Paciente exacerbador con enfermedad pulmonar obstructiva crónica: recomendaciones en procesos diagnósticos,terapéuticos y asistenciales

ObjectiveTo describe an evidence- and experience-based expert consensus on the most relevant issues of patients with COPD exacerbations.MethodsThe Delphi technique was used. Evidence was reviewed by a scientific committee and 60 experts. A questionnaire was prepared containing 3 sections: diagnosis of the exacerbator; treatment, and healthcare processes. The survey was answered in 2 rounds by 60 pneumologists on an online platform. Statements were scored on a Likert scale from 1 (total disagreement) to 9 (total agreement). Agreement and disagreement were defined as a score of 7-9 or 1-3, respectively, given by more than two thirds of the participants.ResultsA total of 48 statements were included, one of which was added in the second round. Consensus was reached in 37 items (78.7%) after the first round (agreement), and in 43 (89.5%) after the second round (42 agreement, 1 disagreement). The statements with the highest proportion of experts agreeing were as follows: in exacerbators, chronic bronchial infection favors lung function decline (93.1%); long-acting bronchodilators should not be withdrawn (93.1%); treatment must be personalized if new exacerbations occur despite optimal bronchodilator treatment (96.6%); management must be coordinated between primary care and the respiratory medicine department (93.1%), and patients must be followed up in specific integrated multicomponent programs (94.8%).ConclusionsThe findings of this study could assist in the diagnosis and treatment of COPD exacerbators in our area.     

Frequent Chronic Obstructive Pulmonary Disease Exacerbators: How Much Real,How Much Fictitious?

ABSTRACT

Exacerbations are important events in the natural history of chronic obstructive pulmonary disease (COPD). The higher the number of COPD exacerbations, the worse are the clinical and economical consequences. The distribution of COPD exacerbations is however highly variable. Some patients do not exhibit exacerbations at all whereas others suffer frequent events (i.e., “frequent COPD exacerbators”). We review the scientific evidence regarding the impact of COPD exacerbation frequency and assess whether or not these frequent exacerbators represent a unique population of COPD patients with higher morbidity and mortality risks. A definition of “frequent COPD exacerbators” is suggested to differentiate it from other related terms, such as “treatment failure” and “recurrence.” The standardization of this terminology seems to be necessary to further identify COPD phenotypes in patients who have an individual susceptibility to develop frequent exacerbations. It can also be of help to refine the most appropriate therapeutic and preventative measures.     

Antimuscarinic use and discontinuation in an older adult population

IntroductionAlthough antimuscarinics are typically the first-line pharmacological treatment option for overactive bladder, patients often discontinue therapy. The aim of this research project is to identify the rate of antimuscarinic discontinuation, switching, and continuation and differences in discontinuation among different antimuscarinics.MethodsUsing the 5% random sample of Medicare Claims Data, we identified a cohort of patients aged ≥ 66 years old who newly initiated antimuscarinics between January 1, 2007 and December 31, 2012. Treatment discontinuation was defined as no subsequent fills of the initial antimuscarinic in the days’ supply plus a 30 day grace period. We ascertained percentages of patients who discontinued antimuscarinics, switched antimuscarinics, or died within 12 months of antimuscarinic initiation. Cox proportional hazards models were used to determine time to discontinuation of individual antimuscarinics relative to oxybutynin immediate-release (IR).ResultsAmong the 42,886 new-users of antimuscarinics, 71.8% discontinued, 10.8% switched, and 3.2% died prior to antimuscarinic discontinuation or switching while only 14.2% continually filled an antimuscarinic for one year. In the multivariable analysis, patients who were initiated on oxybutynin extended-released (ER), tolterodine, trospium, darifenacin, solifenacin, and fesoterodine were significantly less likely to be discontinued therapy compared to oxybutynin IR (p < 0.001).ConclusionAfter one year of antimuscarinic initiation, only 14% of older adult patients continuously utilized their initial antimuscarinic therapy suggesting a need for clinical interventions to improve continual use of antimuscarinics.     

