Acute Pulmonary Infection Research Articles

Outcomes among heart failure patients hospitalized for acute pulmonary embolism and COVID-19 infection: Insight from the National Inpatient Sample.

There is paucity of data regarding the outcomes of hospitalized acute pulmonary embolism (PE) patients with heart failure (HF) and Coronavirus Disease 2019 (COVID-19) infection. We utilized the 2020 National Inpatient Sample (NIS) Database in conducting a retrospective cohort study to investigate the outcomes of hospitalized acute PE patients with HF and COVID-19, looking at its impact on in-hospital mortality, thrombolysis, and thrombectomy utilization as well as hospital length of stay (LOS). A total of 23,413 hospitalized acute PE patients with HF were identified in our study, of which 1.26% (n = 295/23,413) had COVID-19 infection. Utilizing a stepwise survey multivariable logistic regression model that adjusted for confounders, COVID-19 infection among acute PE patients with HF was found to be an independent predictor of overall in-hospital mortality (adjusted odds ratio [aOR]: 2.77; 95% confidence interval [CI], 1.15-6.67; p = 0.023) and thrombolysis utilization (aOR: 5.52; 95% CI, 2.57-11.84; p ≤ 0.001) compared to those without COVID-19. However, there were comparable rates of thrombectomy utilization and LOS among acute PE patients with HF regardless of the COVID-19 infection status. On subgroup analysis, patients with HF with reduced ejection fraction was found to be associated with increased risk for in-hospital mortality (aOR: 3.89; 95% CI, 1.33-11.39; p = 0.013) and thrombectomy utilization (aOR: 4.58; 95% CI, 1.08-19.41; p = 0.042), whereas both HF subtypes were associated with increased thrombolysis utilization. COVID-19 infection among acute PE patients with HF was associated with higher over-all in-hospital mortality and increased thrombolysis utilization but had comparable hospital LOS as well as thrombectomy utilization.

Utility of Blood Culture in Patients with Community-Acquired Pneumonia: A Propensity Score-Matched Analysis Based on a Japanese National Health Insurance Database.

Community-acquired pneumonia (CAP) is an acute pulmonary parenchymal infection acquired outside the hospital. The utility of blood cultures in inpatients with CAP to reduce mortality and length of hospital stay is controversial. This study aimed to determine the utility of blood cultures on the first day of hospitalization for CAP inpatients and its influence on mortality, length of hospital stay, and antibiotics use. We conducted a fact-finding survey on the implementation of blood culture in inpatients with CAP in Japan. A propensity score (PS)-matched analysis based on the National Database of Health Insurance Claims and Specific Health Check-ups of Japan database was conducted. Overall, 163173 patients were included in the analysis, and PS matching extracted 68104 pairs. The results of the comparison between the PS-matched blood culture group and PS-matched control group were as follows: mortality and length of hospital stay were significantly lower in the PS-matched blood culture group than in the control group. The adjusted odds ratio (OR) (95% confidence interval (CI)) for in-hospital mortality with blood culture test was 0.73 (0.68-0.79). Moreover, for days of antibiotic usage, number of antibiotics used were significantly higher in the PS-matched blood culture group than that in the control group. Our findings indicated that performing a blood culture on the first day of hospitalization for inpatients with CAP was associated with reduced mortality. To our knowledge, this is the largest epidemiological study to assess the utility of blood culture in Japanese inpatients with CAP. This testing method shows potential for application in clinical practice.

Blastomycosis: A Review of Mycological and Clinical Aspects.

Blastomycosis is caused by a thermally dimorphic fungus that thrives in moist acidic soil. Blastomyces dermatitidis is the species responsible for most infections in North America and is especially common in areas around the Great Lakes, the St. Lawrence Seaway, and in several south-central and southeastern United States. Other Blastomyces species have more recently been discovered to cause disease in distinct geographic regions around the world. Infection almost always occurs following inhalation of conidia produced in the mold phase. Acute pulmonary infection ranges from asymptomatic to typical community-acquired pneumonia; more chronic forms of pulmonary infection can present as mass-like lesions or cavitary pneumonia. Infrequently, pulmonary infection can progress to acute respiratory distress syndrome that is associated with a high mortality rate. After initial pulmonary infection, hematogenous dissemination of the yeast form of Blastomyces is common. Most often this is manifested by cutaneous lesions, but osteoarticular, genitourinary, and central nervous system (CNS) involvement also occurs. The diagnosis of blastomycosis can be made by growth of the mold phase of Blastomyces spp. in culture or by histopathological identification of the distinctive features of the yeast form in tissues. Detection of cell wall antigens of Blastomyces in urine or serum provides a rapid method for a probable diagnosis of blastomycosis, but cross-reactivity with other endemic mycoses commonly occurs. Treatment of severe pulmonary or disseminated blastomycosis and CNS blastomycosis initially is with a lipid formulation of amphotericin B. After improvement, therapy can be changed to an oral azole, almost always itraconazole. With mild to moderate pulmonary or disseminated blastomycosis, oral itraconazole treatment is recommended.

