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.

MiRNAs in Hematopoiesis and Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is the most common kind of pediatric cancer. Although the cure rates in ALL have significantly increased in developed countries, still 15-20% of patients relapse, with even higher rates in developing countries. The role of non-coding RNA genes as microRNAs (miRNAs) has gained interest from researchers in regard to improving our knowledge of the molecular mechanisms underlying ALL development, as well as identifying biomarkers with clinical relevance. Despite the wide heterogeneity reveled in miRNA studies in ALL, consistent findings give us confidence that miRNAs could be useful to discriminate between leukemia linages, immunophenotypes, molecular groups, high-risk-for-relapse groups, and poor/good responders to chemotherapy. For instance, miR-125b has been associated with prognosis and chemoresistance in ALL, miR-21 has an oncogenic role in lymphoid malignancies, and the miR-181 family can act either as a oncomiR or tumor suppressor in several hematological malignancies. However, few of these studies have explored the molecular interplay between miRNAs and their targeted genes. This review aims to state the different ways in which miRNAs could be involved in ALL and their clinical implications.

Alterations in circulating mitochondrial signals at hospital admission for COPD exacerbation.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) exacerbation (ECOPD) alters the natural course of the disease. To date, only C-reactive protein has been used as a biomarker in ECOPD, but it has important limitations. The mitochondria release peptides (Humanin (HN), FGF-21, GDF-15, MOTS-c and Romo1) under certain metabolic conditions. Here, we aimed to evaluate the pathophysiologic, diagnostic and prognostic value of measuring serum mitochondrial peptides at hospital admission in patients with ECOPD. METHODS: A total of 51 consecutive patients admitted to our hospital for ECOPD were included and followed for 1 year; in addition, 160 participants with stable COPD from our out-patient clinic were recruited as controls. RESULTS: Serum FGF-21 (p < .001), MOTS-c (p < .001) and Romo1 (p = .002) levels were lower, and GDF-15 (p < .001) levels were higher, in patients with ECOPD than stable COPD, but no differences were found in HN. In receiver operating characteristic analysis, MOTS-c (AUC 0.744, 95% CI 0.679-0.802, p < .001) and GDF-15 (AUC 0.735, 95% CI 0.670-0.793, p < .001) had the best diagnostic power for ECOPD, with a diagnostic accuracy similar to that of C-RP (AUC 0.796 95% IC 0.735-0.848, p < .001). FGF-21 (AUC 0.700, 95% CI 0.633-0.761, p < .001) and Romo1 (AUC 0.645 95% CI 0.573-0.712, p = .001) had lower diagnostic accuracy. HN levels did not differentiate patients with ECOPD versus stable COPD (p = .557). In Cox regression analysis, HN (HR 2.661, CI95% 1.009-7.016, p = .048) and MOTS-c (HR 3.441, CI95% 1.252-9.297, p = .016) levels exceeding mean levels were independent risk factors for re-admission. CONCLUSIONS: Most mitochondrial peptides are altered in ECOPD, as compared with stable COPD. MOTS-c and GDF15 levels have a diagnostic accuracy similar to C-RP for ECOPD. HN and MOTS-c independently predict future re-hospitalization.

Mitochondrial Heteroplasmy Shifting as a Potential Biomarker of Cancer Progression.

Cancer is a serious health problem with a high mortality rate worldwide. Given the relevance of mitochondria in numerous physiological and pathological mechanisms, such as adenosine triphosphate (ATP) synthesis, apoptosis, metabolism, cancer progression and drug resistance, mitochondrial genome (mtDNA) analysis has become of great interest in the study of human diseases, including cancer. To date, a high number of variants and mutations have been identified in different types of tumors, which coexist with normal alleles, a phenomenon named heteroplasmy. This mechanism is considered an intermediate state between the fixation or elimination of the acquired mutations. It is suggested that mutations, which confer adaptive advantages to tumor growth and invasion, are enriched in malignant cells. Notably, many recent studies have reported a heteroplasmy-shifting phenomenon as a potential shaper in tumor progression and treatment response, and we suggest that each cancer type also has a unique mitochondrial heteroplasmy-shifting profile. So far, a plethora of data evidencing correlations among heteroplasmy and cancer-related phenotypes are available, but still, not authentic demonstrations, and whether the heteroplasmy or the variation in mtDNA copy number (mtCNV) in cancer are cause or consequence remained unknown. Further studies are needed to support these findings and decipher their clinical implications and impact in the field of drug discovery aimed at treating human cancer.

