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.
Borg scale; dyspnea assessment; COPD; exercise testing
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.
COPD; Dyspnea; Airflow limitation; Diffusing capacity; Exercise; Psychological status; Disease progression
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.
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.
Obesity; COPD; health-related quality of life; symptoms; inhaled medications; exacerbations
The Modified Medical Research Council (MMRC) scale, baseline dyspnea index (BDI) and the oxygen cost diagram (OCD) are widely used tools for evaluation of limitation of activities due to dyspnea in patients with chronic obstructive pulmonary disease (COPD). There is, however, limited information on how these relate with each other and with multiple parameters of physiological impairment.
To study the interrelationships between MMRC, BDI and OCD scales of dyspnea and their correlation with multiple measures of physiological impairment.
MATERIALS AND METHODS:
A retrospective analysis of pooled data of 88 male patients with COPD (GOLD stages II, III and IV) was carried out. Dyspnea was evaluated using the MMRC, BDI and OCD scales. Physiological impairment was assessed by spirometry (FVC % predicted and FEV1 % predicted), arterial blood gas (ABG) analysis and measurement of the 6-min walk distance (6MWD).
The interrelationships between MMRC, BDI and OCD scales were moderately strong. The BDI and OCD scores had strong correlations with ABG abnormalities, weak correlations with spirometric parameters but none with 6MWD. MMRC grades were significantly associated with BDI and OCD scores but did not show clear associations with spirometric parameters, ABG abnormalities and 6MWD.
The MMRC grades of dyspnea and the BDI and OCD scales are moderately interrelated. While the BDI and OCD scales have significant associations with parameters of physiological impairment, the MMRC scale does not.
Baseline dyspnoea index; chronic obstructive pulmonary disease; Modified Medical Research Council scale; oxygen cost diagram
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.
clinicaltrials.gov NCT00102401, http://www.webcitation.org/5X8CX4gLC
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)
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.
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.
Patients with chronic obstructive pulmonary disease (COPD) often experience depression and anxiety, but little information is available regarding Chinese patients with these conditions. The present study assessed depression and anxiety in Chinese patients with COPD.
A case–controlled study was designed with 1100 patients with COPD enrolled in the case group and1100 residents without COPD and respiratory symptoms selected as the control group. Anxiety and depression in both groups were evaluated using the Hospital Anxiety and Depression Scale (HADS). The body mass index,degree of airflow obstruction, dyspnea, and exercise capacity (BODE ) index was used to assess COPD severity. Binary logistic regression models were used to test the association between anxiety and depression.
The patients with COPD were more likely than controls to experience depression (cases, HADS 10.5 ± 3.6, prevalence 35.7%; controls, HADS 8.7 ± 2.7, prevalence 7.2%) and anxiety (cases, HADS 10.4 ± 3.1, prevalence 18.3%; controls, HADS 8.6 ± 2.1, prevalence 5.3%). Subjects with anxious and depressive symptoms had poorer health outcomes including a higher BODE index, a shorter 6-minute-walk distance (6MWD), more dyspnea, and a higher St George’s respiratory questionnaire (SGRQ) score. The prevalence of anxious and depressive symptoms increased with increasing BODE scores. On the basis of binary logistic regression, the BODE index was significantly correlated with anxiety (OR = 1.47, p < 0.001) and depression (OR = 1.51, p < 0.001). Anxious and depressive symptoms were also associated with several factors including younger age, female sex, higher education level, lower household income and history of smoking.
This study confirmed the high prevalence of anxiety and depression in Chinese outpatients with COPD. Patients with COPD who had anxiety and/or depression had a poorer health-related quality of life.
Chinese Clinical Trials Registration(ChiCTR-TRC-12001958)
Chronic obstructive pulmonary disease; Anxiety; Depression; Hospital Anxiety and Depression Scale
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. (ClinicalTrials.gov Identifier: NCT01154127).
COPD; dyspnea; FEV1; exercise tolerance; LAMA; NVA237
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.
Health status, dyspnea and psychological status are important clinical outcomes in chronic obstructive pulmonary disease (COPD). However, forced expiratory volume in one second (FEV1) measured by spirometry, the standard measurement of airflow limitation, has only a weak relationship with these outcomes in COPD. Recently, in addition to spirometry, impulse oscillometry (IOS) measuring lung resistance (R) and reactance (X) is increasingly being used to assess pulmonary functional impairment.
