Residual pulmonary infiltrates, symptoms and diffusion impairment at 1-year after severe COVID-19 infection have different associated factors.

INTRODUCTION: After severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia, patients may show lung sequelae on radiology and functional impairment at the 1-year follow-up. We aimed to describe the persistence of symptoms, radiological alterations, or reduced diffusing capacity of the lung for carbon monoxide (DLCO ) at 1-year follow-up in patients from the Spanish Registry RECOVID. METHODS: RECOVID collected symptom and radiological and functional lung tests data on hospitalized patients with coronavirus disease 2019 during the acute phase and at the 6- and 12-month follow-up visits. RESULTS: Of the 2500 enrolled survivors (90% admitted to the ward), 1874 had follow-up visits for up to a year. Of these, 42% continued to present with symptoms, 27% had radiological sequelae and 31% had reduced DLCO . Independently associated factors included female sex, asthma and the requirement for invasive or non-invasive mechanical ventilation. Complete radiological resolution was 72.2% at 12 months; associated factors with incomplete recovery were age, male sex, oxygen or respiratory support, corticosteroids and an initial SpO2 /FiO2 <450 or CURB-65 ≥2. Reduced DLCO was observed in 31% of patients at 12 months; associated factors were older age, female sex, smoking habit, SpO2 /FiO2 <450 and CURB-65 ≥2 and the requirement of respiratory support.At 12 months, a proportion of the asymptomatic patients showed reduced DLCO (9.5%), radiological findings (25%) or both (11%). CONCLUSIONS: The factors associated with symptom persistence, incomplete radiological resolution and DLCO <80% differed according to age, sex, comorbidities and respiratory support. The burden of symptoms, reduced DLCO and incomplete radiological resolution were considerable in patients with SARS-CoV-2 pneumonia at the 1-year follow-up after hospitalisation.

Early Desaturation During 6-Minute Walk Test is a Predictor of Mortality in COPD.

BACKGROUND: Oxygen desaturation during exercise is mainly observed in severe cases of chronic obstructive pulmonary disease (COPD) and is associated with a worse prognosis, but little is known about the type of desaturation that causes the greatest risk of mortality. MATERIAL AND METHODS: We studied all of the 6-min walk tests performed periodically at a tertiary hospital over a period of 12 years in patients with moderate or severe COPD. We classified patients as non-desaturators if they did not suffer a drop in oxygen saturation (SpO2 < 88%) during the test, early desaturators if the time until desaturation was < 1 min, and non-early desaturators if it was longer than 1 min. The average length of follow-up per patient was 5.6 years. RESULTS: Of the 319 patients analyzed, 126 non-desaturators, 91 non-early desaturators and 102 early desaturators were identified. The mortality analysis showed that early desaturators had a mortality of 73%, while it was 38% for non-early desaturators and 28% for non-desaturators, with a survival of 5.9 years compared to 7.5 years and 9.6 years, respectively (hazard ratio of 3.50; 95% CI 2.3-5.3; p < 0.0001). CONCLUSIONS: The early desaturation seen in patients with chronic obstructive pulmonary disease is associated with greater mortality and is likely responsible for the poor prognosis shown globally in patients who desaturate. The survival of patients with early desaturation is almost 4 years less with respect to non-desaturators, and they, thus, require closer observation.

Trajectories of Severe Exacerbations of Chronic Obstructive Pulmonary Disease and Their Relationship with Mortality Risk.

