Relapsing bronchopneumonia due to community-associated methicillin-resistant Staphylococcus aureus: a case report.

BACKGROUND: The emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has increased the incidence of community-onset MRSA infection. Respiratory tract infections caused by MRSA has been noted for their severity; however, repeated relapses that require extended antibiotic therapy are rare. CASE PRESENTATION: We report a case of relapsing bronchopneumonia caused by CA-MRSA in a 56-year-old man. The patient responded to antibiotics, but repeatedly relapsed after stopping treatment. MRSA was consistently isolated from airway specimens during each relapse. Extended oral antibiotic treatment with trimethoprim/sulfamethoxazole (TMP/SMX) for 6 months achieved infection control. Whole-genome sequencing of the isolated strain revealed that the causative agent was sequence type (ST)1/staphylococcal cassette chromosome mec (SCCmec) type IVa, a clone that is rapidly increasing in Japan. DISCUSSION AND CONCLUSIONS: This patient had an unusual course of MRSA bronchopneumonia with repeated relapses. Although the choice of antibiotics for long-term use in MRSA respiratory tract infections has not been well established, TMP/SMX was effective and well tolerated for long-term therapy in this case. The clinical course of infections related to the rapid emerging clone, ST1/SCCmec type IVa warrants further attention.

Granulocyte-macrophage colony-stimulating factor suppresses induction of type I interferon in infants with severe pneumonia.

BACKGROUND: The underlying mechanisms for infantile bronchopneumonia development remain unknown. METHODS: Peripheral blood mononuclear cell (PBMCs) and serum derived from severe and mild infantile bronchopneumonia were obtained, and the expression of various molecules was detected with enzyme-linked immunosorbent assay and quantitative PCR. Such molecules were also detected in granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced bone marrow-derived NFκB2-/- dendritic cells (DCs) or NIK SMI1 (NF-κB-inducing kinase inhibitor) administrated DCs. RESULTS: The relative mRNA expression levels of type I interferons (IFNs) (IFN-α4, IFN-ß), Th17 cell-associated markers (interleukin-17A, retinoic-acid-receptor-related orphan nuclear receptor gamma, and GM-CSF), and non-canonical NF-κB member (NFκB2) were significantly up-regulated in PBMCs and DCs derived from infantile bronchopneumonia compared with healthy controls. However, compared with Th17 cell-associated markers and non-canonical NF-κB molecules, the expression of IFN-α4 and IFN-ß was significantly inhibited in severe infantile bronchopneumonia compared with mild infantile bronchopneumonia. The relative protein expression of the above molecules also showed a similar expression pattern in the PBMCs or serum. NF-κB2 knockout or NIK SMI1 administration could reverse the diminished expression of IFN-ß in GM-CSF-induced bone marrow-derived DCs. CONCLUSIONS: GM-CSF-dependent non-canonical NF-κB pathway-mediated inhibition of type I IFNs production in DCs contributes to the development of severe bronchopneumonia in infant. IMPACT: Granulocyte-macrophage colony-stimulating factor-dependent non-canonical NF-κB pathway-mediated inhibition of type I IFNs production in dendritic cells is critical for the development of infantile bronchopneumonia. Our findings reveal a possible mechanism underlying the development of severe infantile bronchopneumonia. The results could provide therapeutic molecular target for the treatment of such disease.

Risk factors of peripheral venous catheter-related complication and infection in children with bronchopneumonia.

OBJECTIVE: To investigate the risk factors associated with the peripheral venous catheter-related complication and infection in children with bronchopneumonia. METHODS: A total of 185 patients were divided into case group (n = 114) and control group (n = 71) according to the presence of catheter-related infection and complications related to indwelling needle. We performed a multivariate logistic regression analysis to explore the risk factors associated with the infection. RESULTS: Age was divided into 4 categories (0 < age ≤ 1, 1 < age ≤ 3, 3 < age ≤ 6, age > 6). The case group had a higher percentage of patients with 0 < age ≤ 1 than the control group (21% vs. 9.7%) and the age distribution was significant different between the two groups (P = 0.045). The case group had a longer retention time than the control group (≥ 3 days: 56% vs. 35%, P < 0.001). The results of binary logistics regression analysis revealed that the indwelling time and indwelling site were the factors that influenced the complications or bacterial infection. Among the three indwelling sites, the hand is more prone to infection and indwelling needle-related complications than the head (OR: 2.541, 95% CI 1.032 to 6.254, P = 0.042). The longer the indwelling time, the more likely the infection and indwelling needle related complications (OR: 2.646, 95% CI 1.759 to 3.979, P< 0.001). CONCLUSION: Indwelling time and indwelling site are the influencing factors of complications or bacterial infection, which should be paid more attention to prevent the catheter-related infection in children with bronchophenumonia.

