Biomarkers of Fibrosis in Patients with COVID-19 One Year After Hospital Discharge: A Prospective Cohort Study.

Beyond the acute infection of coronavirus disease (COVID-19), concern has arisen about long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of our study was to analyze if there is any biomarker of fibrogenesis in patients with COVID-19 pneumonia capable of predicting post-COVID-19 pulmonary sequelae. We conducted a multicenter, prospective, observational cohort study of patients admitted to a hospital with bilateral COVID-19 pneumonia. We classified patients into two groups according to severity, and blood sampling to measure matrix metalloproteinase 1 (MMP-1), MMP-7, periostin, and VEGF and respiratory function tests and high-resolution computed tomography were performed at 2 and 12 months after hospital discharge. A total of 135 patients were evaluated at 12 months. Their median age was 61 (interquartile range, 19) years, and 58.5% were men. We found between-group differences in age, radiological involvement, length of hospital stay, and inflammatory laboratory parameters. Differences were found between 2 and 12 months in all functional tests, including improvements in predicted forced vital capacity (98.0% vs. 103.9%; P = 0.001) and DlCO <80% (60.9% vs. 39.7%; P = 0.001). At 12 months, 63% of patients had complete high-resolution computed tomography resolution, but fibrotic changes persisted in 29.4%. Biomarker analysis demonstrated differences at 2 months in periostin (0.8893 vs. 1.437 ng/ml; P < 0.001) and MMP-7 (8.7249 vs. 15.2181 ng/ml; P < 0.001). No differences were found at 12 months. In multivariable analysis, only 2-month periostin was associated with 12-month fibrotic changes (odds ratio, 1.0013; 95% confidence interval, 1.0006-1.00231; P = 0.003) and 12-month DlCO impairment (odds ratio, 1.0006; 95% confidence interval, 1.0000-1.0013; P = 0.047). Our data suggest that early periostin postdischarge could predict the presence of fibrotic pulmonary changes.

Lung function and radiological findings 1 year after COVID-19: a prospective follow-up.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has already affected more than 400 million people, with increasing numbers of survivors. These data indicate that a myriad of people may be affected by pulmonary sequelae of the infection. The aim of this study was to evaluate pulmonary sequelae in patients with bilateral COVID-19 pneumonia according to severity 1 year after hospital discharge. METHODS: COVID-FIBROTIC is a multicenter prospective observational cohort study for admitted patients with bilateral COVID-19 pneumonia. Pulmonary functional outcomes and chest computed tomography sequelae were analyzed 12 months after hospital discharge and we classified patients into three groups according to severity. A post hoc analysis model was designed to establish how functional test changed between groups and over time. A multivariable logistic regression model was created to study prognostic factors for lung diffusion impairment and radiological fibrotic-like changes at 12 months. RESULTS: Among 488 hospitalized patients with COVID-19 pneumonia, 284 patients had completed the entire evaluation at 12 months. Median age was 60.5 ± 11.9 and 55.3% were men. We found between-group differences in male sex, length of hospital stay, radiological involvement and inflammatory laboratory parameters. The functional evaluation of pulmonary sequelae showed that severe patients had statistically worse levels of lung diffusion at 2 months but no between group differences were found in subsequent controls. At 12-month follow up, however, we found impaired lung diffusion in 39.8% unrelated to severity. Radiological fibrotic-like changes at 12 months were reported in 22.7% of patients (102/448), only associated with radiological involvement at admission (OR: 1.55, 95% CI 1.06-2.38; p = 0.02) and LDH (OR: 0.99, 95% CI 0.98-0.99; p = 0.046). CONCLUSION: Our data suggest that a significant percentage of individuals would develop pulmonary sequelae after COVID 19 pneumonia, regardless of severity of the acute process. Trial registration clinicaltrials.gov NCT04409275 (June 1, 2020).

