Pulmonary Infectious Diseases Research Articles

Molecular Imaging of Pulmonary Inflammation and Infection.

Infectious and inflammatory pulmonary diseases are a leading cause of morbidity and mortality worldwide. Although infrequently used in this setting, molecular imaging may significantly contribute to their diagnosis using techniques like single photon emission tomography (SPET), positron emission tomography (PET) with computed tomography (CT) or magnetic resonance imaging (MRI) with the support of specific or unspecific radiopharmaceutical agents. 18F-Fluorodeoxyglucose (18F-FDG), mostly applied in oncological imaging, can also detect cells actively involved in infectious and inflammatory conditions, even if with a low specificity. SPET with nonspecific (e.g., 67Gallium-citrate (67Ga citrate)) and specific tracers (e.g., white blood cells radiolabeled with 111Indium-oxine (111In) or 99mTechnetium (99mTc)) showed interesting results for many inflammatory lung diseases. However, 67Ga citrate is unfavorable by a radioprotection point of view while radiolabeled white blood cells scan implies complex laboratory settings and labeling procedures. Radiolabeled antibiotics (e.g., ciprofloxacin) have been recently tested, although they seem to be quite unspecific and cause antibiotic resistance. New radiolabeled agents like antimicrobic peptides, binding to bacterial cell membranes, seem very promising. Thus, the aim of this narrative review is to provide a comprehensive overview about techniques, including PET/MRI, and tracers that can guide the clinicians in the appropriate diagnostic pathway of infectious and inflammatory pulmonary diseases.

Survival Outcomes of Allogeneic Transplantation in Heavy Smokers.

Allogeneic hematopoietic transplantation (allo-HCT) causes various pulmonary comorbidities including bronchiolitis obliterans (BO), interstitial pneumonia (IP) and pulmonary infectious disease. Smoking is a well-known risk factor of pulmonary dysfunction such as chronic obstruction pulmonary disease. Although smoking probably increases pulmonary comorbidities in allo-HCT patients, the relationship between number of cigarettes and allo-HCT has not been clearly elucidated. In this study, we retrospectively analyzed survival outcomes of 408 patients who received allo-HCT at our center between June 2007 and May 2019 according to pack-years (number of cigarettes smoked per day/20 multiplied by years smoked). The cutoff of 10 pack-years was defined by receiver operating characteristic (ROC) curves. In the univariate analyses, non-relapse mortality (NRM) and overall survival (OS) were inferior in the patients with > 10 pack-years history (n = 171) than those with ≤ 10 pack-years (n = 237) including non-smokers (1y-NRM 26.6% vs 13.9%, P

Pulmonary Complications in Patients with Primary Immunodeficiency Undergoing Hematopoietic Stem Cell Transplantation

<h3>Introduction</h3> Allogeneic hematopoietic stem cell transplantation (HSCT) is curative therapy for a variety of primary immunodeficiency disorders (PIDs). Patients with PID have high rates of pulmonary disease from infections and immune-mediated lung damage, and post-HSCT pulmonary complications account for considerable morbidity and mortality. It is unknown whether pre-HSCT pulmonary disease places PID patients at higher risk for post-HSCT complications. We hypothesize that PID patients with pre-HSCT pulmonary disease have higher risk of transplant-related mortality (TRM), more pulmonary complications, and lower overall survival (OS) compared to PID patients without pre-HSCT pulmonary disease. <h3>Objectives</h3> The primary aim of this study is to compare TRM in PID patients with and without pre-HSCT pulmonary disease. Secondary aims of the study are to compare OS, incidence of non-infectious and infectious pulmonary disease post-HSCT, ICU transfer for any cause, incidence of acute or chronic GVHD, and immune reconstitution. <h3>Methods</h3> This is a single center, retrospective, chart review. All pediatric patients (ages 0-18 years) who underwent allogeneic HSCT for a diagnosis of a PID at Boston Children's Hospital from January 2007-June 2018 (n=115) were included in the analysis. We defined non-infectious pulmonary disease as either functional lung impairment based on pulmonary function tests (PFTs), radiographic evidence of pulmonary disease, or documentation of a specific pulmonary diagnosis. We defined infectious pulmonary disease as either viral, bacterial, fungal or other infection in conjunction with positive radiographic and/or bronch/BAL findings. <h3>Results</h3> Within our cohort, the most common PIDs were SCID (n=28), DOCK8 deficiency (n=16), Wiskott-Aldrich syndrome (n=15), and chronic granulomatous disease (n=9). Of the 115 patients, 54 (47%) had a pre-HSCT diagnosis of pulmonary disease. Pulmonary infection (n=30) and bronchiectasis (n=11) were the most common diagnoses (Fig. 1A). Compared to patients without pre-HSCT lung disease, patients with pre-HSCT lung disease had higher numbers of pulmonary complications after HSCT, such as the need for non-invasive or mechanical ventilation (23 of 54 patients [43%] vs. 12 of 61 patients [20%]) (Fig. 1B). Amongst patients with pre-HSCT lung disease, 1-year survival was 81% compared with 92% in patients without pre-HSCT lung disease. Overall survival was 76% at a median follow up time of 1.6 years versus 89% at a median follow up of 2.7 years in patients with and without pre-HSCT lung disease, respectively (censored logrank p = 0.05) (Fig. 2). <h3>Conclusion</h3> Within our single center study, PID patients with pre-HSCT lung disease had a trend towards more post-HSCT lung complications and lower OS compared to PID patients without pre-HSCT lung disease. Pulmonary risk factors should be carefully considered in PID patients prior to HSCT.