Bronchopneumonia with interstitial pneumonia in feedlot cattle: Epidemiologic characteristics of affected animals.

Bronchopneumonia with interstitial pneumonia (BIP) of feedlot cattle is characterized by gross and histologic lesions of cranioventral bronchopneumonia (BP) and caudodorsal interstitial pneumonia. This study described the characteristics and frequency of BIP in western Canadian feedlot cattle and identified epidemiologic differences between BIP and either BP or acute interstitial pneumonia (AIP). The study of 9909 deaths on 4 western Canadian feedlots included 1105 BIP, 1729 BP, and 878 AIP cases. A population of 55 cases with gross, histopathology, and microbiology data was used to validate the primary data set. BIP was the second most common reason for death (or euthanasia) from respiratory disease (1105/9909 cases), and the observed frequency was twice what was expected from random concurrence of BP and AIP. Based on logistic regression models, epidemiologic characteristics of BIP were comparable to those of BP, although BIP cases were more chronic with more instances of clinical illness prior to death. BIP was epidemiologically distinct from AIP. Specifically, BIP more frequently affected steers than heifers, deaths occurred earlier in the feeding period at lower body weights and lower daily weight gains, and BIP cases had longer durations from the first clinical illness to death and more separate instances of clinical illness prior to death. Furthermore, death from BIP mainly occurred in winter and fall, while death from AIP was most frequent in summer. These findings define BIP as a unique condition of feedlot cattle and suggest that chronic BP may promote the development of fatal interstitial lung disease in at-risk cattle.

Bronchopneumonia with interstitial pneumonia in beef feedlot cattle: Characterization and laboratory investigation.

Bronchopneumonia with interstitial pneumonia (BIP) has been considered a variant of acute interstitial pneumonia (AIP) rather than a distinct disease. This study compared 18 BIP, 24 bronchopneumonia (BP), and 13 AIP cases in feedlot beef cattle. Grossly, BIP cases typically had cranioventral lung lesions of similar morphology and extent as BP cases, but the caudodorsal lung appeared overinflated, bulged on section, and had interlobular edema and emphysema. Gross diagnosis of BIP had 83% sensitivity and 73% specificity relative to histopathology. Histologic lesions of BIP in cranioventral areas were of chronic BP, while caudodorsal lesions included alveolar and bronchiolar damage and inflammation, interstitial hypercellularity, and multifocal hemorrhages. In BIP cases, cranioventral lung lesions were more chronic than caudodorsal lesions. Histologic scores and microbiology data were comparable in cranioventral lung of BIP versus BP cases and caudodorsal lung of BIP versus AIP cases, with differences reflecting a more chronic disease involving less virulent bacteria in BIP versus BP. Mycoplasma bovis infection was similarly frequent among groups, and a viral cause of BIP was not identified. Lesion morphology and similar blood cytokine concentrations among groups argued against sepsis as a cause of lung injury. Surfactant dysfunction was identified in BIP and BP, and was only partially the result of protein exudation. These and other findings establish BIP as a distinct condition in which chronic cranioventral BP precedes acute caudodorsal interstitial lung disease, supporting a role of chronic inflammation in heightened sensitivity to 3-methylindole or another lung toxicant.

Bronchogenic cyst with concurrent chronic suppurative bronchopneumonia in a 10-year-old German shepherd dog.

A 10-year-old spayed female German shepherd dog was transferred for acute respiratory distress and a bulla-like pulmonary lesion identified on referral radiographs. Computed tomography (CT) imaging identified a bronchiole from a dilated left cranial lobar bronchus terminating into a partially fluid-filled, cyst-like pulmonary lesion and surrounding multilobar pulmonary hyperattenuation. After failure of medical management, a left cranial lung lobectomy was done. Histopathology was consistent with a bronchogenic cyst and chronic, suppurative bronchopneumonia of the remaining parenchyma. Bronchogenic cysts with concurrent bronchopneumonia should be considered in older German shepherd dogs with acute respiratory distress that fail medical management. Key clinical message: Canine bronchogenic cyst is an uncommon condition that previously has only been reported in younger German shepherd dogs. This case highlights the importance of considering this condition in a senior German shepherd dog with no prior respiratory history, as well as the difficulty of medical management with concurrent bronchopneumonia.

