Pulmonary thrombosis associated with COVID-19 pneumonia: Beyond classical pulmonary thromboembolism.

BACKGROUND: Classical pulmonary thromboembolism (TE) and local pulmonary thrombosis (PT) have been suggested as mechanisms of thrombosis in COVID-19. However, robust evidence is still lacking because this was mainly based on retrospective studies, in which patients were included when TE was suspected. METHODS: All patients with COVID-19 pneumonia underwent computed tomography and pulmonary angiography in a prospective study. The main objective was to determine the number and percentage of thrombi surrounded by lung opacification (TSO) in each patient, as well as their relationship with percentage of lung involvement (TLI), to distinguish classical TE (with a random location of thrombi that should correspond to a percentage of TSO equivalent to the TLI) from PT. We determined TLI by artificial intelligence. Analyses at patient level (TLI and percentage of TSO) and at thrombi level (TLI and TSO) were performed. RESULTS: We diagnosed TE in 70 out of 184 patients. Three (2-8) thrombi/patient were detected. The percentage of TSO was 100% (75-100) per patient, and TLI was 19.9% (4.6-35.2). Sixty-five patients (92.9%) were above the random scenario with higher percentage of TSO than TLI. Most thrombi were TSO (n = 299, 75.1%). When evaluating by TLI (<10%, 10%-20%, 20%-30% and >30%), percentage of TSO was higher in most groups. Thrombi were mainly in subsegmental/segmental arteries, and percentage of TSO was higher in all locations. CONCLUSIONS: Thrombi in COVID-19 were found within lung opacities in a higher percentage than lung involvement, regardless of TLI and clot location, supporting the hypothesis of local PT rather than "classic TE".

Prevalence and clinical characteristics of patients with rheumatoid arthritis with interstitial lung disease using unstructured healthcare data and machine learning.

OBJECTIVES: Real-world data regarding rheumatoid arthritis (RA) and its association with interstitial lung disease (ILD) is still scarce. This study aimed to estimate the prevalence of RA and ILD in patients with RA (RAILD) in Spain, and to compare clinical characteristics of patients with RA with and without ILD using natural language processing (NLP) on electronic health records (EHR). METHODS: Observational case-control, retrospective and multicentre study based on the secondary use of unstructured clinical data from patients with adult RA and RAILD from nine hospitals between 2014 and 2019. NLP was used to extract unstructured clinical information from EHR and standardise it into a SNOMED-CT terminology. Prevalence of RA and RAILD were calculated, and a descriptive analysis was performed. Characteristics between patients with RAILD and RA patients without ILD (RAnonILD) were compared. RESULTS: From a source population of 3 176 165 patients and 64 241 683 EHRs, 13 958 patients with RA were identified. Of those, 5.1% patients additionally had ILD (RAILD). The overall age-adjusted prevalence of RA and RAILD were 0.53% and 0.02%, respectively. The most common ILD subtype was usual interstitial pneumonia (29.3%). When comparing RAILD versus RAnonILD patients, RAILD patients were older and had more comorbidities, notably concerning infections (33.6% vs 16.5%, p<0.001), malignancies (15.9% vs 8.5%, p<0.001) and cardiovascular disease (25.8% vs 13.9%, p<0.001) than RAnonILD. RAILD patients also had higher inflammatory burden reflected in more pharmacological prescriptions and higher inflammatory parameters and presented a higher in-hospital mortality with a higher risk of death (HR 2.32; 95% CI 1.59 to 2.81, p<0.001). CONCLUSIONS: We found an estimated age-adjusted prevalence of RA and RAILD by analysing real-world data through NLP. RAILD patients were more vulnerable at the time of inclusion with higher comorbidity and inflammatory burden than RAnonILD, which correlated with higher mortality.

A Prospective Study Evaluating Cumulative Incidence and a Specific Prediction Rule in Pulmonary Embolism in COVID-19.