HUBUNGAN EFIKASI DIRI DENGAN KEPATUHAN MINUM OBAT PADA PASIEN TBC DI WILAYAH KERJA PUSKESMAS PARONGPONG KECAMATAN PARONGPONG KABUPATEN BANDUNG BARAT

Tuberkulosis adalah penyakit infeksi paru yang disebabkan oleh Mycobacterium Tuberculosis. Di Indonesia kasus tuberkulosis setiap tahunnya semakin meningkat. Indonesia menepati urutan ke-6 penderita tuberkulosis tertinggi di dunia, sedangkan Jawa Barat menepati urutan pertama. Tujuan penelitian ini adalah untuk melihat adanya hubungan anatar efikasi diri dengan kepatuhan minum obat OAT. Metode penelitian menggunakan desain deskriptif korelasional dengan pendekatan cross sectional dengan melibatkan 23 responden yang sedang menjalani pengobatan di puskesmas parongpong, responden dipilih dengan menggunakan Purposive sampling. Variabel independen adalah efikasi diri, variabel dependent adalah kepatuhan minum obat. Instrumen dalam penelitian ini adalah kuesioner yang dianalisis menggunakan pearson’s r . Hasil dan analisis Efikasi Diri dengan Kepatuhan Minum obat mempunyai hubungan dengan nilai p-value 0,030 atau (p ≤ 0,05) dengan tingkat hubungan sedang (0,454). Efikasi merupakan salah satu faktor yang mempengaruhi kepatuhan minum obat pasien tuberkulosis di wilayah kerja Puskesmas Parongpong. Saran untuk penelitian selanjutnya perlu mengetahui peran kader kesehatan dalam kepatuhan minum obat.

Positive tumour CD47 expression is an independent prognostic factor for recurrence in resected non-small cell lung cancer

BackgroundImmunotherapy is a promising advance in oncology. Limited information exists regarding the interrelationship between CD47 expression and tumour-associated macrophage-related immuno-microenvironment in patients with non-small cell lung cancer (NSCLC). These factors may predict novel immunotherapy efficacy.Patients and methodsCD47 and PD-L1 expression was retrospectively assessed in 191 resected NSCLC specimens via immunohistochemistry. Forty-six patients with pulmonary infectious diseases were enrolled as the control group. The infiltration of macrophages (M2 and M1) and CD8+ T-lymphocytes was evaluated via dual-immunofluorescence staining. Targeted DNA sequencing was performed on NSCLC specimens. Survival analysis was performed using the Cox model.ResultsUsing 2+/3+ as a CD47 positive (CD47pos) expression cut-off, the prevalence of CD47pos expression in NSCLC was 33.0% (63/191), significantly higher than in pulmonary infectious diseases. CD47pos expression was significantly higher in female, non-smoking and adenocarcinoma patients (p=0.020, p<0.001 and p<0.001, respectively). Furthermore, CD47pos expression was significantly correlated with epidermal growth factor receptor mutation (p<0.001). The expression of CD47 (H-score) in NSCLC was negatively correlated with tumour PD-L1 expression (p=0.0346) and tumour mutation burden (p=0.0107). CD47pos expression was independently correlated with poor disease-free survival in patients with resected NSCLC in multivariate Cox regression analysis (p=0.035).ConclusionThis study revealed the demographic, molecular and immuno-microenvironment characteristics of CD47 expression in NSCLC. We identified tumour CD47pos expression as an independent prognostic factor for recurrence in resected NSCLC. Our findings illustrate the potential of anti-CD47 treatment in NSCLC.