Kyste bronchogénique avec bronchopneumonie suppurée chronique concomitante chez un chien berger allemand de 10 ans. Une chienne berger allemand stérilisée âgée de 10 ans a été transférée pour une détresse respiratoire aiguë et une lésion pulmonaire de type bulle identifiée sur les radiographies de référence. L'imagerie par tomodensitométrie (TDM) a identifié une bronchiole d'une bronche lobaire crânienne gauche dilatée se terminant par une lésion pulmonaire ressemblant à un kyste partiellement rempli de liquide et une hyperatténuation pulmonaire multipolaire. Après échec de la prise en charge médicale, une lobectomie pulmonaire crânienne gauche a été effectuée. L'histopathologie était compatible avec un kyste bronchogénique et une bronchopneumonie suppurée chronique du parenchyme restant. Les kystes bronchogéniques avec bronchopneumonie concomitante doivent être envisagés chez les chiens berger allemand âgés souffrant de détresse respiratoire aiguë qui échouent à la prise en charge médicale.Message clinique clé :Le kyste bronchogénique canin est une affection rare qui n'a été signalée auparavant que chez les jeunes bergers allemands. Ce cas met en évidence l'importance de considérer cette condition chez un chien berger allemand âgé sans antécédents respiratoires, ainsi que la difficulté de la prise en charge médicale avec une bronchopneumonie concomitante.(Traduit par Dr Serge Messier).

Mannheimia haemolytica serovars associated with respiratory disease in cattle in Great Britain.

BACKGROUND: Mannheimia haemolytica is commonly associated with respiratory disease in cattle worldwide as a cause of fibrinous pneumonia, bronchopneumonia and pleuritis. M. haemolytica is further subdivided into 12 serovars, however not all are considered to be pathogenic in cattle. The study aim was to determine the most common serovars of M. haemolytica associated with respiratory disease in cattle in Great Britain, which is currently unknown and could be useful information for clinicians when considering preventative strategies. RESULTS: One hundred four M. haemolytica isolates isolated from bovine clinical pathology and post-mortem samples from pneumonia cases between 2016 and 2018 were tested using a multiplex PCR assay to identify M. haemolytica serovars A1, A2 and A6. 46 isolates (44.2%) typed as M. haemolytica serovar A1, 31 (29.8%) as M. haemolytica serovar A2 and 18 isolates (17.3%) as M. haemolytica serovar A6. Nine isolates (8.7%) were not A1, A2 or A6 so were considered to belong to other serovars or were not typable. CONCLUSION: This study highlights the importance of M. haemolytica serovars other than A1 which may be responsible for respiratory disease in cattle and could help guide the veterinarian when making choices on preventative vaccination programmes.

Sleep cycle in children with severe acute bronchopneumonia during mechanical ventilation at different depths of sedation.

BACKGROUND: To investigate the characteristics of sleep cycle in children with severe acute bronchopneumonia treated with invasive mechanical ventilation at different sedation depths. METHODS: We included 35 pediatric patients with severe acute bronchopneumonia treated using mechanical ventilation in Pediatric Intensive Care Unit of Shengjing Hospital of China Medical University. They were divided into deep sedation group (n = 21; ramsay score 5-6) and light sedation group (n = 14; ramsay score3-4) based on sedation depth achieved during mechanical ventilation. Long-term video electroencephalography (EEG) monitoring was performed within the first 24 h after starting mechanical ventilation and after weaning from mechanical ventilation and discontinuing sedatives and analgesics. The results were analyzed and compared with those of normal children to analyze changes in sleep cycle characteristics at different sedation depths and mechanical ventilation stages. RESULTS: There were 29 cases altered sleep architecture. The deep sedation group had a significantly higher incidence of sleep architecture altered, total sleep duration, and non-rapid eye movement sleep-1 (NREM-1) loss incidence than the light sedation group. Moreover, the deep sedation group had a significantly lower awakening number and rapid eye movement sleep (REM) percentage than the light sedation group. The sleep cycle returned to normal in 27 (77%) patients without NREM-1 or REM sleep loss. CONCLUSIONS: Deep sedation during mechanical ventilation allows longer total sleep duration, fewer awakenings, and an increased deep sleep proportion, but sleep architecture is severely altered. After weaning from mechanical ventilation and sedative discontinuation, lightly sedated children exhibit better sleep recovery.

Building Patient Trust in Nurses Can Improve Respiratory Function, Quality of Life and Self-Management Ability in Patients with Bronchopneumonia.

