dominated in the Centers of St. Petersburg (38,3%), Arkhangelsk (36.2%) and Kazan (42.5 per cent).RSVI significantly more often (p&lt;0.01) leads to the development of bronchiolitis (29.4% against 16.3% and 10.0%, with rhinovirus infection and parainfluenza, respectively. Patients with RSUI often develop pneumonia (23,5%) vs 20.6% and 20,0% with rhinovirus infection, and parainfluenza. Patients with RSVI often suffer severe forms of the disease require oxygen support (13,8%) and treatment in the departmentof intensive care (15,9%).Seasonal peaks of hospitalization due to RSVI in all Centres were recorded in December-April 2015 and 2016. Regional differences in monthly intensity of hospitalization of children with RSVI were established.Thus, the high prevalence of RSVI among children in the first year of life, especially with heavy and complicated forms of lower respiratory tract disorders requiring intensive care benefits, represents a socially important issue, which requires monitoring for effective prevention in children at risk.

Clinical Effectiveness of Influenza Vaccination After Allogeneic Hematopoietic Stem Cell Transplantation: A Cross-sectional, Prospective, Observational Study.

BackgroundVaccination is the primary method for preventing influenza respiratory virus infection (RVI). Although the influenza vaccine is able to achieve serological responses in some allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, its clinical benefits are still uncertain.MethodsIn this prospective, cross-sectional study, we retrospectively analyzed the effect of inactivated trivalent influenza vaccination on the prevalence of influenza RVI in a consecutive cohort of 136 allo-HSCT adult recipients who developed 161 RVI over 5 flu seasons (from 2013 to 2018). Respiratory viruses in upper– and/or lower–respiratory tract specimens were tested using multiplex polymerase chain reaction panel assays.ResultsOverall, we diagnosed 74 episodes (46%) of influenza RVI in 70 allo-HSCT recipients. Influenza RVI occurred in 51% of the non-vaccinated compared to 36% of the vaccinated recipients (P = .036). A multivariate analysis showed that influenza vaccination was associated with a lower prevalence of influenza RVI (odds ratio [OR] 0.39, P = .01). A multivariate risk factor analysis of lower–respiratory tract disease (LRTD) identified 2 conditions associated with the probability of influenza RVI progression: influenza vaccination (OR 0.12, 95% confidence interval [CI] 0.014–1, P = .05) and a high-risk immunodeficiency score (OR 36, 95% CI 2.26–575, P = .011). Influenza vaccination was also associated with a lower likelihood of an influenza-related hospital admission (14% vs 2%, P = .04).ConclusionsThis study shows that influenza vaccination may have a clinical benefit in allo-HSCT recipients with virologically-confirmed RVI, in terms of a lower influenza RVI prevalence, slower LRTD progression, and lower likelihood of hospital admission.

Risk Factors for Parainfluenza Virus Lower Respiratory Tract Disease after Hematopoietic Cell Transplantation

Parainfluenza virus (PIV) infection can progress from upper respiratory tract infection (URTI) to lower respiratory tract disease (LRTD) in immunocompromised hosts. Risk factors for progression to LRTD and presentation with LRTD without prior URTI are poorly defined. Hematopoietic cell transplant (HCT) recipients with PIV infection were retrospectively analyzed using standardized definitions of LRTD. PIV was detected in 540 HCT recipients; 343 had URTI alone and 197 (36%) had LRTD (possible, 76; probable, 19; proven, 102). Among 476 patients with positive nasopharyngeal samples, the cumulative incidence of progression to probable/proven LRTD by day 40 was 12%, with a median time to progression of 7 days (range, 2 to 40). In multivariable analysis monocytopenia (hazard ratio, 2.22; P = .011), steroid use ≥1mg/kg prior to diagnosis (hazard ratio, 1.89; P = .018), co-pathogen detection in blood (hazard ratio, 3.21; P = .027), and PIV type 3 (hazard ratio, 3.57; P = .032) were associated with increased progression risk. In the absence of all 4 risk factors no patients progressed to LRTD, whereas progression risk increased to >30% if 3 or more risk factors were present. Viral load or ribavirin use appeared to have no effect on progression. Among 121 patients with probable/proven LRTD, 64 (53%) presented LRTD without prior URTI, and decreased lung function before infection and lower respiratory co-pathogens were risk factors for this presentation. Mortality was unaffected by the absence of prior URTI. We conclude that the risk of progression to probable/proven LRTD exceeded 30% with ≥3 risk factors. To detect all cases of LRTD, virologic testing of lower respiratory samples is required regardless of URTI symptoms.

