Assessment of Health Status in Patients with Newly Diagnosed Chronic Obstructive Pulmonary Disease

Subject

Chronic obstructive pulmonary disease (COPD) is a common disease worldwide. This study aimed to investigate the health status of patients with newly diagnosed COPD.

Methods

A total of 45 healthy controls and 218 patients with newly diagnosed COPD were recruited. Pulmonary function test (PFT) values, COPD assessment test (CAT) scores, exacerbation history, and demographics were recorded.

Results

Forced expiratory volume in 1 s percent (FEV1%) predicted was significantly decreased and the CAT score was significantly increased in patients with COPD compared with healthy controls (P <0.001). Among the COPD patients, the most commonly reported respiratory symptoms were cough (86.7%), sputum (80.3%), and dyspnea (45%). A total of 86.2% patients were in the moderate or severe stage (spirometric classification) of COPD, and 71.5% were in Group C or Group D (combined assessment). A total of 33.9% of the patients had 2 or more exacerbations in the previous year. Nearly half of the patients (45.4%) had a high CAT score of ≥10. Patients with a history of more exacerbations had a higher CAT score.

Conclusions

Most COPD patients were symptomatic and appeared to have moderate to severe airflow limitation or a high risk of exacerbation before definitely being diagnosed with COPD using the PFT.     

Prevalence and Global Initiative for Chronic Obstructive Lung Disease Group Distribution of Chronic Obstructive Pulmonary Disease Detected by Preoperative Pulmonary Function Test

Background

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.

Methods

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.

Results

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.

Conclusions

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.     

Effects of body mass index on task-related oxygen uptake and dyspnea during activities of daily life in COPD

Background

Patients with COPD use a higher proportion of their peak aerobic capacity during the performance of domestic activities of daily life (ADLs) compared to healthy peers, accompanied by a higher degree of task-related symptoms. To date, the influence of body mass index (BMI) on the task-related metabolic demands remains unknown in patients with COPD. Therefore, the aim of our study was to determine the effects of BMI on metabolic load during the performance of 5 consecutive domestic ADLs in patients with COPD.

Methodology

Ninety-four COPD patients and 20 healhty peers performed 5 consecutive, self-paced domestic ADLs putting on socks, shoes and vest; folding 8 towels; putting away groceries; washing up 4 dishes, cups and saucers; and sweeping the floor for 4 min. Task-related oxygen uptake and ventilation were assessed using a mobile oxycon, while Borg scores were used to assess task-related dyspnea and fatigue.

Principal Findings

1. Relative task-related oxygen uptake after the performance of domestic ADLs was increased in patients with COPD compared to healthy elderly, whereas absolute oxygen uptake is similar between groups; 2. Relative oxygen uptake and oxygen uptake per kilogram fat-free mass were comparable between BMI groups; and 3. Borg symptom scores for dyspnea en fatigue were comparable between BMI groups.

Conclusion

Patients with COPD in different BMI groups perform self-paced domestic ADLs at the same relative metabolic load, accompanied by comparable Borg symptom scores for dyspnea and fatigue.     

Airflow limitation or static hyperinflation: which is more closely related to dyspnea with activities of daily living in patients with COPD?

Background

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.

Purpose

To evaluate the correlation between breathlessness during daily activities and airflow limitation or static hyperinflation in COPD.

Methods

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.

Results

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.

Conclusion

Both static hyperinflation and airflow limitation contributed greatly to dyspnea in COPD patients.     

Moderate Intense Physical Activity Depends on Selected Metabolic Equivalent of Task (MET) Cut-Off and Type of Data Analysis

Background

Accelerometry data are frequently analyzed without considering whether moderate-to-vigorous physical activities (MVPA) were performed in bouts of >10 minutes as defined in most physical activity guidelines. We aimed i) to quantify MVPA by using different commonly-applied physical activity guidelines, ii) to investigate the effect of bouts versus non-bouts analysis, and iii) to propose and validate a MVPA non-bouts cut-point to classify (in-) active subjects.

