Description of two fatal cases of melioidosis in Mexican children with acute pneumonia: case report.

BACKGROUND: Melioidosis is an infectious disease caused by Burkholderia pseudomallei. In Mexico, the disease is rarely diagnosed in humans and there is no evidence of simultaneous environmental isolation of the pathogen. Here, we describe clinical profiles of fatal cases of melioidosis in two children, in a region without history of that disease. CASE PRESENTATION: About 48 h before onset of symptoms, patients swam in a natural body of water, and thereafter they rapidly developed fatal septicemic illness. Upon necropsy, samples from liver, spleen, lung, cerebrospinal fluid, and bronchial aspirate tissues contained Burkholderia pseudomallei. Environmental samples collected from the locations where the children swam also contained B. pseudomallei. All the clinical and environmental strains showed the same BOX-PCR pattern, suggesting that infection originated from the area where the patients were swimming. CONCLUSIONS: The identification of B. pseudomallei confirmed that melioidosis disease exists in Sonora, Mexico. The presence of B. pseudomallei in the environment may suggest endemicity of the pathogen in the region. This study highlights the importance of strengthening laboratory capacity to prevent and control future melioidosis cases.

Legionnaire's disease presenting as bilateral central scotomata: a case report.

BACKGROUND: Legionnaire's disease is one of the major causes of community-acquired pneumonia and is occasionally complicated by neurological symptoms. However, reports of ocular lesions due to Legionnaire's disease are limited. CASE PRESENTATION: We report the case of a patient with Legionnaire's disease presenting as bilateral central scotomata due to retinal lesions. The patient consulted due to fever and bilateral central scotomata, as well as other extrapulmonary symptoms. Optical coherence tomography (OCT) showed bilateral accumulations of fluid under the retina, and the patient was diagnosed with bilateral exudative retinal detachment. Later, Legionnaire's disease was confirmed by pulmonary infiltrates on chest imaging and positive urinary antigen for Legionella pneumophila. After administration of antibiotics, the bilateral central scotomata and bilateral subretinal fluid accumulations completely resolved, as did the other extrapulmonary symptoms and the pulmonary infiltrates. Thus, the bilateral central scotomata due to exudative retinal detachment were thought to be caused by Legionnaire's disease. CONCLUSIONS: This case demonstrates that Legionnaire's disease can present as bilateral central scotomata. We may consider the possibility of extrapulmonary involvement complicating Legionnaire's disease when we encounter bilateral ocular lesions in patients with fever and pneumonia.

Immunotherapy-related pneumonitis and bacterial pneumonia after the successful treatment of metastatic malignant melanoma with pembrolizumab: A case report.

INTRODUCTION: Pembrolizumab, a monoclonal antibody targeting programmed cell death-1 (PD-1), is approved as a therapy for unresectable or metastatic melanoma. Immunotherapy-associated pneumonitis is an uncommon event. PATIENT CONCERNS: A 73-year-old man was admitted to our hospital with a history of melanoma on the left side of the face (resected in December 2012) and metastasis to the left lung upper lobe (resected in November 2016). Recurrence of metastasis to the bilateral lungs and left pleura was detected in April 2018. A complete response was achieved following treatment with pembrolizumab, with lower limb rashes the only adverse events occurring during therapy. The patient was readmitted in March 2019 with a productive cough, shortness of breath, and mild fever, and sputum culture identified Escherichia coli. DIAGNOSIS: A diagnosis of pneumonia was made, and although cough and shortness of breath responded to ceftazidime and levofloxacin, but fever and poor appetite persisted. Computed tomography showed no improvement in the bilateral lower lobe lesions. Prednisone was initiated based on a clinical diagnosis of immunotherapy-related pneumonitis. The response to prednisone confirmed the diagnosis. INTERVENTIONS: The patient first received ceftazidime and levofloxacin, but the symptoms persisted. Prednisone was initiated based on a clinical diagnosis of immunotherapy-related pneumonitis. OUTCOME: Complete resolution of the bilateral lung lesions occurred after 45 days of prednisone therapy. CONCLUSION: This case report highlights that both pneumonitis and bacterial pneumonia can occur as complications of anti-PD-1 immunotherapy.

