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Background: Currently, there is conflicting information and guidance on the effective management of Alpha 1 Antitrypsin Deficiency (AATD). Establishing a consensus of assessment and disease management specific to AATD is important for achieving a standardized treatment pathway and for improving patient outcomes. Here, we aim to utilize the Delphi method to establish a European consensus for the assessment and management of patients with severe AATD. Methods: Two rounds of a Delphi survey were completed online by members of the European Alpha-1 Research Collaboration (EARCO). Respondents were asked to indicate their agreement with proposed statements for patients with no respiratory symptoms, stable respiratory disease, and worsening respiratory disease using a Likert scale of 1–7. Levels of agreement between respondents were calculated using a weighted average. Results: Round 1 of the Delphi survey was sent to 103 members of EARCO and 38/103 (36.9%) pulmonologists from across 15 countries completed all 109 questions. Round 2 was sent to all who completed Round 1 and 36/38 (94.7%) completed all 79 questions. Responses regarding spirometry, body plethysmography, high-resolution computed tomography, and the initiation of augmentation therapy showed little variability among physicians, but there was discordance among other aspects, such as the use of low-dose computed tomography in both a research setting and routine clinical care. Conclusions: These results provide expert opinions for the assessment and monitoring of patients with severe AATD, which could be used to provide updated recommendations and standardized treatment pathways for patients across Europe. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of alpha-1 antitrypsin deficiency (AATD) in Macaronesia (i.e., Azores, Madeira, Canary Islands, and Cape Verde archipelagos) is poorly known. Our goal was to update it by selecting the most reliable available articles. Method: Literature search using MEDLINE, Embase (via Ovid), and Google Scholar, until December 2023, for studies on prevalence of AATD in the general population and in screenings, published in peer-reviewed journals. Results: Three studies carried out in the general population of Madeira, La Palma, and Cape Verde, and three screenings carried out in La Palma (2) and Gran Canaria (1) were selected. The frequencies of PI*S in the general population showed an ascending gradient, from South to North, with values (per thousand) of 35 in Cape Verde, 82 in La Palma, and 180 in Madeira. The PI*Z frequencies showed this same gradient, with values of 2 × 1,000 in Cape Verde, 21 in La Palma, and 25 in Madeira. Screenings detected high percentages of defective alleles, including several rare and null alleles, some unique to these islands. Conclusion: The frequencies of PI*S and PI*Z in Madeira are comparable to the highest in the world. Those of the Canary Islands are similar to those of the peninsular population of Spain, and contrast with the low rates of Cape Verde. Screenings detected high numbers of deficient alleles. These results support the systematic investigation of AATD in clinically suspected patients and in relatives of index cases, to reduce underdiagnosis and apply early preventive and therapeutic measures in those affected. [ABSTRACT FROM AUTHOR]

Background: Alpha-1 antitrypsin deficiency (AATD) is an underdiagnosed condition despite being one of the most common inherited disorders in adults that is associated with an increased risk of developing chronic obstructive pulmonary disease (COPD). The aim was to evaluate the frequency of performing AAT levels and associated factors in COPD patients in an audit conducted in 2021–2022, as well as to compare with a previous audit conducted in 2014–2015. Methods: EPOCONSUL 2021 is a cross-sectional audit that evaluated the outpatient care provided to COPD patients in respiratory clinics in Spain based on available data from medical registries. Results: 4225 patients with a diagnosis of COPD from 45 centers were audited in 2021. A total of 1670 (39.5%) patients underwent AAT determination. Being treated at a specialized COPD outpatient clinic (OR 1.88, p = 0.007), age ≤ 55 years old (OR 1.84, p = 0.007) and a FEV1 < 50% (OR 1.86, p < 0.001) were associated with a higher likelihood of being tested for AAT, while Charlson index ≥ 3 (OR 0.63, p < 0.001) and genotyping of AATD availability (OR 0.42, p < 0.001) showed a statistically significant negative association. The analysis of cases included in respiratory units that participated in both audits showed an increase in the proportion of cases with AAT serum level testing available (adjusted OR 2.81, p < 0.001). The percentage of individuals with serum AAT levels < 60 mg/dL (a severe AATD) was 4%. Conclusions: Our analysis identifies significant improvements in adherence to the recommendation to test AAT levels in COPD patients, performed in 4 out of 10 patients, being more likely at younger ages and with higher COPD severity, and with a detection of severe AATD of 4% among those tested, suggesting that clinicians still perform AAT testing in COPD patients selectively. Therefore, efforts are still needed to optimize AATD screening and establish new early detection strategies to reduce morbidity and mortality in these patients. [ABSTRACT FROM AUTHOR]

Poor sleep quality is frequent among COPD patients and it has been related to worse outcomes. The objective of this study was to compare the COPD and Asthma Sleep Impact Scale (CASIS) and the generic Pittsburgh Sleep Quality Index (PSQI) questionnaires as reliable tools for evaluating sleep quality and its relationship with COPD characteristics and survival. Stable COPD patients were prospectively evaluated. Anthropometric, sociodemographic, comorbidity, lung function and treatment data were collected. All patients completed CASIS and PSQI, mMRC dyspnea severity scale, COPD Assessment Test (CAT), sleep apnoea STOP-Bang and Hospital Anxiety and Depression Scale (HADS) questionnaires. Body mass index, airflow Obstruction, Dyspnea and Exacerbations (BODEx) index was calculated. Life status was determined after a mean follow-up of 3.7 (SD 1) years. We included 200 patients, 69.5% male, mean age 65.8 (9) years. Poor sleep was detected in 100 (50%) and 84 patients (42%) according to PSQI and CASIS questionnaires, respectively, with an agreement of 63%. Poor sleep was related to female gender, more severe dyspnea and worse BODEx, HADS and CAT scores according to both questionnaires. PSQI was associated to chronic pain or inferior urinary tract symptoms and CASIS to exacerbations, shorter walked distance in the 6-min walking test and treatment with oral corticosteroids or chronic oxygen. Thirty nine (19.5%) patients died during follow-up. Mortality was not associated to PSQI nor CASIS results. Unlike PSQI, CASIS is more related to COPD severity and its results are not influenced by comorbidities with known impact on sleep quality. In our sample, poor sleep quality was not associated with increased mortality. [ABSTRACT FROM AUTHOR]

Background: The objective of this analysis is to evaluate tobacco use and the level of chronic obstructive pulmonary disease (COPD) knowledge among the general adult population in Spain and to compare these results to those obtained in the 2011 survey. Methods: A cross-sectional, observational, epidemiological study was conducted by telephone interviews and stratified by sex, age, and setting. The study design was identical to that of the study conducted in 2011. Results: Of a total of 89,601 phone contacts, there were 6534 respondents. The average age was 61.5 years. With respect to smoking, 30.9% reported being former smokers and 14.7% were current smokers, 63.6% of whom reported having attempted to quit. Among the current smokers, 19.7% claimed to use electronic cigarettes, although 88% believe these pose a health risk. No significant differences were found in smoking prevalence or frequency of attempts to quit according to residential setting (rural/urban). The highest prevalence of current smoking in men was recorded in the 55–64 years age range (31.6%), while in women it was from 45 to 54 years (34.6%). Smoking has decreased with respect to 2011, from 21.1% to 16.1% in men and from 17.9% to 13.2% in women, with a clear variability according to region. Of the population surveyed, 32.5% had spontaneous knowledge about COPD, with significant geographic variability. The most frequent sources of information about the disease were social media and the Internet (39.6%), followed by the media (35.2%). Conclusions: The prevalence of tobacco use in adults has considerably decreased and there is greater knowledge about COPD in Spain, although there is significant variability according to region, which could explain the geographic variability in the prevalence of COPD. Strategies are needed to increase COPD education and awareness and to reinforce smoking prevention measures among women. [ABSTRACT FROM AUTHOR]

