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  1. Nov 2022
    1. Exacerbation symptoms systematically recorded on daily diary cards accurately detect both reported andunreported exacerbations [6, 12],

      Sería interesante leer:

      6 Seemungal TA, Donaldson GC, Paul EA, et al. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998; 157: 1418–1422.

      12 Seemungal TA, Donaldson GC, Bhowmik A, et al. Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000; 161: 1608–1613.



    1. A previousstudy [13] has suggested that symptoms tend to worsen duringthe 7 days immediately before an exacerbation episode.

      13 Donaldson GC, Wedzicha JA. COPD exacerbations .1: Epidemiology. Thorax 2006 Feb;61(2):164-168 [FREE Full text] [doi: 10.1136/thx.2005.041806] [Medline: 16443707]



    1. Acute changes in lung function (forcedexpiratory volume in 1 s (FEV 1)) or the FEV1/forced vital capacity ratio are not sensitive, and do notcorrelate well with AECOPD [57, 58].

      Acute changes in lung function FEV1 and FEV1/FVC are not sensitive and dote correlate wll with AECOPD

      57 Stevenson NJ, Walker PP, Costello RW, et al. Lung mechanics and dyspnea during exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005; 172: 1510–1516

      58 Parker CM, Voduc N, Aaron SD, et al. Physiological changes during symptom recovery from moderate exacerbations of COPD. Eur Respir J 2005; 26: 420–428.

    2. Studies that have assessed the incidence of symptom-based AECOPDs compared to event-based AECOPDsin the same patients followed over time suggest that observed exacerbation rates are much higher ifsymptom-based definitions are used. The Investigating New Standards for Prophylaxis in ReducingExacerbations (INSPIRE) study compared the incidence of AECOPD using symptom-based definitions anda treatment-based definition and found that the incidence rate was three AECOPDs per patient-year if asymptom-based definition was used and 1.5 AECOPDs per patient-year if an event-based definition wasused, suggesting that 50% of symptom-defined COPD exacerbations are not treated by physicians [27].

      Dato importante. Symptom-based son más diagnosticadas que las event-based.

      27 Wedzicha JA, Calverley PM, Seemungal TA, et al. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. Am J Respir Crit Care Med 2008; 177: 19–26.

    3. A further advantage is that validated tools to capture symptom-basedAECOPDs exist and include patient diary cards [18] and the validated Exacerbation of ChronicPulmonary Disease Tool (EXACT) [19].

      18 Quint JK, Donaldson GC, Hurst JR, et al. Predictive accuracy of patient-reported exacerbation frequency in COPD. Eur Respir J 2011; 37: 501–507.

      19 Leidy NK, Murray LT. Patient-reported outcome (PRO) measures for clinical trials of COPD: the EXACT and E-RS. COPD 2013; 10: 393–398.

    1. ecause of global variability in the available resources to treat patients and local customsaffecting the criteria for hospital visits and admissions, there is substantial variability in reported ECOPD outcomes.(11)

      Importantísimo leer

      • Halpin DMG, Rabe AP, Loke WJ, et al. Epidemiology, Healthcare Resource Utilization, and Mortality of Asthma and COPD in COVID-19: A Systematic Literature Review and Meta-Analyses. J Asthma Allergy 2022; 15: 811-25
    1. Combined initial COPD assessment

      Punto a destacar: - A partir del 2011, se incluye el CAT y el mMRC para tomar en consideración los PROs para guiar el tratamiento en pacientes con COPD. - The newest change regarding this topic in the 2023 guide, is the modification from the ABCD to the ABE assessment tool. This approach recognizes the clinical relevance of exacerbations, independently of the level of symptoms of the patient. CD are joined and form the E, to highlight Exacerbations. This still has to be validated.



    1. Seemungal et al. reported a 7-day prodrome prior to diagnosis ofexacerbation [6]. With this in mind, the use of respiratory RPM has thepotential to reduce COPD treatment delays leading to improved care.Increased respiratory rate has demonstrated predictive ability for ex-acerbations of COPD [7,8]. Shah et al. observed an increased respiratoryrate in the 5 days preceding hospitalization for COPD exacerbations,highlighting the window of opportunity for intervention [7].

      Detalles importantes:

      Seemungal determinó un periodo prodrómico de 7 días. Sin embargo, hay que recordar que las exacerbaciones tienen diferentes presentaciones.