Defining the Mechanistic Correlates of Protection Conferred by Whole-Cell Vaccination against Pseudomonas aeruginosa Acute Murine Pneumonia.

Pseudomonas aeruginosa is a Gram-negative pathogen that causes severe pulmonary infections associated with high morbidity and mortality in immunocompromised patients. The development of a vaccine against P. aeruginosa could help prevent infections caused by this highly antibiotic-resistant microorganism. We propose that identifying the vaccine-induced correlates of protection against P. aeruginosa will facilitate the development of a vaccine against this pathogen. In this study, we investigated the mechanistic correlates of protection of a curdlan-adjuvanted P. aeruginosa whole-cell vaccine (WCV) delivered intranasally. The WCV significantly decreased bacterial loads in the respiratory tract after intranasal P. aeruginosa challenge and raised antigen-specific antibody titers. To study the role of B and T cells during vaccination, anti-CD4, -CD8, and -CD20 depletions were performed prior to WCV vaccination and boosting. The depletion of CD4+, CD8+, or CD20+ cells had no impact on the bacterial burden in mock-vaccinated animals. However, depletion of CD20+ B cells, but not CD8+ or CD4+ T cells, led to the loss of vaccine-mediated bacterial clearance. Also, passive immunization with serum from WCV group mice alone protected naive mice against P. aeruginosa, supporting the role of antibodies in clearing P. aeruginosa We observed that in the absence of T cell-dependent antibody production, mice vaccinated with the WCV were still able to reduce bacterial loads. Our results collectively highlight the importance of the humoral immune response for protection against P. aeruginosa and suggest that the production of T cell-independent antibodies may be sufficient for bacterial clearance induced by whole-cell P. aeruginosa vaccination.

Lateral position during severe mono-lateral pneumonia: an experimental study.

Patients with mono-lateral pneumonia and severe respiratory failure can be positioned in lateral decubitus, with the healthy lung dependent, to improve ventilation-perfusion coupling. Oxygenation response to this manoeuvre is heterogeneous and derecruitment of dependent lung has not been elucidated. Nine pigs (32.2 ± 1.2 kg) were sedated and mechanically ventilated. Mono-lateral right-sided pneumonia was induced with intrabronchial challenge of Pseudomonas aeruginosa. After 24 h, lungs were recruited and the animals were randomly positioned on right or left side. After 3 h of lateral positioning, the animals were placed supine; another recruitment manoeuvre was performed, and the effects of contralateral decubitus were assessed. Primary outcome was lung ultrasound score (LUS) of the dependent lung after 3-h lateral positioning. LUS of the left non-infected lung worsened while positioned in left-lateral position (from 1.33 ± 1.73 at baseline to 6.78 ± 4.49; p = 0.005). LUS of the right-infected lung improved when placed upward (9.22 ± 2.73 to 6.67 ± 3.24; p = 0.09), but worsened in right-lateral position (7.78 ± 2.86 to 13.33 ± 3.08; p < 0.001). PaO2/FiO2 improved in the left-lateral position (p = 0.005). In an animal model of right-lung pneumonia, left-lateral decubitus improved oxygenation, but collapsed the healthy lung. Right-lateral orientation further collapsed the diseased lung. Our data raise potential clinical concerns for the use of lateral position in mono-lateral pneumonia.

A comparison of the CFHH criteria against the Leeds criteria in determining the Pseudomonas aeruginosa status among adults with cystic fibrosis.