Objective: This study aimed to investigate the effect of building Trust in Nurses (TN) on improving respiratory function, quality of life (QoL) and the self-management ability of patients with bronchopneumonia. Methods: A total of 92 patients hospitalized in The Second Affiliated Hospital of Harbin Medical University in China between November 2019 and October 2020 were prospectively included in the study. Patients were randomly assigned to either the TN group (intervention group; n = 46) or routine nursing (control group; n = 46). Clinical symptom improvement time, pre- and post- pulmonary function (PF) after the nursing intervention, QoL, self-management ability, patient compliance and satisfaction in the 2 groups were recorded and compared. Results: Clinical symptom improvement time, including the resolution of cough, lung rales, expectoration and wheezing in the TN group were significantly shorter than in the control group (P < .001). PF, including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and mid-maximum expiratory flow (MMEF) velocity 25% to 75% in the TN group were significantly better than in the control group (P < .001). In addition, patient QoL based on the 36-Item Short Form Health Survey (SF-36) (P < .001), self-management ability based on the Exercise of Self-Care Agency Scale (ESCA) (P < .001), good compliance rate (P = .024) and satisfaction rate (P = .024) in the TN group were all significantly better than in the control group. Conclusion: Building TN was an effective intervention in patients with bronchopneumonia, and was beneficial for improving clinical symptoms, PF, QoL, self-management ability, compliance and the satisfaction rate in patients.

Respiratory Distress and it's Clinical Outcome in Tertiary Care Centre.

Respiratory distress refers to any kind of subjective difficulty in breathing. It manifests as one or more of the following: altered breathing pattern, forced breathing efforts or obstructed breathing. Respiratory distress is defined as a clinical state characterized by increased respiratory rate(tachypnoea) and respiratory efforts. Respiratory distress is a common cause for admission in the RICU. It's the main symptom of various other systemic illness. Respiratory diseases are the most common cause for respiratory distress.Bronchiolitis and pneumonia are the most common cause of respiratory distress. More than 1/3rd of deaths observed in adults presented with severe respiratory distress and respiratory failure. Almost 2/3 rd of deaths were due to pneumonia with or without pleural involvement and made a major contribution to childhood mortality in RICU. MATERIAL: The study included clinical profile and outcome of Respiratory distress patients admitted due to Pneumonia in RICU during the period from October 2020-April 2021. Results on continuous measurements were presented on Mean±SD and results on categorical measurements were presented in Frequency (Percentage). OBSERVATION: Most common causes in our study was bronchopneumonia (39.7%). Among 204 patients in our study, nebulisation was required in 163(79.9%), oxygen in 182(89.2%), NIV in 72(35.3%) and invasive ventilation in 30(14.7%). Mean duration of oxygen, NIV and invasive ventilation requirement in our study was 2.16, 1.93 & 2.06 days respectively. Some patients required ICD insertion in 7(3.43%),bronchoscopic removal of FB in 1,thoracotomy in 1 and adrenaline injection in 1 patient .Inotropic support was required in 18(8.82%) patients. Out of 204 patients in our study, the average duration of stay in RICU was 4.56days, with minimum duration of stay was 4hr and maximum duration of stay was 16 days. The mortality was more in more than 50years (42.85%). The mortality was more in male patients 8(57.16%) compared to female patients 6(42.85%). The most common causes for mortality were bronchopneumonia 4(28.57%) and lobar pneumonia 2(14.28%). CONCLUSION: Respiratory diseases are the most common causes of respiratory distress in adults. Non respiratory diseases causing respiratory distress is 18.62%. Most common diseases causing respiratory distress are bronchopneumonia and lobar pneumonia. Most common non-respiratory cause was DKA. Common presenting complaints in patient with respiratory distress are SOB, cough and fever. Most common respiratory distress signs were tachypnoea, nasal flaring and subcostal retractions. Mortality rate in patient with respiratory distress is 6.87%. Mortality is more in males than females Most common causes of mortality in patients with respiratory distress are bronchopneumonia and lobar pneumonia.

Laboratory investigation of cases of fatal bacterial pneumonia in dairy cows.

