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During bacteremic pneumonia, the prevailing dogma is that bacteria seed from the lungs into the blood. Recently, we have shown that experimental murine sepsis is preceded by intracellular replication within splenic macrophages (Ercoli Nat Microbiol 2018), which shed into the bloodstream initiating invasive disease. Here we aimed to investigate a role for the spleen in the pathogenesis of bacteraemia following pneumonia. We analysed by confocal microscopy the fate of pneumococci during ex vivo human spleen perfusions (REC reference: 18/EM/0057), in spleens during pneumonia in non-human primates (Reyes PLOS one 2016) and mice. During ex vivohumanspleenperfusion, clusters of pneumococci were observed within macrophages and the size of bacterial clusters increased over time. To associate these infectious foci to invasive pneumococcal disease during pneumonia, we analysed spleens in a baboon pneumonia model, and detected pneumococcal clusters in splenic macrophages. To test the functional relevance of these data, we treated intranasally-challenged mice with a single, non-therapeutic sub-MIC dose of azithromycin, known to concentrate inside macrophages. Data showed that bacterial lung-counts were identical in treated and untreated mice. Untreated mice showed signs of disease, had high blood and spleen-counts, whereas mice treated with the non-therapeutic dose showed no signs of disease, had low spleen-counts and no bacteraemia. Thus, the number of pneumococci in the spleen, not the lung, correlates to blood-counts during bacterial pneumonia. We hypothesise that after initial control of invasive infection by the spleen, bacteraemia associated with pneumonia arises from a sub-set of splenic macrophages that are permissive for bacterial replication.

Community-acquired pneumonia (CAP) is one of the most common causes of mortality world-wide. The mortality rate of patients with CAP is influenced by the severity of the disease, treatment failure and the requirement for hospitalization and/or intensive care unit (ICU) management, all of which may be predicted by biomarkers and clinical scoring systems. Areas covered: We review the recent literature examining the efficacy of established and newly-developed clinical scores, biological and inflammatory markers such as C-Reactive protein (CRP), procalcitonin (PCT) and Interleukin-6 (IL-6), whether used alone or in conjunction with clinical severity scores to assess the severity of CAP, predict treatment failure, guide acute in-hospital or ICU admission and predict mortality. Expert commentary: The early prediction of treatment failure using clinical scores and biomarkers plays a developing role in improving survival of patients with CAP by identifying high-risk patients requiring hospitalization or ICU admission; and may enable more efficient allocation of resources. However, it is likely that combinations of scoring systems and biomarkers will be of greater use than individual markers. Further larger studies are needed to corroborate the additive value of these markers to clinical prediction scores to provide a safer and more effective assessment tool for clinicians.

Purpose The purpose of the study is to evaluate the frequency and barriers to use of ultrasound guidance for central venous catheter (CVC) insertion by physicians specializing in critical care and hospital medicine. Materials and methods A national cross-sectional electronic survey of intensivists and hospitalists was administered from November 2014 to January 2015. Results The survey response rate was 5.9% (1013/17 233). Moderate to very frequent use of ultrasound guidance varied by site: internal jugular vein (80%), subclavian vein (31%), and femoral vein (45%). Nearly all physicians (99%) who insert internal jugular CVCs daily use ultrasound guidance, whereas only 46% of physicians who insert subclavian CVCs daily use ultrasound guidance. Use of real-time ultrasound guidance varied by insertion site: internal jugular vein (73%), subclavian vein (28%), and femoral vein (42%). Most physicians (59%) reported not being comfortable with real-time needle tracking at the subclavian site. The most frequently reported barriers to use of ultrasound guidance were (1) limited availability of ultrasound equipment (28%), (2) perception of increased total procedure time (22%), and (3) concern for loss of landmark skills (13%). Conclusions Most intensivists routinely use ultrasound guidance to insert internal jugular CVCs but not subclavian CVCs. The most commonly reported barrier to ultrasound use was limited access to an ultrasound machine.

Purpose Recent data have not demonstrated improved outcomes when guideline-concordant (GC) antibiotics are given to patients with health care–associated pneumonia (HCAP). This study was designed to evaluate the relationship between health outcomes and GC therapy in patients admitted to an intensive care unit (ICU) with HCAP. Materials and methods We performed a population-based cohort study of patients admitted to greater than 150 hospitals in the US Veterans Health Administration system to compare baseline characteristics, bacterial pathogens, and health outcomes in ICU patients with HCAP receiving GC-HCAP therapy, GC community-acquired pneumonia (GC-CAP) therapy, or non-GC therapy. The primary outcome was 30-day patient mortality. Risk factors for the primary outcome were assessed in a multivariable logistic regression model. Results A total of 3593 patients met inclusion criteria and received GC-HCAP therapy (26%), GC-CAP therapy (23%), or non-GC therapy (51%). Patients receiving GC-HCAP had higher 30-day patient mortality compared to GC-CAP patients (34% vs 22%; P Conclusions Our data do not demonstrate improved outcomes among ICU patients with HCAP who received GC-HCAP therapy.