We aimed to identify relationships between IOS measurements and patient-reported outcomes in 65 outpatients with stable COPD. We performed pulmonary function testing, IOS, high-resolution computed tomography (CT), and assessment of health status using the St. George's Respiratory Questionnaire (SGRQ), dyspnea using the Medical Research Council (MRC) scale and psychological status using the Hospital Anxiety and Depression Scale (HADS). We then investigated the relationships between these parameters. For the IOS measurements, we used lung resistance at 5 and 20 Hz (R5 and R20, respectively) and reactance at 5 Hz (X5). Because R5 and R20 are regarded as reflecting total and proximal airway resistance, respectively, the fall in resistance from R5 to R20 (R5-R20) was used as a surrogate for the resistance of peripheral airways. X5 was also considered to represent peripheral airway abnormalities.
R5-R20 and X5 were significantly correlated with the SGRQ and the MRC. These correlation coefficients were greater than when using other objective measurements of pulmonary function, R20 on the IOS and CT instead of R5-R20 and X5. Multiple regression analyses showed that R5-R20 or X5 most significantly accounted for the SGRQ and MRC scores.
IOS measurements, especially indices of peripheral airway function, are significantly correlated with health status and dyspnea in patients with COPD. Therefore, in addition to its simplicity and non-invasiveness, IOS may be a useful clinical tool not only for detecting pulmonary functional impairment, but also to some extent at least estimating the patient's quality of daily life and well-being.
The aim of this study was to evaluate the effects of increasing doses of inhaled histamine on the forced expiratory volume in one second (FEV1), inspiratory lung function parameters (ILPs) and dyspnea in subjects with mild to moderate chronic obstructive pulmonary disease (COPD)
Thirty-nine (27 males and 12 females) stable COPD patients (GOLD stages I and II) inhaled a maximum of six sequential doses of histamine according to ERS standards until one of these provocative doses produced a 20% decrease in FEV1 (PD20). The effects on the FEV1, the forced inspiratory volume in one second (FIV1), inspiratory capacity (IC), forced inspiratory flow at 50% of the vital capacity (FIF50), peak inspiratory flow (PIF) and dyspnea score by a visual analogue scale (VAS) were measured and investigated after each dose step
After each dose of histamine, declines in all of the lung function parameters were detected; the largest decrease was observed in the FEV1. At the PD20 endpoint, more FEV1 responders than ILP responders were found. Among the ILPs, the FIV1 and IC best predicted which patients would reach the PD20 endpoint. No significant correlations were found between any of the lung function parameters and the VAS results
In COPD patients, the FEV1 and ILPs declined after each dose of inhaled histamine. FEV1 was more sensitive to histamine than the ILPs. Of the ILPs, FIV1 and IC were the best predictors of reaching the PD20 endpoint. No statistically significant correlations were found between the lung function parameters and the degree of dyspnea
Chronic obstructive pulmonary disease; Forced expiratory volume 1 second; Inspiratory lung functions parameters; Visual analogue scale
Purpose: Most patients with chronic obstructive pulmonary disease (COPD) complain of dyspnea during and following exercise, and the development of intrinsic positive end-expiratory pressure (PEEP) is thought to contribute to lung hyperinflation and dyspnea. Many people with COPD use pursed lip breathing (PLB) in an attempt to produce extrinsic PEEP to reduce lung hyperinflation and dyspnea during and following exertion. We hypothesized that the use of a threshold, extrinsic PEEP device would reduce post-exercise dyspnea in people with COPD. Methods: A double blind, crossover study was conducted on post-exercise dyspnea in 8 patients with COPD whose exercise tolerance was limited by dyspnea. Subjects performed two identical 6-minute treadmill bouts that led to a Borg dyspnea rating of at least 5/10. Dyspnea, heart rate, and oxygen-hemoglobin saturation (SpO2) were recorded at rest, every 2 minutes during exercise and at 2, 5, and 10 minutes post-exercise. Immediately following the exercise bouts, the subjects used either a threshold PEEP device for 6 breaths at 10 cm H2O or a Sham device. Results: Heart rate and SpO2 were not different between treatments any time point before, during, or after exercise. Dyspnea ratings were not different between devices at rest or during exercise, but were lower in the post-exercise period following use of PEEP (p < 0.05). When asked which device, if any, the subjects would prefer to use to relieve post-exercise dyspnea, 7 of 8 chose the PEEP device and one had no preference. Conclusions: We found that the use of a PEEP device can help reduce postexercise dyspnea in patients with COPD.
