Signature Proteins in Small Extracellular Vesicles of Granulocytes and CD4+ T-Cell Subpopulations Identified by Comparative Proteomic Analysis.

Several studies have described the proteomic profile of different immune cell types, but only a few have also analysed the content of their delivered small extracellular vesicles (sEVs). The aim of the present study was to compare the protein signature of sEVs delivered from granulocytes (i.e., neutrophils and eosinophils) and CD4+ T cells (i.e., TH1, TH2, and TH17) to identify potential biomarkers of the inflammatory profile in chronic inflammatory diseases. Qualitative (DDA) and quantitative (DIA-SWATH) analyses of in vitro-produced sEVs revealed proteome variations depending on the cell source. The main differences were found between granulocyte- and TH cell-derived sEVs, with a higher abundance of antimicrobial proteins (e.g., LCN2, LTF, MPO) in granulocyte-derived sEVs and an enrichment of ribosomal proteins (RPL and RPS proteins) in TH-derived sEVs. Additionally, we found differentially abundant proteins between neutrophil and eosinophil sEVs (e.g., ILF2, LTF, LCN2) and between sEVs from different TH subsets (e.g., ISG15, ITGA4, ITGB2, or NAMPT). A "proof-of-concept" assay was also performed, with TH2 biomarkers ITGA4 and ITGB2 displaying a differential abundance in sEVs from T2high and T2low asthma patients. Thus, our findings highlight the potential use of these sEVs as a source of biomarkers for diseases where the different immune cell subsets studied participate, particularly chronic inflammatory pathologies such as asthma or chronic obstructive pulmonary disease (COPD).

Allergic rhinitis and dental caries: A systematic review.

OBJECTIVE: Dental caries is one of the most common chronic diseases affecting millions of people globally. Some studies revealed the presence of bidirectional relationship between allergic rhinitis (AR) and oral diseases, with each disease having a potential impact on the other. In this study we aimed to systematically review the literature and analyze the available evidence regarding whether AR contributes to the development of dental caries. METHODS: Three authors, members of the YO-IFOS rhinology study group, independently analyzed the data sources (Pubmed, the Cochrane Library, EMBASE, SciELO) for papers assessing the relationship between rhinitis and caries, in adult and pediatric patients. RESULTS: Eight studies met the inclusion criteria (87612 participants). Six studies were performed in children. A total of three studies found an association between AR and dental caries. Only two studies had adjusted the measure of effect for potentially confounding variables. Regarding the quality of the selected studies according to the NICE classification, the most observed methodological limitations detected were: (1) the cross-sectional design of the included studies which could have introduced a simultaneity bias, and (2) not clearly reporting the inclusion and exclusion criteria. CONCLUSION: This systematic review can neither confirm nor deny the presence of an association between AR and caries. Despite the evidence is very scarce to conclude a relationship between AR and caries, the option for examining patients with repetitive caries by an otolaryngologist and those with AR by odontologist should be considered, as these examinations do not possess any risk for the patient.

Analysis of Differentially Expressed MicroRNAs in Serum and Lung Tissues from Individuals with Severe Asthma Treated with Oral Glucocorticoids.

Nowadays, microRNAs (miRNAs) are increasingly used as biomarkers due to their potential contribution to the diagnosis and targeted treatment of a range of diseases. The aim of the study was to analyze the miRNA expression profiles in serum and lung tissue from patients with severe asthma treated with oral corticosteroids (OCS) and those without OCS treatment. For this purpose, serum and lung tissue miRNAs of OCS and non-OCS asthmatic individuals were evaluated by miRNAs-Seq, and subsequently miRNA validation was performed using RT-qPCR. Additionally, pathway enrichment analysis of deregulated miRNAs was conducted. We observed altered expression by the next-generation sequencing (NGS) of 11 miRNAs in serum, of which five (hsa-miR-148b-3p, hsa-miR-221-5p, hsa-miR-618, hsa-miR-941, and hsa-miR-769-5p) were validated by RT-qPCR, and three miRNAs in lung tissue (hsa-miR-144-3p, hsa-miR-144-5p, and hsa-miR-451a). The best multivariate logistic regression model to differentiate individuals with severe asthma, treated and untreated with OCS, was to combine the serum miRNAs hsa-miR-221-5p and hsa-miR-769-5p. Expression of hsa-miR-148b-3p and hsa-miR-221-5p correlated with FEV1/FVC (%) and these altered miRNAs act in key signaling pathways for asthma disease and the regulated expression of some genes (FOXO3, PTEN, and MAPK3) involved in these pathways. In conclusion, there are miRNA profiles differentially expressed in OCS-treated individuals with asthma and could be used as biomarkers of OCS treatment.