Methods

Healthy subjects (n=110;62±6yrs) and patients with Chronic Obstructive Pulmonary Disease (COPD) (n=113;62±5yrs) wore an activity monitor for 7 days. Three Metabolic Equivalent of Task (MET) cut-offs and one individual target (50% VO₂ reserve) were used to define MVPA. First, all minutes of MVPA were summed up (NON-BOUTS). Secondly, only minutes performed in bouts of >10 minutes continuous activity were counted (BOUTS). Receiver operating characteristic (ROC) curve analyses were used to propose and (cross-) validate new MVPA non-bout cut-points based on the criterion of 30 minutes MVPA per day (BOUTS). Likelihood ratios (sensitivity/[1-specificity]) were used to express the association between the proposed MVPA non-bout target and the MVPA bout target of 30 min*day^-1.

Results

MVPA was variable across physical activity guidelines with lowest values for age-specific cut-offs. Selecting a METs cut-point corresponding to 50% VO₂ reserve revealed no differences in MVPA between groups. MVPA’s analyzed in BOUTS in healthy subjects were 2 to 4 fold lower than NON-BOUTS analyses and this was even 3 to 12 fold lower in COPD. The MVPA non-bouts cut-point of 80 min*day^-1 using a 3 METs MVPA threshold delivered positive likelihood ratios of 5.1[1.5-19.6] (healthy subjects) and 2.3[1.6-3.3] (COPD).

Conclusion

MVPA varies upon the selected physical activity guideline/targets and bouts versus non-bouts analysis. Accelerometry measured MVPA non-bouts target of 80 min*day^-1, using a 3 METs MVPA threshold, is associated to the commonly-used MVPA bout target of 30 min*day^-1.     

Skeletal Muscle Abnormalities in Pulmonary Arterial Hypertension

Background

Pulmonary arterial hypertension is a progressive disease that is characterized by dyspnea and exercise intolerance. Impairment in skeletal muscle has recently been described in PAH, although the degree to which this impairment is solely determined by the hemodynamic profile remains uncertain. The aim of this study was to verify the association of structural and functional skeletal muscle characteristics with maximum exercise in PAH.

Methods

The exercise capacity, body composition, CT area of limb muscle, quality of life, quadriceps biopsy and hemodynamics of 16 PAH patients were compared with those of 10 controls.

Results

PAH patients had a significantly poorer quality of life, reduced percentage of lean body mass, reduced respiratory muscle strength, reduced resistance and strength of quadriceps and increased functional limitation at 6MWT and CPET. VO₂ max was correlated with muscular variables and cardiac output. Bivariate linear regression models showed that the association between muscular structural and functional variables remained significant even after correcting for cardiac output.

Conclusion

Our study showed the coexistence of ventilatory and quadriceps weakness in face of exercise intolerance in the same group of PAH patients. More interestingly, it is the first time that the independent association between muscular pattern and maximum exercise capacity is evidenced in PAH, independently of cardiac index highlighting the importance of considering rehabilitation in the treatment strategy for PAH.     

Population Pharmacodynamic Modeling and Simulation of the Respiratory Effect of Acetazolamide in Decompensated COPD Patients

Background

Chronic obstructive pulmonary disease (COPD) patients may develop metabolic alkalosis during weaning from mechanical ventilation. Acetazolamide is one of the treatments used to reverse metabolic alkalosis.

Methods

619 time-respiratory (minute ventilation, tidal volume and respiratory rate) and 207 time-PaCO₂ observations were obtained from 68 invasively ventilated COPD patients. We modeled respiratory responses to acetazolamide in mechanically ventilated COPD patients and then simulated the effect of increased amounts of the drug.

