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Background: The Global Initiative for Obstructive Lung Disease (GOLD) does not promote diffusing capacity for carbon monoxide (Dlco) values in the evaluation of COPD. In GOLD spirometric stage I COPD patients, the clinical and prognostic impact of a low Dlco has not been explored., Research Question: Could a Dlco threshold help define an increased risk of death and a different clinical presentation in these patients?, Study Design and Methods: GOLD stage I COPD patients (n = 360) were enrolled and followed over 109 ± 50 months. Age, sex, pack-years' history, BMI, dyspnea, lung function measurements, exercise capacity, BODE index, and history of exacerbations were recorded. A cutoff value for Dlco was identified for all-cause mortality and the clinical and physiological characteristics of patients above and below the threshold compared. Cox regression analysis explored the predictive power of that cutoff value for all-cause mortality., Results: A Dlco cutoff value of <60% predicted was associated with all-cause mortality (Dlco ≥ 60%: 9% vs Dlco < 60%: 23%, P = .01). At a same FEV 1 % predicted and Charlson score, patients with Dlco < 60% had lower BMI, more dyspnea, lower inspiratory capacity (IC)/total lung capacity (TLC) ratio, lower 6-min walk distance (6MWD), and higher BODE. Cox multiple regression analysis confirmed that after adjusting for age, sex, pack-years history, smoking status, and BMI, a Dlco < 60% is associated with all-cause mortality (hazard ratio [HR], 95% CI = 3.37, 1.35-8.39; P = .009) INTERPRETATION: In GOLD I COPD patients, a Dlco < 60% predicted is associated with increased risk of death and worse clinical presentation. What the cause(s) of this association are and whether they can be treated need to be determined., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The value of the single-breath diffusing capacity of the lungs for carbon monoxide (Dlco) relates to outcomes for patients with COPD. However, little is known about the natural course of Dlco over time, intersubject variability, and factors that may influence Dlco progression., Research Question: What is the natural course of Dlco in patients with COPD over time, and which other factors, including sex differences, could influence this progression?, Study Design and Methods: We phenotyped 602 smokers (women, 33%), of whom 506 (84%) had COPD and 96 (16%) had no airflow limitation. Lung function, including Dlco, was monitored annually over 5 years. A random coefficients model was used to evaluate Dlco changes over time., Results: The mean (± SE) yearly decline in Dlco % in patients with COPD was 1.34% ± 0.015%/y. This was steeper compared with non-COPD control subjects (0.04% ± 0.032%/y; P = .004). Sixteen percent of the patients with COPD, vs 4.3% of the control subjects, had a statistically significant Dlco % slope annual decline (4.14%/y). At baseline, women with COPD had lower Dlco values (11.37% ± 2.27%; P < .001) in spite of a higher FEV 1 % than men. Compared with men, women with COPD had a steeper Dlco annual decline of 0.89% ± 0.42%/y (P = .039)., Interpretation: Patients with COPD have an accelerated decline in Dlco compared with smokers without the disease. However, the decline is slow, and a testing interval of 3 to 4 years may be clinically informative. The lower and more rapid decline in Dlco values in women, compared with men, suggests a differential impact of sex in gas exchange function., Trial Registry: ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: There is partial evidence that COPD is expressed differently in women than in men, namely on symptoms, pulmonary function, exacerbations, comorbidities or prognosis. There is a need to improve the characterization of COPD in females., Methods: We obtained and pooled data of 17 139 patients from 22 COPD cohorts and analysed the clinical differences by sex, establishing the relationship between these characteristics in women and the prognosis and severity of the disease. Comparisons were established with standard statistics and survival analysis, including crude and multivariate Cox-regression analysis., Results: Overall, 5355 (31.2%) women were compared with men with COPD. Women were younger, had lower pack-years, greater FEV 1 %, lower BMI and a greater number of exacerbations (all p < 0.05). On symptoms, women reported more dyspnea, equal cough but less expectoration (p < 0.001). There were no