Melioidosis

Melioidosis is a disorder caused by Gram-negative bacillus Berkholderia pseudomallei. The condition is endemic in Far East Southeastern Asia Northern Australia and India. It presents with recurrent or prolonged febrile illness. There may be a variety of manifestations in the form of septicemia acute localized suppuration acute pulmonary infection chronic suppuration or as a pulmonary mass lesion. It is associated with high mortality. It is treated with third generation cephalosporins.

COMPLICATED PNEUMONIA IN A PATIENT WITH CYSTIC FIBROSIS AND METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS INFECTION

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, resulting in characteristic features of CF, including chronic airway infection and inflammation, airways damage, and progressive lung disease [1]. CF patients experience alterations in their microbiome, which contribute to the development of chronic bacterial lung infections, leading to excessive lung inflammation and impair airway epithelial barrier function [2-3]. Staphylococcus aureus (SA) is considered one of the main causes of the recurrent acute pulmonary infections and progressive lung function decline in patients with CF [4]. Methicillin-resistant Staphylococcus aureus (MRSA) is highly prevalent in CF patients and is typically associated with complications. Despite antibiotic treatment, these infections often become chronic. MRSA is linked to an increased frequency of annual pulmonary exacerbations and a higher rate of hospitalization. We present the case of a 17-year-old female patient, diagnosed with CF since the age of 12, who presented to the emergency room due to dyspnea and worsening chronic respiratory failure, accompanied by a productive cough and greenish sputum. Sputum culture revealed multidrug-resistant SA. Initially, the patient’s clinical course was unfavorable, resulting in the development of a right pneumothorax after a coughing episode. However, with appropriate surgical treatment and antibiotic therapy guided by antimicrobial susceptibility testing (AST), the patient’s condition subsequently improved. When MRSA is detected, it should be promptly eradicated [5]. However, despite the introduction of new antibiotics, there is a lack of consensus regarding the optimal choice of antibiotics, dosing, and duration of treatment. Pneumothorax is a potentially life-threatening complication that can arise in both MRSA lung infections and CF patients. As a result, managing MRSA infections in CF patients continues to pose significant challenges.

Sodium houttuyfonate effectively treats acute pulmonary infection of Pseudomonas aeruginosa by affecting immunity and intestinal flora in mice.

Pseudomonas aeruginosa is a major nosocomial pathogen that frequently causes ventilator-associated pneumonia in specific populations. Sodium houttuyfonate (SH) has shown mild antibacterial activity against P. aeruginosa in vitro, but the mechanism of potent antimicrobial activity of SH against P. aeruginosa infection in vivo remains unclear. Here, using the mouse pneumonia model induced by P. aeruginosa nasal drip to explore the therapeutic effects of SH. We found that SH exhibits dose-dependent therapeutic effects of reducing P. aeruginosa burden and systemic inflammation in pneumonia mice. SH ameliorates inflammatory gene expression and production of inflammatory proteins, such as interleukin-6 (IL-6), nuclear factor kappa-B (NF-κB) and toll-like receptor 4 (TLR4), associated with the TLR4/NF-κB pathway in mice with P. aeruginosa pneumonia. Furthermore, we analyzed the intestinal flora of mice and found that compared with the model group, the abundance and diversity of beneficial bacterial flora of SH treatment groups increased significantly, suggesting that SH can improve the intestinal flora disorder caused by inflammation. In addition, SH improves alpha and beta diversity index and reduces species abundance differences of intestinal flora in pneumonia mice. Taken together, our presented results indicate that SH may effectively alleviate the acute pulmonary infection induced by P. aeruginosa by reducing the disturbance of regulating immunity and intestinal flora in mice.