Results

The effect of acetazolamide on minute ventilation and PaCO₂ levels was analyzed using a nonlinear mixed effect model. The effect of different ventilatory modes was assessed on the model. Only slightly increased minute ventilation without decreased PaCO₂ levels were observed in response to 250 to 500 mg of acetazolamide administered twice daily. Simulations indicated that higher acetazolamide dosage (>1000 mg daily) was required to significantly increase minute ventilation (P<.001 vs pre-acetazolamide administration). Based on our model, 1000 mg per day of acetazolamide would increase minute ventilation by >0.75 L min⁻¹ in 60% of the population. The model also predicts that 45% of patients would have a decrease of PaCO2>5 mmHg with doses of 1000 mg per day.

Conclusions

Simulations suggest that COPD patients might benefit from the respiratory stimulant effect after the administration of higher doses of acetazolamide.     

Incidence and Cost of Pneumonia in Older Adults with COPD in the United States

Objectives

To estimate the incidence of pneumonia by COPD status and the excess cost of inpatient primary pneumonia in elders with COPD.

Study Design

A retrospective, longitudinal study using claims linked to eligibility/demographic data for a 5% sample of fee-for-service Medicare beneficiaries from 2005 through 2007.

Methods

Incidence rates of pneumonia were calculated for elders with and without COPD and for elders with COPD and coexistent congestive heart failure (CHF). Propensity-score matching with multivariate generalized linear regression was used to estimate the excess direct medical cost of inpatient primary pneumonia in elders with COPD as compared with elders with COPD but without a pneumonia hospitalization.

Results

Elders with COPD had nearly six-times the incidence of pneumonia compared with elders without COPD (167.6/1000 person-years versus 29.5/1000 person-years; RR=5.7, p <0 .01); RR increased to 8.1 for elders with COPD and CHF compared with elders without COPD. The incidence of inpatient primary pneumonia among elders with COPD was 54.2/1000 person-years compared with 7/1000 person-years for elders without COPD; RR=7.7, p<0.01); RR increased to 11.0 for elders with COPD and CHF compared with elders without COPD. The one-year excess direct medical cost of inpatient pneumonia in COPD patients was $ 22,697 ($45,456 in cases vs. $ 22,759 in controls (p <0.01)); 70.2% of this cost was accrued during the quarter of the index hospitalization. During months 13 through 24 following the index hospitalization, the excess direct medical cost was $ 5,941 ($23,215 in cases vs. $ 17,274 in controls, p<0.01).

Conclusions

Pneumonia occurs more frequently in elders with COPD than without COPD. The excess direct medical cost in elders with inpatient pneumonia extends up to 24 months following the index hospitalization and represents $28,638 in 2010 dollars.     

Chronic Obstructive Pulmonary Disease (COPD) During the Two Last Years of Life – A Retrospective Study of Decedents

Background

Little is known about the management of patients suffering from chronic obstructive pulmonary disease (COPD) during the last years of life. The aim of the study was to describe how management of COPD is performed in Sweden during the last two years of life.

Methods

From the nationwide Cause of Death register all individuals with COPD as the underlying cause of death during two years were identified in one sparsely and one densely populated area of Sweden. Data were collected from medical records using a pre-defined protocol, especially developed for this purpose.

Results

Of 822 individuals with COPD as underlying cause of death, medical records from 729 were available. The COPD diagnosis was based on lung function measurements in approximately half of the patients and median age at COPD diagnosis was 74 years (range 34-95). Women died at younger age, median 78 years (range 52-96) than did men (80 years (51-99)). The median survival time from diagnosis to death was 6 years in men and women in both areas. Among women and men 8.3% and 4.3% were never smokers, respectively. The structure of COPD management differed between the two areas, with utilization of physiotherapists, dieticians and working therapists being more used in the northern area, likely because of differences in accessibility to care institutions.

Conclusions

In Sweden COPD is mostly diagnosed late in life and often not verified by lung function measurements. Opposite to the general population, women with COPD die at a lower age than men.     

Peripheral endothelial dysfunction is associated with gas exchange inefficiency in smokers

Aims

To assess the cross-sectional association between exercise capacity, gas exchange efficiency and endothelial function, as measured by flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of the brachial artery, in a large-scale population-based survey.