COPD; dyspnea; pursed lip breathing; PEEP; exertion
Because there are no child-friendly, validated, self-report measures of dyspnea or breathlessness, we developed, and provided initial validation, of three, 7-item, pictorial scales depicting three sub-constructs of dyspnea: throat closing, chest tightness, and effort.
We developed the three scales (Throat closing, Chest tightness, and Effort) using focus groups with 25 children. Subsequently, seventy-nine children (29 children with asthma, 30 children with cystic fibrosis. and 20 children who were healthy) aged 6 to 18 years rated each picture in each series, using a 0–10 scale. In addition, each child placed each picture in each series on a 100-cm long Visual Analogue Scale, with the anchors "not at all" and "a lot".
Children aged eight years or older rated the scales in the correct order 75% to 98% correctly, but children less than 8 years of age performed unreliably. The mean distance between each consecutive item in each pictorial scale was equal.
Preliminary results revealed that children aged 8 to 18 years understood and used these three scales measuring throat closing, chest tightness, and effort appropriately. The scales appear to accurately measure the construct of breathlessness, at least at an interval level. Additional research applying these scales to clinical situations is warranted.
Background and aims
Anxiety and depression are common in patients with chronic obstructive pulmonary disease (COPD). The degree of lung function may not explain anxiety and depression. The aim of our study was to assess the psychological aspects of COPD, to test the BODE index (a composite score of body mass, obstruction, dyspnea and exercise capacity), and to evaluate the association between atypical cytologic findings of sputum, bronchoalveolar lavage (BAL) and the pyschological components of the disease.
COPD was classsified according to the GOLD stages based on forced expiratory volume in 1 second (FEV1) in 60 stable patients. The BODE index was calculated for grading COPD. The Hospital anxiety and depression (HAD) scale was used to appraise the anxiety and depression symptoms. Cytologic examination of sputum and BAL samples were performed in each patient. The cytologic findings were classified as normal, mild, moderate or severe atypia.
The overall prevalance of anxiety and depression symptoms was 41.7% and 46.7% respectively. The prevalance of these symptoms increased with increasing BODE stages and correlated well with the severity of atypical BAL cytology results (p < 0.001). Dyspnea and reduced exercise capacity were the predominant mechanisms leading to anxiety and depression symptoms associated with COPD.
We conclude that the BODE index is superior to GOLD stratification for explaining anxiety and depression symptoms in COPD. BAL cytologic findings, which reflect the distal parenchymal lung structure, correlated significantly with the presence of the anxiety and depression symptoms.
Anxiety; bronchoalveolar lavage; BODE index; COPD; depression; GOLD
Chronic obstructive pulmonary disease (COPD) is now regarded as a heterogenous disease, with variable phenotypes. Acute exacerbation of COPD is a major event that alters the natural course of disease. The frequency of COPD exacerbation is variable among patients. We analyzed clinical features, according to the frequency of acute exacerbation in COPD.
Sixty patients, who visited Gyeongsang National University Hospital from March 2010 to October 2010, were enrolled. Patients were divided into two groups, according to their frequency of acute exacerbation. Frequent exacerbator is defined as the patient who has two or more exacerbation per one year. We reviewed patients' medical records and investigated modified Medical Research Council (MMRC) dyspnea scale, smoking history and frequency of acute exacerbation. We also conducted pulmonary function test and 6-minute walking test, calculated body mass index, degree of airway obstruction and dyspnea and exercise capacity (BODE) index and measured CD146 cells in the peripheral blood.
