Assessing the reproducibility and predictive value of objective cough measurement for successful withdrawal of invasive ventilatory support in adult patients.

BACKGROUND: Utilizing clinical tests, such as objective cough measurement, can assist in predicting the success of the weaning process in critically ill patients. METHODS: A multicenter observational analytical study was conducted within a prospective cohort of patients recruited to participate in COBRE-US. We assessed the capability of objective cough measurement to predict the success of the spontaneous breathing trial (SBT) and extubation. Intra- and inter-observer reproducibility of the cough test and was evaluated using the intraclass correlation coefficient (ICC) and Cohen's weighted kappa. We used receiver operating characteristic curves (ROC-curve) to evaluate the predictive ability of objective cough measurement. RESULTS: We recruited 367 subjects who were receiving invasive mechanical ventilation. A total of 451 objective cough measurements and 456 SBTs were conducted. A significant association was found between objective cough measurement and successful SBT (OR: 1.68; 95% CI 1.48-1.90; p = 0.001). The predictive capability of the objective cough test for SBT success had a ROC-curve of 0.58 (95% CI: 0.56-0.61). Objective cough measurement to predict successful extubation had a ROC-curve of 0.61 (95% CI: 0.56-0.66). The intraobserver reproducibility exhibited an ICC of 0.94 (95% CI: 0.89-0.96; p < 0.001), while the interobserver reproducibility demonstrated an ICC of 0.72 (95% CI: 0.51-0.85; p < 0.001). The intraobserver agreement, assessed using Cohen's weighted kappa was 0.94 (95% CI: 0.93-0.99; p < 0.001), whereas the interobserver agreement was 0.84 (95% CI: 0.67 - 0.10; p < 0.001). CONCLUSIONS: The objective measurement of cough using the method employed in our study demonstrates nearly perfect intra-observer reproducibility and agreement. However, its ability to predict success or failure in the weaning process is limited.

Sputum Biomarkers in Wood and Tobacco Smoke Etiotypes of Chronic Obstructive Pulmonary Disease.

Introduction: There is a need to better understand the etiotypes of chronic obstructive pulmonary disease (COPD) beyond the tobacco-smoke (TS-COPD). Wood smoke COPD (WS-COPD) is characterized by greater airway compromise, milder emphysema, and slower rate of lung function decline than TS-COPD. However, it is unclear if these two etiotypes of COPD have differences in sputum biomarker concentrations. Objective was to compare sputum levels of selected sputum biomarkers between WS-COPD and TS-COPD, and healthy controls. Methods: Eighty-eight women (69±12 years) were recruited and classified into: WS-COPD (n=31), TS-COPD (n=29) and controls (n=28). Using ELISA, we determined induced sputum levels of metalloproteinase 9 (MMP-9), chemokine ligand 5 (CCL5), interleukin-8 (IL-8), chemokine ligand 16 (CCL16/HCC-4) and vascular endothelial growth factor (VEGF-1). Differences were analyzed by Kruskal-Wallis and Mann-Whitney-U tests and correlation between airflow limitation and biomarkers by Spearman's test. Results: At similar degree of airflow obstruction, anthropometrics and medications use, the level of sputum CCL5 was higher in TS-COPD than WS-COPD (p=0.03) without differences in MMP-9, IL-8, CCL16/HCC-4, and VEGF-1. Women with WS-COPD and TS-COPD showed significantly higher sputum levels of MMP-9, IL-8 and CCL5 compared with controls (p<0.001). FEV1% predicted correlated negatively with levels of MMP-9 (rho:-0.26; P=0.016), CCL5 (rho:-0.37; P=0.001), IL-8 (rho:-0.42; P<0.001) and VEGF (rho:-0.22; P=0.04). Conclusion: While sputum concentrations of MMP-9, IL-8, and CCL5 were higher in COPD women compared with controls, women with TS-COPD had higher levels of CCL5 compared with those with WS-COPD. Whether this finding relates to differences in pathobiological pathways remains to be determined.

Long-term survival in venous thromboembolic disease: rivaroxaban vs. warfarin - propensity score matching study.