Single-cell transcriptomics reveals distinct cell response between acute and chronic pulmonary infection of Pseudomonas aeruginosa.

Knowledge of the changes in the immune microenvironment during pulmonary bacterial acute and chronic infections is limited. The dissection of immune system may provide a basis for effective therapeutic strategies against bacterial infection. Here, we describe a single immune cell atlas of mouse lungs after acute and chronic Pseudomonas aeruginosa infection using single-cell transcriptomics, multiplex immunohistochemistry, and flow cytometry. Our single-cell transcriptomic analysis revealed large-scale comprehensive changes in immune cell composition and high variation in cell-cell interactions after acute and chronic P. aeruginosa infection. Bacterial infection reprograms the genetic architecture of immune cell populations. We identified specific immune cell types, including Cxcl2+ B cells and interstitial macrophages, in response to acute and chronic infection, such as their proportions, distribution, and functional status. Importantly, the patterns of immune cell response are drastically different between acute and chronic infection models. The distinct molecular signatures highlight the importance of the highly dynamic cell-cell interaction process in different pathological conditions, which has not been completely revealed previously. These findings provide a comprehensive and unbiased immune cellular landscape for respiratory pathogenesis in mice, enabling further understanding of immunologic mechanisms in infection and inflammatory diseases.

Contribution of Lipid Mediators in Divergent Outcomes following Acute Bacterial and Viral Lung Infections in the Obese Host.

Obesity is considered an important comorbidity for a range of noninfectious and infectious disease states including those that originate in the lung, yet the mechanisms that contribute to this susceptibility are not well defined. In this study, we used the diet-induced obesity (DIO) mouse model and two models of acute pulmonary infection, Francisella tularensis subspecies tularensis strain SchuS4 and SARS-CoV-2, to uncover the contribution of obesity in bacterial and viral disease. Whereas DIO mice were more resistant to infection with SchuS4, DIO animals were more susceptible to SARS-CoV-2 infection compared with regular weight mice. In both models, neither survival nor morbidity correlated with differences in pathogen load, overall cellularity, or influx of inflammatory cells in target organs of DIO and regular weight animals. Increased susceptibility was also not associated with exacerbated production of cytokines and chemokines in either model. Rather, we observed pathogen-specific dysregulation of the host lipidome that was associated with vulnerability to infection. Inhibition of specific pathways required for generation of lipid mediators reversed resistance to both bacterial and viral infection. Taken together, our data demonstrate disparity among obese individuals for control of lethal bacterial and viral infection and suggest that dysregulation of the host lipidome contributes to increased susceptibility to viral infection in the obese host.

P251 Disseminated Histoplasmosis in a Ghanaian HIV Patient: Role of Urine Histoplasma Antigen Testing in Rapid Diagnosis

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMBackgroundThe inhalation of the thermally dimorphic fungus Histoplasma capsulatum, may result in a wide spectrum of clinical manifestations, ranging from asymptomatic to acute or chronic pulmonary infection to disseminated infection. Symptomatic infections usually occur with high-level exposures or in immunocompromised patients mainly people with HIV. Despite the improved access to antiretroviral therapy, HIV-associated histoplasmosis remains a significant opportunistic infection in endemic regions including Africa. Unfortunately, histoplasmosis is rarely on the diagnostic radar of clinicians in several African countries such as Ghana due to insufficient awareness, inadequate epidemiological data, and poor fungal diagnostic capacity. Herein, we present a case of disseminated histoplasmosis in an HIV/AIDS patient in a tertiary hospital in Ghana.Case PresentationClinical history: A 43-year-old female was referred to the Dermatology Clinic of the Komfo Anokye Teaching Hospital (KATH) with symptoms of fever, cough, and anorexia. She had a history of a skin rash six weeks prior, which initially began on her face and later spread to the trunk and extremities. She was a known HIV/AIDS patient on anti-retroviral drugs (EFV, TFV, 3TC) with no other chronic conditions. She was anemic with a previous hemoglobin level of 7.6 g/dl. Initial diagnostic workup for cutaneous bacterial or viral infection detected no abnormality.ExaminationShe was semi-conscious, and her nostrils were clogged with crust. The patient appeared pale, warm, and anicteric. The face, trunk, and extremities (including palms) were covered with mucocutaneous erosions, ulcers, multiple papule plaques, and nodules. Examination of the cervix revealed the presence of lymph nodes.InvestigationsA fungal diagnostic work-up was done to rule out cutaneous or disseminated mycosis particularly cryptococcosis which was previously captured as a differential diagnosis. Serum cryptococcal antigen lateral flow assay (LFA) (CrAg LFA, IMMY) and Aspergillus galactomannan (GM) (sona Aspergillus GM LFA, IMMY) tests were both negative, but urine Histoplasma GM enzyme immunoassay (EIA) (clarus Histoplasma GM EIA, IMMY) test was positive with a very high optical density indicating high fungal burden was reported. A skin biopsy was also sent for histopathology and fungal culture. Histopathology analysis revealed the presence of yeast cells with round central nuclei and cytoplasmic clearing. Special staining with Periodic acid–Schiff (PAS) confirmed the presence of yeast cells, suggestive of histoplasmosis. Fungal culture was however negative after 8 weeks of incubation. A diagnosis of disseminated histoplasmosis was made.Treatment and outcomeThe patient was administered 200 mg bid of itraconazole. Few weeks after treatment, most of her skin lesions and ulcers were healed. The patient was discharged on itraconazole after the disappearance of some of her lesions. Few weeks later, the patient was admitted but died due to complications of anemia.ConclusionDisseminated histoplasmosis in HIV may be a relatively common but largely unrecognized condition in Ghana. This case report highlights the need to improve awareness of histoplasmosis among clinicians in Ghana and enhance laboratory capacity to provide timely simple contemporary fungal tests for rapid diagnosis and prompt initiation of effective antifungal agents.

