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1.  Dyspnea severity, changes in dyspnea status and mortality in the general population: the Vlagtwedde/Vlaardingen study 
European Journal of Epidemiology  2012;27(11):867-876.
Dyspnea is a predictor of mortality. The effects of dyspnea severity and changes in dyspnea status on all-cause and cause-specific mortality remain unclear. The Vlagtwedde/Vlaardingen study started in 1965 and subjects were re-examined every 3 years until 1989/1990. Vital status of all 8,465 subjects on December 31st, 2008 was assessed. Associations between mortality and dyspnea severity and changes in dyspnea status were investigated using Cox regression adjusted for gender, age, FEV1 %predicted, place of residence, smoking and BMI. After 43 years of follow-up, 2,883 (39 %) of 7,360 subjects examined for dyspnea severity had died, 1,386 (19 %) due to cardiovascular disease, 267 (4 %) due to chronic obstructive pulmonary disease (COPD). Subjects with moderate and severe dyspnea had increased all-cause and cardiovascular mortality [moderate: HR = 1.3 (95 % CI 1.2–1.5) and 1.4 (1.1–1.6), severe: 1.5 (1.1–2.0) and 1.9 (1.3–2.6) respectively] compared to asymptomatics. Severe dyspnea was significantly associated with COPD mortality [3.3 (2.0–5.2)]. Subjects who lost dyspnea had hazard ratios for all-cause and cause-specific mortality comparable to asymptomatics. Persistent dyspnea and dyspnea development were risk factors for all-cause, cardiovascular and COPD mortality [persistent: 2.0 (1.4–2.8), 1.9 (1.2–3.3) and 3.3 (1.2–8.9), development: 1.5 (1.2–1.8), 2.0 (1.5–2.6) and 3.8 (2.3–6.3) respectively]. Additionally, dyspnea effects on mortality were more pronounced in overweight/obese and older subjects and in subjects with better lung function. These results show that dyspnea is associated with mortality in a severity-dependent manner. Furthermore this study is the first showing that dyspnea remission normalizes mortality risk. Having or developing dyspnea is a risk factor for mortality.
Electronic supplementary material
The online version of this article (doi:10.1007/s10654-012-9736-0) contains supplementary material, which is available to authorized users.
PMCID: PMC3501159  PMID: 23054033
Dyspnea; Dyspnea severity; Dyspnea remission; Mortality; Risk factor; Longitudinal studies
2.  Analysis of longitudinal changes in dyspnea of patients with chronic obstructive pulmonary disease: an observational study 
Respiratory Research  2012;13(1):85.
Guidelines recommend that symptoms as well as lung function should be monitored for the management of patients with chronic obstructive pulmonary disease (COPD). However, limited data are available regarding the longitudinal change in dyspnea, and it remains unknown which of relevant measurements might be used for following dyspnea.
We previously consecutively recruited 137 male outpatients with moderate to very severe COPD, and followed them every 6 months for 5 years. We then reviewed and reanalyzed the data focusing on the relationships between the change in dyspnea and the changes in other clinical measurements of lung function, exercise tolerance tests and psychological status. Dyspnea with activities of daily living was assessed with the Oxygen Cost Diagram (OCD) and modified Medical Research Council dyspnea scale (mMRC), and two dimensions of disease-specific health status questionnaires of the Chronic Respiratory Disease Questionnaire (CRQ) and the St. George’s Respiratory Questionnaire (SGRQ) were also used. Dyspnea at the end of exercise tolerance tests was measured using the Borg scale.
The mMRC, CRQ dyspnea and SGRQ activity significantly worsened over time (p < 0.001), but the OCD did not (p = 0.097). Multiple regression analyses revealed that the changes in the OCD, mMRC, CRQ dyspnea and SGRQ activity were significantly correlated to changes in forced expiratory volume in one second (FEV1) (correlation of determination (r2) = 0.05-0.19), diffusing capacity for carbon monoxide (r2 = 0.04-0.08) and psychological status evaluated by Hospital Anxiety and Depression Scale (r2 = 0.14-0.17), although these correlations were weak. Peak Borg score decreased rather significantly, but was unrelated to changes in clinical measurements.
Dyspnea worsened over time in patients with COPD. However, as different dyspnea measurements showed different evaluative characteristics, it is important to follow dyspnea using appropriate measurements. Progressive dyspnea was related not only to progressive airflow limitation, but also to various factors such as worsening of diffusing capacity or psychological status. Changes in peak dyspnea at the end of exercise may evaluate different aspects from other dyspnea measurements.
PMCID: PMC3519563  PMID: 23006638
COPD; Dyspnea; Airflow limitation; Diffusing capacity; Exercise; Psychological status; Disease progression
3.  Evaluation of Quality of Life with the Chronic Obstructive Pulmonary Disease Assessment Test in Chronic Obstructive Pulmonary Disease and the Effect of Dyspnea on Disease-Specific Quality of Life in These Patients 
Yonsei Medical Journal  2013;54(5):1214-1219.
The chronic obstructive pulmonary disease (COPD) assessment test (CAT) was recently introduced for use in assessing disease-specific quality of life and follow-up of patients with COPD. The purpose of this study was to evaluate the effect of the dyspnea on disease-specific quality of life detected by CAT score in patients with COPD.
Materials and Methods
In this study, 90 stable patients with COPD as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria were included. The level of dyspnea was assessed with the Medical Research Council (MRC) dyspnea scale, and disease-specific quality of life was assessed with CAT score.
The mean±SD age was 68.5±10.9 (range 41-97) years. A significant relationship was established between CAT score, MRC dyspnea scale score and GOLD stage in patients with COPD. There was also a positive correlation between dyspnea scale scores and GOLD stage in the patients (p<0.001), as well as positive correlation between CAT score and dyspnea scale score (p<0.001). CAT score showed a significant correlation with hospitalization and exacerbations (p<0.05).
Dyspnea is an important symptom that may impact quality of life in patients with COPD. CAT was shown to be a simple, fast and intelligible measurement of disease-specific quality of life, and was correlated with levels of dyspnea in patients with COPD.
PMCID: PMC3743182  PMID: 23918572
Chronic obstructive pulmonary disease; dyspnea; quality of life
4.  Proposing a standardized method for evaluating patient report of the intensity of dyspnea during exercise testing in COPD 
Measuring dyspnea intensity associated with exercise provides insights into dyspnea-limited exercise capacity, and has been used to evaluate treatment outcomes for chronic obstructive pulmonary disease (COPD). Three patient-reported outcome scales commonly cited for rating dyspnea during exercise are the modified Borg scale (MBS), numerical rating scale for dyspnea (NRS-D), and visual analogue scale for dyspnea (VAS-D). Various versions of each scale were found. Our objective was to evaluate the content validity of scales commonly used in COPD studies, to explore their ability to capture patients’ experiences of dyspnea during exercise, and to evaluate a standardized version of the MBS.