Lung Function, Radiological Findings and Biomarkers of Fibrogenesis in a Cohort of COVID-19 Patients Six Months After Hospital Discharge / Función pulmonar, hallazgos radiológicos y biomarcadores de la fibrogénesis en una cohorte de pacientes de COVID-19 seis meses después del alta

Introduction Impairment in pulmonary function tests and radiological abnormalities are a major concern in COVID-19 survivors. Our aim is to evaluate functional respiratory parameters, changes in chest CT, and correlation with peripheral blood biomarkers involved in lung fibrosis at two and six months after SARS-CoV-2 pneumonia. Methods COVID-FIBROTIC (clinicaltrials.gov NCT04409275) is a multicenter prospective observational cohort study aimed to evaluate discharged patients. Pulmonary function tests, circulating serum biomarkers, chest radiography and chest CT were performed at outpatient visits. Results In total, 313, aged 61.12±12.26 years, out of 481 included patients were available. The proportion of patients with DLCO<80% was 54.6% and 47% at 60 and 180 days. Associated factors with diffusion impairment at 6 months were female sex (OR: 2.97, 95%CI 1.74–5.06, p=0.001), age (OR: 1.03, 95% CI: 1.01–1.05, p=0.005), and peak RALE score (OR: 1.22, 95% CI 1.06–1.40, p=0.005). Patients with altered lung diffusion showed higher levels of MMP-7 (11.54±8.96 vs 6.71±4.25, p=0.001), and periostin (1.11±0.07 vs 0.84±0.40, p=0.001). 226 patients underwent CT scan, of whom 149 (66%) had radiological sequelae of COVID-19. In severe patients, 68.35% had ground glass opacities and 38.46% had parenchymal bands. Early fibrotic changes were associated with higher levels of MMP7 (13.20±9.20 vs 7.92±6.32, p=0.001), MMP1 (10.40±8.21 vs 6.97±8.89, p=0.023), and periostin (1.36±0.93 vs 0.87±0.39, p=0.001). Conclusion Almost half of patients with moderate or severe COVID-19 pneumonia had impaired pulmonary diffusion six months after discharge. Severe patients showed fibrotic lesions in CT scan and elevated serum biomarkers involved in pulmonary fibrosis.

Introducción El deterioro de la función pulmonar en las pruebas correspondientes y las alteraciones radiológicas son las preocupaciones principales en los supervivientes de la COVID-19. Nuestro objetivo fue evaluar los parámetros de la función respiratoria, los cambios en la TC de tórax y la correlación con los biomarcadores en sangre periférica involucrados en la fibrosis pulmonar a los 2 y a los 6 meses tras la neumonía por SARS-CoV-2. Métodos El ensayo COVID-FIBROTIC (clinicaltrials.gov NCT04409275) es un estudio de cohortes multicéntrico, prospectivo y observacional cuyo objetivo fue evaluar los pacientes dados de alta. Se realizaron pruebas de función pulmonar, detección de biomarcadores en plasma circulante y radiografía y TC de tórax durante las visitas ambulatorias. Resultados En total 313 pacientes, de 61,12±12,26 años, de los 481 incluidos estuvieron disponibles. La proporción de pacientes con DLCO<80% fue del 54,6 y del 47% a los 60 y 180 días. Los factores que se sociaron a la alteración de la difusión a los 6 meses fueron el sexo femenino (OR: 2,97; IC del 95%: 1,74-5,06; p=0,001), la edad (OR: 1,03; IC del 95%: 1,01-1,05; p=0,005) y la puntuación RALE más alta (OR: 1,22; IC del 95%: 1,06-1,40; p=0,005). Los pacientes con alteración de la difusión pulmonar mostraron niveles más altos de MMP-7 (11,54±8,96 frente a 6,71±4,25; p=0,001) y periostina (1,11±0.07 frente a 0,84±0,40; p=0,001). Se le realizó una TC a 226 pacientes de los cuales 149 (66%) presentaban secuelas radiológicas de la COVID-19. En los pacientes graves, el 68,35% mostraban opacidades en vidrio esmerilado y el 38,46%, bandas parenquimatosas. Los cambios fibróticos tempranos se asociaron a niveles más altos de MMP7 (13,20±9,20 frente a 7,92±6,32; p=0,001), MMP1 (10,40±8,21 frente a 6,97±8,89; p=0,023), y periostina (1,36±0,93 frente a 0,87±0,39; p=0,001). Conclusión Casi la mitad de los pacientes con neumonía moderada o grave por COVID-19 presentaba alteración de la difusión pulmonar 6 meses después del alta. Los pacientes graves mostraban lesiones fibróticas en laTC y un aumento de los biomarcadores séricos relacionados con la fibrosis pulmonar

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.

Lung Function, Radiological Findings and Biomarkers of Fibrogenesis in a Cohort of COVID-19 Patients Six Months After Hospital Discharge.

