Obesity in COPD: Comorbidities with Practical Consequences?

COPD and obesity often coexist and there is a complex interaction between them. Our aim was to evaluate the prevalence of obesity in a secondary care COPD population. Furthermore, the presence of comorbidities in obese (COPDOB) and non-obese COPD (COPDNO) individuals was studied. In 1654 COPD patients (aged ≥18 years) who visited a pulmonologist between January 2015 and December 2015, patient characteristics, pulmonary function tests and comorbidities were obtained from the medical records. Subjects were categorized according their BMI as underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2) or obese (BMI ≥30.0 kg/m2). The Charlson comorbidity index and COTE index were used to quantify comorbidities. The prevalence of obesity was 21.8% in our COPD population. Obesity was significantly less common in GOLD stage IV (10.1%) compared to GOLD I (20.5%), II (27.8%) and III (18.9%). COPDOB had different comorbidities compared with COPDNO. Hypertension, diabetes mellitus, atrial fibrillation and congestive heart failure were significantly more prevalent in COPDOB compared with COPDNO. Osteoporosis and lung cancer were significantly more common in COPDNO compared with COPDOB. Obesity is common in patients with COPD and is most prevalent in COPD GOLD I-II and least prevalent in COPD GOLD IV. Obese COPD patients have different comorbidities than non-obese COPD patients. Cardiovascular and metabolic comorbidities, especially hypertension and diabetes mellitus, are highly prevalent in obese COPD patients. Active screening for these conditions should be a priority for physicians treating obese COPD patients.

Obesity in COPD: Revealed and Unrevealed Issues.

The interactions between obesity and chronic obstructive pulmonary disease (COPD) are being increasingly explored. In part, this is due to the globally increasing prevalence rates of obesity. The prevalence of obesity in COPD patients is variable, and it seems that obesity is more common in COPD patients compared with subjects who do not have COPD. However, further studies are encouraged in this area due to observed inconsistencies in the current data. In this review, we focus on the knowledge of the effects of obesity on dyspnea, pulmonary function, exercise capacity and exacerbation risk. Reduction of dyspnea is one of the main therapy targets in COPD care. There is still no consensus as to whether obesity has a negative or even a positive effect on dyspnea in COPD patients. It is hypothesized that obese COPD patients might benefit from favourable respiratory mechanics (less lung hyperinflation). However, despite less hyperinflation, obesity seems to have a negative influence on exercise capacity measured with weight-bearing tests. This negative influence is not seen with weight-supported exercise such as cycling. With respect to severe exacerbations, obesity seems to be associated with better survival. In summary, it is concluded that due to differences in study methodology and cohort selection, there are still too many knowledge gaps to develop guidelines for clinical practice. Further exploration is needed to get conclusive answers.

Proactive palliative care for patients with COPD (PROLONG): a pragmatic cluster controlled trial.

BACKGROUND AND AIM: Patients with advanced chronic obstructive pulmonary disease (COPD) have poor quality of life. The aim of this study was to assess the effects of proactive palliative care on the well-being of these patients. TRIAL REGISTRATION: This trial is registered with the Netherlands Trial Register, NTR4037. PATIENTS AND METHODS: A pragmatic cluster controlled trial (quasi-experimental design) was performed with hospitals as cluster (three intervention and three control) and a pretrial assessment was performed. Hospitals were selected for the intervention group based on the presence of a specialized palliative care team (SPCT). To control for confounders, a pretrial assessment was performed in which hospitals were compared on baseline characteristics. Patients with COPD with poor prognosis were recruited during hospitalization for acute exacerbation. All patients received usual care while patients in the intervention group received additional proactive palliative care in monthly meetings with an SPCT. Our primary outcome was change in quality of life score after 3 months, which was measured using the St George Respiratory Questionnaire (SGRQ). Secondary outcomes were, among others, quality of life at 6, 9 and 12 months; readmissions: survival; and having made advance care planning (ACP) choices. All analyses were performed following the principle of intention to treat. RESULTS: During the year 2014, 228 patients (90 intervention and 138 control) were recruited and at 3 months, 163 patients (67 intervention and 96 control) completed the SGRQ. There was no significant difference in change scores of the SGRQ total at 3 months between groups (-0.79 [95% CI, -4.61 to 3.34], p=0.70). However, patients who received proactive palliative care experienced less impact of their COPD (SGRQ impact subscale) at 6 months (-6.22 [-11.73 to -0.71], p=0.04) and had more often made ACP choices (adjusted odds ratio 3.26 [1.49-7.14], p=0.003). Other secondary outcomes were not significantly different. CONCLUSION: Proactive palliative care did not improve the overall quality of life of patients with COPD. However, patients more often made ACP choices which may lead to better quality of care toward the end of life.