Objective: Bacterial bronchopneumonia occurs in mature dairy cows but much of the information is extrapolated from knowledge of the disease in calves. The study was prompted by perceptions of an increasing occurrence and a paucity of information on fatal Mannheimia haemolytica pneumonia in dairy cows in Ontario. The study objectives were to describe the seasonality, main pathogens involved, and suggested predisposing factors for cases of fatal bacterial bronchopneumonia in mature dairy cows submitted for postmortem examination to a diagnostic laboratory, and to evaluate if the frequency of such submissions has increased over time. Animals: Mature dairy cows. Procedure: Retrospective study of cases submitted for postmortem examination to a diagnostic laboratory from 2007-2020 that were diagnosed as bacterial bronchopneumonia. Results: Most of the postmortem cases of bacterial bronchopneumonia in dairy cows were submitted from November to February (54% of cases). Mannheimia haemolytica was isolated from lung of 61/101 cases. Viruses were only identified in 8/55 cases tested. A minority (29/92) of bacterial isolates had in vitro resistance to antimicrobials used to treat pneumonia. Frequently suggested predisposing factors included recent introductions or movement of animals, recent or imminent calving, inclement weather, concurrent diseases, and poor ventilation in barns. Conclusion and clinical relevance: This study describes seasonal and annual trends, major pathogens, antimicrobial resistance profiles, and suggested predisposing factors in Ontario dairy cows submitted to a diagnostic laboratory for postmortem investigation of pneumonia and provides insights for understanding why outbreaks occur.

Objectif: La bronchopneumonie bactérienne survient chez les vaches laitières matures, mais une grande partie de l'information est extrapolée à partir de la connaissance de la maladie chez les veaux. L'étude a été motivée par la perception d'une occurrence croissante et d'un manque d'information sur la pneumonie mortelle à Mannheimia haemolytica chez les vaches laitières en Ontario. Les objectifs de l'étude étaient de décrire la saisonnalité, les principaux agents pathogènes impliqués et les facteurs prédisposants suggérés pour les cas de bronchopneumonie bactérienne mortelle chez les vaches laitières matures soumises à un examen post-mortem à un laboratoire de diagnostic, et d'évaluer si la fréquence de telles soumissions a augmenté au fil du temps. Animaux: Vaches laitières matures. Procédure: Étude rétrospective des cas soumis pour examen post-mortem à un laboratoire de diagnostic, entre 2007 et 2020, qui ont été diagnostiqués comme une bronchopneumonie bactérienne. Résultats: La plupart des cas post-mortem de bronchopneumonie bactérienne chez les vaches laitières ont été soumis de novembre à février (54 % des cas). Mannheimia haemolytica a été isolée du poumon de 61/101 cas. Des virus n'ont été identifiés que dans 8/55 cas testés. Une minorité (29/92) d'isolats bactériens présentaient une résistance in vitro aux antimicrobiens utilisés pour traiter la pneumonie. Les facteurs prédisposants fréquemment suggérés comprenaient des introductions ou des déplacements récents d'animaux, un vêlage récent ou imminent, des conditions météorologiques défavorables, des maladies concomitantes et une mauvaise ventilation dans les étables. Conclusion et pertinence clinique: Cette étude décrit les tendances saisonnières et annuelles, les principaux agents pathogènes, les profils de résistance aux antimicrobiens et les facteurs prédisposants suggérés chez les vaches laitières de l'Ontario soumises à un laboratoire de diagnostic pour une enquête post-mortem sur la pneumonie et fournit des informations pour comprendre pourquoi les épidémies se produisent.(Traduit par Dr Serge Messier).

Delayed Surgical Management of Acute Type A Aortic Dissection in a Patient with Recent COVID-19 Infection and Post-COVID-19 Bronchopneumonia-Case Report and Review of Literature.

Ever since it was first described in 1760, acute type A aortic dissection has created difficulties in its management. The recent COVID-19 pandemic revealed that extrapulmonary manifestations of this condition may occur, and recent reports suggested that aortic dissection may be amongst them since it shares a common physiopathology, that is, hyper-inflammatory syndrome. Cardiac surgery with cardiopulmonary bypass in the setting of COVID-19-positive patients carries a high risk of postoperative respiratory failure. While the vast majority accept that management of type A aortic dissection requires urgent surgery and central aortic therapy, there are some reports that advocate for delaying surgery. In this situation, the risk of aortic rupture must be balanced with the possible benefits of delaying urgent surgery. We present a case of acute type A dissection with COVID-19-associated bronchopneumonia successfully managed after delaying surgery for 6 days.

Mortality due to respiratory infections: an alert study before COVID-19 pandemic.

