The concept of control in chronic obstructive pulmonary disease: Development of the criteria and validation for use in clinical practice

Guidelines of treatment of chronic obstructive pulmonary disease (COPD) identify symptom reduction and prevention of exacerbations as the main goals of therapy. Initial pharmacological treatment must be guided by these parameters, and effectiveness must be assessed at each clinical visit. However, there is no clear guidance as to how this assessment must be performed. The concept of control has been well developed in asthma, but it has been elusive in COPD. Patients with COPD may not be completely free from symptoms or exacerbations even under optimized therapy; therefore, control in COPD does not mean cure or absence of symptoms, but rather reaching the best clinical status possible according to the level of disease severity. A control tool has been developed based on a cross sectional evaluation of the impact of the disease and a longitudinal evaluation of stability. Low impact is a disease status defined by at least 3 of the following: low levels of dyspnoea, absence of or white sputum, low use of rescue medication and self-declared walking time of more than 30 minutes a day, and stability is the absence of moderate or severe exacerbations in the previous 3 months. Control can also be defined by COPD Assessment Test (CAT) scores ≤ 10 units for patients with FEV1 ≥ 50% and 16 for patients with FEV1 < 50% and stability as a change in CAT ≤ 2 units. Control of COPD is then defined as a status of low impact and stability. The control tool has been validated prospectively in several studies and has demonstrated to be sensitive to clinical changes and to have a good predictive value for poor outcomes. Clinical criteria are more reliable than CAT scores for the evaluation of control. The control tool is a quick and inexpensive method to evaluate clinical status and future risk of exacerbations that can be used at all levels of healthcare. Концепция контроля при лечении хронической обструктивной болезни легких: разработка критериев и валидация для клинического применения (перевод с английского)По данным рекомендаций, при лечении хронической обструктивной болезни легких (ХОБЛ) в качестве главных целей лечения выделяются купирование симптомов и предотвращение обострений. При первоначальной медикаментозной терапии следует руководствоваться именно этими параметрами, а эффективность должна оцениваться при каждом посещении пациентом врача. Однако четких рекомендаций о том, как именно проводить такую оценку, не существует. Концепция контроля хорошо разработана при лечении бронхиальной астмы, однако для ХОБЛ сформулировать таковую оказалось намного труднее. Пациенты с ХОБЛ могут продолжать испытывать симптомы болезни, даже получая оптимальную терапию; таким образом, контроль над ХОБЛ означает не полное излечение или отсутствие симптомов, а достижение наилучшего возможного клинического статуса при данной степени тяжести заболевания. Авторами данной статьи разработан инструмент для определения контроля над ХОБЛ на основе поперечного среза данных о нагрузке на здоровье пациента и лонгитюдинальной оценки стабильности его состояния. Низкая нагрузка определяется как удовлетворяющая минимум 3 критериям из следующих: низкий уровень одышки; отсутствие мокроты или белая мокрота; малое использование симптоматической терапии; 30 мин ходьбы пешком в день согласно самооценке. Стабильность определяется как отсутствие умеренно тяжелых или тяжелых обострений в предшествующие 3 мес. Контроль также осуществляется по результатам теста по оценке степени тяжести ХОБЛ (COPD Assesment Test – CAT) следующим образом: ≤ 10 единиц – для пациентов, у которых показатель объема форсированного выдоха за 1-ю секунду (ОФВ1) составляет ≥ 50 %; ≤ 16 – при ОФВ1 < 50 %; стабильность определяется как изменение оценки по CAT ≤ 2 единиц. Таким образом, контроль над ХОБЛ определяется как состояние стабильно низкой нагрузки на здоровье. Инструмент для определения контроля валидирован проспективно по данным ряда исследований, при этом продемонстрированы чувствительность к изменениям клинического состояния пациентов и бόльшая прогностическая ценность по отношению к негативным исходам. Кли - нические критерии оказались надежнее в определении статуса контроля, чем баллы по CAT. Таким образом, концепция контроля – это быстрый и недорогой метод оценки клинического статуса и риска обострений в будущем, который пригоден к использованию на всех уровнях здравоохранения

Lack of Clinical Control in COPD Patients Depending on the Target and the Therapeutic Option