Development of the ProPal-COPD tool to identify patients with COPD for proactive palliative care.

BACKGROUND: Our objective was to develop a tool to identify patients with COPD for proactive palliative care. Since palliative care needs increase during the disease course of COPD, the prediction of mortality within 1 year, measured during hospitalizations for acute exacerbation COPD (AECOPD), was used as a proxy for the need of proactive palliative care. PATIENTS AND METHODS: Patients were recruited from three general hospitals in the Netherlands in 2014. Data of 11 potential predictors, a priori selected based on literature, were collected during hospitalization for AECOPD. After 1 year, the medical files were explored for the date of death. An optimal prediction model was assessed by Lasso logistic regression, with 20-fold cross-validation for optimal shrinkage. Missing data were handled using complete case analysis. RESULTS: Of 174 patients, 155 patients were included; of those 30 (19.4%) died within 1 year. The optimal prediction model was internally validated and had good discriminating power (AUC =0.82, 95% CI 0.81-0.82). This model relied on the following seven predictors: the surprise question, Medical Research Council dyspnea questionnaire (MRC dyspnea), Clinical COPD Questionnaire (CCQ), FEV1% of predicted value, body mass index, previous hospitalizations for AECOPD and specific comorbidities. To ensure minimal miss out of patients in need of proactive palliative care, we proposed a cutoff in the model that prioritized sensitivity over specificity (0.90 over 0.73, respectively). Our model (ProPal-COPD tool) was a stronger predictor of mortality within 1 year than the CODEX (comorbidity, age, obstruction, dyspnea, and previous severe exacerbations) index. CONCLUSION: The ProPal-COPD tool is a promising multivariable prediction tool to identify patients with COPD for proactive palliative care.

The predictive value of respiratory function tests for non-invasive ventilation in amyotrophic lateral sclerosis.

BACKGROUND: Non-invasive ventilation (NIV) improves survival and quality of life in amyotrophic lateral sclerosis (ALS) patients. The timing of referral to a home ventilation service (HVS), which is in part based on respiratory function tests, has shown room for improvement. It is currently unknown which respiratory function test predicts an appropriate timing of the initiation of NIV. METHODS: We analysed, retrospectively, serial data of five respiratory function tests: forced vital capacity (FVC), peak cough flow (PCF), maximum inspiratory and expiratory pressure (MIP and MEP) and sniff nasal inspiratory pressure (SNIP) in patients with ALS. Patients who had had at least one assessment of respiratory function and one visit at the HVS, were included. Our aim was to detect the test with the highest predictive value for the need for elective NIV in the following 3 months. We analysed time curves, currently used cut-off values for referral, and respiratory function test results between 'NIV indication' and 'no-NIV indication' patients. RESULTS: One hundred ten patients with ALS were included of whom 87 received an NIV indication; 11.5% had one assessment before receiving an NIV indication, 88.5% had two or more assessments. The NIV indication was based on complaints of hypoventilation and/or proven (nocturnal) hypercapnia. The five respiratory function tests showed a descending trend during disease progression, where SNIP showed the greatest decline within the latest 3 months before NIV indication (mean = -22%). PCF at the time of referral to the HVS significantly discriminated between the groups 'NIV-indication' and 'no NIV-indication yet' patients at the first HVS visit: 259 (±92) vs. 348 (±137) L/min, p = 0.019. PCF and SNIP showed the best predictive characteristics in terms of sensitivity. CONCLUSION: SNIP showed the greatest decline prior to NIV indication and PCF significantly differentiated 'NIV-indication' from 'no NIV-indication yet' patients with ALS. Currently used cut-off values might be adjusted and other respiratory function tests such as SNIP and PCF may become part of routine care in patients with ALS in order to avoid non-timely initiation of (non-invasive) ventilation.

Respiratory function in facioscapulohumeral muscular dystrophy 1.