differences in the BODE index score in women (2.4) versus men (2.4) (p = 0.5), but the distribution of all BODE components was highly variable by sex within different thresholds of BODE. On prognosis, 5-year survival was higher in COPD females (86.9%) than in males (76.3%), p < 0.001, in all patients and within each of the specific comorbidities that we assessed. The crude and adjusted RR and 95% C.I. for death in males was 1.82 (1.69-1.96) and 1.73 (1.50-2.00), respectively., Conclusions: COPD in women has some characteristic traits expressed differently than compared to men, mainly with more dyspnea and COPD exacerbations and less phlegm, among others, although long-term survival appears better in female COPD patients., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Some interstitial lung diseases are associated with lung cancer. However, it is unclear whether asymptomatic interstitial lung abnormalities convey an independent risk., Objectives: The goal of this study was to assess whether interstitial lung abnormalities are associated with an increased risk of lung cancer., Methods: Data from all participants in the National Lung Cancer Trial were analyzed, except for subjects with preexisting interstitial lung disease or prevalent lung cancers. The primary analysis included those who underwent low-dose CT imaging; those undergoing chest radiography were included in a confirmatory analysis. Participants with evidence of reticular/reticulonodular opacities, honeycombing, fibrosis, or scarring were classified as having interstitial lung abnormalities. Lung cancer incidence and mortality in participants with and without interstitial lung abnormalities were compared by using Poisson and Cox regression, respectively., Results: Of the 25,041 participants undergoing low-dose CT imaging included in the primary analysis, 20.2% had interstitial lung abnormalities. Participants with interstitial lung abnormalities had a higher incidence of lung cancer (incidence rate ratio, 1.61; 95% CI, 1.30-1.99). Interstitial lung abnormalities were associated with higher lung cancer incidence on adjusted analyses (incidence rate ratio, 1.33; 95% CI, 1.07-1.65). Lung cancer-specific mortality was also greater in participants with interstitial lung abnormalities. Similar findings were obtained in the analysis of participants undergoing chest radiography., Conclusions: Asymptomatic interstitial lung abnormalities are an independent risk factor for lung cancer that can be incorporated into risk score models., (Copyright © 2019. Published by Elsevier Inc.)

Background: The stability of the new GOLD 2017 COPD staging is unknown, as well as the frequency of individual transitions in COPD stages beyond one year., Methods: All COPD participants in the CHAIN cohort were re-analysed according to GOLD 2017 up to five years of follow-up. Their individual changes within COPD stages were aggregated into cohort-wide Markov chains; group stability was evaluated using joinpoint regression., Results: At baseline, 959 COPD patients were distributed according to GOLD 2017 stages as 37.7% in A, 38.3% B, 8.2% C, and 15.7% D. The group proportion of patients in each stage was maintained from years one to five. However, we found significant changes between stages at the individual patient level, especially in the more severe stages. The probability of a patient remaining in the same GOLD 2017 COPD stage for two consecutive years ranged during the five years of follow-up for stage C from 16% to 31% per year, while for D from 23% to 43% per year, indicating substantial variation either increasing or decreasing severity for the vast majority of patients., Conclusions: We conclude that group stability observed in COPD staging according to GOLD 2017 recommendations is paired with a large variability at the individual patient level., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Despite the existing evidence-based smoking cessation interventions, chances of achieving that goal in real life are still low among patients with COPD. We sought to evaluate the clinical consequences of changes in smoking habits in a large cohort of patients with COPD., Methods: CHAIN (COPD History Assessment in Spain) is a Spanish multicenter study carried out at pulmonary clinics including active and former smokers with COPD. Smoking status was certified by clinical history and co-oximetry. Clinical presentation and disease impact were recorded via validated questionnaires, including