The Ratio Serum Creatinine/Serum Cystatin C (a Surrogate Marker of Muscle Mass) as a Predictor of Hospitalization in Chronic Obstructive Pulmonary Disease Outpatients.

BACKGROUND: In chronic obstructive pulmonary disease (COPD), low muscle mass has been associated with several clinical outcomes such as low exercise capacity, hospital admission, and mortality. The Sarcopenia Index (SI) is a novel way to estimate muscle mass based on the ratio of serum creatinine (produced exclusively by muscle)/cystatin C (produced by all nucleated body cells). OBJECTIVES: This study aims to assess the SI in stable COPD outpatients, as compared with a healthy control group, to quantify its relationship with several important clinical features in COPD, and to study its potential usefulness to predict COPD exacerbations and hospital admissions. METHODS: The SI was calculated in 18 healthy control subjects and 65 stable COPD outpatients were included in the study. Patients were prospectively followed for 1 year after being enrolled in the study. RESULTS: COPD patients had a lower SI than controls, that is lower muscle mass. Furthermore, patients with a modified Medical Research Council dyspnea score ≥2, patients with a COPD Assessment Test score ≥10, and patients with a high risk of exacerbation had lower levels of SI compared with patients without these characteristics. SI correlated with FEV1 (r = 0.491, p < 0.001), the 6-min walking test (r = 0.560, p = 0.001), and the Fat-Free Mass Index (r = 0.431, p = 0.017). Univariate and multivariate Cox proportional risk analysis showed that a low SI is an independent predictor of hospital admission in COPD outpatients followed for 1 year (HR 5.16, p = 0.025). CONCLUSIONS: The ratio serum creatinine/serum cystatin C correlates with several COPD characteristics, and it can be used to predict COPD hospitalization.

Vitamin D nutritional status and vitamin D regulated antimicrobial peptides in serum and pleural fluid of patients with infectious and noninfectious pleural effusions.

BACKGROUND: Vitamin D and vitamin D dependent antimicrobial peptides such as Cathelicidin (LL-37) and ß-defensin 2 have an important role in innate and adaptative immunity, but their role in pleural effusions has not been studied before. METHODS: Serum and pleural fluid samples from 152 patients with pleural effusion were collected, corresponding to 45 transudates and 107 exudates, 51 infectious effusions (14 complicated and 37 non-complicated), 44 congestive heart failure effusions and 38 malignant effusions. The levels of 25 OH-vitamin D, 1,25-(OH)2-vitamin D, Vitamin D Binding Protein (VDBP), LL-37 and ß-defensin 2, both in serum and pleural fluid were evaluated in this prospective study. Differences between groups were analysed using unpaired t tests or Mann-Whitney tests. Correlations between data sets were examined using Pearson correlation coefficient or Spearman rank correlation coefficient. Diagnostic accuracy was estimated using ROC curve analysis. RESULTS: Low serum 25 OH vitamin D levels were found in all groups. Infectious effusions (IE) had higher serum and pleural fluid LL-37 levels compared to congestive heart failure or malignant effusions. Among IE, complicated had higher serum and pleural fluid LL-37 levels, and lower serum ß-defensin-2 levels. Positive correlations were found between serum 25 OH-vitamin D levels and serum or pleural 1,25-(OH)2-vitamin D levels, and between 1,25-(OH)2-vitamin D and LL-37 serum. Diagnostic accuracy of the different molecules was moderate at best. CONCLUSIONS: Hypovitaminosis D is highly prevalent in pleural effusions. LL-37 is produced intrapleurally in IE. This production is higher in complicated IE. No evidence of pleural production of ß-defensin 2 was found in any of the groups. Diagnostic accuracy of the different molecules is at the best moderate for discriminating different types of effusions.

