Ciro Casanova

C-reactive protein levels and clinically important predictive outcomes in stable COPD patients

The aim of this study was to determine the relationship between C-reactive protein (CRP) levels and factors known to predict outcome in stable chronic obstructive pulmonary disease (COPD) patients. The following were studied in 130 stable COPD patients: spirometry, lung volume, arterial oxygen tension (Pa,O2), dyspnoea, 6-min walk distance (6MWD), body mass index, fat-free mass index, BODE (body mass index, obstruction, dyspnoea and exercise capacity), health-related quality of life, smoking status, the presence of cardiovascular risk factors or disease, corticosteroid use and number of exacerbations in the previous year. CRP levels were measured in these patients and in 65 controls. Using univariate and multivariate analyses, any possible association with the predictors of outcomes was evaluated. CRP levels were higher in COPD patients than in controls (4.1 versus 1.8 mg·L−1, respectively). Correlation was found with the following variables: forced expiratory volume in one second (FEV1; −0.23), FEV1 % (−0.20), forced vital capacity (FVC; −0.24), FVC % (−0.24), Global Initiative for Chronic Obstructive Lung Disease stage (0.17), BODE (0.17), inspiratory capacity/total lung capacity (−0.20), Pa,O2 (−0.40) and 6MWD (−0.30). Using multivariate analysis, Pa,O2 and 6MWD manifested the strongest negative association with CRP levels. C-reactive protein levels in stable chronic obstructive pulmonary disease patients are best correlated with arterial oxygen tension and 6-min walk distance. This should be considered when C-reactive protein levels are measured in stable chronic obstructive pulmonary disease patients.

The 6-min walk distance in healthy subjects: reference standards from seven countries

The 6-min walk distance (6MWD) predicted values have been derived from small cohorts mostly from single countries. The aim of the present study was to investigate differences between countries and identify new reference values to improve 6MWD interpretation. We studied 444 subjects (238 males) from seven countries (10 centres) ranging 40–80 yrs of age. We measured 6MWD, height, weight, spirometry, heart rate (HR), maximum HR (HRmax) during the 6-min walk test/the predicted maximum HR (HRmax % pred), Borg dyspnoea score and oxygen saturation. The mean±sd 6MWD was 571±90 m (range 380–782 m). Males walked 30 m more than females (p<0.001). A multiple regression model for the 6MWD included age, sex, height, weight and HRmax % pred (adjusted r2 = 0.38; p<0.001), but there was variability across centres (adjusted r2 = 0.09–0.73) and its routine use is not recommended. Age had a great impact in 6MWD independent of the centres, declining significantly in the older population (p<0.001). Age-specific reference standards of 6MWD were constructed for male and female adults. In healthy subjects, there were geographic variations in 6MWD and caution must be taken when using existing predictive equations. The present study provides new 6MWD standard curves that could be useful in the care of adult patients with chronic diseases.

Distance and Oxygen Desaturation During the 6-min Walk Test as Predictors of Long-term Mortality in Patients With COPD

RATIONALE The distance walked in the 6-min walk test (6MWT) predicts mortality in patients with severe COPD. Little is known about its prognostic value in patients with a wider range of COPD severity, living in different countries, and the potential additional impact of oxygen desaturation measured during the test. METHODS We enrolled 576 stable COPD outpatients in Spain and the United States and observed them for at least 3 years (median, 60 months). We measured FEV1, body mass index, Pao2, Charlson comorbidity score, 6-min walk distance (6MWD), and oxygen saturation by pulse oximetry (Spo2) during the 6MWT. Desaturation was defined as a fall in Spo2 > or = 4% or Spo2 < 90%. Regression analysis helped determine the association between these variables and all-cause and respiratory mortality. RESULTS The 6MWD was a good predictor of all-cause and respiratory mortality primarily in patients with FEV1 < 50% of predicted (p < 0.001) after adjusting for all covariates. Patients with desaturation during the 6MWT had a higher mortality rate than patients without desaturation (67% vs 38%, p < 0.001). Oxygen desaturation predicted mortality (relative risk, 2.63; 95% confidence interval, 1.53 to 4.51; p < 0.001) but with less power than Pao2 at rest. CONCLUSIONS The 6MWD helps predict mortality primarily in patients with severe COPD. Although the oxygen desaturation profile during the 6MWT improves the predictive ability of the 6MWD, it appears to be of less relevance than in other lung diseases and than the resting Pao2.