Characteristics of Patients with Lymphangioleiomyomatosis and Pleural Effusion: A Systematic Review.

The characteristics of patients with lymphangioleiomyomatosis (LAM) are poorly defined, as they may present with or without pleural effusion (PE). We performed a systematic review across four electronic databases searching for studies reporting clinical findings, PE characteristics, and the most effective treatment of LAM. Case descriptions and retrospective studies were included, unrestricted by year of publication. The review consisted of 94 studies (199 patients) spanning a period of nearly 55 years. The median age was 38 years (range: 1 month to 69 years), and 79.7% were between 21 and 50 years old. All cases had dyspnea, 95% had a cough, and 87.5% had chest pain. PE was exudative chylothorax, usually unilateral (76%) and right-sided, predominantly lymphocytic, and with proportionately higher levels of proteins than lactate dehydrogenase. Sirolimus was effective in all cases, completely in 87%, and partially in 13%, although the number of patients receiving sirolimus was small. The present study confirmed that LAM and PE mainly occur in women of childbearing age (third to fifth decade of life). PE was usually unilateral and presented as a lymphocyte-predominant chylous exudate. The most effective treatment for PE seems to be sirolimus, although studies with larger series are needed to confirm this.

Characteristics of patients with yellow nail syndrome and pleural effusion.

Yellow nail syndrome (YNS) can be associated with a pleural effusion (PE) but the characteristics of these patients are not well defined. We performed a systematic review across four electronic databases for studies reporting clinical findings, PE characteristics, and most effective treatment of YNS. Case descriptions and retrospective studies were included, unrestricted by year of publication. We reviewed 112 studies (150 patients), spanning a period of nearly 50 years. The male/female ratio was 1.2/1. The median age was 60 years (range: 0-88). Seventy-eight percent were between 41-80 years old. All cases had lymphoedema and 85.6% had yellow nails. PEs were bilateral in 68.3%. The appearance of the fluid was serous in 75.3%, milky in 22.3% and purulent in 3.5%. The PE was an exudate in 94.7% with lymphocytic predominance in 96% with a low count of nucleated cells. In 61 of 66 (92.4%) of patients, pleural fluid protein values were >3 g/dL, and typically higher than pleural fluid LDH. Pleurodesis and decortication/pleurectomy were effective in 81.8% and 88.9% of cases, respectively, in the treatment of symptomatic PEs. The development of YNS and PE occurs between the fifth to eighth decade of life and is associated with lymphoedema. The PE is usually bilateral and behaves as a lymphocyte-predominant exudate. The most effective treatments appear to be pleurodesis and decortication/pleurectomy.

Alpha-1 antitrypsin deficiency and Pi*S and Pi*Z SERPINA1 variants are associated with asthma exacerbations.

