Impact of Early Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis: A multicenter Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: Forced vital capacity (FVC) less than 50% of predicted is one of the main parameters used for Non-Invasive Ventilation (NIV) initiation in Amyotrophic Lateral Sclerosis (ALS). Recent studies suggest that higher values of FVC could be considered as a threshold. The aim of this study is to evaluate whether early use of NIV improves the prognosis of ALS patients compared with standard initiation. METHODS: This is a randomized, parallel, multicenter, open-label, controlled clinical trial, with recruitment at the ALS outpatient multidisciplinary units of six Spanish hospitals. Patients were included when their FVC reached the 75% threshold and were randomized by computer, stratifying by center in an allocation ratio of 1:1 to Early NIV (FVC below 75%) or Standard NIV (FVC below 50%) initiation. The primary outcome was time to death or tracheostomy.Trial registration number ClinicalTrials.gov: NCT01641965. RESULTS: Between May 2012 and June 2014, 42 patients were randomized to two groups, 20 to Early NIV and 22 to Standard NIV initiation. We found differences in survival in favor of the intervention group: an incidence of mortality (2.68 [1.87-5.50] vs. 3.33 [1.34-4.80] person-months) and a median survival (25.2 vs. 19.4 months), although without reaching statistical significance (p = 0.267). CONCLUSIONS: This trial did not reach the primary endpoint of survival; nevertheless, it is the first Randomized Controlled Trial (RCT) to demonstrate the benefits of early NIV in slowing the decline of respiratory muscle strength and reducing adverse events. Although not all the results reached statistical significance, all the analyzed data favor early NIV. In addition, this study demonstrates good tolerance and compliance with early NIV without quality of sleep impairment. These data reinforce the early respiratory evaluation of ALS patients and NIV initiation with an FVC of around 75%.

Survival benefit of multidisciplinary care in amyotrophic lateral sclerosis in Spain: association with noninvasive mechanical ventilation.

PURPOSE: Multidisciplinary care has become the preferred model of care for patients with amyotrophic lateral sclerosis (ALS). It is assumed that the sum of interventions associated with this approach has a positive effect on survival. The objective of the study was to evaluate the impact of a multidisciplinary care approach on the survival of patients with ALS. PATIENTS AND METHODS: We performed a retrospective review of prospectively collected data in a tertiary referral center in Spain. Participants were patients with definite or probable ALS managed in a multidisciplinary care program. We compared demographic and survival data of patients with definite or probable ALS treated in a referral center without and with implementation of a multidisciplinary care program. We performed time-dependent multivariate survival analysis of the use of noninvasive mechanical ventilation (NIMV) and gastrostomy. RESULTS: We evaluated 398 consecutive patients, of whom 54 were treated by a general neurologist and 344 were treated in the multidisciplinary care clinic. Patients receiving multidisciplinary care were older (62 vs 58 years), tended to have bulbar onset disease (30% vs 17.7%), and were more likely to receive riluzole (88.7% vs 29.6%, p<0.01), NIMV (48.8% vs 29.6%, p>0.001), and nutrition via gastrostomy (32.3% vs 3.7%, p<0.01). Kaplan-Meier analysis showed a 6-month increase in survival (log-rank, 16.03, p<0.001). Application of the Andersen-Gill model showed that the variables associated with reduced mortality were reduced time to NIMV and gastrostomy and the duration of both, thus reflecting compliance. CONCLUSIONS: Multidisciplinary care increased the survival of ALS patients in our study population. Timely use of respiratory support and gastrostomy are fundamental aspects of this benefit.