the London Chest Activity of Daily Living (LCADL) and the Hospital Anxiety and Depression Scale (HADS). No specific smoking cessation intervention was carried out. Factors associated with and clinical consequences of smoking cessation were analyzed by multivariate regression and decision tree analyses., Results: One thousand and eighty-one patients with COPD were included (male, 80.8%; age, 65.2 [SD 8.9] years; FEV 1 , 60.2 [20.5]%). During the 2-year follow-up time (visit 2, 906 patients; visit 3, 791 patients), the majority of patients maintained the same smoking habit. Decision tree analysis detected chronic expectoration as the most relevant variable to identify persistent quitters in the future, followed by an LCADL questionnaire (cutoff 9 points). Total anxiety HADS score was the most relevant clinical impact associated with giving up tobacco, followed by the LCADL questionnaire with a cutoff value of 10 points., Conclusions: In this real-life prospective COPD cohort with no specific antismoking intervention, the majority of patients did not change their smoking status. Our study also identifies baseline expectoration, anxiety, and dyspnea with daily activities as the major determinants of smoking status in COPD., Trial Registry: ClinicalTrials.gov; No. NCT01122758; URL: www.clinicaltrials.gov., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Patients with chronic obstructive pulmonary disease (COPD) can be classified into groups A/C or B/D based on symptom intensity. Different threshold values for symptom questionnaires can result in misclassification and, in turn, different treatment recommendations. The primary aim was to find the best fitting cut-points for Global initiative for chronic Obstructive Lung Disease (GOLD) symptom measures, with an modified Medical Research Council dyspnea grade of 2 or higher as point of reference., Methods: After a computerized search, data from 41 cohorts and whose authors agreed to provide data were pooled. COPD studies were eligible for analyses if they included, at least age, sex, postbronchodilator spirometry, modified Medical Research Council, and COPD Assessment Test (CAT) total scores., Main Outcomes: Receiver operating characteristic curves and the Youden index were used to determine the best calibration threshold for CAT, COPD Clinical Questionnaire, and St. Georges Respiratory Questionnaire total scores. Following, GOLD A/B/C/D frequencies were calculated based on current cut-points and the newly derived cut-points., Findings: A total of 18,577 patients with COPD [72.0% male; mean age: 66.3 years (standard deviation 9.6)] were analyzed. Most patients had a moderate or severe degree of airflow limitation (GOLD spirometric grade 1, 10.9%; grade 2, 46.6%; grade 3, 32.4%; and grade 4, 10.3%). The best calibration threshold for CAT total score was 18 points, for COPD Clinical Questionnaire total score 1.9 points, and for St. Georges Respiratory Questionnaire total score 46.0 points., Conclusions: The application of these new cut-points would reclassify about one-third of the patients with COPD and, thus, would impact on individual disease management. Further validation in prospective studies of these new values are needed., (Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The clinical characteristics of patients with emphysema but without airway limitations remain unknown. The goal of this study was to compare the clinical features of current and former smokers without airflow limitation who have radiologic emphysema on chest CT scans vs a control group of current and ex-smokers without emphysema., Methods: Subjects enrolled had anthropometric characteristics recorded, provided a medical history, and underwent low-dose chest CT scanning. The following parameters were also evaluated: pulmonary function tests including diffusion capacity for carbon monoxide (Dlco), the modified Medical Research Council dyspnea score, COPD assessment test (CAT), and 6-min walk test (6MWT). A comparison was conducted between those with and without CT-confirmed emphysema., Results: Of the 203 subjects, 154 had emphysema, and 49 did not. Adjusted group comparisons revealed that a higher proportion of patients with emphysema according to low-dose chest CT scanning had an abnormal Dlco value (< 80%) (46% vs 19%; P = .02), a decrease in percentage of oxygen saturation > 4% during the 6MWT (8.5% vs 0; P = .04), and an altered quality of life (CAT score ≥ 10) (32% vs 