Active and prospective latent tuberculosis are associated with different metabolomic profiles: clinical potential for the identification of rapid and non-invasive biomarkers

ABSTRACT Although 23% of world population is infected with Mycobacterium tuberculosis (M. tb), only 5–10% manifest the disease. Individuals surely exposed to M. tb that remain asymptomatic are considered potential latent TB (LTB) cases. Such asymptomatic M. tb.-exposed individuals represent a reservoir for active TB cases. Although accurate discrimination and early treatment of patients with active TB and asymptomatic M. tb.-exposed individuals are necessary to control TB, identifying those individuals at risk of developing active TB still remains a tremendous clinical challenge. This study aimed to characterize the differences in the serum metabolic profile specifically associated to active TB infected individuals or to asymptomatic M. tb.-exposed population. Interestingly, significant changes in a specific set of metabolites were shared when comparing either asymptomatic house-hold contacts of active TB patients (HHC-TB) or active TB patients (A-TB) to clinically healthy controls (HC). Furthermore, this analysis revealed statistically significant lower serum levels of aminoacids such as alanine, lysine, glutamate and glutamine, and citrate and choline in patients with A-TB, when compared to HHC-TB. The predictive ability of these metabolic changes was also evaluated. Although further validation in independent cohorts and comparison with other pulmonary infectious diseases will be necessary to assess the clinical potential, this analysis enabled the discrimination between HHC-TB and A-TB patients with an AUC value of 0.904 (confidence interval 0.81–1.00, p-value < 0.0001). Overall, the strategy described in this work could provide a sensitive, specific, and minimally invasive method that could eventually be translated into a clinical tool for TB control.

Chicken Cyclo-oxygenases Response in a Pulmonary Infection Disease

Avian infectious bronchitis, associated coronavirus causes inflammation and damage to the lungs. To evaluate the molecular mechanisms behind this event, we investigated variations in the expression level of the proinflammatory factors, cyclo-oxygenase 1 (COX-1) and cyclo-oxygenases 2 (COX-2). In mammals, the increased generation of prostaglandins during the onset of inflammatory responses and activation of immune cell types has been attributed to the induction of COX-2. The recent sequencing of chicken genome and the identification of genes coding COX-1 and COX-2 allowed us to analyze their expression in lung inflammatory disease. The purpose of this study was to examine the relative expression and distribution of COX-1 and COX-2 in organs of normal hens and in hens with avian infection bronchitis. The expression levels of cyclo-oxygenase genes in several organs from uninfected chickens and infected ones were measured using a quantitative reverse transcription-PCR technique. Our results show that the expression level of COX-1 was highly up regulated in spleen, small intestine, lungs, and liver, but modestly up regulated in the pancreas. However, no significant change was observed in the expression levels of COX-2, in the small intestine, liver and spleen; suggesting a constitutive expression of this enzyme. Whereas, COX-2 mRNA expression was significantly decreased in the heart and lungs of infected chickens, ranging from 9-fold to 4-fold, respectively (p<0.05). Contrary to mammals, COX-2 is present constitutively in bird’s cells, while COX-1 is expressed primarily after inflammation.

Predicted therapeutic targets for COVID-19 disease by inhibiting SARS-CoV-2 and its related receptors.

The SARS-CoV-2 causes severe pulmonary infectious disease with an exponential spread-ability. In the present research, we have tried to look into the molecular cause of disease, dealing with the development and spread of the coronavirus disease 2019 (COVID-19). Therefore, different approaches have investigated against disease development and infection in this research; First, We identified hsa-miR-1307-3p out of 1872 pooled microRNAs, as the best miRNA, with the highest affinity to SARS-CoV-2 genome and its related cell signaling pathways. Second, the findings presented that this miRNA had a considerable role in PI3K/Act, endocytosis, and type 2 diabetes, moreover, it may play a critical role in the prevention of GRP78 production and the virus entering, proliferation and development. Third, nearly 1033 medicinal herbal compounds were collected and docked with ACE2, TMPRSS2, GRP78, and AT1R receptors, which were the most noticeable receptors in causing the COVID-19. Among them, there were three common compounds including berbamine, hypericin, and hesperidin, which were more effective and appropriate to prevent the COVID-19 infection. Also, it was revealed some of these chemical compounds which had a greater affinity for AT1R receptor inhibitors can be suitable therapeutic targets for inhibiting AT1R and preventing the adverse side effects of this receptor. According to the result, clinical assessment of these three herbal compounds and hsa-miR-1307-3p may have significant outcomes for the prevention, control, and treatment of COVID-19 infection.

