Bronchial Infection and Temporal Evolution of Bronchiectasis in Patients With Chronic Obstructive Pulmonary Disease.

BACKGROUND: Bronchiectasis (BE) impact the clinical course and prognosis of patients with chronic obstructive pulmonary disease (COPD). Yet, the temporal evolution of BE in these patients is unknown. This study seeks to assess the temporal evolution of BE in persons with COPD. METHODS: 201 moderate-to-severe patients were recruited between 2004 and 2007 and followed up at least every 6 monts (median of 102 months). To investigate the temporal evolution of BE, in 2015 a second high-resolution computed tomography scan (HRCT) was obtained in survivors and compared with the one obtained at recruitment. RESULTS: 99 (49.3%) died during follow-up. The second HRCT could be obtained in 77 patients and showed that (1) in 27.3% of patients BE never developed, in 36.4% they remained stable, in 16.9% they increased in size and/or extension, and in 19.5% new BE emerged; and that (2) the presence of chronic purulent sputum (hazard ratio [HR], 2.8 [95% confidence interval {CI}, 1.3-5.8]), number of hospitalizations due to exacerbatons (HR, 1.2 [95% CI, 1.1-1.5]), and number of pathogenic microorganism (PPM) isolations (HR, 1.1 [95% CI, 1.02-1.3]) were independent risk factors for the progression or development of BE. CONCLUSIONS: The presence of chronic purulent sputum production, number of PPMs isolated in sputum, and number of hospitalizations due to exacerbations of COPD are independent risk factors of BE progression in patients with COPD.

Increased Incidence of Stroke, but Not Coronary Heart Disease, in Elderly Patients With Sleep Apnea.

Background and Purpose- The influence of age on the relationship between obstructive sleep apnea (OSA) and the incidence of hard cardiovascular events remains controversial. We sought to analyze the relationship between OSA and the incidence of stroke and coronary heart disease in a large cohort of elderly patients, as well as to investigate the role of continuous positive airway pressure (CPAP) treatment in these associations. Methods- Post hoc analysis of a prospective observational study of consecutive patients ≥65 years studied for OSA suspicion at 2 Spanish University Hospitals. Patients with an apnea-hypopnea index (AHI) <15 were the reference group. OSA was defined by an AHI ≥15 and classified as untreated (CPAP not prescribed or compliance <4 hours/day), mild-moderate (AHI 15-29), untreated severe (AHI ≥30), and CPAP-treated (AHI ≥15 and CPAP compliance ≥4 hours/day). Results- 859 and 794 elderly patients were included in the stroke and coronary heart disease analyses, respectively. The median (interquartile range) follow-up was 72 (50-88.5) and 71 (51.5-89) months, respectively. Compared with the reference group, the fully adjusted hazard ratios for the incidence of stroke were 3.42 (95% CI, 1.37-8.52), 1.02 (95% CI, 0.41-2.56), and 1.76 (95% CI, 0.62-4.97) for the untreated severe OSA group, CPAP-treated group, and untreated mild-moderate OSA group, respectively. No associations were shown between any of the different OSA groups and coronary heart disease incidence. Conclusions- The incidence of stroke, but not coronary heart disease, is increased in elderly patients with untreated severe OSA. Adequate CPAP treatment may reduce this risk.

Role of sleep apnea and continuous positive airway pressure therapy in the incidence of stroke or coronary heart disease in women.

