Clinical Concepts for Triple Therapy Use in Patients with COPD: A Delphi Consensus.

Purpose: Role of triple therapy in chronic obstructive pulmonary disease (COPD) management is supported by growing evidence, but consensus is lacking on various aspects. We conducted a Delphi survey in respiratory experts on the effects of triple therapy on exacerbation reduction, early optimization, pneumonia risk, and mortality benefits in COPD management. Methods: The study comprised 2-round online surveys and a participant meeting with 21 respiratory experts from 10 countries. The 31-statement questionnaire was prepared using Decipher software after literature review. Responses were recorded using Likert scale ranging from 1 (disagreement) to 9 (agreement) with a consensus threshold of 75%. Results: All experts participated in both surveys and 14/21 attended participant meeting. Consensus was reached on 13/31 questions in first survey and 4/14 in second survey on: mortality benefits of triple therapy; comparable pneumonia risk between single inhaler triple therapy (SITT) and multiple inhaler triple therapy (81%); preference of SITT for patients with high eosinophil count (95%); exacerbation risk reduction and healthcare cost benefits with early initiation of SITT post exacerbation-related hospitalization (<30 days) (86%). No consensus was reached on first line SITT use after first exacerbation resulting in COPD diagnosis (62%). Conclusion: This study demonstrated that there is consensus among experts regarding many of the key concepts about appropriate clinical use and benefits of triple therapy in COPD. More evidence is required for evaluating the benefits of early optimisation of triple therapy.

Distribution of alpha1 antitrypsin rare alleles in six countries: Results from the Progenika diagnostic network.

BACKGROUND: Knowledge of the frequency of rare SERPINA1 mutations could help in the management of alpha1 antitrypsin deficiency (AATD). The present study aims to assess the frequencies of rare and null alleles and their respiratory and hepatic pathogenicity. METHODS: This is a secondary analysis of a study that evaluated the viability of the Progenika diagnostic genotyping system in six different countries by analyzing 30,827 samples from cases of suspected AATD. Allele-specific genotyping was carried out with the Progenika A1AT Genotyping Test which analyses 14 mutations in buccal swabs or dried blood spots samples. SERPINA1 gene sequencing was performed for serum AAT-genotype discrepancies or by request of the clinician. Only cases with rare mutations were included in this analysis. RESULTS: There were 818 cases (2.6%) carrying a rare allele, excluding newly identified mutations. All were heterozygous except for 20 that were homozygous. The most frequent alleles were the M-like alleles, PI*Mmalton and PI*Mheerlen. Of the 14 mutations included in the Progenika panel, there were no cases detected of PI*Siiyama, PI*Q0granite falls and PI*Q0west. Other alleles not included in the 14-mutation panel and identified by gene sequencing included PI*Mwürzburg, PI*Zbristol, and PI*Zwrexham, and the null alleles PI*Q0porto, PI*Q0madrid, PI*Q0brescia, and PI*Q0kayseri. CONCLUSIONS: The Progenika diagnostic network has allowed the identification of several rare alleles, some unexpected and not included in the initial diagnostic panel. This establishes a new perspective on the distribution of these alleles in different countries. These findings may help prioritize allele selection for routine testing and highlights the need for further research into their pathogenetic role.

Trajectories of Spirometric Patterns, Obstructive and PRISm, in a Population-Based Cohort in Latin America.

Background: Preserved ratio impaired spirometry (PRISm) has been associated with adverse outcomes and increased transition to other spirometric categories over time. We aimed to examine its prevalence, trajectories over time, and outcomes in a population-based sample from Latin America. Methods: Data were obtained from two population-based surveys of adults from three cities in Latin America (PLATINO study), conducted on the same individuals 5-9 years after their baseline examination. We estimated the frequency of PRISm defined by FEV1/FVC≥0.70 with FEV1 <80%, describing their clinical characteristics, longitudinal transition trajectories over time, factors associated with the transition. Results: At baseline, 2942 participants completed post-bronchodilator spirometry, and 2026 at both evaluations. The prevalence of normal spirometry was 78%, GOLD-stage 1 10.6%, GOLD 2-4 6.5%, and PRISm was: 5.0% (95% CI 4.2-5.8). PRISm was associated with less schooling, more reports of physician-diagnosis of COPD, wheezing, dyspnea, missing days at work, having ≥2 exacerbations in the previous year but without accelerated lung function decline. Mortality risk was significantly higher in PRISm (HR 1.97, 95% CI 1.2-3.3) and COPD GOLD 1-4 categories (HR 1.79, 95% CI 1.3-2.4) compared with normal spirometry. PRISm at baseline most frequently transitioned to another category at follow-up (46.5%); 26.7% to normal spirometry and 19.8% to COPD. The best predictors of transition to COPD were closeness of FEV1/FVC to 0.70, older age, current smoking, and a longer FET in the second assessment. Conclusion: PRISm, is a heterogeneous and unstable condition prone to adverse outcomes that require adequate follow-up.