The utility of bronchoscopy in immunocompromised patients: a review.

Bronchoscopy is an important tool for the diagnosis of pulmonary disorders in immunocompromised patients. The addition of biopsies to bronchoalveolar lavage improves the diagnostic yield of non-infectious etiologies, although the underlying etiology of the immunocompromised state must be considered and may be influential. Certain unknowns remain, including timing of bronchoscopy and its impact on medical management and mortality. The ongoing role of non-invasive testing for infectious complications prior to bronchoscopy also remains to be defined. This review addresses the role of bronchoscopy in immunocompromised states related to underlying hematologic malignancies, prescription drug use or chemotherapy, and other disorders that predispose patients to infectious or non-infectious pulmonary diseases.

Characterization of gut microbiota in children with pulmonary tuberculosis

BackgroundGut microbiota plays a critical role in many important physiological processes and is linked with various pulmonary infectious diseases. The relationship between pulmonary tuberculosis (PTB) and gut microbiota has been poorly studied. The present study aimed to characterize gut microbiota in pediatric patients with PTB.MethodsA case-controlled study was executed for the characterization of gut microbiota in pediatric PTB patients. Fecal samples were collected from the PTB patients and healthy controls upon admission. In addition, a one-month follow-up assessment was performed to investigate alterations in the gut microbiota post anti-tuberculosis treatment. 16SrDNA sequencing analysis of fecal DNA was completed on the Illumina MiSeq platform.ResultsCompared with healthy controls, the gut microbiota of pediatric patients with PTB was characterized by decreased microbial diversity. PTB patients further presented an up-regulation of the pro-inflammatory bacteria Prevotella, the opportunistic pathogen Enterococcus, as well as a reduction of beneficial bacteria including Ruminococcaceae, Bifidobacteriaceae and prausnitzii. One-month after anti-tuberculosis therapy, the richness of gut microbiota in PTB patients was distinctly depleted.ConclusionsThe gut microbiota of pediatric patients with PTB was significantly distinct from healthy controls. Additionally, the richness of gut microbiota in PTB patients decreased after one-month anti-tuberculosis treatment. It is hypothesized that the homeostasis of gut microbiota in PTB patients may affect the pathogenies of PTB by de-regulation of the hosts’ immune status through the gut-lung axis.

Diagnostic performance of pathology, culture and ROSE of lung biopsy for suspected pulmonary infectious diseases

Objective: To explore the diagnostic performance of CT guided percutaneous lung biopsy (PTLB) with pathology, culture and rapid on-site evaluation (ROSE) in patients with pulmonary infectious diseases. Methods: From January 2016 to June 2018, a retrospective study was implemented in the Department of Pulmonary and Critical Care Medicine of the First Affiliated Hospital of Wenzhou Medical University. Patients who received PTLB, suspected with lung infection were included. The basic information, clinical symptoms, imaging findings, diagnostic methods, complications, and changes in treatment of cases were collected. The diagnostic sensitivity of histopathology, microbial culture, and ROSE were evaluated at the same time. Results: A total of 529 cases were enrolled, including 354 males and 175 females, (59±14) years old in average. Tuberculosis was identified in 197 cases, non-tuberculosis mycobacteria (NTM) pulmonary disease in 8, cryptococcosis in 95, pulmonary aspergillosis in 27, filamentous fungal pneumonia in 3, talaromyces marneffei pulmonary infection in 3 and pulmonary candidiasis in 1, bacterial pneumonia in 39, and pathogen were unknown in 156 cases. A total of 417 cases were submitted for histopathology and microbial culture at the same time, the diagnostic value of pathology and microbial culture were 35.0% (146/417) and 45.6% (190/417), respectively. Combined pathology with microbial culture, the diagnostic value increased to 62.8% (262/417). The diagnostic accuracy of ROSE was 51.8% (71/137). The most common complication of PTLB was pneumothorax 26.1% (138/529). 56.1% (297/529) of the patients received targeted treatment after the diagnosis was confirmed, and 43.9% (232/529) maintained the original treatment. Conclusion: The pathology, microbial culture, and ROSE of PTLB have relative high diagnostic value for pulmonary infectious diseases.