Objective: Respiratory tract infections remain a common problem in clinical practice with high morbidity and mortality worldwide. In Portugal, pneumonia was the third leading death cause in 2018. Due to COVID-19 pandemic, there is a growing concern about the burden of respiratory diseases and preventable risk factors. The present study started before the pandemic and its aim was to determine the occurrence of pneumonia/bronchopneumonia in a postmortem series and to characterize its circumstantial context. Methods: A retrospective anatomopathological study was performed on cases with acute pneumonia/bronchopneumonia at the Medicolegal Portuguese Institute (2011-2017). Results: In an autopsy series of 737 patients, 521 were male and 675 presented comorbidities. The mean age was 63.87 ± 19.8 years. The most common acquisition site was community (65.1%), as natural death (65.5%). Concerning the manner of death, most cases (48.0%) were sudden deaths, followed by accidents (29.2%). A statistically significant association was observed between the medicolegal etiology and the place of infection acquisition, with higher prevalence of natural obitus (91.0%) in community-acquired pneumonia/bronchopneumonia versus higher prevalence of violent obitus in hospital-acquired pneumonia/bronchopneumonia (82.1%) (p < 0.001). Conclusions: Forensic anatomopathological postmortem data may contribute to better understand community and hospital pulmonary infections.

Antibiotic therapy of postoperative bronchopneumonia in patients after lung resections - single-site experience.

INTRODUCTION: Infectious complications after lung surgery are the most important factor that affects mortality and morbidity, prolongs hospital stays and increases financial costs. According to various sources, 30-day mortality after lung resections reaches 123%. Infectious complications account for 2075% of overall mortality. The infections most often present as postoperative pneumonia (POP), and their treatment is based on empirical and targeted antibiotic therapy. Any time lag in initiating effective antibiotic therapy significantly increases morbidity and mortality. Postoperative pneumonia is defined according to current guidelines of the American Thoracic Society of 2016 as nosocomial or ventilator pneumonia in patients after surgery. METHODS: Evaluation of risk factors, infectious agents, morbidity and mortality in patients after lung resections at a single site in the period from 1 January 2018 to 31 December 2019. RESULTS: Of our group of 190 patients, 21 (11.1%) patients had POP which was severe in 6 (33% with POP) patients, and 11 patients with POP required artificial oxygenation for saturation below 92%. Two patients with POP had to be intubated for respiratory failure, and 3 patients required noradrenaline circulatory support. One patient with severe POP died of multiorgan failure after developing refractory sepsis. CONCLUSION: Early identification of lung infection and early initiation of POP therapy are critical points for reducing morbidity and mortality after lung resections. Advanced antibiotic regimens for POP stratify the risk of mortality and infection with multidrug-resistant bacterial strains. However, the regimes require modification according to the epidemiological situation at the site with individualization of the specific procedure. Other research tasks include identification of valid markers of the initial stages of infection, and targeting of antibiotic therapy according to risk stratification and the relationship with physiological flora.

Inhaled Steroids, Circulating Eosinophils, Chronic Airway Infection, and Pneumonia Risk in Chronic Obstructive Pulmonary Disease. A Network Analysis.

Rationale: Treatment of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroids (ICS) is controversial, because it can reduce the risk of future exacerbations of the disease at the expense of increasing the risk of pneumonia.Objectives: To assess the relationship between the presence of chronic bronchial infection (CBI), reduced number of circulating eosinophils, ICS treatment, and the risk of pneumonia in patients with COPD.Methods: This was a post hoc long-term observational study of an historical cohort of 201 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease II-IV) who were carefully characterized (including airway microbiology) and followed for a median of 84 months. Results were analyzed by multivariate Cox regression and network analysis.Measurements and Main Results: Mean age was 70.3 years, 90.5% of patients were male, mean FEV1 was 49%, 71.6% of patients were treated with ICS, 57.2% of them had bronchiectasis, and 20.9% had <100 blood eosinophils/µl. Pathogenic microorganisms were isolated in 42.3% of patients, and 22.4% of patients fulfilled the definition of CBI. During follow-up, 38.8% of patients suffered one or more episodes of pneumonia, with CBI (hazard ratio [HR], 1.635) and <100 eosinophils/µl (HR, 1.975) being independently associated with the risk of pneumonia, particularly when both coexist (HR, 3.126). ICS treatment increased the risk of pneumonia in those patients with <100 eosinophils/µl and CBI (HR, 2.925).Conclusions: Less than 100 circulating eosinophils/µl combined with the presence of CBI increase the risk of pneumonia in patients with COPD treated with ICS.

MiR-216a-5p alleviates LPS-induced inflammation in the human bronchial epithelial cell by inhibition of TGF-ß1 signaling via down-regulating TGFBR2.

