Nontuberculous Mycobacteria Isolates in Respiratory Samples and Mycobacterial Pulmonary Disease in an Area of Northern Spain.

Introduction: The epidemiology of nontuberculous mycobacteria (NTM) is not well known. In this study, we aimed to determine the incidence of NTM isolates and nontuberculous mycobacterial pulmonary disease (NTM-PD) in five closely located hospitals in an area of northern Spain and analyse differences between them. Material and methods: Demographic, microbiological, clinical and radiological data were collected retrospectively from all patients with a NTM isolated from respiratory specimens at five hospitals between 2012 and 2019. Mycobacterium gordonae isolates were excluded. Once the data was collected, it was determined which patients met the NMT-PD criteria. Results: 594 patients were included in the study. The mean incidence rate of NTM isolates across all five hospitals in the period studied was 4.15 per 100,000 person-year, while the rate of NTM-PD was 1.2. The annual number of isolates showed an upward trend over this period, but the same did not occur in the number of cases of NTM-PD. The species most frequently isolated were Mycobacterium avium complex (MAC) and Mycobacterium xenopi and those most frequently causing disease were MAC and Mycobacterium kansassi. There were significant differences between the five centres. Conclusions: Our results are in line with similar studies in Europe in terms of NTM isolation and NTM-PD incidence and species isolated; however, we do not see the upward trend in NTM-PD rates described elsewhere. The great variability in isolation and disease rates, as well as in species isolated in geographically close areas, underlines, in our opinion, the importance of local environmental factors.

Introducción: La epidemiología de las micobacterias no tuberculosas (MNT) no se conoce bien. Nuestro objetivo fue determinar la incidencia de aislamientos de MNT y de enfermedad pulmonar por micobacterias no tuberculosas (EP-MNT) en cinco hospitales del norte de España, próximos entre sí, y analizar las diferencias entre ellos. Material y métodos: Se recopilaron retrospectivamente datos demográficos, microbiológicos, clínicos y radiológicos de todos los pacientes con una MNT aislada en muestra respiratoria entre 2012 y 2019 en los cinco hospitales. Se excluyeron los aislamientos de Mycobacterium gordonae. Una vez recogidos los datos, se determinó qué casos cumplían los criterios de EP-MNT. Resultados: Se incluyeron 594 pacientes. La tasa de incidencia media de aislamientos de NTM en los cinco hospitales fue de 4,15 por 100.000 personas-año y la tasa de EP-MNT fue de 1,2. El número anual de aislamientos mostró una tendencia creciente durante este periodo, pero no así el de EP-MNT. Las especies aisladas con mayor frecuencia fueron Mycobacterium avium complex (MAC) y Mycobacterium xenopi y las que causaron enfermedad con mayor frecuencia fueron MAC y Mycobacterium kansasii. Hubo diferencias significativas entre los cinco centros. Conclusiones: Nuestros resultados están en línea con estudios similares en Europa en términos de aislamiento de MNT, incidencia de EP-MNT y especies aisladas; sin embargo, no vemos la tendencia ascendente en las tasas de EP-MNT descrita en otros lugares. La gran variabilidad entre los cinco hospitales en las tasas de aislamiento y de enfermedad y en las especies aisladas resalta la importancia de los factores ambientales locales.

Predictors of pulmonary embolism in chronic obstructive pulmonary diseases patients admitted for worsening respiratory symptoms: An individual participant data meta-analyses.