Background In response to occupational and environmental exposures, cough can be an isolated symptom reflecting exposure to an irritant with little physiological consequence, or it can be a manifestation of more significant disease. This document reviews occupational and environmental contributions to chronic cough in adults, focusing on aspects not previously covered in the 2006 ACCP Cough Guideline or our more recent systematic review, and suggests an approach to investigation of these factors when suspected. Methods MEDLINE and TOXLINE literature searches were supplemented by articles identified by the cough panel occupational and environmental subgroup members, to identify occupational and environmental aspects of chronic cough not previously covered in the 2006 ACCP Cough Guideline. Based on the literature reviews and the Delphi methodology, the cough panel occupational and environmental subgroup developed guideline suggestions that were approved after review and voting by the full cough panel. Results The literature review identified relevant articles regarding: mechanisms; allergic environmental causes; chronic cough and the recreational and involuntary inhalation of tobacco and marijuana smoke; nonallergic environmental triggers; laryngeal syndromes; and occupational diseases and exposures. Consensus-based statements were developed for the approach to diagnosis due to a lack of strong evidence from published literature. Conclusions Despite increased understanding of cough related to occupational and environmental triggers, there remains a gap between the recommended assessment of occupational and environmental causes of cough and the reported systematic assessment of these factors. There is a need for further documentation of occupational and environmental causes of cough in the future.

Background and objective Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) due to Pseudomonas aeruginosa (PA) are associated with worse outcomes. PA antibiotic resistance is important to determine treatment and may influence clinical outcomes. The aim was to study clinical characteristics and outcomes in patients with AECOPD associated with PA based on their antibiotic resistance. Methods This was a prospective observational study including all patients with AECOPD and positive PA sputum culture admitted in a respiratory ward in a tertiary hospital in Barcelona during 2013–2014. PA was defined as resistant (PA-R) when the antibiogram showed ≥1 resistance. Results Four hundred one patients with AECOPD were evaluated. Of them, 54 (13%) had a positive PA sputum culture. Eighty-two per cent were men, median age was 77 (SD 7) years old and FEV1 was less than 36% (SD 17) of predicted value. PA-R was isolated in 35 patients (66%), and PA-sensitive (PA-S) was isolated in 18 (34%) patients. No differences were found in demographics, lung function and comorbidities among groups. PA-R patients were more likely exposed to prior oral corticosteroids (77% vs 44%, P = 0.03) and antibiotics (77% vs 31%, P = 0.01), respectively. AECOPD patients associated with PA-S were more likely to die at 30 days (odds ratio 13.53, 95% confidence interval: 1.14–69.56, P = 0.03) and 90 days (odds ratio 7.09, 95% confidence interval: 1.33–37.89, P = 0.02), respectively. Conclusion Pseudomonas aeruginosa-resistant affects patients with severe AECOPD and previous use of corticosteroids and antibiotics. The presence of PA-S is associated with higher mortality. These results may suggest increased virulence in PA-S strains causing acute infections.

BACKGROUND Prognostication of patients hospitalized with acute decompensated heart failure (ADHF) is important to patients, providers, and healthcare systems. Few bedside tools exist to prognosticate patients hospitalized with ADHF. OBJECTIVE The objective of this study was to assess the relationship between inferior vena cava (IVC) diameter and postdischarge mortality in patients hospitalized with ADHF. DESIGN Prospective observational study. SETTING A 247-bed urban teaching hospital in Spain PATIENTS Ninety-seven patients hospitalized with ADHF. INTERVENTION None. MEASUREMENTS The IVC diameter and collapsibility were measured by a hospitalist at the time of admission and discharge. Primary outcome was 90-day all-cause mortality. Secondary outcomes were readmission rates at 90 and 180 days, and 180-day all-cause mortality. Patients were followed for 180 days. RESULTS Data from 80 patients were analyzed. From admission to discharge, a significant improvement in IVC maximum (IVCmax) diameter (2.12 vs 1.87 cm; P < 0.001) and IVC collapsibility (25.7% vs 33.1%; P < 0.001) was seen in the total study cohort. During the 90-day follow-up period, 11 patients (13.7%) died. An admission IVCmax diameter ≥1.9 cm was associated with a higher mortality rate at 90 days (25.4% vs 3.4%; P = 0.009) and 180 days (29.3% vs 3.4%; P = .003). In a multivariate Cox proportional hazards regression analysis, admission IVCmax diameter was an independent predictor of 90-day mortality (hazard ratio [HR]: 5.88; 95% confidence interval [CI]: 1.21-28.10; P = 0.025) and 90-day readmission (HR: 3.20; 95% CI: 1.24-8.21; P = 0.016). CONCLUSION In patients hospitalized with acute decompensated heart failure, a dilated IVC by bedside ultrasound at the time of admission is associated with a higher 90-day mortality after hospitalization. Journal of Hospital Medicine 2016. © 2016 Society of Hospital Medicine

An update and literature review assessing the implications for use of macrolide therapy for patients with pneumonia is very relevant. Multiple studies have focused on assessing the efficacy, clinical effectiveness and clinical risks associated with the use of macrolides.The scope of this review is on recently published literature regarding the use of macrolides in patients with pneumonia. Recent evidence suggests that macrolides may benefit several populations of patients with pneumonia that includes ambulatory care, hospitalized patients with nonsevere pneumonia and severe pneumonia patients requiring ICU admission. In addition, there is benefit among patients with pneumococcal pneumonia, particularly those patients hospitalized with severe disease. The contradictory results that emerged from recent randomized controlled trials testing the efficacy of macrolide are discussed. Important remarks are made to the risks of cardiovascular events related to the use of macrolides and the clinical implications for care.A careful decision on the use of macrolides in patients with pneumonia will need to balance the possible beneficial effects and the risks linked to their use.