Introduction: According to the Global Initiative for chronic obstructive lung disease (GOLD), when a treatment is not achieving an appropriate response it should be switched taking into account the predominant treatable trait to target (dyspnea or exacerbations). The objective of the present study was to investigate the lack of clinical control according to the target and medication groups. Materials and Methods: This was a post-hoc analysis of the CLAVE study, an observational, cross-sectional, multicenter study which evaluated the clinical control, and related-factors, in a cohort of 4801 patients with severe chronic obstructive pulmonary disease (COPD). The primary endpoint was the percentage of uncontrolled patients defined as COPD Assessment Test (CAT) >16 or presence of exacerbations in the last 3 months despite receiving long-acting beta2-agonist (LABA) and/or long-acting antimuscarinic antagonist (LAMA) with or without inhaled corticosteroids (ICS). Secondary objectives included the description of sociodemographic and clinical characteristics of patients by therapeutic group and the identification of characteristics potentially associated with the lack of control of COPD including low adherence measured by the test to adherence to inhalers (TAI). Results: In the dyspnea pathway, lack of clinical control was of 25.0% of patients receiving LABA or LAMA in monotherapy, 29.5% by those with LABA + LAMA, 38.3% with LABA + ICS and 37.0% with triple therapy (LABA + LAMA + ICS). In the exacerbation pathway, percentages were 87.1%, 76.7%, 83.3%, and 84.1%, respectively. Low physical activity and high Charlson comorbidity index were independent factor of non-control in all therapeutic groups. Additional factors were lower post-bronchodilator FEV1 and poor adherence to inhalers. Conclusion: There are still room for improvement in COPD control. From the pharmacological perspective, every step in treatment have a pool of uncontrolled patients in which a step-up could be considered according to a trait to target strategy

Testing for alpha-1 antitrypsin in COPD in outpatient respiratory clinics in Spain: A multilevel, cross-sectional analysis of the EPOCONSUL study

Background Alpha-1 antitrypsin deficiency (AATD) is the most common hereditary disorder in adults, but is under-recognized. In Spain, the number of patients diagnosed with AATD is much lower than expected according to epidemiologic studies. The objectives of this study were to assess the frequency and determinants of testing serum α1-antitrypsin (AAT) levels in COPD patients, and to describe factors associated with testing. Methods EPOCONSUL is a cross-sectional clinical audit, recruiting consecutive COPD cases over one year. The study evaluated serum AAT level determination in COPD patients and associations between individual, disease-related, and hospital characteristics. Results A total of 4,405 clinical records for COPD patients from 57 Spanish hospitals were evaluated. Only 995 (22.5%) patients had serum AAT tested on some occasion. A number of patient characteristics (being male [OR 0.5, p < 0.001], ≤55 years old [OR 2.38, p<0.001], BMI≤21 kg/m2 [OR 1.71, p<0.001], FEV1(%)<50% [OR 1.35, p<0.001], chronic bronchitis [OR 0.79, p < 0.001], Charlson index ≥ 3 [OR 0.66, p < 0.001], or history or symptoms of asthma [OR 1.32, p<0.001]), and management at a specialized COPD outpatient clinic [OR 2.73,p<0.001] were identified as factors independently associated with ever testing COPD patients for AATD. Overall, 114 COPD patients (11.5% of those tested) had AATD. Of them, 26 (22.8%) patients had severe deficiency. Patients with AATD were younger, with a low pack-year index, and were more likely to have emphysema (p<0.05). Conclusion Testing of AAT blood levels in COPD patients treated at outpatient respiratory clinics in Spain is infrequent. However, when tested, AATD (based on the serum AAT levels ≤100 mg/dL) is detected in one in five COPD patients. Efforts to optimize AATD case detection in COPD are needed.SEPA

Prevalence of reduced lung diffusing capacity and CT scan findings in smokers without airflow limitation: a population-based study

