Development Of Pulmonary Infection Research Articles

Alveolar macrophage modulation via the gut-lung axis in lung diseases.

Several studies have demonstrated great potential implications for the gut-lung axis in lung disease etiology and treatment. The gut environment can be influenced by diet, metabolites, microbiotal composition, primary diseases, and medical interventions. These changes modulate the functions of alveolar macrophages (AMs) to shape the pulmonary immune response, which greatly impacts lung health. The immune modulation of AMs is implicated in the pathogenesis of various lung diseases. However, the mechanism of the gut-lung axis in lung diseases has not yet been determined. This mini-review aimed to shed light on the critical nature of communication between the gut and AMs during the development of pulmonary infection, injury, allergy, and malignancy. A better understanding of their crosstalk may provide new insights into future therapeutic strategies targeting the gut-AM interaction.

Pulmonary infection is associated with an increased IL-6 in acute exacerbation chronic obstructive pulmonary disease

Objective Acute Exacerbation Chronic Obstructive Pulmonary Disease (AECOPD) is associated with an acute worsening of respiratory symptoms that have effects on lung function, quality of life and health economic burden. In addition, the development of pulmonary infections is a common complication of Chronic Obstructive Pulmonary Disease (COPD). In the pathophysiology of AECOPD, interleukin (IL)-6 is a pleiotropic cytokine that can be produced by inflammatory and primary lung epithelial cells in response to a variety of different stimuli. We aim to investigate the correlation between serum cytokine levels and AECOPD with pulmonary infection. Methods 37 AECOPD patients diagnosed with pulmonary infection and 33 patients diagnosed with AECOPD only were selected. All COPD patients were diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Serum samples for C-reactive protein (CRP) and cytokines were obtained from the patients immediately after admission. Serum concentrations of cytokines were measured using a fluorescent bead immunoassay on a flow cytometer. Logistic regression was used to identify risk factors for AECOPD co-infection of the lungs. Results Serum characterization of our cohort showed patients with AECOPD and pulmonary infection had higher levels of IL-6 and IL-10 compared with the AECOPD group, and IL-6 was independently associated with AECOPD with pulmonary infection. ROC curve analysis showed that IL-6 was a useful predictor of the incidence of pulmonary infection in AECOPD patients. Conclusions Our findings highlight the role of IL-6 in the pathogenesis of AECOPD with pulmonary infection.

Synthesis of Two Epimers of Pseudopaline

Opines are a known group of compounds characterized by an elevated polarity. Recently, two new members of this class, staphylopine and pseudopaline, have been identified in Staphylococcus aureus and Pseudomonas aeruginosa, respectively. These molecules are metal chelators that contribute to the growth of bacteria in particularly metal‐poor environment. Different evidences suggest that these molecules might have an important role in the development of pulmonary infections in humans. Considering the impact of P. aeruginosa infections in cystic fibrosis patients (prevalence up to 70 %), pseudopaline has risen interest as potential source of new therapeutic intervention. We present herein a straightforward synthetic approach for the synthesis of the two epimers of pseudopaline. Starting from a chiral building block, we attribute the absolute configuration to the two obtained diasteroisomers.

New-Onset Diabetes Mellitus in Patients with Idiopathic Membranous Nephropathy Undergoing Tacrolimus and Low-Dose Corticosteroid Therapy

Background: Idiopathic membranous nephropathy (IMN) is the most common cause of nephrotic syndrome in adults. Although various studies have demonstrated the efficacy of tacrolimus combined with corticosteroids for treating IMN, both tacrolimus and corticosteroids have been shown to be diabetogenic, particularly following organ transplantation. Furthermore, the frequency and risk factors for new-onset diabetes mellitus (NODM) in IMN patients treated with tacrolimus plus low-dose corticosteroids remain unclear. Objectives: To evaluate the incidence of NODM in IMN patients undergoing tacrolimus plus low-dose corticosteroid therapy and to confirm the risk factors for NODM development. Methods: This retrospective study recruited 72 eligible patients with biopsy-proven IMN from our center, between September 2013 and June 2018. All subjects were treated with tacrolimus plus low-dose corticosteroids for a minimum of 3 months. The primary outcome was NODM development during the follow-up period. The secondary outcome was complete or partial remission. Patients were divided into 2 groups: patients with NODM (NODM group) and those without NODM (No-NODM group). Demographic and clinical data at baseline and follow-up were assessed. Results: During follow-up, 31 of the 72 patients developed NODM (43.0%). The median time to occurrence was 3 months after treatment initiation. NODM patients were significantly older (median age 59 vs. 40 years) than No-NODM patients. Baseline fasting blood glucose levels were slightly higher in the NODM group; however, the difference was not significant (p = 0.07). Older age was an independent risk factor for NODM (OR 1.73 and 95% CI 1.20–2.47, p = 0.003). Overall kidney remission rates were 80.6%. There was no significant difference in remission rate between groups. There was a significant difference in development of pulmonary infection, which occurred in 7 NODM patients and only in 1 No-NODM patient (p = 0.018). IMN reoccurred in 5 NODM patients but only 1 No-NODM patient. Conclusions: Tacrolimus plus low-dose corticosteroid therapy was an efficient treatment for IMN; however, it was accompanied by increased NODM morbidity, which should be considered serious, due to the increased risk of life-threatening complications. Increasing age was a major risk factor for NODM in IMN patients treated with tacrolimus plus low-dose corticosteroid therapy.