INTRODUCTION AND OBJECTIVES: Asthma is a chronic inflammatory disease of the airways. Asthma patients may experience potentially life-threatening episodic flare-ups, known as exacerbations, which may significantly contribute to the asthma burden. The Pi*S and Pi*Z variants of the SERPINA1 gene, which usually involve alpha-1 antitrypsin (AAT) deficiency, had previously been associated with asthma. The link between AAT deficiency and asthma might be represented by the elastase/antielastase imbalance. However, their role in asthma exacerbations remains unknown. Our objective was to assess whether SERPINA1 genetic variants and reduced AAT protein levels are associated with asthma exacerbations. MATERIALS AND METHODS: In the discovery analysis, SERPINA1 Pi*S and Pi*Z variants and serum AAT levels were analyzed in 369 subjects from La Palma (Canary Islands, Spain). As replication, genomic data from two studies focused on 525 Spaniards and publicly available data from UK Biobank, FinnGen, and GWAS Catalog (Open Targets Genetics) were analyzed. The associations between SERPINA1 Pi*S and Pi*Z variants and AAT deficiency with asthma exacerbations were analyzed with logistic regression models, including age, sex, and genotype principal components as covariates. RESULTS: In the discovery, a significant association with asthma exacerbations was found for both Pi*S (odds ratio [OR]=2.38, 95% confidence interval [CI]= 1.40-4.04, p-value=0.001) and Pi*Z (OR=3.49, 95%CI=1.55-7.85, p-value=0.003)Likewise, AAT deficiency was associated with a higher risk for asthma exacerbations (OR=5.18, 95%CI=1.58-16.92, p-value=0.007) as well as AAT protein levels (OR= 0.72, 95%CI=0.57-0.91, p-value=0.005). The Pi*Z association with exacerbations was replicated in samples from Spaniards with two generations of Canary Islander origin (OR=3.79, p-value=0.028), and a significant association with asthma hospitalizations was found in the Finnish population (OR=1.12, p-value=0.007). CONCLUSIONS: AAT deficiency could be a potential therapeutic target for asthma exacerbations in specific populations.

Correction: Alfaro-Arnedo et al. IGF1R as a Potential Pharmacological Target in Allergic Asthma. Biomedicines 2021, 9, 912.

In the original article [...].

The Recumbent Position Affects Nasal Resistance: A Systematic Review and Meta-Analysis.

OBJECTIVE: Nasal diseases are among the main motives for the early discontinuation of continuous positive airway pressure therapy and for long-term therapeutic compliance with mandibular advancement device. Although our clinical experience leads us to the belief that recumbency impacts nasal airflow in some patient populations, there is no consensus regarding the magnitude of this effect and the specific group of patients who are the most affected by this condition. In this study, we conducted a meta-analysis to assess the effect of the recumbent position on nasal resistance and nasal airflow. REVIEW METHODS: PubMed (Medline), Cochrane Library, EMBASE, Scopus, and SciELO databases were checked for relevant studies by two members of the YO-IFOS study group. The two authors extracted the data. The main outcome was expressed as the difference between nasal resistance and nasal airflow before and after recumbency. RESULTS: Nine studies with a total population of 291 individuals were included in the meta-analysis for nasal resistance after recumbency. We found a statistically significant difference in nasal airway resistance of -0.18 Pa sec/cm3 as compared to before and after recumbency through rhinomanometry (RMM) analysis. A subgroup analysis revealed a variation of -0.20 Pa sec/cm3 for patients with snoring or sleep apnea and - 0.10 Pa sec/cm3 for healthy individuals. Regarding nasal airflow measured with RMM, three studies (n = 32) in asymptomatic controls revealed a statistically significant difference of 47.33 ml/sec. CONCLUSIONS: Recumbency increases nasal resistance and diminishes nasal airflow. This finding is of utmost importance in snorers and sleep apnea patients. Laryngoscope, 132:6-16, 2022.

IGF1R as a Potential Pharmacological Target in Allergic Asthma.