Exercise; Lung Physiology; Tobacco and the lungEjercicio; Fisiología Pulmonar; Tabaco y pulmónExercici; Fisiologia pulmonar; Tabac i pulmóBackground Population distribution of reduced diffusing capacity of the lungs for carbon monoxide (DLCO) in smokers and main consequences are not properly recognised. The objectives of this study were to describe the prevalence of reduced DLCO in a population-based sample of current and former smoker subjects without airflow limitation and to describe its morphological, functional and clinical implications. Methods A sample of 405 subjects aged 40 years or older with postbronchodilator forced expiratory volume in 1 s/forced vital capacity (FVC) >0.70 was obtained from a random population-based sample of 9092 subjects evaluated in the EPISCAN II study. Baseline evaluation included clinical questionnaires, exhaled carbon monoxide (CO) measurement, spirometry, DLCO determination, 6 min walk test, routine blood analysis and low-dose CT scan with evaluation of lung density and airway wall thickness. Results In never, former and current smokers, prevalence of reduced DLCO was 6.7%, 14.4% and 26.7%, respectively. Current and former smokers with reduced DLCO without airflow limitation were younger than the subjects with normal DLCO, and they had greater levels of dyspnoea and exhaled CO, greater pulmonary artery diameter and lower spirometric parameters, 6 min walk distance, daily physical activity and plasma albumin levels (all p<0.05), with no significant differences in other chronic respiratory symptoms or CT findings. FVC and exhaled CO were identified as independent risk factors for low DLCO. Conclusion Reduced DLCO is a frequent disorder among smokers without airflow limitation, associated with decreased exercise capacity and with CT findings suggesting that it may be a marker of smoking-induced early vascular damage.The EPISCAN II study has been a GlaxoSmithKline sponsored study (grant number: not applicable)

Respiratory symptoms and their determinants in the general Spanish population: changes over 20 years

Epidemiology; Respiratory symptomsEpidemiología; Síntomas respiratoriosEpidemiologia; Símptomes respiratorisBackground Few large epidemiological studies have analysed the prevalence of respiratory symptoms and their determinants in the general adult population. We investigated the prevalence and determinants of respiratory symptoms and compared their prevalence with that of two previous studies conducted in 1999 and 2009. Method EPISCAN II was a multicentre, cross-sectional, population-based epidemiological study in individuals older than 40 years. Results A total of 9092 individuals were included. Up to 47.5% reported at least one respiratory symptom, being more frequent in women than in men (49.4% versus 45.5%, p=0.0002) and with wheezing being the most frequent (33.7%) followed by dyspnoea (26.8%). The presence of any symptom was associated with female sex, higher body mass index (BMI), lower forced expiratory volume in 1 s (FEV1 % pred), reduced physical activity, a higher Charlson index and the presence of anxiety and depression. Smoking was also significantly associated with having at least one respiratory symptom in a dose–response fashion (OR: 1.415, 1.916, 2.192 and 2.987 for 0–10, 10–20, 20–30 and >30 pack-years, respectively, all p<0.0001). The prevalence of symptoms remained quite similar over the last 20 years (wheezing 40%, 36% and 33.7% and dyspnoea 10.4%, 9.9% and 13.1% in 1999, 2009 and 2019, respectively). Conclusions Approximately half of the adult Spanish population have respiratory symptoms and this prevalence has remained quite stable over the last 20 years. Smoking remains the main factor associated with respiratory symptoms, but female sex, comorbidities, high BMI and low FEV1 and low physical activity are also significantly associated with respiratory symptoms.The EPISCAN II study was sponsored by GlaxoSmithKline. Funding information for this article has been deposited with the Crossref Funder Registry

Determinants of blood eosinophil levels in the general population and patients with COPD: a population-based, epidemiological study

Epidemiology; Computed tomography; BiomarkersEpidemiología; Tomografía computarizada; BiomarcadoresEpidemiologia; Tomografia computada; BiomarcadorsBackground Blood eosinophils are considered a biomarker for the treatment of chronic obstructive pulmonary disease (COPD). Population-based studies are needed to better understand the determinants of the blood eosinophil count (BEC) in individuals with and without COPD. Methods EPISCAN II is a multicentre, cross-sectional, population-based epidemiological study aimed at investigating the prevalence and determinants of COPD in Spain. Study subjects were randomly selected from the general population, and COPD was defined by a post-bronchodilator FEV1/FVC < 0.7. For the pre-specified outcomes related to BEC, the first 35 COPD and 35 non-COPD subjects were consecutively recruited in 12 of the participating centres with the objective of analysing 400 individuals in each group. Baseline BEC and its association with demographic, clinical and functional variables were analysed. Results A total of 326 COPD and 399 non-COPD subjects were included in the analysis. The mean age (standard deviation [SD]) was 63.2 years (11.0), 46.3% were male, and 27.6% were active smokers. BEC was significantly higher in individuals with COPD [192 cells/μL (SD: 125) vs. 160 cells/μL (SD: 114); p = 0.0003]. In a stepwise multivariate model, being male, active smoker and having a previous diagnosis of asthma were independently associated with having a higher BEC. Conclusions This population-based study estimated the distribution of eosinophils in the healthy adult population and concluded that COPD patients have a significantly higher BEC. Male sex, active smoking and concomitant asthma were significantly associated with a higher BEC.The EPI SCAN II study was funded by an unrestricted grant from GlaxoSmithKline