PURPOSE: Acute exacerbations of COPD (AECOPD) are important factors contributing to mortality risk. The rate of exacerbations varies overtime. An inconsistent pattern of exacerbation occurrence is a common finding. The mortality risk associated with such a pattern is not entirely clear. Our objective was to assess the risk of mortality associated with various possible patterns of AECOPD trajectories. METHODS: This is a multicenter historical cohort study. Four different exacerbation trajectories were defined according to the incidence of severe AECOPD requiring hospital admission 2 years before and after the date of the first visit to the respiratory clinic-Consistent non-exacerbators (NEx): no AECOPD before or after the index date; consistent exacerbators (Ex): at least one AECOPD both before and after the index date; converters to exacerbators (CONV-Ex): no exacerbations before and at least one AECOPD after the index date; converters to non-exacerbators (CONV-NEx): at least one AECOPD before the index date, and no exacerbations after said date. All-cause mortality risk for these trajectories was assessed. RESULTS: A total of 1713 subjects were included in the study: NEx: 1219 (71.2%), CONV-NEx: 225 (13.1%), CONV-Ex: 148 (8.6%), Ex: 121 (7.1%). After correcting for confounding variables, the group with the highest mortality risk was Ex. The CONV-Ex and CONV-Nex groups had a mortality risk between Ex and NEx, with no significant differences between them. CONCLUSION: Different possible trajectories of severe AECOPD before and after a first specialized consultation are associated with different mortality risks. An inconsistent pattern of exacerbations has a mortality risk between Ex and NEx, with no clear differences between CONV-Ex and CONV-NEx.

The COPD Comorbidome in the Light of the Degree of Dyspnea and Risk of Exacerbation.

The BODE group designed a bubble chart, analogous to the solar system, which depicts the prevalence of each disease and its association with mortality and called it a "comorbidome". Although this graph was used to represent mortality and, later, the risk of needing hospital admission, it was not applied to visualize the association between a set of comorbidities and the categories of the GOLD 2017 guidelines, neither according to the degree of dyspnea nor to the risk of exacerbation. For the purpose of knowing to which extent each comorbidity associates with each of the two conditions-most symptomatic group (groups B and D) and highest risk of exacerbation (groups C and D)-we performed a analysis based on the comorbidome. 439 patients were included. Cardiovascular comorbidity (especially cardiac and renal disease) is predominantly observed in patients with a higher degree of dyspnea, whereas bronchial asthma and stroke occur more frequently in subjects at higher risk of exacerbation. This is the first time that the comorbidome is presented based on the categories of the GOLD 2017 document, which we hope will serve as a stimulus for scientific debate.

Health Status in Patients with COPD According to GOLD 2017 Classification: Use of the COMCOLD Score in Routine Clinical Practice.

The COMCOLD score was developed to quantify the impact of comorbidities on health status in patients with chronic obstructive pulmonary disease (COPD). The objective of this study is to evaluate the association between health status in outpatients with COPD according to COMCOLD score and the GOLD 2017 groups according to symptoms (B and D vs. A and C) and exacerbations (C and D vs. A and B). 439 patients were included. The average score was 2.4 ± 3. 48% of cases had a COMCOLD score >0. The most symptomatic patients (B and D vs. A and C) had a higher score: 3 ± 3.3 vs. 1.3 ± 2.1 (p < 0.001), in contrast with the groups with a higher risk of exacerbation (C and D vs. A and B) in which there was no significant difference: 3 ± 3.5 vs. 2.2 ± 3.0 (p = 0.055). The most symptomatic patients (B and D) showed a greater prevalence of depression, peripheral artery disease and heart disease with an adjusted OR of 3.04 [CI95%: 1.36; 6.86], 2.49 [CI95%: 1.17; 5.29], and 4.41 [CI95%: 2.50; 7.75], respectively. Moreover, no relationship was found between the comorbidities defined by the COMCOLD score and the GOLD 2017 groups with the greatest risk of exacerbation (C and D). The greatest effect on health status was found in those patients with COPD belonging to the most symptomatic groups (B and D), with depression, peripheral artery disease, and heart disease being the main comorbidities involved.

The impact of alpha-1 antitrypsin deficiency alleles on lung cancer survival.