      RR parece ser un predictor importante. Se eleva 5 días antes de la hospitalización

      6 T.A. Seemungal, G.C. Donaldson, A. Bhowmik, D.J. Jeffries, J.A. Wedzicha, Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease, Am. J. Respir. Crit. Care Med. 161 (5) (2000 May) 1608–1613, https://doi.org/10.1164/ajrccm.161.5.9908022. PMID: 10806163.

      7 S.A. Shah, C. Velardo, A. Farmer, L. Tarassenko, Exacerbations in chronic obstructive pulmonary disease: identification and prediction using a digital Health system, J. Med. Internet Res. 19 (3) (2017) e69, https://doi.org/10.2196/ jmir.7207. Published 2017 Mar 7.

      8 A.M. Ya ̃nez, D. Guerrero, R. P ́erez de Alejo, F. Garcia-Rio, J.L. Alvarez-Sala, M. Calle-Rubio, R.M. de Molina, M. Valle Falcones, P. Ussetti, J. Sauleda, E. Z. García, J.M. Rodríguez-Gonz ́alez-Moro, M. Franco Gay, M. Torrent, A. Agustí, Monitoring breathing rate at home allows early identification of COPD exacerbations, Chest 142 (6) (2012) 1524–1529.



    1. Lung function changes, such as decreases in peak expiratoryflow rate (PEFR) or FEV1 immediately before exacerbation, aregenerally small and not useful in predicting exacerbations, butlarger decreases in PEFR are associated with dyspnea, longerrecovery time after exacerbations, and the presence of symptom-atic colds (11).

      Importante. Los cambios en el FEV1 inmediatamente antes de las exacerbaciones no son útiles para predecir exacerbaciones.

      11 Seemungal TA, Donaldson GC, Bhowmik A, Jeffries DJ, Wedzicha JA. Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;161:1608–1613. (lo tenemos)



    1. However, it should be stressed thataction plans that contain only minimal or no patient self-management education have not been shown to reduce urgenthealthcare utilisation for COPD. 12

      Importante recalcar que las intervenciones que no involucran acciones propias del paciente, no reducen la utilización del sistema sanitario

      12 Walters JA, Turnock AC, Walters EH, et al. Action plans with limited patient education only for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2010;(5):CD005074

    2. Previous studies suggest that prompt treatment ofexacerbations is associated with better clinical outcomes.

      Importante para justificar el hecho de querer predecir exacerbaciones

      7 Wilkinson T, Donaldson GC, Hurst JR, et al. Early therapy improves outcomes of exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004;169:1298e303.



    1. A history of previous exacerbations isconsidered the best predictor of futureexacerbations and forms the current basis ofrisk stratification in guidelines (22, 23).
      1. Vestbo J, Hurd SS, Agust ́ı AG, Jones PW, Vogelmeier C, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2013;187:347–365.

      2. Kerkhof M, Freeman D, Jones R, Chisholm A, Price DB; Respiratory Effectiveness Group. Predicting frequent COPD exacerbations using primary care data. Int J Chron Obstruct Pulmon Dis 2015;10: 2439–2450

    2. Most previous risk-predictionmodels for COPD exacerbations weredeveloped for use at point of care (5–8);however, an alternative approach is to useroutinely collected health data (9).
      1. Collier R. WHO guidelines on ethical public health surveillance. CMAJ 2017;189:E977



    1. severe exacerbationswere those that required an emergency departmentvisit or admission to hospital. 3,8–10

      exacerbaciones severas

      3 Vogelmeier CF, Criner GJ, Martinez FJ, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 Report. GOLD Executive Summary. Am J Respir Crit Care Med 2017; 195: 557–82.

      8 Albert RK, Connett J, Bailey WC, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med 2011; 365: 689–98.

      9 Criner GJ, Connett JE, Aaron SD, et al. Simvastatin for the prevention of exacerbations in moderate-to-severe COPD. N Engl J Med 2014; 370: 2201–10.

      10 Aaron SD, Vandemheen KL, Fergusson D, et al. Tiotropium in combination with placebo, salmeterol, or fluticasone–salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med 2007; 146: 545.