BACKGROUND: Pseudomonas aeruginosa (PA) status influences management decisions in cystic fibrosis (CF) but diagnostic approaches vary. We evaluated the ability of the CFHealthHub (CFHH) criteria, which consist of two major and four minor statements, in diagnosing chronic PA infection among adults with CF. METHODS: In this retrospective cross-sectional analysis, we compared the CFHH criteria against the Leeds criteria. Data were collected between 1st January and 31st December 2016 from all adults with CF receiving care at Sheffield, excluding those with lung transplantation (n = 7) or on ivacaftor (n = 13). The CFHH criteria PA status were cross-tabulated against the Leeds criteria, and clinical outcomes between chronic PA vs non chronic PA for both criteria were compared. RESULTS: This analysis included 186 adults with CF (90 females, median age 27 years, median baseline FEV1 78.5%). The CFHH criteria diagnosed more cases of chronic PA (116/186, 62.4% vs 79/186, 42.5%), and 37/107 cases of non-chronic PA according to the Leeds criteria were deemed chronic PA by the CFHH criteria. The magnitude of difference in %FEV1 decline between chronic PA vs non chronic PA was slightly greater for the CFHH criteria (-0.6%, 95% CI -1.8 to 0.6%) compared to the Leeds criteria (-0.2%, 95% CI -1.3 to 1.0%). CONCLUSIONS: The CFHH criteria detected more chronic PA cases yet still retained similar levels of discrimination for health outcomes in comparison to the Leeds criteria. These findings provide preliminary evidence for the validity of the CFHH criteria among adults with CF.

The application of metagenomic next-generation sequencing in diagnosing Chlamydia psittaci pneumonia: a report of five cases.

BACKGROUND: Chlamydia psittaci pneumonia is a zoonotic infectious disease caused by Chlamydia psittaci. Diagnostic tools, including culture, serologic test and PCR-based methods, are available but prone to false negative results. CASE PRESENTATION: This report included five cases of Chlamydia psittaci pneumonia. Symptoms and signs common to all 5 cases included fever, coughing, generalized muscle ache, and most notably, inflammatory infiltration of the lungs upon chest CT and X-ray. Metagenomic next-generation sequencing (mNGS) revealed the presence of Chlamydia psittaci in biopsy lung tissue in 3 cases and bronchoalveolar lavage fluid in the remaining 2 cases. Three patients responded to doxycycline plus moxifloxacin; two patients responded to moxifloxacin alone. CONCLUSIONS: mNGS could be used to diagnose Chlamydia psittaci pneumonia.

Graphene-based sensing of oxygen transport through pulmonary membranes.

Lipid-protein complexes are the basis of pulmonary surfactants covering the respiratory surface and mediating gas exchange in lungs. Cardiolipin is a mitochondrial lipid overexpressed in mammalian lungs infected by bacterial pneumonia. In addition, increased oxygen supply (hyperoxia) is a pathological factor also critical in bacterial pneumonia. In this paper we fabricate a micrometer-size graphene-based sensor to measure oxygen permeation through pulmonary membranes. Combining oxygen sensing, X-ray scattering, and Atomic Force Microscopy, we show that mammalian pulmonary membranes suffer a structural transformation induced by cardiolipin. We observe that cardiolipin promotes the formation of periodic protein-free inter-membrane contacts with rhombohedral symmetry. Membrane contacts, or stalks, promote a significant increase in oxygen gas permeation which may bear significance for alveoli gas exchange imbalance in pneumonia.

Diagnosis of severe respiratory infections in immunocompromised patients.

An increasing number of critically ill patients are immunocompromised. Acute hypoxemic respiratory failure (ARF), chiefly due to pulmonary infection, is the leading reason for ICU admission. Identifying the cause of ARF increases the chances of survival, but may be extremely challenging, as the underlying disease, treatments, and infection combine to create complex clinical pictures. In addition, there may be more than one infectious agent, and the pulmonary manifestations may be related to both infectious and non-infectious insults. Clinically or microbiologically documented bacterial pneumonia accounts for one-third of cases of ARF in immunocompromised patients. Early antibiotic therapy is recommended but decreases the chances of identifying the causative organism(s) to about 50%. Viruses are the second most common cause of severe respiratory infections. Positive tests for a virus in respiratory samples do not necessarily indicate a role for the virus in the current acute illness. Invasive fungal infections (Aspergillus, Mucorales, and Pneumocystis jirovecii) account for about 15% of severe respiratory infections, whereas parasites rarely cause severe acute infections in immunocompromised patients. This review focuses on the diagnosis of severe respiratory infections in immunocompromised patients. Special attention is given to newly validated diagnostic tests designed to be used on non-invasive samples or bronchoalveolar lavage fluid and capable of increasing the likelihood of an early etiological diagnosis.