Background: Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history. Methods: The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels < 11 μM and/or proteinase inhibitor genotypes PI*ZZ, PI*SZ and compound heterozygotes or homozygotes of other rare deficient variants. We describe the characteristics of the individuals included from February 2020 to May 2022. Results: A total of 1044 individuals from 15 countries were analysed. The most frequent genotype was PI*ZZ (60.2%), followed by PI*SZ (29.2%). Among PI*ZZ patients, emphysema was the most frequent lung disease (57.2%) followed by COPD (57.2%) and bronchiectasis (22%). Up to 76.4% had concordant values of FEV1(%) and KCO(%). Those with impairment in FEV1(%) alone had more frequently bronchiectasis and asthma and those with impairment in KCO(%) alone had more frequent emphysema and liver disease. Multivariate analysis showed that advanced age, male sex, exacerbations, increased blood platelets and neutrophils, augmentation and lower AAT serum levels were associated with worse FEV1(%). Conclusions: EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function. Trial registrationwww.clinicaltrials.gov (ID: NCT04180319) [ABSTRACT FROM AUTHOR]

Background: Persistent airflow limitation and dyspnoea may reduce chronic obstructive pulmonary disease (COPD) patients exercise capacity and physical activity, undermining their physical status and quality of life. Long-acting muscarinic antagonists and long-acting beta-2 agonists (LAMA/LABA) combinations are amongst moderate-to-severe COPD recommended treatments. This article analyses LAMA/LABA combinations effect on COPD patients exercise capacity and physical activity outcomes. Methods: A systematic review and meta-analysis of double-blind randomized controlled trials comparing LAMA/LABA combinations against monotherapy or placebo was conducted. Results: Seventeen articles were identified (N = 4041 patients). In endurance shuttle walk test and constant work rate cycle ergometry, LAMA/LABA combinations obtained better results than placebo, but not monotherapy, whereas in 6-min walking test, results favoured LAMA/LABA over monotherapy (four studies), but not over placebo (one study). Moreover, LAMA/LABA combinations obtained better results than placebo in number of steps per day, reduction in percentage of inactive patients and daily activity-related energy expenditure, and better than monotherapy when measuring time spent on ≥ 1.0–1.5, ≥ 2.0 and ≥ 3.0 metabolic equivalents of task activities. Conclusions: LAMA/LABA combinations in COPD patients provided better results than monotherapy or placebo in most exercise capacity and physical activity outcomes. [ABSTRACT FROM AUTHOR]

Inhaled bronchodilators (alone or in combination) are the cornerstone of treatment for symptomatic patients with COPD, either as initial/first-line treatment or for second-line/treatment escalation in patients who experience persistent symptoms or exacerbations on monotherapy. The Global Initiative for Chronic Obstructive Lung Disease 2022 report recommends initial pharmacological treatment with a long-acting muscarinic antagonist (LAMA) or a long-acting β2-agonist (LABA) as monotherapy for most patients, or dual bronchodilator therapy (LABA/LAMA) in patients with more severe symptoms, regardless of exacerbation history. The recommendations for LABA/LAMA are broader in the American Thoracic Society treatment guidelines, which strongly recommend LABA/LAMA combination therapy over LAMA or LABA monotherapy in patients with COPD and dyspnea or exercise intolerance. However, despite consistent guideline recommendations, real-world prescribing data indicate that LAMA and/or LABA without an inhaled corticosteroid are not the most widely prescribed therapies in COPD. This article reviews global and regional/national guideline recommendations for the use of LABA/LAMA in COPD, examines the evidence for the effectiveness and safety of LABA/LAMA versus other therapies and offers a practical guide for clinicians to help ensure appropriate use of LABA/LAMA therapy. [ABSTRACT FROM AUTHOR]

Background: 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. [ABSTRACT FROM AUTHOR]

Background and objective: The concept of clinical control in COPD has been developed to help in treatment decisions, but it requires validation in prospective studies. Methods: This international, multicentre, prospective study aimed to validate the concept of control in COPD. Patients with COPD were classified as controlled/uncontrolled by clinical criteria or CAT scores at baseline and followed up for 18 months. The main outcome was the difference in rate of a composite endpoint of moderate and severe exacerbations or death over the 18‐month follow‐up period. Results: A total of 307 patients were analysed (mean age = 68.6 years and mean FEV1% = 52.5%). Up to 65% and 37.9% of patients were classified as controlled by clinical criteria or CAT, respectively. Controlled patients had significantly less exacerbations during follow‐up (by clinical criteria: 1.1 vs 2.6, P < 0.001; by CAT: 1.1 vs 1.9, P = 0.014). Time to first exacerbation was significantly prolonged for patients controlled by clinical criteria only (median: 93 days, IQR: 63; 242 vs 274 days, IQR: 221; 497 days; P < 0.001). Control status by clinical criteria was a better predictor of exacerbations compared to CAT criteria (AUC: 0.67 vs 0.57). Conclusion: Control status, defined by easy‐to‐obtain clinical criteria, is predictive of future exacerbation risk and time to the next exacerbation. The concept of control can be used in clinical practice at each clinical visit as a complement to the current recommendations of initial treatment proposed by guidelines. [ABSTRACT FROM AUTHOR]

Alpha-1 antitrypsin deficiency (AATD) is a rare and underdiagnosed disease that is associated with the development of liver disease in adults and children and pulmonary emphysema in adults. Several studies have shown that there is limited knowledge about the disease and its diagnosis among health care providers, and there is an important inequity in the access to specialized care and appropriate treatment across Europe. The European Commision and the European Respiratory Society (ERS) recommend that the care of patients with AATD must be organized in reference centers at national or regional levels. These reference centers must provide optimal clinical care in terms of adequate diagnostic techniques, such as phenotyping and genotyping, and ensure access to treatment according to guidelines. Reference centers should also provide continuous medical education for health care professionals, genetic counseling, collaboration with patient associations and promote collaborative research and clinical trials with new and existing treatments for the disease. These centers must have a registry of their activity and collaborate with large, international, multicenter registries, such as the European Alpha-1 antitrypsin Deficiency Research Collaboration (EARCO) international registry, which is endorsed by the ERS, and aims to recruit up to 3,000 patients over a period of three years and prospectively follow them to better understand the natural history of the disease and the impact of different treatments on outcomes in a real life setting. International collaboration and standardized collection of high-quality prospective data will provide new insights into the clinical manifestations and prognosis of AATD. [ABSTRACT FROM AUTHOR]

Background: Bronchodilators are the mainstay of pharmacological treatment in chronic obstructive pulmonary disease (COPD), and long-acting muscarinic antagonist (LAMA) monotherapy is recommended as initial treatment for Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups B, C, and D.Main Body: Tiotropium bromide was the first LAMA available for COPD in clinical practice and, because of its long duration of action, is administered once daily. Tiotropium was initially available as an inhalation powder delivered via a dry-powder inhaler (DPI). Later, tiotropium also became available as an inhalation spray delivered via a soft mist inhaler (SMI). The SMI was designed to overcome or minimize some of the issues associated with other inhaler types (eg, the need for strong inspiratory airflow with DPIs). Results of short- and long-term randomized, controlled clinical trials of tiotropium in patients with COPD indicated tiotropium was safe and significantly improved lung function, health-related quality of life, and exercise endurance, and reduced dyspnea, lung hyperinflation, exacerbations, and use of rescue medication compared with placebo or active comparators. These positive efficacy findings triggered the evaluation of tiotropium in fixed-dose combination with olodaterol (a long-acting β2-agonist). In this review, we provide an overview of studies of tiotropium for the treatment of COPD, with a focus on pivotal studies.Conclusion: Tiotropium is safe and efficacious as a long-term, once-daily LAMA for the maintenance treatment of COPD and for reducing COPD exacerbations. The SMI generates a low-velocity, long-duration aerosol spray with a high fine-particle fraction, which results in marked lung drug deposition. In addition, high inspiratory flow rates are not required. [ABSTRACT FROM AUTHOR]