BACKGROUND: Pulmonary embolism (PE) and acute exacerbation of chronic obstructive pulmonary disease (COPD) have similar clinical symptoms, making PE diagnosis challenging. Previous studies have shown that the prevalence of PE among COPD patients admitted with worsening respiratory symptoms was not negligible, but that systematic search for PE did not provide a clinical benefit. Predictive factors for PE remain unknown. OBJECTIVE: to identify predictive factors for PE among COPD patients with worsening respiratory symptoms. METHODS: We conducted an individual participant data meta-analysis which included the patients from the prospective PEP cohort and those randomized to the intervention arm in the SLICE trial which included a systematic search for PE in COPD patients admitted for worsening respiratory symptoms. Univariable and multivariable analysis were used to assess factors associated with the diagnosis of PE during the initial management. RESULTS: Among 1110 COPD patients, PE was diagnosed in 61 (5.49 %; 95 %CI 4.15 %-6.84 %). In univariable analysis, BNP (Brain natriuretic peptide) (odds ratio [OR] 1.02 per 100 ng/L increase, 95 %CI 1.01-1.04), prothrombin time (OR 0.78, 95 %CI 0.65-0.94), fibrinogen (OR 0.80, 95 %CI 0.64-0.98), atrial fibrillation (OR 4.74, 95 %CI 1.84-10.80), respiratory rate ≥30 min (OR 2.34, 95 %CI 1.13-4.6) and recent medical immobilization (OR 1.79, 95 %CI 0.99-3.13]) were associated with the risk of PE diagnosed during the initial management. In multivariable analysis, respiratory rate ≥30 (OR 2.77, 95 %CI 1.08-6.71) was a predictive factor for PE, as well as BNP (OR 1.02, 95 %CI 1.00-1.05) with an area under the curve =0.64, negative predictive value =0.15 (95 %CI 0.09-0.23), sensitivity =0.78 (95 %CI 0.74-0.82) and specificity =0.46 (95 %CI 0.29-0.63). CONCLUSION: Among patients with COPD admitted for worsening respiratory symptoms, respiratory rate and BNP levels are predictor of PE, but with limited discriminatory power.

Change in physical activity related to admission for exacerbation in COPD patients.

INTRODUCTION: The aim of this study was to determine the impact of hospitalizations on levels of physical activity (PA) and whether other factors were associated with subsequent changes in PA. METHODS: Prospective observational cohort study with a nested case-control study, with follow-up 60 days from the index hospital admission. Nine hospitals participated in the study. Patients were recruited consecutively. Several variables and questionnaires of the clinical baseline status of the patients were recorded including: the COPD Assessment Test (CAT), the Hospital Anxiety-Depression scale (HADS), comorbidities and the Yale Physical Activity Survey. Patients' data related to admission and up to two months after discharge were also recorded. RESULTS: 883 patients were studied: 79.7% male; FEV1 48%; Charlson index 2; 28.7% active smokers. The baseline PA level for the total sample was 23 points. A statistically significant difference in PA was found between patients readmitted up to 2 months after the index admission and those not readmitted (17vs. 27, p < 0.0001). Multivariable linear regression analysis identified the following as predictors of the decrease of PA from baseline (index admission) up to 2 months follow-up: admission for COPD exacerbation in the two months prior to the index admission; readmission up to 2 months after the index admission; baseline HAD depressive symptoms, worse CAT score, and patient-reported "need for help". CONCLUSIONS: In a cohort of admitted COPD patients, we identified a strong relationship between hospitalization for exacerbation and PA. In addition, some other potentially modifiable factors were found associated with the change in PA level after an admission.

Adjusted D-dimer cutoff levels to rule out pulmonary embolism in patients hospitalized for COPD exacerbation: results from the SLICE trial.

BACKGROUND: For patients with suspected pulmonary embolism (PE), age- or clinically-adjusted D-dimer threshold level can be used to define a negative test that safely excludes PE and reduces the use of imaging. However, the utility of this approach in patients hospitalized for chronic obstructive pulmonary disease (COPD) exacerbation is undefined. METHODS: We ran an analysis of the patients hospitalized for COPD exacerbation and randomized to the intervention in the SLICE trial. Using the conventional strategy as the reference, we compared the proportion of patients with a negative D-dimer result, and the negative predictive value and sensitivity of three D-dimer threshold strategies for initial PE or subsequent diagnosis of venous thromboembolism (VTE): the age-adjusted strategy, the Wells-adjusted strategy, and the YEARS-adjusted strategy. RESULTS: We included 368 patients. Using a conventional threshold, 182 (49.5%) patients had negative D-dimer values, of whom 1 (0.6%) had PE (sensitivity, 94.1%). The use of an age-adjusted threshold increased the number of patients in whom PE could be excluded from 182 to 233 patients (63.3%), and the proportion of false-negative findings increased from 0.5% to 1.7% (sensitivity, 76.5%). With the use of the Wells or YEARS strategies, 64.4% and 71.5% had negative values, and the proportion of false-negative findings was 2.5% (sensitivity, 64.7%) and 2.7% (sensitivity, 58.8%), respectively. CONCLUSIONS: In patients hospitalized for COPD exacerbation, compared with the conventional strategy, age- or clinically-adjusted strategies of D-dimer interpretation were associated with a larger proportion of patients in whom PE was ruled out with a higher failure rate. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT02238639 .