Rationale: Abnormal values of hypercoagulability biomarkers, such as D-dimer, have been described in Coronavirus Disease 2019 (COVID-19), which has also been associated with disease severity and in-hospital mortality. COVID-19 patients with pneumonia are at greater risk of pulmonary embolism (PE). However, the real incidence of PE is not yet clear, since studies have been limited in size, mostly retrospective, and PE diagnostic procedures were only performed when PE was clinically suspected. Objectives: (1) To determine the incidence, clinical, radiological, and biological characteristics, and clinical outcomes of PE among patients hospitalized for COVID-19 pneumonia with D-dimer > 1,000 ng/mL. (2) To develop a prognostic model to predict PE in these patients. Methods: Single-center prospective cohort study. Consecutive confirmed cases of COVID-19 pneumonia with D-dimer > 1,000 ng/mL underwent computed tomography pulmonary angiography (CTPA). Demographic and laboratory data, comorbidities, CTPA scores, treatments administered, and clinical outcomes were analyzed and compared between patients with and without PE. A risk score was constructed from all these variables. Results: Between 6 April 2020 and 2 February 2021, 179 consecutive patients were included. The overall incidence of PE was 39.7% (71 patients) (CI 95%, 32-47%). In patients with PE, emboli were located mainly in segmental/subsegmental arteries (67%). Patients with PE did not differ from the non-PE group in sex, age, or risk factors for thromboembolic disease. Higher urea, D-Dimer, D-dimer-to-ferritin and D-dimer-to-lactate dehydrogenase (LDH) ratios, platelet distribution width (PDW), and neutrophil-to-lymphocyte ratio (NLR) values were found in patients with PE when compared to patients with non-PE. Besides, lymphocyte counts turned out to be lower in patients with PE. A score for PE prediction was constructed with excellent overall performance [area under the ROC curve-receiver operating characteristic (AUC-ROC) 0.81 (95% CI: 0.73-0.89)]. The PATCOM score stands for Pulmonary Artery Thrombosis in COVID-19 Mallorca and includes platelet count, PDW, urea concentration, and D-dimer-to-ferritin ratio. Conclusion: COVID-19 patients with pneumonia and D-dimer values > 1,000 ng/mL were presented with a very high incidence of PE, regardless of clinical suspicion. Significant differences in urea, D-dimer, PDW, NLR, and lymphocyte count were found between patients with PE and non-PE. The PATCOM score is presented in this study as a promising PE prediction rule, although validation in further studies is required.

Different Faces of Idiopathic Pulmonary Fibrosis With Preserved Forced Vital Capacity / Diferentes caras de la fibrosis pulmonar idiopática con capacidad vital forzada preservada

Introduction Idiopathic pulmonary fibrosis (IPF) is progressive and irreversible. Some discrepancies about IPF staging exists, especially in mild phases. Forced vital capacity (FVC) higher than 80% has been considered early or mild IPF even for the design of clinical trials. Methods Spanish multicentre, observational, retrospective study of IPF patients diagnosed between 2012 and 2016, based on the ATS/ERS criteria, which presented FVC greater or equal 80% at diagnosis. Clinical and demographic characteristics, lung function, radiological pattern, treatment, and follow-up were analyzed. Results 225 IPF patients were included, 72.9% were men. The mean age was 69.5 years. The predominant high-resolution computed tomography (HRCT) pattern was consistent usual interstitial pneumonia (UIP) (51.6%). 84.7% of patients presented respiratory symptoms (exertional dyspnea and/or cough) and 33.33% showed oxygen desaturation below 90% in the 6min walking test (6MWT). Anti-fibrotic treatment was initiated at diagnosis in 55.11% of patients. Median FVC was 89.6% (IQR 17) and 58.7% of patients had a decrease of diffusion lung capacity for carbon monoxide (DLCO) below 60% of theoretical value; most of them presented functional progression (61.4%) and higher mortality at 3 years (20.45%). A statistically significant correlation with the 3-years mortality was observed between DLCO <60% and consistent UIP radiological pattern. Conclusions Patients with preserved FVC but presenting UIP radiological pattern and moderate–severe DLCO decrease at diagnosis associate an increased risk of progression, death or lung transplantation. Therefore, in these cases, preserved FVC would not be representative of early or mild IPF.