14%; P = .01). A detailed analysis of the CAT questionnaire items revealed that more patients with emphysema had a score ≥ 1 in the "chest tightness" (P = .05) and "limitation when doing activities at home" (P < .01) items compared with those with no emphysema. They also experienced significantly more exacerbations in the previous year (0.19 vs 0.04; P = .02)., Conclusions: A significant proportion of smokers with emphysema according to low-dose chest CT scanning but without airway limitation had alterations in their quality of life, number of exacerbations, Dlco values, and oxygen saturation during the 6MWT test., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The COPD-Lung Cancer Screening Score (COPD-LUCSS) is a tool designed to help identify patients with COPD with the highest risk of developing lung cancer (LC). The COPD-LUCSS includes the determination of radiological emphysema, a potential limitation for its implementation in clinical practice. The diffusing capacity for carbon monoxide (DLCO) is a surrogate marker of emphysema and correlates well with CT-determined emphysema., Objective: To explore the use of the COPD-LUCSS using the DLCO instead of radiological emphysema, as a tool to identify patients with COPD at higher risk of LC death., Methods: The Body Mass Index, Airflow Obstruction, Dyspnea, Exercise Performance international cohort database was analyzed. By logistic regression analysis, we confirmed that the other parameters included in the COPD-LUCSS (age > 60, pack-years > 60, BMI < 25) were independently associated with LC death. We selected the best cutoff value for DLCO that independently predicted LC death. We then integrated the new COPD-LUCSS-DLCO assigning points to each parameter according to its hazard ratio value in the Cox regression model. The score ranges from 0 to 8 points., Results: By regression analysis, age > 60, BMI <25 kg/m(2), pack-year history > 60, and DLCO < 60% were independently associated with LC diagnosis. Two COPD-LUCSS-DLCO risk categories were identified: low risk (scores 0-3) and high risk (scores 3.5-8). In comparison to patients at low risk, risk of death from LC increased 2.4-fold (95% CI, 2.0-2.7) in the high-risk category., Conclusions: The COPD-LUCSS using DLCO instead of CT-determined emphysema is a useful tool to identify patients with COPD at risk of LC death and may help in its implementation in clinical practice., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Asthma-COPD overlap syndrome (ACOS) has been recently described by international guidelines. A stepwise approach to diagnosis using usual features of both diseases is recommended although its clinical application is difficult., Methods: To identify patients with ACOS, a cohort of well-characterized patients with COPD and up to 1 year of follow-up was analyzed. We evaluated the presence of specific characteristics associated with asthma in this COPD cohort, divided into major criteria (bronchodilator test > 400 mL and 15% and past medical history of asthma) and minor criteria (blood eosinophils > 5%, IgE > 100 IU/mL, or two separate bronchodilator tests > 200 mL and 12%). We defined ACOS by the presence of one major criterion or two minor criteria. Baseline characteristics, health status (COPD Assessment Test [CAT]), BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index, rate of exacerbations, and mortality up to 1 year of follow-up were compared between patients with and without criteria for ACOS., Results: Of 831 patients with COPD included,125 (15%) fulfilled the criteria for ACOS, and 98.4% of them sustained these criteria after 1 year. Patients with ACOS were predominantly male (81.6%), with symptomatic mild to moderate disease (67%), who were receiving inhaled corticosteroids (63.2%). There were no significant differences in baseline characteristics, and only survival was worse in patients with non-ACOS COPD after 1 year of follow-up (P < .05)., Conclusions: The proposed ACOS criteria are present in 15% of a cohort of patients with COPD and these patients show better 1-year prognosis than clinically similar patients with COPD with no ACOS criteria., Trial Registry: ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objective: The modified Medical Research Council (mMRC) dyspnea, the COPD Assessment Test (CAT), and the Clinical COPD Questionnaire (CCQ) have been interchangeably proposed by GOLD (Global Initiative for Chronic Obstructive Lung Disease) for assessing