A two-stage procedure was used, with each stage involving one-on-one interviews with COPD patients who had recently completed a clinic-based exercise event on a treadmill or cycle ergometer. An open-ended elicitation interview technique was used to understand patients’ experiences of exercise-induced dyspnea, followed by patients completing the three scales. The cognitive interviewing component of the study involved specific questions to evaluate the patients’ perspectives of the content and format of the scales. Results from Stage 1 were used to develop a standardized version of the MBS, which was then subjected to further content validity assessment during Stage 2.
Thirteen patients participated in the two-stage process (n = 6; n = 7). Mean forced expiratory volume in 1 second (FEV1) percent predicted was 40%, mean age 57 years, and 54% were male. Participants used a variety of terms to describe the intensity and variability of exercise-induced dyspnea. Subjects understood the instructions and format of the standardized MBS, and were able to easily select a response to report the level of dyspnea associated with their recent standardized exercise.
This study provides initial evidence in support of using a standardized version of the MBS version for quantifying dyspnea intensity associated with exercise in patients with COPD.
PMCID: PMC3379870  PMID: 22745534
Borg scale; dyspnea assessment; COPD; exercise testing
5.  Identifying adults at risk of COPD who need confirmatory spirometry in primary care 
Canadian Family Physician  2011;57(2):e51-e57.
To examine the usefulness of a symptom-based case-finding questionnaire (CFQ) and the Medical Research Council (MRC) dyspnea scale in identifying which individuals with known risk factors for chronic obstructive pulmonary disease (COPD) require targeted spirometry in primary care.
Cross-sectional study.
Three community primary care practices in Ontario.
Men and women 40 years of age and older with a smoking history of 20 pack-years or more.
Main outcome measures
We administered a CFQ for the presence of cough, sputum, wheeze, dyspnea, and recurrent respiratory infections (possible range of scores from 0 to 5) and applied the MRC dyspnea scale to assess the severity of COPD (possible range of scores from 1 to 5). Spirometric measures of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were collected, with COPD defined as a postbronchodilator FEV1/FVC of less than 0.7 and FEV1 of less than 80% of the predicted value. Using spirometric data to confirm the diagnosis of COPD, likelihood ratios, pretest and posttest probabilities, and area under a receiver operating characteristic curve were calculated for the total CFQ and MRC scores.
Scores for the CFQ and MRC dyspnea scale were available for 996 and 829 participants, respectively. The likelihood ratios for a total CFQ score of 3 or higher and an MRC dyspnea score of 4 or 5 were 1.82 (95% confidence interval [CI] 1.48 to 2.22) and 4.22 (95% CI 2.08 to 8.56), respectively. The likelihood ratios for a total CFQ score of 2 or less and an MRC dyspnea score of 1 were 0.75 (95% CI 0.66 to 0.85) and 0.50 (95% CI 0.39 to 0.65), respectively. Area under the receiver operating characteristic curve was 0.62 (95% CI 0.58 to 0.67; P < .001) for the total CFQ scores and 0.64 (95% CI 0.60 to 068; P < .001) for the MRC dyspnea scores.
In adults with known risk factors, the likelihood of having moderate to severe COPD is increased in those who report 3 or more common respiratory symptoms and marked functional limitation resulting from dyspnea. However, selecting individuals for spirometry based on symptoms alone will identify less than half of those with moderate to severe COPD.
PMCID: PMC3038833  PMID: 21642706
6.  Effect of Dyspnea Induced by Breath-holding on Maximal Muscular Strength of Patients with COPD 
[Purpose] The purpose of the present study was to clarify the effect of dyspnea induced by breath-holding on maximum muscular strength of patients with COPD. [Subjects] This study recruited 14 COPD subjects via public posting. [Methods] Dyspnea was assessed by the modified Borg scale. The subject asked to stop breathing at end-expiration and to hold their breath with a nose clip for as long as possible. Both total breath-holding time and threshold time of dyspnea were measured with a chronograph. Dyspnea reserve time (DRT) was defined by subtracting the threshold time of perception dyspnea from total breath-holding time in order to calculate the 50% DRT. The muscular strengths of maximal handgrip contraction were measured at baseline, 50% threshold time of dyspnea (subliminal point of dyspnea), and the 50% DRT (supraliminal point of dyspnea). [Results] The maximal handgrip at the supraliminal point of dyspnea was significantly lower than the baseline and subliminal point of dyspnea values. There was no statistically significant difference in maximal muscular strength between baseline and the subliminal point of dyspnea value. [Conclusion] The present results demonstrate that dyspnea induced by breath-holding aggravates weakness in the maximum muscular strength of patients with COPD.
PMCID: PMC3944300  PMID: 24648643
Breath-holding; Dyspnea; Muscular Strength
7.  Randomized Controlled Trial of an Internet-Based Versus Face-to-Face Dyspnea Self-Management Program for Patients With Chronic Obstructive Pulmonary Disease: Pilot Study 
People with chronic obstructive pulmonary disease (COPD) continue to experience dyspnea with activities of daily living (ADL) despite optimal medical management. Information and communication technologies may facilitate collaborative symptom management and could potentially increase the reach of such interventions to those who are unable to attend face-to-face pulmonary rehabilitation or self-management programs.
The purpose of this randomized study was to test the efficacy of two 6-month dyspnea self-management programs, Internet-based (eDSMP) and face-to-face (fDSMP), on dyspnea with ADL in people living with COPD.
We randomly assigned 50 participants with moderate to severe COPD who were current Internet users to either the eDSMP (n = 26) or fDSMP (n = 24) group. The content of the two programs was similar, focusing on education, skills training, and ongoing support for dyspnea self-management, including independent exercise. The only difference was the mode (Internet/personal digital assistant [PDA] or face-to-face) in which the education sessions, reinforcement contacts, and peer interactions took place. Participants returned to one of two academic clinical sites for evaluation at 3 and 6 months. The primary outcome of dyspnea with ADL was measured with the Chronic Respiratory Questionnaire. Secondary outcomes of exercise behavior, exercise performance, COPD exacerbations, and mediators, such as self-efficacy and social support, were also measured. A satisfaction survey was administered and a semistructured exit interview was conducted at the final visit.