In each box plot, the median value is indicated by the center horizontal black line, the 25th and 75th percentiles are indicated by the lower and upper box horizontal lines, and the mean value is indicated by the center horizontal white line. Clinical and functional characteristics of individuals with alpha-1 antitrypsin deficiency: EARCO international registry. [Extracted from the article]

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality, with exacerbations contributing strongly to the overall severity and burden of disease at the individual level. Many patients with COPD are managed predominantly in the primary care setting; therefore, primary care physicians (PCPs) must be aware of and understand the causes, effects, and management of COPD exacerbations. This review offers practical information about how exacerbations are defined in the treatment setting, pathogenic and environmental causes, options for exacerbation treatment and prevention, and suggestions for improving care in the clinic. Exacerbations have a strong negative effect on patients and are associated with an increased risk of further exacerbations and decreases in lung function. Thus, it is important that exacerbations not requiring hospitalization be identified and confidently managed in the clinical setting. Understanding treatment options for acute exacerbations and maintenance treatment to prevent future exacerbations may help PCPs better understand what they can do to support their patients. This review aims to provide useful guidance for PCPs to identify exacerbations and adjust their practice for optimal management of exacerbations in patients with COPD. It also aims to encourage PCPs that they have an important task in integrating effective COPD management into the primary care setting. [ABSTRACT FROM AUTHOR]

COPD is often misdiagnosed and inappropriately treated in many patients. COPD is a distinct disease from adult-onset asthma; however, some patients with COPD may present with several forms of airway disease described as asthma-COPD overlap (ACO). Bronchodilators and inhaled corticosteroids (ICS) both have a place in standard maintenance treatment of COPD and asthma; however, recommendations for use differ widely. In patients with COPD, long-acting bronchodilators are effective initial monotherapy treatment, whereas ICS monotherapy is recommended as initial treatment in patients with asthma. Clinicians need to be confident in their diagnosis to ensure that correct treatment is given because misguided treatment decisions can result in significantly increased safety risks for patients. This review highlights the differences in diagnosis and treatment between COPD, asthma, and ACO and discusses the data supporting guideline recommendations for use of bronchodilators in COPD treatment in contrast to asthma or ACO. [ABSTRACT FROM AUTHOR]

The incidence of chronic obstructive pulmonary disease (COPD) is rising in the United States, and the disease represents a significant source of morbidity and mortality. Primary care providers face many challenges in COPD diagnosis and treatment, as different clinical phenotypes require personalized treatment approaches. Patient adherence and inhaler technique also contribute to treatment outcomes. Around 48% of primary care providers are unaware of guidelines and recommendations for COPD diagnosis and treatment, which may lead to misdiagnosis or undertreatment of COPD symptoms. Inadequately treated COPD can impair patients' quality of life and ability to perform everyday activities. Long-acting bronchodilator therapy is the cornerstone treatment for patients with COPD; combinations of bronchodilators of different pharmacological classes have shown improved efficacy vs monotherapy. We review the rationale behind fixed-dose dual bronchodilator therapy, evidence for the 4 currently Food and Drug Administration-approved long-acting anticholinergic bronchodilators/long-acting β2-agonists fixed combinations, patient suitability for the available inhaler devices, and practical guidance to optimize personalized care for patients with COPD. [ABSTRACT FROM AUTHOR]

Background This study aimed to identify the relevant factors for the choice of an inhaler device by physicians and the selection of the most important characteristics of a device according to different characteristics of patients with COPD. Method In this two-round Delphi survey, 96 Spanish COPD-expert pulmonologists completed an internet-based, self-administered questionnaire, which consisted of a first part with 19 items related to the prioritization of the drug or the device, the experience, ability and preference of the patient, and the experience and preferences of the healthcare professional. For each item, responses were grouped into three categories based on a 9-point Likert-type scale, calculating the response frequency and the degree of consensus. The second part included 18 items related to the inhalation devices with the aim to identify the main characteristics of a device for 8 different profiles of patients with COPD. Results Experts considered that the selection of a device was relevant when choosing the treatment for COPD patients, although 62.5% of them prioritised the selection of the drug over the device. The experience of the patient (89.6%) and his/her ability to handle the device (97.9%), together with coordination (96.9%), ability to learn (87.5%) and adherence to therapy (84.4%) were the main aspects considered in the selection of inhalation device. The panel identified Respimat ® as the most adequate device for patients with either low inspiratory flow or severely impaired lung function and Spiromax ® for patients with either impaired fine motor skills or older than 70 years. Conclusions Selection of the inhalation device is recognized by specialists as a strategic therapeutic decision and should be based on the characteristics of the individual patient. Some devices may be more adequate for different patient profiles. [ABSTRACT FROM AUTHOR]

Clinical practice guidelines are ubiquitous and are developed to provide recommendations for the management of many diseases, including chronic obstructive pulmonary disease. The development of these guidelines is burdensome, demanding a significant investment of time and money. In Europe, the majority of countries develop their own national guidelines, despite the potential for overlap or duplication of effort. A concerted effort and consolidation of resources between countries may alleviate the resource-intensity of maintaining individual national guidelines. Despite significant resource investment into the development and maintenance of clinical practice guidelines, their implementation is suboptimal. Effective strategies of guideline dissemination must be given more consideration, to ensure adequate implementation and improved patient care management in the future. [ABSTRACT FROM AUTHOR]

According to the current clinical practice guidelines for chronic obstructive pulmonary disease (COPD), the addition of inhaled corticosteroids (ICS) to long-acting β2 agonist therapy is recommended in patients with moderate-to-severe disease and an increased risk of exacerbations. However, ICS are largely overprescribed in clinical practice, and most patients are unlikely to benefit from long-term ICS therapy.Evidence from recent randomized-controlled trials supports the hypothesis that ICS can be safely and effectively discontinued in patients with stable COPD and in whom ICS therapy may not be indicated, without detrimental effects on lung function, health status, or risk of exacerbations. This article summarizes the evidence supporting the discontinuation of ICS therapy, and proposes an algorithm for the implementation of ICS withdrawal in patients with COPD in clinical practice.Given the increased risk of potentially serious adverse effects and complications with ICS therapy (including pneumonia), the use of ICS should be limited to the minority of patients in whom the treatment effects outweigh the risks. [ABSTRACT FROM AUTHOR]

Background: Long-acting bronchodilators are the cornerstone of pharmacologic treatment of COPD. The new combination of long-acting muscarinic antagonist (LAMA) tiotropium (TIO) and long acting beta-agonists (LABA) olodaterol (OLO) has been introduced as fist line therapy for COPD. This article analyses the evidence of efficacy and safety of the TIO/OLO combination.Methods: A systematic review and metaanalysis of randomized controlled trials (RCT) with a period of treatment of at least 6 weeks, in patients with COPD confirmed by spirometry, comparing combined treatment with TIO/OLO (approved doses only), with any of the mono-components or any other active comparator administered as an inhalator.Results: A total of 10 Randomized controlled trials (RCT) were identified (N = 10,918). TIO/OLO significantly improved trough FEV1 from baseline to week 12 versus TIO, OLO and LABA/ICS (0.06 L, 0.09 L and between 0.04 and 0.05 L, respectively). TIO/OLO improved transitional dyspnea index (TDI) and St. George's Respiratory Questionnaire (SGRQ) compared with mono-components, with patients more likely to achieve clinically important improvements in TDI (risk ratio [RR]: 1.17, 95% confidence interval [CI]: [1.07, 1.28] versus TIO and RR: 1.14, 95%CI: [1.01, 1.28] versus OLO) and in SGRQ (RR: 1.21, 95%CI: [1.12, 1.30] versus TIO and RR: 1.28, 95%CI: [1.18, 1.40] versus OLO). Patients treated with TIO/OLO showed a significant reduction in the use of rescue medication and no significant differences in frequency of general and serious adverse events were observed between TIO/OLO and mono-components.Conclusions: Treatment with TIO/OLO provided significant improvements in lung function versus mono-components and LABA/ICS with more patients achieving significant improvements in dyspnea and health status. No differences in adverse events were observed compared with other active treatments.Clinical Trial Registration: PROSPERO register of systematic reviews ( CRD42016040162 ). [ABSTRACT FROM AUTHOR]