Effectiveness of Treatment With Dual Bronchodilation (LABA/LAMA) Compared With Combination Therapy (LABA/ICS) for Patients With COPD: A Population-Based Study

BackgroundInitiation of treatment of COPD with a combination of a long-acting beta-agonist (LABA) and an inhaled corticosteroid (ICS) is frequent irrespective of the risk of exacerbations.MethodWe performed a retrospective, population-based, observational study aimed at comparing the effectiveness of a LABA/long-acting antimuscarinic agent (LAMA) and LABA/ICS in patients with COPD over a one-year follow-up. Data were obtained from an administrative healthcare claims database. The primary outcome was the risk of first exacerbation. A sensitivity analysis was conducted in a propensity-score matched population.ResultsThe population consisted of 14,046 COPD patients; 11,329 (80.6%) initiated LABA/ICS and 2717 (19.4%) LABA/LAMA. The matched population included 1650 patients in each arm. During follow-up, 69.6% patients in the LABA/ICS group and 64.4% in the LABA/LAMA group presented an exacerbation. The mean time to the first exacerbation was 6.03 months (95% confidence interval (CI): 5.94–6.12) for LABA/ICS and 6.4 months (95%CI: 6.21–6.59) for LABA/LAMA; p < 0.001. The time to scalation to triple therapy was also significantly prolonged in LABA/LAMA. Similar results were obtained in the matched population. LABA/LAMA was associated with a significantly lower risk of exacerbations and escalation to triple therapy compared to LABA/ICS, except in patients with frequent exacerbations and high blood eosinophils in which no differences were observed in the time to first exacerbation.ConclusionInitiation of treatment with LABA/LAMA was associated with a lower risk of exacerbation and escalation to triple therapy compared to LABA/ICS in the majority of patients with COPD in primary care.     

Incidence,Predictors, and Clinical Implications of Discontinuing Therapy with Inhaled Long-Acting Bronchodilators among Patients with Chronic Obstructive Pulmonary Disease

Incidence, predictors and effect of discontinuation of long-acting bronchodilators on the risk of death or hospital admission among adults with Chronic Obstructive Pulmonary Disease (COPD) were assessed in a large population-based prospective study carried out by linking Italian healthcare utilization databases. Specifically, the cohort of 17,490 beneficiaries of the National Health Service in the Italian Region of Lombardy, aged 40 years or older, who started long-acting bronchodilators therapy during 2005–2008 was followed from first dispensation until 2012. During this period, patients who experienced discontinuation of long-acting bronchodilators were identified. Hospitalizations for COPD and deaths for any cause (composite clinical outcome) were also identified during follow-up. A Cox proportional hazards model was fitted to identify predictors of discontinuation. The case-crossover design was used to assess the implications of treatment discontinuation on the clinical outcome risk. Cumulative incidences of discontinuation were, respectively, 67%, 80%, and 92% at 6 months, 1 year, and 5 years since initial treatment. Significant predictors of discontinuation were female gender, younger age, starting treatment with fixed-dose combination of inhaled bronchodilators and corticosteroids, using antibiotics, inhaled long-acting bronchodilators and corticosteroids and not using short-acting bronchodilators, other respiratory drugs and systemic corticosteroids during follow-up. Odds ratios (95% confidence intervals) for the clinical outcome associated with not discontinuing long-acting bronchodilators was 0.64 (0.50 to 0.82). In conclusion, in the real-life setting, discontinuation of inhaled long-acting bronchodilators in adults with COPD is high even after just 6 months, even though persistence to these drugs reduces the risk of severe outcomes.     

Triple Therapy for the Management of COPD: A Review

Triple therapy for COPD consists of a long-acting anti-cholinergic bronchodilator, a long-acting beta-agonist bronchodilator, and an inhaled corticosteroid. Guidelines from the Canadian Thoracic Society advocate triple therapy for some patients with moderate-to-severe COPD. The objective of this review was to evaluate the evidence based clinical efficacy of triple therapy compared to dual bronchodilator therapy (long-acting anti-cholinergic bronchodilator + beta-agonist bronchodilator) or long-acting anti-cholinergic bronchodilator monotherapy for managing COPD. A systematic literature search was conducted to identify relevant clinical evaluations of triple therapy in the management of moderate to severe COPD. Databases searched included: Medline; EMBASE; CINAHL and PubMed (non-Medline records only). Of 2,314 publications, 4 articles evaluated triple therapy for the management of COPD. Hospitalization rates for COPD exacerbations, reported in 2 trials, were significantly reduced with triple therapy compared to long-acting anti-cholinergic bronchodilator monotherapy, with reported relative risks of 0.53 (95% CI: 0.33, 0.86, p = 0.01) and 0.35 (95% CI: 0.16–0.78, p = 0.011). Exacerbation data is inconsistent between the two trials reporting this outcome. Lung function, dyspnea and quality of life data show statistical significant changes with triple therapy compared to long-acting anti-cholinergic bronchodilator monotherapy but the changes do not reach clinical importance. Triple therapy does decrease the number of hospitalizations for severe/acute COPD exacerbations compared with long-acting anti-cholinergic bronchodilator monotherapy. There is insufficient evidence to determine if triple therapy is superior to dual bronchodilator therapy.     