BACKGROUND: Venous thromboembolic disease (VTE) is characterized by obstruction of venous blood flow by a thrombus. Survival data, frequency of disease recurrence, and bleeding rate in patients on anticoagulant therapy with warfarin compared to rivaroxaban in the Latin American population are limited in VTE. METHODS: A retrospective cohort study with propensity score matching analysis was conducted in patients with pulmonary embolism and/or deep vein thrombosis anticoagulated with warfarin or rivaroxaban treated. Survival analysis was performed using a Kaplan-Meier curve for each of the intervention groups, and it was compared using a Log Rank test. RESULTS: Of 2193 potentially eligible patients with a suspected diagnosis of VTE, 505 patients entered the analysis; of these, 285 subjects were managed with warfarin and 220 anticoagulated with rivaroxaban. Major bleeding at 12 months occurred in 2.7% (6/220) of patients treated with Rivaroxaban, compared to 10.2% (29/285) in the Warfarin group in the unmatched population (p = 0.001). In the matched population, bleeding at 12 months occurred in 2.9% (6/209) of patients on Rivaroxaban and in 11.0% (23/209) of patients on Warfarin (p = 0.001). The survival rates at 6 months were 97.1% for Rivaroxaban and 97.6% for Warfarin (p = 0.76). At 12 months, the survival rates were 94.7% for Rivaroxaban and 95.7% for Warfarin (p = 0.61). CONCLUSION: In the treatment of VTE, there is no differences on 6 and 12-month survival or a reduction in the occurrence of new thromboembolic events when comparing rivaroxaban to warfarin. However, a lower risk of major bleeding is observed at 12 months with Rivaroxaban.

The effect of combining different sampling tools on the performance of electromagnetic navigational bronchoscopy for the evaluation of peripheral lung lesions and factors associated with its diagnostic yield.

BACKGROUND: We assessed the performance of Electromagnetic navigational bronchoscopy (ENB) as a standalone diagnostic technique and the performance of different sampling tools used during the procedure. METHODS: We recruited 160 consecutive patients who underwent ENB for peripheral lung lesions (PLL) at a tertiary care centre. The diagnostic performance of ENB and sampling tools was assessed using a logistic regression model and a ROC-curve in which the dependent variable was diagnostic success. A multivariate model was built to predict diagnostic success before performing ENB to select the best candidates for the procedure. RESULTS: Most patients with PLLs in the study were male (65%), with a mean age of 67.9 years. The yield was 66% when the most common techniques were used together as suction catheter + transbronchial biopsy forceps (TBBx) + bronchoalveolar lavage + bronchial washing (p < 0.001) and increased to 69% when transbronchial needle aspiration (TBNA) and cytology brush were added (p < 0.001). Adding diagnostic techniques such as TBBx and TBNA resulted in an increase in diagnostic performance, with a statistically significant trend (p = 0.002). The logistic model area-under the ROC-curve for diagnostic success during ENB was 0.83 (95% CI:0.75-0.90; p < 0.001), and a logit value ≥ 0.12 was associated with ≥ 50% probability of diagnostic success. CONCLUSIONS: ENB, as a stand-alone diagnostic tool for the evaluation of PLLs when performed by experienced operators using a multi-modality technique, has a good diagnostic yield. The probability of having a diagnostic ENB could be assessed using the proposed model.

Utilization of spontaneous breathing trial, objective cough test, and diaphragmatic ultrasound results to predict extubation success: COBRE-US trial.