RATIONALE: It is unknown whether obstructive sleep apnea (OSA) may be a risk factor for incident cardiovascular events in women. OBJECTIVES: We sought to investigate whether OSA increases the incidence of a composite of stroke or coronary heart disease (CHD) in women, and the role of continuous positive airway pressure (CPAP) treatment on this association. METHODS: This was a prospective, observational study conducted in two Spanish teaching hospitals between 1998 and 2007. Consecutive women referred for suspected OSA and free of previous stroke and CHD were analyzed. Women with an apnea-hypopnea index (AHI) less than 10 comprised the control group, and those with an AHI greater than or equal to 10 were diagnosed with OSA and classified as CPAP-treated (adherence ≥ 4 h/d) or untreated (adherence < 4 h/d or not prescribed). The follow-up ended in December 2010. MEASUREMENTS AND MAIN RESULTS: A total of 967 women were studied (median follow-up, 6.8 yr; interquartile range, 5.2-8.2). The untreated OSA group showed a greater incidence rate of the composite outcome than the control group (2.19 vs. 0.54 per 100 person-years; P < 0.0005). Compared with the control group, the fully adjusted hazard ratios for the composite outcome incidence were 2.76 (95% confidence interval [CI], 1.35-5.62) for the untreated OSA group, and 0.91 (95% CI, 0.43-1.95) for the CPAP-treated group. When the type of cardiovascular event was separately assessed, untreated OSA showed a stronger association with incident stroke (adjusted hazard ratio, 6.44; 95% CI, 1.46-28.3) than with CHD (adjusted hazard ratio, 1.77; 95% CI, 0.76-4.09). CONCLUSIONS: In women, untreated OSA is associated with increased incidence of serious cardiovascular outcomes, particularly incident stroke. Adequate CPAP treatment seems to reduce this risk.

Artificial Intelligence Applied to Forced Spirometry in Primary Care.

Introduction: This study aims to create an artificial intelligence (AI) based machine learning (ML) model capable of predicting a spirometric obstructive pattern using variables with the highest predictive power derived from an active case-finding program for COPD in primary care. Material and methods: A total of 1190 smokers, aged 30-80 years old with no prior history of respiratory disease, underwent spirometry with bronchodilation. The sample was analyzed using AI tools. Based on an exploratory data analysis (EDA), independent variables (according to mutual information analysis) were trained using a gradient boosting algorithm (GBT) and validated through cross-validation. Results: With an area under the curve close to unity, the model predicted a spirometric obstructive pattern using variables with the highest predictive power: FEV1_theoretical_pre values. Sensitivity: 93%. Positive predictive value: 94%. Specificity: 97%. Negative predictive value: 96%. Accuracy: 95%. Precision: 94%. Conclusion: An ML model can predict the presence of an obstructive pattern in spirometry in a primary care smoking population with no prior diagnosis of respiratory disease using the FEV1_theoretical_pre values with an accuracy and precision exceeding 90%. Further studies including clinical data and strategies for integrating AI into clinical workflow are needed.

Introducción: Este estudio tiene como objetivo crear un modelo de aprendizaje automático (ML) basado en inteligencia artificial (IA) capaz de predecir un patrón obstructivo espirométrico utilizando variables con el mayor poder predictivo derivado de un programa activo de búsqueda de casos de enfermedad pulmonar obstructiva crónica (EPOC) en Atención Primaria. Materiales y métodos: Un total de 1.190 fumadores, de entre 30 y 80 años, sin antecedentes de enfermedad respiratoria, fueron sometidos a espirometría con IA artificial. Sobre la base de un análisis de datos exploratorio (EDA), las variables independientes (según el análisis de información mutua) se entrenaron utilizando un algoritmo de gradiente de aumento (GBT) y se validaron mediante validación cruzada. Resultados: Con un área bajo la curva cercana a la unidad, el modelo predijo un patrón obstructivo espirométrico utilizando los valores del FEV1 prebroncodilatador. Sensibilidad: 93%. Valor predictivo positivo: 94%. Especificidad: 97%. Valor predictivo negativo: 96%. Precisión: 95%. Precisión: 94%. Conclusión: Un modelo ML puede predecir la presencia de un patrón obstructivo en la espirometría en una población fumadora de atención primaria sin diagnóstico previo de enfermedad respiratoria utilizando los valores FEV1 prebroncodilatadores con una exactitud y precisión superiores al 90%. Se necesitan más estudios que incluyan datos clínicos y estrategias para integrar la IA en el flujo de trabajo clínico.

Long-term continuous positive airway pressure compliance in females with obstructive sleep apnoea.