Unravelling young COPD and pre-COPD in the general population

COPD; General populationMPOC; Població generalEPOC; Población generalBackground Chronic obstructive pulmonary disease (COPD) is commonly diagnosed when the airflow limitation is well established and symptomatic. We aimed to identify individuals at risk of developing COPD according to the concept of pre-COPD and compare their clinical characteristics with 1) those who have developed the disease at a young age, and 2) the overall population with and without COPD. Methods The EPISCAN II study is a cross-sectional, population-based study that aims to investigate the prevalence of COPD in Spain in subjects ≥40 years of age. Pre-COPD was defined as the presence of emphysema >5% and/or bronchial thickening by computed chromatography (CT) scan and/or diffusing capacity of the lung for carbon monoxide (DLCO) 0.70. Young COPD was defined as FEV1/FVC <0.70 in a subject ≤50 years of age. Demographic and clinical characteristics were compared among pre-COPD, young COPD and the overall population with and without COPD. Results Among the 1077 individuals with FEV1/FVC 0.70, 350 underwent both DLCO testing and chest CT scanning. Of those, 78 (22.3%) subjects fulfilled the definition of pre-COPD. Subjects with pre-COPD were older, predominantly women, less frequently active or ex-smokers, with less frequent previous diagnosis of asthma but with higher symptomatic burden than those with young COPD. Conclusions 22.3% of the studied population was at risk of developing COPD, with similar symptomatic and structural changes to those with well-established disease without airflow obstruction. This COPD at-risk population is different from those that develop COPD at a young age.The EPISCAN II study was sponsored by GlaxoSmithKline

Current challenges in chronic bronchial infection in patients with chronic obstructive pulmonary disease

Currently, chronic obstructive pulmonary disease (COPD) patients and their physicians face a number of significant clinical challenges, one of which is the high degree of uncertainty related to chronic bronchial infection (CBI). By reviewing the current literature, several challenges can be identified, which should be considered as goals for research. One of these is to establish the bases for identifying the biological and clinical implications of the presence of potentially pathogenic microorganisms in the airways that should be more clearly elucidated according to the COPD phenotype. Another urgent area of research is the role of long-term preventive antibiotics. Clinical trials need to be carried out with inhaled antibiotic therapy to help clarify the profile of those antibiotics. The role of inhaled corticosteroids in patients with COPD and CBI needs to be studied to instruct the clinical management of these patients. Finally, it should be explored and confirmed whether a suitable antimicrobial treatment during exacerbations may contribute to breaking the vicious circle of CBI in COPD. The present review addresses the current state of the art in these areas to provide evidence which will enable us to progressively plan better healthcare for these patients

Palliative care and prognosis in COPD : a systematic review with a validation cohort

Current recommendations to consider initiation of palliative care (PC) in COPD patients are often based on an expected poor prognosis. However, this approach is not evidence-based, and which and when COPD patients should start PC is controversial. We aimed to assess whether current suggested recommendations for initiating PC were sufficiently reliable. We identified prognostic variables proposed in the literature for initiating PC; then, we ascertained their relationship with 1-year mortality, and finally, we validated their utility in our cohort of 697 patients hospitalized for COPD exacerbation. From 24 articles of 499 screened, we selected 20 variables and retrieved 48 original articles in which we were able to calculate the relationship between each of them and 1-year mortality. The number of studies where 1-year mortality was detailed for these variables ranged from 9 for previous hospitalizations or FEV ≤30% to none for albumin ≤25 mg/dL. The percentage of 1-year mortality in the literature for these variables ranged from 5% to 60%. In the validation cohort study, the prevalence of these proposed variables ranged from 8% to 64%; only 10 of the 18 variables analyzed in our cohort reached statistical significance with Cox regression analysis, and none overcame an area under the curve ≥0.7. We conclude that none of the suggested criteria for initiating PC based on an expected poor vital prognosis in COPD patients in the short or medium term offers sufficient reliability, and consequently, they should be avoided as exclusive criteria for considering PC or at least critically appraised