Methods

The study population was comprised of 1416 volunteers 25 to 85 years old. Oxygen uptake at anaerobic threshold (VO₂@AT), peak exercise (peakVO₂) and ventilatory efficiency (VE vs. VCO₂ slope and VE/VCO₂@AT) were assessed on a breath-by-breath basis during incremental symptom-limited cardiopulmonary exercise. FMD and NMD measurements at rest were performed using standardised ultrasound techniques.

Results

Multivariable logistic regression analyses revealed a significant association between FMD and ventilatory efficiency in current smokers but not in ex-smokers or non-smokers. There was no association between FMD and VO₂@AT or peak VO₂. In current smokers, for each one millimetre decrement in FMD, VE/VCO₂@AT improved by -3.6 (95% CI -6.8, -0.4) in the overall population [VE vs. VCO₂ slope -3.9 (-7.1, -0.6)]. These results remained robust after adjusting for all major influencing factors. Neither exercise capacity nor ventilatory efficiency was significantly associated with NMD.

Conclusion

In current smokers, FMD is significantly associated with ventilatory efficiency. This result may be interpreted as a potential clinical link between smoking and early pulmonary vasculopathy due to smoking.     

The Continuum of Physiological Impairment during Treadmill Walking in Patients with Mild-to-Moderate COPD: Patient Characterization Phase of a Randomized Clinical Trial

Background

To have a better understanding of the mechanisms of exercise limitation in mild-to-moderate chronic obstructive pulmonary disease (COPD), we compared detailed respiratory physiology in patients with COPD and healthy age- and sex-matched controls.

Methods

Data were collected during the pre-treatment, patient characterization phase of a multicenter, randomized, double-blind, crossover study. Patients with COPD met Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 or 2 spirometric criteria, were symptomatic, and had evidence of gas trapping during exercise. All participants completed pulmonary function and symptom-limited incremental treadmill exercise tests.

Results

Chronic activity-related dyspnea measured by Baseline Dyspnea Index was similarly increased in patients with GOLD 1 (n = 41) and 2 (n = 63) COPD compared with controls (n = 104). Plethysmographic lung volumes were increased and lung diffusing capacity was decreased in both GOLD groups. Peak oxygen uptake and work rate were reduced in both GOLD groups compared with controls (p<0.001). Submaximal ventilation, dyspnea, and leg discomfort ratings were higher for a given work rate in both GOLD groups compared with controls. Resting inspiratory capacity, peak ventilation, and tidal volume were reduced in patients with GOLD 2 COPD compared with patients with GOLD 1 COPD and controls (p<0.001).

Conclusions

Lower exercise tolerance in patients with GOLD 1 and 2 COPD compared with controls was explained by greater mechanical abnormalities, greater ventilatory requirements, and increased subjective discomfort. Lower resting inspiratory capacity in patients with GOLD 2 COPD was associated with greater mechanical constraints and lower peak ventilation compared with patients with GOLD 1 COPD and controls.

Trial Registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01072396","term_id":"NCT01072396"}}NCT01072396     

Clinical Characteristics with an Impact on ADL Functions of PD Patients with Cognitive Impairment Indicative of Dementia

Background

Dementia in Parkinson’s disease (PD) is defined as cognitive decline severe enough to affect activities of daily living function (ADL). The aim of our exploratory study was to compare two groups of PD patients. Both groups had cognitive deficits severe enough to justify diagnosis of dementia, but they differed according to caregivers’ rating on ADL dysfunction. Parameters which differed between the two groups were interpreted to affect the caregivers’ perception of ADL dysfunction in PD patients with cognitive impairment indicative of Parkinson’s disease dementia.