To test the hypothesis that wheelchair dependency and (kypho-)scoliosis are risk factors for developing respiratory insufficiency in facioscapulohumeral muscular dystrophy, we examined 81 patients with facioscapulohumeral muscular dystrophy 1 of varying degrees of severity ranging from ambulatory patients to wheelchair-bound patients. We examined the patients neurologically and by conducting pulmonary function tests: Forced Vital Capacity, Forced Expiratory Volume in 1 second, and static maximal inspiratory and expiratory mouth pressures. We did not find pulmonary function test abnormalities in ambulant facioscapulohumeral muscular dystrophy patients. Even though none of the patients complained of respiratory dysfunction, mild to severe respiratory insufficiency was found in more than one third of the wheelchair-dependent patients. Maximal inspiratory pressures and maximal expiratory pressures were decreased in most patients, with a trend that maximal expiratory pressures were more affected than maximal inspiratory pressures. Wheelchair-dependent patients with (kypho-)scoliosis showed the most restricted lung function. Wheelchair-dependent patients with (kypho-)scoliosis are at risk for developing respiratory function impairment. We advise examining this group of facioscapulohumeral muscular dystrophy patients periodically, even in the absence of symptoms of respiratory insufficiency, given its frequency and impact on daily life and the therapeutic consequences.

[When is a venous blood gas analysis sufficient in the emergency department?] / Wanneer volstaat een veneuze bloedgas op de SEH?

Blood gas analysis plays an important role in the initial assessment of a patient in the emergency ward. We present three different patient cases to illustrate when to opt for a venous or an arterial blood gas analysis. Arterial punctures are more painful and carry a higher risk of complications compared to venous punctures. It is possible to use a venous blood gas to screen for acute acid/base disturbances. Ventilatory compensation or anion gap cannot be calculated reliably with a venous blood gas. On the other hand, the diagnosis diabetic keto-acidosis can be made with a venous blood gas; this mode of sampling can also be used for lactate measurement at the emergency department as an independent prognostic marker for mortality. Venous blood gas analyses are not able to assess oxygenation. Pulse oximetry is a non-invasive alternative for arterial blood gas sampling. The use of a venous blood gas to assess a patient's ventilation is limited, whereas it can be used to diagnose carbomonoxide intoxication or methaemoglobinaemia.

The view of pulmonologists on palliative care for patients with COPD: a survey study.

INTRODUCTION: Early palliative care is not a common practice for patients with COPD. Important barriers are the identification of patients for palliative care and the organization of such care in this patient group. OBJECTIVE: Pulmonologists have a central role in providing good quality palliative care for patients with COPD. To guide future research and develop services, their view on palliative care for these patients was explored. METHODS: A survey study was performed by the members of the Netherlands Association of Physicians for Lung Diseases and Tuberculosis. RESULTS: The 256 respondents (31.8%) covered 85.9% of the hospital organizations in the Netherlands. Most pulmonologists (92.2%) indicated to distinguish a palliative phase in the COPD trajectory, but there was no consensus about the different criteria used for its identification. Aspects of palliative care in COPD considered important were advance care planning conversation (82%), communication between pulmonologist and general practitioner (77%), and identification of the palliative phase (75.8%), while the latter was considered the most important aspect for improvement (67.6%). Pulmonologists indicated to prefer organizing palliative care for hospitalized patients with COPD themselves (55.5%), while 30.9% indicated to prefer cooperation with a specialized palliative care team (SPCT). In the ambulatory setting, a multidisciplinary cooperation between pulmonologist, general practitioner, and a respiratory nurse specialist was preferred (71.1%). CONCLUSION: To encourage pulmonologists to timely initiate palliative care in COPD, we recommend to conduct further research into more specific identification criteria. Furthermore, pulmonologists should improve their skills of palliative care, and the members of the SPCT should be better informed about the management of COPD to improve care during hospitalization. Communication between pulmonologist and general practitioner should be emphasized in training to improve palliative care in the ambulatory setting.

Effects of long-acting bronchodilators and prednisolone on inspiratory lung function parameters in stable COPD.