Wheezing independently predicts viral infection in children with community-acquired pneumonia.

AIM: To assess whether there was a difference in the frequency of symptoms and signs among children with community-acquired pneumonia (CAP) with viral or bacterial infection. METHODS: A prospective cross-sectional study was conducted in Salvador, Brazil. Children less than 5-years-old hospitalized with CAP were recruited. Viral or only bacterial infection was diagnosed by an investigation of 11 viruses and 8 bacteria. Bacterial infection was diagnosed by blood culture, detection of pneumococcal DNA in acute buffy coat, and serological tests. Viral infection was diagnosed by detection of respiratory virus in nasopharyngeal aspirate and serological tests. Viral infection comprised only viral or mixed viral-bacterial infection subgroups. RESULTS: One hundred and eighty-eight patients had a probable etiology established as only viral (51.6%), mixed viral-bacterial (30.9%), and only bacterial infection (17.5%). Asthma was registered for 21.4%. Report of wheezing (47.4% vs 21.2%; P = 0.006), rhonchi (38.0% vs 15.2%; P = 0.01), and wheezing detected on physical examination (51.0% vs 9.1%; P < 0.001) were the differences found. Among children with asthma, detected wheezing was the only different finding when children with viral infection were compared with those with only bacterial infection (75.0% vs 0%; P = 0.008). By multivariable analysis, viral infection (AdjOR [95% CI]: 9.6; 95%CI: 2.7-34.0), asthma (AdjOR [95% CI]: 4.6; 95%CI: 1.9-11.0), and age (AdjOR [95% CI]: 0.95; 95%CI: 0.92-0.97) were independently associated with wheezing on physical examination. The positive predictive value of detected wheezing for viral infection was 96.3% (95% CI: 90.4-99.1%). CONCLUSION: Wheezing detected on physical examination is an independent predictor of viral infection.

Colistin Use in Patients with Chronic Kidney Disease: Are We Underdosing Patients?

Colistin is administered as its inactive prodrug colistimethate (CMS). Selection of an individualized CMS dose for each patient is difficult due to its narrow therapeutic window, especially in patients with chronic kidney disease (CKD). Our aim was to analyze CMS use in patients with CKD. Secondary objectives were to assess the safety and efficacy of CMS in this special population. In this prospective observational cohort study of CMS-treated CKD patients, CKD was defined as the presence of a glomerular filtration rate (GFR) < 60 mL/min/m² for more than 3 months. The administered doses of CMS were compared with those recently published in the literature. Worsened CKD at the end of treatment (EOT) was evaluated with the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria. Colistin plasma concentrations (Css) were measured using high-performance liquid chromatography. Fifty-nine patients were included. Thirty-six (61.2%) were male. The median age was 76 (45⁻95) years and baseline GFR was 36.6 ± 13.6. The daily mean CMS dosage used was compared with recently recommended doses (3.36 vs. 6.07; p < 0.001). Mean Css was 0.9 (0.2⁻2.9) mg/L, and Css was <2 mg/L in 50 patients (83.3%). Clinical cure was achieved in 43 (72.9%) patients. Worsened renal function at EOT was present in 20 (33.9%) patients and was reversible in 10 (52.6%). The CMS dosages used in this cohort were almost half those currently recommended. The mean achieved Css were under the recommended target of 2 mg/dL. Despite this, clinical cure rate was high. In this patient cohort, the incidence of nephrotoxicity was similar to those found in other recent studies performed in the general population and was reversible in 52.6%. These results suggest that CMS is safe and effective in patients with CKD and may encourage physicians to adjust dosage regimens to recent recommendations in order to optimize CMS treatments.

ABL kinase inhibition promotes lung regeneration through expansion of an SCGB1A1+ SPC+ cell population following bacterial pneumonia.