Background: We aimed to determine whether treatment with oseltamivir was associated with decreased mortality among patients admitted to intensive care units (ICUs) with severe influenza and whether early therapy (within 48 hours of symptoms onset) was associated with improved survival rates. Methods: This was a prospective observational study of patients with confirmed influenza who were admitted to 184 ICUs in Spain. The primary outcomes were to investigate the association of ICU mortality with oseltamivir therapy by comparing patients who are untreated (UT group) with those who are treated (all treated; AT group) and those in early treatment (ET) and late treatment (LT) groups. We also assessed the associations of both ET and LT with ICU mortality and compared the results. Findings: We enrolled 4,175 patients of whom 3,537 met the inclusion criteria. Most patients were diagnosed with influenza pneumonia (84·7%). When comparing the AT (n=3,439) and UT (n=98) groups, the former had higher survival after adjusting for severity and confounding factors (Hazard ratio [HR] 0·67; p=0·03). We included 3,388 patients to compare the ET and LT groups. In the multivariable analysis, ICU mortality was lower in the ET group, having an odds ratio of 0·7 (p=0·004). When propensity score matching was applied to a matched cohort (ET, n=790; LT, n=2,522), the ET group had lower ICU mortality (HR 0·78; p=0·008) compared with the LT group, even after a competing risks analysis (sub-HR 0·79; p=0·01). Interpretation: Oseltamivir treatment is associated with better survival rates in patients admitted to ICU with severe influenza, especially when initiated within 48 hours of illness onset. Funding Statement: SEMICYUC (Spanish Society of Critical Care) and Ricardo Barri Casanovas Foundation. Declaration of Interests: JSN-V-T has received research funding from F. Hoffman-La Roche for separate work. He is currently seconded to the Department of Health and Social Care, England (DHSC). The views expressed in this paper are those of the authors and not necessarily those of DHSC. CG-V has received the INTENSIFICACIO Grant- a grant supported by the Catalan Health Agency [PERIS (Pla estrategic de recerca i innovacio en salut – ‘Strategic Plan for Research and Innovation in HealthCare’)]. All other authors declare no competing interests. Ethics Approval Statement: The study was approved by the Joan XXIII University Hospital Ethics Committee (IRB#11809). All data were anonymised, allowing the requirement for informed consent to be waived.

Fibroblast growth factor 21 (FGF21) predicts severity of illness, clinical stability and mortality in community-acquired pneumonia. Validation is needed to confirm the application of FGF21 in clinical practice.http://ow.ly/SYI730nuRc1

Pore-forming toxins are the most common virulence factor in pathogenic bacteria. They lead to membrane permeabilization and cell death. Herein, we show that respiratory epithelial cells (REC) undergoing bacterial pore-forming toxin (PFT)-induced necroptosis simultaneously experienced caspase activation independently of RIPK3. MLKL deficient REC treated with a pan-caspase inhibitor were protected in an additive manner against PFT-induced death. Subsequently, cleaved versions of caspases-2, -4 and -10 were detected within REC undergoing necroptosis by immunoblots and monoclonal antibody staining. Caspase activation was observed in lung samples from mice and non-human primates experiencing Gram-negative and Gram-positive bacterial pneumonia, respectively. During apoptosis, caspase activation normally leads to cell shrinkage, nuclear condensation, and immunoquiescent death. In contrast, caspase activity during PFT-induced necroptosis increased the release of alarmins to the extracellular milieu. Caspase-mediated alarmin release was found sufficient to activate resting macrophages, leading to Interleukin-6 production. In a mouse model of Gram-negative pneumonia, deletion of caspases -2 and -11, the mouse orthologue of caspase-4, reduced pulmonary inflammation, immune cell infiltration and lung damage. Thus, our study describes a previously unrecognized role for caspase activation in parallel to necroptosis, and indicates that their activity plays a critical pro-inflammatory role during bacterial pneumonia.

Chronic obstructive pulmonary disease (COPD) is a frequent comorbid condition associated with increased morbidity and mortality. Pneumonia is the most common infectious disease condition. The purpose of this review is to evaluate the impact of pneumonia in patients with COPD. We will evaluate the epidemiology and factors associated with pneumonia. We are discussing the clinical characteristics of COPD that may favor the development of infections conditions such as pneumonia. Over the last 10 years, there is an increased evidence that COPD patients treated with inhaled corticosteroids are at increased risk to develp pneumonia. We will review the avaialbe information as well as the possible mechanism for this events. We also discuss the impact of influenza and pneumococcal vaccination in the prevention of pneumonia in COPD patients.

