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

Estructura cristalina y molecular de la 2-Cloro Isonitroacetanilida

En este trabajo se presenta la estructura cristalina y molecular de la 2-cloro isonitrosoacetanilida, derivado de la isonitrosoacetanilida, serie que constituye una línea de investigación de la Sección de Cristalografía del C.S.I.C. de Barcelona. La estructura ha sido resuelta por difracción de rayos-X. Las dimensiones de la celda elemental son: (...

Estructura cristalina y molecular de la dihidrazida malonica anhidra

[ES] En este trabajo se presenta la estructura cristalina y molecular de la hidracida malónica anhidra. La estructura cristalina ha sido resuelta por difracción de Rayos X. Las dimensiones de la celda elemental son: a = 6.986Å, b0 = 4.828Å, c0 = 17.619Å, β = 93.490, V = 593.19Å y su grupo espacial es el P21/c, Z = 4.[EN] In this paper, the crystal and molecular structure of the nalonic dihydrazide has been solved by means of the X-Ray difraction and the direct methods. The unit cell dimensions are: a = 6.986Å, b0 = 4.828Å, c0 = 17.619Å, β = 93.490, V = 593.19Å y su grupo espacial es el P21/c, Z = 4.Peer reviewe

Estructura cristalina y molecular de la dihidrazida malonica anhidra

[ES] En este trabajo se presenta la estructura cristalina y molecular de la hidracida malónica anhidra. La estructura cristalina ha sido resuelta por difracción de Rayos X. Las dimensiones de la celda elemental son: a = 6.986Å, b0 = 4.828Å, c0 = 17.619Å, β = 93.490, V = 593.19Å y su grupo espacial es el P21/c, Z = 4.[EN] In this paper, the crystal and molecular structure of the nalonic dihydrazide has been solved by means of the X-Ray difraction and the direct methods. The unit cell dimensions are: a = 6.986Å, b0 = 4.828Å, c0 = 17.619Å, β = 93.490, V = 593.19Å y su grupo espacial es el P21/c, Z = 4.Peer reviewe

Withdrawal of inhaled corticosteroids versus continuation of triple therapy in patients with COPD in real life: observational comparative effectiveness study

MPOC; Eficàcia; Corticoides inhalatsEPOC; Eficacia; Corticosteroides inhaladosCOPD; Effectiveness; Inhaled corticosteroidsBackground Inhaled corticosteroids (ICS) are indicated for prevention of exacerbations in patients with COPD, but they are frequently overprescribed. ICS withdrawal has been recommended by international guidelines in order to prevent side effects in patients in whom ICS are not indicated. Method Observational comparative effectiveness study aimed to evaluate the effect of ICS withdrawal versus continuation of triple therapy (TT) in COPD patients in primary care. Data were obtained from the Optimum Patient Care Research Database (OPCRD) in the UK. Results A total of 1046 patients who withdrew ICS were matched 1:4 by time on TT to 4184 patients who continued with TT. Up to 76.1% of the total population had 0 or 1 exacerbation the previous year. After controlling for confounders, patients who discontinued ICS did not have an increased risk of moderate or severe exacerbations (adjusted HR: 1.04, 95% confidence interval (CI) 0.94–1.15; p = 0.441). However, rates of exacerbations managed in primary care (incidence rate ratio (IRR) 1.33, 95% CI 1.10–1.60; p = 0.003) or in hospital (IRR 1.72, 95% CI 1.03–2.86; p = 0.036) were higher in the cessation group. Unsuccessful ICS withdrawal was significantly and independently associated with more frequent courses of oral corticosteroids the previous year and with a blood eosinophil count ≥ 300 cells/μL. Conclusions In this primary care population of patients with COPD, composed mostly of infrequent exacerbators, discontinuation of ICS from TT was not associated with an increased risk of exacerbation; however, the subgroup of patients with more frequent courses of oral corticosteroids and high blood eosinophil counts should not be withdrawn from ICS.The study was funded by a Grant from Boehringer Ingelheim

Long-term effect of α1-antitrypsin augmentation therapy on the decline of FEV1 in deficient patients: an analysis of the AIR database

Lung structure and function; COPD and smokingEstructura y función pulmonar; EPOC y tabaquismoEstructura i funció pulmonar; MPOC i tabaquismeBackground Patients with ZZ (Glu342Lys) α-1-antitrypsin deficiency (ZZ-AATD) who received augmentation therapy with α-1-antitrypsin (AAT) in randomised controlled trials over 2–3 years failed to show a significant reduction of the annual decline of forced expiratory volume in 1 s (FEV1). Methods To compare the trajectory of FEV1 change during 4 or more years in ZZ-AATD patients with emphysema receiving or not receiving intravenous augmentation therapy, a retrospective analysis of FEV1 values entered in the Alpha-1 International Registry (AIR) of ZZ-AATD patients from five different European countries (Germany, UK, Spain, Italy and the Netherlands) was performed. The post-bronchodilator FEV1 % predicted values for baseline and follow-up over time from patients were analysed using linear mixed effects models. Results Data of 374 patients were analysed: 246 untreated and 128 treated with intravenous AAT augmentation therapy. The mean±sd follow-up duration of the untreated group was 8.60±3.34 years and 8.59±2.62 years for the treated group. The mixed effects model analysis showed a mean FEV1 decline of −0.931% predicted per year (95% CI −1.144 to −0.718) in the untreated group and a decline of −1.016% predicted per year (95% CI −1.319 to −0.7145) in the treated group. The likelihood ratio test showed no difference between the two groups (p=0.71). Conclusion In our study population, we could not detect a significant difference in the annual decline of FEV1 by AAT augmentation treatment over a mean period of 8.6 years. Other approaches are needed to validate any benefit of augmentation therapy.This study was supported by Stichting AIR

Amerindian Ancestry Influences Genetic Susceptibility to Chronic Obstructive Pulmonary Disease

The contribution of genetic ancestry on chronic obstructive pulmonary disease (COPD) predisposition remains unclear. To explore this relationship, we analyzed the associations between 754,159 single nucleotide polymorphisms (SNPs) and risk of COPD (n = 214 cases, 193 healthy controls) in Talca, Chile, considering the genetic ancestry and established risk factors. The proportion of Mapuche ancestry (PMA) was based on a panel of 45 Mapuche reference individuals. Five PRDM15 SNPs and two PPP1R12B SNPs were associate with COPD risk (p = 0.05 to 5x10(-4)) in those individuals with lower PMA. Based on linkage disequilibrium and sliding window analyses, an adjacent PRDM15 SNPs were associated with COPD risk in the lower PMA group (p = 10(-3) to 3.77x10(-8)). Our study is the first to report an association between PPP1R12B and COPD risk, as well as effect modification between ethnicity and PRDM15 SNPs in determining COPD risk. Our results are biologically plausible given that PPP1R12B and PRDM15 are involved in immune dysfunction and autoimmunity, providing mechanistic evidence for COPD pathogenesis and highlighting the importance to conduct more genome wide association studies (GWAS) in admixed populations with Amerindian descent