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).

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.

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.

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.

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.

Accelerated telomere attrition in children and teenagers with α1-antitrypsin deficiency.

Numerous studies have shown that oxidative stress accelerates telomere shortening in several lung pathologies. Since oxidative stress is involved in the pathophysiology of α1-antitrypsin deficiency (AATD), we hypothesised that telomere shortening would be accelerated in AATD patients. This study aimed to assess telomere length in AATD patients and to study its association with α1-antitrypsin phenotypes.Telomere length, telomerase activity, telomerase reverse transcriptase (hTERT) expression and biomarkers of oxidative stress were measured in 62 children and teenagers (aged 2-18 years) diagnosed with AATD and 18 controls (aged 3-16 years).Our results show that intermediate-risk (MZ; SZ) and high-risk (ZZ) AATD patients have significantly shorter telomeres and increased oxidative stress than controls. Correlation studies indicate that telomere length was related to oxidative stress markers in AATD patients. Multiple hypothesis testing revealed an association between telomere length, telomerase activity, hTERT expression and AATD phenotypes; high-risk patients showed shorter telomeres, lower hTERT expression and decreased telomerase activity than intermediate-risk and low-risk patients.AATD patients show evidence of increased oxidative stress leading to telomere attrition. An association between telomere and α1-antitrypsin phenotypes is observed suggesting that telomere length could be a promising biomarker for AATD disease progression.

[How do Sick People and Their Caregivers Live Non-Invasive Ventilation? Systematic Literature Review of Qualitative Research]. / ¿Cómo viven la ventilación no invasiva los enfermos y sus cuidadores?.

Introduction: W 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 id described basic, and difficulties being narrated: lack of time, overload of work, technocentrism, inexperience. Conclulsions: 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.

Accuracy of PaO2 /FiO2 calculated from SpO2 for severity assessment in ED patients with pneumonia.

BACKGROUND AND OBJECTIVE: Assessment of oxygenation in patients with community-acquired pneumonia is critical for treatment. The accuracy of percutaneous oxygen saturation (SpO2 ) determined by pulse oximetry is uncertain, and it has limited value in patients receiving supplemental oxygen. We hypothesized that calculation of partial arterial oxygen concentration/inspired oxygen faction (PaO2 /FiO2 ) from SpO2 by the Ellis or Rice equations might adequately correlate with PaO2 /FiO2 measured by arterial blood gases. METHODS: We studied 1004 patients with pneumonia in the emergency department with simultaneous measurement of SpO2 and PaO2 from two cohorts from Valencia, Spain and Utah, USA. We compared SpO2 with measured SaO2 , compared the equations' accuracy in calculating PaO2 /FiO2 and determined how often patients would be misclassified at clinically important thresholds. We compared estimated PaO2 /FiO2 to measured PaO2 /FiO2 using the Spearman correlation. RESULTS: Pairwise correlation of SpO2 with SaO2 was moderate (rho = 0.66; P < 0.01). Both equations performed similarly among patients with lower PaO2 /FiO2 ratios. The Ellis equation estimated PaO2 /FiO2 from SpO2 more accurately than the Rice equation in patients with PaO2 /FiO2 ≥200. Simple agreement between calculated and measured P/F was 91% and 92%, respectively. CONCLUSIONS: The Ellis equation was more accurate than the Rice equation for estimating PaO2 /FiO2 , especially at higher levels of P/F ratio. Estimation of PaO2 /FiO2 from SpO2 is accurate enough for initial oxygenation assessment. Ellis and Rice equations could misclassify 20% and 30% of patients, respectively, at higher levels of PaO2 /FiO2 . For patients with abnormal oxygenation falling near thresholds for clinical decision making, arterial blood gas measurement preferably on room air is more accurate.

Does prolonged onset of symptoms have a prognostic significance in community-acquired pneumonia?

BACKGROUND AND OBJECTIVE: Severity assessment is made at the time of the initial clinical presentation in patients with community-acquired pneumonia (CAP). It is unclear how the gap between time of presentation and duration of symptoms onset may impact clinical outcomes. Here we evaluate the association of prolonged onset of symptoms (POS) and the impact on clinical outcomes among hospitalized patients with CAP. METHODS: This was a prospective, multicentre study of CAP in Spain. The primary outcomes were the clinical factors associated with POS defined as days from symptoms onset to pneumonia diagnosis >7 days. The secondary outcomes were intensive care unit (ICU) admission, the presence of suppurative complications, septic shock and 30-day mortality. RESULTS: We enrolled 1038 patients diagnosed of CAP: 152 (14.6%) patients had a POS. In multivariate analysis, the presence of prior corticosteroid therapy, alcohol abuse, prior antibiotic therapy, and confusion, urea, respiratory rate, blood pressure and age 65 years or older score 0-1 was independently associated with POS. Patients with POS had a higher incidence of suppurative complications, but not of 30-day mortality when compared with a shorter onset of symptoms. CONCLUSIONS: Approximately 15% of patients diagnosed with CAP had POS. Risk factors associated with POS were previous corticosteroids and antibiotic therapy, alcoholism and less severe pneumonia. POS was associated with a higher rate of suppurative complications and less need for ICU admission.