Introducción La fibrosis pulmonar idiopática (FPI) es progresiva e irreversible. Existen algunas discrepancias sobre la estadificación de la FPI, especialmente en las fases leves. La capacidad vital forzada (FVC) superior al 80% se ha considerado una FPI temprana o leve incluso para el diseño de ensayos clínicos. Métodos Estudio español multicéntrico, observacional, retrospectivo de pacientes con FPI diagnosticados entre 2012-2016, en función de los criterios ATS/ERS, que presentaban FVC mayor o igual al 80% al diagnóstico. Se analizaron características clínicas y demográficas, función pulmonar, patrón radiológico, tratamiento y seguimiento. Resultados Se incluyeron 225 pacientes con FPI, el 72,9% eran varones. La edad media fue de 69,5 años. El patrón predominante en la tomografía computarizada de alta resolución (TCAR) fue compatible con neumonía intersticial usual (NIU) (51,6%). El 84,7% de los pacientes presentó síntomas respiratorios (disnea de esfuerzo o tos) y el 33,33% mostró desaturación con una saturación de oxígeno inferior al 90% en la prueba de la marcha de los 6min (PM6M). El tratamiento antifibrótico se inició en el momento del diagnóstico en el 55,11% de los pacientes. La mediana de la CVF fue del 89,6% (RIC 17) y el 58,7% de los pacientes presentó una disminución de la capacidad pulmonar de difusión del monóxido de carbono (DLCO) por debajo del 60% del valor teórico; la mayoría presentó progresión funcional (61,4%) y una mayor mortalidad a los 3 años (20,45%). Se observó una correlación estadísticamente significativa de la mortalidad a los 3 años entre una DLCO<60% y el patrón radiológico compatible con UIP. Conclusiones Los pacientes con FVC conservada pero que presentan patrón radiológico de NIU y disminución moderada-grave de la de DLCO en el momento del diagnóstico se asociaron a un mayor riesgo de progresión, fallecimiento o tener que recibir un trasplante de pulmón. Por lo tanto, en estos casos, una FVC preservada no sería representativa de una FPI temprana o leve

Different Faces of Idiopathic Pulmonary Fibrosis With Preserved Forced Vital Capacity.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is progressive and irreversible. Some discrepancies about IPF staging exists, especially in mild phases. Forced vital capacity (FVC) higher than 80% has been considered early or mild IPF even for the design of clinical trials. METHODS: Spanish multicentre, observational, retrospective study of IPF patients diagnosed between 2012 and 2016, based on the ATS/ERS criteria, which presented FVC greater or equal 80% at diagnosis. Clinical and demographic characteristics, lung function, radiological pattern, treatment, and follow-up were analyzed. RESULTS: 225 IPF patients were included, 72.9% were men. The mean age was 69.5 years. The predominant high-resolution computed tomography (HRCT) pattern was consistent usual interstitial pneumonia (UIP) (51.6%). 84.7% of patients presented respiratory symptoms (exertional dyspnea and/or cough) and 33.33% showed oxygen desaturation below 90% in the 6min walking test (6MWT). Anti-fibrotic treatment was initiated at diagnosis in 55.11% of patients. Median FVC was 89.6% (IQR 17) and 58.7% of patients had a decrease of diffusion lung capacity for carbon monoxide (DLCO) below 60% of theoretical value; most of them presented functional progression (61.4%) and higher mortality at 3 years (20.45%). A statistically significant correlation with the 3-years mortality was observed between DLCO <60% and consistent UIP radiological pattern. CONCLUSIONS: Patients with preserved FVC but presenting UIP radiological pattern and moderate-severe DLCO decrease at diagnosis associate an increased risk of progression, death or lung transplantation. Therefore, in these cases, preserved FVC would not be representative of early or mild IPF.

Prevalence of pulmonary embolism in patients with COVID-19 pneumonia and high D-dimer values: A prospective study.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) pneumonia is associated to systemic hyper-inflammation and abnormal coagulation profile. D-dimer elevation is particularly frequent, and values higher than 1µg/mL have been associated with disease severity and in-hospital mortality. Previous retrospective studies found a high pulmonary embolism (PE) prevalence, however, it should be highlighted that diagnoses were only completed when PE was clinically suspected. MATERIAL AND METHODS: Single-center prospective cohort study. Between April 6th and April 17th 2020, consecutive confirmed cases of COVID-19 pneumonia with D-dimer >1 µg/mL underwent computed tomography pulmonary angiography (CTPA) to investigate the presence and magnitude of PE. Demographic and laboratory data, comorbidities, CTPA scores, administered treatments, and, clinical outcomes were analysed and compared between patients with and without PE. RESULTS: Thirty consecutive patients (11 women) were included. PE was diagnosed in 15 patients (50%). In patients with PE, emboli were located mainly in segmental arteries (86%) and bilaterally (60%). Patients with PE were significantly older (median age 67.0 (IQR 63.0-73.0) vs. 57.0 (IQR 48.0-69.0) years, p = .048) and did not differ in sex or risk factors for thromboembolic disease from the non-PE group. D-dimer, platelet count, and, C reactive protein values were significantly higher among PE patients. D-dimer values correlated with the radiologic magnitude of PE (p<0.001). CONCLUSIONS: Patients with COVID-19 pneumonia and D-dimer values higher than 1 µg/mL presented a high prevalence of PE, regardless of clinical suspicion. We consider that these findings could contribute to improve the prognosis of patients with COVID-19 pneumonia, by initiating anticoagulant therapy when a PE is found.