Poor sleep and attention deficits are common in COPD. To assess the relationship between self-reported poor sleep and attention deficits in COPD. We also studied the association between self-reported sleep and the attention tests with the objective characteristics of sleep. Fifty-nine COPD patients were prospectively studied. Self-reported sleep quality was assessed using the Pittsburgh sleep quality index (PSQI). Objective characteristics of sleep were assessed by actigraphy and polysomnography. Attention was evaluated with the Oxford sleep resistance test (OSLER) and the Psychomotor vigilance test (PVT). 28 (47 %) patients referred poor sleep (PSQI >5). In the OSLER test they showed earlier sleep onset than patients with good sleep, median (Interquartil range): 31.2 min (25.4–40) vs 40 min (28.5–40), p: 0.048. They also spent more time making errors: 4.5 % (0.6–7.6) of total test time vs 0.7 % (0.2–5.3), p: 0.048. In PVT, patients with poor sleep presented a greater dispersion of the reaction time values with a higher value in the slowest 10 % of the reactions, 828 (609–1667) msec. vs 708 (601–993) msec, p: 0.028. No association was found between self-reported poor sleep and objective sleep variables. We found no correlation between OSLER and PVT results and polysomnographic variables except between sleep efficiency and PVT response speed (β: 0.309, p: 0.018). Self-reported poor sleep in COPD is associated with attention deficits. Sleep quality should be included in future studies of this facet of cognition in COPD, as well as to assess its potential usefulness as a therapeutic target. • Poor sleep quality is frequent in COPD patients. • Self-reported poor sleep is associated with attention deficits in COPD patients. • COPD patients with reported poor sleep make more errors and have slower reactions. • Pittsburgh questionnaire and polysomnographic variables are not related in COPD. [ABSTRACT FROM AUTHOR]

Chronic infections are associated with exacerbation in patients with chronic obstructive pulmonary disease (COPD). The major objective of the management of these patients is the prevention and effective treatment of exacerbations. Patients that have increased sputum production, associated with purulence and worsening shortness of breath, are the ones that will benefit from antibiotic therapy. It is important to give the appropriate antibiotic therapy to prevent treatment failure, relapse, and the emergence of resistant pathogens. In some patients, systemic corticosteroids are also indicated to improve symptoms. In order to identify which patients are more likely to benefit from these therapies, clinical guidelines recommend stratifying patients based on their risk factor associated with poor outcome or recurrence. It has been identified that patients with more severe disease, recurrent infection and presence of purulent sputum are the ones that will be more likely to benefit from this therapy. Another approach related to disease prevention could be the use of prophylactic antibiotics during steady state condition. Some studies have evaluated the continuous or the intermittent use of antibiotics in order to prevent exacerbations. Due to increased bacterial resistance to antibiotics and the presence of side effects, several antibiotics have been developed to be nebulized for both treatment and prevention of acute exacerbations. There is a need to design long-term studies to evaluate these interventions in the natural history of the disease. The purpose of this publication is to review our understanding of the role of bacterial infection in patients with COPD exacerbation, the role of antibiotics, and future interventions. [ABSTRACT FROM AUTHOR]

The natural disease course of chronic obstructive pulmonary disease (COPD) is often punctuated by exacerbations: acute events of symptom worsening associated with significant morbidity and healthcare resource utilization; reduced quality of life; and increased risk of hospitalization and death. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommend that patients at risk of exacerbations (GOLD Groups C and D) receive a long-acting muscarinic antagonist (LAMA) or a long-acting β2-agonist (LABA)/LAMA combination, respectively, as preferred initial treatments. The latter recommendation is based on recent trial evidence demonstrating the superior efficacy of a fixed-dose LABA/LAMA over an inhaled corticosteroid (ICS)/LABA in exacerbation prevention. ICS in combination with a LABA is also indicated for prevention of exacerbations, but the use of ICS is associated with an increased risk of adverse events such as pneumonia, and offers limited benefits beyond those provided by LABA or LAMA monotherapy. In this review, we examine evidence from a number of pivotal studies of LABAs and LAMAs, administered as monotherapy or as part of dual or triple combination therapy, with a specific focus on their effect on exacerbations. We also discuss a new proposed treatment paradigm for the management of COPD that takes into account this recent evidence and adopts a more cautious approach to the use of ICS. In alignment with GOLD 2017, we suggest that ICS should be reserved for patients with concomitant asthma or in whom exacerbations persist despite treatment with LABA/LAMA. [ABSTRACT FROM AUTHOR]

Alpha-1 antitrypsin deficiency (AATD) is a common hereditary disorder caused by mutations in the SERPINA1 gene, which encodes alpha-1 antitrypsin (AAT; also known as alpha 1-proteinase inhibitor, A1-PI). An important function of A1-PI in the lung is to inhibit neutrophil elastase, one of various proteolytic enzymes released by activated neutrophils during inflammation. Absence or deficiency of A1-PI leads to an imbalance between elastase and anti-elastase activity, which results in progressive, irreversible destruction of lung tissue, and ultimately the development of chronic obstructive pulmonary disease with early-onset emphysema. AATD is under-diagnosed, patients can experience long delays before obtaining an accurate diagnosis, and the consequences of delayed diagnosis or misdiagnosis can be severe. Currently, A1-PI therapy is the only available treatment that addresses disease etiology in patients with AATD; however, demonstrating clinical efficacy of A1-PI therapy is challenging. In order to show therapeutic efficacy with traditional endpoints such as forced expiratory volume in one second and mortality, large sample sizes and longer duration trials are required. However, AATD is a rare, slow progressive disease, which can take decades to manifest clinically and recruiting sufficient numbers of patients into prolonged placebo-controlled trials remains a significant obstacle. Despite this, the Randomized, placebo-controlled trial of augmentation therapy in Alpha 1-Proteinase Inhibitor Deficiency (RAPID) and RAPID Extension trial, the largest clinical program completed to date, utilized quantitative chest computed tomography as a sensitive and specific measure of the extent of emphysema. Findings from the RAPID/RAPID Extension program definitively confirmed the benefits of A1-PI therapy in slowing disease progression and provided evidence of a disease-modifying effect of A1-PI therapy in patients with AATD. These findings suggest that the early introduction of treatment in patients with severe emphysema-related AATD may delay the time to death, lung transplantation or crippling respiratory complaints. In addition, there is now limited evidence that A1-PI therapy provides a gain of more than five life-years, supporting previous observations based on registry data. With the clinical efficacy of A1-PI therapy now demonstrated, further studies are required to assess long-term outcomes. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) imposes a substantial burden on individuals with the disease, which can include a range of symptoms (breathlessness, cough, sputum production, wheeze, chest tightness) of varying severities. We present an overview of the biomedical literature describing reported relationships between COPD symptoms and disease burden in terms of quality of life, health status, daily activities, physical activity, sleep, comorbid anxiety, and depression, as well as risk of exacerbations and disease prognosis. In addition, the substantial variability of COPD symptoms encountered (morning, daytime, and nighttime) is addressed and their implications for disease burden considered. The findings from this narrative review, which mainly focuses on real-world and observational studies, demonstrate the impact of COPD symptoms on the burden of disease and that improved recognition and understanding of their impact is central to alleviating this burden. [ABSTRACT FROM AUTHOR]