Continuous positive airway pressure (CPAP) is the treatment of choice for obstructive sleep apnoea (OSA), but compliance and variables involved in long-term CPAP adherence in females with OSA are unknown. We performed an observational study including all consecutive females diagnosed with CPAP who started CPAP treatment in two Spanish teaching hospitals between 1999 and 2007 and were followed-up until December 2010. The Kaplan-Meier method was used to calculate the probability of continuing with CPAP treatment and a multivariate Cox regression analysis was used to identify baseline predictors of CPAP dropout. We analysed 708 females, median (interquartile range) age 60 (52-67) years and apnoea-hypopnoea index 43.0 (27.2-66.8). Females were followed for a median of 6.2 (4.2-7.7) years. The probability of still being on CPAP at 5 and 10 years was 82.8% and 79.9%, respectively. The median CPAP use was 6 (interquartile range 4-7) h · day(-1). In the multivariate analysis, independent baseline predictors of CPAP dropout were psychoactive medication (hazard ratio 1.47, 95% CI 1.03-2.08), age (hazard ratio 1.01, 95% CI 1.00-1.03) and CPAP pressure (hazard ratio 0.89, 95% CI 0.81-0.96). Long-term CPAP adherence in females with OSA is good. Psychoactive medication and increasing age were independent predictors of CPAP dropout, whereas higher CPAP was associated with continued treatment.

Cardiovascular mortality in obstructive sleep apnea in the elderly: role of long-term continuous positive airway pressure treatment: a prospective observational study.

RATIONALE: Obstructive sleep apnea (OSA) is a risk factor for cardiovascular death in middle-aged subjects, but it is not known whether it is also a risk factor in the elderly. OBJECTIVES: To investigate whether OSA is a risk factor for cardiovascular death and to assess whether continuous positive airway pressure (CPAP) treatment is associated with a change in risk in the elderly. METHODS: Prospective, observational study of a consecutive cohort of elderly patients (≥65 yr) studied for suspicion of OSA between 1998 and 2007. Patients with an apnea-hypopnea index (AHI) less than 15 were the control group. OSA was defined as mild to moderate (AHI, 15-29) or severe (AHI, ≥30). Patients with OSA were classified as CPAP-treated (adherence ≥ 4 h/d) or untreated (adherence < 4 h/d or not prescribed). Participants were monitored until December 2009. The end point was cardiovascular death. A multivariate Cox survival analysis was used to determine the independent impact of OSA and CPAP treatment on cardiovascular mortality. MEASUREMENTS AND MAIN RESULTS: A total of 939 elderly were studied (median follow-up, 69 mo). Compared with the control group, the fully adjusted hazard ratios for cardiovascular mortality were 2.25 (confidence interval [CI], 1.41 to 3.61) for the untreated severe OSA group, 0.93 (CI, 0.46 to 1.89) for the CPAP-treated group, and 1.38 (CI, 0.73 to 2.64) for the untreated mild to moderate OSA group. CONCLUSIONS: Severe OSA not treated with CPAP is associated with cardiovascular death in the elderly, and adequate CPAP treatment may reduce this risk.

Cardiovascular mortality in women with obstructive sleep apnea with or without continuous positive airway pressure treatment: a cohort study.

BACKGROUND: Obstructive sleep apnea (OSA) is a risk factor for cardiovascular death in men, but whether it is also a risk factor in women is unknown. OBJECTIVE: To investigate whether OSA is a risk factor for cardiovascular death in women and assess whether continuous positive airway pressure (CPAP) treatment is associated with a change in risk. DESIGN: Prospective, observational cohort study. SETTING: 2 sleep clinics in Spain. PATIENTS: All women consecutively referred for suspected OSA between 1998 and 2007. INTERVENTION: Every woman had a diagnostic sleep study. Women with an apnea-hypopnea index (AHI) less than 10 were the control group. Obstructive sleep apnea was diagnosed when the AHI was 10 or higher (classified as mild to moderate [AHI of 10 to 29] or severe [AHI ≥30]). Patients with OSA were classified as CPAP-treated (adherence ≥4 hours per day) or untreated (adherence <4 hours per day or not prescribed). Participants were followed until December 2009. MEASUREMENTS: The end point was cardiovascular death. RESULTS: 1116 women were studied (median follow-up, 72 months [interquartile range, 52 to 88 months]). The control group had a lower cardiovascular mortality rate (0.28 per 100 person-years [95% CI, 0.10 to 0.91]) than the untreated groups with mild to moderate OSA (0.94 per 100 person-years [CI, 0.10 to 2.40]; P = 0.034) or severe OSA (3.71 per 100 person-years [CI, 0.09 to 7.50]; P < 0.001). Compared with the control group, the fully adjusted hazard ratios for cardiovascular mortality were 3.50 (CI, 1.23 to 9.98) for the untreated, severe OSA group; 0.55 (CI, 0.17 to 1.74) for the CPAP-treated, severe OSA group; 1.60 (CI, 0.52 to 4.90) for the untreated, mild to moderate OSA group; and 0.19 (CI, 0.02 to 1.67) for the CPAP-treated, mild to moderate OSA group. LIMITATION: The study was observational and not randomized, and OSA was diagnosed by 2 different methods. CONCLUSION: Severe OSA is associated with cardiovascular death in women, and adequate CPAP treatment may reduce this risk. PRIMARY FUNDING SOURCE: None.