The study was stopped early due to multiple technical challenges with the eDSMP, but follow-up was completed on all enrolled participants. Data were available for 39 participants who completed the study (female: 44%; age: 69.5 ± 8.5 years; percent predicted forced expiratory volume in 1 s: 49.6 ± 17.0%). The fDSMP and eDSMP showed similar clinically meaningful changes in dyspnea with ADL from baseline to 3 months (fDSMP: + 3.3 points; eDSMP: + 3.5 points) and sustained these improvements at 6 months (fDSMP: + 4.0 points; eDSMP: + 2.5 points; time effects P < .001; group by time P = .51). Self-reported endurance exercise time (P = .001), physical functioning (P = .04), and self-efficacy for managing dyspnea (P = .02) also showed positive improvements over time in both groups with no significant differences with respect to program modality. Participants who completed the study reported favorable satisfaction with the programs.
Although there were numerous technical challenges with the eDSMP, both dyspnea self-management programs were effective in reducing dyspnea with ADL in the short term. Our findings will need to be confirmed in a larger randomized trial with more mature Web and personal digital assistant tools, use of a control group, and longer follow-up.
Trial registration NCT00102401,
PMCID: PMC2483918  PMID: 18417444
Dyspnea; pulmonary disease; chronic disease; self-care; self-efficacy; health behavior; health education; exercise; monitoring; Internet; cellular phone; telemedicine; randomized controlled trial; Personal Digital Assistant (PDA)
8.  Symptoms and impact of symptoms on function and health in patients with chronic obstructive pulmonary disease and chronic heart failure in primary health care 
Patients with chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) seem to have several symptoms in common that impact health. However, methodological differences make this difficult to compare.
Comparisons of symptoms, impact of symptoms on function and health between patients with COPD and CHF in primary health care (PHC).
The study is cross sectional, including patients with COPD (n=437) and CHF (n=388), registered in the patient administrative systems of PHC. The patients received specific questionnaires – the Memorial Symptom Assessment Scale, the Medical Research Council dyspnea scale, and the Fatigue Impact Scale – by mail and additional questions about psychological and physical health.
The mean age was 70±10 years and 78±10 years for patients with COPD and CHF respectively (P=0.001). Patients with COPD (n=273) experienced more symptoms (11±7.5) than the CHF patients (n=211) (10±7.6). The most prevalent symptoms for patients with COPD were dyspnea, cough, and lack of energy. For patients with CHF, the most prevalent symptoms were dyspnea, lack of energy, and difficulty sleeping. Experience of dyspnea, cough, dry mouth, feeling irritable, worrying, and problems with sexual interest or activity were more common in patients with COPD while the experience of swelling of arms or legs was more common among patients with CHF. When controlling for background characteristics, there were no differences regarding feeling irritable, worrying, and sexual problems. There were no differences in impact of symptoms or health.
Patients with COPD and CHF seem to experience similar symptoms. There were no differences in how the patients perceived their functioning according to their cardinal symptoms; dyspnea and fatigue, and health. An intervention for both groups of patients to optimize the management of symptoms and improve function is probably more relevant in PHC than focusing on separate diagnosis groups.
PMCID: PMC4111648  PMID: 25071370
chronic obstructive pulmonary disease; chronic heart failure; symptom; function; health
9.  Predictors of Mortality in Patients with Stable COPD 
Journal of General Internal Medicine  2008;23(11):1829-1834.
To determine which easily available clinical factors are associated with mortality in patients with stable COPD and if health-related quality of life (HRQoL) provides additional information.
Five-year prospective cohort study.
Five outpatient clinics of a teaching hospital.
Six hundred stable COPD patients recruited consecutively.
The variables were age, FEV1%, dyspnea, previous hospital admissions and emergency department visits for COPD, pack-years of smoking, comorbidities, body mass index, and HRQoL measured by Saint George’s Respiratory Questionnaire (SGRQ), Chronic Respiratory Questionnaire (CRQ), and Short-Form 36 (SF-36). Logistic and Cox regression models were used to assess the influence of these variables on mortality and survival.
FEV1%(OR: 0.62, 95% CI 0.5 to 0.75), dyspnea (OR 1.92, 95% CI 1.2 to 3), age (OR 2.41, 95% CI 1.6 to 3.6), previous hospitalization due to COPD exacerbations (OR 1.53, 1.2 to 2) and lifetime pack-years (OR 1.15, 95% CI 1.1 to 1.2) were independently related to respiratory mortality. Similarly, these factors were independently related to all-cause mortality with dyspnea having the strongest association (OR 1.54, 95% CI 1.1 to 2.2). HRQoL was an independent predictor of respiratory and all-cause mortality only when dyspnea was excluded from the models, except scores on the SGRQ were associated with all-cause mortality with dyspnea in the model.
Among patients with stable COPD, FEV1% was the main predictor of respiratory mortality and dyspnea of all-cause mortality. In general, HRQoL was not related to mortality when dyspnea was taken into account, and CRQ and SGRQ behaved in similar ways regarding mortality.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-008-0783-x) contains supplementary material, which is available to authorized users.
PMCID: PMC2585660  PMID: 18795373
chronic obstructive pulmonary disease; mortality; health-related quality of life
10.  Continuing to Confront COPD International Patient Survey: methods, COPD prevalence, and disease burden in 2012–2013 
The Continuing to Confront COPD International Patient Survey aimed to estimate the prevalence and burden of COPD globally and to update findings from the Confronting COPD International Survey conducted in 1999–2000.
Materials and methods
Chronic obstructive pulmonary disease (COPD) patients in 12 countries worldwide were identified through systematic screening of population samples. Telephone and face-to-face interviews were conducted between November 2012 and May 2013 using a structured survey that incorporated validated patient-reported outcome instruments. Eligible patients were adults aged 40 years and older who were taking regular respiratory medications or suffered with chronic respiratory symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of chronic bronchitis. The burden of COPD was measured with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale.
Of 106,876 households with at least one person aged ≥40 years, 4,343 respondents fulfilled the case definition of COPD and completed the full survey. COPD prevalence ranged from 7% to 12%, with most countries falling within the range of 7%–9%. In all countries, prevalence increased with age, and in all countries except the US was greater among men (range 6%–14%) than among women (range 5%–11%). A significant disease burden was observed when considering COPD symptoms or health status, and showed wide variations across countries. Prevalence of moderate-to-severe dyspnea (mMRC scale ≥2) ranged from 27% to 61%, and mean CAT score ranged from 16.0 to 24.8, indicating medium-to-high impairment.
This survey, representing 12 countries, showed similar rates of estimated COPD prevalence across countries that were higher than those reported a decade ago in the original Confronting COPD International Survey. A significant burden of COPD was demonstrated by symptoms and health care-resource use, similar to that reported in the original survey.