Background: Stroke survivors experience long-term disability also affecting informal caregivers (ICG). With current technology, social media might be the only way for ICG to gain training/access support. What resources are available for ICG of older adults who survived stroke (OASS)? Objective: To identify/analyze types of bilingual social media resources available to ICG of OASS Methods: Facebook data was bilingually collected (Spanish), including most popular groups and pages based on search engines containing terms such as stroke, CVA, caregiver. Similar numbers of groups (35 English vs. 52 Spanish) and pages (32 English vs. 34 Spanish) were analyzed. Data included pages and groups’ information, numbers-of-likes, type-of-organization and resources provided. Results: English-Facebook resources were more popular for pages and groups (3820/2010 vs. 190/7; p

Background Unexplained chronic cough (UCC) causes significant impairments in quality of life. Effective assessment and treatment approaches are needed for UCC. Methods This systematic review of randomized controlled trials (RCTs) asked: What is the efficacy of treatment compared with usual care for cough severity, cough frequency, and cough-related quality of life in patients with UCC? Studies of adults and adolescents aged > 12 years with a chronic cough of > 8 weeks' duration that was unexplained after systematic investigation and treatment were included and assessed for relevance and quality. Based on the systematic review, guideline suggestions were developed and voted on by using the American College of Chest Physicians organization methodology. Results Eleven RCTs and five systematic reviews were included. The 11 RCTs reported data on 570 participants with chronic cough who received a variety of interventions. Study quality was high in 10 RCTs. The studies used an assortment of descriptors and assessments to identify UCC. Although gabapentin and morphine exhibited positive effects on cough-related quality of life, only gabapentin was supported as a treatment recommendation. Studies of inhaled corticosteroids (ICS) were affected by intervention fidelity bias; when this factor was addressed, ICS were found to be ineffective for UCC. Esomeprazole was ineffective for UCC without features of gastroesophageal acid reflux. Studies addressing nonacid gastroesophageal reflux disease were not identified. A multimodality speech pathology intervention improved cough severity. Conclusions The evidence supporting the diagnosis and management of UCC is limited. UCC requires further study to establish agreed terminology and the optimal methods of investigation using established criteria for intervention fidelity. Speech pathology-based cough suppression is suggested as a treatment option for UCC. This guideline presents suggestions for diagnosis and treatment based on the best available evidence and identifies gaps in our knowledge as well as areas for future research.

Rationale: Testing for underlying etiology is a key part of bronchiectasis management, but it is unclear whether the same extent of testing is required across the spectrum of disease severity. Objectives: The aim of the present study was to identify the etiology of bronchiectasis across European cohorts and according to different levels of disease severity. Methods: We conducted an analysis of seven databases of adult outpatients with bronchiectasis prospectively enrolled at the bronchiectasis clinics of university teaching hospitals in Monza, Italy; Dundee and Newcastle, United Kingdom; Leuven, Belgium; Barcelona, Spain; Athens, Greece; and Galway, Ireland. All the patients at every site underwent the same comprehensive diagnostic workup as suggested by the British Thoracic Society. Measurements and Main Results: Among the 1,258 patients enrolled, an etiology of bronchiectasis was determined in 60%, including postinfective (20%), chronic obstructive pulmonary disease related (15%), connective tissue disease related (10%), immunodeficiency related (5.8%), and asthma related (3.3%). An etiology leading to a change in patient's management was identified in 13% of the cases. No significant differences in the etiology of bronchiectasis were present across different levels of disease severity, with the exception of a higher prevalence of chronic obstructive pulmonary disease-related bronchiectasis (P < 0.001) and a lower prevalence of idiopathic bronchiectasis (P = 0.029) in patients with severe disease. Conclusions: Physicians should not be guided by disease severity in suspecting specific etiologies in patients with bronchiectasis, although idiopathic bronchiectasis appears to be less common in patients with the most severe disease.

Limited data are available regarding the etiologic impact of health care-associated pneumonia (HCAP) in lung transplant recipients. Therefore, our aim was to evaluate the microbiologic differences between HCAP and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) in lung transplant recipients with a radiographically confirmed diagnosis of pneumonia.We performed a retrospective cohort study of lung transplant recipients with pneumonia at one transplant center over a 7-year period. Eligible patients included lung transplant recipients who developed a first episode of radiographically confirmed pneumonia ≥ 48 h following transplantation. HCAP, HAP, and VAP were classified according to the American Thoracic Society/Infectious Diseases Society of America 2005 guidelines. χ² and Student t tests were used to compare categorical and continuous variables, respectively.Sixty-eight lung transplant recipients developed at least one episode of pneumonia. HCAP (n = 42; 62%) was most common, followed by HAP/VAP (n = 26; 38%) stratified in HAP (n = 20; 77%) and VAP (n = 6; 23%). Pseudomonas aeruginosa was the predominantly isolated organism (n = 22; 32%), whereas invasive aspergillosis was uncommon (10%). Multiple-drug resistant (MDR) pathogens were less frequently isolated in patients with HCAP compared with HAP/VAP (5% vs 27%; P = .009). Opportunistic pathogens were less frequently identified in lung transplant recipients with HCAP than in those with HAP/VAP (7% vs 27%; P = .02). Lung transplant recipients with HCAP had a similar mortality at 90 days (n = 9 [21%] vs n = 4 [15%]; P = .3) compared with patients with HAP/VAP.HCAP was the most frequent infection in lung transplant recipients. MDR pathogens and opportunistic pathogens were more frequently isolated in HAP/VAP. There were no differences in 30- and 90-day mortality between lung transplant recipients with HCAP and those with HAP/VAP.