Physical Activity Is Associated with Attenuated Disease Progression in Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) progression is variable and affects several disease domains, including decline in lung function, exercise capacity, muscle strength, and health status as well as changes in body composition. We aimed to assess the longitudinal association of physical activity (PA) with these a priori selected components of disease progression. METHODS: We studied 114 COPD patients from the PAC-COPD cohort (94% male, mean [SD], 70 yr [8 yr] of age, 54 [16] forced expiratory volume in 1 s % predicted) at baseline and 2.6 yr (0.6 yr) later. Baseline PA was assessed by accelerometry. Multivariable general linear models were built to assess the association between PA and changes in lung function, functional exercise capacity, muscle strength, health status, and body composition. All models were adjusted for confounders and the respective baseline value of each measure. RESULTS: Per each 1000 steps higher baseline PA, forced expiratory volume in 1 s declined 7 mL less (P < 0.01), forced vital capacity 9 mL less (P = 0.03) and carbon monoxide diffusing capacity 0.10 mL·min·mm Hg less (P = 0.04), while the St George's Respiratory Questionnaire symptom domain deteriorated 0.4 points less (P = 0.03), per year follow-up. Physical activity was not associated with changes in functional exercise capacity, muscle strength, other domains of health status or body composition. CONCLUSIONS: Higher PA is associated with attenuated decline in lung function and reduced health status (symptoms domain) deterioration in moderate-to-very severe COPD patients.

Noninvasive ventilation for severely acidotic patients in respiratory intermediate care units : Precision medicine in intermediate care units.

BACKGROUND: Severe acidosis can cause noninvasive ventilation (NIV) failure in chronic obstructive pulmonary disease (COPD) patients with acute hypercapnic respiratory failure (AHRF). NIV is therefore contraindicated outside of intensive care units (ICUs) in these patients. Less is known about NIV failure in patients with acute cardiogenic pulmonary edema (ACPE) and obesity hypoventilation syndrome (OHS). Therefore, the objective of the present study was to compare NIV failure rates between patients with severe and non-severe acidosis admitted to a respiratory intermediate care unit (RICU) with AHRF resulting from ACPE, COPD or OHS. METHODS: We prospectively included acidotic patients admitted to seven RICUs, where they were provided NIV as an initial ventilatory support measure. The clinical characteristics, pH evolutions, hospitalization or RICU stay durations and NIV failure rates were compared between patients with a pH ≥ 7.25 and a pH < 7.25. Logistic regression analysis was performed to determine the independent risk factors contributing to NIV failure. RESULTS: We included 969 patients (240 with ACPE, 540 with COPD and 189 with OHS). The baseline rates of severe acidosis were similar among the groups (45 % in the ACPE group, 41 % in the COPD group, and 38 % in the OHS group). Most of the patients with severe acidosis had increased disease severity compared with those with non-severe acidosis: the APACHE II scores were 21 ± 7.2 and 19 ± 5.8 for the ACPE patients (p < 0.05), 20 ± 5.7 and 19 ± 5.1 for the COPD patients (p < 0.01) and 18 ± 5.9 and 17 ± 4.7 for the OHS patients, respectively (NS). The patients with severe acidosis also exhibited worse arterial blood gas parameters: the PaCO2 levels were 87 ± 22 and 70 ± 15 in the ACPE patients (p < 0.001), 87 ± 21 and 76 ± 14 in the COPD patients, and 83 ± 17 and 74 ± 14 in the OHS patients (NS)., respectively Further, the patients with severe acidosis required a longer duration to achieve pH normalization than those with non-severe acidosis (patients with a normalized pH after the first hour: ACPE, 8 % vs. 43 %, p < 0.001; COPD, 11 % vs. 43 %, p < 0.001; and OHS, 13 % vs. 51 %, p < 0.001), and they had longer RICU stays, particularly those in the COPD group (ACPE, 4 ± 3.1 vs. 3.6 ± 2.5, NS; COPD, 5.1 ± 3 vs. 3.6 ± 2.1, p < 0.001; and OHS, 4.3 ± 2.6 vs. 3.7 ± 3.2, NS). The NIV failure rates were similar between the patients with severe and non-severe acidosis in the three disease groups (ACPE, 16 % vs. 12 %; COPD, 7 % vs. 7 %; and OHS, 11 % vs. 4 %). No common predictive factor for NIV failure was identified among the groups. CONCLUSIONS: ACPE, COPD and OHS patients with AHRF and severe acidosis (pH ≤ 7.25) who are admitted to an RICU can be successfully treated with NIV in these units. These results may be used to determine precise RICU admission criteria.

Transcutaneous Carbon Dioxide Monitoring in Subjects With Acute Respiratory Failure and Severe Hypercapnia.