This observational study assessed the relationship between nighttime, early-morning and daytime chronic obstructive pulmonary disease (COPD) symptoms and exacerbations and healthcare resource use. COPD symptoms were assessed at baseline in patients with stable COPD using a standardised questionnaire during routine clinical visits. Information was recorded on exacerbations and healthcare resource use during the year before baseline and during a 6-month follow-up period. The main objective of the analysis was to determine the predictive nature of current symptoms for future exacerbations and healthcare resource use. 727 patients were eligible (65.8% male, mean age: 67.2 years, % predicted forced expiratory volume in 1 second: 52.8%); 698 patients (96.0%) provided information after 6 months. Symptoms in any part of the day were associated with a prior history of exacerbations (allp< 0.05) and nighttime and early-morning symptoms were associated with the frequency of primary care visits in the year before baseline (bothp< 0.01). During follow-up, patients with baseline symptoms during any part of the 24-hour day had more exacerbations than patients with no symptoms in each period (allp< 0.05); there was also an association between 24-hour symptoms and the frequency of primary care visits (allp≤ 0.01). Although there was a significant association between early-morning and daytime symptoms and exacerbations during follow-up (bothp< 0.01), significance was not maintained when adjusted for potential confounders. Prior exacerbations were most strongly associated with future risk of exacerbation. The results suggest 24-hour COPD symptoms do not independently predict future exacerbation risk. [ABSTRACT FROM PUBLISHER]

Identifying patients at risk of exacerbations and managing them appropriately to reduce this risk represents an important clinical challenge. Numerous treatments have been assessed for the prevention of exacerbations and their efficacy may differ by patient phenotype. Given their centrality in the treatment of COPD, there is strong rationale for maximizing bronchodilation as an initial strategy to reduce exacerbation risk irrespective of patient phenotype. Therefore, in patients assessed as frequent exacerbators (>1 exacerbation/year) we propose initial bronchodilator treatment with a long-acting muscarinic antagonist (LAMA)/ long-acting β2-agonist (LABA). For those patients who continue to experience >1 exacerbation/year despite maximal bronchodilation, we advocate treating according to patient phenotype. Based on currently available data on adding inhaled corticosteroids (ICS) to a LABA, ICS might be added to a LABA/LAMA combination in exacerbating patients who have an asthma-COPD overlap syndrome or high blood eosinophil counts, while in exacerbators with chronic bronchitis, consideration should be given to treating with a phosphodiesterase (PDE)-4 inhibitor (roflumilast) or high-dose mucolytic agents. For those patients who experience frequent bacterial exacerbations and/or bronchiectasis, addition of mucolytic agents or a macrolide antibiotic (e.g. azithromycin) should be considered. In all patients at risk of exacerbations, pulmonary rehabilitation should be included as part of a comprehensive management plan. [ABSTRACT FROM AUTHOR]

One of the main goals of treatment of chronic obstructive pulmonary disease (COPD) is the prevention of exacerbations. Bronchodilators and anti-inflammatories are the first line therapy for treatment of COPD; however, these drugs are not effective in suppressing all infective exacerbations. In fact, the use of inhaled corticosteroids in patients with COPD and chronic bronchial infection may even increase the bacterial load in the airways and increase the risk of pneumonia. In this context, the use of long-term or intermittent antibiotic treatment has shown to prevent COPD exacerbations and hospitalizations. These effects may be achieved by reducing bacterial load in the airways in stable state and/or bronchial inflammation. The drugs more extensively studied are macrolides, followed by quinolones. The long-term use of antibiotics is associated with an increased risk of potentially serious adverse events and development of bacterial resistance. Therefore, the indication of long-term antibiotic therapy must be determined on a case by case basis taking into account the potential risks and benefits. In general, this treatment may be indicated in patients with severe or very severe COPD with frequent or severe exacerbations despite optimal pharmacological and non pharmacological treatment. These patients should be carefully monitored based on clinical and microbiological assessments. The most appropriate drug and regime administration, as well as the optimal duration of therapy are issues that still require further investigation. [ABSTRACT FROM AUTHOR]

Alpha-1 antitrypsin deficiency (AATD) is associated with an increased risk of pulmonary emphysema and liver disease. The growing interest in this deficiency in Spain led to the development of the Spanish Registry of Patients with Alpha-1 Antitrypsin Deficiency (REDAAT) in 1993. At present, the REDAAT is a network of more than 350 health care professionals and the database includes a total of 511 individuals. The adult population included consists of 469 individuals (91.8% of the total) and their phenotype distribution is: 348 Pi*ZZ (74.2%), 100 Pi*SZ (21.3%) and 21 carriers of rare variants (4.5%). The most frequent diagnosis is lung disease (74.6%). Patients with chronic obstructive pulmonary disease (COPD) registered in the REDAAT constitute approximately 15% of the expected cases of AATD-related COPD in Spain. Pi*ZZ showed more severe impairment in lung function and younger age at baseline compared with Pi*SZ. The mean decline in FEV1 in the Pi*ZZ subgroup was -23 ml/year (SD:142.8), being -18 ml/year (SD:108.8) in Pi*SZ. Forty-five percent of the Pi*ZZ individuals received augmentation therapy. A total of 61 deaths was recorded. The characteristics of the REDAAT population demonstrate some differential trends compared to other series: distribution of phenotypes, inclusion of children and patients treated with replacement therapy. Patients with the Pi*SZ phenotype were older and had milder lung function impairment. The most important challenge of this registry is to collect good quality long-term data that will allow better understanding of the natural history of the disease in real life. [ABSTRACT FROM AUTHOR]

Background: Few studies have investigated the 24-hour symptom profile in patients with COPD or how symptoms during the 24-hour day are inter-related. This observational study assessed the prevalence, severity and relationship between night-time, early morning and daytime COPD symptoms and explored the relationship between 24-hour symptoms and other patient-reported outcomes. Methods: The study enrolled patients with stable COPD in clinical practice. Baseline night-time, early morning and daytime symptoms (symptom questionnaire), severity of airflow obstruction (FEV1), dyspnoea (modified Medical Research Council Dyspnoea Scale), health status (COPD Assessment Test), anxiety and depression levels (Hospital Anxiety and Depression Scale), sleep quality (COPD and Asthma Sleep Impact Scale) and physical activity level (sedentary, moderately active or active) were recorded. Results: The full analysis set included 727 patients: 65.8% male, mean ± standard deviation age 67.2 ± 8.8 years, % predicted FEV1 52.8 ± 20.5%. In each part of the 24-hour day, >60% of patients reported experiencing ⩾1 symptom in the week before baseline. Symptoms were more common in the early morning and daytime versus night-time (81.4%, 82.7% and 63.0%, respectively). Symptom severity was comparable for each period assessed. Overall, in the week before baseline, 56.7% of patients had symptoms throughout the whole 24-hour day (3 parts of the day); 79.9% had symptoms in ⩾2 parts of the 24-hour day. Symptoms during each part of the day were inter-related, irrespective of disease severity (all p < 0.001). Early morning and daytime symptoms were associated with the severity of airflow obstruction (p < 0.05 for both). Nighttime, early morning and daytime symptoms were all associated with worse dyspnoea, health status and sleep quality, and higher anxiety and depression levels (all p < 0.001 versus patients without symptoms in each corresponding period). In each part of the 24-hour day, there was also an association between symptoms and a patient's physical activity level (p < 0.05 for each period). Conclusions: More than half of patients experienced COPD symptoms throughout the whole 24-hour day. There was a significant relationship between night-time, early morning and daytime symptoms. In each period, symptoms were associated with worse patient-reported outcomes, suggesting that improving 24-hour symptoms should be an important consideration in the management of COPD. [ABSTRACT FROM AUTHOR]