The number of frequent exacerbators and infrequent exacerbators was 20 and 40, respectively. The frequent exacerbator group had more severe airway obstruction (forced expiratory volume in one second [FEV1], 45% vs. 65.3%, p=0.001; FEV1/forced vital capacity, 44.3% vs. 50.5%, p=0.046). MMRC dyspnea scale and BODE index were significantly higher in the frequent exacerbator group (1.8 vs. 1.1, p=0.016; 3.9 vs. 2.1, p=0.014, respectively). The fraction of CD146 cells significantly increased in the frequent exacerbator group (2.0 vs. 1.0, p<0.001).
Frequent exacerbator had more severe airway obstruction and higher symptom score and BODE index. However, circulating endothelial cells measured by CD146 needed to be confirmed in the future.
Pulmonary Disease, Chronic Obstructive; Phenotype; Endothelial Cells
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.
lung disease, obstructive; spirometry; peak expiratory flow rate (PEFR); ambulatory monitoring; self-care
Background and aims
Recently a multidimensional grading system based on the body mass index (B), degree of airflow obstruction (O), dyspnea (D) and exercise capacity (E) - the BODE index - has begun to be used increasingly for the evaluation of chronic obstructive pulmonary disease (COPD) patients. The aim of our study was to investigate the relationship between the BODE index and disease duration, annual exacerbation and hospitalization rates, health related quality of life and systemic inflammatory markers like C-reactive protein (CRP), tumor necrosis factor (TNF)-α and interleukin (IL)-8.
Materials and methods
In 88 stable COPD patients we evaluated the body-mass index, pulmonary function tests, Modified Medical Research Council dyspnea scale and six-minute walk test (6 MWT). BODE scores were determined. Disease duration, number of exacerbations and hospitalization in the previous year were recorded. We also performed arterial blood gases analysis, administered the St. George's Respiratory Questionnaire (SGRQ) and measured serum levels of CRP, TNF-α, IL-8.
According to BODE score 52% of patients were BODE 1, 21% BODE 2, 15% BODE 3 and 12% were BODE 4. There was a significant relationship between BODE index and COPD stage as classified according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) (p < 0.001). Correlations between BODE score and disease duration (p = 0.011), number of exacerbations (p < 0.001) and hospitalizations (p < 0.001) in the last year were also observed. SGRQ symptom, activity, emotion scores and total scores were found to be significantly correlated to BODE (p < 0.001). Serum CRP levels and BODE were also correlated (p = 0.014); however, no correlation was found between serum levels of TNF-α and IL-8 and BODE.
As the BODE index shows a strong correlation with various prognostic and follow up parameters of COPD and systemic inflammation, its use should be considered for the evaluation of COPD patients.
Biomarkers; BODE index; COPD; quality of life
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.
chronic obstructive pulmonary disease; COPD; dyspnea; emergency department; exacerbation; slow vital capacity; spirometry
COPD is a major cause of disability, but little is known about how disability develops in this condition.
We analyzed data from the FLOW (Function, Living, Outcomes, and Work) Study which enrolled 1,202 Kaiser Permanente Northern California members with COPD at baseline and re-evaluated 1,051 subjects at 2 year follow-up. We tested the specific hypothesis that the development of specific non-respiratory impairments (abnormal body composition and muscle strength) and functional limitations (decreased lower extremity function, poor balance, mobility-related dyspnea, reduced exercise performance, and decreased cognitive function) will determine the risk of disability in COPD, after controlling for respiratory impairment (FEV1 and oxygen saturation). The Valued Life Activities Scale was used to assess disability in terms of a broad range of daily activities. The primary disability outcome measure was defined as an increase in the proportion of activities that cannot be performed of 3.3% or greater from baseline to 2-year follow-up (the estimated minimal important difference). Multivariable logistic regression was used for analysis.
Respiratory impairment measures were related to an increased prospective risk of disability (multivariate OR 1.75; 95% CI 1.26 to 2.44 for 1 litre decrement of FEV1 and OR 1.57 per 5% decrement in oxygen saturation; 95% CI 1.13 to 2.18). Non-respiratory impairment (body composition and lower extremity muscle strength) and functional limitations (lower extremity function, exercise performance, and mobility-related dyspnea) were all associated with an increased longitudinal risk of disability after controlling for respiratory impairment (p<0.05 in all cases). Non-respiratory impairment and functional limitations were predictive of prospective disability, above-and-beyond sociodemographic characteristics, smoking status, and respiratory impairment (area under the receiver operating characteristic curve increased from 0.65 to 0.75; p<0.001).