BACKGROUND: Asthma is a chronic lung disease characterized by reversible airflow obstruction, airway hyperresponsiveness (AHR), mucus overproduction and inflammation. Although Insulin-like growth factor 1 receptor (IGF1R) was found to be involved in asthma, its pharmacological inhibition has not previously been investigated in this pathology. We aimed to determine if therapeutic targeting of IGF1R ameliorates allergic airway inflammation in a murine model of asthma. METHODS: C57BL/6J mice were challenged by house dust mite (HDM) extract or PBS for four weeks and therapeutically treated with the IGF1R tyrosine kinase inhibitor (TKI) NVP-ADW742 (NVP) once allergic phenotype was established. RESULTS: Lungs of HDM-challenged mice exhibited a significant increase in phospho-IGF1R levels, incremented AHR, airway remodeling, eosinophilia and allergic inflammation, as well as altered pulmonary surfactant expression, all of being these parameters counteracted by NVP treatment. HDM-challenged lungs also displayed augmented expression of the IGF1R signaling mediator p-ERK1/2, which was greatly reduced upon treatment with NVP. CONCLUSIONS: Our results demonstrate that IGF1R could be considered a potential pharmacological target in murine HDM-induced asthma and a candidate biomarker in allergic asthma.

Impact of sleep apnoea-hypopnoea syndrome on diabetic neuropathy. A systematic review. / Impacto del síndrome de apnea-hipopnea del sueño en la neuropatía diabética. Revisión sistemática.

INTRODUCTION: Diabetes mellitus and sleep apnoea-hypopnoea syndrome appear to be related, but it is not well defined whether there is an increased risk of peripheral neuropathy in patients with both diseases. For this reason, we conducted a systematic review. METHODS: Bibliographic search in 3 electronic databases using a predefined strategy and the PRISMA methodology. Only original studies (any type of design) published from 2000 onwards in English, French, Portuguese or Spanish were included. A study quality scale was established. RESULTS: Twelve articles were selected, of which six studied type 2 diabetic patients. The overall prevalence of sleep apnoea-hypopnoea syndrome was 43.7% (1,559/3,564 patients). Diabetic neuropathy was more frequent in patients with sleep apnoea-hypopnoea syndrome in nine studies, although significantly only in four (60% vs 27%, P<.001; 64.5% vs 36%, P=.03; 37% vs 23.4%, P<.02; 66.6% vs 0%, P=.007). In one study, diabetic neuropathy was more frequent in patients without sleep apnoea-hypopnoea syndrome (although not statistically significant) and in 2 no comparison was made between patients with/without sleep apnoea/hypopnoea syndrome. CONCLUSIONS: The observed results suggest a relationship between diabetes mellitus and sleep apnoea-hypopnoea syndrome in the occurrence of diabetic neuropathy.

Clinical and inflammatory characteristics of patients with asthma in the Spanish MEGA project cohort.

INTRODUCTION: The MEGA (MEchanism underlying the Genesis and evolution of Asthma) project is a multicenter cohort study carried out in eight Spanish hospitals, gathering clinical, physiological, and molecular data from patients with asthma and multimorbidities in order to gain insight into the different physiopathological mechanisms involved in this disorder. MATERIAL AND METHODS: We report the baseline clinical and physiological characteristics and biomarker measures of adult participants in the project with the aim of better understanding the natural history and underlying mechanisms of asthma as well as the associated multimorbidities across different levels of severity. We carried out a detailed clinical examination, pulmonary function testing, measurement of fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick tests, chest computed tomography scan, asthma questionnaires, and multimorbidity assessment in 512 asthmatic patients. RESULTS: When compared to patients with milder disease, severe asthmatic patients showed greater presence of symptoms, more exacerbations, lower asthma control, increased airflow obstruction, and higher frequency of chronic rhinosinusitis with nasal polyps, severe rhinitis, anxiety and depression, gastroesophageal reflux, and bronchiectasis. CONCLUSION: The MEGA project succeeded in recruiting a high number of asthma patients, especially those with severe disease, who showed lower control and higher frequency of multimorbidities.

Usefulness of triglyceride levels in pleural fluid.