Guía clínica SEPAR-ALAT de diagnóstico y tratamiento de la EPOC

Puntos clave: – La enfermedad pulmonar obstructiva cronica (EPOC) se caracteriza por la presencia de obstruccion cronica y poco reversible al flujo aereo, que se asocia a una reaccion inflamatoria anomala, principalmente frente al humo del tabaco. – La obstruccion al flujo aereo se define por la espirometria cuando el cociente volumen espiratorio forzado en el primer segundo/capacidad vital forzada (FEV1/FVC) tras broncodilatacion es menor de 0,7 (o por debajo del limite inferior de la normalidad en personas mayores de 60 anos). – La EPOC se asocia a inflamacion cronica con remodelacion que afecta a las vias aereas, parenquima y arterias pulmonares. – La gravedad de la EPOC se clasifica por el valor del FEV1 posbroncodilatador, estando tambien relacionada con la existencia de sintomas, atrapamiento aereo, insuficiencia respiratoria, afectacion sistemica y comorbilidad asociada. – La prevalencia de la EPOC en la poblacion adulta es del 9% en Espana y oscila entre el 8 y el 20% en Latinoamerica. La EPOC representa la cuarta causa de muerte en Espana y en el mundo.

Lung cancer in patients with chronic obstructive pulmonary disease-- incidence and predicting factors.

RATIONALE Little is known about the clinical factors associated with the development of lung cancer in patients with chronic obstructive pulmonary disease (COPD), although airway obstruction and emphysema have been identified as possible risk factors. OBJECTIVES To explore incidence, histologic type, and factors associated with development of lung cancer diagnosis in a cohort of outpatients with COPD attending a pulmonary clinic. METHODS A cohort of 2,507 patients without initial clinical or radiologic evidence of lung cancer was followed a median of 60 months(30–90). At baseline, anthropometrics, smoking history, lung function,and body composition were recorded. Time to diagnosis and histologic type of lung cancer was then registered. Cox analysis was used to explore factors associated with lung cancer diagnosis. MEASUREMENTS AND MAIN RESULTS A total of 215 of the 2,507 patients with COPD developed lung cancer (incidence density of 16.7 cases per 1,000 person-years). The most frequent type was squamous cell carcinoma (44%). Lung cancer incidence was lower in patients with worse severity of airflow obstruction. Global Initiative for Chronic Obstructive Lung Disease Stages I and II, older age, lower body mass index,and lung diffusion capacity of carbon monoxide less than 80%were associated with lung cancer diagnosis. CONCLUSIONS Incidence density of lung cancer is high in outpatients with COPD and occurs more frequently in older patients with milder airflow obstruction (Global Initiative for Chronic Obstructive Lung Disease Stages I and II) and lower body mass index. A lung diffusion capacity of carbon monoxide less than 80% is associated with cancer diagnosis. Squamous cell carcinoma is the most frequent histologic type. Knowledge of these factors may help direct efforts for early detection of lung cancer and disease management.

C-Reactive Protein Levels and Survival in Patients With Moderate to Very Severe COPD

BACKGROUND Serum levels of C-reactive protein (CRP) are increased in patients with COPD and correlate modestly with variables predictive of outcomes. In epidemiologic studies, CRP level is associated with all-cause mortality in patients with mild-to-moderate disease. OBJECTIVE To determine if CRP levels are associated with survival in patients with moderate to very severe COPD in comparison with other well-known prognostic parameters of the disease. METHODS In 218 stable patients with COPD, we measured baseline serum CRP level, BODE (body mass index, obstruction, dyspnea, and exercise capacity) index and its components, arterial oxygenation (Pao(2)), inspiratory capacity (IC) to total lung capacity (TLC) ratio, and Charlson comorbidity score. We followed up the patients over time and evaluated the strength of the association between the variables and all-cause mortality. RESULTS During the follow-up time (median, 36 months; 25th to 75th percentiles, 24 to 50 months), 54 patients (25%) died. CRP levels were similar between survivors and the deceased (median, 3.8 mg/L; 95% confidence interval, 1.9 to 8.1; vs median, 4.5 mg/L; 95% confidence interval, 2.1 to 11.5; p = 0.22) and was not significantly associated with survival. CONCLUSIONS In this population of patients with clinically moderate to very severe COPD, the level of CRP level was not associated with survival compared with other prognostic clinical tools such as the BODE index, modified Medical Research Council scale, 6-min walk distance, percentage of predicted FEV(1), IC/TLC ratio < 0.25, and Pao(2). Other long-term studies of well-characterized patients with COPD could help determine the exact role of CRP levels as a biomarker in patients with clinical COPD.