PMCID: PMC4057333  PMID: 24944511
chronic obstructive pulmonary disease; patient perspective; prevalence; patient-reported outcomes
11.  A Multivariate Model for Predicting Respiratory Status in Patients with Chronic Obstructive Pulmonary Disease 
To develop and validate a multivariate model for predicting respiratory status in patients with advanced chronic obstructive pulmonary disease (COPD).
Prospective, double-blind study of peak flow monitoring.
Albuquerque Veterans Affairs Medical Center.
Male veterans with an irreversible component of airflow obstruction on baseline pulmonary function tests.
This study was conducted between January 1995 and May 1996. At entry, subjects were instructed in the use of the modified Medical Research Council Dyspnea Scale and a mini–Wright peak flow meter equipped with electronic storage. For the next 6 months, they recorded their dyspnea scores once daily and peak expiratory flow rates twice daily, before and after the use of bronchodilators. Patients were blinded to their peak expiratory flow rates, and medical care was provided in the customary manner. Readings were aggregated into 7-day sampling intervals, and interval means were calculated for dyspnea score and peak expiratory flow rate parameters. Intervals from all subjects were then pooled and randomized to separate groups for model development (training set) and validation (test set). In the training set, logistic regression was used to identify variables that predicted future respiratory status. The dependent variable was the log odds that the subject would attain his highest level of dyspnea in the next 7 days. The final model was used to stratify the test set into “high-risk” and “low-risk” categories. The analysis was repeated for 3-day intervals.
Of the 40 patients considered eligible for study, 8 declined to participate, 4 could not master the technique of peak flow monitoring, and 6 had no fluctuations in their dyspnea level. The remaining 22 subjects form the basis of this report. Fourteen (64%) of the latter completed the 6-month protocol. Data from the 8 who were dropped or died were included up to the point of withdrawal. For 7-day forecasts, mean dyspnea score and mean daily prebronchodilator peak expiratory flow rate were identified as predictor variables. The adjusted odds ratio (OR) for mean dyspnea score was 2.71 (95% confidence interval [CI] 1.79, 4.12) per unit. For mean prebronchodilator peak expiratory flow rate, it was 1.05 (95% CI 1.01, 1.09) per percentage predicted. For 3-day forecasts, the model was composed of mean dyspnea score and mean daily bronchodilator response. The ORs for these terms were 2.66 (95% CI 2.06, 3.44) per unit and 0.980 (95% CI 0.962, 0.998) per percentage of improvement over baseline, respectively. For a given level of dyspnea, higher prebronchodilator peak expiratory flow rate and lower bronchodilator response were poor prognostic findings. When the models were applied to the test sets, “high-risk” intervals were 4 times more likely to be followed by maximal symptoms than “low-risk” intervals.
Dyspnea scores and certain peak expiratory flow rate parameters are independent predictors of respiratory status in patients with COPD. However, our results suggest that monitoring is of little benefit except in patients with the most advanced form of this disease, and its contribution to their management is modest at best.
PMCID: PMC1496987  PMID: 9686712
lung disease, obstructive; spirometry; peak expiratory flow rate (PEFR); ambulatory monitoring; self-care
12.  Dyspnea assessment and adverse events during sputum induction in COPD 
The inhalation of normal or hypertonic saline during sputum induction (SI) may act as an indirect bronchoconstrictive stimulus leading to dyspnea and lung function deterioration. Our aim was to assess dyspnea and adverse events in COPD patients who undergo SI following a safety protocol.
Sputum was induced by normal and hypertonic (4.5%) saline solution in 65 patients with COPD of varying severity. In order to minimize saline-induced bronchoconstriction a protocol based on the European Respiratory Society sputum induction Task group report was followed. Dyspnea change was scored using the Borg scale and lung function was assessed by spirometry and oximetry.
Borg score changes [median(IQR) 1.5(0–2)] were observed during SI in 40 subjects; 16 patients required temporary discontinuation of the procedure due to dyspnea-general discomfort and 2 did not complete the session due to dyspnea-wheezing. The change in Borg dyspnea score was significantly correlated with oxygen saturation and heart rate changes and with discontinuation of the procedure due to undesired symptoms. 19 subjects presented an hyperresponsive reaction (decline>20% from baseline FEV1). No significant correlation between Borg changes and FEV1decline was found. Patients with advanced COPD presented significantly greater Borg and oxygen saturation changes than patients with less severe disease (p = 0.02 and p = 0.001, respectively). Baseline FEV1, oxygen saturation and 6MWT demonstrated significant diagnostic values in distinguishing subjects who develop an adverse physiologic reaction during the procedure.
COPD patients undergoing SI following a safety protocol do not experience major adverse events. Dyspnea and oxygen desaturation is more likely to occur in patients with disease in advanced stages, leading to short discontinuation or less frequently to termination of the procedure. Baseline FEV1, oxygen saturation and 6MWT may have a prognostic value for the development of these adverse events and might be useful to be evaluated in advance.
PMCID: PMC1524986  PMID: 16808839
13.  Anemia and iron deficiency in COPD patients: prevalence and the effects of correction of the anemia with erythropoiesis stimulating agents and intravenous iron 
Little is known about iron deficiency (ID) and anemia in Chronic Obstructive Pulmonary Disease (COPD). The purposes of this study were: (i) To study the prevalence and treatment of anemia and ID in patients hospitalized with an exacerbation of COPD. (ii) to study the hematological responses and degree of dyspnea before and after correction of anemia with subcutaneous Erythropoiesis Stimulating Agents (ESAs) and intravenous (IV) iron therapy, in ambulatory anemic patients with both COPD and chronic kidney disease.
(i) We examined the hospital records of all patients with an acute exacerbation of COPD (AECOPD) to assess the investigation, prevalence, and treatment of anemia and ID. (ii) We treated 12 anemic COPD outpatients with the combination of ESAs and IV-iron, given once weekly for 5 weeks. One week later we measured the hematological response and the severity of dyspnea by Visual Analogue Scale (VAS).
(i) Anemia and iron deficiency in hospitalized COPD patients: Of 107 consecutive patients hospitalized with an AECOPD, 47 (43.9%) were found to be anemic on admission. Two (3.3%) of the 60 non-anemic patients and 18 (38.3%) of the 47 anemic patients had serum iron, percent transferrin saturation (%Tsat) and serum ferritin measured. All 18 (100%) anemic patients had ID, yet none had oral or IV iron subscribed before or during hospitalization, or at discharge. (ii) Intervention outpatient study: ID was found in 11 (91.7%) of the 12 anemic ambulatory patients. Hemoglobin (Hb), Hematocrit (Hct) and the VAS scale scores increased significantly with the ESAs and IV-iron treatment. There was a highly significant correlation between the ∆Hb and ∆VAS; rs = 0.71 p = 0.009 and between the ∆Hct and ∆VAS; rs = 0.8 p = 0.0014.