The determination of pleural fluid triglycerides (PF-TRIG) is useful in the diagnosis of chylothorax, but its diagnostic value for other causes of pleural effusions is unknown. The aim of this study was to evaluate the usefulness of PF-TRIG in the diagnosis of other pleural effusions and investigate the origin of their increase in these fluids. We studied 390 pleural effusions (75 tuberculous, 107 neoplastic, 39 parapneumonic, 30 miscellaneous, 42 idiopathic, and 97 transudates). The correlation was analyzed with the PF-TRIG values as the dependent variable and serum triglycerides (S-TRIG) and the pleural fluid/serum protein ratio (PF/S PROT ratio) as independent variables. The PF-TRIG was significantly higher in exudates. The sensitivity of PF-TRIG for identifying exudates was 84.3%, specificity 61.9%. The correlation between PF-TRIG and S-TRIG was significant in the exudates and in the total pleural effusions. There was a significant correlation between PF-TRIG and S-TRIG and capillary permeability, which worsened when looking at the transudates and exudates separately. No correlations were found between the PF-TRIG and the number of red cells and white cells in any of the groups. Except for diagnosing a chylothorax, the determination of triglycerides in pleural fluid does not appear to be justified. The cause of the increase in PF-TRIG in exudates could not be established because the correlations obtained were insufficient to be able to predict PF-TRIG values from their serum values and the measurement of capillary permeability.

Identification of Pleural Response Patterns: A Cluster Analysis.

BACKGROUND: Pleural effusion occurs as a response of the pleura to aggressions. The pleura reacts differently according to the type of injury. However, pleural reactions have not yet been characterized. The objective of this study was to identify homogeneous clusters of patients based on the analytical characteristics of their pleural fluid and identify pleural response patterns. METHODS: A prospective study was conducted of consecutive patients seen in our unit for pleural effusion. Principal component and cluster analyses were carried out to identify pleural response patterns based on a combination of pleural fluid biomarkers. RESULTS: A total of 1613 patients were grouped into six clusters, namely: cluster 1 (10.5% of the cohort, primarily composed of patients with malignant pleural effusions); cluster 2 (17.4%, pleural effusions with inflammatory biomarkers); cluster 3 (16.1%, primarily composed of patients with infectious pleural effusions); cluster 4 (2.5%, a subcluster of cluster 3, superinfectious effusions); cluster 5 (23.4%, paucicellular pleural effusions); and cluster 6 (30.1%, miscellaneous). Significant differences were observed across clusters in terms of the analytical characteristics of PF (p<0.001 for all), age (p<0.001), and gender (p=0.016). A direct relationship was found between the type of cluster and the etiology of pleural effusion. CONCLUSION: Pleural response is heterogeneous. The pleura may respond differently to the same etiology or similarly to different etiologies, which hinders diagnosis of pleural effusion.

CD26 and Asthma: a Comprehensive Review.

Asthma is a heterogeneous and chronic inflammatory family of disorders of the airways with increasing prevalence that results in recurrent and reversible bronchial obstruction and expiratory airflow limitation. These diseases arise from the interaction between environmental and genetic factors, which collaborate to cause increased susceptibility and severity. Many asthma susceptibility genes are linked to the immune system or encode enzymes like metalloproteases (e.g., ADAM-33) or serine proteases. The S9 family of serine proteases (prolyl oligopeptidases) is capable to process peptide bonds adjacent to proline, a kind of cleavage-resistant peptide bonds present in many growth factors, chemokines or cytokines that are important for asthma. Curiously, two serine proteases within the S9 family encoded by genes located on chromosome 2 appear to have a role in asthma: CD26/dipeptidyl peptidase 4 (DPP4) and DPP10. The aim of this review is to summarize the current knowledge about CD26 and to provide a structured overview of the numerous functions and implications that this versatile enzyme could have in this disease, especially after the detection of some secondary effects (e.g., viral nasopharyngitis) in type II diabetes mellitus patients (a subset with a certain risk of developing obesity-related asthma) upon CD26 inhibitory therapy.