Monocyte distribution width (MDW) and DECAF: two simple tools to determine the prognosis of severe COPD exacerbation.

Monocyte distribution width (MDW) has been associated with inflammation and poor prognosis in various acute diseases. Chronic obstructive pulmonary disease (COPD) exacerbations (ECOPD) are associated with mortality. The objective of this study was to evaluate the utility of the MDW as a predictor of ECOPD prognosis. This retrospective study included patient admissions for ECOPD. Demographic, clinical and biochemical information; intensive care unit (ICU) admissions; and mortality during admission were recorded. A total of 474 admissions were included. MDW was positively correlated with the DECAF score (r = 0.184, p < 0.001) and C-reactive protein (mg/dL) (r = 0.571, p < 0.001), and positively associated with C-RP (OR 1.115 95% CI 1.076-1.155, p < 0.001), death (OR 9.831 95% CI 2.981- 32.417, p < 0.001) and ICU admission (OR 11.204 95% CI 3.173-39.562, p < 0.001). High MDW values were independent risk factors for mortality (HR 3.647, CI 95% 1.313-10.136, p = 0.013), ICU admission (HR 2.550, CI 95% 1.131-5.753, p = 0.024), or either mortality or ICU admission (HR 3.084, CI 95% 1.624-5.858, p = 0.001). In ROC analysis, a combined MDW-DECAF score had better diagnostic power (AUC 0.777 95% IC 0.708-0.845, p < 0.001) than DECAF (p = 0.023), MDW (p = 0.026) or C-RP (p = 0.002) alone. MDW is associated with ECOPD severity and predicts mortality and ICU admission with a diagnostic accuracy similar to that of DECAF and C-RP. The MDW- DECAF score has better diagnostic accuracy than MDW or DECAF alone in identifying mortality or ICU admission.

Circulating levels of mitochondrial oxidative stress-related peptides MOTS-c and Romo1 in stable COPD: A cross-sectional study.

Background: MOTS-c and Romo1 are mitochondrial peptides that are modulated by oxidative stress. No previous studies have explored circulating levels of MOTS-c in patients with chronic obstructive pulmonary disease (COPD). Methods: We enrolled 142 patients with stable COPD and 47 smokers with normal lung function in an observational cross-sectional study. We assessed serum levels of both MOTS-c and Romo1 and associated these findings with clinical characteristics of COPD. Results: Compared with smokers with normal lung function, patients with COPD had lower levels of MOTS-c (p = 0.02) and higher levels of Romo1 (p = 0.01). A multivariate logistic regression analysis revealed that above-median MOTS-c levels were positively associated with Romo1 levels (OR 1.075, 95% CI 1.005-1.150, p = 0.036), but no association was found with other COPD characteristics. Below-median levels of circulating MOTS-c were associated with oxygen desaturation (OR 3.25 95% CI 1.456-8.522, p = 0.005) and walking <350 meters (OR 3.246 95% CI 1.229-8.577, p = 0.018) in six-minute walk test. Above-median levels of Romo1 were positively associated with current smoking (OR 2.756, 95% CI 1.133-6.704, p = 0.025) and negatively associated with baseline oxygen saturation (OR 0.776 95% CI 0.641-0.939, p = 0.009). Conclusions: Reduced levels of circulating MOTS-c and increased levels of Romo1 were detected in patients diagnosed with COPD. Low levels of MOTS-c were associated with oxygen desaturation and poorer exercise capacity using 6 min walk test. Romo1 was associated with current smoking and baseline oxygen saturation. Trial registration: www.clinicaltrials.gov; No.: NCT04449419; URL: www.clinicaltrials.gov. Date of registration: June 26, 2020.