Feasibility of a genotyping system for the diagnosis of alpha1 antitrypsin deficiency: a multinational cross-sectional analysis.

INTRODUCTION: Currently, strategies for improving alpha1 antitrypsin deficiency (AATD) diagnosis are needed. Here we report the performance of a multinational multiplex-based genotyping test on dried blood spots and buccal swabs sent by post or courier and with web registration for subjects with suspected AATD in Argentina, Brazil, Chile, Colombia, Spain, and Turkey. METHODS: This was an observational, cross-sectional analysis of samples from patients with suspected AATD from March 2018 to January 2022. Samples were coded on a web platform and sent by post or courier to the central laboratory in Northern Spain. Allele-specific genotyping for the 14 most common mutations was carried out with the A1AT Genotyping Test (Progenika-Grifols, Spain). SERPINA1 gene sequencing was performed if none of the mutations were found or one variant was detected in heterozygous status and the AAT serum level was < 60 mg/dl, or if requested by the clinician in charge. RESULTS: The study included 30,827 samples: 30,458 (94.7%) with final results after direct genotyping and 369 (1.1%) with additional gene sequencing. Only 0.3% of the samples were not processed due to their poor quality. The prevalence of the most frequent allele combinations was MS 14.7%, MZ 8.6%, SS 1.9%, SZ 1.9%, and ZZ 0.9%. Additionally, 70 cases with new mutations were identified. Family screening was conducted in 2.5% of the samples. Samples from patients with respiratory diseases other than COPD, including poorly controlled asthma or bronchiectasis, also presented AATD mutations. CONCLUSIONS: Our results confirm the viability of this diagnostic system for genotyping AATD conducted simultaneously in different countries. The system has proved satisfactory and can improve the timely diagnosis of AATD.

Upper Limb Anaerobic Metabolism Capacity is Reduced in Mild and Moderate COPD Patients.

Limited information is available regarding the role of anaerobic metabolism capacity on GOLD 1 and 2 COPD patients during upper limb exercise. We aimed to compare the upper limb anaerobic power capacity, blood lactate concentration, cardiovascular and respiratory responses, in male COPD patients versus healthy subjects during the 30-s Wingate anaerobic test (WAnT). The rate of fatigue and time constant of the power output decay (τ, tau) were also calculated and a regression analysis model was built to assess the predictors of τ in these patients. Twenty-four male COPD patients (post-bronchodilator FEV1 73.2 ± 15.3% of predicted) and 17 healthy subjects (FEV1 103.5 ± 10.1% of predicted) underwent the WAnT. Measurements were performed at rest, at the end of the WAnT, and during 3' and 5' of recovery time. Peak power (p = 0.04), low power (p = 0.002), and mean power output (p = 0.008) were significantly lower in COPD patients than in healthy subjects. Power output decreased exponentially in both groups, but at a significantly faster rate (p = 0.007) in COPD patients. The time constant of power decay was associated with resistance (in ohms) and fat-free mass (r2 = 0.604, adjusted r2 = 0.555, and p = 0.002). Blood lactate concentration was significantly higher in healthy subjects at the end of the test, as well as during 3' and 5' of recovery time (p < 0.01). Compared with healthy subjects, COPD patients with GOLD 1 and 2 presented lower upper limb anaerobic capacity and a faster rate of power output decrease during a maximal intensity exercise. Also, the WAnT proved to be a valid tool to measure the upper limb anaerobic capacity in these patients.