BACKGROUND: The results of clinical and weaning readiness tests and the spontaneous breathing trial (SBT) are used to predict the success of the weaning process and extubation. METHODS: We evaluated the capacity of the cuff leak test, rate of rapid and shallow breathing, cough intensity, and diaphragmatic contraction velocity (DCV) to predict the success of the SBT and extubation in a prospective, multicenter observational study with consecutive adult patients admitted to four intensive care units. We used receiver operating characteristic (ROC) curves to assess the tests' predictive capacity and built predictive models using logistic regression. RESULTS: We recruited 367 subjects who were receiving invasive mechanical ventilation and on whom 456 SBTs were performed, with a success rate of 76.5%. To predict the success of the SBT, we derived the following equation: (0.56 × Cough) - (0.13 × DCV) + 0.25. When the cutoff point was ≥ 0.83, the sensitivity was 91.5%, the specificity was 22.1%, and the overall accuracy was 76.2%. The area under the ROC curve (AUC-ROC) was 0.63. To predict extubation success, we derived the following equation: (5.7 × SBT) + (0.75 × Cough) - (0.25 × DCV) - 4.5. When the cutoff point was ≥ 1.25, the sensitivity was 96.8%, the specificity was 78.4%, and the overall accuracy was 91.5%. The AUC-ROC of this model was 0.91. CONCLUSION: Objective measurement of cough and diaphragmatic contraction velocity could be used to predict SBT success. The equation for predicting successful extubation, which includes SBT, cough, and diaphragmatic contraction velocity values, showed excellent discriminative capacity.

The Challenges of Spirometric Diagnosis of COPD.

Chronic obstructive pulmonary disease (COPD) is one of the top causes of morbidity and mortality worldwide. Although for many years its accurate diagnosis has been a focus of intense research, it is still challenging. Due to its simplicity, portability, and low cost, spirometry has been established as the main tool to detect this condition, but its flawed performance makes it an imperfect COPD diagnosis gold standard. This review aims to provide an up-to-date literature overview of recent studies regarding COPD diagnosis; we seek to identify their limitations and establish perspectives for spirometric diagnosis of COPD in the XXI century by combining deep clinical knowledge of the disease with advanced computer analysis techniques.

Association between erectile dysfunction and the severity of obstruction to airflow in patients with chronic obstructive pulmonary disease / Asociación entre disfunción eréctil y la severidad de la obstrucción al flujo aéreo en pacientes con enfermedad pulmonar obstructiva crónica

Objectives: The objective of this study was to explore a possible association between ED and the severity of airflow obstruction in patients with COPD. Materials and methods: A cross-sectional study was conducted using the International Index Erectile Function (IIEF), a scale validated and translated to Spanish. Bivariate analyses between subgroups were made for quantitative variables using a t-test for means and Mann­Whitney U for medians; qualitative variables were compared using the χ2 test or Fisher's test, depending on distribution. Confusion bias in the association between ED and airflow obstruction was controlled using a logistic regression model. Results: The Spanish version of the IIEF-15 scale was valid and applicable to the Colombian population. The prevalence of ED in COPD patients living at high altitudes was similar to that found at sea level. Such prevalence is higher than in general population. Beta-blockers increased 7 times the risk of ED, but we found no association between the degree of airflow obstruction and ED. Conclusion: Although the severity of COPD is not associated with ED, the prevalence of ED in COPD is higher than in general population. Therefore, ED screening in COPD patients using the IIEF could be justified. The strong association between beta-blockers and ED had not been previously described in patients with COPD but must be considered in their clinical management.

Objetivos: Explorar una posible asociación entre DE y severidad de la obstrucción al flujo aéreo en pacientes con EPOC. Materiales y métodos: Estudio de corte transversal aplicando el Índice Internacional de Función Eréctil (IIFE), validado y traducido al español. Se realizó análisis bivariado para variables cuantitativas usando prueba-t para medias y U de Mann Whitney para medianas; las variables cualitativas fueron comparadas usando prueba de Chi2 o test de Fisher, según distribución. Los sesgos de confusión en la asociación entre DE y obstrucción al flujo aéreo fueron controlados usando un modelo de regresión logística. Resultados: La versión en español de la escala IIFE-15 fue aplicable en población colombiana. La prevalencia de DE en pacientes con EPOC viviendo a gran altura fue similar a lo encontrado a nivel del mar. Esta prevalencia es mayor que en población general. El uso de beta-bloqueadores aumentó hasta siete veces el riesgo de DE, pero no se encontró asociación entre el grado de obstrucción y la DE. Conclusiones: Aunque la severidad de la EPOC no está asociada con DE, la prevalencia de DE en EPOC es mayor que en población general. Está justificada la realización de tamizaje usando el IIFE. La asociación fuerte entre beta-bloqueadores y DE no se ha descrito previamente en pacientes con EPOC, pero debe considerarse en su manejo.