Time Trends in Glucocorticoid Use in Rheumatoid Arthritis During the Biologics Era: 1999-2018

ObjectivesTo examine time trends in glucocorticoid (GC) use among patients diagnosed with rheumatoid arthritis (RA) during the biologic era.MethodsA population-based inception cohort of RA patients diagnosed during 1999 – 2018 was followed longitudinally through their medical records until death, migration or 12/31/2020. All patients fulfilled 1987 American College of Rheumatology classification criteria for RA. GC start and stop dates were collected along with dosages in prednisone equivalents. The cumulative incidence of GC initiation and discontinuation adjusted for the competing risk of death was estimated. Cox models adjusted for age and sex were used to compare trends between time periods.ResultsThe study population included 399 patients (71% female) diagnosed in 1999 – 2008 and 430 patients (67% female) diagnosed in 2009 – 2018. GC use was initiated within 6 months of meeting RA criteria in 67% of patients in 1999-2008 and 71% of patients in 2009-2018, corresponding to a 29% increase in hazard for initiation of GC in 2009-2018 (adjusted hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 1.09-1.53). Among GC users, similar rates of GC discontinuation within 6 months after GC initiation were observed in patients with RA incidence in 1999 – 2008 and 2009 – 2018 (39.1% versus 42.9%, respectively), with no significant association in adjusted Cox models (HR: 1.11; 95% CI: 0.93-1.31).ConclusionMore patients are initiating GCs early in their disease course now compared to previously. The rates of GC discontinuation were similar, despite the availability of biologics.     

Project PriMo: Sharing principles and practices of bronchodilator therapy monitoring in COPD: A consensus initiative for optimizing therapeutic appropriateness among Italian specialists

BackgroundEven after publication of the 2011 update of GOLD report, some fundamental questions in the management of COPD are still open and this may weaken the applicability of these guidelines in everyday clinical practice.ObjectiveTo assess the level of consensus amongst Italian respirologists on different topics related to diagnosis, monitoring and role of bronchodilator therapy in COPD, by using the Delphi technique.MethodsA Delphi study was undertaken between July and November 2011, when two questionnaires were consecutively sent to a panel of experts to be answered anonymously. After each round, the data were aggregated at group level of question topics and structured feedback was given to the panel.ResultsA first-round questionnaire was sent to 208 pulmonologists randomly selected from different Italian regions. The 132 respondents (63% of those initially selected) were from northern (53%), central (19%) and southern (28%) Italy. A second-round questionnaire was sent to all the first-round respondents, and a response was received from 110 of them (83%). The main topics that reached the pre-defined cut off for consensus (67% or more) were: a) bronchodilator therapy with long-acting bronchodilators could be beneficial in patients with airflow limitation even in the absence of symptoms, b) in patients not fully controlled with one long-acting bronchodilator, maximizing bronchodilation (i.e. adding another bronchodilator with a different mechanism of action) is the preferable option; and c) the use of inhaled corticosteroids (ICSs) as add on therapy should be considered in severe patients with frequent exacerbations.ConclusionsItalian specialists agree on several aspects of the diagnosis and treatment of COPD and expert opinion could support everyday decision process in the management of COPD.     