Gender differences in the perception of asthma respiratory symptoms in five Latin American countries.

OBJECTIVES: To determine the differences between sexes in perceptions of asthma symptoms, asthma control, daily activities, and symptom exacerbation in Latin American countries. METHODS: This cross-sectional study was performed using data from the Latin America Asthma Insight and Management (LA-AIM) study (n = 2167) carried out in Argentina, Brazil, Mexico, Venezuela, and Puerto Rico. Face-to-face interviews were conducted, and patients orally completed a 53-question survey assessing five main domains of asthma: symptoms, impact on daily activities, disease control, exacerbation, and treatment/medication. RESULTS: Of the 2167 participants, 762 (35.2%) were males and 1405 (64.8%) were females. Male participants smoked more than females, but history of rhinitis and allergies was more common in females (p < 0.05). Women aged 18-40 years had a higher proportion of uncontrolled asthma compared to men of the same age (37.8% and 30.0%, respectively). A higher proportion of symptomatic females reported more frequent symptoms (daytime cough, shortness of breath, breathlessness/wheezing, sputum, tightness in the chest, etc.) than males (p < 0.05). Females also experienced more limitations in sports/recreational activities, normal physical exertion, social activities, sleep, and daily activities. Females consulted with health professionals more often than males (67.8% and 59.6%, respectively; p < 0.05). Asthma caused a feeling of lack of control over life in 42.6% of females and 31.4% of males. CONCLUSION: In Latin America, females report more asthma symptoms, poorer asthma control, more impact on their daily activities, and more visits with health professionals than males.

Update on and future perspectives for the diagnosis of alpha-1 antitrypsin deficiency in Brazil.

Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disorder caused by a mutation in the SERPINA1 gene, which encodes the protease inhibitor alpha-1 antitrypsin (AAT). Severe AATD predisposes individuals to COPD and liver disease. Early diagnosis is essential for implementing preventive measures and limiting the disease burden. Although national and international guidelines for the diagnosis and management of AATD have been available for 20 years, more than 85% of cases go undiagnosed and therefore untreated. In Brazil, reasons for the underdiagnosis of AATD include a lack of awareness of the condition among physicians, a racially diverse population, serum AAT levels being assessed in a limited number of individuals, and lack of convenient diagnostic tools. The diagnosis of AATD is based on laboratory test results. The standard diagnostic approach involves the assessment of serum AAT levels, followed by phenotyping, genotyping, gene sequencing, or combinations of those, to detect the specific mutation. Over the past 10 years, new techniques have been developed, offering a rapid, minimally invasive, reliable alternative to traditional testing methods. One such test available in Brazil is the A1AT Genotyping Test, which simultaneously analyzes the 14 most prevalent AATD mutations, using DNA extracted from a buccal swab or dried blood spot. Such advances may contribute to overcoming the problem of underdiagnosis in Brazil and elsewhere, as well as being likely to increase the rate detection of AATD and therefore mitigate the harmful effects of delayed diagnosis.

Perspective of Pulmonary Rehabilitation Centers in Latin America.

Pulmonary rehabilitation (PR) is a mandatory component of a comprehensive treatment of patients with chronic respiratory disease. However, there is no officially published data about PR Centers in Latin America.The objetive is to identify Latin American Pulmonary Rehabilitation Centers and evaluate their characteristics and organizational aspects.A cross-sectional study with the Pulmonary Rehabilitation Centers indicated by the Latin American Respiratory and Physiotherapy Societies and by our own personal survey among physicians and physiotherapists. An eletronic transmission questionnaire with 20 questions was sent to the Coordinator of each one of the Centers.217 Pulmonary Rehabilitation Centers were found throughout Latin America and a total of 160 (73.7%) Centers answered the questionnaire. Of these, 65.8% had private administration; 68.8% had an associated program for patients with heart disease; programs lasted an average of 24 sessions; the rehabilitation team consisted mainly of physiotherapists, physicians and dietitians; 90.6% of the centers evaluated the patients with different questionnaires; 91.9% used treadmill and 90.6% bicycle for exercises of lower limbs and 80.1% proprioceptive neuromuscular facilitation technique with weights to train the upper limbs of their patients; 55.6% had an educational program and 36.9% presented a home-based program.There has been a great increase in the number of Latin American Pulmonary Rehabilitation Centers, presenting diversity in organizational aspects.