ID is common in COPD patients but is rarely looked for or treated. Yet correction of the ID in COPD patients with ESAs and IV iron can improve the anemia, the ID, and may improve the dyspnea.
PMCID: PMC3946070  PMID: 24564844
Iron deficiency; Anemia; COPD; Renal failure; Erythropoietin
14.  Prevalence and Global Initiative for Chronic Obstructive Lung Disease Group Distribution of Chronic Obstructive Pulmonary Disease Detected by Preoperative Pulmonary Function Test 
PLoS ONE  2015;10(1):e0115787.
Despite being a major public health problem, chronic obstructive pulmonary disease (COPD) remains underdiagnosed, and only 2.4% COPD patients are aware of their disease in Korea. The objective of this study was to estimate the prevalence of COPD detected by spirometry performed as a preoperative screening test and to determine the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group distribution and self-awareness of COPD.
We reviewed the medical records of adults (age, ≥40 years) who had undergone spirometry during preoperative screening between April and August 2013 at a tertiary hospital in Korea. COPD was defined as a postbronchodilator forced expiratory volume in 1 s/forced vital capacity ratio of <0.7. We analyzed self-administered COPD questionnaires for the assessment of the frequency of acute exacerbation over the previous year and dyspnea severity using the modified Medical Research Council dyspnea scale and COPD assessment test.
Among 3029 patients aged >40 years who had undergone spirometry as a preoperative screening test, 474 (15.6%; 404 men; median age, 70 years; range, 44–93 years) were diagnosed with COPD. Only 26 (5.5%) patients reported previous diagnosis of COPD (2.1%), emphysema (0.8%), or chronic bronchitis (2.5%). The GOLD group distribution was as follows: 63.3% in group A, 31.2% in group B, 1.7% in group C, and 3.8% in group D.
The prevalence of COPD diagnosed by preoperative spirometry was 15.6%, and only 5.5% patients were aware of their disease. Approximately one-third of the COPD patients belonged to GOLD groups B, C, and D, which require regular treatment.
PMCID: PMC4308080  PMID: 25625286
15.  Obesity and COPD: Associated Symptoms, Health-related Quality of Life, and Medication Use 
COPD  2011;8(4):275-284.
There is little data about the combined effects of COPD and obesity. We compared dyspnea, health-related quality of life (HRQoL), exacerbations, and inhaled medication use among patients who are overweight and obese to those of normal weight with COPD.
We performed secondary data analysis on 364 Veterans with COPD. We categorized subjects by body mass index (BMI). We assessed dyspnea using the Medical Research Council (MRC) dyspnea scale and HRQoL using the St. George's Respiratory Questionnaire. We identified treatment for an exacerbation and inhaled medication use in the past year. We used multiple logistic and linear regression models as appropriate, with adjustment for age, COPD severity, smoking status, and comorbidities.
The majority of our population was male (n=355, 98%) and either overweight (n=115, 32%) or obese (n=138, 38%). Obese and overweight subjects had better lung function (obese: mean FEV1 55.4% ±19.9% predicted, overweight: mean FEV1 50.0% ±20.4% predicted) than normal weight subjects (mean FEV1 44.2% ±19.4% predicted), yet obese subjects reported increased dyspnea [adjusted OR of MRC score ≥2= 4.91 (95% CI 1.80, 13.39], poorer HRQoL, and were prescribed more inhaled medications than normal weight subjects. There was no difference in any outcome between overweight and normal weight patients.
Despite having less severe lung disease, obese patients reported increased dyspnea and poorer HRQoL than normal weight patients. The greater number of inhaled medications prescribed for obese patients may represent overuse. Obese patients with COPD likely need alternative strategies for symptom control in addition to those currently recommended.
PMCID: PMC3169653  PMID: 21809909
Obesity; COPD; health-related quality of life; symptoms; inhaled medications; exacerbations
16.  Knowledge about COPD among users of primary health care services 
Chronic obstructive pulmonary disease (COPD) is often underdiagnosed, which might be attributable to a lack of knowledge about the disease among the general population. The objective of this study was to evaluate COPD-related knowledge among primary care users in an urban area in Brazil.
This study was carried out at primary care clinics (PCCs), including 12 general PCCs and 26 family health PCCs, in the city of Goiânia, Brazil. Between May 2013 and February 2014, we interviewed 674 PCC users, applying a questionnaire designed to assess COPD-related knowledge. Satisfactory knowledge of COPD was defined as knowing at least two of its symptoms and that smoking is a risk factor for the disease.
Of the 674 users interviewed, only 9.2% recognized the term “COPD”, 75.1% recognized the term “emphysema”, and 15.7% did not recognize either term. We found that recognizing either term was associated with a higher level of education (P<0.001). The prevalence of satisfactory knowledge of COPD was 16.2%, and having such knowledge was associated with being over 60 years of age. The COPD symptom known by the greatest proportion of users (70.6%) was dyspnea, and most (87.5%) knew that smoking is a risk factor, whereas only a few (4.9%) knew that exposure to wood smoke is also a risk factor. The most frequently cited sources of knowledge were the media (43.1%) and a relative with COPD (36.4%).
Most of the PCC users evaluated did not know the term “COPD” but were familiar with the term “emphysema”. The level of basic knowledge about the disease was low in this population. These results should alert health care administrators to the need for interventions aimed at increasing the diagnosis rate and thus promoting the early treatment of COPD.
PMCID: PMC4279667  PMID: 25565794
primary care; underdiagnosis; health professional; perception
17.  Dyspnea affective response: comparing COPD patients with healthy volunteers and laboratory model with activities of daily living 
Laboratory-induced dyspnea (breathing discomfort) in healthy subjects is widely used to study perceptual mechanisms, yet the relationship between laboratory-induced dyspnea in healthy volunteers and spontaneous dyspnea in patients with chronic lung disease is not well established. We compared affective responses to dyspnea 1) in COPD patients vs. healthy volunteers (HV) undergoing the same laboratory stimulus; 2) in COPD during laboratory dyspnea vs. during activities of daily living (ADL).
We induced moderate and high dyspnea levels in 13 COPD patients and 12 HV by increasing end-tidal CO2 (PETCO2) during restricted ventilation, evoking air hunger. We used the multidimensional dyspnea profile (MDP) to measure intensity of sensory qualities (e.g., air hunger (AH) and work/effort (W/E)) as well as immediate discomfort (A1) and secondary emotions (A2). Ten of the COPD subjects also completed the MDP outside the laboratory following dyspnea evoked by ADL.