Background Methicillin-resistant Staphylococcus aureus (MRSA) has been shown to survive on ambient surfaces for extended periods of time. Leftover MRSA environmental contamination in a hospital room places future patients at risk. Manual disinfection supplemented by pulsed xenon ultraviolet (PX-UV) light disinfection has been shown to greatly decrease the MRSA bioburden in hospital rooms. However, the effect of PX-UV in the absence of manual disinfection has not been evaluated. Methods Rooms that were previously occupied by a MRSA-positive patient (current colonization or infection) were selected for the study immediately postdischarge. Five high-touch surfaces were sampled, before and after PX-UV disinfection, in each hospital room. The effectiveness of the PX-UV device on the concentration of MRSA was assessed employing a Wilcoxon signed-rank test for all 70 samples with MRSA in 14 rooms, as well as by surface location. Results The final analysis included 14 rooms. Before PX-UV disinfection there were a total of 393 MRSA colonies isolated from the 5 high-touch surfaces. There were 100 MRSA colonies after disinfection by the PX-UV device and the overall reduction was statistically significant ( P Conclusions Our study results suggest that PX-UV light effectively reduces MRSA colony counts in the absence of manual disinfection. These findings are important for hospital and environmental services supervisors who plan to adapt new technologies as an adjunct to routine manual disinfection.

We review the literature on the use of point-of-care ultrasound to evaluate and manage pleural effusions. Point-of-care ultrasound is more sensitive than physical exam and chest radiography to detect pleural effusions, and avoids many negative aspects of computerized tomography. Additionally, point-of-care ultrasound can assess pleural fluid volume and character, revealing possible underlying pathologies and guiding management. Thoracentesis performed with ultrasound guidance has lower risk of pneumothorax and bleeding complications. Future research should focus on the clinical effectiveness of point-of-care ultrasound in the routine management of pleural effusions and how new technologies may expand its clinical utility.

Background and objective Secreted mucins play a key role in antibacterial defence in the airway, but have not previously been characterized in non-cystic fibrosis (CF) bronchiectasis patients. We aim to investigate the relationship between secreted mucins levels and the presence of bacterial colonization due to potentially pathogenic microorganisms (PPM) in the airways of stable bronchiectasis patients. Methods Clinically stable bronchiectasis patients were studied prospectively at two centres. Patients with other pulmonary conditions were excluded. Spontaneous sputum was subject to bacterial culture, and secreted mucins (MUC2, MUC5AC and MUC5B) were measured in sputum supernatants by ELISA. Results A total of 50 patients were included. PPM were identified from sputum samples in 30 (60%), with Pseudomonas aeruginosa (n = 10) and Haemophilus influenzae (n = 10) as the most common PPM. There were no baseline differences among airway colonized and non-colonized patients. Patients with airways colonized by PPM presented higher levels of airway MUC2. No differences in MUC5AC levels were found among groups, whereas MUC5B levels were undetectable. Patients with P. aeruginosa colonization expressed the highest levels of MUC2. High levels of MUC2 and MUC5AC are also correlated with disease severity using the Bronchiectasis Severity Index. Conclusions Airway MUC2 levels were higher in bronchiectasis patients colonized with PPM compared with those without airway colonization, especially in patients with P. aeruginosa. These findings suggest that airway-secreted mucins levels may play a role in the pathogenesis of airway infection in non-CF bronchiectasis.

BACKGROUND Successful management of chronic cough has varied in the primary research studies in the reported literature. One of the potential reasons relates to a lack of intervention fidelity to the core elements of the diagnostic and/or therapeutic interventions that were meant to be used by the investigators. METHODS We conducted a systematic review to summarize the evidence supporting intervention fidelity as an important methodologic consideration in assessing the effectiveness of clinical practice guidelines used for the diagnosis and management of chronic cough. We developed and used a tool to assess for five areas of intervention fidelity. Medline (PubMed), Scopus, and the Cochrane Database of Systematic Reviews were searched from January 1998 to May 2014. Guideline recommendations and suggestions for those conducting research using guidelines or protocols to diagnose and manage chronic cough in the adult were developed and voted upon using CHEST Organization methodology. RESULTS A total of 23 studies (17 uncontrolled prospective observational, two randomized controlled, and four retrospective observational) met our inclusion criteria. These articles included 3,636 patients. Data could not be pooled for meta-analysis because of heterogeneity. Findings related to the five areas of intervention fidelity included three areas primarily related to the provider and two primarily related to the patients. In the area of study design , 11 of 23 studies appeared to be underpinned by a single guideline/protocol; for training of providers , two of 23 studies reported training, and zero of 23 reported the use of an intervention manual; and for the area of delivery of treatment , when assessing the treatment of gastroesophageal reflux disease, three of 23 studies appeared consistent with the most recent guideline/protocol referenced by the authors. For receipt of treatment , zero of 23 studies mentioned measuring concordance of patient-interventionist understanding of the treatment recommended, and zero of 23 mentioned measuring enactment of treatment , with three of 23 measuring side effects and two of 23 measuring adherence. The overall average intervention fidelity score for all 23 studies was poor (20.74 out of 48). CONCLUSIONS Only low-quality evidence supports that intervention fidelity strategies were used when conducting primary research in diagnosing and managing chronic cough in adults. This supports the contention that some of the variability in the reporting of patients with unexplained or unresolved chronic cough may be due to lack of intervention fidelity. By following the recommendations and suggestions in this article, researchers will likely be better able to incorporate strategies to address intervention fidelity, thereby strengthening the validity and generalizability of their results that provide the basis for the development of trustworthy guidelines.