INTRODUCTION: Impairment in pulmonary function tests and radiological abnormalities are a major concern in COVID-19 survivors. Our aim is to evaluate functional respiratory parameters, changes in chest CT, and correlation with peripheral blood biomarkers involved in lung fibrosis at two and six months after SARS-CoV-2 pneumonia. METHODS: COVID-FIBROTIC (clinicaltrials.gov NCT04409275) is a multicenter prospective observational cohort study aimed to evaluate discharged patients. Pulmonary function tests, circulating serum biomarkers, chest radiography and chest CT were performed at outpatient visits. RESULTS: In total, 313, aged 61.12 ± 12.26 years, out of 481 included patients were available. The proportion of patients with DLCO < 80% was 54.6% and 47% at 60 and 180 days. Associated factors with diffusion impairment at 6 months were female sex (OR: 2.97, 95%CI 1.74-5.06, p = 0.001), age (OR: 1.03, 95% CI: 1.01-1.05, p = 0.005), and peak RALE score (OR: 1.22, 95% CI 1.06-1.40, p = 0.005). Patients with altered lung diffusion showed higher levels of MMP-7 (11.54 ± 8.96 vs 6.71 ± 4.25, p = 0.001), and periostin (1.11 ± 0.07 vs 0.84 ± 0.40, p = 0.001). 226 patients underwent CT scan, of whom 149 (66%) had radiological sequelae of COVID-19. In severe patients, 68.35% had ground glass opacities and 38.46% had parenchymal bands. Early fibrotic changes were associated with higher levels of MMP7 (13.20 ± 9.20 vs 7.92 ± 6.32, p = 0.001), MMP1 (10.40 ± 8.21 vs 6.97 ± 8.89, p = 0.023), and periostin (1.36 ± 0.93 vs 0.87 ± 0.39, p = 0.001). CONCLUSION: Almost half of patients with moderate or severe COVID-19 pneumonia had impaired pulmonary diffusion six months after discharge. Severe patients showed fibrotic lesions in CT scan and elevated serum biomarkers involved in pulmonary fibrosis.

INTRODUCCIÓN: El deterioro de la función pulmonar en las pruebas correspondientes y las alteraciones radiológicas son las preocupaciones principales en los supervivientes de la COVID-19. Nuestro objetivo fue evaluar los parámetros de la función respiratoria, los cambios en la TC de tórax y la correlación con los biomarcadores en sangre periférica involucrados en la fibrosis pulmonar a los 2 y a los 6 meses tras la neumonía por SARS-CoV-2. MÉTODOS: El ensayo COVID-FIBROTIC (clinicaltrials.gov NCT04409275) es un estudio de cohortes multicéntrico, prospectivo y observacional cuyo objetivo fue evaluar los pacientes dados de alta. Se realizaron pruebas de función pulmonar, detección de biomarcadores en plasma circulante y radiografía y TC de tórax durante las visitas ambulatorias. RESULTADOS: En total 313 pacientes, de 61,12 ± 12,26 años, de los 481 incluidos estuvieron disponibles.La proporción de pacientes con DLCO < 80% fue del 54,6 y del 47% a los 60 y 180 días.Los factores que se asociaron a la alteración de la difusión a los 6 meses fueron el sexo femenino (OR: 2,97; IC del 95%: 1,74-5,06; p = 0,001), la edad (OR: 1,03; IC del 95%: 1,01-1,05; p = 0,005) y la puntuación RALE más alta (OR: 1,22; IC del 95%: 1,06-1,40; p = 0,005). Los pacientes con alteración de la difusión pulmonar mostraron niveles más altos de MMP-7 (11,54 ± 8,96 frente a 6,71 ± 4,25; p = 0,001) y periostina (1,11 ± 0.07 frente a 0,84 ± 0,40; p = 0,001). Se le realizó una TC a 226 pacientes de los cuales 149 (66%) presentaban secuelas radiológicas de la COVID-19. En los pacientes graves, el 68,35% mostraban opacidades en vidrio esmerilado y el 38,46%, bandas parenquimatosas. Los cambios fibróticos tempranos se asociaron a niveles más altos de MMP7 (13,20 ± 9,20 frente a 7,92 ± 6,32; p = 0,001), MMP1 (10,40 ± 8,21 frente a 6,97 ± 8,89; p = 0,023), y periostina (1,36 ± 0,93 frente a 0,87 ± 0,39; p = 0,001). CONCLUSIÓN: Casi la mitad de los pacientes con neumonía moderada o grave por COVID-19 presentaba alteración de la difusión pulmonar 6 meses después del alta. Los pacientes graves mostraban lesiones fibróticas en laTC y un aumento de los biomarcadores séricos relacionados con la fibrosis pulmonar.