Different studies have shown that carrying an alpha-1 antitrypsin (AAT) deficiency allele is an independent risk factor for developing lung cancer (LC). However, to date, little is known regarding whether carrying a deficiency allele may be a prognostic factor in the evolution of LC. A prospective observational study was carried out which consecutively included patients diagnosed with LC in University Hospital "Nuestra Señora de Candelaria" between December 2017 and August 2020. A blood sample was taken from each of the patients in order to determine both AAT serum concentration and genotype. Based on AAT genotype, patients were divided into the deficiency (Pi*≠MM) or non-deficiency (Pi*=MM) group. One hundred and sixty-four patients were included. The average length of follow-up was 13±10 months. Patients were classified as stage I (4.2%), stage II (8.3%), stage III (31.2%) and stage IV (56.3%), according to tumour, node and metastasis (TNM) staging. Twenty-eight patients (17%) were carriers of a deficiency allele (6 Pi*MS, 1 Pi*MZ, 1 Pi*MMheerlen). No significant differences were found with respect to baseline characteristics between Pi*≠MM and Pi*=MM. Patients in the Pi*≠MM group had a higher risk of death in the first 6 months after the LC diagnosis compared to Pi*=MM subjects (HR =2.04; 95% CI: 1.04-4.0; P=0.038). The presence of an AAT deficiency genotype could be a potential prognostic marker in LC. However, larger studies that justify these findings are needed.

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.

Clinical outcomes and lung ultrasound findings in COVID-19 follow up: Calm comes after the storm?

INTRODUCTION: There is still an undiscovered territory about the sequelae and lung ultrasound (LUS) findings after SARS-CoV2 acute infection. This study aims to investigate the post-COVID period from a clinical, psychosocial, and radiological point of view, analyze LUS on COVID-19 follow-up and detect whether these outcomes are related to the patient situation. METHODS: We conducted an observational study on patients diagnosed with SARS-CoV2 pneumonia and admitted to the University Hospital of La Candelaria (Tenerife, Spain) from 1st March to 31st August 2020. We performed a descriptive analysis on post-COVID manifestations, LUS score, health-related quality of life measured through the Euroqol 5D-5L questionnaire, and lung function parameters on follow-up, and we compared these variables to the outcomes during the hospital admission. RESULTS: 77 patients were included; the mean age was 57 years and the follow-up mean time from hospital discharge was 16 weeks. 87% of the cases had symptoms on follow-up, the most common was dyspnea (65%); these manifestations were more frequent in females (p = 0,015). 76,5% of the cases had lung aeration alteration in LUS on follow-up; lower PaO2/FiO2 and greater CRP and IL-6 levels on admission were related to LUS score ≥1. CONCLUSIONS: Almost 90% of the patients had persistent symptoms after 16 weeks of hospital discharge due to COVID-19, the most common manifestation presented was dyspnea. Altered lung aeration pattern in LUS was observed on more than 70% of the patients on follow-up.

A new, three-dimensional approach to the GOLD COPD assessment tool.

BACKGROUND: The 2-dimensional, 4-quadrant 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD A-D assessment tool (GOLD2017) does not include lung function variables to classify patients into different risk groups. The previous 2011 tool (GOLD2011) classified cases in the upper-quadrants (higher risk groups) regardless of whether they had a history of exacerbations or worse lung function. We hypothesized that a modified, three-dimensional classification (GOLD3D) that separately includes assessment of lung function and exacerbations history would improve the ability to predict adverse events. METHODS: A total of 1303 COPD patients were included in a historical cohort study. The ability of GOLD3D to predict outcomes (all-cause death and hospitalizations due to severe exacerbation) was compared with GOLD2017 and GOLD2011. RESULTS: Mean follow-up was 45.0 ± 28.0 months. Two hundred and twenty-eight patients (17.5%) died and 337 (25.9%) subjects suffered at least a severe exacerbation that required hospital admission. The area under the receiver-operating characteristics curve for mortality prediction was slightly but significantly higher for GOLD3D than for GOLD2011. The area under the curve for prediction of severe exacerbations was significantly higher for GOLD3D than for GOLD2011 and GOLD2017. A worse ventilatory obstruction was associated in most cases with a higher mortality risk and a higher exacerbation risk for the GOLD2017 A-D groups. CONCLUSIONS: The proposed GOLD3D classification system upgrades the previous ones, and is advantageous in predicting future adverse events.