Background To determine generic utilities for Spanish chronic obstructive pulmonary disease (COPD) patients stratified by different classifications: GOLD 2007, GOLD 2013, GesEPOC 2012 and BODEx index. Methods Multicentre, observational, cross-sectional study. Patients were aged ⩾40 years, with spirometrically confirmed COPD. Utility values were derived from EQ-5D-3 L. Means, standard deviations (SD), medians and interquartile ranges (IQR) were computed based on the different classifications. Differences in median utilities between groups were assessed by non-parametric tests. Results 346 patients were included, of which 85.5% were male with a mean age of 67.9 (SD = 9.7) years and a mean duration of COPD of 7.6 (SD = 5.8) years; 80.3% were ex-smokers and the mean smoking history was 54.2 (SD = 33.2) pack-years. Median utilities (IQR) by GOLD 2007 were 0.87 (0.22) for moderate; 0.80 (0.26) for severe and 0.67 (0.42) for very-severe patients (p < 0.001 for all comparisons). Median utilities by GOLD 2013 were group A: 1.0 (0.09); group B: 0.87 (0.13); group C: 1.0 (0.16); group D: 0.74 (0.29); comparisons were statistically significant (p < 0.001) except A vs C. Median utilities by GesEPOC phenotypes were 0.84 (0.33) for non exacerbator; 0.80 (0.26) for COPD-asthma overlap; 0.71 (0.62) for exacerbator with emphysema; 0.72 (0.57) for exacerbator with chronic bronchitis (p < 0.001). Comparisons between patients with or without exacerbations and between patients with COPD-asthma overlap and exacerbator with chronic bronchitis were statistically-significant (p < 0.001). Median utilities by BODEx index were: group 0-2: 0.89 (0.20); group 3-4: 0.80 (0.27); group 5-6: 0.67 (0.29); group 7-9: 0.41 (0.31). All comparisons were significant (p < 0.001) except between groups 3-4 and 5-6. Conclusion Irrespective of the classification used utilities were associated to disease severity. Some clinical phenotypes were associated with worse utilities, probably related to a higher frequency of exacerbations. GOLD 2007 guidelines and BODEx index better discriminated patients with a worse health status than GOLD 2013 guidelines, while GOLD 2013 guidelines were better able to identify a smaller group of patients with the best health. [ABSTRACT FROM AUTHOR]

Patients with chronic obstructive pulmonary disease (COPD) may experience variability in symptoms during the day, even in periods of stability. Morning is the most troublesome time of the day for the majority of patients, complicating the performance of daily activities and resulting in a substantial impact on quality of life. Morning symptoms are related to the severity of the disease and are the cause of high worker absenteeism and increased economic burden. Patient-reported outcome (PRO) questionnaires have been developed to identify this variability in symptoms and to evaluate the impact of the disease in patients' lives. Several PRO questionnaires have already been used to assess the effect of therapeutic interventions on symptoms in the morning, such as the Capacity of Daily Living during the Morning (CDML) and the Global Chest Symptoms Questionnaire (GCSQ), both of which have been validated in clinical trials. Results of pharmacological trials indicate that the use of a bronchodilator with a fast onset of action produces a signiicant improvement in respiratory symptoms in the morning. Glycopyrronium bromide, a once-daily, long- acting muscarinic antagonist (LAMA), is selective for human M3 and M1 receptors over the M2 receptor . Receptor kinetics showing more rapid equilibration with the M3 receptor for glycopyrronium bromide than for tiotropium bromide may be the reason for the difference in onset of the bronchodilator effect. Glycopyrronium bromide's rapid onset of action may reduce the frequency and intensity of morning symptoms in COPD. [ABSTRACT FROM AUTHOR]

Background: Physical activity such as walking is strongly recommended for patients with chronic obstructive pulmonary disease (COPD). Methods: We undertook a multicenter observational study on COPD patients, collecting the daily walking time, COPD severity score (COPDSS), functional status [London Chest Activity of Daily Living (LCADL) questionnaire], health-related quality of life (QoL) rating [five-item EuroQL (EQ-5D) and Airways Questionnaire 20 (AQ20)], and anxiety and depression rating (Hospital Anxiety and Depression Scale). Multivariate logistic regression modeling was performed to identify the independent predictors of a low walking time (<30 min/day). Results: We included 4,574 patients with a mean (±standard deviation) age of 67.1 ± 10.0 years, with a mean FEV (%) of 54.0 ± 23.7. The mean daily walking time was 73.6 ± 67.1 min (58.9 % at ≥60 min and 13.7 % at <30 min). A strong direct relationship was observed between daily walking time and better QoL (EQ-5D and AQ20) and functional status (LCADL; p < 0.001 in all cases). The independent predictors of a low walking time were a worse score in EQ-5D [odds ratio (OR) (95 % confidence interval per one-point increase of 0.23 (0.15-0.35)], a higher COPDSS [OR per one-point increase of 1.04 (1.02-1.07)], and the presence of depression [OR 1.58 (1.25-2.01)]. Conclusions: After adjustment for age and severity of symptoms, poor health status, severity of COPD, and depression are the main factors associated with a low walking time in COPD patients. [ABSTRACT FROM AUTHOR]

The article discusses a research study on the predictors of outcomes in exacerbations of mild to moderate chronic obstructive pulmonary disease (COPD) not treated with antibiotics. The study assesses the clinical response in relation to Anthonisen criteria and point-of-care serum C-reactive protein (CRP) tests using multivariate logistic regression analysis. Results reveal the association of increased risk of failure without antibiotics to increase in sputum purulence and CRP concentration.

Background: Exacerbations are a major cause of disability, hospital admissions, and increased healthcare costs in patients with chronic obstructive pulmonary disease (COPD). This study investigated the clinical outcomes of outpatients with moderate to severe exacerbated COPD and their related costs. Methods: An observational study on the outcomes of ambulatory exacerbations of COPD was conducted. The course of the exacerbation was evaluated at a follow-up visit at 4 weeks. A cost analysis that encompassed the use of healthcare resources for treatment of the exacerbation was performed. Results: A total of 260 patients were included, with a mean age of 68.3 years and a mean FEV (% predicted) of 58.9 %. Twenty-two percent of patients had significant cardiovascular comorbidity. The most frequently prescribed antibiotics were moxifloxacin in 137 cases and amoxicillin-clavulanate in 50 cases. The rate of failure at 4 weeks was 12.5 %, with no differences between the two most prescribed antibiotics; however, patients treated with moxifloxacin had symptoms for 1.9 fewer days ( P = 0.01). The mean cost of the exacerbation was €344.96 (95 % CI: €48.55-€641.78), with 9.6 % of the costs for drugs and 72.9 % for hospital care of patients for whom treatment had failed. Conclusions: Antibiotic treatment of our population was in compliance with local guidelines. The rate of failure observed in our study was lower than that reported in previous studies; however, the small percentage of patients that required hospital attention generated almost two-thirds of the total costs of the exacerbations. [ABSTRACT FROM AUTHOR]

Introduction: COPD exacerbations have a negative impact on lung function, decrease quality of life (QoL) and increase the risk of death. The objective of this study was to assess the course of health status after an outpatient or inpatient exacerbation in patients with COPD. Methods: This is an epidemiological, prospective, multicentre study that was conducted in 79 hospitals and primary care centres in Spain. Four hundred seventy-six COPD patients completed COPD assessment test (CAT) and Clinical COPD Questionnaire (CCQ) questionnaires during the 24 hours after presenting at hospital or primary care centres with symptoms of an exacerbation, and also at weeks 4-6. The scores from the CAT and CCQ were evaluated and compared at baseline and after recovery from the exacerbation. Results: A total of 164 outpatients (33.7%) and 322 inpatients (66.3%) were included in the study. The majority were men (88.2%), the mean age was 69.4 years (SD = 9.5) and the mean FEV1 (%) was 47.7% (17.4%). During the exacerbation, patients presented high scores in the CAT: [mean: 22.0 (SD = 7.0)] and the CCQ: [mean: 4.4 (SD = 1.2)]. After recovery there was a significant reduction in the scores of both questionnaires [CAT: mean: -9.9 (SD = 5.1) and CCQ: mean: -3.1 (SD = 1.1)]. Both questionnaires showed a strong correlation during and after the exacerbation and the best predictor of the magnitude of improvement in the scores was the severity of each score at onset. Conclusions: Due to their good correlation, CAT and CCQ can be useful tools to measure health status during an exacerbation and to evaluate recovery. However, new studies are necessary in order to identify which factors are influencing the course of the recovery of health status after a COPD exacerbation. [ABSTRACT FROM AUTHOR]

