Overnight desaturation in interstitial lung diseases: links to pulmonary vasculopathy and mortality.

Background: Overnight desaturation predicts poor prognosis across interstitial lung diseases (ILDs). The aim of the present study was to investigate whether nocturnal desaturation is associated with pulmonary vasculopathy and mortality. Methods: A retrospective single centre study of 397 new ILD patients was carried out including patients with idiopathic pulmonary fibrosis (IPF) (n=107) and patients with non-IPF fibrotic ILD (n=290). This is the largest study to date of the effect of significant nocturnal desaturation (SND) (≥10% of total sleep time with oxygen saturation ≤90% measured by pulse oximetry). Results: The prevalence of SND was 28/107 (26.2%) in IPF and 80/290 (27.6%) in non-IPF ILD. The prevalence of SND was higher in non-IPF ILDs than in IPF (p=0.025) in multivariate analysis. SND was associated with noninvasive markers of pulmonary hypertension (PH): tricuspid regurgitation velocity (TRV) (p<0.0001), brain natriuretic peptide (p<0.007), carbon monoxide transfer coefficient (p<0.0001), A-a gradient (p<0.0001), desaturation >4% in 6-min walking test (p<0.03) and pulmonary artery diameter (p<0.005). SND was independently associated with high echocardiographic PH probability in the entire cohort (OR 2.865, 95% CI 1.486-5.522, p<0.002) and in non-IPF fibrotic ILD (OR 3.492, 95% CI 1.597-7.636, p<0.002) in multivariate analysis. In multivariate analysis, SND was associated with mortality in the entire cohort (OR 1.734, 95% CI 1.202-2.499, p=0.003) and in IPF (OR 1.908, 95% CI 1.120-3.251, p=0.017) and non-IPF fibrotic ILD (OR 1.663, 95% CI 1.000-2.819, p=0.041). Separate models with exclusion of each one of the diagnostic subgroups showed that no subgroup was responsible for this finding in non-IPF ILDs. SND was a stronger marker of 5-year mortality than markers of PH. Conclusion: SND was associated with high echocardiographic probability and mortality and was a stronger predictor of mortality in IPF and non-IPF ILDs grouped together to power the study.

Chronic Thromboembolic Pulmonary Hypertension after Pulmonary Embolism in SARS-CoV-2.

INTRODUCTION: Chronic thromboembolic pulmonary disease (CTEPD) consists of persistent pulmonary vascular obstruction on imaging and involves long-term functional limitations, with or without chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to evaluate the incidence and risk factors of both persistent pulmonary vascular defects and CTEPH after hospitalization in patients with COVID-19 and PE during a 2-year follow-up. METHODS: A prospective observational study was carried out in a tertiary hospital center. Patients were hospitalized between March 2020 and December 2021 with a diagnosis of PE during SARS-CoV-2 infection. Patients received anticoagulant treatment for at least 3 months and were followed up for 2 years. Between the third and fourth months after discharge, all patients were evaluated for the presence of residual thrombotic defects by CTPA and/or perfusion pulmonary scintigraphy. Clinical findings, lung function tests with DLCO, exercise capacity, and echocardiograms were also assessed. RESULTS: Of the 133 patients included, 18% had persistent thrombotic defects on lung imaging at follow-up. The incidence of CTEPD was 0.75% at 2 years of follow-up. Patients with persistent defects were significantly older, had a higher prevalence of systemic arterial hypertension, higher D-dimer and NT-proBNP levels, and more severe PE at diagnosis. Furthermore, there was a higher prevalence of right ventricular dysfunction on echocardiogram at diagnosis of PE (25.0% vs. 2.7%, p = 0.006). This was the only variable independently related to persistent defects in multivariate analyses (OR: 8.13 [95% CI: 1.82-36.32], p = 0.006). CONCLUSION: The persistence of thrombotic defects after PE is a common finding after SARS-CoV-2 infection, affecting 18% of the population. However, the incidence of CTEPH appears to be lower (0.75%) in COVID-19-related PE compared to that previously observed in PE unrelated to COVID-19.

Persistent Respiratory Failure and Re-Admission in Patients with Chronic Obstructive Pulmonary Disease Following Hospitalization for COVID-19.