BACKGROUND We conducted a systematic review on the management of psychogenic cough, habit cough, and tic cough to update the recommendations and suggestions of the 2006 guideline on this topic. METHODS We followed the American College of Chest Physicians (CHEST) methodologic guidelines and the Grading of Recommendations, Assessment, Development, and Evaluation framework. The Expert Cough Panel based their recommendations on data from the systematic review, patients' values and preferences, and the clinical context. Final grading was reached by consensus according to Delphi methodology. RESULTS The results of the systematic review revealed only low-quality evidence to support how to define or diagnose psychogenic or habit cough with no validated diagnostic criteria. With respect to treatment, low-quality evidence allowed the committee to only suggest therapy for children believed to have psychogenic cough. Such therapy might consist of nonpharmacologic trials of hypnosis or suggestion therapy, or combinations of reassurance, counseling, and referral to a psychologist, psychotherapy, and appropriate psychotropic medications. Based on multiple resources and contemporary psychologic, psychiatric, and neurologic criteria ( Diagnostic and Statistical Manual of Mental Disorders , 5th edition and tic disorder guidelines), the committee suggests that the terms psychogenic and habit cough are out of date and inaccurate. CONCLUSIONS Compared with the 2006 CHEST Cough Guidelines, the major change in suggestions is that the terms psychogenic and habit cough be abandoned in favor of somatic cough syndrome and tic cough, respectively, even though the evidence to do so at this time is of low quality.

Administration of medications via aerosolization is potentially an ideal strategy to treat airway diseases. This delivery method ensures high concentrations of the medication in the targeted tissues, the airways, with generally lower systemic absorption and systemic adverse effects. Aerosolized antibiotics have been tested as treatment for bacterial infections in patients with cystic fibrosis (CF), non-CF bronchiectasis (NCFB), and ventilator-associated pneumonia (VAP). The most successful application of this to date is treatment of infections in patients with CF. It has been hypothesized that similar success would be seen in NCFB and in difficult-to-treat hospital-acquired infections such as VAP. This review summarizes the available evidence supporting the use of aerosolized antibiotics and addresses the specific considerations that clinicians should recognize when prescribing an aerosolized antibiotic for patients with CF, NCFB, and VAP.

National Institute for Health Research Respiratory Biomedical Research Unit, Royal Brompton Hospital, and Fibrosis Research Group, Centre for Leukocyte Biology, National Heart Lung Institute, Imperial College, London, UK, and Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, and Circadian Group, Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia, Department of Pulmonary Medicine, Zhongshan Hospital, and Qingpu Branch, Fudan University, Shanghai, China, South Texas Veterans Health Care System, University of Texas Health Science Center, San Antonio, Texas, USA, and Centre for Heart, Lung and Vascular Health, School of Health and Exercise Sciences, Faculty of Health and Social Development, University of British Columbia, Kelowna, British Columbia, Canada

Background and objective Current guidelines recommend empirical treatment against Pseudomonas aeruginosa in community-acquired pneumonia (CAP) patients with specific risk factors. However, evidence to support these recommendations is limited. We evaluate the risk factors and the impact of antimicrobial therapy in patients hospitalized with CAP due to P. aeruginosa. Methods We performed a retrospective population-based study of >150 hospitals. Patients were included if they had a diagnosis of CAP and P. aeruginosa was identified as the causative pathogen. Univariate and multivariate analyses were performed using the presence of risk factors and 30-day mortality as the dependent measures. Results Seven hundred eighty-one patients with P. aeruginosa pneumonia were identified in a cohort of 62 689 patients with pneumonia (1.1%). Of these, 402 patients (0.6%) were included in the study and 379 (0.5%) were excluded due to health care-associated pneumonia or immunosuppression. In patients with CAP due to P. aeruginosa, 272 (67.8%) had no documented risk factors. These patients had higher rates of dementia and cerebrovascular disease. Empirical antibiotic therapy against P. aeruginosa within the first 48 h of presentation was independently associated with lower 30-day mortality in patients with CAP due to P. aeruginosa (hazard ratio (HR) 0.42, 95% confidence interval (CI): 0.23–0.76) and in patients without risk factors for P. aeruginosa CAP (HR 0.40, 95% CI: 0.21–0.76). Conclusions Risk factor recommended by current guidelines only detect one third of the patients admitted with CAP due to P. aeruginosa. Risk factors did not define the whole benefit observed due to empirical therapy covering P. aeruginosa.