Idiopathic Pulmonary Fibrosis: Epidemiology, Natural History, Phenotypes.

Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. It is characterized by a chronic, progressive, fibrotic interstitial lung disease of unknown cause that occurs primarily in older adults. Its prevalence and incidence have appeared to be increasing over the last decades. Despite its unknown nature, several genetic and environmental factors have been associated with IPF. Moreover, its natural history is variable, but could change depending on the currently suggested phenotypes: rapidly progressive IPF, familial, combined pulmonary fibrosis and emphysema, pulmonary hypertension, and that associated with connective tissue diseases. Early recognition and accurate staging are likely to improve outcomes and induce a prompt initiation of antifibrotics therapy. Treatment is expected to be more effective in the early stages of the disease, while developments in treatment aim to improve the current median survival of 3⁻4 years after diagnosis.

Ceftolozane/tazobactam for the treatment of multidrug resistant Pseudomonas aeruginosa: experience from the Balearic Islands.

A prospective, descriptive observational study of consecutive patients treated with ceftolozane/tazobactam in the reference hospital of the Balearic Islands (Spain), between May 2016 and September 2017, was performed. Demographic, clinical, and microbiological variables were recorded. The later included resistance profile, molecular typing, and whole genome sequencing of isolates showing resistance development. Fifty-eight patients were treated with ceftolozane/tazobactam. Thirty-five (60.3%) showed respiratory tract infections, 21 (36.2%) received monotherapy, and 37 (63.8%) combined therapy for ≥ 72 h, mainly with colistin (45.9%). In 46.6% of the patients, a dose of 1/0.5 g/8 h was used, whereas 2/1 g/8 h was used in 41.4%. In 56 of the cases (96.6%), the initial Pseudomonas aeruginosa isolates recovered showed a multidrug resistant (MDR) phenotype, and 50 of them (86.2%) additionally met the extensively drug resistant (XDR) criteria and were only susceptible colistin and/or aminoglycosides (mostly amikacin). The epidemic high-risk clone ST175 was detected in 50% of the patients. Clinical cure was documented in 37 patients (63.8%) and resistance development in 8 (13.8%). Clinical failure was associated with disease severity (SOFA), ventilator-dependent respiratory failure, XDR profile, high-risk clone ST175, negative control culture, and resistance development. In 6 of the 8 cases, resistance development was caused by structural mutations in AmpC, including some mutations described for the first time in vivo, whereas in the other 2, by mutations in OXA-10 leading to the extended spectrum OXA-14. Although further clinical experience is still needed, our results suggest that ceftolozane/tazobactam is an attractive option for the treatment of MDR/XDR P. aeruginosa infections.

Noninvasive ventilation for severely acidotic patients in respiratory intermediate care units : Precision medicine in intermediate care units.