SARS-CoV-2 in the Air Surrounding Patients during Nebulizer Therapy.

Nebulizer therapy is commonly used for patients with obstructive pulmonary disease or acute pulmonary infections with signs of obstruction. It is considered a “potential aerosol-generating procedure,” and the risk of disease transmission to health care workers is uncertain. The aim of this pilot study was to assess whether nebulizer therapy in hospitalized COVID-19 patients is associated with increased dispersion of SARS-CoV-2. Air samples collected prior to and during nebulizer therapy were analyzed by RT-PCR and cell culture. Total aerosol particle concentrations were also quantified. Of 13 patients, seven had quantifiable virus in oropharynx samples, and only two had RT-PCR positive air samples. For both these patients, air samples collected during nebulizer therapy had higher SARS-CoV-2 RNA concentrations compared to control air samples. Also, for particle sizes 0.3–5 µm, particle concentrations were significantly higher during nebulizer therapy than in controls. We were unable to cultivate virus from any of the RT-PCR positive air samples, and it is therefore unknown if the detected virus were replication-competent; however, the significant increase in smaller particles, which can remain airborne for extended periods of time, and increased viral RNA concentrations during treatment may indicate that nebulizer therapy is associated with increased risk of SARS-CoV-2 transmission.

Detection via in vitro amplification of lasR gene associated with virulent attribute of Pseudomonas aeruginosa from acute pulmonary infections

Pseudomonas aeruginosa is the most ubiquitous pulmonary pathogen of human which causes successfully unscrupulous infections in patients with the suppressed immune system of every age group and is considered as the first or second key pathogen in the research. The most lethal and persistent pathogen that caused the acute ventilator-acquired pneumonia (VAP) infection is P. aeruginosa. The Quorum sensing (QS) system is present in P. aeruginosa which regulates the expression of various virulence factors. In the current study, the contribution of lasR gene of pathogenic P. aeruginosa responsible for acute pulmonary infections was investigated. The objectives of the current work were; to screen the pathogenic P. aeruginosa from acute (VAP) through endotracheal tract (ETT) secretions and blood, to identify and characterize pathogenic strains by biochemical testing and virulence assays and to detect lasR, gene of P. aeruginosa responsible from acute pulmonary infections. The samples included secretions (Endotracheal tract) and Blood samples from patients with acute Ventilator-associated pneumonia (VAP). Samples were provided by the Microbiology laboratory of GCU Lahore. Total four strains of P. aeruginosa were selected as most virulent after confirmatory test of antibiotic sensitivity and virulence assays. Mutation was induced in wild strains via ethidium bromide. Molecular characterization of P. aeruginosa strains and lasR gene was done. Sequence analysis results after BLAST at NCBI confirmed P. aeruginosa strains and the presence of lasR gene which is involved in multiple virulence factors and is responsible for acute pulmonary infections. Wild and mutant strains of this bacterium showed resistance to the most commonly used antibiotics. Hence, it can be concluded that P. aeruginosa is involved in hospital-acquired and ventilator-acquired pneumonia and is a highly efficient multidrug-resistant pathogenic bacteria. Also, lasR gene sequence can be used as the diagnostic marker to identify the virulent lasR gene sequence from this opportunistic pathogen in the future.