symptoms in patients with COPD. However, there are no data on the prognostic value of these tools in terms of mortality. We endeavored to evaluate the prognostic value of the CAT and CCQ scores and compare them with mMRC dyspnea., Methods: We analyzed the ability of these tests to predict mortality in an observational cohort of 768 patients with COPD (82% men; FEV1, 60%) from the COPD History Assessment in Spain (CHAIN) study, a multicenter observational Spanish cohort, who were monitored annually for a mean follow-up time of 38 months., Results: Subjects who died (n = 73; 9.5%) had higher CAT (14 vs 11, P = .022), CCQ (1.6 vs 1.3, P = .033), and mMRC dyspnea scores (2 vs 1, P < .001) than survivors. Receiver operating characteristic analysis showed that higher CAT, CCQ, and mMRC dyspnea scores were associated with higher mortality (area under the curve: 0.589, 0.588, and 0.649, respectively). CAT scores ≥ 17 and CCQ scores > 2.5 provided a similar sensitivity than mMRC dyspnea scores ≥ 2 to predict all-cause mortality., Conclusions: The CAT and the CCQ have similar ability for predicting all-cause mortality in patients with COPD, but were inferior to mMRC dyspnea scores. We suggest new thresholds for CAT and CCQ scores based on mortality risk that could be useful for the new GOLD grading classification., Trial Registry: ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov.

Background: There is no universal consensus on the best staging system for chronic obstructive pulmonary disease (COPD). Although documents (eg, the Global Initiative for Chronic Obstructive Lung Disease [GOLD] 2007) have traditionally used forced expiratory volume in 1 s (FEV1) for staging, clinical parameters have been added to some guidelines (eg, GOLD 2011) to improve patient management. As part of the COPD Cohorts Collaborative International Assessment (3CIA) initiative, we aimed to investigate how individual patients were categorised by GOLD 2007 and 2011, and compare the prognostic accuracy of the staging documents for mortality., Methods: We searched reports published from Jan 1, 2008, to Dec 31, 2014. Using data from cohorts that agreed to participate and had a minimum amount of information needed for GOLD 2007 and 2011, we did a patient-based pooled analysis of existing data. With use of raw data, we recalculated all participant assignments to GOLD 2007 I-IV classes, and GOLD 2011 A-D stages. We used survival analysis, C statistics, and non-parametric regression to model time-to-death data and compare GOLD 2007 and GOLD 2011 staging systems to predict mortality., Findings: We collected individual data for 15 632 patients from 22 COPD cohorts from seven countries, totalling 70 184 person-years. Mean age of the patients was 63·9 years (SD 10·1); 10 751 (69%) were men. Based on FEV1 alone (GOLD 2007), 2424 (16%) patients had mild (I), 7142 (46%) moderate (II), 4346 (28%) severe (III), and 1670 (11%) very severe (IV) disease. We compared staging with the GOLD 2007 document with that of the new GOLD 2011 system in 14 660 patients: 5548 (38%) were grade A, 2733 (19%) were grade B, 1835 (13%) were grade C, and 4544 (31%) were grade D. GOLD 2011 shifted the overall COPD severity distribution to more severe categories. There were nearly three times more COPD patients in stage D than in former stage IV (p<0·05). The predictive capacity for survival up to 10 years was significant for both systems (p<0·01) but area under the curves were only 0·623 (GOLD 2007) and 0·634 (GOLD 2011), and GOLD 2007 and 2011 did not differ significantly. We identified the percent predicted FEV1 thresholds of 85%, 55% and 35% as better to stage COPD severity for mortality, which are similar to the ones used previously., Interpretation: Neither GOLD COPD classification schemes have sufficient discriminatory power to be used clinically for risk classification at the individual level to predict total mortality for 3 years of follow-up and onwards. Increasing intensity of treatment of patients with COPD due to their GOLD 2011 reclassification is not known to improve health outcomes. Evidence-based thresholds should be searched when exploring the prognostic ability of current and new COPD multicomponent indices., Funding: None., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: The COPD Assessment Test (CAT) has been proposed for assessing health status in COPD, but little is known about its longitudinal changes. The objective of this study was to evaluate 