Current therapeutic interventions for the treatment of respiratory infections are hampered by the evolution of multidrug resistance in pathogens as well as the lack of effective cellular targets. Despite the identification of multiple region-specific lung progenitor cells, the identity of molecules that might be therapeutically targeted in response to infections to promote activation of progenitor cell types remains elusive. Here, we report that loss of Abl1 specifically in SCGB1A1-expressing cells leads to a significant increase in the proliferation and differentiation of bronchiolar epithelial cells, resulting in dramatic expansion of an SCGB1A1+ airway cell population that coexpresses SPC, a marker for type II alveolar cells that promotes alveolar regeneration following bacterial pneumonia. Furthermore, treatment with an Abl-specific allosteric inhibitor enhanced regeneration of the alveolar epithelium and promoted accelerated recovery of mice following pneumonia. These data reveal a potential actionable target that may be exploited for efficient recovery after pathogen-induced infections.

Outcomes and risk factors after adjuvant surgical treatments for Mycobacterium avium complex lung disease.

BACKGROUND: Limited information is currently available on the postoperative outcomes of Mycobacterium avium complex lung disease (MAC-LD). OBJECTIVE: To show the outcomes of pulmonary resection and identify risk factors after adjuvant surgical treatments for MAC-LD. METHODS: One hundred and eight patients underwent adjuvant lung resection for MAC-LD at two hospitals between January 2008 and July 2016. We retrospectively evaluated outcomes and risk factors. RESULTS: Postoperative complications occurred in 14 patients (13%). After lung resection, 98 out of 108 patients (91%) achieved sputum culture conversion, eight (8.2%) of whom developed microbiological recurrence during the follow-up period. As a result, the success rate of adjuvant surgical treatments for MAC-LD with drug resistance was 83%. A multivariable analysis showed that a longer period from the initial medical treatment to surgery (hazard ratio, 1.01; 95% confidence interval, 1.00-1.02; p = 0.008) was independently associated with an increased risk of unfavorable outcomes after adjuvant surgery. CONCLUSIONS: Adjuvant surgical treatments for MAC-LD have acceptable outcomes. Better control of the disease may be achieved in some patients with drug resistance and indications for surgery through surgical treatments, and pulmonary resection needs to be performed earlier rather than continuing chemotherapy in these patients because it reduces unfavorable outcomes.

Histopathological Changes Caused by Inflammation and Oxidative Stress in Diet-Induced-Obese Mouse following Experimental Lung Injury.

Obesity has been identified as a risk factor for adverse outcomes of various diseases. However, information regarding the difference between the response of obese and normal subjects to pulmonary inflammation is limited. Mice were fed with the control or high-fat diet to establish the lean and diet-induced obese (DIO) mice. Escherichia coli was intranasally instilled to reproduce non-fatal acute pneumonia model. After infection, serum samples and lung tissues were obtained at 0, 12, 24, and 72 h. DIO mice exhibited increased serum triglyceride (TG) and total cholesterol (TC) contents as well as pulmonary resistin, IL-6, and leptin levels compared with lean mice. E. coli infection caused an acute suppurative inflammation in the lung with increased lung index and serum TG and TC contents; elevated pulmonary tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, IL-8, and leptin levels; and oxidative stress in mice. Interestingly, almost all the above-mentioned parameters peaked at 12 h after infection in the lean-E. coli group but after 12 h in the DIO-E. coli group. These results indicated that the DIO mice presented a delayed inflammatory response and oxidative stress in non-fatal acute pneumonia induced by E. coli infection.

Mechanism-Based Disease Progression Model Describing Host-Pathogen Interactions During the Pathogenesis of Acinetobacter baumannii Pneumonia.