[Influence of Clinical Practice Guidelines on the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis. Data from the Registry of the Spanish Society of Pulmonology and Thoracic Surgery]. / Influencia de las guías de práctica clínica en el diagnóstico y tratamiento de la fibrosis pulmonar idiopática. Datos del Registro de la Sociedad Española de Neumología y Cirugía Torácica.

Objective: The objective of the study was to analyze the diagnostic process and the time until the start of treatment of patients with idiopathic pulmonary fibrosis in relation to the publication of successive clinical practice guide. Material and methods: Multicenter, observational, ambispective study, in which patients includes in the idiopathic pulmonary fibrosis registry of the Spanish Society of Pulmonologist and Thoracic Surgery were analyzed. An electronic data collection notebook was enabled on the society's website. Sociodemographic and clinical variables were collected at diagnosis and follow-up of the patients. Results: From January 2012 to december 2019, 1064 patients were included in the registry, with 929 finally analyzed. The diagnosis process varied depending on the year in which it was performed, and the radiological pattern observed in the high-resolution computed tomography. Up to 26.3% of the cases (244) were diagnosed with chest high-resolution computed tomography and clinical evaluation. Surgical biopsy was used up to 50.2% of cases diagnosed before 2011, while it has been used in 14.2% since 2018. The median time from the onset of symptoms to diagnosis was 360 days (IQR 120-720), taking more than 2 years in the 21.0% of patients. A percentage of 79.4 of patients received antifibrotic treatment. The average time from diagnosis to the antifibrotic treatment has been 309 ± 596.5 days, with a median of 49 (IQR 0-307). Conclusions: The diagnostic process, including the time until diagnosis and the type of test used, has changed from 2011 to 2019, probably due to advances in clinical research and the publication of diagnostic-therapeutic consensus guidelines.

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.

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.

Varicella-zoster virus pneumonia in an adult population: has mortality decreased?

Varicella-zoster virus (VZV) pneumonia is one of the most serious complications of this infection in adults. The objective of this study was to analyze the epidemiological and clinical characteristics in a large sample of patients with VZV pneumonia. This was a 10-y retrospective, descriptive, observational study. We studied 46 patients with VZV pneumonia, 21 men and 25 women, with a mean age 36 +/-11 y. A contact with an index case was observed in 57%, 76 were active smokers, 6.5% consumed drugs and 2 women were pregnant. The symptoms were: fever (83%), cough (83%), dyspnoea (63%), pleuritic pain (70%), and haemoptysis (6%) and started 3-5 days after the onset of blisters, except in 11% in whom respiratory symptoms appeared first. Arterial blood gases showed a mean PO(2)/FiO(2) of 308 +/-101 and 30 patients had a PO(2) of <55 mmHg--11 of these (4%) were admitted to the ICU, 8 required mechanical ventilation. Comparison of patients in the ICU with those on the general ward showed differences in the duration of fever (6.1 +/- 4.2 vs 3.2 +/- 1.1 days, p <0.001), mean stay (16.8+/-9.3 vs 7.2+/-2.4 days, p <0.001) and complications such as acute renal failure (p = 0.01) and acute respiratory failure (p < 0.001). Despite the severity of disease, no patient died. Once diagnosed, 98% were treated with acyclovir, combined with steroids in 6 and with antibiotics in 3 complicated with bacterial pneumonia. The prevalence for the period was 0.33 cases/100,000 inhabitants/y. In conclusion, VZV pneumonia has a severe course and accounts for a high percentage of admissions to the intensive care unit. The absence of mortality may be related to early treatment with acyclovir. Smoking was a risk factor for VZV pneumonia.

Hypertension and sleep apnea-hypopnea syndrome: changes in echocardiographic abnormalities depending on the presence of hypertension and treatment with CPAP.

INTRODUCTION: Sleep apnea-hypopnea syndrome (SAHS) is an emerging disease with high prevalence. There is controversy as to whether cardiac abnormalities are due to the disease itself or to the arterial hypertension frequently associated with this disease. OBJECTIVES: To analyze echocardiographic abnormalities in a population of SAHS patients depending on the presence or absence of hypertension at the time of diagnosis and after six months of treatment with continuous positive airway pressure (CPAP). METHODS: We studied 85 consecutive patients diagnosed with SAHS who required treatment with CPAP (Hypertensive: 43, nonhypertensive: 42). We performed a baseline echocardiogram after six months of treatment. We analyzed morphological (wall thickness, diameters, ejection fraction) and functional (peak E- and A-wave velocities, deceleration time, Tei index) parameters of the left and right ventricles. RESULTS: Hypertensive patients were older and had higher blood pressure values, but there were no differences between groups in other clinical parameters. The hypertensive group had greater septal thickness (hypertensive: 12.1+/-2.3; nonhypertensive: 10.8+/-2.1mm; p=0.01). There were also differences in impairment of left (hypertensiveHT: 92.9%, nonhypertensive: 65%, p=0.002) and right (hypertensive: 74.4%, nonhypertensive: 42.1%, p=0.006) ventricular filling. After six months of treatment, an improvement of the myocardial performance index was noted in nonhypertensive patients (baseline Tei: 0.55+/-0.1 vs. 6-month Tei: 0.49+/-0.1; p=0.01), whereas no significant change was observed in hypertensive patients. CONCLUSIONS: Cardiac abnormalities in SAHS patients are increased in the presence of associated hypertension. Treatment with CPAP for six months improves cardiac abnormalities in nonhypertensive patients but not in hypertensive patients.