Importance of the SARS-CoV-2 genome and spike protein in the immunopathogenesis of COVID-19 and in the efficacy of vaccines.

Coronavirus (CoV) infections cause respiratory and enteric diseases with clinical manifestations ranging from faint to severe, even lead to death of patients. High connectivity between nations and infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represent a global health problem as the coronavirus disease 19 (COVID-19). This CoV-2 that cause SARS, which appeared in Wuhan, China, in December 2019 originated COVID-19 and declared as pandemic a few months posterior its appearance. In this review, the genomic and spike protein characteristics of SARS-CoV-2, the role of SARS-CoV-2 in the COVID-19 pathogenesis, cytokine storm, the role of cytotoxic T and B cells against SARS-CoV-2, as well as the vaccines efficacy (taking into account mutations in the spike protein) are described.

Los coronavirus (CoV) causan enfermedades respiratorias y entéricas leves, graves o críticas, pudiendo ocasionar la muerte del paciente. Debido a la alta conectividad entre naciones y a la transmisión, actualmente la COVID-19 representa un verdadero problema de salud pública en todo el mundo. El CoV-2 causante del síndrome respiratorio agudo grave (SARS-CoV-2) apareció a finales de diciembre de 2019 en Wuhan, China, y en marzo de 2020 la COVID-19 fue declarada pandemia. En esta revisión se describen las características del genoma y de la proteína espiga del SARS-CoV-2, su papel en la inmunopatogénesis de la COVID-19, la tormenta de citocinas, la actividad citotóxica inducida por células T y la producción de anticuerpos contra el SARS-CoV-2 mediada por células B, así como la eficacia de algunas vacunas, tomando en cuenta las mutaciones presentes en la proteína espiga.

Associations between serum mitokine levels and outcomes in stable COPD: an observational prospective study.

Mitokines (Humanin (HN), GDF15 and FGF21) are produced as a result of mitochondrial dysfunction and may have major roles in chronic inflammation, malnutrition and exercise capacity in people with COPD. Except for GDF15, studies on this subject are lacking. A total of 165 patients with stable COPD and 49 smokers without COPD were enrolled. We assessed their serum mitokine levels and clinical characteristics at baseline. We recorded moderate and severe exacerbation for the next 12 months. Baseline serum HN (p = 0.037) and GDF-15 (p = 0.013) levels were higher in the COPD group. High HN levels were independently associated with a high risk of exacerbation (HRE) (OR 2.798, 95% CI 1.266-6.187, p = 0.011), malnutrition (OR 6.645, 95% CI 1.859-23.749, p = 0.004), and 6MWD (OR 0.995, 95% CI 0.991-0.999, p = 0.008), and future moderate (HR 1.826, 95% CI 1.181-2.822, p = 0.007) and severe exacerbations (HR 3.445, 95% CI 1.357-8.740, p = 0.009). High GDF15 levels were associated with HRE (OR 3.028, 95% CI 1.134-8.083, p = 0.027), 6MWD (OR 0.995, 95% CI 0.990-0.999, p = 0.017) and predicted desaturation in 6MWT (OR 3.999, 95% CI 1.487-10.757, p = 0.006). High FGF21 levels were associated with HRE (OR 2.144, 95% CI 1.000-4.600, p = 0.05), and predicted future severe exacerbation (HR 4.217, 95% CI 1.459-12.193, p = 0.008). The mitokine levels were higher in patients with COPD than smokers without COPD, and were associated with important clinical outcomes such as exercise capacity and COPD exacerbation. Among the mitokines, HN showed the strongest association with COPD and may serve as a future risk biomarker in this disease.Trial registation NCT04449419.

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.

Pulmonologists' Opinion on the Use of Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease Patients in Spain: A Cross-Sectional Survey.