Demographic and clinical profile of idiopathic pulmonary fibrosis patients in Spain: the SEPAR National Registry.

BACKGROUND: Little is known on the characteristics of patients diagnosed with idiopathic pulmonary fibrosis (IPF) in Spain. We aimed to characterize the demographic and clinical profile of IPF patients included in the IPF National Registry of the Spanish Respiratory Society (SEPAR). METHODS: This is a prospective, observational, multicentre and nationwide study that involved 608 IPF patients included in the SEPAR IPF Registry up to June 27th, 2017, and who received any treatment for their disease. IPF patients were predominantly males, ex-smokers, and aged in their 70s, similar to other registries. RESULTS: Upon inclusion, mean ± SD predicted forced vital capacity was 77.6% ± 19.4, diffusing capacity for carbon monoxide was 48.5% ± 17.7, and the 6-min walk distance was 423.5 m ± 110.4. The diagnosis was mainly established on results from the high-resolution computed tomography in the proper clinical context (55.0% of patients), while 21.2% of patients required invasive procedures (surgical lung biopsy) for definitive diagnosis. Anti-fibrotic treatment was prescribed in 69.4% of cases, 51.5% pirfenidone and 17.9% nintedanib, overall with a good safety profile. CONCLUSIONS: The SEPAR IPF Registry should help to further characterize current characteristics and future trends of IPF patients in Spain and compare/pool them with other registries and cohorts.

Cytotoxic Natural Killer Subpopulations as a Prognostic Factor of Malignant Pleural Effusion.

BACKGROUND: Malignant pleural effusion (MPE) is a sign of advanced disease of poor prognosis. As natural killer (NK) cells are involved in the first line of tumour defence, we aimed to validate a new diagnostic and prognostic indicator for MPE based on NK subpopulations of pleural fluid (PF) and peripheral blood (PB). METHODS: NK subpopulations were determined in PF and PB in 71 patients with malignant, paramalignant or benign pleural effusion. The receiver operating characteristic (ROC) curves, Kaplan-Meier, multivariable Cox model and decision trees created with the CHAID (Chi-square automatic interaction detector) methodology were employed. RESULTS: We demonstrated that the PF/PB ratios of the CD56 bright CD16- and CD56 dim CD16- NK subpopulations were higher (p = 0.013 and p = 0.003, respectively) in MPEs and paramalignant pleural effusions (PPEs) than in benign ones, with an AUC of 0.757 and 0.741, respectively. The PF/PB ratio of CD16+ NK and CD57+ NK obtained a higher hazard ratio (HR) in the crude Cox's regression analysis. In the adjusted Cox's regression analysis, the PF/PB ratio of CD16+ NK gave the highest HR (HR 6.1 [1.76-21.1]) (p = 0.004). In the decision tree created for the MPE prognosis, we observed that the main predictor variable among the studied clinical, radiological, and analytical variables was lung mass, and that 92.9% of the patients who survived had a PF/PB ratio of the CD56 dim CD16+ NK subpopulation ≤ 0.43. CONCLUSIONS: Our data suggest that both the PF/PB ratios of cytotoxic subpopulations CD57+ NK and CD16+ NK are useful as a prognostic factor of MPE. Other subpopulations (CD56 bright CD16- and CD56 dim CD16- NK) could help to diagnose MPE.

Pulmonary cysts in smoking-related interstitial fibrosis: a form of pseudocyst secondary to pulmonary interstitial emphysema / Quistes pulmonares en el contexto de la fibrosis intersticial pulmonar relacionada con el tabaco: una forma de seudoquiste secundario a enfisema intersticial pulmonar

Smoking-related interstitial fibrosis is a distinct form of fibrosis, found in smokers, which has striking histopathological features. We present a case of pulmonary interstitial fibrosis with cysts in a 58-year-old woman who was a significant active smoker, presenting with a 7 month history of progressive dyspnea. TAC revealed thin-walled pulmonary cysts. An open lung biopsy was performed and the histopathological study showed hyaline fibrous thickening of the alveolar septa, respiratory bronchiolitis and cysts in the thickness of the interlobar septa. Immunohistochemically, the absence of an epithelial, vascular or lymphatic endothelial lining of the cysts would suggest that the cysts had been caused by pulmonary interstitial emphysema. Immunohistochemistry is essential in the differential diagnosis that includes, in this case, true cysts, pseudocysts and pulmonary lymphangiectasia