BACKGROUND: Severe acidosis can cause noninvasive ventilation (NIV) failure in chronic obstructive pulmonary disease (COPD) patients with acute hypercapnic respiratory failure (AHRF). NIV is therefore contraindicated outside of intensive care units (ICUs) in these patients. Less is known about NIV failure in patients with acute cardiogenic pulmonary edema (ACPE) and obesity hypoventilation syndrome (OHS). Therefore, the objective of the present study was to compare NIV failure rates between patients with severe and non-severe acidosis admitted to a respiratory intermediate care unit (RICU) with AHRF resulting from ACPE, COPD or OHS. METHODS: We prospectively included acidotic patients admitted to seven RICUs, where they were provided NIV as an initial ventilatory support measure. The clinical characteristics, pH evolutions, hospitalization or RICU stay durations and NIV failure rates were compared between patients with a pH ≥ 7.25 and a pH < 7.25. Logistic regression analysis was performed to determine the independent risk factors contributing to NIV failure. RESULTS: We included 969 patients (240 with ACPE, 540 with COPD and 189 with OHS). The baseline rates of severe acidosis were similar among the groups (45 % in the ACPE group, 41 % in the COPD group, and 38 % in the OHS group). Most of the patients with severe acidosis had increased disease severity compared with those with non-severe acidosis: the APACHE II scores were 21 ± 7.2 and 19 ± 5.8 for the ACPE patients (p < 0.05), 20 ± 5.7 and 19 ± 5.1 for the COPD patients (p < 0.01) and 18 ± 5.9 and 17 ± 4.7 for the OHS patients, respectively (NS). The patients with severe acidosis also exhibited worse arterial blood gas parameters: the PaCO2 levels were 87 ± 22 and 70 ± 15 in the ACPE patients (p < 0.001), 87 ± 21 and 76 ± 14 in the COPD patients, and 83 ± 17 and 74 ± 14 in the OHS patients (NS)., respectively Further, the patients with severe acidosis required a longer duration to achieve pH normalization than those with non-severe acidosis (patients with a normalized pH after the first hour: ACPE, 8 % vs. 43 %, p < 0.001; COPD, 11 % vs. 43 %, p < 0.001; and OHS, 13 % vs. 51 %, p < 0.001), and they had longer RICU stays, particularly those in the COPD group (ACPE, 4 ± 3.1 vs. 3.6 ± 2.5, NS; COPD, 5.1 ± 3 vs. 3.6 ± 2.1, p < 0.001; and OHS, 4.3 ± 2.6 vs. 3.7 ± 3.2, NS). The NIV failure rates were similar between the patients with severe and non-severe acidosis in the three disease groups (ACPE, 16 % vs. 12 %; COPD, 7 % vs. 7 %; and OHS, 11 % vs. 4 %). No common predictive factor for NIV failure was identified among the groups. CONCLUSIONS: ACPE, COPD and OHS patients with AHRF and severe acidosis (pH ≤ 7.25) who are admitted to an RICU can be successfully treated with NIV in these units. These results may be used to determine precise RICU admission criteria.

Ausencia de correlación entre marcadores de inflamación pulmonar y sistémica en pacientes con enfermedad pulmonar obstructiva crónica: un análisis bi-compartimental simultáneo / Lack of Correlation Between Pulmonary and Systemic Inflammation Markers in Patients with Chronic Obstructive Pulmonary Disease: A Simultaneous, Two-Compartmental Analysis

Introducción: El origen de la inflamación sistémica en pacientes con enfermedad pulmonar obstructiva crónica (EPOC) es poco conocido, y una de las hipótesis más aceptadas es el paso de la inflamación del pulmón a la sangre (spill-over). Objetivo: Evaluar la relación entre la inflamación pulmonar y sistémica en la EPOC mediante la cuantificación de diversos marcadores inflamatorios en esputo y suero obtenidos en el mismo individuo de forma simultánea. Metodología: De 133 pacientes de la cohorte PAC-EPOC se evaluaron las relaciones entre diferentes variables inflamatorias (TNFα, IL-6, IL-8) en suero y esputo. Como objetivo secundario se evaluaron las relaciones de las variables inflamatorias de suero con la función pulmonar. Resultados: Los valores de los marcadores inflamatorios fueron claramente superiores en esputo que en suero. No se hallaron correlaciones relevantes (en valor absoluto, r = 0,03-0,24) entre los marcadores inflamatorios en sangre y en esputo. Tampoco se identificaron asociaciones significativas entre dichos marcadores, con variables de función pulmonar como el FEV1, DLCO y la PaO2. Conclusiones: En pacientes con EPOC estable no existe correlación entre la inflamación pulmonar y sistémica, lo que sugiere mecanismos patogénicos diferentes

Introduction: The origin of systemic inflammation in chronic obstructive pulmonary disease (COPD) patients remains to be defined, but one of the most widely accepted hypothesis is the ‘spill over’ of inflammatory mediators from the lung to the circulation. Objective: To evaluate the relationship between pulmonary and systemic inflammation in COPD quantifying several inflammatory markers in sputum and serum determined simultaneously. Methodology: Correlations between various inflammatory variables (TNF-α, IL6, IL8) in sputum and serum were evaluated in 133 patients from the PAC-COPD cohort study. A secondary objective was the evaluation of relationships between inflammatory variables and lung function. Results: Inflammatory markers were clearly higher in sputum than in serum. No significant correlation was found (absolute value, r = 0.03-0.24) between inflammatory markers in blood and in sputum. There were no significant associations identified between those markers and lung function variables, such as FEV1, DLCO and PaO2 neither. Conclusions: We found no correlation between pulmonary and systemic inflammation in patients with stable COPD, suggesting different pathogenic mechanisms

Lack of Correlation Between Pulmonary and Systemic Inflammation Markers in Patients with Chronic Obstructive Pulmonary Disease: A Simultaneous, Two-Compartmental Analysis. / Ausencia de correlación entre marcadores de inflamación pulmonar y sistémica en pacientes con enfermedad pulmonar obstructiva crónica: un análisis bi-compartimental simultáneo.