Pseudomonas aeruginosa associated pulmonary infections and in vitro amplification virulent rhamnolipid (rhlR) gene.

Pseudomonas aeruginosa is a common opportunistic pathogenic bacterium with the ability to develop a strong communication pathway by quorum sensing system and different virulent factors. Among the various important secretions of P. aeruginosa rhamnolipid is important biological detergent, believed to be involved in the development of the biofilm and intercellular communication. It readily dissolves the lung surfactants that are then easily catalyzed by the phospholipases and in this way is involved in the acute pulmonary infection. research work was designed to investigate virulence and gene associated with virulence in P. aeruginosa responsible for pulmonary infections. In current study polymerase chain reaction (PCR) was used for the detection of the rhlR (rhamnolipid encoding) gene of isolated strains. A number of assays were performed that ensured its virulent behavior. Disc diffusion method was used to check its antibiotic resistance. Isolated strains were resistant to a number of antibiotics applied. It was found that males are more prone to respiratory infections as compared to females. Male members with age of 44-58 and 59-73 are at a higher risk, while females with age of 44-58 are also at a risk of pulmonary infections. Antibiotic resistance was observed by measuring zone of inhibition in strains GCU-SG-M4, GCU-SG-M3, GCU-SG-M5, GCU-SG-M2, GCU-SG-M1 and GCU-SG-M6. GCU-SG-M2 was resistant to fluconazole (FLU), clarithromycin (CLR), cefixime (CFM) and Penicillin (P10). No zone of inhibition was observed. But it showed unusual diffused zone around the Ak and MEM antibiotic discs. rhl R gene and 16s rRNA gene were characterized and analyzed. Findings from current study would help in raising awareness about antibiotic resistance of P. aeruginosa, and also the sequence of rhl R gene can be used as the diagnostic marker sequence to identify the virulent rhl R gene sequence from the samples when isolated from sputum of Pneumonia patients.

Primary Oral Histoplasmosis in Immunocompetent Host: Case Series with Review of Literature.

Histoplasmosis, a systemic mycosis caused by Histoplasma capsulatum manifests clinically in immunocompromised subjects as acute or chronic pulmonary infection or as a progressive disseminated disease. In oral region it clinically presents as multiple, granular and painful ulcers or verrucous growth. It is rare to find primary oral lesion of histoplasmosis in immunocompetent patient free from systemic disease. In presence of any unusual oral lesion possibility of Histoplasmosis should be considered and prompt diagnosis be attained with exclusion of false negative results as non-specific manifestation of disease may lead to gruesome misdiagnosis of lesion and inadequate treatment. In the present paper two cases of oral histoplasmosis in immunocompetent host have been discussed along with updated review of literature.

COVID 19 Outbreak and Care Givers' Management Approach of their Children who undergoing Hemodialysis

Background: COVID-19 is an acute pulmonary infection caused by a coronavirus and characterized by several clinical characteristics ranging from asymptomatic to respiratory failure that required special care. Aim: Evaluate the impact management approach for caregivers regarding prevention and control strategies of COVID19 for their children undergoing hemodialysis. Study Design: Quasi-experimental design was used. Setting: The study was conducted at pediatrics dialysis units at Mansoura University Children’s Hospital. Subjects: A convenient sample of (34) children undergoing hemodialysis therapy & their caregivers who accompanied them. Tools: three tools used in this study; Tool (I): Include three parts: Socio-demographic characteristics of the studied children, Clinical information of the studied children undergoing hemodialysis, and Sociodemographic characteristics of children's caregivers. Tool (II): included two parts; Knowledge of caregivers related to hemodialysis, knowledge of caregivers related to COVID19, and Preventive and control strategies of Covid19 used by caregivers for their children undergoing hemodialysis therapy. Tool (III): Strategies and precautions followed by caregivers related to hemodialysis therapy and preventive and control strategies of Covid19 used by caregivers for their children undergoing hemodialysis therapy. Results: The results revealed that there was a statistically significant effect on caregiver’s knowledge regarding hemodialysis, COVID-19. In addition to there was a statistically significant difference in the application of COVID19 prevention precautions followed by caregivers for their children undergoing hemodialysis through the program phases with P<0.001.Conclusion: a significant improvement of caregiver’s knowledge regarding the hemodialysis, COVID-19 post & follow up implementation phases compared with the pre-implementation phase. In addition to there was also a significant improvement in the application of preventive and control strategies of Covid19 followed by studied caregivers for their children who undergoing hemodialysis after the program application. Recommendation: Infectious disease guidelines of the COVID-19 epidemic should be conducted by healthcare staff in pediatric dialysis centers in order to reduce the transmission of infection among children with chronic renal failure.