Obstructive sleep apnea and cardiovascular events in elderly patients.

INTRODUCTION: In recent decades, life expectancy has increased considerably. The cardiovascular effects of Obstructive Sleep Apnea (OSA) in the elderly lead to patient disability and high resource consumption. Intermittent nocturnal hypoxia leads to hemodynamic stress and adrenergic activation, which promotes cardiovascular disease. However, chronic intermittent hypoxia may protect elderly patients from cardiovascular events (CVE) due to biological adaptation. AREAS COVERED: OSA patients are at increased risk of cardiovascular events. The severity of OSA increases cardiovascular risk, and this association also exists in the elderly. This article reviews the association between OSA, CPAP treatment, and CVE, particularly stroke and coronary heart disease (CHD), in the elderly. MEDLINE and the Cochrane Collaboration databases were searched from inception to July 2021. EXPERT COMMENTARY: Although a positive association between OSA and the incidence of cardiovascular disease in the elderly has been established, the role of sleep apnea in certain cardiovascular events remains controversial. Most authors agree that untreated OSA is a risk factor for stroke or worse stroke prognosis. However, the association between OSA and CHD is usually less pronounced than between OSA and stroke, especially in the elderly.

Combined intermittent and sustained hypoxia is a novel and deleterious cardio-metabolic phenotype.

STUDY OBJECTIVES: Chronic obstructive pulmonary disease and obstructive sleep apnea overlap syndrome is associated with excess mortality, and outcomes are related to the degree of hypoxemia. People at high altitudes are susceptible to periodic breathing, and hypoxia at altitude is associated with cardio-metabolic dysfunction. Hypoxemia in these scenarios may be described as superimposed sustained hypoxia (SH) plus intermittent hypoxia (IH), or overlap hypoxia (OH), the effects of which have not been investigated. We aimed to characterize the cardio-metabolic consequences of OH in mice. METHODS: C57BL/6J mice were subjected to either SH (FiO2 = 0.10), IH (FiO2 = 0.21 for 12 h, and FiO2 oscillating between 0.21 and 0.06, 60 times/hour, for 12 h), OH (FiO2 = 0.13 for 12 h, and FiO2 oscillating between 0.13 and 0.06, 60 times/hour, for 12 h), or room air (RA), n = 8/group. Blood pressure and intraperitoneal glucose tolerance test were measured serially, and right ventricular systolic pressure (RVSP) was assessed. RESULTS: Systolic blood pressure transiently increased in IH and OH relative to SH and RA. RVSP did not increase in IH, but increased in SH and OH by 52% (p < .001) and 20% (p = .001). Glucose disposal worsened in IH and improved in SH, with no change in OH. Serum low- and very-low-density lipoproteins increased in OH and SH, but not in IH. Hepatic oxidative stress increased in all hypoxic groups, with the highest increase in OH. CONCLUSIONS: OH may represent a unique and deleterious cardio-metabolic stimulus, causing systemic and pulmonary hypertension, and without protective metabolic effects characteristic of SH.

Clinical efficacy and safety of budesonide-formoterol in non-cystic fibrosis bronchiectasis.