COPD patients and HV reported similar levels of immediate discomfort relative to sensory intensity. COPD patients and HV reported anxiety and frustration during laboratory-induced dyspnea; variation among individuals far outweighed the small differences between subject groups. COPD patients reported similar intensities of sensory qualities, discomfort, and emotions during ADL vs. during moderate laboratory dyspnea. Patients with COPD described limiting ADL to avoid greater dyspnea.
In this pilot study, we found no evidence that a history of COPD alters the affective response to laboratory-induced dyspnea, and no difference in affective response between dyspnea evoked by this laboratory model and dyspnea evoked by ADL.
PMCID: PMC3663820  PMID: 23621986
Dyspnea; Symptom assessment; COPD
18.  Utility of the CAT in the therapy assessment of COPD exacerbations in China 
Chronic obstructive pulmonary disease (COPD) exacerbations are accompanied with increased systemic inflammation, which accelerate the pulmonary function injury and impair the quality of life. Prompt and effective treatments for COPD exacerbations slow down the disease progression, but an objective instrument to assess the efficacy of the treatments following COPD exacerbations is lacking nowadays. The COPD Assessment Test (CAT) is an 8-item questionnaire designed to assess and quantify health status and symptom burden in COPD patients. We hypothesize that the change in CAT score is related to the treatment response following COPD exacerbations.
78 inpatients with clinician-diagnosed acute exacerbation of COPD (AECOPD) completed the CAT, St George’s Respiratory Questionnaire (SGRQ) and modified Medical Research Council (mMRC) Dyspnea Scale both at exacerbation and the 7th day of therapy, and a subgroup of 39 patients performed the pulmonary function test. Concentrations of serum C-reactive protein (CRP) and plasma fibrinogen were assayed at the same time. Correlations between the CAT and other measurements were examined.
After 7 days’ therapy, the CAT and SGRQ scores, mMRC grades, as well as the concentrations of CRP and fibrinogen all decreased significantly (P < 0.001). Meanwhile, the FEV1% predicted had a significant improvement (P < 0.001). The CAT scores were significantly correlated with concurrent concentrations of CRP and fibrinogen, SGRQ scores, FEV1% predicted and mMRC grades (P < 0.05). The change in CAT score was positively correlated with the change of CRP (r = 0.286, P < 0.05), SGRQ score (r = 0.725, P < 0.001) and mMRC grades (r = 0.593, P < 0.001), but not with fibrinogen (r = 0.137, P > 0.05) or FEV1% predicted (r = -0.101, P > 0.05). No relationship was found between the changes of SGRQ score and CRP and fibrinogen (P>0.05).
The CAT is associate with the changes of systemic inflammation following COPD exacerbations. Moreover, the CAT is responsive to the treatments, similar to other measures such as SGRQ, mMRC dyspnea scale and pulmonary function. Therefore, the CAT is a potentially useful instrument to assess the efficacy of treatments following COPD exacerbations.
PMCID: PMC3995795  PMID: 24618290
Chronic obstructive pulmonary disease assessment test; Exacerbation; Inflammatory biomarkers; Pulmonary function; Therapy assessment
19.  Gender and respiratory factors associated with dyspnea in chronic obstructive pulmonary disease 
Respiratory Research  2007;8(1):18.
We had shown that COPD women expressed more dyspnea than men for the same degree of airway obstruction.
Evaluate gender differences in respiratory factors associated with dyspnea in COPD patients.
In a FEV1 % matched population of 100 men and women with COPD we measured: age, MMRC, FEV1, FVC, TLC, IC/TLC, PaO2, PaCO2, DLCO, Pimax, P0.1, Ti/Ttot, BMI, ffmi, 6MWD and VAS scale before and after the test, the Charlson score and the SGRQ. We estimated the association between these parameters and MMRC scores. Multivariate analysis determined the independent strength of those associations.
MMRC correlated with: BMI (men:-0.29, p = 0.04; women:-0.28, p = 0.05), ffmi (men:-0.39, p = 0.01), FEV1 % (men:-0.64, p < 0.001; women:-0.29, p = 0.04), FVC % (men:-0.45, p = 0.001; women:-0.33, p = 0.02), IC/TLC (men:-0.52, p < 0.001; women: -0.27, p = 0.05), PaO2 (men:-0.59, p < 0.001), PaCO2 (men:0.27, p = 0.05), DLCO (men:-0.54, p < 0.001), P0.1/Pimax (men:0.46, p = 0.002; women:0.47, p = 0.005), dyspnea measured with the Visual Analog Scale before (men:0.37, p = 0.04; women:0.52, p = 0.004) and after 6MWD (men:0.52, p = 0.002; women:0.48, p = 0.004) and SGRQ total (men:0.50, p < 0.001; women:0.59, p < 0.001). Regression analysis showed that P0.1/Pimax in women (r2 = 0.30) and BMI, DLCO, PaO2 and P0.1/Pimax in men (r2 = 0.81) were the strongest predictors of MMRC scores.
In mild to severe COPD patients attending a pulmonary clinic, P0.1/Pimax was the unique predictor of MMRC scores only in women. Respiratory factors explain most of the variations of MMRC scores in men but not in women. Factors other than the respiratory ones should be included in the evaluation of dyspnea in women with COPD.
PMCID: PMC1821020  PMID: 17341300
20.  Spirometric Correlates of Dyspnea Improvement Among Emergency Department Patients With Chronic Obstructive Pulmonary Disease Exacerbation 
Respiratory care  2008;53(7):892-896.
To examine whether change in slow vital capacity (SVC) correlates to dyspnea improvement during emergency department (ED) treatment of chronic obstructive pulmonary disease (COPD) exacerbation.
We performed a prospective cohort study and enrolled consecutive patients during a 3-week period. ED patients ≥ 55 years old with COPD exacerbation were asked to perform bedside spirometry shortly after ED arrival and again at discharge. SVC was measured first, then forced expiratory volume in the first second (FEV1), peak expiratory flow (PEF), and forced vital capacity (FVC). Concurrent with spirometry, patients rated their dyspnea on a 10-cm visual analogue scale.
Thirty-six patients were enrolled. The median ED stay was 271 min (interquartile range 219–370 min). Seventy-one percent of the patients reported dyspnea improvement during their ED stay. Change in SVC was significantly higher among the patients whose dyspnea improved than among those whose did not (median increase of 0.15 L vs median decrease of 0.25 L, respectively, p < 0.01). By contrast, the change in spirometry values were similar for FEV1, PEF, and FVC (all p > 0.30). Spearman correlation supported these findings: SVC r = 0.45 (p = 0.02) versus nonsignificant correlation with FEV1 (r = 0.33), PEF (r = −0.22), and FVC (r = 0.35).