BACKGROUND: Transcutaneous carbon dioxide (P(tcCO2)) monitoring is being used increasingly to assess acute respiratory failure. However, there are conflicting findings concerning its reliability when evaluating patients with high levels of P(aCO2). Our study evaluates the accuracy of this method in subjects with respiratory failure according to the severity of hypercapnia. METHODS: We included subjects with respiratory failure, admitted to a respiratory intermediate care unit, who required arterial blood gas analysis. Simultaneously, P(tcCO2) was measured using a digital monitor. Relations between P(aCO2) and P(tcCO2) were assessed by the Pearson correlation coefficient. Bland-Altman analysis was used to test data dispersion, and an analysis of variance test was used to compare the differences between P(aCO2) and the corresponding P(tcCO2) at different levels (level 1, <50 mm Hg; level 2, 50-60 mm Hg; level 3, >60 mm Hg). RESULTS: Eighty-one subjects were analyzed. The main diagnosis was COPD exacerbation (45%). P(tcCO2) correlated well with P(aCO2) (r2 = 0.93, P < .001). Bland-Altman analysis showed a mean P(aCO2) - P(tcCO2) difference of 4.9 ± 4.4 with 95% limits of agreement ranging from -3.6 to 13.4. The difference between variables increased in line with P(aCO2) severity: level 1, 1.7 ± 3.2 mm Hg; level 2, 3.7 ± 2.8; level 3, 6.8 ± 4.7 (analysis of variance, P < .001). CONCLUSIONS: Our study showed an acceptable agreement of P(tcCO2) monitoring with arterial blood gas analysis. However, we should consider that P(tcCO2) underestimates P(aCO2) levels, and its accuracy depends on the level of hypercapnia, so this method would not be suitable for acute patients with severe hypercapnia.

Inspiratory capacity-to-total lung capacity ratio and dyspnoea predict exercise capacity decline in COPD.

BACKGROUND AND OBJECTIVE: Exercise capacity decline is a predictor of mortality in patients with chronic obstructive pulmonary disease (COPD). Static pulmonary hyperinflation is a key determinant of exercise performance, but its effect on the longitudinal decline in exercise capacity remains unknown. We aimed to study the relationship between the inspiratory capacity-to-total lung capacity (IC/TLC) ratio and exercise capacity decline in COPD. METHODS: We measured IC/TLC and other relevant clinical and functional variables in 342 clinically stable patients with COPD. The 6-min walk distance (6MWD) was determined at recruitment and after a mean ± SD of 1.7 ± 0.3 years. The annual rate of change in 6MWD was calculated. Multiple imputation to account for losses during follow up was implemented, and multivariate regression was used to analyze predictive factors of 6MWD decline. RESULTS: Mean decline rate in the 6MWD was 21.9 ± 34.1 m/year. In the bivariate analysis, patients with lower levels of IC/TLC had greater 6MWD decline (-27.4 ± 42.5, -24.9 ± 36.5 and -13.4 ± 39.9 m/year in the first, second and third tertile of IC/TLC, respectively; P-for-trend = 0.018). From other potential risk factors considered, dyspnoea, health status, serum C-reactive protein and Borg dyspnoea score at the end of the exercise test were related to exercise capacity decline. In the multivariate regression model, only IC/TLC (ß = 0.7 m/year per each percentage unit of IC/TLC; P = 0.007) and dyspnoea (mMRC ≥ 2) (ß = -14.6 m/year; P = 0.013) were associated with the annual rate of 6MWD change. CONCLUSION: IC/TLC and dyspnoea in clinically stable patients with COPD predict their exercise capacity decline and may help to guide early therapeutic interventions.

Benefits of physical activity on COPD hospitalisation depend on intensity.