COVID-19 in young and middle-aged adults: predictors of poor outcome and clinical differences.

INTRODUCTION: Young and middle-aged adults are the largest group of patients infected with SARS-CoV-2 and some of them develop severe disease. OBJECTIVE: To investigate clinical manifestations in adults aged 18-65 years hospitalized for COVID-19 and identify predictors of poor outcome. Secondary objectives: to explore differences compared to the disease in elderly patients and the suitability of the commonly used community-acquired pneumonia prognostic scales in younger populations. METHODS: Multicenter prospective registry of consecutive patients hospitalized for COVID-19 pneumonia aged 18-65 years between March and May 2020. We considered a composite outcome of "poor outcome" including intensive care unit admission and/or use of noninvasive ventilation, continuous positive airway pressure or high flow nasal cannula oxygen and/or death. RESULTS: We identified 513 patients < 65 years of age, from a cohort of 993 patients. 102 had poor outcomes (19.8%) and 3.9% died. 78% and 55% of patients with poor outcomes were classified as low risk based on CURB and PSI scores, respectively. A multivariate Cox regression model identified six independent factors associated with poor outcome: heart disease, absence of chest pain or anosmia, low oxygen saturation, high LDH and lymphocyte count < 800/mL. CONCLUSIONS: COVID-19 in younger patients carries significant morbidity and differs in some respects from this disease in the elderly. Baseline heart disease is a relevant risk factor, while anosmia and pleuritic pain are associated to better prognosis. Hypoxemia, LDH and lymphocyte count are predictors of poor outcome. We consider that CURB and PSI scores are not suitable criteria for deciding admission in this population.

Effect of a Pulmonary Embolism Diagnostic Strategy on Clinical Outcomes in Patients Hospitalized for COPD Exacerbation: A Randomized Clinical Trial.

Importance: Active search for pulmonary embolism (PE) may improve outcomes in patients hospitalized for exacerbations of chronic obstructive pulmonary disease (COPD). Objective: To compare usual care plus an active strategy for diagnosing PE with usual care alone in patients hospitalized for COPD exacerbation. Design, Setting, and Participants: Randomized clinical trial conducted across 18 hospitals in Spain. A total of 746 patients were randomized from September 2014 to July 2020 (final follow-up was November 2020). Interventions: Usual care plus an active strategy for diagnosing PE (D-dimer testing and, if positive, computed tomography pulmonary angiogram) (n = 370) vs usual care (n = 367). Main Outcomes and Measures: The primary outcome was a composite of nonfatal symptomatic venous thromboembolism (VTE), readmission for COPD, or death within 90 days after randomization. There were 4 secondary outcomes, including nonfatal new or recurrent VTE, readmission for COPD, and death from any cause within 90 days. Adverse events were also collected. Results: Among the 746 patients who were randomized, 737 (98.8%) completed the trial (mean age, 70 years; 195 [26%] women). The primary outcome occurred in 110 patients (29.7%) in the intervention group and 107 patients (29.2%) in the control group (absolute risk difference, 0.5% [95% CI, -6.2% to 7.3%]; relative risk, 1.02 [95% CI, 0.82-1.28]; P = .86). Nonfatal new or recurrent VTE was not significantly different in the 2 groups (0.5% vs 2.5%; risk difference, -2.0% [95% CI, -4.3% to 0.1%]). By day 90, a total of 94 patients (25.4%) in the intervention group and 84 (22.9%) in the control group had been readmitted for exacerbation of COPD (risk difference, 2.5% [95% CI, -3.9% to 8.9%]). Death from any cause occurred in 23 patients (6.2%) in the intervention group and 29 (7.9%) in the control group (risk difference, -1.7% [95% CI, -5.7% to 2.3%]). Major bleeding occurred in 3 patients (0.8%) in the intervention group and 3 patients (0.8%) in the control group (risk difference, 0% [95% CI, -1.9% to 1.8%]; P = .99). Conclusions and Relevance: Among patients hospitalized for an exacerbation of COPD, the addition of an active strategy for the diagnosis of PE to usual care, compared with usual care alone, did not significantly improve a composite health outcome. The study may not have had adequate power to assess individual components of the composite outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT02238639.