1-year CAT variability in patients with stable COPD and to relate its variations to changes in other disease markers., Methods: We evaluated the following variables in smokers with and without COPD at baseline and after 1 year: CAT score, age, sex, smoking status, pack-year history, BMI, modified Medical Research Council (mMRC) scale, 6-min walk distance (6MWD), lung function, BODE (BMI, obstruction, dyspnea, exercise capacity) index, hospital admissions, Hospital and Depression Scale, and the Charlson comorbidity index. In patients with COPD, we explored the association of CAT scores and 1-year changes in the studied parameters., Results: A total of 824 smokers with COPD and 126 without COPD were evaluated at baseline and 441 smokers with COPD and 66 without COPD 1 year later. At 1 year, CAT scores for patients with COPD were similar (± 4 points) in 56%, higher in 27%, and lower in 17%. Of note, mMRC scale scores were similar (± 1 point) in 46% of patients, worse in 36%, and better in 18% at 1 year. One-year CAT changes were best predicted by changes in mMRC scale scores (β-coefficient, 0.47; P < .001). Similar results were found for CAT and mMRC scale score in smokers without COPD., Conclusions: One-year longitudinal data show variability in CAT scores among patients with stable COPD similar to mMRC scale score, which is the best predictor of 1-year CAT changes. Further longitudinal studies should confirm long-term CAT variability and its clinical applicability., Trial Registry: ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov.

Background: COPD is an independent risk factor for lung cancer, especially in patients with mild to moderate disease., Objective: To determine if performing lung cancer screening in GOLD 1 and 2 COPD patients, results in reduced lung cancer mortality., Methods: This study compared patients with mild to moderate COPD from 2 cohorts matched for age, gender, BMI, FEV1%, pack-yrs history and smoking status. The screening group (SG) had an annual low dose computed tomography (LDCT). The control group (CG) was prospectively followed with usual care. Lung cancer incidence and mortality densities were compared between groups., Results: From an initial sample of 410 (SG) and 735 (CG) patients we were able to match 333 patients from each group. At the same follow-up time lung cancer incidence density was 1.79/100 person-years in the SG and 4.14/100 person-years in the CG (p = 0.004). The most frequent histological type was adenocarcinoma in both SG and CG (65% and 46%, respectively), followed by squamous cell carcinoma (25% and 37%, respectively). Eighty percent of lung cancers in the SG (16/20) were diagnosed in stage I, and all of CG cancers (35/35) were in stage III or IV. Mortality incidence density from lung cancer (0.08 vs. 2.48/100 person-years, p < 0.001) was lower in the SG., Conclusions: This pilot study in patients with mild to moderate COPD suggests that screening with LDCT detects lung cancer in early stages, and could decrease lung cancer mortality in that high risk group. Appropriately designed studies should confirm these important findings., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: The new Global Initiative for Chronic Obstructive Lung Disease (GOLD) update includes airflow limitation, history of COPD exacerbations, and symptoms to classify and grade COPD severity. We aimed to determine their distribution in 11 well-defined COPD cohorts and their prognostic validity up to 10 years to predict time to death., Methods: Spirometry in all 11 cohorts was postbronchodilator. Survival analysis and C statistics were used to compare the two GOLD systems by varying time points., Results: Of 3,633 patients, 1,064 (33.6%) were in new GOLD patient group A (low risk, less symptoms), 515 (16.3%) were B (low risk, more symptoms), 561 (17.7%) were C (high risk, less symptoms), and 1,023 (32.3%) were D (high risk, more symptoms). There was great heterogeneity of this distribution within the cohorts ( x (2) , P < .01). No differences were seen in the C statistics of old vs new GOLD grading to predict mortality at 1 year (0.635 vs 0.639, P = .53), at 3 years (0.637 vs 0.645, P = .21), or at 10 years (0.639 vs 0.642, P = .76)., Conclusions: The new GOLD grading produces an uneven split of the COPD population, one third each in A and D patient groups, and its prognostic validity to predict time to death is no different than the old GOLD staging based in spirometry only.