    2. In reporting our prediction model, we followedrecommendations set by the Transparent Reporting of aMultivariable Prediction Model for Individual Prognosisor Diagnosis (TRIPOD) statement.

      Es necesarion que nosotros hagamos esto?

      1. Collins GS, Reitsma JB, Altman DG, Moons K. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD Statement. BMC Med 2015; 13: 1
    3. Inclinical practice, a history of two or more exacerbationsand one severe exacerbation per year is used toguide therapeutic choices for exacerbation prevention.3

      Esto es lo que en la práctica clínica se considera para guiar el tratamiento en exacerbaciones

      Vogelmeier CF, Criner GJ, Martinez FJ, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 Report. GOLD Executive Summary. Am J Respir Crit Care Med 2017; 195: 557–82.

    1. A Cochrane review [ 31 ] has summarized the impact of remote monitoring technologyfor people with COPD.

      Janjua, S.; Carter, D.; Threapleton, C.J.; Prigmore, S.; Disler, R.T. Telehealth Interventions: Remote Monitoring and Consultations for People with Chronic Obstructive Pulmonary Disease (COPD). Cochrane Database Syst. Rev. 2021, 7, CD013196.



    1. The methodology used in the ECLIPSE study has been described indetail elsewhere.9

      ECLIPSE methodology

      1. Vestbo J , Anderson W , Coxson HO , et al ; ECLIPSE investigators . Evaluation of COPD longitudinally to identify predictive surrogate end-points (ECLIPSE). Eur Respir J. 2008; 31 ( 4 ): 869 - 873 .
    2. Exacerbations of COPD accel-erate disease progression5-7

      Interesante de leer

      1. Tanabe N , Muro S , Hirai T , et al . Impact of exacerbations on emphysema progression in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2011 ; 183 ( 12 ): 1653 - 1659 .

      2. Donaldson GC , Seemungal TA , Bhowmik A , Wedzicha JA . Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax. 2002 ; 57 ( 10 ): 847 - 852.

      3. Vestbo J , Edwards LD , Scanlon PD , et al ; ECLIPSE Investigators . Changes in forced expiratory volume in 1 second over time in COPD. N Engl J Med. 2011 ; 365 ( 13 ): 1184 - 1192 .



    1. xacerbation wasdefined on the basis of symptom-based diagnosis such asincreased cough and sputum production, a change of sputumcolor, and worsening of dyspnea from a stable state andbeyond-normal day-to-day variations, i.e., showing acute onsetand necessitating a change in regular medication, in accor-dance with a previous report [21]. Moderate exacerbationsrequired a prescription for antibiotics and/or systemic corticos-teroids, and severe exacerbations required hospitalization [22].

      Definición de exacerbación

      1. Calverley PM, Anderson JA, Celli B, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007;356:775–89



    1. Full methodology is avail-able elsewhere and is summarized in e-Appendix 1. 16,17

      Methods supplement



    1. The mostcommon statistical method was logistic regression (11 out of 25 different statistical methods analysed)followed by Cox regression (10), and correlation analysis between an index (or a multivariable regressionequation) with the outcome (three). Finally, Poisson regression model, negative binomial regression modeland random forest model were each used once.

      Métodos estadísticos. Leer los papers que están siendo estudiados

      Bertens (29) Ya lo tienes

      Motegi (43) Motegi T, Jones RC, Ishii T, et al. A comparison of three multidimensional indices of COPD severity as predictors of future exacerbations. Int J COPD 2013; 8: 259–271.

      Almagro (23) Almagro P, Soriano JB, Cabrera FJ, et al. Short- and medium-term prognosis in patients hospitalized for COPD exacerbation: the CODEX index. Chest 2014; 145: 972–980.

      Suetomo (48) Suetomo M, Kawayama T, Kinoshita T, et al. COPD assessment tests scores are associated with exacerbated chronic obstructive pulmonary disease in Japanese patients. Respir Investig 2014; 52: 288–295

      Mullerova (45) Müllerova H, Maselli DJ, Locantore N, et al. Hospitalized Exacerbations of COPD. Chest 2015; 147: 999–1007.

      Thomsen (50) Thomsen M, Ingebrigtsen TS, Marott JL, et al. Inflammatory biomarkers and exacerbations in chronic obstructive pulmonary disease. JAMA 2013; 309: 2353–2361.