La fibrosis intersticial relacionada con el tabaco es una forma especial de fibrosis con histología característica que ocurre en fumadores. Presentamos un caso de fibrosis intersticial pulmonar con quistes en una mujer de 58 años con historia de tabaquismo importante, que refería disnea progresiva en los últimos 7 meses. La TAC reveló quistes pulmonares de paredes delgadas. Se realizó una biopsia pulmonar abierta y el estudio histopatológico mostró engrosamiento fibroso hialino de los septos alveolares, bronquiolitis respiratoria y quistes en el espesor de los septos interlobares. Inmunohistoquímicamente, la ausencia de revestimiento epitelial, endotelial vascular y linfático de los quistes, apoya que estos son causados por enfisema intersticial pulmonar. La inmunohistoquímica es esencial en el diagnóstico diferencial que incluye en este caso, quistes verdaderos, seudoquistes y linfangiectasia pulmonar

Prognosis and Follow-Up of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF), a devastating progressive interstitial lung disease (ILD) with no known cause, is the most common and deadly of the idiopathic interstitial pneumonias. With a median survival of 3⁻5 years following diagnosis, IPF is characterized by a progressive decline in lung function and quality of life in most patients. Prognostic factors recognized classically that influence mortality include functional, clinical and radiological parameters. However, in recent years, there has also been progress in the knowledge of genetic factors and biomarkers that may be useful in the prognostic evaluation of these patients. On the other hand, the monitoring of the disease throughout its evolution is key to improving the prognosis of the patients, as it allows for taking therapeutic measures based on this evolution, even early remission for lung transplantation. This article reviews the main prognostic factors of the disease, as well as the most useful way to monitor the disease follow-up.

Asthma and influenza vaccination in elderly hospitalized patients: Matched case-control study in Spain.

OBJECTIVES: Influenza infection is an exacerbating factor for asthma, and its prevention is critical in managing asthmatic patients. We investigated the effect of influenza vaccination on asthmatic and non-asthmatic patients hospitalized with laboratory-confirmed influenza in Spain. METHODS: We made a matched case-control study to assess the frequency of hospitalization for influenza in people aged ≥65 years. Hospitalized patients with unplanned hospital admissions were recruited from 20 hospitals representing seven Spanish regions. Cases were defined as those hospitalized due to a laboratory-confirmed influenza infection and controls were matched by age, sex, and hospital. Data were obtained from clinical records, and patients stratified by clinical asthma history. Vaccination status and asthma due to influenza infection were analyzed according to sociodemographic variables and medical risk conditions. Multivariable analysis was made using conditional logistic regression models. RESULTS: 582 hospitalized patients with influenza (15.8% asthmatic) and 1,570 hospitalized patients without influenza (7.9% asthmatic) were included. In the multivariable conditional logistic regression using unvaccinated and non-asthmatic patients as the reference group, vaccination significantly prevented influenza in non-asthmatic patients (aOR = 0.63; 95% CI: 0.45, 0.88) and also showed a trend for a possibly protective effect in asthmatic patients (aOR = 0.79; 95% CI: 0.34, 1.81). CONCLUSION: Our results suggest that influenza vaccination could be a protective factor for asthmatic patients, although the results are inconclusive and further research is required. Practically, given the better clinical evolution of vaccinated asthma cases, and the lack of better evidence, the emphasis on vaccination of this group should continue.

Effectiveness and safety of outpatient parenteral antimicrobial therapy in acute exacerbation of chronic obstructive pulmonary disease.

AIM: We analysed the effectiveness and safety of outpatient parenteral antibiotic therapy (OPAT) in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in patients admitted to home hospitalisation units (HHU). METHODS: Retrospective multicentre study of patients with AECOPD included in the Spanish OPAT Registry during 2 years period. RESULTS: Twenty-seven hospitals included 562 episodes in 361 patients diagnosed COPD GOLD III-IV. The most frequently isolated pathogen was Pseudomonas aeruginosa (38%) and the most frequently used antibiotic was piperacillin-tazobactam (20%). The effectiveness of OPAT defined as the rate of improvement or recovery was 93.4%. The safety of OPAT defined as no adverse drug events and no infectious or catheter-related complications was 89.3%. Moreover, the risk of hospital readmission was not greater in patients with AECOPD aged >80 years. No differences in the effectiveness or safety were observed when OPAT was administered by patients and/or caregivers. CONCLUSION: Patients with AECOPD who require parenteral antimicrobial therapy can be managed effectively and safely in HHU, avoiding hospital stays, readmissions and complications.