Asociación Latinoamericana del Tórax (ALAT): 30 años de historia / Associação Latino-Americana de Tórax (ALAT): 30 anos de história / No disponible

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The Glittre ADL-Test Differentiates COPD Patients with and without Self-Reported Functional Limitation.

The Glittre ADL-test is based on important and common activities of daily living (ADLs), and it is an useful test to objectively distinguish patients with and without self-reported functional limitations. This study aims to analyze if difficulty to perform ADLs, as self-reported by patients with COPD, would reflect a worse Glittre ADL-test performance. In the first visit, patients were evaluated for clinical and nutritional status, spirometry, maximal cardiopulmonary exercise test on a treadmill. One week later, the patients performed two Glittre ADL-tests. Maximal voluntary ventilation (MVV) and the VEGlittre/MVV, VO2Glittre/VO2peak, and HRGlittre/HRpeak ratios were calculated to analyze the ventilatory, metabolic, and cardiac reserves. The London Chest Activity of Daily Living (LCADL) scale was only answered after the two Glittre ADL-test were performed. Patients were splited into two subgroups based on the anchor question of the LCADL: those with and those without self-reported ADL limitation. Sixty-two COPD patients were included (65.3 ± 8.6 years, FEV1 62 ± 22%pred). Those with ADL limitation (39 patients) completed the Glittre ADL-test with a significantly longer time (p = 0.002), as well as higher VEGlittre/MVV (p = 0.005) and lower oxygen pulse (p = 0.021) than those without ADL limitation. The time spent to perform the Glittre ADL-test was significantly associated with total LCADL score (ρ = 0.327, p < 0.05). A cutoff of 253 s was able to distinguish those patients without and with ADL limitation. COPD patients who self-reported ADL limitation according to the LCADL scale took a longer time to perform the Glittre ADL-test with higher VEGlittre/MVV and lower oxygen pulse than those without ADL limitation.

Frequency of Osteoporosis and Vertebral Fractures in Chronic Obstructive Pulmonary Disease (COPD) Patients / Incidencia de osteoporosis y fracturas vertebrales en pacientes con enfermedad pulmonar obstructiva crónica (EPOC)

Background: Osteoporosis is a systemic skeletal disease characterized by low bone mass and/or microarchitectural deterioration of bone. Osteoporosis is a risk factor for fractures specially in patients with advanced COPD. The aim of this cross-sectional study was to determine the frequency of osteoporosis and vertebral fracture in COPD patients. Methods: We evaluated 91 COPD patients and compared to 82 healthy subjects (control group) matched for gender and age. We measured the bone mineral density by means of dual energy X-ray absorptiometry (DXA), evaluating the lumbar vertebra (L1-L4), proximal femur and total femur and evaluated vertebral fractures in thoracic and lumbar spine using X-ray. We questioned patients whether they had had any fall that resulted in any fracture in the past five years. Results: Males comprised 60.4% of COPD group and 57.3% of the control group. Mean age was 66.2 ± 9.2 years for COPD group and 64.,2 ± 8.8 for the control group. The frequency of osteoporosis in the COPD group was 29.7% and 18.3% in control group (p = 0.007). The frequency of vertebral fractures was 18.6% in the COPD group and 9.0% in control group (p = 0.06). The frequency of reported falls at resulting in any fracture was 36.3% in the COPD group and 7.3% in control group (p = 0.001). Conclusions: Our data indicate that COPD patients present a high frequency of osteoporosis and falls seem to be an important factor for vertebral fracture