      Moberg (42) Moberg M, Vestbo J, Martinez G, et al. Validation of the i-BODE index as a predictor of hospitalization and mortality in patients with COPD Participating in pulmonary rehabilitation. COPD 2014; 11: 381–387.

      Takahashi (49) Takahashi T, Muro S, Tanabe N, et al. Relationship between periodontitis-related antibody and frequent exacerbations in chronic obstructive pulmonary disease. PLoS One 2012; 7: e40570.

      Faganello (33) Faganello MM, Tanni SE, Sanchez FF, et al. BODE index and GOLD staging as predictors of 1-year exacerbation risk in chronic obstructive pulmonary disease. Am J Med Sci 2010; 339: 10–14

      Garcia-Aymerich (34) Garcia-Aymerich J, Farrero E, Félez MA, et al. Risk factors of readmission to hospital for a COPD exacerbation: a prospective study. Thorax 2003; 58: 100–105.

      Ko (39) Ko FW, Tam W, Tung AH, et al. A longitudinal study of serial BODE indices in predicting mortality and readmissions for COPD. Respir Med 2011; 105: 266–273.

      Echave (32) Echave-Sustaeta J, Comeche Casanova L, Garcia Lujan R, et al. Prognosis following acute exacerbation of COPD treated with non-invasive mechanical ventilation. Arch Bronconeumol 2010; 46: 405–410.

      Lee (40) Lee SD, Huang MS, Kang J, et al. The COPD assessment test (CAT) assists prediction of COPD exacerbations in high-risk patients. Respir Med 2014; 108: 600–608.

      Moy (44) Moy ML, Teylan M, Danilack VA, et al. An index of daily step count and systemic inflammation predicts clinical outcomes in chronic obstructive pulmonary disease. Ann Am Thorac Soc 2014; 11: 149–157

      Hurst (36) Hurst JR, Vestbo J, Anzueto A, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med 2010; 363: 1128–1138

      Amalakuhan (28) Amalakuhan B, Kiljanek L, Parvathaneni A, et al. A prediction model for COPD readmissions: catching up, catching our breath, and improving a national problem. J Community Hosp Intern Med Perspect 2012; 2: 9915.

    2. In order to come up with high-quality prediction models for exacerbations in COPD patients, a standardmethodology for developing the models should be adopted [55]

      Leer cita 55

      Moons KG, Kengne AP, Woodward M, et al. Risk prediction models: I. Development, internal validation, and assessing the incremental value of a new (bio)marker. Heart 2012; 98: 683–690.



    1. CODEX was designed to predict mortality and hospitalreadmission in 3–12 months after discharge of patients hospi-talized for AECOPD.6

      CODEX Leer

      Almagro P, Soriano JB, Cabrera FJ, et al; Working Group on COPD, Spanish Society of Internal Medicine. Short- and medium-term prognosis in patients hospitalized for COPD exacerbation: the CODEX index. Chest. 2014;145(5):972–980.



    1. Conventional threshold-basedalgorithms, adopted in the majority of reviewed stud-ies (n ¼ 12), show poor performance in early detect-ing respiratory exacerbations or identifying severityand duration in COPD, 13,53 with the best reportedaccuracy being 73% of exacerbations detected. 52 ; bestsensitivity/specificity 66%/93%55 24 h before hospi-talization.

      Estudio donde se creó una alarma.

      1. Pinnock H, Hanley J, McCloughan L, et al. Effective ness of telemonitoring integrated into existing clinical services on hospital admission for exacerbation of chronic obstructive pulmonary disease: researcher blind, multicentre, randomised controlled trial. BMJ 2013; 347: f6070

      2. Halpin DMG, Laing-Morton T, Spedding S, et al. A randomised controlled trial of the effect of automated interactive calling combined with a health risk forecast on frequency and severity of exacerbations of COPD assessed clinically and using EXACT PRO. Prim Care Respir J 2011; 20: 324–331.

      3. Sund ZM, Powell T, Greenwood R, et al. Remote daily real-time monitoring in patients with COPD – a feasibility study using a novel device. Respir Med 2009; 103: 1320–1328.

      4. Yanez AM, Guerrero D, Perez De Alejo R, et al. Monitoring breathing rate at home allows early identification of COPD exacerbations. Chest 2012; 142:1524–1529.