BACKGROUND Since the publication of the 2006 American College of Chest Physicians (CHEST) cough guidelines, a variety of tools has been developed or further refined for assessing cough. The purpose of the present committee was to evaluate instruments used by investigators performing clinical research on chronic cough. The specific aims were to (1) assess the performance of tools designed to measure cough frequency, severity, and impact in adults, adolescents, and children with chronic cough and (2) make recommendations or suggestions related to these findings. METHODS By following the CHEST methodologic guidelines, the CHEST Expert Cough Panel based its recommendations and suggestions on a recently published comparative effectiveness review commissioned by the US Agency for Healthcare Research and Quality, a corresponding summary published in CHEST , and an updated systematic review through November 2013. Recommendations or suggestions based on these data were discussed, graded, and voted on during a meeting of the Expert Cough Panel. RESULTS We recommend for adults, adolescents (≥ 14 years of age), and children complaining of chronic cough that validated and reliable health-related quality-of-life (QoL) questionnaires be used as the measurement of choice to assess the impact of cough, such as the Leicester Cough Questionnaire and the Cough-Specific Quality-of-Life Questionnaire in adult and adolescent patients and the Parent Cough-Specific Quality of Life Questionnaire in children. We recommend acoustic cough counting to assess cough frequency but not cough severity. Limited data exist regarding the performance of visual analog scales, numeric rating scales, and tussigenic challenges. CONCLUSIONS Validated and reliable cough-specific health-related QoL questionnaires are recommended as the measurement of choice to assess the impact of cough on patients. How they compare is yet to be determined. When used, the reporting of cough severity by visual analog or numeric rating scales should be standardized. Previously validated QoL questionnaires or other cough assessments should not be modified unless the new version has been shown to be reliable and valid. Finally, in research settings, tussigenic challenges play a role in understanding mechanisms of cough.

The purpose is to report and describe four cases of Echinococcus vogeli hydatidosis in Colombia. Four E. vogeli polycystic hydatidosis cases are presented, two males and two females, aged 18 to 68 years old, from four separate forest Colombian regions. The initial diagnosis of the cystic disease was radiologically obtained, and parasite presence was confirmed through study of the histological material. The locations of the cysts were hepatic in three cases and mesenteric in the other. Surgical resection was performed on all four patients, complemented by albendazole in two of them. Review of clinical findings, diagnoses, and treatment for E. vogeli hydatidosis.

Background Inadequate environmental disinfection represents a serious risk for health care–associated infections. Technologic advancements in disinfection practices, including no-touch devices, offer significant promise to improve infection control. We evaluated one such device, portable pulsed xenon ultraviolet (PX-UV) units, on microbial burden during an implementation trial across 4 Veterans Affairs hospitals. Methods Environmental samples were collected before and after terminal room cleaning: 2 facilities incorporated PX-UV disinfection into their cleaning protocols and 2 practiced manual disinfection only. Specimens from 5 high-touch surfaces were collected from rooms harboring methicillin-resistant Staphylococcus aureus (MRSA) or aerobic bacteria colonies (ABC). Unadjusted pre-post count reductions and negative binomial regression modeled PX-UV versus manual cleaning alone. Results Seventy samples were collected. Overall, PX-UV reduced MRSA and ABC counts by 75.3% and 84.1%, respectively, versus only 25%-30% at control sites. Adjusting for baseline counts, manually cleaned rooms had significantly higher residual levels than PX-UV sites. Combined analyses revealed an incident rate ratio of 5.32 (P = .0024), with bedrails, tray tables, and toilet handrails also showing statistically superior PX-UV disinfection. Conclusions This multicenter study demonstrates significantly reduced disinfection across several common pathogens in facilities using PX-UV devices. Clinical impact of laboratory reductions on infection rates was not assessed, representing a critical future research question. However, such approaches to routine cleaning suggest a practical strategy when integrated into daily hospital operations.

Community-acquired pneumonia (CAP) is an important cause of death around the globe. Up to 30% of patients admitted to hospital for CAP develop cardiovascular complications (i.e. new/worsening heart failure, new/worsening arrhythmias, myocardial infarctions and/or strokes), acutely and up to 10 years thereafter. Cardiac complications result from complex interactions between preexisting conditions, relative ischaemia, upregulation of the sympathetic system, systemic inflammation and direct pathogen-mediated damage to the cardiovascular system. The exact mechanisms underlying the direct host-pathogen interactions are of great interest to identify potential therapeutic and preventative targets for CAP. In this review, we summarize the epidemiological data, risk factors and the pathogen-driven cardiovascular damage affecting patients with CAP.

Community acquired pneumonia (CAP) is associated with high rates of morbidity and mortality, especially among the elderly. Antibiotic treatment for CAP in the elderly is particularly challenging for many reasons, including compliance issues, immunosuppression, polypharmacy and antimicrobial resistance. There are few available antibiotics that are able to address these concerns. Areas covered: After a systematic review of the current literature, we describe seven novel antibiotics that are currently in advanced stages of development (phase 3 and beyond) and show promise for the treatment of CAP in those over the age of 65. These antibiotics are: Solithromycin, Pristinamycin, Nemonaxacin, Lefamulin, Omadacycline, Ceftobiprole and Delafloxacin. Using a novel conceptual framework designed by the present authors, known as the 'San Antonio NIPS model', we evaluate their strengths and weaknesses based on their ability to address the unique challenges that face the elderly. Expert opinion: All seven antibiotics have potential value for effective utilization in the elderly, but to varying degrees based on their NIPS model score. The goal of this model is to reorganize a clinician's focus on antibiotic choices in the elderly and bring attention to a seldom discussed topic that may potentially become a health-care crisis in the next decade.