New clinical and seasonal evidence of infections by Human Parainfluenzavirus.

Human Parainfluenzaviruses (PIVs) account for a significant proportion of viral acute respiratory infections (ARIs) in children, and are also associated with morbidity and mortality in adults, including nosocomial infections. This work aims to describe PIV genotypes and their clinical and epidemiological distribution. Between December 2016 and December 2017, 6121 samples were collected, and submitted to viral culture and genomic quantification, specifically Parainfluenza 1–4 (PIV1–4), Influenza A and B, Respiratory Syncytial Virus (RSV) A and B, Adenovirus, Metapneumovirus, Coronavirus, Rhinovirus, and Enterovirus. Normalized viral load, as (log10) copies/103 cells, was calculated as virus Ct, determined by multiple qRT-PCR, as a function of the Ct of β-globin. PIV was confirmed in 268 cases (4.37%), and linked to both upper and lower respiratory tract disease, being more frequent in children than in adults (5.23 and 2.43%, respectively). PIV1 and PIV3 were most common (31 and 32.5%, of total PIV positive samples, respectively), with distribution being similar in children and adults, as was viral load. PIV type was correlated with seasonality: PIV3 being more frequent in winter and spring, PIV1 in summer, and PIV 4 in fall. No correlation between vial load and clinical severity was found. Novel findings were that PIV viral load was higher in fall than in other seasons, and PIV4, classically linked to mild respiratory symptoms, was circulating, in children and adults, at all levels of symptoms throughout the year.

A chimeric glycoprotein formulated with a combination adjuvant induces protective immunity against both human respiratory syncytial virus and parainfluenza virus type 3

Human respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3) are major causes of serious lower respiratory tract disease in infants. Currently there is no licensed vaccine against RSV or PIV3. To make an effective bivalent subunit vaccine, a chimeric truncated FRHN protein containing the N-terminal ectodomain of the RSV fusion (F) protein linked to the C-terminal ectodomain of the PIV3 haemagglutinin-neuraminidase (HN) protein was produced in HEK293T cells. Mice, cotton rats and hamsters were immunized intramuscularly (IM) with both RSV F and PIV3 HN (FR+HN) or FRHN, formulated with TriAdj, which consists of poly(I:C), innate defense regulator peptide and poly[di(sodium carboxylatoethylphenoxy)]-phosphazene. Both formulations were immunogenic and elicited full protection from RSV; however, animals vaccinated with FRHN/TriAdj were significantly better protected from PIV3 than animals vaccinated with FR+HN/TriAdj. To develop a potentially more effective subunit vaccine, a chimeric glycoprotein (FRipScHN), encoding the RSV F ectodomain stabilized in the pre-fusion form linked to PIV3 HN was generated. Intramuscular vaccination with FRipScHN/TriAdj induced virus neutralizing antibodies followed by complete protection from RSV and PIV3 replication in the lungs of challenged cotton rats. Furthermore, intranasal vaccination with FRipScHN/TriAdj significantly reduced both RSV and PIV3 replication in cotton rats. Mucosal immunization with FRipScHN/TriAdj also elicited strong antigen-specific mucosal and systemic immune responses in a lamb model. In conclusion, the chimeric FRipScHN protein combined with TriAdj has potential for development of a safe, effective, bivalent vaccine against both RSV and PIV3.

Antibiotic Exposure Prior to Respiratory Viral Infection Is Associated with Progression to Lower Respiratory Tract Disease in Allogeneic Hematopoietic Cell Transplant Recipients