Background: The Living with COPD (LCOPD), COPD and Asthma Fatigue Scale (CAFS), and COPD and Asthma Sleep Impact Scale (CASIS) are instruments developed to assess the overall impact of chronic obstructive pulmonary disease (COPD) on daily life, fatigue, and sleep impairment, respectively. Objectives: To assess the usefulness of these instruments and to identify factors associated with the concepts they measure. Method: The questionnaires were administered to patients with moderate to severe COPD. Descriptive analyses of sociodemographic and clinical data were performed, and bivariate and multivariate analyses were used to identify factors associated with the overall impact of COPD on patients' lives, fatigue, and sleep impairment. Results: A total of 408 patients was included (mostly males, 91.2%), with an average age of 68 years (SD = 9.3). Statistically significant differences were observed in the scores of the three questionnaires with regard to level of education, presence of chronic cough or expectoration, level of dyspnea, number of exacerbations, physical activity level, presence of depression and anxiety, and number of treatments indicated for COPD. The LCOPD and CAFS questionnaires also discriminated between different levels of airflow obstruction and, in the case of CAFS, age and gender. Linear regression showed that level of dyspnea, physical activity, and presence of anxiety were significantly related to the LCOPD, CAFS and CASIS scores. The presence of depression was significant in the LCOPD and CAFS questionnaires and chronic cough was significant in the CAFS questionnaire. Conclusions: The LCOPD, CAFS, and CASIS instruments are valid and useful in understanding the overall impact of COPD on daily life, fatigue, and sleep impairment in patients with moderate to severe COPD. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) management is still controversial. There is widespread use of ICS in COPD patients probably because this disease is characterized by airway inflammation, as well as the evident therapeutic benefits of ICS in asthma. Nevertheless, in contrast to asthma, airway inflammation in COPD is characterized by an increased number of neutrophils and macrophages and is largely unresponsive to corticosteroids. Clinical trials have failed to show that ICS slow disease progression or reduce mortality. However, in large clinical trials, ICS have been shown to reduce COPD exacerbations and improve health status and symptoms. The risk of side effects, such as pneumonia, oral candidiasis or diabetes, must lead us to determine which patients will benefit more from this treatment and the most appropriate dose. [ABSTRACT FROM AUTHOR]

Background: Patients with alpha-1 antitrypsin deficiency (AATD), commonly categorized as a rare disease, have been affected by the changes in healthcare management brought about by COVID-19. This study's aim was to identify the changes that have taken place in AATD patient care as a result of the COVID-19 pandemic in Spain and to propose experts' recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation. Methods: A qualitative descriptive case study with a holistic single-case design was conducted, using focus groups with experts in AATD clinical management, including 15 health professionals with ties to the Spanish health system (12 pneumologists and 2 hospital pharmacists from 11 different hospitals in Spain) and 1 patient representative. Results: COVID-19 has had a major impact on numerous aspects of AATD clinical patient management in Spain, including diagnostic, treatment, and follow-up phases. The experts concluded that there is a need to strengthen coordination between Primary Care and Hospital Care and improve the coordination processes across all the organizations and actors involved in the healthcare system. Regarding telemedicine and telecare, experts have concluded that it is necessary to promote this methodology and to develop protocols and training programs. Experts have recommended developing personalized and precision medicine, and patient participation in decision-making, promoting self-care and patient autonomy to optimize their healthcare and improve their quality of life. The possibility of monitoring and treating AATD patients from home has also been proposed by experts. Another result of the study was the recommendation of the need to ensure that plasma donations are made on a regular basis by a sufficient number of healthy individuals. Conclusion: The study advances knowledge by highlighting the challenges faced by health professionals and changes in AATD patient management in the context of the COVID-19 pandemic. It also proposes experts' recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation. This work could serve as a reference study for physicians on their daily clinical practice with AATD patients and may also provide guidance on the changes to be put in place for the post-pandemic situation. [ABSTRACT FROM AUTHOR]

The term phenotype as applied to chronic obstructive pulmonary disease (COPD) is defined as "those attributes of the disease that, alone or combined, describe the differences in clinically meaningful parameters between individuals with COPD". Among those described, there are four that are associated with prognostic factors and especially with a different response to the treatments that are currently available. These phenotypes are: asthma-COPD overlap, exacerbator, chronic bronchitis and emphysema. The overlap phenotype presents with an incompletely reversible obstruction to airflow accompanied by increased reversibility of the obstruction. Because of its underlying inflammatory profile, it usually has a good therapeutic response to inhaled corticosteroids (ICS) together with bronchodilators. The exacerbator type is characterized by the presence of at least two exacerbations in the previous year and, in addition to treatment with long-acting bronchodilators, may require the use of anti-inflammatory drugs such as ICS or roflumilast if it is associated with regular cough and expectoration. The chronic bronchitis phenotype is defined by the presence of productive cough with sputum on most days; when exacerbations are frequent, it responds to anti-inflammatories. Finally, the emphysema phenotype has a poor response to the anti-inflammatory drugs that are currently available; long-acting bronchodilators and respiratory therapy are the foundation of treatment. Understanding the peculiarities of the different COPD phenotypes should allow us to provide more personalized treatment in which patient characteristics are considered in addition to their severity in order to guide treatment decisions. [ABSTRACT FROM AUTHOR]

Since the end of the 1980s augmentation therapy with alpha-1 antitrypsin (AAT) from human plasma has been available for specific treatment of emphysema due to AAT deficiency. Intravenous augmentation therapy has demonstrated to be safe and weekly infusions of AAT have demonstrated to result in plasma AAT concentration above those considered protective for the lungs. Randomized, placebo-controlled clinical trials have confirmed a reduction in the decline in lung density in patients receiving augmentation therapy. This is the first example of an antiprotease effective in restoring the protease/antiprotease imbalance in the lungs and changing the natural history of congenital emphysema. On the basis of the results obtained with the long-term infusion of AAT, there is growing interest in the possible use of antiprotease treatment in patients with smokers COPD. However, no drugs are yet available to increase antiprotease protection of the lower airways of smokers. [Copyright &y& Elsevier]

Chronic bronchitis has been defined as the presence of chronic productive cough for 3 months in each of 2 succesive years in a patient in whom other causes of chronic cough have been excluded. Chronic cough and sputum production are associated with lung function decline and an increased rate of exacerbations of COPD, and these symptoms have been suggested as a predictive marker for respiratory-specific and all-cause mortality. The characteristics of chronic bronchitis fit into the new definition of clinical phenotype of COPD because they identify a subgroup of patients with a different prognosis and with different underlying pathogenic mechanisms of the disease. In contrast, the identification of the phenotype of chronic bronchitis in patients with severe COPD and frequent exacerbations is relevant because there is a specific anti-inflammatory medication for this type of patient with an inhibitor of phosphodiesterase 4. [ABSTRACT FROM AUTHOR]