AIM To determine the ability of intrapulmonary percussive ventilation (IPV) to promote airway clearance in spontaneously breathing patients and those on mechanical ventilation. METHODS An artificial lung was used to simulate a spontaneously breathing patient (Group 1), and was then connected to a mechanical ventilator to simulate a patient on mechanical ventilation (Group 2). An 8.5 mm endotracheal tube (ETT) connected to the test lung, simulated the patient airway. Artificial mucus was instilled into the mid-portion of the ETT. A filter was attached at both ends of the ETT to collect the mucus displaced proximally (mouth-piece filter) and distally (lung filter). The IPV machine was attached to the proximal end of the ETT and was applied for 10-min each to Group 1 and 2. After each experiment, the weight of the various circuit components were determined and compared to their dry weights to calculate the weight of the displaced mucus. RESULTS In Group 1 (spontaneously breathing model), 26.8% ± 3.1% of the simulated mucus was displaced proximally, compared to 0% in Group 2 (the mechanically ventilated model) with a P-value of < 0.01. In fact, 17% ± 1.5% of the mucus in Group 2 remained in the mid-portion of the ETT where it was initially instilled and 80% ± 4.2% was displaced distally back towards the lung (P < 0.01). There was an overall statistically significant amount of mucus movement proximally towards the mouth-piece in the spontaneously breathing (SB) patient. There was also an overall statistically significant amount of mucus movement distally back towards the lung in the mechanically ventilated (MV) model. In the mechanically ventilated model, no mucus was observed to move towards the proximal/mouth piece section of the ETT. CONCLUSION This bench model suggests that IPV is associated with displacement of mucus towards the proximal mouthpiece in the SB patient, and distally in the MV model.

Introduction Patients with severe community-acquired pneumonia (CAP) are believed to have an exaggerated inflammatory response to bacterial infection. Therapies aiming to modulate the inflammatory response have been largely unsuccessful, perhaps reflecting that CAP is a heterogeneous disorder that cannot be modulated by a single anti-inflammatory approach. We hypothesize that the host inflammatory response to pneumonia may be characterized by distinct cytokine patterns, which can be harnessed for personalized therapies. Methods Here, we use hierarchical cluster analysis of cytokines to examine if patterns of inflammatory response in 13 hospitalized patients with CAP can be defined. This was a secondary data analysis of the Community-Acquired Pneumonia Inflammatory Study Group (CAPISG) database. The following cytokines were measured in plasma and sputum on the day of admission: interleukin (IL)-1β, IL-1 receptor antagonist (IL-1ra), IL-6, CXCL8 (IL-8), IL-10, IL-12p40, IL-17, interferon (IFN)γ, tumor necrosis factor (TNF)α, and CXCL10 (IP-10). Hierarchical agglomerative clustering algorithms were used to evaluate clusters of patients within plasma and sputum cytokine determinations. Results A total of thirteen patients were included in this pilot study. Cluster analysis identified distinct inflammatory response patterns of cytokines in the plasma, sputum, and the ratio of plasma to sputum. Conclusions Inflammatory response patterns in plasma and sputum can be identified in hospitalized patients with CAP. Characterization of the local and systemic inflammatory response may help to better discriminate patients for enrollment into clinical trials of immunomodulatory therapies.

Background Limited data are available regarding the impact of the potential validation of the Canadian Thoracic Society (CTS) guidelines recommendations in classifying patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in simple and complex. The aim of the present study was to assess the CTS recommendations regarding risk stratification on clinical outcomes among patients hospitalized with an AECOPD. Methods We developed a retrospective cohort study of patients admitted to one tertiary hospital with a diagnosis of AECOPD. The main clinical outcome was the percentage of treatment failure. Secondary outcomes were 30-day, 90-day, and 1-year readmission and mortality rate, length of stay in hospital, intensive care unit (ICU) admission rate, time to readmission, and time to death. Multivariate analyses were performed using 1-year mortality rate as the dependent measures. Results One hundred forty-three patients composed the final study population, most of them (106 [74.1%)] classified as complex acute exacerbation (C-AE) of COPD. C-AE patients had similar rate of treatment failure compared with simple acute exacerbation (S-AE) of COPD (31.1% vs. 27%; p = 0.63). There were no differences regarding the length of stay in hospital, ICU admission rate, and 30-day, 90-day, and 1-year readmission rate. C-AE patients had faster declined measures on time to death (691.6 ± 430 days vs. 998.1 ± 355 days; p = 0.02). In the multivariate analysis, after adjusting for comorbidity, lung function and previous treatment, C-AE patients had a significant higher mortality at one year (Odds Ratio [OR] = 4.9 (Confidence Interval [CI] 95%: 1.16-21); p = 0.031). Conclusions In hospitalized patients with an AECOPD, CTS classification, according to the presence of risk factors, was not associated with worse short-term clinical outcomes although it is related with long-term mortality.

Bronchopulmonary C-fibers and a subset of mechanically sensitive, acid-sensitive myelinated sensory nerves play essential roles in regulating cough. These vagal sensory nerves terminate primarily in the larynx, trachea, carina, and large intrapulmonary bronchi. Other bronchopulmonary sensory nerves, sensory nerves innervating other viscera, as well as somatosensory nerves innervating the chest wall, diaphragm, and abdominal musculature regulate cough patterning and cough sensitivity. The responsiveness and morphology of the airway vagal sensory nerve subtypes and the extrapulmonary sensory nerves that regulate coughing are described. The brainstem and higher brain control systems that process this sensory information are complex, but our current understanding of them is considerable and increasing. The relevance of these neural systems to clinical phenomena, such as urge to cough and psychologic methods for treatment of dystussia, is high, and modern imaging methods have revealed potential neural substrates for some features of cough in the human.