Evaluation of the multimorbidity network and its relationship with clinical phenotypes in chronic obstructive pulmonary disease: The GALAXIA study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous condition, in which taking into consideration clinical phenotypes and multimorbidity is relevant to disease management. Network analysis, a procedure designed to study complex systems, allows to represent connections between the distinct features found in COPD. METHODS: Network analysis was applied to a cohort of patients with COPD in order to explore the degree of connectivity between different diseases, taking into account the presence of two phenotypic traits commonly used to categorize patients in clinical practice: chronic bronchitis (CB+ /CB- ) and the history of previous severe exacerbations (Ex+ /Ex- ). The strength of association between diseases was quantified using the correlation coefficient Phi (ɸ). RESULTS: A total of 1726 patients were included, and 91 possible links between 14 diseases were established. Although the four phenotypically defined groups presented a similar underlying comorbidity pattern, with special relevance for cardiovascular diseases and/or risk factors, classifying patients according to the presence or absence of CB implied differences between groups in network density (mean ɸ: 0.098 in the CB- group and 0.050 in the CB+ group). In contrast, between-group differences in network density were small and of questionable significance when classifying patients according to prior exacerbation history (mean ɸ: 0.082 among Ex- subjects and 0.072 in the Ex+ group). The degree of connectivity of any given disease with the rest of the network also varied depending on the selected phenotypic trait. The classification of patients according to the CB- /CB+ groups revealed significant differences between groups in the degree of conectivity between comorbidities. On the other side, grouping the patients according to the Ex- /Ex+ trait did not disclose differences in connectivity between network nodes (diseases). CONCLUSIONS: The multimorbidity network of a patient with COPD differs according to the underlying clinical characteristics, suggesting that the connections linking comorbidities between them vary for different phenotypes and that the clinical heterogeneity of COPD could influence the expression of latent multimorbidity. Network analysis has the potential to delve into the interactions between COPD clinical traits and comorbidities and is a promising tool to investigate possible specific biological pathways that modulate multimorbidity patterns.

Characteristics of patients referred to Canary Island pneumology outpatient services for chronic obstructive pulmonary disease: the EPOCan study.

OBJECTIVE: Assessing patients with chronic obstructive pulmonary disease (COPD) accounts for 30% of all pneumology outpatient evaluations. COPD is a heterogeneous disease and generates a massive public health problem. Overall morbidity, particularly cardiovascular disease, challenges patient management. This is an observational, multicentre study, performed at four hospitals in the Canary Islands (Spain), aimed at characterising patients with COPD referred to pneumology outpatient services. Demographic variables, lung function, and morbidity were assessed. RESULTS: Of the 877 included patients, 44.9% were active smokers with a mean (± SD) age of 68.2 ± 10.3 years. The median (IQR) score for the Charlson comorbidity index was 2 (2), and 70.6% of the patients were assigned high risk according to the Spanish Guidelines for COPD (GesEPOC) 2021. The degree of airflow obstruction defined by the GOLD 2021 stages 1, 2, 3, and 4 corresponded to 13.6%, 49%, 31%, and 6.3% of patients, respectively. The most frequently associated morbidities were arterial hypertension (59.5%), dyslipidaemia (54.3%), and type 2 diabetes mellitus (31.2%); 32% of the patients suffered heart disease. There is a high prevalence of active smoking, type 2 diabetes mellitus, and heart disease in patients referred for COPD to Canary Island pneumology outpatient services.

Impact of diabetes mellitus on the risk of severe exacerbation in patients with chronic obstructive pulmonary disease.

INTRODUCTION: Suffering type 2 diabetes mellitus (T2DM) appears to promote the occurrence of respiratory infections. However, studies to evaluate the risk of hospital admission due to exacerbations in patients with chronic obstructive pulmonary disease (COPD) and concomitant T2DM are scarce. MATERIALS AND METHODS: Prospective, observational study with a maximum follow-up of 18 months. Information on lung function, body mass index, degree of dyspnea, number of exacerbations, comorbidities and pneumococcal vaccination was obtained. Patients were classified into the categories COPD with (COPD/+T2DM) and without T2DM (COPD/-T2DM). RESULTS: A total of 121 patients with COPD were enrolled. Forty-seven (38%) of the study participants were diabetic. The presence of T2DM increased the risk of hospital admission due to COPD exacerbation (OR 2.66; P = 0.031), but no significant difference in the total number of exacerbations was detected. CONCLUSIONS: The risk of hospital admission in the course of exacerbation seems to be higher in COPD/+T2DM patients than in COPD/-T2DM subjects.