Background: Chronic obstructive pulmonary disease (COPD) has been associated with worse clinical evolution/survival during a hospitalization for SARS-CoV2 (COVID-19). The objective of this study was to learn the situation of these patients at discharge as well as the risk of re-admission/mortality in the following 12 months. Methods: We carried out a subanalysis of the RECOVID registry. A multicenter, observational study that retrospectively collected data on severe acute COVID-19 episodes and follow-up visits for up to a year in survivors. The data collection protocol includes general demographic data, smoking, comorbidities, pharmacological treatment, infection severity, complications during hospitalization and required treatment. At discharge, resting oxygen saturation (SpO2), dyspnea according to the mMRC (modified Medical Research Council) scale and long-term oxygen therapy prescription were recorded. The follow-up database included the clinical management visits at 6 and 12 months, where re-admission and mortality were recorded. Results: A total of 2047 patients were included (5.6% had a COPD diagnosis). At discharge, patients with COPD had greater dyspnea and a greater need for prescription home oxygen. After adjusting for age, sex and Charlson comorbidity index, patients with COPD had a greater risk of hospital re-admission due to respiratory causes (HR 2.57 [1.35-4.89], p = 0.004), with no significant differences in survival. Conclusion: Patients with COPD who overcome a serious SARS-CoV2 infection show a worse clinical situation at discharge and a greater risk of re-admission for respiratory causes.

Is the long-term mortality similar in COVID-19 and community-acquired pneumonia?

Introduction: There are no data on the association of type of pneumonia and long-term mortality by the type of pneumonia (COVID-19 or community-acquired pneumonia [CAP]) on long-term mortality after an adjustment for potential confounding variables. We aimed to assess the type of pneumonia and risk factors for long-term mortality in patients who were hospitalized in conventional ward and later discharged. Methods: Retrospective analysis of two prospective and multicentre cohorts of hospitalized patients with COVID-19 and CAP. The main outcome under study was 1-year mortality in hospitalized patients in conventional ward and later discharged. We adjusted a Bayesian logistic regression model to assess associations between the type of pneumonia and 1-year mortality controlling for confounders. Results: The study included a total of 1,693 and 2,374 discharged patients in the COVID-19 and CAP cohorts, respectively. Of these, 1,525 (90.1%) and 2,249 (95%) patients underwent analysis. Until 1-year follow-up, 69 (4.5%) and 148 (6.6%) patients from the COVID-19 and CAP cohorts, respectively, died (p = 0.008). However, the Bayesian model showed a low probability of effect (PE) of finding relevant differences in long-term mortality between CAP and COVID-19 (odds ratio 1.127, 95% credibility interval 0.862-1.591; PE = 0.774). Conclusion: COVID-19 and CAP have similar long-term mortality after adjusting for potential confounders.

Treatment of COVID-19 during the Acute Phase in Hospitalized Patients Decreases Post-Acute Sequelae of COVID-19.

BACKGROUND: The post-acute sequelae of SARS-CoV-2 (PASC) infection have caused a significant impact on our health system, but there is limited evidence of approved drugs focused on its prevention. Our objective was to identify risk factors that can determine the presence of PASC, with special attention to the treatment received in the acute phase, and to describe the profile of persistent symptoms in a multidisciplinary Post-Coronavirus Disease-19 (COVID-19) Unit. METHODS: This one-year prospective observational study included patients following an acute COVID-19 infection, irrespective of whether they required hospital admission. A standardized symptom questionnaire and blood sampling were performed at the first follow-up visit, and demographic and clinical electronic data were collected. We compared subjects with PASC with those who had fully recovered. Multivariate logistic regression was performed to identify factors associated with PASC in hospitalized patients, and Kaplan-Meier curves were used to assess duration of symptoms according to disease severity and treatments received in the acute phase. RESULTS: 1966 patients were evaluated; 1081 had mild disease, 542 moderate and 343 severe; around one third of the subjects had PASC, and were more frequently female, with obesity, asthma, and eosinophilia during acute COVID-19 disease. Patients who received treatment with dexamethasone and remdesivir during the course of the acute illness showed a lower median duration of symptoms, compared with those who received none of these treatments. CONCLUSION: Treatment with dexamethasone and/or remdesivir may be useful to reduce the impact of PASC secondary to SARS-CoV-2 infection. In addition, we identified female gender, obesity, asthma, and disease severity as risk factors for having PASC.

Predictors and changes of physical activity in idiopathic pulmonary fibrosis.