The present study aims to disentangle the independent effects of the quantity and the intensity of physical activity on the risk reduction of chronic obstructive pulmonary disease (COPD) hospitalisations.177 patients from the Phenotype Characterization and Course of COPD (PAC-COPD) cohort (mean±sd age 71±8 years, forced expiratory volume in 1 s 52±16% predicted) wore the SenseWear Pro 2 Armband accelerometer (BodyMedia, Pittsburgh, PA, USA) for eight consecutive days, providing data on quantity (steps per day, physically active days and daily active time) and intensity (average metabolic equivalent tasks) of physical activity. Information on COPD hospitalisations during follow-up (2.5±0.8 years) was obtained from validated centralised datasets. During follow-up 67 (38%) patients were hospitalised. There was an interaction between quantity and intensity of physical activity in their effects on COPD hospitalisation risk. After adjusting for potential confounders in the Cox regression model, the risk of COPD hospitalisation was reduced by 20% (hazard ratio (HR) 0.79, 95% CI 0.67-0.93; p=0.005) for every additional 1000 daily steps at low average intensity. A greater quantity of daily steps at high average intensity did not influence the risk of COPD hospitalisations (HR 1.01, p=0.919). Similar results were found for the other measures of quantity of physical activity. Greater quantity of low-intensity physical activity reduces the risk of COPD hospitalisation, but high-intensity physical activity does not produce any risk reduction.

Characterisation and prognosis of undiagnosed chronic obstructive pulmonary disease patients at their first hospitalisation.

BACKGROUND: Under-diagnosis of COPD is an important unmet medical need. We investigated the characteristics and prognosis of hospitalised patients with undiagnosed COPD. METHODS: The PAC-COPD cohort included 342 COPD patients hospitalised for the first time for an exacerbation of COPD (2004-2006). Patients were extensively characterised using sociodemographic, clinical and functional variables, and the cohort was followed-up through 2008. We defined "undiagnosed COPD" by the absence of any self-reported respiratory disease and regular use of any pharmacological respiratory treatment. RESULTS: Undiagnosed COPD was present in 34% of patients. They were younger (mean age 66 vs. 68 years, p = 0.03), reported fewer symptoms (mMRC dyspnoea score, 2.1 vs. 2.6, p < 0.01), and had a better health status (SGRQ total score, 29 vs. 40, p < 0.01), milder airflow limitation (FEV1% ref., 59% vs. 49%, p < 0.01), and fewer comorbidities (two or more, 40% vs. 56%, p < 0.01) when compared with patients with an established COPD diagnosis. Three months after hospital discharge, 16% of the undiagnosed COPD patients had stopped smoking (vs. 5%, p = 0.019). During follow-up, annual hospitalisation rates were lower in undiagnosed COPD patients (0.14 vs. 0.25, p < 0.01); however, this difference disappeared after adjustment for severity. Mortality was similar in both groups. CONCLUSIONS: Undiagnosed COPD patients have less severe disease and lower risk of re-hospitalisation when compared with hospitalised patients with known COPD.

Exome sequencing identifies titin mutations causing hereditary myopathy with early respiratory failure (HMERF) in families of diverse ethnic origins.

BACKGROUND: Hereditary myopathy with early respiratory failure (HMERF) was described in several North European families and recently linked to a titin gene (TTN) mutation. We independently studied HMERF-like diseases with the purpose to identify the cause, refine diagnostic criteria, and estimate the frequency of this disease among myopathy patients of various ethnic origins. METHODS: Whole exome sequencing analysis was carried out in a large U.S. family that included seven members suffering from skeletal muscle weakness and respiratory failure. Subsequent mutation screening was performed in further 45 unrelated probands with similar phenotypes. Studies included muscle strength evaluation, nerve conduction studies and concentric needle EMG, respiratory function test, cardiologic examination, and muscle biopsy. RESULTS: A novel TTN p.Gly30150Asp mutation was identified in the highly conserved A-band of titin that co-segregated with the disease in the U.S. family. Screening of 45 probands initially diagnosed as myofibrillar myopathy (MFM) but excluded based on molecular screening for the known MFM genes led to the identification of a previously reported TTN p.Cys30071Arg mutation in one patient. This same mutation was also identified in a patient with suspected HMERF. The p.Gly30150Asp and p.Cys30071Arg mutations are localized to a side chain of fibronectin type III element A150 of the 10th C-zone super-repeat of titin. CONCLUSIONS: Missense mutations in TTN are the cause of HMERF in families of diverse origins. A comparison of phenotypic features of HMERF caused by the three known TTN mutations in various populations allowed to emphasize distinct clinical/pathological features that can serve as the basis for diagnosis. The newly identified p.Gly30150Asp and the p.Cys30071Arg mutation are localized to a side chain of fibronectin type III element A150 of the 10th C-zone super-repeat of titin.