Increase in SVC significantly correlated with dyspnea improvement among ED patients with moderate-to-severe COPD exacerbation. Change in SVC merits consideration when evaluating therapeutic response during COPD exacerbation.
PMCID: PMC3523353  PMID: 18593490
chronic obstructive pulmonary disease; COPD; dyspnea; emergency department; exacerbation; slow vital capacity; spirometry
21.  COPD management costs according to the frequency of COPD exacerbations in UK primary care 
The economic burden of chronic obstructive pulmonary disease (COPD) exacerbations is significant, but the impact of other sources on the overall cost of COPD management is largely unknown. We aimed to estimate overall costs for patients experiencing none, one, or two or more exacerbations per year in the UK.
A retrospective cohort of prevalent COPD patients was identified in the Clinical Practice Research Datalink UK database. Patients with information recorded for at least 12 months before and after cohort entry date were included (first prevalent COPD diagnosis confirmed by spirometry on/after April 1, 2009). Patients were categorized as having none, one, or two or more moderate-to-severe COPD exacerbations in the 12 months after cohort entry and further classified by the Global initiative for chronic Obstructive Lung Disease (GOLD) category of airflow obstruction and the Medical Research Council dyspnea scale. Study outcomes included counts of general practitioner interactions, moderate-severe COPD exacerbations, and non-COPD hospitalizations. Estimated resource use costs were calculated using National Health Service reference costs for 2010–2011.
The cohort comprised 58,589 patients (mean age 69.5 years, mean dyspnea grade 2.5, females 46.6%, current smokers 33.1%). The average total annual per patient cost of COPD management, excluding medications, was £2,108 for all patients and £1,523, £2,405, and £3,396 for patients experiencing no, one, or two or more moderate-to-severe exacerbations, respectively. General practitioner interactions contributed most to these annual costs, accounting for £1,062 (69.7%), £1,313 (54.6%), and £1,592 (46.9%) in patients with no, one, or two or more moderate-to-severe exacerbations, respectively.
Disease management strategies focused on reducing costs in primary care may help reduce total COPD costs significantly.
PMCID: PMC3890403  PMID: 24426781
chronic obstructive pulmonary disease; frequent exacerbations; infrequent exacerbations; health resources; health care costs
22.  Disturbed Sleep among COPD Patients is Longitudinally Associated with Mortality and Adverse COPD Outcomes 
Sleep Medicine  2012;13(5):476-483.
To investigate the cross-sectional association between COPD severity and disturbed sleep and the longitudinal association between disturbed sleep and poor health outcomes.
98 adults with spirometrically-confirmed COPD were recruited through population-based, random-digit telephone dialing. Sleep disturbance was evaluated using a 4-item scale assessing insomnia symptoms as: difficulty falling asleep, nocturnal awakening, morning tiredness, and sleep duration adequacy. COPD severity was quantified by: FEV1 and COPD Severity Score, which incorporates COPD symptoms, requirement for COPD medications and oxygen, and hospital-based utilization. Subjects were assessed one year after baseline to determine longitudinal COPD exacerbations and emergency utilization and were followed for a median 2.4 years to assess all-cause mortality.
Sleep disturbance was cross-sectionally associated with cough, dyspnea, and COPD Severity Score but not FEV1. In multivariable logistic regression, controlling for sociodemographics and body-mass index, sleep disturbance longitudinally predicted both incident COPD exacerbations (OR=4.7; p=0.018) and respiratory-related emergency utilization (OR=11.5; p=0.004). In Cox proportional hazards analysis, controlling for the same covariates, sleep disturbance predicted poorer survival (HR=5.0; p=0.013). For all outcomes, these relationships persisted after also controlling for baseline FEV1 and COPD Severity Score.
Disturbed sleep is cross-sectionally associated with worse COPD and is longitudinally predictive of COPD exacerbations, emergency health care utilization, and mortality.
PMCID: PMC3336048  PMID: 22429651
chronic obstructive pulmonary disease; cognitive performance; insomnia; mortality; outcomes
23.  CAT correlates positively with respiratory rate and is a significant predictor of the impact of COPD on daily life of patients: a cross sectional study 
The pathophysiological changes of COPD tend to worsen with progression, triggering limiting symptoms and implying the decrease in the activities of daily living and quality of life. The COPD Assessment Test (CAT) is a questionnaire designed to measure the impact of COPD on the health status. The aim of this study was to evaluate the impact of the disease through the CAT in a Brazilian sample of COPD patients and to correlate symptoms at rest with the CAT score in these patients.
Study of cases with COPD patients was conducted by pulmonary rehabilitation program (RP). Respiratory rate (RR) and symptoms (dyspnea by Modified Borg Scale Dyspnea Index; symptoms by CAT) were analyzed at the beginning of the RP.
The study analyzed 28 COPD patients, both genders, age 65.93 ± 7.84 years and many patients ranging from severe and very severe disease. The majority of patients were rated by CAT with low impact-disease (n = 13/46, 4%);medium (n = 11/39, 3%) and the high impact-diseases were observed in a few subjects (n = 4/14.3%). The difference between all CAT scores was significant, p = 0.000. There was a positive correlation between respiratory rate and CAT scores impact-level (r = 0.585, p = 0.001). The results obtained by the Borg Scale revealed a high presence of symptoms in these COPD patients but no association with CAT.
The CAT is a sensitive tool to assess the current health status of COPD patients, and in Southern Brazil it is positively correlated with respiratory rate.
PMCID: PMC4258018  PMID: 25485107
CAT; COPD; Dyspnea; Rehabilitation
24.  Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD) 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at:
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at: member_giacomini.htm.
For more information on the economic analysis, please visit the PATH website:
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website:
The objective of this evidence-based analysis was to determine the effectiveness and cost-effectiveness of smoking cessation interventions in the management of chronic obstructive pulmonary disease (COPD).
Clinical Need: Condition and Target Population
Tobacco smoking is the main risk factor for COPD. It is estimated that 50% of older smokers develop COPD and more than 80% of COPD-associated morbidity is attributed to tobacco smoking. According to the Canadian Community Health Survey, 38.5% of Ontarians who smoke have COPD. In patients with a significant history of smoking, COPD is usually present with symptoms of progressive dyspnea (shortness of breath), cough, and sputum production. Patients with COPD who smoke have a particularly high level of nicotine dependence, and about 30.4% to 43% of patients with moderate to severe COPD continue to smoke. Despite the severe symptoms that COPD patients suffer, the majority of patients with COPD are unable to quit smoking on their own; each year only about 1% of smokers succeed in quitting on their own initiative.