Methodology/Principal Findings

Thirty of 131 Parkinson’s disease patients fulfilled the Movement Disorders Society Task Force – recommended, cognitive Level-I-criteria for dementia. According to standardized caregiver ratings, volunteers were grouped into 18 patients with (ADL-) and 12 without instrumental activities of daily living dysfunction (ADL+). Caregiver activities of daily living function ratings closely correlated with self-estimates of patients and those of physician (p<0.001). ADL- patients performed worse on tests assessing visual-construction (p<0.05) and attention (p=0.03) than ADL+ patients. Moreover, the postural instability and gait disorder subtype was more frequent in ADL- patients (p=0.009). ADL- patients tended to have more communication problems (p=0.05), more anxiety (p=0.05) and showed a tendency to be treated more often with neuroleptics (p=0.049) than ADL+.

Conclusions/Significance

Results indicate that worse attention, visual-construction abilities, the postural instability and gait disorder subtype, communication problems, medication and presence of anxiety are related to activities of daily living dysfunctions in Parkinson’s disease patients with cognitive decline indicative of dementia. Our data suggests that not only cognitive factors but also non-cognitive factors seem to be linked to the diagnosis of Parkinson’s disease dementia associated with significant impact on instrumental activities of daily living function. Further studies with larger sample sizes are needed to verify our results.     

New GOLD classification: longitudinal data on group assignment

Rationale

Little is known about the longitudinal changes associated with using the 2013 update of the multidimensional GOLD strategy for chronic obstructive pulmonary disease (COPD).

Objective

To determine the COPD patient distribution of the new GOLD proposal and evaluate how this classification changes over one year compared with the previous GOLD staging based on spirometry only.

Methods

We analyzed data from the CHAIN study, a multicenter observational Spanish cohort of COPD patients who are monitored annually. Categories were defined according to the proposed GOLD: FEV₁%, mMRC dyspnea, COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ), and exacerbations-hospitalizations. One-year follow-up information was available for all variables except CCQ data.

Results

At baseline, 828 stable COPD patients were evaluated. On the basis of mMRC dyspnea versus CAT, the patients were distributed as follows: 38.2% vs. 27.2% in group A, 17.6% vs. 28.3% in group B, 15.8% vs. 12.9% in group C, and 28.4% vs. 31.6% in group D. Information was available for 526 patients at one year: 64.2% of patients remained in the same group but groups C and D show different degrees of variability. The annual progression by group was mainly associated with one-year changes in CAT scores (RR, 1.138; 95%CI: 1.074-1.206) and BODE index values (RR, 2.012; 95%CI: 1.487-2.722).

Conclusions

In the new GOLD grading classification, the type of tool used to determine the level of symptoms can substantially alter the group assignment. A change in category after one year was associated with longitudinal changes in the CAT and BODE index.     

Exploring Metrics to Express Energy Expenditure of Physical Activity in Youth

Background

Several approaches have been used to express energy expenditure in youth, but no consensus exists as to which best normalizes data for the wide range of ages and body sizes across a range of physical activities. This study examined several common metrics for expressing energy expenditure to determine whether one metric can be used for all healthy children. Such a metric could improve our ability to further advance the Compendium of Physical Activities for Youth.

Methods

A secondary analysis of oxygen uptake (VO₂) data obtained from five sites was completed, that included 947 children ages 5 to 18 years, who engaged in 14 different activities. Resting metabolic rate (RMR) was computed based on Schofield Equations [Hum Nutr Clin Nut. 39(Suppl 1), 1985]. Absolute oxygen uptake (ml.min^-1), oxygen uptake per kilogram body mass (VO₂ in ml.kg^-1.min^-1), net oxygen uptake (VO₂ – resting metabolic rate), allometric scaled oxygen uptake (VO₂ in ml.kg^-0.75.min^-1) and YOUTH-MET (VO₂.[resting VO₂] ^-1) were calculated. These metrics were regressed with age, sex, height, and body mass.

Results

Net and allometric-scaled VO₂, and YOUTH-MET were least associated with age, sex and physical characteristics. For moderate-to-vigorous intensity activities, allometric scaling was least related to age and sex. For sedentary and low-intensity activities, YOUTH-MET was least related to age and sex.