Introducción: La osteoporosis es una enfermedad sistémica esquelética caracterizada por una baja densidad ósea y/o un deterioro de la microarquitectura del hueso. Constituye un factor de riesgo de fracturas, especialmente en pacientes con EPOC avanzada. El objetivo de este estudio transversal fue determinar la incidencia de osteoporosis y de fracturas vertebrales en pacientes con EPOC. Métodos: Se evaluaron 91 pacientes con EPOC y se compararon con 82 sujetos sanos (grupo control) emparejados por sexo y edad. Se midió la densidad mineral ósea mediante densitometría ósea (DXA) de la vértebra lumbar (L1-L4), el fémur proximal y el fémur total. Las fracturas en vértebras torácicas y lumbares se evaluaron mediante rayos X. Se preguntó a los pacientes por posibles caídas en los últimos cinco años que pudieran haber resultado en fractura. Resultados: Los hombres representaron el 60,4% del grupo EPOC y el 57,3% del grupo control. La edad media fue 66,2 ± 9,2 años en el grupo EPOC, y 64,2 ± 8,8 años en el grupo control. La incidencia de osteoporosis en el grupo EPOC fue del 29,7%, y del 18,3% en el grupo control (p = 0,06). Se registró una incidencia de caídas resultantes en fracturas del 36,3% en el grupo EPOC y del 7,3% en el grupo control (p = 0,001). Conclusión: Nuestros datos sugieren que los pacientes con EPOC presentan una mayor incidencia de osteoporosis. Las caídas parecen ser un factor relevante en la fractura vertebral

The Importance of Inhaler Adherence to Prevent COPD Exacerbations.

It has been shown that the better outcomes of chronic obstructive pulmonary disease (COPD) are closely associated with adherence to drug therapy, independent of the treatment administered. The clinical trial Towards a Revolution in COPD Health (TORCH) study clearly showed in a three year follow up that patients with good adherence to their inhaler treatment presented a longer time before the first exacerbation, a lower susceptibility to exacerbation and lower all-cause mortality. The Latin American Study of 24-hour Symptoms in Chronic Obstructive Pulmonary Disease (LASSYC), a real-life study, evaluated the self-reported inhaler adherence in COPD patients in seven countries in a cross-sectional non-interventional study and found that approximately 50% of the patients had good adherence, 30% moderate adherence and 20% poor adherence. Adherence to inhaler may be evaluated by the specific inhaler adherence questionnaire, the Test of Adherence to Inhalers (TAI). Several factors may predict the incorrect use of inhalers or adherence in COPD outpatient, including the number of devices and the daily dosing frequency. Ideally, patient education, simplicity of the device operation, the use of just one device for multiple medications and the best adaptation of the patient to the inhaler should guide the physician in prescribing the device.

Frequency of Osteoporosis and Vertebral Fractures in Chronic Obstructive Pulmonary Disease (COPD) Patients.

BACKGROUND: Osteoporosis is a systemic skeletal disease characterized by low bone mass and/or microarchitectural deterioration of bone. Osteoporosis is a risk factor for fractures specially in patients with advanced COPD. The aim of this cross-sectional study was to determine the frequency of osteoporosis and vertebral fracture in COPD patients. METHODS: We evaluated 91 COPD patients and compared to 82 healthy subjects (control group) matched for gender and age. We measured the bone mineral density by means of dual energy X-ray absorptiometry (DXA), evaluating the lumbar vertebra (L1-L4), proximal femur and total femur and evaluated vertebral fractures in thoracic and lumbar spine using X-ray. We questioned patients whether they had had any fall that resulted in any fracture in the past five years. RESULTS: Males comprised 60.4% of COPD group and 57.3% of the control group. Mean age was 66.2±9.2 years for COPD group and 64.2±8.8 for the control group. The frequency of osteoporosis in the COPD group was 29.7% and 18.3% in control group (p=0.007). The frequency of vertebral fractures was 18.6% in the COPD group and 9.0% in control group (p=0.06). The frequency of reported falls at resulting in any fracture was 36.3% in the COPD group and 7.3% in control group (p=0.001). CONCLUSIONS: Our data indicate that COPD patients present a high frequency of osteoporosis and falls seem to be an important factor for vertebral fracture.

Outcomes for symptomatic non-obstructed individuals and individuals with mild (GOLD stage 1) COPD in a population based cohort.