Echocardiographic abnormalities in patients with COPD at their first hospital admission.

Cardiovascular disease accounts for significant morbidity and mortality in chronic obstructive pulmonary disease (COPD). Its prevalence and mechanisms of association have not been elucidated. The study aimed to assess the prevalence of echocardiographic abnormalities and potential risk factors in patients with COPD at their first exacerbation requiring hospital admission. Transthoracic echocardiography was prospectively performed in 342 patients (forced expiratory volume in 1 s 52 ± 16% predicted) 3 months after discharge. Significant cardiac alterations were present in 64% of patients; 27% left- and 48% right-heart disorders. The most common were right ventricle enlargement (30%) and pulmonary hypertension (19%). Left ventricle enlargement was present in 6%, left ventricle systolic dysfunction in 13%, left ventricle diastolic impairment in 12% and left atrial dilatation in 29%. Echocardiographic abnormalities were unrelated to COPD severity and were more frequent in patients with self-reported cardiac disease. They were also observed in 63% of patients with no known cardiac disease or cardiovascular risk factors other than smoking. We conclude that cardiac abnormalities are highly prevalent in COPD patients at the time of their first severe exacerbation, even in the absence of established cardiac disease or cardiovascular risk factors. Considering the prognostic and therapeutic implications of cardiac comorbidity, echocardiography should be considered in the assessment of patients with clinically significant COPD.

Physical activity in COPD patients: patterns and bouts.

The present study aims to describe the pattern of physical activity and the frequency, duration and intensity of physical activity bouts in patients with chronic obstructive pulmonary disease (COPD), to assess how these patterns differ according to COPD severity, and to explore whether these patients meet the general guidelines for physical activity for older adults. 177 patients (94% male, mean±sd age 71±8 years and forced expiratory volume in 1 s 52±16% predicted) wore the SenseWear Pro2 Armband accelerometer for eight consecutive days. Physical activity bouts were defined as periods of ≥10 min above 1.5 metabolic equivalent tasks and classified according to their median intensity. Patients engaged in activity a median of 153 min·day(-1) and 57% of that time was spent in bouts. Median frequencies of bouts per day were four and three for all and moderate-to-vigorous intensities, respectively. With increasing COPD severity, time in physical activity, proportion of time in bouts and frequency of bouts decreased. 61% of patients fulfilled the recommended physical activity guidelines. In conclusion, COPD patients of all spirometric severity stages engage in physical activity bouts of moderate-to-vigorous intensities. Patients with severe and very severe COPD perform their daily activities in fewer and shorter bouts than those in mild and moderate stages.

Validación del cuestionario de actividad física de Yale en pacientes con enfermedad pulmonar obstructiva crónica / Validation of the Yale Physical Activity Survey in Chronic Obstructive Pulmonary Disease Patients

IntroducciónLos pacientes con enfermedad pulmonar obstructiva crónica (EPOC) se caracterizan por una actividad física limitada. Sorprendentemente, apenas se dispone de investigación sobre los cuestionarios para medir la actividad física en la EPOC. El objetivo del presente estudio fue validar el cuestionario Yale Physical Activity Survey en pacientes con EPOC.MétodosUn total de 172 pacientes de 8 hospitales universitarios españoles usaron un acelerómetro (SenseWear®PrO2Armband) durante 8 días y contestaron el cuestionario. Los análisis estadísticos de comparación de ambos instrumentos incluyeron: a) correlación de Spearman; b) coeficiente de correlación intraclase (CCI) y gráficos de Bland-Altman; c) distribución de las medidas del acelerómetro según los terciles del cuestionario, y d) la curva receiver operating characteristic (ROC) para detectar a los pacientes sedentarios.ResultadosEl 94% de los participantes eran hombres, el 28% eran fumadores y el 7% eran trabajadores activos; la edad media (±DE) fue de 70 (8) años, el volumen espiratorio medio en el primer segundo (VEMS) posbroncodilatador fue de 52 (15) como porcentaje del valor de referencia, y la mediana (p25-p75) de pasos fue de 5.702 (3.273-9.253) pasos/día. Las correlaciones de Spearman fueron débiles o moderadas (desde 0,29 hasta 0,52, todas las p<0,001). Los CCI mostraron concordancias débiles (desde 0,34 hasta 0,40, todas las p<0,001). Los gráficos de Bland-Altman mostraron una gran variabilidad en la concordancia. Se encontraron diferencias significativas en las medidas del acelerómetro según los terciles del cuestionario (todas las p<0,001). El área bajo la curva ROC para identificar el sedentarismo fue de 0,71 (intervalo de confianza del 95%: 0,63-0,79)(AU)