The Combined Use of Pleural Fluid Parameters Improves Diagnostic Accuracy in Complicated Pleural Infection/Empyema. / La combinación de la determinación de parámetros bioquímicos del líquido pleural mejora la predicción diagnóstica de la infección pleural complicada/empiema.

INTRODUCTION: Identifying infectious pleural effusions (IPE) that will progress to complicated infection or empyema is challenging. The purpose of this study was to determine whether a model based on multiple biochemical parameters in pleural fluid can predict which IPEs will produce empyema. METHODS: A prospective study was performed of all cases of IPEs treated in our unit. IPEs were classified as uncomplicated or complicated (empyema). Logistic regression was used to estimate the risk for complicated pleural infection (empyema). A predictive model was developed using biochemical parameters in pleural fluid. Discriminatory power (areas under the ROC curve), calibration, and diagnostic accuracy of the model were assessed. RESULTS: A total of 177 patients were included in the study (74 with uncomplicated infectious pleural effusion, and 103 with complicated pleural effusion/empyema). The area under the curve (AUC) for the model (pH, lactate dehydrogenase and interleukin 6) was 0.9783, which is significantly superior to the AUC of the individual biochemical parameters alone (0.921, 0.949, and 0.837, respectively; P<.001 using all parameters). The rate of correct classification of infectious pleural effusions was 96% [170/177: 72/74 (97.3%) for uncomplicated and 98/103 (95.1%) for complicated effusion (empyema)]. CONCLUSION: The multiple-marker model showed better diagnostic performance for predicting complicated infectious pleural effusion (empyema) compared to individual parameters alone.

Influenza A H1N1 Community-Acquired Pneumonia: Characteristics and Risk Factors-A Case-Control Study.

Introduction: Influenza A H1N1 community-acquired pneumonia (CAP) is a quite frequent respiratory disease. Despite being considered more serious than other CAPs, there are very few studies comparing its characteristics with noninfluenza CAP. We aim to establish the differences between pneumonia due to H1N1 virus and pneumonia not caused by H1N1 influenza virus and to determine the probability that a pneumonia is due to an H1N1 virus infection based on the most relevant variables. Methods: We used a case-control study where cases were H1N1 CAP patients with confirmed microbiological diagnosis and controls were patients with CAP admitted to hospital. H1N1 and other influenza types were discarded among controls. We calculated the probability of being a case or control using multivariate logistic regression. Results: We included 99 cases and 270 controls. Cases were younger than controls (53 vs 71 years, respectively). Mortality was much higher for H1N1 patients (13% vs 0.3%), and admission to intensive care unit was more frequent for H1N1 cases. The variables most associated with presenting H1N1 CAP were bilateral affectation on chest X-rays (OR: 5.70; 95% CI 2.69-10.40), followed by presence of arthromyalgias, with cases presenting close to three times more arthromyalgias compared to controls. Low leukocytes count and high AST values were also significantly associated with H1N1 CAP. H1N1 CAPs are characterized by bilateral affectation, low leukocyte count, presence of arthromyalgias, and high AST. Conclusions: A few and easy to obtain clinical parameters might be extremely useful to distinguish H1N1 CAP from CAPs of other origin.

Diagnosis of infectious pleural effusion using predictive models based on pleural fluid biomarkers.

INTRODUCTION: Diagnosis of pleural infection (PI) may be challenging. The purpose of this paper is to develop and validate a clinical prediction model for the diagnosis of PI based on pleural fluid (PF) biomarkers. METHODS: A prospective study was conducted on pleural effusion. Logistic regression was used to estimate the likelihood of having PI. Two models were built using PF biomarkers. The power of discrimination (area under the curve) and calibration of the two models were evaluated. RESULTS: The sample was composed of 706 pleural effusion (248 malignant; 28 tuberculous; 177 infectious; 48 miscellaneous exudates; and 212 transudates). Areas under the curve for Model 1 (leukocytes, percentage of neutrophils, and C-reactive protein) and Model 2 (the same markers plus interleukin-6 [IL-6]) were 0.896 and 0.909, respectively (not significant differences). However, both models showed higher capacity of discrimination than their biomarkers when used separately (P < 0.001 for all). Rates of correct classification for Models 1 and 2 were 88.2% (623/706: 160/177 [90.4%] with infectious pleural effusion [IPE] and 463/529 [87.5%] with non-IPE) and 89.2% (630/706: 153/177 [86.4%] of IPE and 477/529 [90.2%] of non-IPE), respectively. CONCLUSIONS: The two predictive models developed for IPE showed a good diagnostic performance, superior to that of any of the markers when used separately. Although IL-6 contributes a slight greater capacity of discrimination to the model that includes it, its routine determination does not seem justified.