BACKGROUND: We aimed to study the adverse outcomes of symptomatic and asymptomatic non-obstructed individuals and those with mild COPD longitudinally in participants from three Latin-American cities. METHODS: Two population-based surveys of adults with spirometry were conducted for these same individuals with a 5- to 9-year interval. We evaluated the impact of respiratory symptoms (cough, phlegm, wheezing or dyspnea) in non-obstructed individuals, and among those classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1, COPD on exacerbation frequency, mortality and FEV1 decline, compared with asymptomatic individuals without airflow obstruction or restriction. RESULTS: Non-obstructed symptomatic individuals had a marginal increased risk of mortality (HR 1.3; 95% CI 0.9-1.94), increased FEV1 decline (-4.5 mL/year; 95% CI -8.6, -0.4) and increased risk of 2+ exacerbations in the previous year (OR 2.6; 95% CI 1.2-6.5). Individuals with GOLD stage 1 had a marginal increase in mortality (HR 1.5; 95% CI 0.93-2.3) but a non-significant impact on FEV1 decline or exacerbations compared with non-obstructed individuals. CONCLUSIONS: The presence of respiratory symptoms in non-obstructed individuals was a predictor of mortality, lung-function decline and exacerbations, whereas the impact of GOLD stage 1 was mild and inconsistent. Respiratory symptoms were associated with asthma, current smoking, and the report of heart disease. Spirometric case-finding and treatment should target individuals with moderate-to-severe airflow obstruction and those with restriction, the groups with consistent increased mortality.

Demographic Characteristics and Clinical Outcomes in Patients from Latin America Versus the Rest of the World: A TIOSPIR® Post-Hoc Analysis / Características demográficas y resultados clínicos en pacientes de Latinoamérica respecto al resto del mundo: un análisis post-hoc de TIOSPIR®

Introduction: Geographical variations may impact outcomes in chronic obstructive pulmonary disease (COPD). We evaluated differences in baseline characteristics and outcomes between patients enrolled in Latin America compared with the rest of the world (RoW) in the TIOtropium Safety and Performance In Respimat® (TIOSPIR®) trial. Methods: TIOSPIR(R), a 2-3-year, randomized, double-blind trial (n=17116; treated set), compared safety and efficacy of once-daily tiotropium Respimat® 5 and 2.5μg with tiotropium HandiHaler® 18μg. This post-hoc analysis pooled data from all treatment arms to assess mortality, exacerbations, cardiac events, and serious adverse events (SAEs) between both regions. Results: At baseline, patients enrolled in Latin America (n=1000) versus RoW (n=16116) were older, with higher pack-years of smoking history and more exacerbations, but less cardiac history. In this analysis, patients in Latin America versus RoW had an increased risk of death (hazard ratio [HR] [95% confidence interval (CI)]: 1.52 [1.24-1.86]; P<.0001) or moderate-to-severe exacerbation (HR [95% CI]: 1.29 [1.18-1.41]; P<.0001), but a lower risk of severe exacerbation (HR [95% CI]: 0.82 [0.68-0.98]; P=.0333). SAE rates in Latin America were lower versus RoW (incidence rate ratio [IRR] [95% CI]: 0.82 [0.72-0.92]), including cardiac disorders (IRR [95% CI]: 0.68 [0.48-0.97]). Risk of major adverse cardiovascular events were similar (HR [95% CI]: 0.99 [0.71-1.40]; P=.9677). Conclusions: TIOSPIR® patients in Latin America had a higher risk of death or moderate-to-severe exacerbation, but a lower risk of severe exacerbation than those in RoW. Geographical differences may impact outcomes in COPD trials (AU)