ConclusiónEl cuestionario Yale Physical Activity Survey es una herramienta válida para clasificar la actividad física que realizan los pacientes con EPOC, pero no para cuantificarla. El índice resumen del cuestionario, originado de tan solo 7 preguntas, muestra los mejores resultados de validez, sugiriendo que debería considerarse un instrumento de cribado para identificar a los pacientes que corren riesgo de sedentarismo(AU)

BackgroundPatients with chronic obstructive pulmonary disease (COPD) perform limited physical activity. Surprisingly, there is a lack of research in COPD about the validity of physical activity questionnaires. Our aim was to validate the Yale Physical Activity Survey in COPD patients in order to quantify and classify their levels of physical activity.Methods172 COPD patients from 8 university hospitals in Spain wore an accelerometer (SenseWear®Pro2Armband) for 8 days and answered the questionnaire 15 days later. Statistical analyses used to compare both tools measures included: (i) Spearman's correlation coefficient, (ii) intraclass correlation coefficient (ICC) and Bland-Altman plots, (iii) distribution of accelerometer measurements according to tertiles of the questionnaire, and (iv) receiver operating characteristic (ROC) curves to detect sedentary patients.Results94% of participants were men, 28% were active smokers and 7% were currently working. Mean (standard deviation) age was 70 (8) years, mean post-bronchodilator FEV1 was 52 (15)% predicted, and median (p25-p75) steps taken was 5,702 (3,273-9,253) steps per day−1. Spearman correlations were low to moderate (from 0.29 to 0.52, all P<.001). ICCs showed weak agreement (from 0.34 to 0.40, all P <.001). A wide variability in agreement was observed in the Bland-Altman plots. Significant differences in accelerometer measurements were found according to questionnaire tertiles (all P <.001). The area under the ROC for identifying sedentarism was 0.71 (95% CI: 0.63-0.79).ConclusionsThe Yale Physical Activity Survey may be a valid tool to classify, but not to quantify, physical activity performed by COPD patients. The summary index of this questionnaire, based on seven short questions, shows the best validity properties. This suggests that it should be considered a screening tool to identify patients at risk for sedentarism(AU)

[Validation of the Yale Physical Activity Survey in chronic obstructive pulmonary disease patients]. / Validación del cuestionario de actividad física de Yale en pacientes con enfermedad pulmonar obstructiva crónica.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) perform limited physical activity. Surprisingly, there is a lack of research in COPD about the validity of physical activity questionnaires. Our aim was to validate the Yale Physical Activity Survey in COPD patients in order to quantify and classify their levels of physical activity. METHODS: 172 COPD patients from 8 university hospitals in Spain wore an accelerometer (SenseWear(®)Pro(2)Armband) for 8 days and answered the questionnaire 15 days later. Statistical analyses used to compare both tools measures included: (i) Spearman's correlation coefficient, (ii) intraclass correlation coefficient (ICC) and Bland-Altman plots, (iii) distribution of accelerometer measurements according to tertiles of the questionnaire, and (iv) receiver operating characteristic (ROC) curves to detect sedentary patients. RESULTS: 94% of participants were men, 28% were active smokers and 7% were currently working. Mean (standard deviation) age was 70 (8) years, mean post-bronchodilator FEV(1) was 52 (15)% predicted, and median (p25-p75) steps taken was 5,702 (3,273-9,253) steps per day(-1). Spearman correlations were low to moderate (from 0.29 to 0.52, all P<.001). ICCs showed weak agreement (from 0.34 to 0.40, all P<.001). A wide variability in agreement was observed in the Bland-Altman plots. Significant differences in accelerometer measurements were found according to questionnaire tertiles (all P<.001). The area under the ROC for identifying sedentarism was 0.71 (95% CI: 0.63-0.79). CONCLUSIONS: The Yale Physical Activity Survey may be a valid tool to classify, but not to quantify, physical activity performed by COPD patients. The summary index of this questionnaire, based on seven short questions, shows the best validity properties. This suggests that it should be considered a screening tool to identify patients at risk for sedentarism.

Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes. METHODS: To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomarkers of systemic and bronchial inflammation, sputum microbiology, CT of the thorax and echocardiography were assessed. COPD groups were identified by partitioning cluster analysis and validated prospectively against cause-specific hospitalisations and all-cause mortality during a 4 year follow-up. RESULTS: Three COPD groups were identified: group 1 (n=126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV(1)) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n=125, 69 years) showed milder airflow limitation (FEV(1) 63% predicted); and group 3 (n=91, 67 years) combined a similarly milder airflow limitation (FEV(1) 58% predicted) with a high proportion of obesity, cardiovascular disorders, diabetes and systemic inflammation. During follow-up, group 1 had more frequent hospitalisations due to COPD (HR 3.28, p<0.001) and higher all-cause mortality (HR 2.36, p=0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p=0.014). CONCLUSIONS: In patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated: 'severe respiratory COPD', 'moderate respiratory COPD', and 'systemic COPD'.

Predicting nocturnal hypoventilation in hypercapnic chronic obstructive pulmonary disease patients undergoing long-term oxygen therapy.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients are very sensitive to changes in pulmonary mechanics and central ventilation control during sleep and may develop significant gas exchange alterations with increased hypoxemia and hypercapnia. Oxygen therapy improves nocturnal desaturation but can worsen hypoventilation. OBJECTIVES: To analyze the prevalence of nocturnal hypoventilation (NHV) in hypercapnic COPD patients and to determine predictive factors for this phenomenon. METHODS: This was a prospective multicenter study which enrolled 80 clinically stable COPD patients with hypercapnic respiratory failure who fulfilled the conventional criteria for long-term oxygen therapy (LTOT). All patients had undergone pulmonary function testing, blood gas analysis, and respiratory polygraphy. Arterial blood gas samples were obtained while patients were awake and during sleep. NHV was considered when an increase in PaCO2 >10 mm Hg was observed in any nocturnal arterial blood gas sample as compared to the awake levels. RESULTS: Seventeen patients (21%) developed NHV. NHV was associated with the values of BMI, hemoglobin, hematocrits, DLCO, and PaO2 reached after oxygen administration. In the logistic regression analysis BMI (OR 1.26, 95% CI 1.068-1.481; p = 0.006) and the diurnal increase of PaO2 after O2 (OR 0.89, 95% CI 0.807-0.972; p = 0.010) were the variables that best discriminated with a sensitivity of 82% and a specificity of 78%. CONCLUSIONS: NHV is a relatively common finding in stable hypercapnic COPD patients undergoing LTOT and it is related to a higher BMI and lower PaO2 after oxygen administration.

Sleep hypoventilation due to increased nocturnal oxygen flow in hypercapnic COPD patients.

UNLABELLED: This study shows the risks and benefits of increasing the nocturnal oxygen flow in hypercapnic COPD patients undergoing LTOT, as recommended by some COPD treatment guidelines to avoid nocturnal desaturation. BACKGROUND AND OBJECTIVE: Several COPD treatment guidelines recommend increasing oxygen flow during sleep to avoid nocturnal desaturation. However, such an increase could have deleterious clinical and gas exchange effects. The objective of this study was to evaluate short-term gas exchange alterations produced by increasing the nocturnal oxygen flow rate. METHODS: Thirty-eight COPD patients with chronic hypercapnic respiratory failure were evaluated. In a cross-over study, patients were randomly assigned to receive the daytime oxygen flow rate on one night and an additional litre on the alternate night. Nocturnal pulse oximetry and arterial blood gases at awakening were measured, in each patient, on two consecutive days. RESULTS: The administration of 1 L more oxygen during the night resulted in improved parameters of nocturnal oxygenation (oxygen pulse oximetry saturation-SpO2; percentage of sleep time spent at SpO2<90%-CT90; PaO2 at awakening). Nevertheless, such an increase in oxygen flow during the night was also associated with greater hypercapnia and acidosis (p<0.05) the next morning. CONCLUSIONS: The increase of oxygen flow in severe COPD patients with established daytime hypercapnia improved nocturnal oxygenation but it also led to greater hypercapnia and respiratory acidosis at awakening in a considerable proportion of these patients.