Background: Phenotypic characterization of patients with COPD may have potential prognostic and therapeutic implications. Available information on the relationship between emphysema and the clinical presentation in patients with COPD is limited to advanced stages of the disease. The objective of this study was to describe emphysema presence, severity, and distribution and its impact on clinical presentation of patients with mild to moderate COPD., Methods: One hundred fifteen patients with COPD underwent clinical and chest CT scan evaluation for the presence, severity, and distribution of emphysema. Patients with and without emphysema and with different forms of emphysema distribution (upper/lower/core/peel) were compared. The impact of emphysema severity and distribution on clinical presentation was determined., Results: Fifty percent of the patients had mild homogeneously distributed emphysema (1.84; 0.76%-4.77%). Upper and core zones had the more severe degree of emphysema. Patients with emphysema were older, more frequently men, and had lower FEV(1)%, higher total lung capacity percentage, and lower diffusing capacity of the lung for carbon monoxide. No differences were found between the clinical or physiologic parameters of the different emphysema distributions., Conclusions: In patients with mild to moderate COPD, although the presence of emphysema has an impact on physiologic presentation, its severity and distribution seem to have little impact on clinical presentation.

Background: Electromagnetic navigation bronchoscopy (ENB) has been developed as a novel ancillary tool for the bronchoscopic diagnosis of pulmonary nodules. Despite successful navigation in 90% of patients, ENB diagnostic yield does not generally exceed 70%. We sought to determine whether the presence of a bronchus sign on CT imaging conditions diagnostic yield of ENB and might account for the discrepancy between successful navigation and diagnostic yield., Methods: We conducted a prospective, single-center study of ENB in 51 consecutive patients with pulmonary nodules. ENB was chosen as the least invasive diagnostic technique in patients with a high surgical risk, suspected metastatic disease, or advanced-stage disease, or in those who demanded a preoperative diagnosis prior to undergoing curative resection. We studied patient and technical variables that might condition diagnostic yield, including size, cause, location, distance to the pleural surface, and fluorodeoxyglucose uptake of a given nodule; the presence of a bronchus sign on CT imaging; registration point divergence; and the minimum distance from the tip of the locatable guide to the nodule measured during the procedure., Results: The diagnostic yield of ENB was 67% (34/51). The sensitivity and specificity of ENB for malignancy in this study were 71% and 100%, respectively. ENB was diagnostic in 79% (30/38) patients with a bronchus sign on CT imaging but only in 4/13 (31%) with no discernible bronchus sign. Univariate analysis identified the bronchus sign (P = .005) and nodule size (P = .04) as statistically significant variables conditioning yield, but on multivariate analysis, only the bronchus sign remained significant (OR, 7.6; 95% CI, 1.8-31.7). No procedure-related complications were observed., Conclusions: ENB diagnostic yield is highly dependent on the presence of a bronchus sign on CT imaging.

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.

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.