BACKGROUND: The aim of this study is to evaluate the efficacy and safety of medium-dose formoterol-budesonide combined inhaled treatment in a single inhaler compared with high-dose budesonide treatment in patients with non-cystic fibrosis (non-CF) bronchiectasis. METHODS: This is a 12-month randomized, double-blind, parallel-groups clinical trial, to run in 40 patients with non-CF bronchiectasis diagnosed by high-resolution CT scan of the chest, receiving formoterol-budesonide combined treatment (18/640 µg daily) or budesonide treatment (1,600 µg daily). Variables concerning clinical condition, health-related quality of life (HRQL), lung function, ß(2)-adrenergic agonist use, potentially pathogenic microorganism (PPM) isolates, and medication side effects were analyzed by intention-to-treat analysis. RESULTS: The study group receiving a formoterol-budesonide combined treatment showed a significant improvement, both clinically and statistically, of symptoms (dyspnea, number of coughs, and rescue ß(2)-adrenergic agonist-free days). Furthermore, we observed an HRQL improvement, with no changes in functional parameters or in PPM isolates, together with an important reduction in overall side effects, especially for those related to inhaled steroids, compared with the high-dose budesonide treatment group. CONCLUSIONS: Inhaled medium-dose formoterol-budesonide combined treatment in a single inhaler is more effective and safe compared with high-dose budesonide treatment in patients with non-CF bronchiectasis. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00728715; URL: www.clinicaltrials.gov.

[Treatment of non-cystic fibrosis bronchiectasis]. / Tratamiento de las bronquiectasias no debidas a fibrosis quística.

Bronchiectasis is currently growing in importance due to both the increase in the number of diagnoses made as well as the negative impact that its presence has on the baseline disease that generates it. A fundamental aspect in these patients is the colonization and infection of the bronchial mucous by potentially pathogenic microorganisms (PPM), which are the cause in most cases of the start of the chronic inflammatory process that results in the destruction and dilatation of the bronchial tree that is characteristic in these patients. The treatment of the colonization and chronic bronchial infection in these patients should be based on prolonged antibiotic therapy in its different presentations. Lately, the inhaled form is becoming especially prominent due to its high efficacy and limited production of important adverse effects. However, one must not overlook the fact that the management of patients with bronchiectasis should be multidisciplinary and multidimensional. In addition to antibiotic treatment, the collaboration of different medical and surgical specialties is essential for the management of the exacerbations, nutritional aspects, respiratory physiotherapy, muscle rehabilitation, complications, inflammation and bronchial hyperreactivity and the hypersecretion that characterizes these patients.

Factors associated with bronchiectasis in patients with COPD.

BACKGROUND: Previous studies have shown a high prevalence of bronchiectasis in patients with moderate to severe COPD. However, the factors associated with bronchiectasis remain unknown in these patients. The objective of this study is to identify the factors associated with bronchiectasis in patients with moderate to severe COPD. METHODS: Consecutive patients with moderate (50% < FEV(1) ≤ 70%) or severe (FEV(1) ≤ 50%) COPD were included prospectively. All subjects filled out a clinical questionnaire, including information about exacerbations. Peripheral blood samples were obtained, and lung function tests were performed in all patients. Sputum samples were provided for monthly microbiologic analysis for 6 months. All the tests were performed in a stable phase for at least 6 weeks. High-resolution CT scans of the chest were used to diagnose bronchiectasis. RESULTS: Ninety-two patients, 51 with severe COPD, were included. Bronchiectasis was present in 53 patients (57.6%). The variables independently associated with the presence of bronchiectasis were severe airflow obstruction (OR, 3.87; 95% CI, 1.38-10.5; P = .001), isolation of a potentially pathogenic microorganism (PPM) (OR, 3.59; 95% CI, 1.3-9.9; P = .014), and at least one hospital admission due to COPD exacerbations in the previous year (OR, 3.07; 95% CI, 1.07-8.77; P = .037). CONCLUSION: We found an elevated prevalence of bronchiectasis in patients with moderate to severe COPD, and this was associated with severe airflow obstruction, isolation of a PPM from sputum, and at least one hospital admission for exacerbations in the previous year.