Recent publications note an association between antibiotic exposure and respiratory viral infections (RVIs). Antibiotics affect microbiota and impair immune response against RVIs in mice, and low microbiome diversity is associated with pulmonary complications including viral lower respiratory tract disease (LRTD) in hematopoietic cell transplantation (HCT) recipients. In this study, we examined whether antibiotic exposure was associated with increased risk of disease progression in RVIs post-transplantation. We analyzed patients who underwent allogeneic HCT (June 2008 to February 2016) and had their first RVI due to parainfluenza virus (PIV), respiratory syncytial virus (RSV), or human metapneumovirus (MPV) during the initial 100 days post-transplantation. Antibiotic exposure in the 3 weeks before RVI onset was defined as (1) use of specific antibiotics versus none of these antibiotics and (2) number of antibiotic-days. Cox proportional hazards models were used to examine associations between antibiotic exposures and risk of viral disease progression to proven/probable/possible LRTD. Ninety HCT recipients (84 adults, 6 children) fulfilled study criteria; 33 progressed to LRTD. The number of antibiotic-days was associated with progression to LRTD after adjusting for neutropenia, steroid use, and either lymphopenia (hazard ratio, 1.41 [95% confidence interval, 1.04 to 1.92], P = .027) or monocytopenia (hazard ratio, 1.46 [95% confidence interval, 1.11 to 1.91], P = .006). Specific antibiotic classes was not associated with the outcome. Cumulative antibiotic exposure immediately before RVI onset is a risk factor for disease progression following PIV, RSV, and MPV infections post-transplantation. Larger cohort studies are needed to determine the impact of specific antibiotics or antibiotic classes on disease severity.

Risk Factors for Depression in Patients with Chronic Obstructive Pulmonary Disease.

BackgroundDepression is a major comorbidity in patients with chronic obstructive pulmonary disease (COPD). The aim of this prospective study was to investigate socio-demographic and clinical factors and serum markers of inflammation, including cytokines that, may be a cause or an association with COPD-related depression.Material/MethodsThis study enrolled 53 patients who were hospitalized in the Department of Respiratory Medicine of Hefei First People’s Hospital, China between October 2015 and October 2016. Patients were consecutively recruited who were diagnosed with COPD and without lower respiratory tract disease, psychiatric disorders, or a family history of cognitive disorders. All patients were investigated for symptoms of depression. Lung function testing included forced expiratory volume in 1 second (FEV1). Serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) were measured.ResultsOf the 53 patients with COPD, 40 (75.47%) patients had symptoms of depression. Univariate analysis showed that gender, smoking, a high level of education, duration of a cough, FEV1, and serum CRP level were associated with depression. A multivariate logistic regression model identified two risk factors for depression in patients with COPD: serum CRP level and FEV1.ConclusionsThe findings of this study showed that the risk factors for COPD-related depression included male gender, heavy smoking, higher academic qualifications, and duration of cough, but the two strongest risk factors were a high serum CRP level and low FEV1.

Characteristics and Outcomes of Coronavirus Infection in Children: The Role of Viral Factors and an Immunocompromised State.

Immunocompromised children might be predisposed to serious infections from human coronaviruses (HCoVs), including strains OC43, NL63, HKU1, and 229E; however, the virologic and clinical features of HCoV infection in immunocompromised children have not been compared to those in nonimmunocompromised children. We retrospectively analyzed a cohort of children who presented to Seattle Children's Hospital and in whom HCoV was detected by a multiplex respiratory polymerase chain reaction assay of a nasal sample between October 2012 and March 2016. Lower respiratory tract disease (LRTD) was defined as possible or definite infiltrate seen in chest imaging, need for oxygen, or abnormal lung examination in conjunction with a physician diagnosis of LRTD. We used logistic regression modeling to evaluate risk factors for LRTD and LRTD that necessitated oxygen use (severe LRTD), including an immunocompromised state, in children with HCoV infection. The median ages of 85 immunocompromised and 1152 nonimmunocompromised children with HCoV infection were 6.3 and 1.6 years, respectively. The prevalence of LRTD and of severe LRTD did not differ greatly between the immunocompromised and nonimmunocompromised patients (22% vs 26% [LRTD] and 15% vs 11% [severe LRTD], respectively); however, in a multivariable model, an immunocompromised state was associated with an increased likelihood of severe LRTD (adjusted odds ratio, 2.5 [95% confidence interval, 1.2-4.9]; P = .01). Younger age, having an underlying pulmonary disorder, and the presence of respiratory syncytial virus were also associated with LRTD or severe LRTD in multivariable models. The risks of LRTD or severe LRTD did not differ among the children with different HCoV strains. The presence of a copathogen and host factors, including an immunocompromised state, were associated with increased risk for severe LRTD. Recognizing risk factors for severe respiratory illness might assist in risk stratification.