The emergence of highly resistant bacteria is a serious threat to global public health. The host immune response is vital for clearing bacteria from the infected host; however, the current drug development paradigm does not take host-pathogen interactions into consideration. Here, we used a systems-based approach to develop a quantitative, mechanism-based disease progression model to describe bacterial dynamics, host immune response, and lung injury in an immunocompetent rat pneumonia model. Previously, Long-Evans rats were infected with Acinetobacter baumannii (A. baumannii) strain 307-0294 at five different inocula and total lung bacteria, interleukin-1beta (IL-1ß), tumor necrosis factor-α (TNF-α), cytokine-induced neutrophil chemoattractant 1 (CINC-1), neutrophil counts, and albumin were quantified. Model development was conducted in ADAPT5 version 5.0.54 using a pooled approach with maximum likelihood estimation; all data were co-modeled. The final model characterized host-pathogen interactions during the natural time course of bacterial pneumonia. Parameters were estimated with good precision. Our expandable model will integrate drug effects to aid in the design of optimized antibiotic regimens.

Pathophysiology of Escherichia coli pneumonia: Respective contribution of pathogenicity islands to virulence.

Ventilator-associated pneumonia (VAP) remains the most frequent life-threatening nosocomial infection. Enterobacteriaceae including Escherichia coli are increasingly involved. If a cumulative effect of pathogenicity islands (PAIs) has been shown for E. coli virulence in urinary tract or systemic infections, very little is known regarding pathophysiology of E. coli pneumonia. This study aimed to determine the role of each of the 7 PAIs present in pathogenic E. coli strain 536 in pneumonia pathophysiology. We used mutant strains to screen pathophysiological role of PAI in a rat pneumonia model. We also test individual gene mutants within PAI identified to be involved in pneumonia pathogenesis. Finally, we determined the prevalence of these genes of interest in E. coli isolates from feces and airways of ventilated patients. Only PAIs I and III were significantly associated with rat pneumonia pathogenicity. Only the antigen-43 (Ag43) gene in PAI III was significantly associated with bacterial pathogenicity. The prevalence of tested genes in fecal and airway isolates of ventilated patients did not differ between isolates. In contrast, genes encoding Ag43, the F17-fimbriae subunits, HmuR and SepA were more prevalent in VAP isolates with statistical significance for hmuR when compared to airway colonizing isolates. The E. coli PAIs involved in lung pathogenicity differed from those involved in urinary tract and bloodstream infections. Overall, extraintestinal E. coli virulence seems to rely on a combination of numerous virulence genes that have a cumulative effect depending on the infection site.

Pneumonia infection in mice reveals the involvement of the feoA gene in the pathogenesis of Acinetobacter baumannii.

Acinetobacter baumannii has emerged in the last decade as an important nosocomial pathogen. To identify genes involved in the course of a pneumonia infection, gene expression profiles were obtained from A. baumannii ATCC 17978 grown in mouse infected lungs and in culture medium. Gene expression analysis allowed us to determine a gene, the A1S_0242 gene (feoA), over-expressed during the pneumonia infection. In the present work, we evaluate the role of this gene, involved in iron uptake. The inactivation of the A1S_0242 gene resulted in an increase susceptibility to oxidative stress and a decrease in biofilm formation, in adherence to A549 cells and in fitness. In addition, infection of G. mellonella and pneumonia in mice showed that the virulence of the Δ0242 mutant was significantly attenuated. Data presented in this work indicated that the A1S_0242 gene from A. baumannii ATCC 17978 strain plays a role in fitness, adhesion, biofilm formation, growth, and, definitively, in virulence. Taken together, these observations show the implication of the feoA gene plays in the pathogenesis of A. baumannii and highlight its value as a potential therapeutic target.

Recurrent wheezing in neonatal pneumonia is associated with combined infection with Respiratory Syncytial Virus and Staphylococcus aureus or Klebsiella pneumoniae.