Simple and Autonomous Sleep Signal Processing System for the Detection of Obstructive Sleep Apneas.

Obstructive sleep apnea (OSA) is a common sleep disorder characterized by repetitive upper airway obstruction, intermittent hypoxemia, and recurrent awakenings during sleep. The most used treatment for this syndrome is a device that generates a positive airway pressure­Continuous Positive Airway Pressure (CPAP), but it works continuously, whether or not there is apnea. An alternative consists on systems that detect apnea episodes and produce a stimulus that eliminates them. Article focuses on the development of a simple and autonomous processing system for the detection of obstructive sleep apneas, using polysomnography (PSG) signals: electroencephalography (EEG), electromyography (EMG), respiratory effort (RE), respiratory flow (RF), and oxygen saturation (SO2). The system is evaluated using, as a gold standard, 20 PSG tests labeled by sleep experts and it performs two analyses. A first analysis detects awake/sleep stages and is based on the accumulated amplitude in a channel-dependent frequency range, according to the criteria of the American Academy of Sleep Medicine (AASM). The second analysis detects hypopneas and apneas, based on analysis of the breathing cycle and oxygen saturation. The results show a good estimation of sleep events, where for 75% of the cases of patients analyzed it is possible to determine the awake/asleep states with an effectiveness of >92% and apneas and hypopneas with an effectiveness of >55%, through a simple processing system that could be implemented in an electronic device to be used in possible OSA treatments.

Cost-utility analysis of an integrated care program for children with asthma in a medium-income country.

OBJECTIVE: To evaluate the cost-utility of an integrated care program (ASMAIRE Infantil Program [PAI]) for children with asthma compared with standard of care. METHODS: A decision-analytic model was used to compare an integrated care program compared to the standard of care in children with asthma in Bogota, Colombia. Baseline characteristics of the patients were established according to the distribution of patients in the PAI database. Other inputs were obtained from published meta-analysis, local registries, medical bills, general mortality data, and expert opinion. Costs were presented in 2017 Colombian pesos. Outcomes included quality-adjusted life-years (QALYs). Costs and outcomes were discounted by 5% per year. Incremental cost-utility ratios were presented for PAI compared with standard of care. Univariate and multivariate probabilistic sensitivity analyses were conducted to assess model robustness to parameter uncertainty. RESULTS: The model predicted that patients that are part of the PAI would accrue more QALYs than patients on standard of care. The incremental results suggest that the PAI is a cost-effective treatment (incremental cost-utility ratio of Colombian pesos $33 753 817/QALY) compared with standard of care. Sensitivity analyses suggest that results are most sensitive to cost of care (with and without PAI) and costs of severe exacerbation. However, the PAI is cost-effective irrespective of variation in any of the input parameters. CONCLUSION: Our model predicted that an integrated intervention for the management of asthma in pediatric patients improves QALYs, reduces number of disease related exacerbations compared to standard therapy and is cost-effective for the long-term control of the disease in Colombia.

Aspiration in the Fiberoptic Endoscopic Evaluation of Swallowing Associated with an Increased Risk of Mortality in a Cohort of Patients Suspected of Oropharyngeal Dysphagia.

There is a general lack of published studies on the risk of mortality due to alterations in the safety of swallowing detected during the fiberoptic endoscopic evaluation of swallowing (FEES). We aimed at assessing the risk of mortality of the detection of aspiration, penetration, and pharyngeal residues by FEES. A cohort of consecutively evaluated patients suspected of experiencing oropharyngeal dysphagia undergoing FEES at a tertiary care university hospital were prospectively followed up on to assess mortality. The FEES findings, comorbidities, and potential confounders were studied as predictors of death using a Cox multivariate regression analysis. A total of 148 patients were included, 85 of whom were male (57.4%). The mean age (± standard deviation) was 52.7 years (± 22.1). The median of the follow-up time was 4.5 years. The most frequent conditions were stroke in 50 patients (33.8%), brain and spine traumas in 27 (18.2%), and neurodegenerative diseases in 19 (12.8%). Variables associated with mortality in bivariate analyses were age > 65 years (p < 0.001), pneumonia (p = 0.046), aspiration of any consistency (p < 0.001), and pharyngeal residues (p = 0.017). Variables independently associated with mortality in the Cox multivariate model were age (> 65 years) [adjusted hazard ratio (HR) 5.76; 95% CI 2.72 to 17.19; p = 0.001] and aspiration (adjusted HR: 3.96; 95% CI 1.82 to 14.64; p = 0.003). Aspiration detected by FEES and an age > 65 years are independent predictors of mortality in patients with oropharyngeal dysphagia.