Conclusions

No energy expenditure metric completely eliminated the influence of age, physical characteristics, and sex. The Adult MET consistently overestimated EE. YOUTH-MET was better for expressing energy expenditure for sedentary and light activities, whereas allometric scaling was better for moderate and vigorous intensity activities. From a practical perspective, The YOUTH-MET may be the more feasible metric for improving of the Compendium of Physical Activities for Youth.     

Cardiac Autonomic Modulation Is Determined by Gender and Is Independent of Aerobic Physical Capacity in Healthy Subjects

Background

Aerobic physical capacity plays an important role in reducing morbidity and mortality rates in subjects with cardiovascular diseases. This action is often related to an improvement in the autonomic modulation of heart rate variability (HRV). However, controversies remain regarding the effects of physical training on cardiac autonomic control in healthy subjects. Therefore, our objective was to investigate whether aerobic capacity interferes with the autonomic modulation of HRV and whether gender differences exist.

Methods

Healthy men and women (N=96) were divided into groups according to aerobic capacity: low (VO₂: 22-38 ml/kg^-1 min^-1), moderate (VO₂: 38-48 ml/kg^-1 min^-1) and high (VO₂ >48 ml/kg^-1 min^-1.) We evaluated the hemodynamic parameters and body composition. The autonomic modulation of HRV was investigated using spectral analysis. This procedure decomposes the heart rate oscillatory signal into frequency bands: low frequency (LF=0.04-0.15Hz) is mainly related to sympathetic modulation, and high frequency (HF=0.15-0.5Hz) corresponds to vagal modulation.

Results

Aerobic capacity, regardless of gender, determined lower values of body fat percentage, blood pressure and heart rate. In turn, the spectral analysis of HRV showed that this parameter did not differ when aerobic capacity was considered. However, when the genders were compared, women had lower LF values and higher HF values than the respective groups of men.

Conclusion

The results suggest that aerobic physical capacity does not interfere with HRV modulation; however, the cardiac modulatory balance differs between genders and is characterized by a greater influence of the autonomic vagal component in women and by the sympathetic component in men.     

End Criteria for Reaching Maximal Oxygen Uptake Must Be Strict and Adjusted to Sex and Age: A Cross-Sectional Study

Objective

To describe different end criteria for reaching maximal oxygen uptake (VO_2max) during a continuous graded exercise test on the treadmill, and to explore the manner by which different end criteria have an impact on the magnitude of the VO_2max result.

Methods

A sample of 861 individuals (390 women) aged 20–85 years performed an exercise test on a treadmill until exhaustion. Gas exchange, heart rate, blood lactate concentration and Borg Scale_6–20 rating were measured, and the impact of different end criteria on VO_2max was studied;VO₂ leveling off, maximal heart rate (HR_max), different levels of respiratory exchange ratio (RER), and postexercise blood lactate concentration.

Results

Eight hundred and four healthy participants (93%) fulfilled the exercise test until voluntary exhaustion. There were no sex-related differences in HR_max, RER, or Borg Scale rating, whereas blood lactate concentration was 18% lower in women (P<0.001). Forty-two percent of the participants achieved a plateau in VO₂; these individuals had 5% higher ventilation (P = 0.033), 4% higher RER (P<0.001), and 5% higher blood lactate concentration (P = 0.047) compared with participants who did not reach a VO₂ plateau. When using RER ≥1.15 or blood lactate concentration ≥8.0 mmol•L^–1, VO_2max was 4% (P = 0.012) and 10% greater (P<0.001), respectively. A blood lactate concentration ≥8.0 mmol•L^–1 excluded 63% of the participants in the 50–85-year-old cohort.

Conclusions

A range of typical end criteria are presented in a random sample of subjects aged 20–85 years. The choice of end criteria will have an impact on the number of the participants as well as the VO_2max outcome. Suggestions for new recommendations are given.     

The unique alterations of hippocampus and cognitive impairment in chronic obstructive pulmonary disease

Background

Cognitive impairment has been found in chronic obstructive pulmonary disease (COPD) patients. However, the structural alteration of the brain and underlying mechanisms are poorly understood.