INTRODUCTION: The origin of systemic inflammation in chronic obstructive pulmonary disease (COPD) patients remains to be defined, but one of the most widely accepted hypothesis is the 'spill over' of inflammatory mediators from the lung to the circulation. OBJECTIVE: To evaluate the relationship between pulmonary and systemic inflammation in COPD quantifying several inflammatory markers in sputum and serum determined simultaneously. METHODOLOGY: Correlations between various inflammatory variables (TNF-α, IL6, IL8) in sputum and serum were evaluated in 133 patients from the PAC-COPD cohort study. A secondary objective was the evaluation of relationships between inflammatory variables and lung function. RESULTS: Inflammatory markers were clearly higher in sputum than in serum. No significant correlation was found (absolute value, r=0.03-0.24) between inflammatory markers in blood and in sputum. There were no significant associations identified between those markers and lung function variables, such as FEV1, DLCO and PaO2 neither. CONCLUSIONS: We found no correlation between pulmonary and systemic inflammation in patients with stable COPD, suggesting different pathogenic mechanisms.

Differential effects of smoking and COPD upon circulating myeloid derived suppressor cells.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by an enhanced and persistent innate and acquired immune response to tobacco smoking. Myeloid-derived suppressor cells (MDSCs) modulate T-cell responses by down-modulating the T cell receptor ζ chain (TCR ζ) through the catabolism of l-arginine. The effects of smoking on MDSCs and their potential participation in COPD immunopathogenesis have not been explored so far. METHODS: To investigate it, we compared the level of circulating Lineage-/HLA-DR-/CD33+/CD11b+ MDSCs, the serum concentration of arginase I (ARG I) and the expression of peripheral T-cell receptor ζ chain (TCR ζ) in never smokers, smokers with normal spirometry and COPD patients. Flow cytometry was used to quantify circulating MDSCs and TCR ζ expression. Serum ARG I levels were determined by ELISA. RESULTS: The main findings of this study were that: (1) current smoking upregulates and activates circulating MDSCs both in smoker controls and COPD patients; and, (2) at variance with the smokers with normal spirometry, in patients with COPD this effect persists after quitting smoking and is accompanied by a significant and specific down-regulation of the TCR ζ chain expression in circulating T lymphocytes. CONCLUSION: Smoking modulates circulating MDSCs. Their regulation appears altered in patients with COPD.

Características de pacientes asmáticos ingresados en una unidad de cuidados respiratorios intermedios / Characteristics of Asthma Patients Admitted to an Intermediate Respiratory Care Unit

Introducción: Las unidades de cuidados respiratorios intermedios (UCRI) permiten la monitorización continua y la ventilación mecánica no invasiva (VMNI) en los pacientes con insuficiencia respiratoria grave que habitualmente ingresan en unidades de cuidados intensivos (UCI). La utilidad de las UCRI en el manejo de las agudizaciones graves del asma nunca ha sido evaluada. Métodos: Se recogieron de forma prospectiva y sistemática los datos clínicos de pacientes ingresados en la UCRI con el diagnóstico principal de asma bronquial agudizada, se evaluó el fracaso terapéutico (intubación o fallecimiento) y su evolución hasta 6meses tras el alta, comparada con un grupo de pacientes ingresados en planta de hospitalización convencional pareados por edad y sexo, con el mismo diagnóstico principal. Resultados: Se incluyeron un total de 74 pacientes asmáticos (37 ingresan en la UCRI y 37 en planta) con una edad media (±DE) de 58±20 años, predominantemente mujeres (67%), con diagnóstico previo y tratamiento de asma persistente. La causa principal de ingreso en la UCRI fue insuficiencia respiratoria grave. Los pacientes que ingresaron en la UCRI presentaron más afectación radiológica (infiltrados alveolares) y tenían una pCO2 significativamente mayor. Diez pacientes ingresados en la UCRI precisaron VMNI. No hubo diferencias entre ambos grupos en fracasos terapéuticos, ni en seguimiento a los 6meses del alta. Conclusiones: Los pacientes con agudizaciones graves del asma pueden ser atendidos en una UCRI, evitando ingresos en la UCI y con un pronóstico similar a las agudizaciones más leves que son ingresadas en una planta de hospitalización convencional(AU)