1363. Does Genotypic Testing Improve Treatment Outcomes in Drug-Resistant Tuberculosis?

BackgroundTreatment of drug-resistant tuberculosis (DR-TB) requires toxic and complex drug regimens. Dismal outcomes occur due to a delay in the report of susceptibility results. WHO endorses genotypic tests like line probe assay (Mtbdrsl) for an early diagnosis enabling start of robust treatment regimens. Data correlating Mtbdrsl and specific mutations with outcome are rare.MethodsA concurrent cohort study was conducted on all patients diagnosed to have DR-TB between January 2016 and June 2017 in the departments of Pulmonary Medicine and Infectious Diseases at a tertiary care center in India. Patients aged >18 years with a positive Mtbdrsl (done on culture) or Mycobacterial culture were prospectively followed up till completion of therapy for assessment of outcomes. Patients were divided into 2 groups based on diagnostic method used: culture group and Mtbdrsl group. Risk factors for adverse outcomes were assessed.ResultsTotal of 82 patients, of which 62.2% were males with a mean age of 32 years were included; 50 in the Mtbdrsl group and 32 in the culture group. Among these, 40.2% were multi-drug-resistant Tuberculosis (MDR-TB), 53.7% were Pre–XDR (pre-extensively drug resistant i.e, quinolone-resistant tuberculosis) and 6.1% were XDR (extensively drug-resistant TB). Isolated pulmonary involvement (46.3%) was common followed by disseminated TB (29.3%). Overall good outcome was seen in 39/82 (14.6% cured and 32.9% completed treatment) and bad outcome in 43/82 (41.5% lost to follow up, 7.3% treatment failure and 3.7% died). Good outcome was noted in Mtbdrsl group was 22/50 (44%) vs. 17/32 (53.1%) in the culture group. Mtbdrsl group had 140 days mean decrease in time to initiation of appropriate therapy but the odds of having a better outcome was 0.693 (CI: 0.284–1.690, P = 0.499). Among the 15 different types of mutations, FQ mutations gyrA 94Gly and gyrA 90Val comprised 15% each with gyrA 94Gly noted to have a poorer outcome [OR 2.5 (CI 0.471–13.265)]. All 5 patients with XDR TB (50 % had rrs 1401Gly mutation) had a poor outcome.ConclusionContrary to what is expected, Mtbdrsl did not significantly contribute to better treatment outcomes. High-risk mutation gyrA 94Gly was prevalent and associated with poorer outcomes. Small sample size and a wide variety of mutations preclude generalizability of our results.Disclosures All authors: No reported disclosures.

HMGN2 regulates non-tuberculous mycobacteria survival via modulation of M1 macrophage polarization.

Non‐tuberculous mycobacteria (NTM), also known as an environmental and atypical mycobacteria, can cause the chronic pulmonary infectious diseases. Macrophages have been suggested as the main host cell to initiate the innate immune responses to NTM infection. However, the molecular mechanism to regulate the antimicrobial immune responses to NTM is still largely unknown. Current study showed that the NTM clinical groups, Mycobacterium abscessus and Mycobacterium smegmatis, significantly induced the M1 macrophage polarization with the characteristic production of nitric oxide (NO) and marker gene expression of iNOS, IFNγ, TNF‐α, IL1‐β and IL‐6. Interestingly, a non‐histone nuclear protein, HMGN2 (high‐mobility group N2), was found to be spontaneously induced during NTM‐activated M1 macrophage polarization. Functional studies revealed that HMGN2 deficiency in NTM‐infected macrophage promotes the expression of M1 markers and the production of NO via the enhanced activation of NF‐κB and MAPK signalling. Further studies exhibited that HMGN2 knock‐down also enhanced IFNγ‐induced M1 macrophage polarization. Finally, we observed that silencing HMGN2 affected the survival of NTM in macrophage, which might largely relevant to enhanced macrophage polarization into M1 phenotype under the NTM infection. Collectively, current studies thus suggested a novel function of HMGN2 in regulating the anti‐non‐tuberculous mycobacteria innate immunity of macrophage.