Worldwide Effects of Coronavirus Disease Pandemic on Tuberculosis Services, January-April 2020.

Coronavirus disease has disrupted tuberculosis services globally. Data from 33 centers in 16 countries on 5 continents showed that attendance at tuberculosis centers was lower during the first 4 months of the pandemic in 2020 than for the same period in 2019. Resources are needed to ensure tuberculosis care continuity during the pandemic.

Changing epidemiology of nontuberculous mycobacterial lung disease over the last two decades in a region of the Basque country.

Recent studies suggest an increasing prevalence of nontuberculous mycobacteria (NTM) lung disease. The aim of the present study was to describe incidence rates of NTM lung disease and trends therein in our area over a 20-year period. This was a retrospective study of all cases of NTM lung disease between 1997 and 2016 that met the 2007 American Thoracic Society criteria. We analysed the annual incidence rates, species of mycobacteria isolated, trends over time and annual mortality in 327 patients. Mycobacterium kansasii was the most common mycobacterium isolated (84%), followed by Mycobacterium avium complex (MAC) (13%). We compared two periods: 1997-2006 (257 cases, 79%) and 2007-2016 (70 cases, 21%). The incidence rates tended to decrease across these years, with a peak of incidence in 2000 with 10.6 cases per 100 000. There was a clearly decreasing trend in M. kansasii infection, not only in the first period (incident rate ratio (IRR) 0.915, 95% CI 0.88-0.90; p<0.0001) but also in the second (IRR 0.869, 95% CI 0.780-1.014; p=0.080), reaching 1.8 per 100 000 in 2016. In contrast, MAC infection tended to increase across the two periods (IRR 1.251, 95% CI 1.081-1.447; p=0.003). In our region, the incidence of NTM lung disease has notably decreased in recent years. M. kansasii had high incidence rates in the first decade but clearly decreased in the second decade.

The rationale, design, and methods of a randomized, controlled trial to evaluate the efficacy and safety of an active strategy for the diagnosis and treatment of acute pulmonary embolism during exacerbations of chronic obstructive pulmonary disease.

INTRODUCTION: Some previous studies have suggested a high prevalence of pulmonary embolism (PE) during exacerbations of chronic obstructive pulmonary disease (ECOPD). The SLICE trial aims to assess the efficacy and safety of an active strategy for the diagnosis and treatment of PE (vs usual care) in patients hospitalized because of ECOPD. METHODS: SLICE is a phase III, prospective, international, multicenter, randomized, open-label, and parallel-group trial. A total of 746 patients hospitalized because of ECOPD will be randomized in a 1:1 fashion to receive either an active strategy for the diagnosis and anticoagulant treatment of PE or usual care (ie, standard care without any diagnostic test for diagnosing PE). The primary outcome is a composite of all-cause death, non-fatal (recurrent) venous thromboembolism (VTE), or readmission for ECOPD within 90 days after enrollment. Secondary outcomes are (a) death from any cause within 90 days after enrollment, (b) non-fatal (recurrent) VTE within 90 days after enrollment, (c) readmission within 90 days after enrollment, and (d) length of hospital stay. RESULTS: Enrollment started in September 2014 and is expected to proceed until 2020. Median age of the first 443 patients was 71 years (interquartile range, 64-78), and 26% were female. CONCLUSIONS: This multicenter trial will determine the value of detecting PEs in patients with ECOPD. This has implications for COPD patient morbidity and mortality. TRIAL REGISTRATION NUMBER: NCT02238639.