Asthma in older people hospitalized with influenza in Spain: A case-control study.

BACKGROUND: Influenza infection is an exacerbating factor for asthma, and its prevention is critical in older patients with asthma. OBJECTIVE: This study investigated the association between asthma and influenza-related hospitalization, in Spain, of patients ages ≥ 65 years and their clinical evolution. METHODS: A multicenter case-control study was carried out in 20 Spanish hospitals during the 2013-2014 and 2014-2015 influenza seasons. Patients ages ≥ 65 years hospitalized with laboratory-confirmed influenza with and without asthma were matched with controls according to the presence of asthma, sex, age, hospital, and date of hospitalization. RESULTS: A total of 561 patients with influenza (15.9% with asthma) and 1258 patients without influenza (8.0% with asthma) were included as cases and controls, respectively. The adjusted risk of influenza for patients with asthma was calculated by multivariate conditional logistic regression. The adjustment variables were the following: smoker/nonsmoker, pneumonia in the 2 years before hospital admission, previous oral treatment with corticosteroids, influenza vaccination during the seasonal campaign, Barthel index (ordinal scale used to measure performance in activities of daily living), level of education, obesity, and the presence of other comorbidities. Patients with asthma presented a great risk of influenza (adjusted odds ratio 2.64 [95% confidence interval, 1.77-3.94]). Compared with patients without asthma, patients with asthma had more symptoms, and these had been present for longer before admission but presented a lower hospital or postdischarge mortality. CONCLUSION: This study indicated that asthma was associated with hospitalization from influenza A infection. Although patients with asthma and with influenza had more symptoms, hospital or postdischarge mortality was lower, probably due to a better response to medical treatment.

Predicting Malignant and Paramalignant Pleural Effusions by Combining Clinical, Radiological and Pleural Fluid Analytical Parameters.

BACKGROUND: The usefulness of clinical, radiological and pleural fluid analytical parameters for diagnosing malignant and paramalignant pleural effusion is not clearly stated. Hence this study aimed to identify possible predictor variables of diagnosing malignancy in pleural effusion of unknown aetiology. METHODS: Clinical, radiological and pleural fluid analytical parameters were obtained from consecutive patients who had suffered pleural effusion of unknown aetiology. They were classified into three groups according to their final diagnosis: malignant, paramalignant and benign pleural effusion. The CHAID (Chi-square automatic interaction detector) methodology was used to estimate the implication of the clinical, radiological and analytical variables in daily practice through decision trees. RESULTS: Of 71 patients, malignant (n = 31), paramalignant (n = 15) and benign (n = 25), smoking habit, dyspnoea, weight loss, radiological characteristics (mass, node, adenopathies and pleural thickening) and pleural fluid analytical parameters (pH and glucose) distinguished malignant and paramalignant pleural effusions (all with a p < 0.05). Decision tree 1 classified 77.8% of malignant and paramalignant pleural effusions in step 2. Decision tree 2 classified 83.3% of malignant pleural effusions in step 2, 73.3% of paramalignant pleural effusions and 91.7% of benign ones. CONCLUSIONS: The data herein suggest that the identified predictor values applied to tree diagrams, which required no extraordinary measures, have a higher rate of correct identification of malignant, paramalignant and benign effusions when compared to techniques available today and proved most useful for usual clinical practice. Future studies are still needed to further improve the classification of patients.

Normativa sobre el tratamiento farmacológico de la fibrosis pulmonar idiopática / Guidelines for the medical treatment of idiopathic pulmonary fibrosisGuidelines for the medical treatment of idiopathic pulmonary fibrosis