&lt;p&gt;A community-acquired lung abscess attributable to odontogenic flora&lt;/p&gt;

A lung abscess is an infectious pulmonary disease characterized by pus-filled cavity formation and often an air-fluid level. In this article, we described an indolent community-acquired lung abscess suspected as a tumor previously. A 56-year-old male presented with cough and expectoration for 2 months and hemoptysis for 2 weeks. His physical examinations, whole blood count and C-reactive protein level were normal. The chest computed tomography (CT) scan showed a 40×38×39 mm high-density mass in the right upper pulmonary lobe, with irregular borders. The pathology of a CT-guided percutaneous needle aspiration biopsy showed numerous inflammatory cells and bacteria infiltration without tumor lesions. Bacteriological detection of lung tissue revealed the cause was odontogenic flora. A next-generation sequencing demonstrated the etiologic correlation between lung abscess and periodontitis. After a 2-month pathogen-directed oral antibiotics therapy combined with chlorhexidine gargle oral care, this patient showed a remarkable improvement. Periodontitis can be a cause of a lung abscess, which would be taken into account in the treatment regimes preventing infectious recurrence.

Regulation of lung immunity by dendritic cells: Implications for asthma, chronic obstructive pulmonary disease and infectious disease.

Since the first description of dendritic cells by Steinman and Cohn in 1973, this important cell type has gained increasing attention. Over 4000 papers have been published on this topic annually during the last few years. At the beginning, dendritic cells were recognized for their immune stimulatory properties and their importance in initiating an adaptive immune response. Later, it was found that dendritic cells do not only initiate but also regulate immune responses. This attribute makes the so-called regulatory dendritic cells highly important for the prevention of exaggerated immune responses. Immune cells make contact with different Ags every day and must be tightly controlled to prevent excessive inflammation and subsequent organ destruction, particularly in organs such as the gut and lungs. Here, we give a brief overview of our current knowledge on how immune responses are controlled by dendritic cells, highlighting how they are involved in the induction of peripheral tolerance. We focus on what is known about these processes in the lung, with a closer look at their role in the induction and control of diseases such as bronchial asthma, chronic obstructive pulmonary disease and lung infections. Finally, we summarize some current approaches to modulate the behavior of dendritic cells that may hopefully lead to future therapeutics to control exaggerated immune responses.

The association between adherence to national antibiotic guidelines and mortality, readmission and length of stay in hospital inpatients: results from a Norwegian multicentre, observational cohort study

BackgroundClinical antibiotic prescribing guidelines are essential in defining responsible use in the local context. Our objective was to investigate the association between adherence to national antibiotic prescribing guidelines and patient outcomes across a wide range of infectious diseases in hospital inpatients.MethodsOver five months in 2014, inpatients receiving antibiotics under the care of pulmonary medicine, infectious diseases and gastroenterology specialties across three university hospitals in Western Norway were included in this observational cohort study. Patient and antibiotic prescribing data gathered from electronic medical records included indication for antibiotics, microbiology test results, discharge diagnoses, length of stay (LOS), comorbidity, estimated glomerular filtration rate (eGFR) on admission and patient outcomes (primary: 30-day mortality; secondary: in-hospital mortality, 30-day readmission and LOS). Antibiotic prescriptions were classified as adherent or non-adherent to national guidelines according to documented indication for treatment. Patient outcomes were analysed according to status for adherence to guidelines using multivariate logistic, linear and competing risk regression analysis with adjustments made for comorbidity, age, sex, indication for treatment, seasonality and whether the patient was admitted from an institution or not.ResultsIn total, 1756 patients were included in the study. 30-day-mortality and in-hospital mortality were lower (OR = 0.48, p = 0.003 and OR = 0.46, p = 0.001) in the guideline adherent group, compared to the non-adherent group. Adherence to guideline did not affect 30-day readmission. In linear regression analysis there was a trend towards shorter LOS when LOS was analysed for patients discharged alive (predicted mean difference − 0.47, 95% CI (− 1.02, 0.07), p = 0.081). In competing risk analysis of LOS, the adherent group had a subdistribution hazard ratio (SHR) of 1.17 95% CI (1.02, 1.34), p = 0.025 for discharge compared to the non-adherent group.ConclusionsAdhering to antibiotic guidelines when treating infections in hospital inpatients was associated with favourable patient outcomes in terms of mortality and LOS.