Smoking cessation is the process of discontinuing the practice of inhaling a smoked substance. Smoking cessation can help to slow or halt the progression of COPD. Smoking cessation programs mainly target tobacco smoking, but may also encompass other substances that can be difficult to stop smoking due to the development of strong physical addictions or psychological dependencies resulting from their habitual use.
Smoking cessation strategies include both pharmacological and nonpharmacological (behavioural or psychosocial) approaches. The basic components of smoking cessation interventions include simple advice, written self-help materials, individual and group behavioural support, telephone quit lines, nicotine replacement therapy (NRT), and antidepressants. As nicotine addiction is a chronic, relapsing condition that usually requires several attempts to overcome, cessation support is often tailored to individual needs, while recognizing that in general, the more intensive the support, the greater the chance of success. Success at quitting smoking decreases in relation to:
a lack of motivation to quit,
a history of smoking more than a pack of cigarettes a day for more than 10 years,
a lack of social support, such as from family and friends, and
the presence of mental health disorders (such as depression).
Research Question
What are the effectiveness and cost-effectiveness of smoking cessation interventions compared with usual care for patients with COPD?
Research Methods
Literature Search
Search Strategy
A literature search was performed on June 24, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations (1950 to June Week 3 2010), EMBASE (1980 to 2010 Week 24), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Library, and the Centre for Reviews and Dissemination for studies published between 1950 and June 2010. A single reviewer reviewed the abstracts and obtained full-text articles for those studies meeting the eligibility criteria. Reference lists were also examined for any additional relevant studies not identified through the search. Data were extracted using a standardized data abstraction form.
Inclusion Criteria
English-language, full reports from 1950 to week 3 of June, 2010;
either randomized controlled trials (RCTs), systematic reviews and meta-analyses, or non-RCTs with controls;
a proven diagnosis of COPD;
adult patients (≥ 18 years);
a smoking cessation intervention that comprised at least one of the treatment arms;
≥ 6 months’ abstinence as an outcome; and
patients followed for ≥ 6 months.
Exclusion Criteria
case reports
case series
Outcomes of Interest
≥ 6 months’ abstinence
Quality of Evidence
The quality of each included study was assessed taking into consideration allocation concealment, randomization, blinding, power/sample size, withdrawals/dropouts, and intention-to-treat analyses.
The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence:
Summary of Findings
Nine RCTs were identified from the literature search. The sample sizes ranged from 74 to 5,887 participants. A total of 8,291 participants were included in the nine studies. The mean age of the patients in the studies ranged from 54 to 64 years. The majority of studies used the Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD staging criteria to stage the disease in study subjects. Studies included patients with mild COPD (2 studies), mild-moderate COPD (3 studies), moderate–severe COPD (1 study) and severe–very severe COPD (1 study). One study included persons at risk of COPD in addition to those with mild, moderate, or severe COPD, and 1 study did not define the stages of COPD. The individual quality of the studies was high. Smoking cessation interventions varied across studies and included counselling or pharmacotherapy or a combination of both. Two studies were delivered in a hospital setting, whereas the remaining 7 studies were delivered in an outpatient setting. All studies reported a usual care group or a placebo-controlled group (for the drug-only trials). The follow-up periods ranged from 6 months to 5 years. Due to excessive clinical heterogeneity in the interventions, studies were first grouped into categories of similar interventions; statistical pooling was subsequently performed, where appropriate. When possible, pooled estimates using relative risks for abstinence rates with 95% confidence intervals were calculated. The remaining studies were reported separately.
Abstinence Rates
Table ES1 provides a summary of the pooled estimates for abstinence, at longest follow-up, from the trials included in this review. It also shows the respective GRADE qualities of evidence.
Summary of Results*
Abbreviations: CI, confidence interval; NRT, nicotine replacement therapy.
Statistically significant (P < 0.05).
One trial used in this comparison had 2 treatment arms each examining a different antidepressant.
Based on a moderate quality of evidence, compared with usual care, abstinence rates are significantly higher in COPD patients receiving intensive counselling or a combination of intensive counselling and NRT.
Based on limited and moderate quality of evidence, abstinence rates are significantly higher in COPD patients receiving NRT compared with placebo.
Based on a moderate quality of evidence, abstinence rates are significantly higher in COPD patients receiving the antidepressant bupropion compared to placebo.
PMCID: PMC3384371  PMID: 23074432
25.  Once-daily NVA237 improves exercise tolerance from the first dose in patients with COPD: the GLOW3 trial 
Exercise limitation, dynamic hyperinflation, and exertional dyspnea are key features of symptomatic chronic obstructive pulmonary disease (COPD). We assessed the effects of glycopyrronium bromide (NVA237), a once-daily, long-acting muscarinic antagonist, on exercise tolerance in patients with moderate to severe COPD.
Patients were randomized to a cross-over design of once-daily NVA237 50 μg or placebo for 3 weeks, with a 14-day washout. Exercise endurance, inspiratory capacity (IC) during exercise, IC and expiratory volumes from spirometry, plethysmographic lung volumes, leg discomfort and dyspnea under exercise (Borg scales), and transition dyspnea index were measured on Days 1 and 21 of treatment. The primary endpoint was endurance time during a submaximal constant-load cycle ergometry test on Day 21.
A total of 108 patients were randomized to different treatment groups (mean age, 60.5 years; mean post-bronchodilator, forced expiratory volume in 1 second [FEV1] 57.1% predicted). Ninety-five patients completed the study. On Day 21, a 21% difference in endurance time was observed between patients treated with NVA237 and those treated with placebo (P < 0.001); the effect was also significant from Day 1, with an increase of 10%. Dynamic IC at exercise isotime and trough FEV1 showed significant and clinically relevant improvements from Day 1 of treatment that were maintained throughout the study. This was accompanied by inverse decreases in residual volume and functional residual capacity. NVA237 was superior to placebo (P < 0.05) in decreasing leg discomfort (Borg CR10 scale) on Day 21 and exertional dyspnea on Days 1 and 21 (transition dyspnea index and Borg CR10 scale at isotime). The safety profile of NVA237 was similar to that of the placebo.
NVA237 50 μg once daily produced immediate and significant improvement in exercise tolerance from Day 1. This was accompanied by sustained reductions in lung hyperinflation (indicated by sustained and significant improvements in IC at isotime), and meaningful improvements in trough FEV1 and dyspnea. Improvements in exercise endurance increased over time, suggesting that mechanisms beyond improved lung function may be involved in enhanced exercise tolerance. ( Identifier: NCT01154127).
PMCID: PMC3430121  PMID: 22973092
COPD; dyspnea; FEV1; exercise tolerance; LAMA; NVA237

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