Factors Influencing Hospital Stay for Pulmonary Embolism. A Cohort Study. / Factores que influyen en la estancia hospitalaria por embolia pulmonar. Un estudio de cohortes.

INTRODUCTION: The aim of this study was to identify factors influencing hospital stay due to pulmonary embolism. METHODS: We performed a retrospective cohort study of patients hospitalized between 2010 and 2015. Patients were identified using information recorded in hospital discharge reports (ICD-9-CM codes 415.11 and 415.19). RESULTS: We included 965 patients with a median stay of 8 days (IQR 6-13 days). Higher scores on the simplified Pulmonary Embolism Severity Index (sPESI) were associated with increased probability of longer hospital stay. The probability of a hospital stay longer than the median was 8.65 (95% CI 5.42-13.79) for patients referred to the Internal Medicine Department and 1.54 (95% CI 1.07-2.24) for patients hospitalized in other departments, compared to those referred to the Pneumology Department. Patients with grade 3 on the modified Medical Research Council dyspnea scale had an odds ratio of 1.63 (95% CI: 1.07-2.49). The likelihood of a longer than median hospital stay was 1.72 (95% CI: 0.85-3.48) when oral anticoagulation (OAC) was initiated 2-3 days after admission, and 2.43 (95% CI: 1.16-5.07) when initiated at 4-5 days, compared to OAC initiation at 0-1 days. CONCLUSIONS: sPESI grade, the department of referral from the Emergency Department, the grade of dyspnea and the time of initiating OAC were associated with a longer hospital stay.

Discordance of physician clinical judgment vs. pneumonia severity index (PSI) score to admit patients with low risk community-acquired pneumonia: a prospective multicenter study.

BACKGROUND: The relationship between clinical judgment and the pneumonia severity index (PSI) score in deciding the site of care for patients with community-acquired pneumonia (CAP) has not been well investigated. The objective of the study was to determine the clinical factors that influence decision-making to hospitalize low-risk patients (PSI ≤2) with CAP. METHODS: An observational, prospective, multicenter study of consecutive CAP patients was performed at five hospitals in Spain. Patients admitted with CAP and a PSI ≤2 were identified. Admitting physicians completed a patient-specific survey to identify the clinical factors influencing the decision to admit a patient. The reason for admission was categorized into 1 of 6 categories. We also assessed whether the reason for admission was associated with poorer clinical outcomes [intensive care unit (ICU) admission, 30-day mortality or readmission]. RESULTS: One hundred and fifty-five hospitalized patients were enrolled. Two or more reasons for admission were seen in 94 patients (60.6%), including abnormal clinical test results (60%), signs of clinical deterioration (43.2%), comorbid conditions (28.4%), psychosocial factors (28.4%), suspected H1N1 pneumonia (20.6%), and recent visit to the emergency department (ED) in the past 2 weeks (7.7%). Signs of clinical deterioration and abnormal clinical test results were associated with poorer clinical outcomes (P<0.005). CONCLUSIONS: Low-risk patients with CAP and a PSI ≤2 are admitted to the hospital for multiple reasons. Abnormal clinical test results and signs of clinical deterioration are two specific reasons for admission that are associated with poorer clinical outcomes in low risk CAP patients.