In-Hospital Cardiac Arrest after Emotional Stress in a Patient Hospitalized with Gastrointestinal Symptoms and Chronic Anxiety Disorder

Background: We report an acute emotional stress–induced in-hospital cardiac arrest in a patient admitted with gastrointestinal symptoms after experiencing chronic anxiety disorder. Case Presentation: The patient was admitted to the Second Xiangya Hospital, Central South University, with gastrointestinal symptoms and chronic anxiety disorder, and experienced cardiac arrest during hospitalization after acute emotional stress. Malignant ventricular tachycardia and cardiogenic shock were evidenced in this patient after the acute emotional stress. Severe and extensive coronary spasm was confirmed by emergency coronary angiography, and coronary spasm was relieved by intracoronary injection of nitroglycerin. The patient recovered from myocardial infarction with nonobstructive coronary arteries. However, the patient developed acute kidney dysfunction and severe pulmonary infection and eventually died of respiratory circulatory failure on the ninth day after the successful rescue. Conclusions: Acute emotional stress on top of chronic anxiety disorder in patients hospitalized for noncardiovascular reasons might lead to the development of life-threatening cardiovascular diseases, including coronary artery spasm and myocardial infarction with nonobstructive coronary arteries. Psychological management is of importance to improve the outcome of these patients.

Gram-Positive Pneumonia: Possibilities Offered by Phage Therapy.

Pneumonia is an acute pulmonary infection whose high hospitalization and mortality rates can, on occasion, bring healthcare systems to the brink of collapse. Both viral and bacterial pneumonia are uncovering many gaps in our understanding of host–pathogen interactions, and are testing the effectiveness of the currently available antimicrobial strategies. In the case of bacterial pneumonia, the main challenge is antibiotic resistance, which is only expected to increase during the current pandemic due to the widespread use of antibiotics to prevent secondary infections in COVID-19 patients. As a result, alternative therapeutics will be necessary to keep this disease under control. This review evaluates the advantages of phage therapy to treat lung bacterial infections, in particular those caused by the Gram-positive bacteria Streptococcus pneumoniae and Staphylococcus aureus, while also highlighting the regulatory impediments that hamper its clinical use and the difficulties associated with phage research.

Identification and assessment of pulmonary Cryptococcus neoformans infection by blood serum surface-enhanced Raman spectroscopy

Cryptococcus neoformans (C. neoformans) is a causative agent for acute pulmonary infection, which can further develop to lethal meningoencephalitis if untreated. The meningoencephalitis infection can be prevented, if timely treatment on pulmonary cryptococcal infection can be implemented based on its early diagnosis and accurate assessment. In this study, blood serum surface-enhanced Raman spectroscopy (SERS) method was investigated on identification and assessment of pulmonary C. neoformans infection. The serum SERS measurements were collected from the mice infected with C. neoformans and the healthy mice, in which the infected mice were further divided into four subgroups according to the duration of infection. Based on those SRES measurements, biochemical differences were analyzed among those different groups to investigate the potential biomarkers for identifying and assessing the pulmonary C. neoformans infection. Furthermore, partial least square (PLS) analysis followed by linear discriminant analysis (LDA) model was employed to identify pulmonary cryptococcal infection and to assess the degrees of infection with the accuracies of 96.7% and 85.3%, respectively. Therefore, our study has demonstrated the great clinical potential of using serum SERS technique for an accurate identification and assessment of pulmonary cryptococcal infection.

The Human Microbiome, an Emerging Key-Player in the Sex Gap in Respiratory Diseases.