Introducción: Las variaciones geográficas pueden afectar a los resultados en la enfermedad pulmonar obstructiva crónica (EPOC). Evaluamos las diferencias en las características basales y los resultados de los pacientes incluidos en Latinoamérica en comparación con el resto del mundo (RdM) en el ensayo TIOtropium Safety and Performance In Respimat(R)® (TIOSPIR(R)). Métodos: TIOSPIR(R), es un estudio aleatorizado, doble ciego de 2-3 años de duración (n=17.116; conjunto tratado), comparó la seguridad y la eficacia del tiotropio Respimat® una vez al día en dosis de 5 y 2,5μg con respecto al tiotropio HandiHaler® 18μg. Este análisis post-hoc reunió datos de todos los brazos de tratamiento para evaluar la mortalidad, las exacerbaciones, los acontecimientos cardíacos y los acontecimientos adversos graves (AAG) entre ambas regiones. Resultados: Al inicio del estudio, los pacientes reclutados en América Latina (n=1.000) versus RdM (n=16.116) eran de mayor edad, con más paquetes/año de consumo de tabaco en sus antecedentes y más exacerbaciones, pero menos antecedentes cardíacos. En este análisis, los pacientes de Latinoamérica versus RdM tenían un mayor riesgo de muerte (razón de riesgo [HR] intervalo de confianza del 95% [IC 95%]: 1,52 [1,24-1,86]; p<0,0001) y de exacerbación moderada a grave (HR [IC 95%]: 1,29 [1,18-1,41]; p<0,0001), pero menor riesgo de exacerbación grave (HR [IC 95%]: 0,82 [0,68-0,98]; p=0,0333). Las tasas de AAG en Latinoamérica fueron más bajas frente al RdM (tasa de incidencia [IRR] [IC 95%]: 0,82 [0,72-0,92]), incluidos los trastornos cardíacos (IRR [IC 95%]: 0,68 [0,48-0,97]). El riesgo de acontecimientos cardiovasculares adversos mayores fue similar (HR [IC 95%]: 0,99 [0,71-1,40]; p=0,9677). Conclusiones: Los pacientes de TIOSPIR® en Latinoamérica tuvieron un mayor riesgo de muerte y de exacerbación moderada a grave, pero un menor riesgo de exacerbación grave que aquellos en el RdM. Las diferencias geográficas pueden afectar los resultados en los ensayos de la EPOC (AU)

Variability in Quality of Life Outcomes Following a Pulmonary Rehabilitation Program in Patients With COPD.

PURPOSE: Pulmonary rehabilitation (PR) improves exercise tolerance in patients with chronic obstructive pulmonary disease. However, it is unclear why some patients do not improve quality of life during a training program. Our objective was to evaluate the differences between patients with chronic obstructive pulmonary disease who improve and those who do not improve quality of life during a pulmonary rehabilitation program. METHODS: Seventy-three patients underwent a PR program. All patients trained at 80% (legs) and 50% (arms) of their maximum load. Incremental and endurance tests, 6-min walk test, and health-related quality of life with the St George Respiratory Questionnaire (SGRQ) were measured. We subdivided the groups based on a decrease ≥4 points in the pre- and post-PR SGRQ total score (G1); <4-point change in the SGRQ total score (G2); and an increase in scores ≥4 points (G3). RESULTS: Exacerbation frequency (P = .004) and SGRQ total scores (P < .001) were lower in G1 and G2 than in G3. G1 (P = .0007) and G2 (P = .0005) significantly improved 6-min walk test distance. Before PR, G1 and G2 walked greater distances than G3 (P = .003); however, the difference was no longer significant after PR (P = .34). A significant load increase was seen after PR for the 3 groups (P < .05). We found a significant correlation between the SGRQ and the Charlson index (r = 0.78, P < .0001), exacerbation frequency (r = 0.72, P < .0001), and basal dyspnea index (r = -0.48, P < .0001). CONCLUSION: Patients whose quality of life did not improve after comprehensive PR presented a higher number of disease-related exacerbations with comorbidities.

Chronic Obstructive Pulmonary Disease Exacerbations Are Influenced by Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) is associated with different pulmonary diseases, including chronic obstructive pulmonary disease (COPD). Whether GERD is contributory to COPD severity remains unclear. This study aims to evaluate the contribution of GERD to the clinical manifestation of COPD based on ventilatory parameters and yearly clinical exacerbations. We studied 48 patients (56% females, age 66 years) with COPD. All patients underwent high-resolution manometry and esophageal pH monitoring. The patients were separated into two groups according to the presence of GERD. GERD was present in 21 (44%) patients. GERD + and GERD - groups did not differ in regard to gender, age, and body mass index. Pulmonary parameters were not different in the absence or presence of GERD. The number of yearly exacerbations was higher in patients GERD+. The severity of GERD (as measured by DeMeester score) correlated with the number of exacerbations. Our results show the following: 1) GERD does not influence pulmonary parameters and 2) GERD is associated with a higher number of annual clinical exacerbations. We believe GERD must be objectively tested in patients with COPD because the prevalence of GERD in these patients is underestimated when only symptoms are considered. GERD treatment might decrease the frequency of episodes of exacerbation.

Demographic Characteristics and Clinical Outcomes in Patients from Latin America Versus the Rest of the World: A TIOSPIR® Post-Hoc Analysis.