Prognostic ability of the distance-saturation product in the 6-minute walk test in patients with chronic obstructive pulmonary disease.

INTRODUCTION: The product (DSP) of the distance walked (meters) and minimum oxygen saturation obtained during the 6-minute walk test (6MWT) has been proposed as a predictor of mortality in idiopathic pulmonary fibrosis and in bronchiectasis not related to cystic fibrosis. OBJECTIVE: The aim of this study was to determine the DSP's ability to predict mortality in patients with chronic obstructive pulmonary disease (COPD) at the outpatient level and compare it to the BODE index and meters walked in the 6MWT. MATERIAL AND METHODS: Descriptive observational study in a cohort of patients with COPD being treated at outpatient pulmonology clinics. Each of the patients completed the 6MWT following ATS/ERS protocols and their BODE index and DSP were calculated. RESULTS: About 103 patients were included. The average length of follow-up was 36 months. Patients who died showed a lower number of meters walked in the 6MWT (P < 0.001), as well as a lower DSP (P < 0.001). A 6MWT < 334 m, a DSP < 290 and a BODE ≥ 4 showed good prognostic ability at 3 years (AUC 71%, 69% and 70.4%, respectively). The 6MWT was superior to the BODE index in predicting mortality during the first year of follow-up (P = 0.023). We did not find any differences between DSP and meters walked in the 6MWT. CONCLUSIONS: The DSP is a good predictor of mortality, although it does not offer a better prognostic ability than that of meters walked in the 6MWT.

Biomarkers of acute respiratory distress syndrome in adults hospitalised for severe SARS-CoV-2 infection in Tenerife Island, Spain.

OBJECTIVE: The dramatic spread of SARS-CoV-2 infections calls for reliable, inexpensive tools to quickly identify patients with a poor prognosis. In this study, acute respiratory distress syndrome (ARDS) was assessed within 72 h after admission of each of 153 consecutive, SARS-CoV-2 infected, adult patients to either of two hospitals in Tenerife, Spain, using suitable routine laboratory tests for lymphocyte counts, as well as ferritin, lactate dehydrogenase (LDH), and C-reactive protein levels. Results were correlated with the patients' respiratory function, defined through their pulse oximetric saturation/fraction of inspired oxygen (SpO2/FiO2) ratio. RESULTS: Within 72 h from admission, criteria matched ARDS (SpO2/FiO2 < 235) in 13.1% of cases. We found a significant, negative correlation between SpO2/FiO2 ratios and D-dimer, ferritin, and LDH levels (- 0.31, - 0.32, and - 0.41; p = 0.004, 0.004, and < 0.0001, respectively). In patients with ARDS, the mean LDH was 373 U/L (CI95%: 300.6-445.3), but only 298 U/L (CI95%: 274.7-323.1) when they did not develop the syndrome (p = 0.015). None of the additionally evaluated biomarkers correlated with the SpO2/FiO2 ratios. Serum LDH levels in patients hospitalised for COVID-19 correlate with ARDS, as defined by their SpO2/FiO2 ratio, and might help to predict said complication.

Comparison of the prognostic capability of two comorbidity indices in patients with chronic obstructive pulmonary disease, in real-life clinical practice.

BACKGROUND: Comorbidities are a major cause of death in chronic obstructive pulmonary disease (COPD). The COPD-comorbidity test (COTE) index was designed to measure comorbidity burden in this disease. The objective of this study was to compare the capability of COTE and the non-COPD specific Charlson comorbidity index (CCI) to predict all-cause mortality in real-life conditions. METHODS: Retrospective observational study, carried out in two different series of consecutive COPD patients including, respectively, 790 and 439 subjects. The COTE and non-age-adjusted CCI indices were calculated and the values of the C-statistic for predicting all-cause mortality were compared for both indices. RESULTS: Median follow-up was 54 months and there were 321 deaths within this period of time. The value of the C-statistic for the CCI was significantly higher than for the COTE index in both groups. CONCLUSION: When used in real-life clinical practice, the value of the CCI to predict all-cause mortality in COPD seems higher than that of the COTE index.