The sex gap is well-documented in respiratory diseases such as cystic fibrosis and chronic obstructive pulmonary disease. While the differences between males and females in prevalence, severity and prognosis are well-established, the pathophysiology of the sex difference has been poorly characterized to date. Over the past 10 years, metagenomics-based studies have revealed the presence of a resident microbiome in the respiratory tract and its central role in respiratory disease. The lung microbiome is associated with host immune response and health outcomes in both animal models and patient cohorts. The study of the lung microbiome is therefore an interesting new avenue to explore in order to understand the sex gap observed in respiratory diseases. Another important parameter to consider is the gut-lung axis, since the gut microbiome plays a crucial role in distant immune modulation in respiratory diseases, and an intestinal “microgenderome” has been reported: i.e., sexual dimorphism in the gut microbiome. The microgenderome provides new pathophysiological clues, as it defines the interactions between microbiome, sex hormones, immunity and disease susceptibility. As research on the microbiome is increasing in volume and scope, the objective of this review was to describe the state-of-the-art on the sex gap in respiratory medicine (acute pulmonary infection and chronic lung disease) in the light of the microbiome, including evidence of local (lung) or distant (gut) contributions to the pathophysiology of these diseases.

Single-Cell Transcriptional Heterogeneity of Neutrophils During Acute Pulmonary Cryptococcus neoformans Infection.

Neutrophils are critical as the first-line defense against fungal pathogens. Yet, previous studies indicate that neutrophil function is complex during Cryptococcus neoformans (Cn) infection. To better understand the role of neutrophils in acute pulmonary cryptococcosis, we analyzed neutrophil heterogeneity by single-cell transcriptional analysis of immune cells in the lung of Cn-infected mice from a published dataset. We identified neutrophils by reference-based annotation and identified two distinct neutrophil subsets generated during acute Cn infection: A subset with an oxidative stress signature (Ox-PMN) and another with enhanced cytokine gene expression (Cyt-PMN). Based on gene regulatory network and ligand-receptor analysis, we hypothesize that Ox-PMNs interact with the fungus and generate ROS, while Cyt-PMNs are longer-lived neutrophils that indirectly respond to Cn-derived ligands and cytokines to modulate cell-cell communication with dendritic cells and alveolar macrophages. Based on the data, we hypothesized that, during in vivo fungal infection, there is a division of labor in which each activated neutrophil becomes either Ox-PMN or Cyt-PMN.

Adipose-Derived Mesenchymal Stem Cells Ameliorating Pseudomonas aeruginosa-induced Acute Lung Infection via Inhibition of NLRC4 Inflammasome.

Background Pseudomonas aeruginosa (PA) is one of the most common Gram-negative bacteria causing hospital-acquired pulmonary infection, with high drug resistance and mortality. Therefore, it is urgent to introduce new non-antibiotic treatment strategies. Mesenchymal stem cells (MSCs), as important members of the stem cell family, were demonstrated to alleviate pathological damage in acute lung injury. However, the potential mechanism how MSC alleviate acute lung infection caused by PA remains unclear.ObjectiveThe purpose of this study was to investigate the effects of Adipose-derived mesenchymal stem cells (ASCs) on acute pulmonary infections and the possible mechanisms how ASCs reduce pulmonary inflammation induced by PA.MethodsThe therapeutic and mechanistic effects of ASCs on PA pulmonary infection were evaluated respectively in a murine model as well as in an in vitro model stimulated by PA and co-cultured with ASCs.Results1. ASCs treatment significantly reduced the bacterial load, inflammation of lung tissue and histopathological damage by PA. 2. PA infection mainly activated Nod-like receptor containing a caspase activating and recruitment domain 4 (NLRC4) inflammasome in the lung of mice. ASCs attenuated acute lung infection in mice by inhibiting NLRC4 inflammasome activation. 3. NLRC4−/− mice showed a significant improvement in survival rate and lung bacterial load after PA infection. 4. ASCs mainly increased expression and secretion of STC‐1 in response to PA‐stimulated NLRC4 inflammasome activation.ConclusionsPA infection attenuated macrophage phagocytosis through activation of NLRC4 inflammasome in macrophages, which eventually led to pulmonary inflammatory damage in mouse; ASCs reduced the activation of NLRC4 inflammasome in macrophages induced by PA infection, thereby increasing the phagocytic ability of macrophages, and ultimately improving lung tissue damage in mouse; ASCs may inhibit NLRC4 inflammasome through the secretion of STC-1.