Tsr Chemoreceptor Interacts With IL-8 Provoking E. coli Transmigration Across Human Lung Epithelial Cells.

Bacterial colonization of epithelial surfaces and subsequent transmigration across the mucosal barrier are essential for the development of infection. We hypothesized that the methyl-accepting proteins (MCPs), known as chemoreceptors expressed on Escherichia coli (E. coli) bacterial surface, play an important role in mediating bacterial transmigration. We demonstrated a direct interaction between human interleukin-8 (IL-8) and Tsr receptor, a major MCP chemoreceptor. Stimulation of human lung epithelial cell monolayer with IL-8 resulted in increased E. coli adhesion and transmigration of the native strain (RP437) and a strain expressing only Tsr (UU2373), as compared to a strain (UU2599) with Tsr truncation. The augmented E. coli adhesion and migration was associated with a higher expression of carcinoembryonic antigen-related cell adhesion molecule 6 and production of inflammatory cytokines/chemokines, and a lower expression of the tight junction protein claudin-1 and the plasma membrane protein caveolin-1 in lung epithelial cells. An increased E. coli colonization and pulmonary cytokine production induced by the RP437 and UU2373 strains was attenuated in mice challenged with the UU2599 strain. Our results suggest a critical role of the E. coli Tsr chemoreceptor in mediating bacterial colonization and transmigration across human lung epithelium during development of pulmonary infections.

Cholinergic Pathway Suppresses Pulmonary Innate Immunity Facilitating Pneumonia After Stroke.

Temporary immunosuppression has been identified as a major risk factor for the development of pneumonia after acute central nervous system injury. Although overactivation of the sympathetic nervous system was previously shown to mediate suppression of systemic cellular immune responses after stroke, the role of the parasympathetic cholinergic anti-inflammatory pathway in the antibacterial defense in lung remains largely elusive. The middle cerebral artery occlusion model in mice was used to examine the influence of the parasympathetic nervous system on poststroke immunosuppression. We used heart rate variability measurement by telemetry, vagotomy, α7 nicotinic acetylcholine receptor-deficient mice, and parasympathomimetics (nicotine, PNU282987) to measure and modulate parasympathetic activity. Here, we demonstrate a rapidly increased parasympathetic activity in mice after experimental stroke. Inhibition of cholinergic signaling by either vagotomy or by using α7 nicotinic acetylcholine receptor-deficient mice reversed pulmonary immune hyporesponsiveness and prevented pneumonia after stroke. In vivo and ex vivo studies on the role of α7 nicotinic acetylcholine receptor on different lung cells using bone marrow chimeric mice and isolated primary cells indicated that not only macrophages but also alveolar epithelial cells are a major cellular target of cholinergic anti-inflammatory signaling in the lung. Thus, cholinergic pathways play a pivotal role in the development of pulmonary infections after acute central nervous system injury.

Clinical analysis of pulmonary infection in patients with hepatitis B virus-related acute-on-chronic liver failure