Introduction: Identifying the variables that guide decision-making in relation to the use of inhaled corticosteroids (ICS) can contribute to the appropriate use of these drugs. The objective of this study was to identify the clinical variables that physicians consider most relevant for prescribing or withdrawing ICS in COPD. Methods: A cross-sectional survey was conducted in Spain from November 2020 to May 2021. Therapeutic decisions on the use of ICS in 11 hypothetical COPD patient profiles were collected using an online survey answered by specialists with experience in the management of patients with COPD. Mixed-effects logistic regression was used to analyze the impact of patients' characteristics in the therapeutic decision for prescribing ICS or proceeding to its withdrawal. Results: A total of 74 pulmonologists agreed to collaborate in the survey and answered the questionnaire. The results showed great variability, with only 2 profiles achieving consensus for starting or withdrawing the treatment. The frequency and severity of exacerbations influenced the decision to prescribe ICS in a dose-response fashion (1 exacerbation odds ratio (OR) = 1.86, 95% confidence interval (CI) 1.02 to 3.43, two exacerbations OR = 11.6, 95% CI: 4.47 to 30.2 and three OR = 123, 95% CI: 25 to 601). Similarly, increasing blood eosinophils and history of asthma were associated with ICS use. On the other hand, pneumonia reduced the probability of initiating treatment with ICS (OR = 0.54 [0.29 to 0.98]). Lung function and dyspnea degree did not influence the clinician's therapeutic decision. The results for withdrawal of ICS were similar but in the opposite direction. Conclusion: In accordance with guidelines, exacerbations, blood eosinophils and history of asthma or pneumonia are the factors considered by pulmonologist for the indication or withdrawal of ICS. However, the agreement in prescription or withdrawal of ICS when confronted with hypothetical cases is very low, suggesting a great variability in clinical practice.

High parathyroid hormone predicts exacerbations in COPD patients with hypovitaminosis D.

BACKGROUND: Hypovitaminosis D has been linked to deterioration in clinical parameters and lung function in COPD. As a response to low levels of vitamin D serum Parathyroid Hormone (iPTH) is increased in some, but not all, patients. The aim of this study was to determine whether COPD patients with elevated PTH levels are at higher risk of COPD exacerbations and hospitalizations. METHODS: 166 COPD outpatients were randomly preselected. Clinical and analytical characteristics were assessed at baseline. After excluding patients with other conditions known to disturb calcium metabolism 141 patients were identified. Except one, all patients were prospectively followed for 12 months after obtaining the blood samples. Hypovitaminosis D was considered when serum 25(OH)D < 30 ng/mL. Secondary hyperparathyroidism was considered when serum iPTH was higher than normal (50 pg/mL) in patients with hypovitaminosis D. COPD exacerbations and hospital admissions were recorded during the follow-up. RESULTS: Prevalence of hypovitaminosis D in COPD patients was 89.3%, prevalence of secondary hyperparathyroidism associated with hypovitaminosis D was 22,9%. Cox proportional risk analysis showed that patients belonging to the high iPTH-low 25(OH)D group were at a higher risk of moderate COPD exacerbations (HR 1.81 (CI95% 1.043-3.127), p = 0.035) and hospital admissions (HR 5.45 (CI95% 2.018-14.720), p = 0.002) as compared with those with normal iPTH-low 25(OH)D levels. CONCLUSIONS: COPD patients with hypovitaminosis D and elevated iPTH have higher risk of moderate exacerbations and hospitalizations than those with hypovitaminosis D and normal iPTH.

Mechanisms of Immunosuppressive Tumor Evasion: Focus on Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is a malignancy with high heterogeneity in its biological features and treatments. Although the overall survival (OS) of patients with ALL has recently improved considerably, owing to the application of conventional chemo-therapeutic agents, approximately 20% of the pediatric cases and 40-50% of the adult patients relapse during and after the treatment period. The potential mechanisms that cause relapse involve clonal evolution, innate and acquired chemoresistance, and the ability of ALL cells to escape the immune-suppressive tumor response. Currently, immunotherapy in combination with conventional treatment is used to enhance the immune response against tumor cells, thereby significantly improving the OS in patients with ALL. Therefore, understanding the mechanisms of immune evasion by leukemia cells could be useful for developing novel therapeutic strategies.