High prevalence of house dust mite sensitization in children with severe asthma living at high altitude in a tropical country.

BACKGROUND: Some studies, mainly in Europe, have shown a low level of sensitization to house dust mite (HDM) allergens at high altitude (HA). Differently, some others in tropical countries have shown a higher level. The aim of this study was to evaluate allergens sensitization, including HDM, in children with severe asthma (SA), residents at HA in a tropical middle-income developing country. METHODS: Observational, analytical, cross-sectional study in children aged 6-15 years old with SA at HA (2640 m). Skin prick tests (SPT), serum IgE, exhaled fraction of nitric oxide (FENO ), spirometry, and asthma questionnaire (ACT) were performed. Associations were explored by Pearson or Spearman coefficients. RESULTS: We included 61 children. Most patients were male (61.3%), median age: 10 years (Interquartile range [IQR]: 8-12), median BMI: 17 kg/m2 (IQR: 16-20); Median of positive SPT: 2 (IQR: 2-3). At least one SPT was positive in 88.7% of patients and 87.9% were positive for at least one HDM. Serum IgE: 348 UI/mL (IQR: 154-760) and FENO : 22 ppb (IQR: 9-41). Prebronchodilator values were (% predicted): FVC: 109.7% (±15.5%), FEV1 : 98.4% (±16.3); FEV1 /FVC: 82% (±8%). SPT were inversely correlated with the FEV1 /FVC (Rho: -0.34; 95% CI: -0.55 a -0.09; P = 0.008). CONCLUSIONS: These children with SA living at HA in a tropical middle-income developing country have a high prevalence of HDM sensitization. One explanation for this might be that tropical conditions, such as temperature and humidity, could modify the effect of the altitude on asthma.

Accuracy of a Laryngopharyngeal Endoscopic Esthesiometer (LPEER) for Evaluating Laryngopharyngeal Mechanosensitivity: A Validation Study in a Prospectively Recruited Cohort of Patients.

Recent studies have shown an association between alterations in laryngopharyngeal mechanosensitivity (LPMS) and dysphagia, obstructive sleep apnea, and chronic cough hypersensitivity syndrome. A previous reliability study of a new laryngopharyngeal endoscopic esthesiometer and rangefinder (LPEER) showed high intra- and inter-rater reliability; however, its accuracy has not been tested. We performed an accuracy study of the LPEER in a prospectively and consecutively recruited cohort of 118 patients at two tertiary care university hospitals. Most of the patients were suffering from dysphagia, and all of them underwent a standard clinical evaluation and fiberoptic endoscopic evaluation of swallowing with sensory testing (FEESST) using a new sensory testing protocol. The sensory test included determinations of the laryngeal adductor reflex threshold (LART), the cough reflex threshold (CRT) and the gag reflex threshold (GRT). Abnormalities on these reflex thresholds were evaluated for associations with major alterations in swallowing safety (pharyngeal residues, penetration, and aspiration). We evaluated the discriminative capacity of the LPMS test using ROC curves and the area under the curve (AUC-ROC) and its relationship with the eight-point penetration-aspiration scale (PAS) using the Spearman's ρ correlation coefficient (SCC). We found a positive correlation between the PAS and LART (SCC 0.47; P < 0.001), CRT (SCC 0.46; P < 0.001) and GRT (SCC 0.34; P = 0.002). The AUC-ROC values for detecting a PAS ≥7 were as follows: LART, 0.83 (P < 0.0001); CRT, 0.79 (P < 0.0001); GRT, 0.72 (P < 0.0001). In this study, the LPEER showed good accuracy for evaluating LPMS. These results justify further validation studies in independent populations.