Rationale: Identification of risk factors for lung cancer can help in selecting patients who may benefit the most from smoking cessation interventions, early detection, or chemoprevention., Objective: To evaluate whether the presence of emphysema on low-radiation-dose CT (LDCT) of the chest is an independent risk factor for lung cancer., Methods: The study used data from a prospective cohort of 1,166 former and current smokers participating in a lung cancer screening study. All individuals underwent a baseline LDCT and spirometry followed by yearly repeat LDCT studies. The incidence density of lung cancer among patients with and without emphysema on LDCT was estimated. Stratified and multiple regression analyses were used to assess whether emphysema is an independent risk factor for lung cancer after adjusting for age, gender, smoking history, and the presence of airway obstruction on spirometry., Results: On univariate analysis, the incidence density of lung cancer among individuals with and without emphysema on LDCT was 25.0 per 1,000 person-years and 7.5 per 1,000 person-years, respectively (risk ratio [RR], 3.33; 95% confidence interval [CI], 1.41 to 7.85). Emphysema was also associated with increased risk of lung cancer when the analysis was limited to individuals without airway obstruction on spirometry (RR, 4.33; 95% CI, 1.04 to 18.16). Multivariate analysis showed that the presence of emphysema (RR, 2.51; 95% CI, 1.01 to 6.23) on LDCT but not airway obstruction (RR, 2.10; 95% CI, 0.79 to 5.58) was associated with increased risk of lung cancer after adjusting for potential cofounders., Conclusions: Results suggest that the presence of emphysema on LDCT is an independent risk factor for lung cancer.

Objectives: To compare gender differences in the clinical expression of COPD patients attending a pulmonary clinic., Materials and Methods: We compared 53 FEV1-matched men and women with COPD attending a pulmonary clinic. We studied age, smoking pack-years history, Pa(O2), Pa(CO2), functional residual capacity, body mass index (BMI), dyspnea, 6-min walk distance (6MWD), health-related quality of life, presence of comorbidities, and exacerbations in the previous year., Results: Women were younger (57 years vs 65 years, p < 0.05), smoked less (48 pack-years vs 69 pack-years, p < 0.05), had better Pa(O2) (74 mm Hg vs 67 mm Hg, p < 0.05), lower Pa(CO2) (40 mm Hg vs 45 mm Hg, p < 0.05), lower BMI (25 vs 28, p < 0.05), more exacerbations in the last year (1 vs 0, p < 0.05), and fewer comorbidities (Charlson score 2 vs score 4, p < 0.05) than men. Even though women had the same FEV1, better oxygenation, better Pa(CO2), and fewer comorbidities, they performed poorer in walking distance (6MWD percentage of predicted, 87% vs 105%; p = 0.05), had worse quality-of-life scores (Saint George's Respiratory Questionnaire [SGRQ] symptoms score, 51 vs 41, p < 0.05; SGRQ activity score, 58 vs 47, p < 0.05), and had a higher degree of dyspnea (Modified Medical Research Council scale > 2, 28% vs 6%, p = 0.05)., Conclusions: In a population of patients with COPD attending a pulmonary clinic, there are gender-related differences in the clinical expression of COPD that need further attention.

The pressure-time index (PTI = Pmouth/Pi max x Ti/Ttot) has been validated by Ramonatxo (J. Appl. Physiol. 78 (1995) 646 and by Jabour (Am. Rev. Respir. Dis. 144 (1991) 531 as a noninvasive tool for the assessment of inspiratory muscles load. Nobody until now has evaluated the correlation between the PTI and diaphragmatic activity. Further, the PTI has not been compared with another measures of respiratory muscle load such as the transdiaphragmatic pressure index or TTdi. The purpose of our study was to test the hypothesis that the PTI measured at the mouth (PTIm) is a noninvasive reflection of TTdf and electromyographic activity of the diaphragm (EMGdf). We studied 6 patients with COPD and 5 normal individuals at rest and during a CO2 rebreathing trial and simultaneously measured PTIm, TTdi and EMGdi. The curves of PTIm and EMGdi follows the same trend during the CO2 rebreathing trial with strong and significant correlation between these parameters (r = 0.89 P < 0.05 and r = 0.82 P < 0.05 for PaCO2 of 45 and 53 mmHg respectively). We conclude that PTIm measured as Pmouth/Pi max x Ti/Ttot is an adequate noninvasive method that reflect not only the diaphragmatic activity but also the inspiratory muscles load.