Influence of Ag Photodeposition Conditions over SERS Intensity of Ag/ZnO Microspheres for Nanomolar Detection of Methylene Blue.

Surface enhanced Raman spectroscopy (SERS) is considered a versatile and multifunctional technique with the ability to detect molecules of different species at very low molar concentration. In this work, hierarchical ZnO microspheres (ZnO MSs) and Ag/ZnO MSs were fabricated and decorated by hydrothermal and photodeposition methods, respectively. For Ag deposition, precursor molar concentration (1.9 and 9.8 mM) and UV irradiation time (5, 15, and 30 min) were evaluated by SEM, TEM, X-ray diffraction and Raman spectroscopy. X-ray diffraction showed a peak at 37.9° corresponding to the (111) plane of Ag, whose intensity increases as precursor concentration and UV irradiation time increases. SEM images confirmed the formation of ZnO MSs (from 2.5 to 4.5 µm) building by radially aligned two-dimensional ZnO nanosheets with thicknesses below 30 nm. The Raman spectra of Ag/ZnO MSs exhibited a vibration mode at 486 cm-1 which can be directly associated to Ag deposition on ZnO MSs surface. The performance of SERS substrate was evaluated using rhodamine 6G. The SERS substrate grown at 9.8 mM during 30 min showed the best SERS activity and the ability to detect methylene blue at 10-9 M.

Telerehabilitation Programme as a Maintenance Strategy for COPD Patients: A 12-Month Randomized Clinical Trial.

BACKGROUND: There is uncertainty regarding efficacy of telehealth-based approaches in COPD patients for sustaining benefits achieved with intensive pulmonary rehabilitation (PR). RESEARCH QUESTION: To determine whether a maintenance pulmonary telerehabilitation (TelePR) programme, after intensive initial PR, is superior to usual care in sustaining over time benefits achieved by intensive PR. STUDY DESIGN AND METHODS: A multicentre open-label pragmatic parallel-group randomized clinical trial was conducted. Two groups were created at completion of an 8-week intensive outpatient hospital PR programme. Intervention group (IG) patients were given appropriate training equipment and instructed to perform three weekly training sessions and send performance data through an app to a web-based platform. Patients in the control group (CG) were advised to exercise regularly (usual care). RESULTS: Ninety-four patients (46 IG, 48 CG) were randomized. The analysis of covariance showed non-significant improvements in 6-min walk distance [19.9m (95% CI -4.1/+43.8)] and Chronic Respiratory Disease Questionnaire - Emotion score [0.4 points (0-0.8)] in the IG. Secondary linear mixed models showed improvements in the IG in Short Form-36 mental component summary [9.7, (4.0-15.4)] and Chronic Respiratory Disease Questionnaire - Emotion [0.5, (0.2-0.9)] scores, but there was no association between compliance and outcomes. Acute exacerbations were associated with a marginally significant decrease in 6-minute walk distance of 15.8m (-32.3/0.8) in linear models. CONCLUSIONS: The TelePR maintenance strategy was both feasible and safe but failed to show superiority over usual care, despite improvements in some HRQoL domains. Acute exacerbations may have an important negative influence on long-term physical function. CLINICALTRIALS. GOV IDENTIFIER: NCT03247933.

Natural Course of the Diffusing Capacity of the Lungs for Carbon Monoxide in COPD: Importance of Sex.