Both viral and bacterial infections can be associated with wheezing episodes in children; however, information regarding combined infections with both viral and bacterial pathogens in full term neonates is limited. We sought to investigate the effects of viral-bacterial codetection on pneumonia severity and recurrent wheezing. A retrospective cohort study was conducted on neonates admitted to our hospital with pneumonia from 2009 to 2015. Of 606 total cases, 341 were diagnosed with RSV only, and 265 were diagnosed with both RSV and a potential bacterial pathogen. The leading four species of bacteria codetected with RSV were Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Enterobacter cloacae. Neonates with RSV and a potential bacterial pathogen were significantly more likely to have worse symptoms, higher C-reactive protein values and more abnormal chest x-ray manifestations with Bonferroni correction for multiple comparisons (P < 0.01). On Cox regression analysis, an increased risk of recurrent wheezing was found for neonates positive for RSV-Staphylococcus aureus and RSV-Klebsiella pneumoniae. Our findings indicate that the combination of bacteria and RSV in the neonatal airway is associated with more serious clinical characteristics. The presence of RSV and Staphylococcus aureus or Klebsiella pneumoniae may provide predictive markers for wheeze.

Spectrum of pathogen- and model-specific histopathologies in mouse models of acute pneumonia.

Pneumonia may be caused by a wide range of pathogens and is considered the most common infectious cause of death in humans. Murine acute lung infection models mirror human pathologies in many aspects and contribute to our understanding of the disease and the development of novel treatment strategies. Despite progress in other fields of tissue imaging, histopathology remains the most conclusive and practical read out tool for the descriptive and semiquantitative evaluation of mouse pneumonia and therapeutic interventions. Here, we systematically describe and compare the distinctive histopathological features of established models of acute pneumonia in mice induced by Streptococcus (S.) pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Legionella pneumophila, Escherichia coli, Middle East respiratory syndrome (MERS) coronavirus, influenza A virus (IAV) and superinfection of IAV-incuced pneumonia with S. pneumoniae. Systematic comparisons of the models revealed striking differences in the distribution of lesions, the characteristics of pneumonia induced, principal inflammatory cell types, lesions in adjacent tissues, and the detectability of the pathogens in histological sections. We therefore identified core criteria for each model suitable for practical semiquantitative scoring systems that take into account the pathogen- and model-specific patterns of pneumonia. Other critical factors that affect experimental pathologies are discussed, including infectious dose, time kinetics, and the genetic background of the mouse strain. The substantial differences between the model-specific pathologies underscore the necessity of pathogen- and model-adapted criteria for the comparative quantification of experimental outcomes. These criteria also allow for the standardized validation and comparison of treatment strategies in preclinical models.

Inflammation and chronic colonization of Haemophilus influenzae in sputum in COPD patients related to the degree of emphysema and bronchiectasis in high-resolution computed tomography.

The presence of bacteria in the lower airways in COPD results in inflammation, further airway structural damage, and might lead to repeated exacerbations. We have previously shown that chronic colonization of Haemophilus influenzae during stable disease is related to increased inflammation, and we now aimed to relate previous findings of bacterial colonization and inflammation to the degree of radiological findings of bronchiectasis and emphysema. Thirty-nine patients with COPD were included in their stable state, and a high-resolution computed tomography of the lung was performed. They were followed-up monthly for up to a maximum of 6 months or until exacerbation, and they answered questionnaires, performed spirometry, and induced sputum at every visit. Thirty-five patients had emphysema with an emphysema degree of median 20% (interquartile range 10-50), and five patients had bronchiectasis, of which only four could expectorate sputum. The degree of emphysema correlated with several inflammatory mediators in sputum, such as interleukin-8 concentration, myeloperoxidase activity, and Leukotriene B4 concentration. Ten patients were chronically colonized with H. influenzae (ie, had a positive culture for H. influenzae at all visits). The four sputum patients with bronchiectasis were chronically colonized with H. influenzae and showed higher degree of H. influenzae growth compared to patients without bronchiectasis. During exacerbation, there was no longer any correlation between emphysema degree and inflammation, but patients with bronchiectasis showed higher sputum purulence score than patients without bronchiectasis. Emphysema and bronchiectasis in COPD patients show different clinical features. The presence of emphysema is more related to inflammation, while bronchiectasis is associated with bacterial colonization. We believe that both emphysema and bronchiectasis are therefore COPD phenotypes of highest impact and need evaluation to prevent further disease progression.