Objective To investigate the clinical features of pulmonary infection in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). Methods A total of 666 hospitalized patients with HBV-ACLF in Department of Liver Disease of Fuzhou Infectious Diseases Hospital were retrospectively analyzed. Data of demographic and clinical parameters (sex, age, presence of liver cirrhosis and diabetes), complications (spontaneous bacterial peritonitis, hepatorenal syndrome, hepatic encephalopathy, and upper gastrointestinal hemorrhage), and baseline biochemical parameters were collected from the medical records database. Univariate and multivariate regression analyses were performed to determine the independent risk factors of pulmonary infection in patients with ACLF. Distributions of the pathogenic bacteria were further analyzed. Student t test was used for the means consistent with normal distribution, while non-parametric statistics were used for the data consistent with abnormal distribution. Mann-Whitney U test was used for the data between two groups. Chi square test and Fisher exact probability method were used for comparing the count data. Results A total of 125 out of 666 patients with ACLF developed pulmonary infection. The incidence of pulmonary infection was 18.76% (125/666). Most patients were infected with fungi (54.84%). The incidence rate of pulmonary infection in patients with liver failure over 60 years (41.18%) was significantly higher than that in patients under 60 years (16.91%; χ2=19.136, P<0.01). The incidence of cirrhosis or diabetes in the 125 patients with pulmonary infection was higher than patients with no pulmonary infection. The difference between the two groups was statistically significant (P<0.01). Levels of albumin, cholesterol, alpha-fetoprotein, white blood cell count, hemoglobin, plasma thromboplastin antecedent, international normalized ratio (INR), and serum sodium were all significantly different between the two groups (all P<0.05). The incidence of spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatic encephalopathy in patients with pulmonary infection were significantly higher than those without pulmonary infection (P<0.01). Spontaneous bacterial peritonitis, age, albumin, hemoglobin and serum sodium were important factors in the development of the pulmonary infection. And albumin, hemoglobin and serum sodium were protective factors. Conclusions Pulmonary infection, as one of the common and serious complications, significantly affects the prognosis of liver failure patients. Prediction of pulmonary infection in the early stage is essential. Patients with elder age, spontaneous bacterial peritonitis, low albumin level, low serum sodium level and low hemoglobin level should be timely monitored to prevent the development of pulmonary infection. Key words: Hepatitis B virus; Liver failure; Pneumonia; Prognosis; Regression analysis

Pulmonary infections following immunosuppressive treatments during hospitalization worsen the short-term vital prognosis for patients with connective tissue disease-associated interstitial pneumonia

Objective. Connective tissue disease-associated interstitial pneumonia (CTD-IP) significantly affects the mortality of patients with CTD. The purpose of the present study is to identify causes and risk factors for death during hospitalization for immunosuppressive treatment of CTD-IP.Methods. A multicenter, retrospective study was conducted that collected data from patients with CTD who had been hospitalized for commencing or intensifying immunosuppressive treatment of CTD-IP using a standardized case report form. Risk factors were identified using the Cox proportional hazard regression model.Results. A total of 322 CTD-IP patients were enrolled with rheumatoid arthritis (n = 84), systemic lupus erythematosus (n = 13), polymyositis (n = 33), dermatomyositis (n = 69), systemic sclerosis (n = 55), mixed connective tissue disease (n = 21), microscopic polyangiitis (n = 19), and overlap syndrome (n = 28). Of the 42patients who died during hospitalization, 22 died from CTD-IP, 15 from CTD-IP and pulmonary infection, 2 from pulmonary infection, and 3 from other causes. Age ≥ 65 years and development of pulmonary infections after commencing or intensifying immunosuppressive treatments were identified as risk factors for death during hospitalization after adjusting for covariates.Conclusion. Careful consideration of the benefit–risk balance of immunosuppressive treatment for CTD-IP is indispensable for improving the short-term vital prognosis of these patients.

A rat model of pulmonary infection after cardiac transplant.

Cardiac allograft rejection and infection are leading causes of morbidity and mortality after transplant. The lack of an animal model has hindered related research. We have developed a rat model of pulmonary infection after cardiac transplant to address this issue. Lewis rats received Wistar rat heart allografts, cardiac rejection was induced by cessation of cyclosporine injection, and pulmonary infection was induced by Pseudomonas aeruginosa intrabronchial inoculation. Development of pulmonary infection and/or heart rejection was assessed by histopathology. Histopathologic findings showed that a dose of 2 × 108 colony forming units of Pseudomonas aeruginosa intrabronchial inoculation is sufficient to cause severe pneumonia without being lethal to transplanted animals. Daily administration of 10 mg/kg of cyclosporine reliably suppressed rejection, and withdrawal for 7 days can obtain a consistent International Society for Heart and Lung Transplantation 3R rejection. The current study represents a simple and effective rat model of pulmonary infection along, or in combination, with rejection after heart transplant, which can be used for research of infection-rejection in cardiac transplant settings.