INTRODUCTION: Geographical variations may impact outcomes in chronic obstructive pulmonary disease (COPD). We evaluated differences in baseline characteristics and outcomes between patients enrolled in Latin America compared with the rest of the world (RoW) in the TIOtropium Safety and Performance In Respimat® (TIOSPIR®) trial. METHODS: TIOSPIR®, a 2-3-year, randomized, double-blind trial (n=17116; treated set), compared safety and efficacy of once-daily tiotropium Respimat® 5 and 2.5µg with tiotropium HandiHaler® 18µg. This post-hoc analysis pooled data from all treatment arms to assess mortality, exacerbations, cardiac events, and serious adverse events (SAEs) between both regions. RESULTS: At baseline, patients enrolled in Latin America (n=1000) versus RoW (n=16116) were older, with higher pack-years of smoking history and more exacerbations, but less cardiac history. In this analysis, patients in Latin America versus RoW had an increased risk of death (hazard ratio [HR] [95% confidence interval (CI)]: 1.52 [1.24-1.86]; P<.0001) or moderate-to-severe exacerbation (HR [95% CI]: 1.29 [1.18-1.41]; P<.0001), but a lower risk of severe exacerbation (HR [95% CI]: 0.82 [0.68-0.98]; P=.0333). SAE rates in Latin America were lower versus RoW (incidence rate ratio [IRR] [95% CI]: 0.82 [0.72-0.92]), including cardiac disorders (IRR [95% CI]: 0.68 [0.48-0.97]). Risk of major adverse cardiovascular events were similar (HR [95% CI]: 0.99 [0.71-1.40]; P=.9677). CONCLUSIONS: TIOSPIR® patients in Latin America had a higher risk of death or moderate-to-severe exacerbation, but a lower risk of severe exacerbation than those in RoW. Geographical differences may impact outcomes in COPD trials.

Physiological Requirements to Perform the Glittre Activities of Daily Living Test by Subjects With Mild-to-Severe COPD.

BACKGROUND: The Glittre activities of daily living (ADL) test is supposed to evaluate the functional capacity of COPD patients. The physiological requirements of the test and the time taken to perform it by COPD patients in different disease stages are not well known. The objective of this work was to compare the metabolic, ventilatory, and cardiac requirements and the time taken to carry out the Glittre ADL test by COPD subjects with mild, moderate, and severe disease. METHODS: Spirometry, Medical Research Council questionnaire, cardiopulmonary exercise test, and 2 Glittre ADL tests were evaluated in 62 COPD subjects. Oxygen uptake (V̇O2 ), carbon dioxide production, pulmonary ventilation, breathing frequency, heart rate, SpO2 , and dyspnea were analyzed before and at the end of the tests. Maximum voluntary ventilation, Glittre peak V̇O2 /cardiopulmonary exercise test (CPET) peak V̇O2 , Glittre V̇E/maximum voluntary ventilation, and Glittre peak heart rate/CPET peak heart rate ratios were calculated to analyze their reserves. RESULTS: Subjects carried out the Glittre ADL test with similar absolute metabolic, ventilatory, and cardiac requirements. Ventilatory reserve decreased progressively from mild to severe COPD subjects (P < .001 for Global Initiative for Chronic Obstructive Lung Disease [GOLD] 1 vs GOLD 2, P < .001 for GOLD 1 vs GOLD 3, and P < .001 for GOLD 2 vs GOLD 3). Severe subjects with COPD presented a significantly lower metabolic reserve than the mild and moderate subjects (P = .006 and P = .043, respectively) and significantly lower Glittre peak heart rate/CPET peak heart rate than mild subjects (P = .01). Time taken to carry out the Glittre ADL test was similar among the groups (P = .82 for GOLD 1 vs GOLD 2, P = .19 for GOLD 1 vs GOLD 3, and P = .45 for GOLD 2 vs GOLD 3). CONCLUSIONS: As the degree of air-flow obstruction progresses, the COPD subjects present significant lower ventilatory reserve to perform the Glittre ADL test. In addition, metabolic and cardiac reserves may differentiate the severe subjects. These variables may be better measures to differentiate functional performance than Glittre ADL time.