Characteristics of patients admitted for the first time for COPD exacerbation.

BACKGROUND: This study describes the characteristics of a large sample of patients hospitalised for the first time for a chronic obstructive pulmonary disease (COPD) exacerbation. METHODS: All subjects first admitted for a COPD exacerbation to nine teaching Spanish hospitals during January 2004-March 2006, were eligible. COPD diagnosis was confirmed by spirometry under stability. At admission, sociodemographic data, lifestyle, previous treatment and diagnosis of respiratory disease, lung function and Charlson index of co-morbidity were collected. A comprehensive assessment, including dyspnea, lung function, six-minute walking test, and St. George's Respiratory Questionnaire (SGRQ), was completed 3 months after admission, during a clinically stable disease period. RESULTS: Three-hundred and forty-two patients (57% of the eligible) participated in the study: 93% males, mean (SD) age 68 (9) years, 42% current smokers, 50% two or more co-morbidities, 54% mild-to-moderate dyspnea, post-bronchodilator FEV(1) 52 (16)% of predicted (54% mild-to-moderate COPD in ATS/ERS stages), 6-min walking distance 440 m, total SGRQ score 37 (18), and 36% not report respiratory disease. The absence of a previous COPD diagnosis, positive bronchodilator test, female gender, older age, higher DLco and higher BMI were independently associated with less severe COPD. CONCLUSIONS: We show that the patients admitted after presenting with their first COPD exacerbation have a wide range of severity, with a large proportion of patients in the less advanced COPD stages.

Physical activity and clinical and functional status in COPD.

BACKGROUND: The mechanisms underlying the benefits of regular physical activity in the evolution of COPD have not been established. Our objective was to assess the relationship between regular physical activity and the clinical and functional characteristics of COPD. METHODS: Three hundred forty-one patients were hospitalized for the first time because of a COPD exacerbation in nine teaching hospitals in Spain. COPD diagnosis was confirmed by spirometry under stable conditions. Physical activity before the first COPD hospitalization was measured using the Yale questionnaire. The following outcome variables were studied under stable conditions: dyspnea, nutritional status, complete lung function tests, respiratory and peripheral muscle strength, bronchial colonization, and systemic inflammation. RESULTS: The mean age was 68 years (SD, 9 years), 93% were men, 43% were current smokers, and the mean postbronchodilator FEV(1) was 52% predicted (SD, 16% predicted). Multivariate linear regression models were built separately for each outcome variable and adjusted for potential confounders (including remaining outcomes if appropriate). When patients with the lowest quartile of physical activity were compared to patients in the other quartiles, physical activity was associated with significantly higher diffusing capacity of the lung for carbon monoxide (Dlco) [change in the second, third, and fourth quartiles of physical activity, compared with first quartile (+ 6%, + 6%, and + 9% predicted, respectively; p = 0.012 [for trend])], expiratory muscle strength (maximal expiratory pressure [Pemax]) [+ 7%, + 5%, and + 9% predicted, respectively; p = 0.081], 6-min walking distance (6MWD) [+ 40, + 41, and + 45 m, respectively; p = 0.006 (for trend)], and maximal oxygen uptake (Vo(2)peak) [+ 55, + 185, and + 81 mL/min, respectively; p = 0.110 (for trend)]. Similarly, physical activity reduced the risk of having high levels of circulating tumor necrosis factor alpha (odds ratio, 0.78, 0.61, and 0.36, respectively; p = 0.011) and C-reactive protein (0.70, 0.51, and 0.52, respectively; p = 0.036) in multivariate logistic regression. CONCLUSIONS: More physically active COPD patients show better functional status in terms of Dlco, Pemax, 6MWD, Vo(2)peak, and systemic inflammation.