The 6-min walking distance: long-term follow up in patients with COPD

The 6-min walking distance (6MWD) test is used in clinical practice and research into patients with chronic obstructive pulmonary disease (COPD). However, little is known about natural long-term change in this parameter. The 6MWD was measured at baseline and then annually for 5 yrs in 294 patients with COPD and its annual rate of decline was determined. Forced expiratory volume in one second (FEV1) was also measured and the relationship between changes in both markers was explored. At baseline, the median 6MWD was 380 m (range 160–600 m). It declined by 19% (16 m·yr-1) over the 5 yrs compared with baseline in patients with American Thoracic Society/European Respiratory Society stage III COPD (FEV1 30–50% predicted) and by 26% (15 m·yr-1) in patients with stage IV COPD (FEV1 <30% pred). Over the 5-yr follow-up, the proportion of patients with a minimal clinically significant decline of 54 m increased with the severity of the disease. It was 24% in stage II, 45% in stage III, and 63% in stage IV disease. In contrast, the rate of decline of FEV1 was greater in patients with milder airflow obstruction and lesser in patients with lower absolute FEV1 values. In conclusion, the 6-min walking distance test provides increasingly useful information as the severity of chronic obstructive pulmonary disease increases.

Validation and comparison of reference equations for the 6-min walk distance test

Exercise impairment as measured by the 6-min walk distance (6MWD) test afflicts many patients with chronic obstructive pulmonary disease (COPD) and is known to predict mortality. Reference equations for the 6MWD in adults have been published but not yet validated. The present authors prospectively followed 1,379 COPD patients for 55±30 months and tested the predictive value of the baseline 6MWD in metres, the 6MWD work (kg·m−1) and as a percentage of predicted values the 6MWD in meters according to two reference equations. All-cause mortality was the validating outcome. The best threshold values were identified for each of the tests using receiver operating characteristic (ROC) curves. The threshold values obtained were: 350 m for the 6MWD, 25,000 kg·m−1 for the 6MWD work, and 67 and 54% predicted for the two reference equations. All modalities of the testing were similar at predicting COPD mortality and correlated well with the 6MWD test. In conclusion, all modalities of testing predict mortality in chronic obstructive pulmonary disease equally well. In the 6-min walk distance test, a value <350 m is associated with increased mortality and should be regarded as abnormal.

The Progression of Chronic Obstructive Pulmonary Disease Is Heterogeneous

RATIONALE Chronic obstructive pulmonary disease (COPD) is thought to result in rapid and progressive loss of lung function usually expressed as mean values for whole cohorts. OBJECTIVES Longitudinal studies evaluating individual lung function loss and other domains of COPD progression are needed. METHODS We evaluated 1,198 stable, well-characterized patients with COPD (1,100 males) recruited in two centers (Florida and Tenerife, Spain) and annually monitored their multidomain progression from 1997 to 2009. Patients were followed for a median of 64 months and up to 10 years. Their individual FEV(1) (L) and BODE index slopes, expressed as annual change, were evaluated using regression models for repeated measures. A total of 751 patients with at least three measurements were used for the analyses. MEASUREMENTS AND MAIN RESULTS Eighteen percent of patients had a statistically significant FEV(1) slope decline (-86 ml/yr; 95% confidence interval [CI], -32 to -278 ml/yr). Higher baseline FEV(1) (relative risk, 1.857; 95% CI, 1.322-2.610; P < 0.001) and low body mass index (relative risk, 1.071; 95% CI, 1.035-1.106; P < 0.001) were independently associated with FEV(1) decline. The BODE index had a statistically significant increase (0.55, 0.20-1.37 point/yr) in only 14% of patients and these had more severe baseline obstruction. Concordance between FEV1 and BODE change was low (κ Cohen, 16%). Interestingly, 73% of patients had no significant slope change in FEV1 or BODE. Only the BODE change was associated with mortality in patients without FEV(1) progression. CONCLUSIONS The progression of COPD is very heterogeneous. Most patients show no statistically significant decline of FEV(1) or increase in BODE. The multidimensional evaluation of COPD should offer insight into response to COPD management.

Increased gastro-oesophageal reflux disease in patients with severe COPD

The prevalence and clinical consequences of gastro-oesophageal reflux disease (GERD) in chronic obstructive pulmonary disease (COPD) are not well characterised. The present study prospectively studied 42 males with COPD (forced expiratory volume in one second % predicted: 35%, range 20–49) and 16 healthy volunteers of similar age without respiratory or gastro-oesophageal symptoms. The diagnosis of GERD was confirmed using oesophageal 24 h pH monitoring. In the current study group, reflux symptoms were measured using the Vigneri score, cough and dyspnoea with the modified Medical Research Council questionnaire, and pulmonary function with bronchodilator response and health status using St Georges Respiratory Questionnaire. Pathological reflux was documented in 26 out of 42 patients (62%) and in three volunteers (19%). In patients with GERD, 15 patients (58%) did not report any reflux symptoms. There were no differences in symptoms, health status, bronchodilator treatment and pulmonary function test between patients with and without GERD. Oxygen desaturation coincided with episodes of increased oesophageal acidity in 40% of patients with GERD. Patients with severe chronic obstructive pulmonary disease have a high prevalence of asymptomatic gastro-oesophageal reflux. The association between this reflux and oxygen desaturation deserves further attention.