Концепция контроля при лечении хронической обструктивной болезни легких: разработка критериев и валидация для клинического применения (перевод с английского)

Guidelines of treatment of chronic obstructive pulmonary disease (COPD) identify symptom reduction and prevention of exacerbations as the main goals of therapy. Initial pharmacological treatment must be guided by these parameters, and effectiveness must be assessed at each clinical visit. However, there is no clear guidance as to how this assessment must be performed. The concept of control has been well developed in asthma, but it has been elusive in COPD. Patients with COPD may not be completely free from symptoms or exacerbations even under optimized therapy; therefore, control in COPD does not mean cure or absence of symptoms, but rather reaching the best clinical status possible according to the level of disease severity. A control tool has been developed based on a cross sectional evaluation of the impact of the disease and a longitudinal evaluation of stability. Low impact is a disease status defined by at least 3 of the following: low levels of dyspnoea, absence of or white sputum, low use of rescue medication and self-declared walking time of more than 30 minutes a day, and stability is the absence of moderate or severe exacerbations in the previous 3 months. Control can also be defined by COPD Assessment Test (CAT) scores ≤ 10 units for patients with FEV1 ≥ 50% and 16 for patients with FEV1 &lt; 50% and stability as a change in CAT ≤ 2 units. Control of COPD is then defined as a status of low impact and stability. The control tool has been validated prospectively in several studies and has demonstrated to be sensitive to clinical changes and to have a good predictive value for poor outcomes. Clinical criteria are more reliable than CAT scores for the evaluation of control. The control tool is a quick and inexpensive method to evaluate clinical status and future risk of exacerbations that can be used at all levels of healthcare.По данным рекомендаций, при лечении хронической обструктивной болезни легких (ХОБЛ) в качестве главных целей лечения выделяются купирование симптомов и предотвращение обострений. При первоначальной медикаментозной терапии следует руководствоваться именно этими параметрами, а эффективность должна оцениваться при каждом посещении пациентом врача. Однако четких рекомендаций о том, как именно проводить такую оценку, не существует. Концепция контроля хорошо разработана при лечении бронхиальной астмы, однако для ХОБЛ сформулировать таковую оказалось намного труднее. Пациенты с ХОБЛ могут продолжать испытывать симптомы болезни, даже получая оптимальную терапию; таким образом, контроль над ХОБЛ означает не полное излечение или отсутствие симптомов, а достижение наилучшего возможного клинического статуса при данной степени тяжести заболевания. Авторами данной статьи разработан инструмент для определения контроля над ХОБЛ на основе поперечного среза данных о нагрузке на здоровье пациента и лонгитюдинальной оценки стабильности его состояния. Низкая нагрузка определяется как удовлетворяющая минимум 3 критериям из следующих: низкий уровень одышки; отсутствие мокроты или белая мокрота; малое использование симптоматической терапии; 30 мин ходьбы пешком в день согласно самооценке. Стабильность определяется как отсутствие умеренно тяжелых или тяжелых обострений в предшествующие 3 мес. Контроль также осуществляется по результатам теста по оценке степени тяжести ХОБЛ (COPD Assesment Test – CAT) следующим образом: ≤ 10 единиц – для пациентов, у которых показатель объема форсированного выдоха за 1-ю секунду (ОФВ1) составляет ≥ 50 %; ≤ 16 – при ОФВ1 &lt; 50 %; стабильность определяется как изменение оценки по CAT ≤ 2 единиц. Таким образом, контроль над ХОБЛ определяется как состояние стабильно низкой нагрузки на здоровье. Инструмент для определения контроля валидирован проспективно по данным ряда исследований, при этом продемонстрированы чувствительность к изменениям клинического состояния пациентов и бόльшая прогностическая ценность по отношению к негативным исходам. Кли - нические критерии оказались надежнее в определении статуса контроля, чем баллы по CAT. Таким образом, концепция контроля – это быстрый и недорогой метод оценки клинического статуса и риска обострений в будущем, который пригоден к использованию на всех уровнях здравоохранения