BACKGROUND: Different clinical predictors of physical activity (PA) have been described in idiopathic pulmonary fibrosis (IPF), but studies are lacking evaluating the potential role of muscle strength and anxiety and depression symptoms in PA limitation. Moreover, little is known about the impact of changes in PA in the course of the disease. The aim of the present study was to investigate the relationship between baseline PA and a wide range of variables in IPF, to assess its longitudinal changes at 12 months and its impact on progression free-survival. METHODS: PA was assessed by accelerometer and physiological, clinical, psychological factors and health-related quality of life were evaluated in subjects with IPF at baseline and at 12 month follow-up. Predictors of PA were determined at baseline, evolution of PA parameters was described and the prognostic role of PA evolution was also established. RESULTS: Forty participants with IPF were included and 22 completed the follow-up. At baseline, subjects performed 5765 (3442) daily steps and spent 64 (44) minutes/day in moderate to vigorous PA. Multivariate regression models showed that at baseline, a lower six-minute walked distance, lower quadriceps strength (QMVC), and a higher depression score in the Hospital Anxiety and Depression scale were associated to lower daily step number. In addition, being in (Gender-Age-Physiology) GAP III stage, having a BMI ≥ 25 kg/m2 and lower QMVC or maximum inspiratory pressure were factors associated with sedentary behaviour. Adjusted for age, gender and forced vital capacity (FVC) (%pred.) a lower progression-free survival was evidenced in those subjects that decreased PA compared to those that maintained, or even increased it, at 12 months [HR 12.1 (95% CI, 1.9-78.8); p = 0.009]. CONCLUSION: Among a wide range of variables, muscle strength and depression symptoms have a predominant role in PA in IPF patients. Daily PA behaviour and its evolution should be considered in IPF clinical assessment and as a potential complementary indicator of disease prognosis.

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.

Impact of high-flow oxygen therapy during exercise in idiopathic pulmonary fibrosis: a pilot crossover clinical trial.

BACKGROUND: Supplemental oxygen delivered with standard oxygen therapy (SOT) improves exercise capacity in patients with idiopathic pulmonary fibrosis (IPF). Although high-flow nasal cannula oxygen therapy (HFNC) improves oxygenation in other respiratory diseases, its impact on exercise performance has never been evaluated in IPF patients. We hypothesized that HFNC may improve exercise capacity in IPF subjects compared to SOT. METHODS: This was a prospective, crossover, pilot randomized trial that compared both oxygenation methods during a constant submaximal cardiopulmonary exercise test (CPET) in IPF patients with exertional oxygen saturation (SpO2) ≤ 85% in the 6-min walking test. The primary outcome was endurance time (Tlim). Secondary outcomes were muscle oxygen saturation (StO2) and respiratory and leg symptoms. RESULTS: Ten IPF patients [71.7 (6) years old, 90% males] were included. FVC and DLCO were 58 ± 11% and 31 ± 13% pred. respectively. Tlim during CPET was significantly greater using HFNC compared to SOT [494 ± 173 vs. 381 ± 137 s, p = 0.01]. HFNC also associated with a higher increase in inspiratory capacity (IC) [19.4 ± 14.2 vs. 7.1 ± 8.9%, respectively; p = 0.04], and a similar trend was observed in StO2 during exercise. No differences were found in respiratory or leg symptoms between the two oxygen devices. CONCLUSIONS: This is the first study demonstrating that HFNC oxygen therapy improves exercise tolerance better than SOT in IPF patients with exertional desaturation. This might be explained by changes in ventilatory mechanics and muscle oxygenation. Further and larger studies are needed to confirm the benefits of HFNC in IPF patients and its potential usefulness in rehabilitation programs.

Incidence of pulmonary embolism in patients with non-invasive respiratory support during COVID-19 outbreak.

While the incidence of thrombotic complications in critically ill patients is very high, in patients under non-invasive respiratory support (NIS) is still unknown. The specific incidence of thrombotic events in each of the clinical scenarios within the broad spectrum of severity of COVID-19, is not clearly established, and this has not allowed the implementation of thromboprophylaxis or anticoagulation for routine care in COVID-19. Patients admitted in a semi-critical unit treated initially with NIS, especially Continuous-Positive Airway Pressure (CPAP), were included in the study. The cumulative incidence of pulmonary embolism was analyzed and compared between patients with good response to NIS and patients with clinical deterioration that required orotracheal intubation. 93 patients were included and 16% required mechanical ventilation (MV) after the NIS. The crude cumulative incidence of the PE was 14% (95%, CI 8-22) for all group. In patients that required orotracheal intubation and MV, the cumulative incidence was significantly higher [33% (95%, CI 16-58)] compared to patients that continued with non-invasive support [11% (CI 5-18)] (Log-Rank, p = 0.013). Patients that required mechanical ventilation were at higher risk of PE for a HR of 4.3 (95%CI 1.2-16). In conclusion, cumulative incidence of PE is remarkably higher in critically patients with a potential impact in COVID-19 evolution. In this context, patients under NIS are a very high-risk group for developing PE without a clear strategy regarding thromboprophylaxis.