Chest physiotherapy effectiveness to reduce hospitalization and mechanical ventilation length of stay, pulmonary infection rate and mortality in ICU patients

Although physiotherapy is an integral part of the multiprofessional team in most ICUs there is only limited evidence concerning the effectiveness of its procedures. The objectives of this study were to verify if physiotherapy care provided within 24 h/day for hospitalized patients in the ICU reduce the length of stay, mechanical ventilation support, pulmonary infection and mortality compared to a physiotherapy care provided within 6 h/day. A cohort study was designed to assess differences between one hospital where patients were given physiotherapy care for 24 h/day and another hospital with only 6 h/day. We considered the following as outcome measurements: clinical diagnosis, medication in use, presence of associated diseases, APACHE II and SOFA scores, ICU and mechanical ventilation length of stay, development of pulmonary infections and survival. One hundred and forty-six patients were enrolled. Patients admitted in the service A presented a lower length of stay in mechanical ventilation (p < 0.0001), ICU stay (p = 0.0003), respiratory infections (p = 0.0043) than patients admitted in service B. No difference was found for APACHE II score (p = 0.8) and SOFA scores (p = 0.2) between groups. The mortality risk was OR 1.3 (1.01-2.33) (p = 0.04) for patients in the service B. The presence of a physiotherapist in the intensive care unit contributes decisively to the early recovery of the patient, reducing mechanical ventilation support need, number of hospitalization days, incidence of respiratory infection and risk of mortality.

Nosocomial Infection After Septic Shock Among Intensive Care Unit Patients

To measure the incidence of nosocomial infection (NI) among patients with septic shock according to the place of septic shock acquisition and to evaluate the increase in the risk of pulmonary infection associated with septic shock. Prospective cohort study. Two intensive care units (ICUs) of a French university hospital. The study included a total of 209 septic shock patients during the period December 1, 2001 through April 30, 2005. The place of septic shock acquisition for 108 patients was the community; for 87, the hospital; and for 14, the ICU. To evaluate the impact of septic shock on the development of pulmonary infection, a competitive and adjusted hazard ratio (aHR) model was applied to nontrauma ICU patients. Among the 209 study patients, 48 (23%) experienced 66 NIs after septic shock. There was no significant difference in the NI attack rates according to place of acquisition: for the community acquisition group, 24 cases per 100 patients (95% confidence interval [CI], 16-32); for the hospital acquisition group, 20 cases per 100 patients (95% CI, 11-28); and for the ICU acquisition group, 36 cases per 100 patients (95% CI, 11-61) (P = .3). For nontrauma ICU patients, the presence of community-acquired septic shock was found to be independently associated with a higher incidence of pulmonary infection, compared with the absence of septic shock (aHR, 2.12 [95% CI, 1.08-4.16]; P = .03). The risk of NI did not differ by the place of septic shock acquisition. The risk of pulmonary infection was higher for ICU patients with community-acquired septic shock who were admitted for underlying nontrauma disease. Studies are needed to investigate the pathogenic mechanisms that facilitate pulmonary infection in this population, taking into account exposure to invasive devices and immunosuppression after the initial phase of septic shock.

Neutrophil migration during endotoxemia.

Endotoxemia is marked by a global activation of inflammatory responses, which can lead to shock, multiple organ failure, and the suppression of immune and wound healing processes. Neutrophils (PMNs) play a central role in some of these responses by accumulating in tissues and releasing reactive oxygen species and proteases that injure host structures. This review focuses on altered PMN migratory responses that occur during endotoxemia and their consequences in the development of pulmonary infection. The inflammatory mediators that might be responsible for these altered responses are discussed. The oxidant potential of PMNs is increased after exposure to endotoxin both in vitro and during clinical and experimental endotoxemia. However, other functions such as chemotaxis and phagocytosis are often depressed in these same cells. Endotoxin exposure renders PMNs hyperadhesive to endothelium. The sum of these effects produces activated inflammatory cells that are incapable of leaving the vasculature. As such, the endotoxic PMN is more likely to promote tissue injury from within microvascular beds than to clear pathogens from extravascular sites. Moreover, the functional characteristics of endotoxic PMNs are similar to those observed during trauma, burn injury, sepsis, surgery, and other inflammatory conditions. Accordingly, several clinical conditions might have a common effector in the activated, yet migratorially dysfunctional, PMN. Direct effects of endotoxin on PMNs as well as effects of endogenous mediators released during endotoxemia are discussed. Understanding PMN behavior during endotoxemia may provide basic and critical insights that can be applied to a number of inflammatory scenarios.

Development of pulmonary infection in mice inoculated with Blastomyces dermatitidis conidia.