Background: Socioeconomic status (SES) is an important determinant of health and premature death. However, the impact of poor SES on the health status of patients with chronic obstructive pulmonary disease (COPD) has not been well determined. Objective: It was our aim to assess the impact of SES on the quality of life in COPD patients. Methods: This was a cross-sectional, observational, multicenter study. A total of 4,574 patients completed the EuroQol 5-dimension questionnaire (EQ-5D) and the Airways Questionnaire 20 (AQ20). SES was based on the subject's occupation and educational level. Occupational categories were based on the major group classification of the International Standard Classification of Occupations. Results: The mean age of the population was 67.1 years and the mean forced expiratory volume was 43.4%. There was a gradient of impairment in health-related quality of life (HRQoL) according to the educational level, with significantly worse scores for the EQ-5D and the AQ20 for medium and low educational levels compared with high education (p < 0.001). Similarly, HRQoL was also significantly impaired in more unskilled workers, with a gradient of the AQ20 from 8.6 units (SD 4.8) in class I to 10.1 units (4.6) in class V (p < 0.001) and from 0.75 units in class I to 0.63 units in class V for the EQ-5D index, as well as from 62.9 units in class I to 55.6 units in class V for the EQ-5D visual analogue scale (p < 0.001 for all comparisons). These differences remained significant after controlling for covariates. Conclusions: Patients with a lower educational level and belonging to the unskilled professional groups had a poorer HRQoL. This is evident even in a country where access to health care services is universal and free. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Differential diagnosis of asthma and chronic obstructive pulmonary disease (COPD) is based on a combination of the patient's medical history, physical examination findings, and confirmation of the presence of reversible or irreversible airflow obstruction using spirometry. Differentiating between asthma and COPD is essential for determining the appropriate drug therapy. Inhaled corticosteroids are the most effective medications currently available for the control of asthma. However, the basis for treatment in COPD is an inhaled, long-acting bronchodilator. Taking all of this into account, it is important to increase awareness of the differences between the two diseases to promote optimal treatment. A further difficulty in the management of obstructive lung diseases is that in some individuals, there may be characteristics of both asthma and COPD. These may be patients with asthma who started to smoke and developed chronic airflow obstruction with a high degree of reversibility or heavy smokers with a genetic background that leads to the production of an eosinophilic response to inhaled particles and results in clinical features similar to those of chronic asthma. These patients are usually excluded from clinical trials of asthma treatments because they smoke and are excluded from trials of COPD because they either have a history of asthma or show great airflow reversibility. This review is dedicated to the analysis of the characteristics and treatment of this particular group of patients with obstructive lung disease, which has been described as the "overlap" phenotype between asthma and COPD. [ABSTRACT FROM AUTHOR]

Background: Elevated circulating levels of several inflammatory biomarkers have been described in selected patient populations with COPD, although less is known about their population-based distribution. The aims of this study were to compare the levels of several systemic biomarkers between stable COPD patients and healthy subjects from a population-based sample, and to assess their distribution according to clinical variables. Methods: This is a cross-sectional study design of participants in the EPI-SCAN study (40-80 years of age). Subjects with any other condition associated with an inflammatory process were excluded. COPD was defined as a postbronchodilator FEV1/FVC < 0.70. The reference group was made of non-COPD subjects without respiratory symptoms, associated diseases or prescription of medication. Subjects were evaluated with quality-of-life questionnaires, spirometry and 6-minute walk tests. Serum C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukins (IL-6 and IL-8), alpha1-antitrypsin, fibrinogen, albumin and nitrites/nitrates (NOx) were measured. Results: We compared 324 COPD patients and 110 reference subjects. After adjusting for gender, age, BMI and tobacco consumption, COPD patients showed higher levels of CRP (0.477 ± 0.023 vs. 0.376 ± 0.041 log mg/L, p = 0.049), TNF-a (13.12 ± 0.59 vs. 10.47 ± 1.06 pg/mL, p = 0.033), IL-8 (7.56 ± 0.63 vs. 3.57 ± 1.13 pg/ml; p = 0.033) and NOx (1.42 ± 0.01 vs. 1.36 ± 0.02 log nmol/l; p = 0.048) than controls. In COPD patients, serum concentrations of some biomarkers were related to severity and their exercise tolerance was related to serum concentrations of CRP, IL-6, IL-8, fibrinogen and albumin. Conclusions: Our results provide population-based evidence that COPD is independently associated with low-grade systemic inflammation, with a different inflammatory pattern than that observed in healthy subjects. [ABSTRACT FROM AUTHOR]

Background: Bacterial colonisation in chronic obstructive pulmonary disease (COPD) contributes to airway inflammation and modulates exacerbations. We assessed risk factors for bacterial colonisation in COPD. Methods: Patients with stable COPD consecutively recruited over 1 year gave consent to provide a sputum sample for microbiologic analysis. Bronchial colonisation by potentially pathogenic microorganisms (PPMs) was defined as the isolation of PPMs at concentrations of =102 colony-forming units (CFU)/mL on quantitative bacterial culture. Colonised patients were divided into high (>105 CFU/mL) or low (<105 CFU/mL) bacterial load. Results: A total of 119 patients (92.5% men, mean age 68 years, mean forced expiratory volume in one second [FEV1] [% predicted] 46.4%) were evaluated. Bacterial colonisation was demonstrated in 58 (48.7%) patients. Patients with and without bacterial colonisation showed significant differences in smoking history, cough, dyspnoea, COPD exacerbations and hospitalisations in the previous year, and sputum colour. Thirty-six patients (62% of those colonised) had a high bacterial load. More than 80% of the sputum samples with a dark yellow or greenish colour yielded PPMs in culture. In contrast, only 5.9% of white and 44.7% of light yellow sputum samples were positive (P < 0.001). Multivariate analysis showed an increased degree of dyspnoea (odds ratio [OR] = 2.63, 95% confidence interval [CI] 1.53-5.09, P = 0.004) and a darker sputum colour (OR = 4.11, 95% CI 2.30-7.29, P < 0.001) as factors associated with the presence of PPMs in sputum. Conclusions: Almost half of our population of ambulatory moderate to very severe COPD patients were colonised with PPMs. Patients colonised present more severe dyspnoea, and a darker colour of sputum allows identification of individuals more likely to be colonised. [ABSTRACT FROM AUTHOR]

Large, multicenter, randomized controlled trials in COPD have recently been completed. The largest of these studies are "Towards a Revolution in COPD Health" (TORCH) and "Understanding Potential Long-Term Impacts on Function with Tiotropium" (UPLIFT®). These studies make considerable contributions to understanding the natural history of COPD. The objective of this article is to review the data from these different trials in order to find what can be learnt of the management of COPD. The long-term improvements in lung function, health-related quality of life, and possibly survival from the use of long-acting bronchodilators in these trials suggest an influence on the progression of the disease. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To describe the characteristics of patients and exacerbations that may determine the choice of an antibacterial in exacerbations of chronic bronchitis (ECB). METHODS: This was a multicentre, observational study in ECB. A group of 225 primary-care practitioners were randomly selected to include 1007 patients. A logistic regression model was used to identify the characteristics of the physicians, patients and exacerbations associated with the choice of an antibacterial. RESULTS: The mean age of the patients was 67.6 years (± SD 11) and 72.1% were male. In 91.4% of patients, the exacerbation was type I or II according to Anthonisen’s classification. Most exacerbations (68.2%) were treated with moxifloxacin while only 31.8% were treated with other antibacterials. The more experienced practitioners (those with the longest professional careers and those who had higher numbers of patient-visits for chronic bronchitis) prescribed moxifloxacin more frequently (per each year of experience: OR 1.05; 95% CI 1.02, 1.07; per each additional patient-visit per week: OR 1.02; 95% CI 1.003, 1.04). The probability of receiving moxifloxacin increased with the severity of baseline dyspnoea (OR 1.94; 95% CI 1.27, 2.96) and decreased in smokers (OR 0.54; 95% CI 0.36, 0.81) and in patients receiving oral corticosteroids (OR 0.61; 95% CI 0.41, 0.90). CONCLUSIONS: Prescription of moxifloxacin in primary care is significantly associated with more years of physician practice and with a higher severity of disease. The use of oral corticosteroids in exacerbations is commonly associated with other antibacterials (non-quinolones), either to improve antibacterial efficacy or because of doubtful bacterial aetiology, thus the preference for a narrow-spectrum antibacterial combined with an anti-inflammatory drug. [ABSTRACT FROM AUTHOR]