Mapping IPF helps identify geographic regions at higher risk for disease development and potential triggers.

BACKGROUND AND OBJECTIVE: The relationship between IPF development and environmental factors has not been completely elucidated. Analysing geographic regions of idiopathic pulmonary fibrosis (IPF) cases could help identify those areas with higher aggregation and investigate potential triggers. We hypothesize that cross-analysing location of IPF cases and areas of consistently high air pollution concentration could lead to recognition of environmental risk factors for IPF development. METHODS: This retrospective study analysed epidemiological and clinical data from 503 patients registered in the Observatory IPF.cat from January 2017 to June 2019. Incident and prevalent IPF cases from the Catalan region of Spain were graphed based on their postal address. We generated maps of the most relevant air pollutant PM2.5 from the last 10 years using data from the CALIOPE air quality forecast system and observational data. RESULTS: In 2018, the prevalence of IPF differed across provinces; from 8.1 cases per 100 000 habitants in Barcelona to 2.0 cases per 100 000 in Girona. The ratio of IPF was higher in some areas. Mapping PM2.5 levels illustrated that certain areas with more industry, traffic and shipping maintained markedly higher PM2.5 concentrations. Most of these locations correlated with higher aggregation of IPF cases. Compared with other risk factors, PM2.5 exposure was the most frequent. CONCLUSION: In this retrospective study, prevalence of IPF is higher in areas of elevated PM2.5 concentration. Prospective studies with targeted pollution mapping need to be done in specific geographies to compile a broader profile of environmental factors involved in the development of pulmonary fibrosis.

EGFR and KRAS Mutations in the Non-Tumoral Lung. Prognosis in Patients with Adenocarcinoma.

Tumor recurrence is frequent and survival rates remain extremely low in lung adenocarcinoma (ADC). We hypothesize that carcinogenic factors will promote loco-regional modifications not only in the future tumor, but throughout the exposed lung. OBJECTIVE: To analyze whether the most prevalent mutations observed in ADC can also be observed in the non-neoplastic lung tissue, as well as the short-term prognosis implications of this finding. METHODS: Non-tumoral lung parenchyma specimens obtained during surgery from 47 patients with EGFR and/or KRAS abnormalities in their ADC tumors underwent similar genomic testing. Short-term outcomes were also recorded. RESULTS: The same mutations were present in the tumor and the histologically normal tissue in 21.3% of patients (SM group). Although local recurrences were similar in both groups, distant metastases were more frequent in the former (60 vs. 5.4%, p < 0.001). Moreover, SM patients showed lower time-to-progression (8.5 vs. 11.7 months, p < 0.001) and disease-free survival (8.5 vs. 11.2 months, p < 0.001). COX regression showed a higher risk of progression or death (DFS) in the SM group (HR 5.94, p < 0.01]. Similar results were observed when adjusting for potential confounding variables. CONCLUSIONS: These results confirm that genetic changes are present in the apparently normal lung in many ADC patients, and this finding has prognostic implications.

Hospital admissions and mortality in patients with COPD exacerbations and vertebral body compression fractures.

BACKGROUND: Vertebral compression fractures (VCF) are common in COPD patients, with osteoporosis being the main cause. The clinical impact of VCF derives mostly from both pain and chest deformity, which may lead to ventilatory and physical activity limitations. Surprisingly, the consequences of VCF on the quality outcomes of hospital care are poorly known. OBJECTIVE: To assess these indicators in patients hospitalized due to a COPD exacerbation (ECOPD) who also have VCF. METHODS: Clinical characteristics and quality care indicators were assessed in two one-year periods, one retrospective (exploratory) and one prospective (validation), in all consecutive patients hospitalized for ECOPD. Diagnosis of VCF was based on the reduction of >20% height of the vertebral body evaluated in standard lateral chest X-ray (three independent observers). RESULTS: From the 248 patients admitted during the exploratory phase, a third had at least one VCF. Underdiagnosis rate was 97.6%, and patients with VCF had more admissions (normalized for survival), longer hospital stays, and higher mortality than patients without (4 [25th-75th percentiles, 2-8] vs 3 [1-6] admissions, P<0.01; 12 [6-30] vs 9 [6-18] days, P<0.05; and 50 vs 32.1% deaths, P<0.01, respectively). The risk of dying in the two following years was also higher in VCF patients (odds ratio: 2.11 [1.2-3.6], P<0.01). The validation cohort consisted of 250 patients who showed very similar results. The logistic regression analysis indicated that both VCF and age were factors independently associated with mortality. CONCLUSION: Although VCF is frequently underdiagnosed in patients hospitalized for ECOPD, it is strongly associated with a worse prognosis and quality care outcomes.