Introduction: Intermediate respiratory care units (IRCU) provide continuous monitoring and non-invasive mechanical ventilation (NIMV) in patients with severe respiratory failure who are usually admitted to intensive care units (ICUs). The usefulness of IRCU in managing severe asthma exacerbations has never been evaluated. Methods: Clinical data were prospectively and systematically compiled from patients admitted to the IRCU with a principal diagnosis of bronchial asthma exacerbation. We assessed therapeutic failure (intubation or exitus) and patient evolution up until 6 months after discharge compared with a group of patients admitted to a conventional hospital ward, paired for age and sex, and with the same principal diagnosis. Results: A total of 74 asthma patients were included (37 admitted to IRCU and 37 to the hospital ward) with a mean age (±SD) of 58±20, who were predominantly women (67%), with previous diagnosis of asthma and persistent asthma treatment. The main cause of admittance to the IRCU was severe respiratory failure. The patients who were admitted to the IRCU presented more radiological affectation (alveolar infiltrates) and had significantly higher pCO2. Ten patients admitted to the IRCU required non-invasive mechanical ventilation (NIMV). There were no differences between the two groups regarding either therapeutic failure or the 6-month follow-up after discharge. Conclusions: Patients with severe asthma exacerbations can be managed in an IRCU while avoiding hospitalization in an ICU and demonstrating a prognosis similar to milder exacerbations treated in conventional hospital wards(AU)

HLA distribution in COPD patients.

BACKGROUND: Auto-immunity may contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD), particularly to the presence of emphysema. Auto-immune diseases are characterized by an abnormal distribution of HLA class II alleles (DR and DQ). The distribution of DRB1 and DQB1 alleles has not been investigated in COPD. METHODS: To this end, HLA medium-low resolution typing was performed following standardized protocols in 320 clinically stable COPD patients included in the PAC-COPD study. Results were compared with controls of the same geographical and ethnic origin, and potential relationships with the severity of airflow limitation and lung diffusing capacity impairment were explored in patients with COPD. RESULTS: The distribution of DRB1 and DQB1 alleles in COPD was similar to that of controls except for a significantly higher prevalence of DRB1*14 in patients with severe airflow limitation and low diffusing capacity. CONCLUSIONS: By and large, HLA distribution was similar in COPD patients and controls, but the HLA class II allele DRB1*14 may contribute to the pathogenesis of severe COPD with emphysema.

Characteristics of asthma patients admitted to an intermediate respiratory care unit.

INTRODUCTION: Intermediate respiratory care units (IRCU) provide continuous monitoring and non-invasive mechanical ventilation (NIMV) in patients with severe respiratory failure who are usually admitted to intensive care units (ICU). The usefulness of IRCU in managing severe asthma exacerbations has never been evaluated. METHODS: Clinical data were prospectively and systematically compiled from patients admitted to the IRCU with a principal diagnosis of bronchial asthma exacerbation. We assessed therapeutic failure (intubation or exitus) and patient evolution up until 6 months after discharge compared with a group of patients admitted to a conventional hospital ward, paired for age and sex, and with the same principal diagnosis. RESULTS: A total of 74 asthma patients were included (37 admitted to IRCU and 37 to the hospital ward) with a mean age (±SD) of 58±20, who were predominantly women (67%), with previous diagnosis of asthma and persistent asthma treatment. The main cause of admittance to the IRCU was severe respiratory failure. The patients who were admitted to the IRCU presented more radiological affectation (alveolar infiltrates) and had significantly higher pCO(2). Ten patients admitted to the IRCU required NIMV. There were no differences between the two groups regarding either therapeutic failure or the 6-month follow-up after discharge. CONCLUSIONS: Patients with severe asthma exacerbations can be managed in an IRCU while avoiding hospitalization in an ICU and demonstrating a prognosis similar to milder exacerbations treated in conventional hospital wards.