Development of non-respiratory impairment and functional limitations, which reflect the systemic nature of COPD, appear to be critical determinants of disablement. Prevention and treatment of disability require a comprehensive approach to the COPD patient.
Salmeterol and fluticasone combination (SFC) has anti-inflammatory effects and improves clinical symptoms in patients with chronic obstructive pulmonary disease (COPD). However, the anti-inflammatory mechanism of SFC remains unclear. In this study, we investigated the inflammatory responses of COPD, as well as the relationship of the inflammatory factors with the levels of CD4+CD25+Foxp3+ regulatory T cells (Foxp3+Tregs) after SFC therapy.
Twenty-one patients with moderate or severe COPD received treatment with 50/500 μg of SFC twice a day for 12 weeks. Before and after treatment, the patients were evaluated using the Modified Medical Research Council (MMRC) dyspnea scale and by conducting a 6-min walk test. The number of neutrophils, monocytes and lymphocytes in induced sputum were counted. Levels of cytokines, including pre-inflammatory IL-8, TNF-α, IL-17A and cytokine IL-10, in the sputum supernatant and peripheral blood were measured by ELISA. The proportion of Foxp3+Tregs in the total CD4+ T cell of the peripheral blood was determined by flow cytometry. The relationship between IL-17A levels and the percentage of Foxp3+Tregs was analyzed by statistical analysis.
After treatment with SFC, the forced expiratory volume in 1 s as a percentage of predicted values (FEV1%) and the 6-min walk distance in the COPD patients significantly increased, while dyspnea scores decreased. The total number of cells, neutrophils, and the percentage of neutrophils in induced sputum reduced notably, while the proportion of monocytes was significantly increased. Levels of the inflammatory cytokines IL-8, TNF-α, and IL-17A in the sputum supernatant and in the blood were markedly lowered, while IL-10 levels were unchanged. The proportion of Foxp3+Tregs in the total CD4+T cell population in the peripheral blood was drastically higher than that before treatment. The level of IL-17A was negatively correlated with the proportion of Foxp3+Tregs in CD4+T cells.
SFC can reduce the levels of inflammatory factors and improve symptoms of COPD. The levels of inflammatory factors are associated with the variation of Foxp3+Tregs in COPD.
This study was registered with http://www.chictr.org (Chinese Clinical Trial Register) as follows: ChiCTR-TNC-10001270
T-lymphocytes; inflammatory mediators; chronic obstructive pulmonary disease; salmeterol and fluticasone propionate
The association between disease markers and health status (HS) overtime is unclear. The aim of this study was to verify the predictors of HS at baseline and after three years in Chronic Obstructive Pulmonary Disease (COPD) patients.
Ninety-five consecutive COPD patients (66% male, age = 67 ± 9 y, FEV1 = 58 ± 23%) underwent the following evaluations at baseline and after three years: body composition, pulse oximetry (SpO2), six-minute walk distance (6MWD), Modified edical Research Council dyspnea scale (MMRC) and Saint George's Respiratory Questionnaire (SGRQ). The Charlson comorbidity index and BODE index were calculated. COPD exacerbations during the follow-up were evaluated. At baseline, age, gender, smoking, SpO2, BODE index or its components (BMI, MMRC, FEV1 and 6MWD), and Charlson index were included in a multiple linear regression analysis with the baseline SGRQ total score as the dependent variable. After three years, we included the final values of the variables plus the number of exacerbations and the final SGRQ total score as the dependent variable.
SGRQ total score (42 ± 19% vs 44 ± 19%; p = 0.041) and activity domain (52 ± 21% vs 60 ± 22%; p < 0.001) deteriorated during follow-up. At baseline, BODE index was selected as a predictor of SGRQ total score (R2 = 0.46; p < 0.001); after three years, BODE index and age were the predictors (R2 = 0.49; p < 0.001). When the BODE index was replaced by its variables, MMRC was selected as the only variable associated with the SGRQ total score (R2 = 0.58; p < 0.001). After three years, MMRC, FEV1 and number of exacerbations were selected as predictors of SGRQ total score (R2 = 0.63; p < 0.001).