Utilidad de la punción aspirativa transbronquial guiada con ultrasonografía endobronquial en el diagnóstico de la tuberculosis mediastínica / Role of endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of mediastinal tuberculosis

Introducción: La tuberculosis (TBC) ganglionar mediastínica es rara y su presentación intratorácica es un reto diagnóstico. La punción aspirativa transbronquial guiada por ultrasonografía endobronquial (PATb-USEB) podría ser útil para su diagnóstico, pero no disponemos de estudios que evalúen su eficacia en nuestro medio. Métodos: Se analizaron retrospectivamente todos los pacientes con TBC ganglionar mediastínica aislada diagnosticados entre 2008 y 2014. Se identificaron los pacientes con diagnóstico definitivo a quienes se les realizó PATb-USEB. Resultados: Se identificaron 29 casos, siendo la PATb-USEB diagnóstica en 28 pacientes (96,6%). Los hallazgos citológicos confirmaron granulomas en el 93% de los casos. El cultivo fue positivo en 14 (48,2%) y la PCR para Mycobacterium tuberculosis, en el 30% de los casos en los que se realizó. El 84% de los pacientes eran inmigrantes y al compararlos con la población nativa se encontraron diferencias significativas en el estado inmunológico y el rendimiento del cultivo. No se registraron complicaciones derivadas del procedimiento. Conclusión: La PATb-USEB es una técnica de primera línea, efectiva y segura en el diagnóstico de pacientes con sospecha de TBC mediastínica (AU)

Introduction: Mediastinal tuberculosis (TB) is rare and a diagnostic challenge. Transbronchial needle aspiration guided by endoscopic ultrasonography (EBUS-TBNA) is an essential tool for staging and diagnosing patients with lung cancer but to date there are no studies in our environment evaluating its efficacy in mediastinal TB. Methods: Patients with a final diagnosis of isolated intrathoracic tuberculous lymphadenitis over a 6-year period were included. We analyzed the cases on whom EBUS-TBNA was performed. Results: Forty-six patients with mediastinal lymphadenopathy without pulmonary involvement were identified and 29 underwent EBUS-TBNA. In 28 of 29 patients (96.6%) EBUS-TBNA was diagnostic and cytological findings confirmed granulomas in 93% of cases. Microbiological investigation revealed positive TB culture in 14 (48.2%) and positive PCR for Mycobacterium tuberculosis in 30% of cases on whom it was carried out. Eighty-four per cent of the patients were immigrants and when compared with the native population we found statistical differences in immune status and culture yield. Conclusion: EBUS-TB (AU)

[Role of endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of mediastinal tuberculosis]. / Utilidad de la punción aspirativa transbronquial guiada con ultrasonografía endobronquial en el diagnóstico de la tuberculosis mediastínica.

INTRODUCTION: Mediastinal tuberculosis (TB) is rare and a diagnostic challenge. Transbronchial needle aspiration guided by endoscopic ultrasonography (EBUS-TBNA) is an essential tool for staging and diagnosing patients with lung cancer but to date there are no studies in our environment evaluating its efficacy in mediastinal TB. METHODS: Patients with a final diagnosis of isolated intrathoracic tuberculous lymphadenitis over a 6-year period were included. We analyzed the cases on whom EBUS-TBNA was performed. RESULTS: Forty-six patients with mediastinal lymphadenopathy without pulmonary involvement were identified and 29 underwent EBUS-TBNA. In 28 of 29 patients (96.6%) EBUS-TBNA was diagnostic and cytological findings confirmed granulomas in 93% of cases. Microbiological investigation revealed positive TB culture in 14 (48.2%) and positive PCR for Mycobacterium tuberculosis in 30% of cases on whom it was carried out. Eighty-four per cent of the patients were immigrants and when compared with the native population we found statistical differences in immune status and culture yield. CONCLUSION: EBUS-TBNA is a safe and effective technique in the diagnosis of patients with suspected mediastinal TB.