Anti-tissue antibodies are related to lung function in chronic obstructive pulmonary disease.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is a multicomponent disease. Autoimmunity can contribute to the pathogenesis of COPD. OBJECTIVES: This study investigates the prevalence of circulating antinuclear antibodies (ANA) and anti-tissue (AT) antibodies, two common markers of autoimmunity, in COPD and their relationship with several components of the disease. METHODS: We determined lung function, the serum titers of ANA and AT by immunofluorescence, and the serum levels of C-reactive protein (CRP) by high sensitivity nephelometry in 328 patients with clinically stable COPD and in 67 healthy controls recruited in the PAC-COPD study. Multiple linear and logistic regression analysis was used to analyze results. MEASUREMENTS AND MAIN RESULTS: The prevalence of abnormal ANA and AT titers was 34% and 26% in patients and 3% and 6% in controls, respectively. Levels of AT greater than or equal to 1:320 were seen in 21% of patients with COPD and were independently associated with the severity of airflow limitation and gas transfer impairment (P < 0.05). Neither ANA or AT titers was related to body mass index, current smoking status, use of inhaled steroids, the Charlson index, or serum C-reactive protein values. CONCLUSIONS: Between a quarter and a third of patients with clinically stable COPD present abnormal titers of circulating ANA and AT. The observed relationship between AT and lung function supports a role for autoimmunity in the pathogenesis of COPD.

Low erythropoietin plasma levels during exacerbations of COPD.

BACKGROUND: It is known that pro-inflammatory cytokines suppress in vitro the gene expression and protein production of erythropoietin (Epo). We hypothesized that systemic inflammation in patients with chronic obstructive pulmonary disease (COPD) may influence Epo production, particularly during episodes of exacerbation of the disease (ECOPD) where an inflammatory burst is known to occur. OBJECTIVES: We compared the plasma levels of Epo and high-sensitivity (hs) C-reactive protein (hsC-RP) in patients hospitalized because of ECOPD (n = 26; FEV(1): 48 +/- 15% predicted), patients with clinically stable COPD (n = 31; FEV(1): 49 +/- 17% predicted), smokers with normal lung function (n = 9), and healthy never smokers (n = 9). METHODS: Venous blood samples were taken between 9 and 10 a.m. after an overnight fast into tubes with EDTA (10 ml) or without EDTA (10 ml). Plasma levels of Epo (R&D Systems Inc., Minneapolis, Minn., USA) and hsC-RP (BioSource, Belgium) were determined by ELISA. RESULTS: Log-Epo plasma levels were significantly lower (0.46 +/- 0.32 mU/ml) in ECOPD than in stable COPD (1.05 +/- 0.23 mU/ml), smokers (0.95 +/- 0.11 mU/ml) and never smokers with normal lung function (0.92 +/- 0.19 mU/ml) (p < 0.01, each). In a subset of 8 COPD patients who could be studied both during ECOPD and clinical stability, log-Epo increased from 0.49 +/- 0.42 mU/ml during ECOPD to 0.97 +/- 0.19 mU/ml during stability (p < 0.01). In patients with COPD log-Epo was significantly related to hsC-RP (r = -0.55, p < 0.0001) and circulating neutrophils (r = -0.48, p < 0.0001). CONCLUSIONS: These results show that the plasma levels of Epo are reduced during ECOPD likely in relation to a burst of systemic inflammation.

Non-cytotoxic variants of the Kid protein that retain their auto-regulatory activity.

Kid and Kis are, respectively, the toxin and antitoxin encoded by the parD operon of plasmid R1. The recently solved crystal structure of Kid has revealed that this protein closely resembles the CcdB toxin of plasmid F. In CcdB, the residues involved in toxicity are located at the carboxy-terminal end of the protein. However, an analogous information on the Kid toxin was not available. Here, we have characterized a collection of non-toxic mutants of the Kid protein and identified the residues that affected the toxicity but not the co-regulatory activity of Kid. These are located in two discrete regions of the protein, at the amino and carboxy-terminal ends. Particularly, residues E18 and R85, that are conserved in the Escherichia coli ChpAK and RelE toxins, are affected by amino-acid changes that alter neither the overall structure of the protein nor its state of association, as shown by CD and sedimentation equilibrium analyses. However, thermal denaturation and intrinsic tryptophan fluorescence emission data point to subtle local changes at the N-terminal end of the protein. The implications of these results in the current model on the structure and function of Kid-related bacterial toxins are discussed.