OBJECTIVE: Bronchopneumonia is a common respiratory infection disease and is the leading cause of hospitalization in children under 5 years of age. Inflammation is the primary response caused by bronchopneumonia. But the detailed underlying mechanism of inflammation in bronchopneumonia remains unclear. Therefore, this study focused on studying the effect of miR-216a-5p on inflammation induced by bronchopneumonia and investigate the potential mechanism underlying it. METHODS: Human bronchial epithelial cells (BEAS-2B) were stimulated using lipopolysaccha-rides (LPS) to trigger bronchopneumonia in vitro. The production of interleukin (IL)-1ß, IL-6, and Tumor necrosis factor (TNF)-α was measured using the enzyme-linked immunosorbent assay. The luciferase assay was conducted to explore the relationship between miR-216a-5p and TGFBR2. Quantitative real-time polymerase chain reaction and western blot were used to detect the gene expression. RESULTS: miR-216a-5p gene expression decreased in BEAS-2B cells stimulated by LPS. Overexpression of miR-216a-5p suppressed the elevated levels of IL-1ß, IL-6, and TNF-α induced by LPS. Transforming growth factor-beta receptor 2 (TGFBR2) proved to be a direct target of miR-216a-5p, and they negatively modulated TGFBR2 expression. In addition, overexpression of miR-216a-5p inhibited LPS-induced protein levels of TGFBR2,transforming growth factor (TGF)-ß1, and phosphorylation of SMAD family member 2 (smad2),. This ectopic expression of miR-216a-5p was restored by overexpressed TGFBR2. CONCLUSION: miR-216a-5p was decreased in LPS-stimulated BEAS-2B cells. Overexpressed miR-216a-5p suppressed LPS-induced inflammation in BEAS-2B cells by inhibition of TGF-ß1 signaling via down-regulating TGFBR2. miR-216a-5p may be a valuable target for anti-inflammation treatment in bronchopneumonia.Bronchopneumonia is a common respiratory infection disease and is the main cause of hospitalization in children under 5 years of age. Inflammation is a primary response caused by bronchopneumonia. But the detailed underlying mechanism of inflammation in bronchopneumonia remains unclear. Therefore, this study focused on studying the effect of miR-216a-5p on inflammation caused by bronchopneumonia and investigate the potential mechanism underlying it. In this study, human bronchial epithelial cells (BEAS-2B) were stimulated using lipopolysaccharides (LPS) to trigger bronchopneumonia in vitro. miR-216a-5p was decreased in BEAS-2B cells stimulated by LPS. Overexpression of miR-216a-5p suppressed the elevated levels of interleukin (IL)-1ß, IL-6, and Tumor necrosis factor (TNF)-α induced by LPS. Transforming growth factor-beta receptor 2 (TGFBR2) proved to be a direct target of miR-216a-5p, and they negatively modulated TGFBR2 expression. In addition, overexpression of miR-216a-5p inhibited LPS-induced protein levels of TGFBR2,transforming growth factor-beta 1 (TGF-ß1), and phosphorylation of SMAD family member 2 (smad2. This ectopic overexpression of miR-216a-5p was restored by overexpressed TGFBR2. In conclusion, miR-216a-5p was decreased in LPS-stimulated BEAS-2B cells. Overexpressed miR-216a-5p suppressed LPS-induced inflammation in BEAS-2B cells by inhibition of TGF-ß1 signaling via down-regulating TGFBR2. miR-216a-5p may be a valuable target for anti-inflammation treatment in bronchopneumonia.

Utility of CDC Screening Guidelines and Autopsy Findings in Identifying Decedents Who Die of SARS-CoV-2 Infection.

ABSTRACT: We assess the utility of a Centers for Disease Control and Prevention (CDC) guidelines-based coronavirus disease 2019 (COVID-19) screening checklist for postmortem severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surveillance, detailing the relationship between the histologic findings at autopsy and attribution of death to COVID-19.SARS-CoV-2 nasopharyngeal swabs were collected at the time of autopsy in all "checklist-positive" decedents. Additional "checklist-negative" decedents were randomly tested daily. Lung slides were blindly reviewed by 3 pathologists, assessing for the presence of diffuse alveolar damage (DAD) and other findings. Sixteen decedents had positive postmortem SARS-CoV-2 nasopharyngeal swabs and underwent complete autopsies. Seven decedents had positive screening checklists. Of these, 4 had DAD and 1 had COVID-19-associated thromboembolic disease. Of the 9 decedents with negative screening checklists, 2 had DAD, but only 1 was attributed to COVID-19; the other was likely drug related. Acute bronchopneumonia was the second most common finding, and aspiration was the likely etiology in cases without concomitant DAD. COVID-19-related DAD was identified more commonly in decedents who screened positive by CDC checklist, but false-negatives did occur. Medical examiner offices should maintain a low threshold for random testing of decedents even when COVID-19 is not suspected.