Of mice or men? Developing an ex vivo model of Staphylococcus aureus infection in the cystic fibrosis lung

Staphylococcus aureus is one of the dominant organisms isolated from the airways of cystic fibrosis (CF) patients, particularly early in life, and is usually regarded as pathogenic. However, there remains significant gaps in our understanding of the role of S. aureus in the progression of pulmonary infection and lung disease in CF. Mouse models of S. aureus lung infection, even in CF animals, frequently demonstrate pneumonia and abscesses of the lung, a phenomenon very rarely observed in people with CF. Furthermore, live host models are associated with high costs and are limited in duration and sample size for ethical reasons. Most in vitro models fail to consider the influence of host tissue interaction or spatial structure on the development and persistence of infection. We have previously described an ex vivo pig lung model (EVPL) of cystic fibrosis for Pseudomonas aeruginosa lung infection. Here we show the progression of this model to support the growth of Staphylococcus aureus. Our data suggests that, in our model, S. aureus cells may preferentially aggregate in artificial sputum rather than adhere to lung tissue. In the context of historical case reports, this result potentially reflects the clinical situation in cystic fibrosis more accurately than mouse models and could have substantial clinical significance.

Loop-mediated isothermal amplification for detection of Legionella pneumophila in respiratory specimens of hospitalized patients in Ahvaz, southwest Iran.

BackgroundLegionnaires’ disease is an important public health problem that can cause substantial mortality and morbidity. Legionnaires’ disease-risk estimation may be compromised by uncertainties in Legionella-detection methods. The aim of this study was the detection of L. pneumophila in respiratory specimens of hospitalized patients with respiratory symptoms by culture, PCR, and loop-mediated isothermal amplification (LAMP) methods.MethodsSputum and bronchoalveolar lavage samples were obtained from patients with pneumonia admitted to teaching hospitals in Ahvaz, Iran from June 2016 to March 2017. Isolation of Legionella spp. was done by culturing the samples directly onto buffered charcoal–yeast extract and modified Wadowsky–Yee agar medium. Then, PCR and LAMP assays were performed for detection of L. pneumophila via its mip gene in respiratory specimens.ResultsA total of 100 respiratory specimens were collected. Our results showed that 1% of the samples were culture positive for Legionella spp., and 3% and 7% of samples were positive for L. pneumophila using the mip gene on PCR and LAMP assays, respectively.ConclusionLegionnaires’ disease should be considered in the diagnosis of pulmonary infectious diseases. Also, the LAMP assay is a faster method with higher sensitivity and specificity than conventional methods, such as PCR and culture, for laboratory diagnosis of Legionnaires’ disease.

Protective Features of Autophagy in Pulmonary Infection and Inflammatory Diseases.

Autophagy is a highly conserved catabolic process involving autolysosomal degradation of cellular components, including protein aggregates, damaged organelles (such as mitochondria, endoplasmic reticulum, and others), as well as various pathogens. Thus, the autophagy pathway represents a major adaptive response for the maintenance of cellular and tissue homeostasis in response to numerous cellular stressors. A growing body of evidence suggests that autophagy is closely associated with diverse human diseases. Specifically, acute lung injury (ALI) and inflammatory responses caused by bacterial infection or xenobiotic inhalation (e.g., chlorine and cigarette smoke) have been reported to involve a spectrum of alterations in autophagy phenotypes. The role of autophagy in pulmonary infection and inflammatory diseases could be protective or harmful dependent on the conditions. In this review, we describe recent advances regarding the protective features of autophagy in pulmonary diseases, with a focus on ALI, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), tuberculosis, pulmonary arterial hypertension (PAH) and cystic fibrosis.

Long-term expanding human airway organoids for disease modeling.

Organoids are self‐organizing 3D structures grown from stem cells that recapitulate essential aspects of organ structure and function. Here, we describe a method to establish long‐term‐expanding human airway organoids from broncho‐alveolar resections or lavage material. The pseudostratified airway organoids consist of basal cells, functional multi‐ciliated cells, mucus‐producing secretory cells, and CC10‐secreting club cells. Airway organoids derived from cystic fibrosis (CF) patients allow assessment of CFTR function in an organoid swelling assay. Organoids established from lung cancer resections and metastasis biopsies retain tumor histopathology as well as cancer gene mutations and are amenable to drug screening. Respiratory syncytial virus (RSV) infection recapitulates central disease features, dramatically increases organoid cell motility via the non‐structural viral NS2 protein, and preferentially recruits neutrophils upon co‐culturing. We conclude that human airway organoids represent versatile models for the in vitro study of hereditary, malignant, and infectious pulmonary disease.