BACKGROUND: The value of the single-breath diffusing capacity of the lungs for carbon monoxide (Dlco) relates to outcomes for patients with COPD. However, little is known about the natural course of Dlco over time, intersubject variability, and factors that may influence Dlco progression. RESEARCH QUESTION: What is the natural course of Dlco in patients with COPD over time, and which other factors, including sex differences, could influence this progression? STUDY DESIGN AND METHODS: We phenotyped 602 smokers (women, 33%), of whom 506 (84%) had COPD and 96 (16%) had no airflow limitation. Lung function, including Dlco, was monitored annually over 5 years. A random coefficients model was used to evaluate Dlco changes over time. RESULTS: The mean (± SE) yearly decline in Dlco % in patients with COPD was 1.34% ± 0.015%/y. This was steeper compared with non-COPD control subjects (0.04% ± 0.032%/y; P = .004). Sixteen percent of the patients with COPD, vs 4.3% of the control subjects, had a statistically significant Dlco % slope annual decline (4.14%/y). At baseline, women with COPD had lower Dlco values (11.37% ± 2.27%; P < .001) in spite of a higher FEV1 % than men. Compared with men, women with COPD had a steeper Dlco annual decline of 0.89% ± 0.42%/y (P = .039). INTERPRETATION: Patients with COPD have an accelerated decline in Dlco compared with smokers without the disease. However, the decline is slow, and a testing interval of 3 to 4 years may be clinically informative. The lower and more rapid decline in Dlco values in women, compared with men, suggests a differential impact of sex in gas exchange function. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov.

Information Needs in COPD After an Educational Programme: Influence in Exacerbations and Admissions.

Introduction: Improving patients' information needs (IN) may contribute to better control in COPD. This study analyses IN using Lung Information Needs Questionnaire (LINQ) following an educational intervention, evaluates how clinical characteristics modify IN, and studies high IN as a prognostic factor for COPD exacerbations and hospital admissions. Methods: Cohort of 143 patients with initial diagnosis of COPD included in a structured educational program. Two months after completing the program, IN was assessed using LINQ. Correlations between IN and clinical variables of COPD and distribution of IN in different clinical groups were analyzed. Univariate and multivariate analysis was performed to determine influence of IN on exacerbations and COPD admissions over the following year. Results: LINQ scored 6.3±2.9. There were no differences in LINQ scoring between different clinical groups, but LINQ score positively correlated with age (r=0.184, p=0.029). High IN was a predictor of COPD hospitalizations (HR 2.3 [95% CI 1.1-5.1] (p=0.029)) but not of less severe exacerbations (p=0.334). Conclusion: IN was not associated with any clinical variables, but it correlated with age. High IN proved to be an independent predictor of admissions.

Mitochondrial DNA Mutation Analysis in Breast Cancer: Shifting From Germline Heteroplasmy Toward Homoplasmy in Tumors.

Studies have suggested a potential role of somatic mitochondrial mutations in cancer development. To analyze the landscape of somatic mitochondrial mutation in breast cancer and to determine whether mitochondrial DNA (mtDNA) mutational burden is correlated with overall survival (OS), we sequenced whole mtDNA from 92 matched-paired primary breast tumors and peripheral blood. A total of 324 germline variants and 173 somatic mutations were found in the tumors. The most common germline allele was 663G (12S), showing lower heteroplasmy levels in peripheral blood lymphocytes than in their matched tumors, even reaching homoplasmic status in several cases. The heteroplasmy load was higher in tumors than in their paired normal tissues. Somatic mtDNA mutations were found in 73.9% of breast tumors; 59% of these mutations were located in the coding region (66.7% non-synonymous and 33.3% synonymous). Although the CO1 gene presented the highest number of mutations, tRNA genes (T,C, and W), rRNA 12S, and CO1 and ATP6 exhibited the highest mutation rates. No specific mtDNA mutational profile was associated with molecular subtypes of breast cancer, and we found no correlation between mtDNA mutational burden and OS. Future investigations will provide insight into the molecular mechanisms through which mtDNA mutations and heteroplasmy shifting contribute to breast cancer development.