Intratracheal injection of Balb/cByJ mice with 10(4) Blastomyces dermatitidis conida produces chronic pulmonary and disseminated blastomycosis characterized by pyogranulomatous inflammation. To study the evolution of the pulmonary infection, mice were killed at varying intervals after inoculation, their lungs cultured and examined histologically. Nodular intraalveolar infiltrates of macrophages (M phi) were seen on Day 1 with occasional admixed polymorphonuclear leukocytes (PMN). Phagocytized yeast forms within M phi were evident by Day 5. By Day 28 pyogranulomas, which developed first as central microabscesses associated with a peripheral zone of M phi and giant cells containing internalized yeast, were a prominent feature of the infection. Lymphocytic and plasmacytic infiltrates, accumulating next to granulomas, formed the major peripheral component of the granuloma by Day 35. Formation of pyogranulomas was coincident with the host's failure to contain fungal growth measured by the sharp rise in colony-forming units recovered from lungs. Antibody against B. dermatitidis was first detected at Day 35 by enzyme immunoassay, but not until Day 63 by double immunodiffusion. During the 4 wk after inoculation, pulmonary lavage fluid contained > 90% M phi and < 3% PMN. On day 28, PMN rose to 17%, reaching 40% on Day 42. These data contribute to our knowledge of this model and help form the basis for investigations into the roles of fungal pathogenic and host defense mechanisms in blastomycosis.

Biosynthesis and distribution of N-carboxyalkyl amino acids (opines) in bacteria

Opines are a known group of compounds characterized by an elevated polarity. Recently, two new members of this class, staphylopine and pseudopaline, have been identified in Staphylococcus aureus and Pseudomonas aeruginosa, respectively. These molecules are metal chelators that contribute to the growth of bacteria in particularly metal‐poor environment. Different evidences suggest that these molecules might have an important role in the development of pulmonary infections in humans. Considering the impact of P. aeruginosa infections in cystic fibrosis patients (prevalence up to 70 %), pseudopaline has risen interest as potential source of new therapeutic intervention. We present herein a straightforward synthetic approach for the synthesis of the two epimers of pseudopaline. Starting from a chiral building block, we attribute the absolute configuration to the two obtained diasteroisomers.

Cystic fibrosis related lung diseases in young adults with minimal impairment.

A small fraction of patients with cystic fibrosis (CF) survive to adulthood with exceptionally mild pulmonary impairment, in marked contrast to the usual natural history of CF. 6 young adults with CF with a high clinical score were studied to assess lung function, roentgenography, bacteriology, and the distribution of ventilation and perfusion. 1 such patient died during the course of the study from a cause other than CF-related respiratory failure, and the autopsy findings were reviewed. Although a few individuals showed normal and near-normal pulmonary function, evidence for mild to moderate obstructive airways disease was present in most tests performed, particularly the maximal expiratory flow between 25 and 75% of vital capacity. The helium dilution technique of determining total lung capacity generally underestimated the values by the technique of roentgenographic planimetry which were within the normal range. Lung scintigraphy revealed matched subsegmental defects in ventilation and perfusion, with 2 subjects showing mismatched defects. The histological findings in the deceased patient were similar to those in infants before the development of pulmonary infection and showed an abnormally thick and uneven basement membrane of the bronchial epithelium. These findings support the view that CF-related lung disease in these patients is qualitatively similar to the early disease in children, but is exceptionally slow to develop in a favored few who nonetheless have greater functional disturbance than their lack of symptoms would suggest.

Observations on the Pathogenesis of Pulmonary Suppuration in the Albino Rat.

The well recognized syndrome of pulmonary suppuration in the albino rat is, as in many human affections, an advanced stage of the condition. The earlier manifestations of the disease are imperfectly understood and the common appellation “pneumonia” for the well developed lesion is a reflection of this lack of knowledge of the fundamental nature of the process. The lesions of the lungs vary greatly according to the stage and extent of the process but the essential nature of the completely developed disease is that of chronic lung abscesses. We have been particularly impressed with the frequent occurrence of atelectasis in white rats which are apparently in perfect health. These observations lead us to suggest that atelectasis subsequent to bronchial obstruction is a primary factor in the development of pulmonary infection in the white rat. To substantiate this hypothesis it is necessary to show that obstructive atelectasis occurs in white rats showing no evidence of pulmonary infection and that organisms may gain an entrance to the lungs and selectively localize in the collapsed lobes. The probable pathway of infection has been indicated by Jones, who isolated organisms occurring in the environmental atmosphere, from the lungs of several laboratory animals. The regularity with which the cultures were positive varied directly with the amount of dust in the atmosphere. It is a well known fact that after bacteria have once gained entrance into the body their ability to proliferate and invade the host is greatly increased by an obstruction to the part. Our own observations have clearly shown that an obstructive atelectasis is a very common finding in white rats. This condition has been observed many times in animals showing no gross or microscopic evidence of pulmonary infection. The atelectatic areas vary in size from a minute portion at the tip of a lobe to a massive collapse of the entire right side and the infra-cardiac lobe.