La fibrosis pulmonar idiopática es una enfermedad intersticial fibrosante limitada al pulmón, con mal pronóstico. Su incidencia ha aumentado en los últimos años, probablemente por la optimización de los métodos diagnósticos y el aumento en la esperanza de vida. En 2013 se publicó la normativa SEPAR sobre el diagnóstico y tratamiento de la fibrosis pulmonar idiopática. Desde entonces, se han publicado los resultados de ensayos clínicos y metaanálisis que han supuesto, con base en la evidencia científica, la introducción de pirfenidona y nintedanib en el tratamiento de la enfermedad. En 2015 se ha actualizado el consenso internacional de 2011, en el que se describen los cambios en las recomendaciones terapéuticas. Debido a ello cabía actualizar el apartado de la normativa sobre el tratamiento farmacológico de la fibrosis pulmonar idiopática. No se tratarán aspectos diagnósticos ni el tratamiento no farmacológico, ya que no se han producido cambios relevantes desde la normativa de 2013

Idiopathic pulmonary fibrosis is defined as chronic fibrosing interstitial pneumonia limited to the lung, with poor prognosis. The incidence has been rising in recent years probably due to improved diagnostic methods and increased life expectancy. In 2013, the SEPAR guidelines for the diagnosis and treatment for idiopathic pulmonary fibrosis were published. Since then, clinical trials and meta-analyses have shown strong scientific evidence for the use of pirfenidone and nintedanib in the treatment of idiopathic pulmonary fibrosis. In 2015, the international consensus of 2011 was updated and new therapeutic recommendations were established, prompting us to update our recommendation for the medical treatment of idiopathic pulmonary fibrosis accordingly. Diagnostic aspects and non-pharmacological treatment will not be discussed as no relevant developments have emerged since the 2013 guidelines

Guidelines for the medical treatment of idiopathic pulmonary fibrosis. / Normativa sobre el tratamiento farmacológico de la fibrosis pulmonar idiopática.

Idiopathic pulmonary fibrosis is defined as chronic fibrosing interstitial pneumonia limited to the lung, with poor prognosis. The incidence has been rising in recent years probably due to improved diagnostic methods and increased life expectancy. In 2013, the SEPAR guidelines for the diagnosis and treatment for idiopathic pulmonary fibrosis were published. Since then, clinical trials and meta-analyses have shown strong scientific evidence for the use of pirfenidone and nintedanib in the treatment of idiopathic pulmonary fibrosis. In 2015, the international consensus of 2011 was updated and new therapeutic recommendations were established, prompting us to update our recommendation for the medical treatment of idiopathic pulmonary fibrosis accordingly. Diagnostic aspects and non-pharmacological treatment will not be discussed as no relevant developments have emerged since the 2013 guidelines.

¿Cómo viven la ventilación no invasiva los enfermos y sus cuidadores? Revisión bibliográfica sistemática de investigaciones cualitativas / How do sick people their caregivers live non-invasive ventilation? Systematic literature review of qualitative research

Introducción. Sabemos que la ventilación no invasiva (VNI) es un soporte ventilatorio de elección, aunque a veces fracasa, por intolerancia, falta de adherencia, incumplimiento, etc. ¿Cómo podemos anticiparnos a ese fracaso? Objetivo. Explorar la evidencia cualitativa sobre las vivencias de las personas en tratamiento con VNI y sus cuidadores formales e informales. Método. Revisión bibliográfica sistemática de artículos originales indexados entre 2005 y 2015 que estudian la VNI en población adulta con metodología cualitativa, en seis bases de datos. Evaluación por pares de la calidad científica con herramienta del Programa CASPe. Metasíntesis cualitativa de los hallazgos. Resultados. 15 artículos cumplen criterios de selección, basados en la Teoría Fundamentada y en Fenomenología, que utilizan: entrevistas, observación y grupo focal, tanto a enfermos como a familias y profesionales de salud. Destaca la sensación de angustia y pérdida de control, aunque la VNI les alivia la disnea (ambivalencia). Búsqueda del bienestar cotidiano a través de rutinas y participación activa. Interacción dependencia/autonomía, sobre todo en la toma de decisiones, y se encuentran divergencias que hacen complejo el proceso de información y voluntades anticipadas. La sabiduría práctica de enfermería se describe como básica, y se manifiestan dificultades: falta de tiempo, sobrecarga de trabajo, tecnocentrismo, inexperiencia. Conclusiones. La evidencia cualitativa del tratamiento con VNI, aunque escasa, es variada, pues se exploran diferentes parcelas (situaciones agudas, crónicas, terminales), y desde diferentes puntos de vista. Integrar esos hallazgos en nuestra práctica profesional nos ayudará a aumentar la adherencia y el éxito del tratamiento, pero sobre todo a mejorar la calidad de vida de los pacientes ventilados y sus familias (AU)