[Usefulness of the N-terminal fraction of brain natriuretic peptide for deciding when to refer patients with sleep apnea-hypopnea syndrome to the cardiologist]. / ¿Cuándo remitir al cardiólogo al paciente con síndrome de apneas-hipopneas durante el sueño? Utilidad del NT-proBNP.

INTRODUCTION AND OBJECTIVE: When sleep apnea-hypopnea syndrome (SAHS) and cardiovascular disease occur concurrently, prognosis is affected. Echocardiography can detect structural cardiac abnormalities but using this technique in all patients would place a heavy burden on resources. The objective of this study was to investigate whether the N-terminal fraction of brain natriuretic peptide (NT-proBNP) can be used as a marker for silent heart disease. PATIENTS AND METHODS: NT-proBNP concentration was measured in the 114 consecutive patients with SAHS who underwent echocardiography before starting treatment. Left and right ventricular systolic and diastolic function, as well as structural abnormalities, were studied. Correlations between NT-proBNP concentration and the abnormalities detected were investigated. A receiver operating characteristics (ROC) curve was plotted for NT-proBNP concentration and cardiac abnormalities. RESULTS: Data for 98 patients were finally analyzed. NT-proBNP concentration was significantly correlated with ventricular septal thickness (r=0.63), posterior wall thickness (r=0.45), and left ventricular end-diastolic diameter (r=0.51) (P<.0001 for all correlations). The area under the ROC curve was significant (0.870; 95% confidence interval, 0.801-0.939; P<.0001). Assuming that specificity would be more useful for clinical practice, we calculated that NT-proBNP concentrations below 100 and 200 pg/mL could rule out structural abnormalities with a reliability of 90% and 100%, respectively. CONCLUSIONS: NT-proBNP concentration was strongly correlated with echocardiographic abnormalities and so could be a useful tool for identifying patients who should be referred to the cardiologist.

[Noninvasive mechanical ventilation in Valencia, Spain: from theory to practice]. / Ventilación mecánica no invasiva en la Comunidad Valenciana: de la teoría a la práctica.

OBJECTIVE: To obtain representative data on the frequency of use and availability of resources for noninvasive mechanical ventilation (NIV) in hospitals (acute respiratory failure) and at home (chronic respiratory failure). METHOD: We sent a purpose-designed questionnaire to all the hospitals in the Autonomous Community of Valencia, Spain and followed up with a telephone interview. RESULTS: Seventy percent of the hospitals responded to the survey. NIV was used to treat patients with acute respiratory episodes in 100% of the intensive care units and in 88% of the respiratory medicine departments. The most common diseases were chronic obstructive pulmonary disease (COPD) (mean [SD] 60% [20%]), obesity hypoventilation syndrome (22% [12%]), neuromuscular diseases (6.5% [8%]), and kyphoscoliosis (6.5% [7%]). Other diseases accounted for 4% [11%] of cases. Emergency departments used NIV in 69% of patients, internal medicine departments in 37%, hospital-based home care units in 19%, and other departments in 12%. None of the hospitals that responded to the survey had an intermediate care unit and considerable differences were found in terms of NIV systems used. Home NIV was provided by 88% of hospitals. Patients using home NIV had COPD (31% [18%]), obesity hypoventilation syndrome (30% [18%]), neuromuscular diseases (16% [23%]), kyphoscoliosis (12% [10%]), and other diseases (11% [17%]). Patient numbers varied greatly from one hospital to the next. Home NIV was delivered using a nasal interface in 65% (32%) of cases, an oral-nasal interface in 33% (33%), a tracheostomy tube in 2% (3%), and a mouthpiece in 1% (32%). Only 31.3% of hospitals has a specialized home NIV unit. Home monitoring was performed mainly by service providers. We calculated that home NIV was used in 29 individuals per 100 000 population. Only 50% of the respiratory medicine departments surveyed had written hospitalization protocols; the corresponding percentages for other departments were 44% for home care units, 19% for emergency departments, and 12% for internal medicine departments. CONCLUSIONS: We observed differences in the type of requirement used, and considerable deficiencies in the availability of human and material resources and support systems. Although NIV is mostly used in hospitals to treat patients with acute respiratory failure, home NIV is also very common and is characterized by greater variability in terms of the number and type of patients. We also observed deficiencies in terms of written protocols for patients with acute and chronic disease.