Reliability of a laryngo-pharyngeal esthesiometer and a method for measuring laryngo-pharyngeal mechano-sensitivity in a prospectively recruited cohort of patients.

BACKGROUND: There are not reliable methods for measuring laryngo-pharyngeal mechano-sensitivity (LPMS). We aimed to determine the reliability of a new method for measuring LPMS using a new laryngo-pharyngeal esthesiometer (LPEER) in a prospective cohort of dysphagic stroke and non-dysphagic patients. The patients underwent clinical and endoscopic evaluations of swallowing (FESSST). The LPMS assessments consisted of measurements by an expert and a novel rater of the laryngeal-adductor reflex threshold (LART), cough reflex threshold (CRT) and gag reflex threshold (GRT) using the LPEER. We assessed the Bland-Altman limits of agreement, the intraclass correlation coefficients (ICCs) and Spearman correlation coefficients (SCCs). For the inter-rater comparisons, we contrasted the expert and novel raters. A total of 1608 measurements were obtained from 34 dysphagic stroke patients and 33 non-dysphagic patients. The intra-rater ICCs for all reflex thresholds were >0.90. The inter-rater ICCs were 0.87 for the LART, 0.79 for the CRT and 0.70 for the GRT. The intra-rater SCCs for all reflex thresholds were above 0.88 (P < 0.0001). The inter-rater SCC were 0.80 for the LART, 0.79 for the CRT and 0.70 for the GRT (all P < 0.0001). The Bland-Altman plots revealed good agreement for the LART and CRT and moderate agreement for the GRT. The median normal value was 0.14 mN for the LART, 4.4 mN for the CRT and 11.9 mN for the GRT. The median thresholds values in patients with aspiration were LART: 1.31 mN; CRT: 32.9 mN and GRT: 32.9 mN (all P < 0.006 vs normal thresholds). The LPEER exhibited substantial to excellent intra- and inter-rater reliability.

Design, development and validation of a new laryngo-pharyngeal endoscopic esthesiometer and range-finder based on the assessment of air-pulse variability determinants.

BACKGROUND: Laryngo-pharyngeal mechano-sensitivity (LPMS) is involved in dysphagia, sleep apnea, stroke, irritable larynx syndrome and cough hypersensitivity syndrome among other disorders. These conditions are associated with a wide range of airway reflex abnormalities. However, the current device for exploring LPMS is limited because it assesses only the laryngeal adductor reflex during fiber-optic endoscopic evaluations of swallowing and requires a high degree of expertise to obtain reliable results, introducing intrinsic expert variability and subjectivity. METHODS: We designed, developed and validated a new air-pulse laryngo-pharyngeal endoscopic esthesiometer with a built-in laser range-finder (LPEER) based on the evaluation and control of air-pulse variability determinants and on intrinsic observer variability and subjectivity determinants of the distance, angle and site of stimulus impact. The LPEER was designed to be capable of delivering precise and accurate stimuli with a wide range of intensities that can explore most laryngo-pharyngeal reflexes. RESULTS: We initially explored the potential factors affecting the reliability of LPMS tests and included these factors in a multiple linear regression model. The following factors significantly affected the precision and accuracy of the test (P < 0.001): the tube conducting the air-pulses, the supply pressure of the system, the duration of the air-pulses, and the distance and angle between the end of the tube conducting the air-pulses and the site of impact. To control all of these factors, an LPEER consisting of an air-pulse generator and an endoscopic laser range-finder was designed and manufactured. We assessed the precision and accuracy of the LPEER's stimulus and range-finder according to the coefficient of variation (CV) and by looking at the differences between the measured properties and the desired values, and we performed a pilot validation on ten human subjects. The air-pulses and range-finder exhibited good precision and accuracy (CV < 0.06), with differences between the desired and measured properties at <3 % and a range-finder measurement error of <1 mm. The tests in patients demonstrated obtainable and reproducible thresholds for the laryngeal adductor, cough and gag reflexes. CONCLUSIONS: The new LPEER was capable of delivering precise and accurate stimuli for exploring laryngo-pharyngeal reflexes.