Introduction. We know that non-invasive ventilation (NIV) is a basic ventilator support, but sometimes it fails, because of intolerance, lack of adherence, breach, etc. How can we anticipate that failure? We intend to explore the qualitative evidence on the experiences of people with this treatment and their formal and informal caregivers. Method. Systematic literature review of original articles indexed from 2005 to 2015, which study the NIV in adult population with qualitative methodology in six databases. Peer review of scientific quality with tool of the CASPe Program. Qualitative metasynthesis of the findings. Results. 15 articles met selection criteria, based on Grounded Theory and Phenomenology, which use interviews, observation and focus group, directed both patients, and families and health professionals. Its studies emphasize the feeling of anxiety and loss of control, although the NIV relieves them dyspnea (ambivalence). Search daily well-being through routines and active participation. Interaction dependence/autonomy, especially in decision-making, finding differences that make complex the process information and advance directives. Practical wisdom of nursing care 24 hours with patients is described basic, and difficulties being narrated: lack of time, overload of work, technocentrism, inexperience. Conclusions. The qualitative evidence of treatment with VNI is varied although scarce; different plots (acute situations, chronic, terminals) are explored, from different points of view. The integration of these findings in our practice will help us to increase adherence and become the treatment successful, but especially to improve the quality of life of ventilated patients and their families (AU)

Síndrome platipnea-ortodeoxia cardiaco: una causa «misteriosa» de hipoxemia / Cardiac platypnea-orthodeoxia syndrome: A «mysterious» cause of hypoxemia

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Análisis de la utilización del dímero D en urgencias: ajuste por edad, uso inapropiado y predicción de extensión y gravedad de la embolia pulmonar / D-dimer testing in the emergency department: age adjustment, inappropriateuse, and ability to predict the extension and severity of pulmonary embolism

Objetivos: Valorar la mejora de la precisión diagnóstica del dímero D (DD) al ajustar por la edad aplicando la fórmula publicada por Douma et al., así como evaluar la adecuación de la solicitud del DD a la sospecha clínica y relacionar sus valores con la extensión y gravedad de la embolia pulmonar. Método: Estudio observacional, retrospectivo que incluye 1.833 pacientes atendidos en el servicio de urgencias de nuestro hospital a lo largo de 1 año, a los que se solicitó determinación del DD. Se calculó sensibilidad, especificidad, valor predictivo positivo y negativo de su valor utilizando el punto de corte de nuestro centro (250 μg/mL) y ajustado por edad (fórmula de Douma et al. modificada) y se correlacionó con la extensión y gravedad de la embolia pulmonar cuando la hubo. Resultados: El ajuste por edad del valor de DD supone aumentar la proporción de casos verdaderos negativos, la especificidad y el valor predictivo positivo de esta determinación. Se encuentra una correlación significativa entre el valor del DD con la extensión de la embolia pulmonar (r = 0,41, p < 0,05) pero no con la gravedad clínica del episodio. Conclusiones: El ajuste del DD por la edad mejora la precisión diagnóstica de la embolia pulmonar, aunque, en nuestro entorno, su sospecha no se establece siguiendo las guías recomendadas. El valor del DD se relaciona con la extensión pero no con la gravedad de la embolia pulmonar (AU)

Objectives: To evaluate whether using D-dimer test results adjusted for age according to the formula proposed by Douma et al. improves diagnostic accuracy; to assess the appropriateness of ordering D-dimer tests on clinical suspicion of pulmonary embolism; and to explore the association of test results with the extension and severity of the embolism. Methods: Retrospective observational study of 1833 cases in which D-dimer testing was ordered for patients in our hospital’s emergency department in the course of a year. We calculated sensitivity, specificity, and positive and negative predictive values using our hospital’s D-dimer cutoff of 250 μg/mL adjusted for age with a modification of Douma et al.’s formula. When information about pulmonary embolism extension and severity was on record, we assessed the correlation with test results. Results: Adjusting D-dimer level for age increased the number of true negatives and the specificity and positive predictive value of the test. D-dimer level correlated significantly with the extension of pulmonary embolism (r=0.41, P<.05) but not with clinical severity. Conclusions: Adjusting the D-dimer test result by age improves accuracy in the diagnosis of pulmonary embolism, even though clinical suspicion in Spain does not follow guideline recommendations. Our findings suggest that Ddimer level correlates with the extension but not the severity of pulmonary embolism (AU)