Utilization Pattern of Mineralocorticoid Receptor Antagonists in Contemporary Patients Hospitalized With Acute Decompensated Heart Failure: A Single-Center Experience

BackgroundRecent studies have broadened the potential use of mineralocorticoid receptor antagonist (MRA) in patients with systolic heart failure after cardiovascular hospitalization. Real-world data on safety and tolerability of MRA initiation during hospitalization for acute decompensated heart failure (ADHF) are lacking. We examined the patterns of utilization of MRAs in patients admitted for ADHF in contemporary clinical practice.Methods and ResultsWe reviewed consecutive hospitalized patients admitted with a primary diagnosis of ADHF from March to June 2011. The treatment patterns of MRA use or discontinuation before, during, and after hospitalization were reviewed and analyzed retrospectively. In the study cohort of 500 patients, 106 patients (21%) were on MRAs before admission. During hospitalization, preadmission and newly started MRAs were discontinued in 64 out of 177 (36%), with worsening renal function being the most common identifiable reason. In a multivariate analysis, high admission creatinine was the only significant predictor of MRA discontinuation during hospitalization (P = .01). Of the 394 patients who did not receive MRA before admission, 81 were eligible for MRAs, but only 17 (21%) were initiated. After a median follow up of 57 days, 21 additional patients discontinued MRAs; of 72 eligible patients for MRA, 55 patients (76%) were still appropriately taking it.ConclusionsDespite recent data, MRAs are still underutilized in patients admitted with ADHF who are otherwise eligible for it. Elevated serum creatinine and worsening of renal function are the most common cause of in-hospital discontinuation, which highlights the importance of meticulous follow-up after MRA initiation.     

Documento de consenso «Uso adecuado de los corticoides inhalados en la enfermedad pulmonar obstructiva crónica»

IntroductionIndications for inhaled corticosteroids (IC) in combination with long-acting bronchodilators (LABD) are well defined in clinical practice guidelines. However, there are some doubts about their efficacy and safety. The aim of this document is to establish an expert consensus to clarify these issues.MethodA coordinator group was formed, which systematically reviewed the scientific evidence with the aim of identifying areas of uncertainty about the efficacy of ICs, the adverse effects associated with their use and criteria for withdrawal. Their proposals were submitted to a panel of experts and the Delphi technique was used to test the level of consensus.ResultsTwenty-five experts participated in the panel, and consensus was reached on the use of IC in the mixed chronic obstructive pulmonary disease (COPD)-asthma phenotype and in frequent exacerbators, and on not using IC in association with LABD for improving lung function in COPD. There was no general consensus on restricting the use of IC to prevent adverse effects. The panel did agree that IC withdrawal is feasible but should be undertaken gradually, and patients who have discontinued must be evaluated in the short term.ConclusionsConsensus was reached regarding the indication of IC in mixed COPD-asthma and frequent exacerbator phenotypes. The potential for adverse effects must be taken into consideration, but there is no consensus on whether limiting use is justified. The withdrawal of ICs was uniformly agreed to be feasible.     

Adherence to Long-Acting Inhaled Therapies among Patients with Chronic Obstructive Pulmonary Disease (COPD)

Abstract

Background: Long-acting inhaled medications are an important component of the treatment of patients with chronic obstructive pulmonary disease (COPD), yet few studies have examined the determinants of medication adherence among this patient population. Objective: We sought to identify factors associated with adherence to long-acting beta-agonists (LABA) and inhaled corticosteroids (ICS) among patients with COPD. Methods: We performed secondary analysis of baseline data collected in a randomized trial of 376 Veterans with spirometrically confirmed COPD. We used electronic pharmacy records to assess adherence, defined as a medication possession ratio of ≥0.80. We investigated the following exposures: patient characteristics, disease severity, medication regimen complexity, health behaviors, confidence in self-management, and perceptions of provider skill. We performed multivariable logistic regression, clustered by provider, to estimate associations. Results: Of the 167 patients prescribed LABA, 54% (n = 90) were adherent to therapy while only 40% (n = 74) of 184 the patients prescribed ICS were adherent. Higher adherence to LABA and ICS was associated with patient perception of their provider as being an “expert” in diagnosing and managing lung disease [For LABA: OR = 21.70 (95% CI 6.79, 69.37); For ICS OR = 7.93 (95% CI 1.71, 36.67)]. Factors associated with adherence to LABA, but not ICS, included: age, education, race, COPD severity, smoking status, and confidence in self-management. Conclusions: Adherence to long-acting inhaled medications among patients with COPD is poor, and determinants of adherence likely differ by medication class. Patient perception of clinician expertise in lung disease was the factor most highly associated with adherence to long-acting therapies.     