Methods

Thirty-seven mild-to-moderate COPD patients, forty-eight severe COPD patients, and thirty-one control subjects were recruited for cognitive test and neuroimaging studies. Serum levels of S100B,pulmonary function and arterial blood gas levels were also evaluated in each subject.

Results

The hippocampal volume was significantly smaller in COPD patients compared to the control group. It is positively correlated with a mini mental state examination (MMSE) score, SaO₂ in mild-to-moderate COPD patients, the levels of PaO₂ in both mild-to-moderate and severe COPD patients. Higher S100B concentrations were observed in mild-to-moderate COPD patients, while the highest S100B level was found in severe COPD patients when compared to the control subjects. S100B levels are negatively associated with MMSE in both mild-to-moderate and severe COPD patients and also negatively associated with the hippocampal volume in the total COPD patients.

Conclusions

Hippocampal atrophy based on quantitative assessment by magnetic resonance imaging does occur in COPD patients, which may be associated with cognitive dysfunction and the most prevalent mechanism accountable for hippocampal atrophy is chronic hypoxemia in COPD. Higher serum S100B levels may be peripheral biochemical marker for cognitive impairment in COPD.     

Cluster Analysis in Patients with GOLD 1 Chronic Obstructive Pulmonary Disease

Background

We hypothesized that heterogeneity exists within the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 spirometric category and that different subgroups could be identified within this GOLD category.

Methods

Pre-randomization study participants from two clinical trials were symptomatic/asymptomatic GOLD 1 chronic obstructive pulmonary disease (COPD) patients and healthy controls. A hierarchical cluster analysis used pre-randomization demographics, symptom scores, lung function, peak exercise response and daily physical activity levels to derive population subgroups.

Results

Considerable heterogeneity existed for clinical variables among patients with GOLD 1 COPD. All parameters, except forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC), had considerable overlap between GOLD 1 COPD and controls. Three-clusters were identified: cluster I (18 [15%] COPD patients; 105 [85%] controls); cluster II (45 [80%] COPD patients; 11 [20%] controls); and cluster III (22 [92%] COPD patients; 2 [8%] controls). Apart from reduced diffusion capacity and lower baseline dyspnea index versus controls, cluster I COPD patients had otherwise preserved lung volumes, exercise capacity and physical activity levels. Cluster II COPD patients had a higher smoking history and greater hyperinflation versus cluster I COPD patients. Cluster III COPD patients had reduced physical activity versus controls and clusters I and II COPD patients, and lower FEV₁/FVC versus clusters I and II COPD patients.

Conclusions

The results emphasize heterogeneity within GOLD 1 COPD, supporting an individualized therapeutic approach to patients.

Trial registration

www.clinicaltrials.gov. NCT01360788 and NCT01072396.     

Nephrogenic Systemic Fibrosis in Denmark– A Nationwide Investigation

Background

Nephrogenic systemic fibrosis is a debilitating and painful disorder with an increased stimulation of the connective tissue in the skin and systemic tissues. The disease is associated with exposure to gadolinium-based contrast agent used in magnetic resonance imaging in patients with renal impairment.

Methods

The prevalence of nephrogenic systemic fibrosis has so far never been determined at a national level. In 2009, Denmark was the first country to design a guideline for the tracing of nephrogenic systemic fibrosis patients. The aim of this paper is to communicate the main findings of this quest.

Results

The outcome of the nationwide investigation revealed that Denmark had 65 patients with nephrogenic systemic fibrosis and thereby the highest prevalence of nephrogenic systemic fibrosis worldwide with 65 per 5.6 million inhabitants, or 12 per million.

Conclusions

The nationwide investigation in Denmark revealed the highest prevalence of NSF worldwide. This may be rooted in a high level of awareness of NSF both among doctors, politicians and, not least, the media, combined with the fact that a nationwide NSF investigation was initiated.