HS deteriorated significantly over the three-year period and the predictors of HS do not change over time. BODE index and dyspnea were predictors at baseline and after three years. Exacerbation was also a predictor of HS after three years.
COPD; Health status; BODE index; dyspnea
This study aimed to investigate the effects of weekly singings classes on pulmonary function parameters and quality of life (QoL) of COPD patients. Forty-three patients were randomized to weekly classes of singing practice, or handcraft work. They performed spirometry and completed maximal respiratory pressure measurements, evaluations of dyspnea, and the Saint George’s Respiratory Questionnaire, before and after 24 training classes. A functional evaluation, immediately after 10 minutes of singing practice, was also performed at the end of the study. Fifteen subjects completed the study in each group. In comparison to controls the singing group exhibited transitory elevations on the dyspnea Borg scale (p = 0.02), and inspiratory capacity (p = 0.01), and decreases of expiratory reserve volume (p = 0.03), just after a short session of singing. There was a significant difference on changes of maximal expiratory pressures in the comparison between groups at the end of training. While the control group showed deterioration of maximal expiratory pressure, the singing group exhibited a small improvement (p = 0.05). Both groups showed significant improvements of QoL in within group comparisons. We have concluded that singing classes are a well tolerated activity for selected subjects with COPD. Regular practice of singing may improve QoL, and preserve the maximal expiratory pressure of these patients.
COPD; pulmonary function tests; breathing exercises
Dyspnea while performing the activities of daily living has been suggested to be a better measurement than peak dyspnea during exercise. Furthermore, the inspiratory capacity (IC) has been shown to be more closely related to exercise tolerance and dyspnea than the FEV1, because dynamic hyperinflation is the main cause of shortness of breath in patients with COPD. However, breathlessness during exercise is measured in most studies to evaluate this relationship.
To evaluate the correlation between breathlessness during daily activities and airflow limitation or static hyperinflation in COPD.
We examined 167 consecutive outpatients with stable COPD. The Baseline Dyspnea Index (BDI) was used to evaluate dyspnea with activities of daily living. The relationship between the BDI score and the clinical measurements of pulmonary function was then investigated.
The Spearman rank correlation coefficients (Rs) between the BDI score and the FEV1(L), FEV1(%pred) and FEV1/FVC were 0.60, 0.56 and 0.56, respectively. On the other hand, the BDI score also correlated with the IC, IC/predicted total lung capacity (TLC) and IC/TLC (Rs = 0.45, 0.46 and 0.47, respectively). Although all of the relationships studied were strongly correlated, the correlation coefficients were better between dyspnea and airflow limitation than between dyspnea and static hyperinflation. In stepwise multiple regression analyses, the BDI score was most significantly explained by the FEV1 (R2 = 26.2%) and the diffusion capacity for carbon monoxide (R2 = 14.4%) (Cumulative R2 = 40.6%). Static hyperinflation was not a significant factor for clinical dyspnea on the stepwise multiple regression analysis.
Both static hyperinflation and airflow limitation contributed greatly to dyspnea in COPD patients.
Chronic obstructive pulmonary disease; Airflow limitation; Hyperinflation; Dyspnea; Baseline Dyspnea Index
In obstructive lung diseases such as asthma and COPD dyspnea is a common respiratory symptom with different characteristics given the different pathogenic mechanisms: in COPD initially it can occur during exertion but then it increases progressively along with the airflow obstruction, whereas in asthma it occurs episodically and is caused by transient bronchoconstriction.
The language of dyspnea includes a large range of clinical descriptors which have been evaluated for their correlation (of one or several descriptors) with underlying physiologic/physiopathologic mechanisms. These studies were done in asthma rather than in COPD, and dyspnea descriptors were found to be useful in identifying patients with life-threatening asthma. However further studies are needed to further explore such descriptors and their clinical utility.
This review discusses dyspnea mechanisms in various obstructive lung disease subsets as well as the descriptors of dyspnea and their utility in clinical practice.
Descriptors; dyspnea; exercise testing; obstructive lung diseases