The role of long-acting muscarinic antagonist/long-acting β agonist fixed-dose combination treatment for chronic obstructive pulmonary disease in China: a narrative review

ObjectiveTo provide an overview of the existing international and Chinese evidence regarding dual bronchodilator inhalation therapy and to make recommendations for the further improvement of chronic obstructive pulmonary disease (COPD) management in clinical practice in China.BackgroundCOPD is a progressive lung disease that is characterized by persistent airflow limitation and is a major contributor to the disease burden in China. Symptoms in Chinese patients are relatively more severe. Currently, many Chinese COPD patients are undertreated. Dual bronchodilator therapy consisting of a long-acting muscarinic antagonist (LAMA) and a long-acting β agonist (LABA) is considered a good choice for COPD patients due to the increased bronchodilation without an increase in adverse events; these combinations can fill in the gap in currently available COPD treatments and provide new pharmacotherapy options for Chinese patients. LAMA/LABA fixed-dose combinations (FDCs) have become more important in clinical practice and guidelines in China regarding their therapeutic effects and safety.MethodsClinical trials on LAMA/LABA in COPD were retrieved in ClinicalTrials.gov, while important COPD guidelines published in English or Chinese were found in PubMed and Wanfang Database.ConclusionsWe recommend the adoption of a clinical pathway in China that includes an assessment and management algorithm that considers the clinical characteristics in China and classifies the phenotypic characteristics of COPD according to a suitable system. Based on the current information, we can conclude that LAMA/LABA FDCs are a suitable and economically viable choice to reduce symptoms and improve the quality of life (QoL) of patients.     

Triple versus LAMA/LABA combination therapy for Japanese patients with COPD: A systematic review and meta-analysis

BackgroundIn symptomatic COPD patients with a history of exacerbations, additional treatment with inhaled corticosteroid (ICS) to long-acting muscarinic antagonist (LAMA) and long-acting beta-agonist (LABA) combination therapy is recommended based on the evidence of low incidence of exacerbations but with a caution for pneumonia. However, ethnic differences may affect the response to drugs. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of this treatment in the Japanese population (PROSPERO: CRD42020191978).MethodsWe searched relevant randomized control trials and analyzed the exacerbations, quality of life, lung function, and adverse events including pneumonia and mortality as the outcomes of interest.ResultsWe identified a total of three RCTs (N = 632). Treatment with ICS/LAMA/LABA triple therapy significantly decreased the exacerbations (rate ratio, 0.56; 95% CI, 0.38 to 0.85) and improved the trough FEV₁ (mean difference, 0.04; 95% CI, 0.01 to 0.07) compared to LAMA/LABA therapy. However, triple therapy showed a significantly higher incidence of pneumonia compared to LAMA/LABA (odds ratio, 3.38; 95% CI, 1.58 to 7.22). Concerning other adverse events including mortality, there were no significant difference between these therapies.ConclusionsIn the current meta-analysis of the Japanese population, we confirmed that triple therapy causes a higher incidence of pneumonia than LAMA/LABA treatment but is a more preferable treatment since it showed a lower incidence of exacerbations and higher trough FEV₁ in patients with symptomatic moderate to severe COPD. However, since the sample sizes were not statistically large enough, further trials involving Japanese patients are needed.     

Treatment patterns and intensification within 5 year of follow-up of the first-line anti-TNFα used for the treatment of IBD: Results from the VERNE study

BackgroundAnti-TNFα represent one of the main treatment approaches for the management of inflammatory bowel diseases (IBD). Therefore,the evaluation of their treatment patterns over time provides valuable insights about the clinical value of therapies and associated costs.AimsTo assess the treatment patterns with the first anti-TNFα in IBD.MethodsRetrospective, observational study.Results310 IBD patients were analyzed along a 5-year follow-up period. 56.2% of Crohn's disease (CD) patients started with adalimumab (ADA), while 43.8% started with infliximab (IFX). 12.9% of ulcerative colitis (UC) patients initiated with ADA, while 87.1% initiated with IFX. Treatment intensification was required in 28.9% of CD and 37.1% of UC patients. Median time to treatment intensification was shorter in UC than in CD (5.3 vs. 14.3 months; p = 0.028). Treatment discontinuation due to reasons other than remission were observed in 40.7% of CD and 40.5% of UC patients, although, in UC patients there was a trend to lower discontinuation rates with IFX (36.6%) than with ADA (66.7%). Loss of response accounted for approximately one-third of discontinuations, in both CD and UC.ConclusionsAround one-third of IBD biologic-naive patients treated with an anti-TNFα required treatment intensification (earlier in UC) and around 40% discontinued the anti-TNFα due to inappropriate disease control.