Isolation of Drug-Resistant Gallibacterium anatis from Calves with Unresponsive Bronchopneumonia, Belgium.

Gallibacterium anatis is an opportunistic pathogen, previously associated with deaths in poultry, domestic birds, and occasionally humans. We obtained G. anatis isolates from bronchoalveolar lavage samples of 10 calves with bronchopneumonia unresponsive to antimicrobial therapy. Collected isolates were multidrug-resistant to extensively drug-resistant, exhibiting resistance against 5-7 classes of antimicrobial drugs. Whole-genome sequencing revealed 24 different antimicrobial-resistance determinants, including genes not previously described in the Gallibacterium genus or even the Pasteurellaceae family, such as aadA23, blaCARB-8, tet(Y), and qnrD1. Some resistance genes were closely linked in resistance gene cassettes with either transposases in close proximity or situated on putative mobile elements or predicted plasmids. Single-nucleotide polymorphism genotyping revealed large genetic variation between the G. anatis isolates, including isolates retrieved from the same farm. G. anatis might play a hitherto unrecognized role as a respiratory pathogen and resistance gene reservoir in cattle and has unknown zoonotic potential.

Activation of Heme Oxygenase Expression by Cobalt Protoporphyrin Treatment Prevents Pneumonic Plague Caused by Inhalation of Yersinia pestis.

Pneumonic plague, caused by the Gram-negative bacteria Yersinia pestis, is an invasive, rapidly progressing disease with poor survival rates. Following inhalation of Y. pestis, bacterial invasion of the lungs and a tissue-damaging inflammatory response allows vascular spread of the infection. Consequently, primary pneumonic plague is a multiorgan disease involving sepsis and necrosis of immune tissues and the liver, as well as bronchopneumonia and rampant bacterial growth. Given the likely role of the hyperinflammatory response in accelerating the destruction of tissue, in this work we evaluated the therapeutic potential of the inducible cytoprotective enzyme heme oxygenase 1 (HO-1) against primary pneumonic plague. On its own, the HO-1 inducer cobalt protoporphyrin IX (CoPP) provided mice protection from lethal challenge with Y. pestis CO92 with improved pulmonary bacterial clearance and a dampened inflammatory response compared to vehicle-treated mice. Furthermore, CoPP treatment combined with doxycycline strongly enhanced protection in a rat aerosol challenge model. Compared to doxycycline alone, CoPP treatment increased survival, with a 3-log decrease in median bacterial titer recovered from the lungs and the general absence of a systemic hyperinflammatory response. In contrast, treatment with the HO-1 inhibitor SnPP had no detectable impact on doxycycline efficacy. The combined data indicate that countering inflammatory toxicity by therapeutically inducing HO-1 is effective in reducing the rampant growth of Y. pestis and preventing pneumonic plague.

Targeting novel genes for simultaneous detection of five fungal and bacterial agents from BAL samples using multiplex PCR assay.

The main purpose of our study was to evaluate multiplex PCR assay targeting novel genes for detection of five fungal and bacterial agents in BAL samples; because many fungi and bacteria that cause respiratory infections have similar clinical symptoms, diagnosing and differentiating them are therefore essential to controlling and treating them. A total of 100 BAL specimens from a mycobacterium and mycology laboratory were collected from patients suspected of having TB or other respiratory diseases. Novel DNA targets for Aspergillus, Nocardia, Cryptococcus, and Streptomyces were found using modified comparative genomic analysis. Afterward, the primers were designed based on novel targets, and the sensitivity and specificity of the newly designed primers were evaluated. These primers, along with specific primers for M. tuberculosis (SDR), were used in a multiplex PCR assay. The results showed the culture test to be more sensitive than the PCR assay in detecting M. tuberculosis. However, in the detection of Aspergillus, the PCR assay was more sensitive than the culture test. We also found one positive culture and two positive PCR assays for Nocardiosis. Cryptococcal infections and Streptomyces associated with lung diseases were not identified by the culture test nor by the PCR assay. The multiplex PCR is one of the cheapest molecular diagnostic tests readily available for BAL samples in clinical laboratories. This assay can be used for early reports of the causative agents and for treating patients with appropriate drugs at an early stage.