BACKGROUND: In chronic obstructive pulmonary disease (COPD), there is a poor correlation between forced expiratory volume in 1 s (FEV1) and dyspnea following bronchodilator use. Better correlations have been observed between inspiratory lung function parameters (ILPs) and dyspnea, which drives our interest in ILPs. However, the acute and prolonged effects of long-acting bronchodilators and oral corticosteroids on ILPs have not been well investigated. Therefore, the aim of this study was to investigate the effects of these treatments on the ILPs, FEV1, dyspnea (visual analog scale (VAS)) and clinical COPD questionnaire (CCQ). METHODS: Twenty-eight stable COPD patients had their ILPs and FEV1 measured both before and 2 h after the use of a single dose of 18 mcg bronchodilator tiotropium and 50 mcg salmeterol. Thereafter, the patients were randomized to 2 weeks of treatment with 30 mg oral prednisolone once daily or oral placebo in combination with daily treatment with these two bronchodilators. Four weeks after the cessation of the randomized treatment, the ILPs and FEV1 were again measured. After each intervention, any change in the VAS score was assessed. RESULTS: With both bronchodilators, significant improvements in ILPs were demonstrated (p < 0.005), with the exception of changes in ILPs inspiratory capacity (IC) and forced inspiratory flow at 50% of the vital capacity (FIF50) after tiotropium inhalation. After 2 weeks of treatment with prednisolone, significant differences were found for ILP forced inspiratory volume in 1 s (FIV1) and FEV1 compared with placebo. These differences were no longer present 4 weeks after the cessation of prednisolone. Significant relationships between ILPs and VAS scores were only found after 2 weeks of treatment with prednisolone or placebo. CONCLUSIONS: After a single dose of long-acting bronchodilator salmeterol, significant improvements are observed in all ILPs and in FIV1 and PIF after tiotropium. Two weeks of oral corticosteroid treatment improved the FIV1 and FEV1. The dyspnea VAS score was only significantly correlated with the ILPs after 2 weeks of oral corticosteroid treatment.

Non-invasive ventilation abolishes the IL-6 response to exercise in muscle-wasted COPD patients: a pilot study.

Systemic inflammation in patients with chronic obstructive pulmonary disease (COPD) has been related to the development of comorbidities. The level of systemic inflammatory mediators is aggravated as a response to exercise in these patients. The aim of this study was to investigate whether unloading of the respiratory muscles attenuates the inflammatory response to exercise in COPD patients. In a cross-over design, eight muscle-wasted stable COPD patients performed 40 W constant work-rate cycle exercise with and without non-invasive ventilation support (NIV vs control). Patients exercised until symptom limitation for maximally 20 min. Blood samples were taken at rest and at isotime or immediately after exercise. Duration of control and NIV-supported exercise was similar, both 12.9 ± 2.8 min. Interleukin- 6 (IL-6) plasma levels increased significantly by 25 ± 9% in response to control exercise, but not in response to NIV-supported exercise. Leukocyte concentrations increased similarly after control and NIV-supported exercise by ∼15%. Plasma concentrations of C-reactive protein, carbonylated proteins, and production of reactive oxygen species by blood cells were not affected by both exercise modes. This study demonstrates that NIV abolishes the IL-6 response to exercise in muscle-wasted patients with COPD. These data suggest that the respiratory muscles contribute to exercise-induced IL-6 release in these patients.

Can COPD patients who hyperinflate during daily life activities be identified by laboratory tests?

BACKGROUND: Identification of patients with chronic obstructive pulmonary disease (COPD) who develop dynamic hyperinflation (DH) during activities in daily life (ADL) is important, because of the association between DH and dyspnea and exercise limitation. OBJECTIVE: We aimed to answer the question whether measurements of DH during metronome-paced tachypnea (MPT) or cardiopulmonary exercise testing (CPET) can be used to identify patients who develop DH during ADL. METHODS: DH was measured by tracking changes in inspiratory capacity during CPET, MPT and ADL. Bland-Altman plots were used to evaluate agreement in DH between methods. With a receiver operating characteristic (ROC) analysis, the overall accuracy of MPT and CPET to identify patients who hyperinflate during ADL was assessed. RESULTS: There are broad limits of agreement in DH between methods. ROC curve analyses showed good overall accuracy of both CPET and MPT to identify patients who hyperinflate during ADL. For CPET, area under the curve (AUC) = 0.956 (95% CI 0.903-1.009). For MPT, AUC = 0.840 (95% CI 0.699-0.981). Sensitivity and specificity to identify patients who hyperinflate during ADL with CPET were 96 and 83%, respectively, and with MPT, they were 89 and 77%, respectively. CONCLUSION: Both CPET and MPT can serve as screening tools to identify patients who are susceptible to developing DH during ADL. In practice, MPT is the most simple and inexpensive surrogate. However, the sensitivity of MPT is not optimal. When DH does not occur during CPET, it is unlikely to occur during ADL.

The effect of bronchodilators administered via aerochamber or a nebulizer on inspiratory lung function parameters.

BACKGROUND: In chronic obstructive pulmonary disease (COPD) the clinical efficacy of bronchodilator therapy delivered via a nebulizer versus an aerochamber on FEV1 is controversial. No studies comparing changes in inspiratory pulmonary function parameters (ILPs) using these inhaler devices are currently available. This information might be of interest because due to dynamic bronchial compression, the relationship between the ILPs and dyspnea is more reliable than that between FEV1 and dyspnea. Therefore, our study aimed to investigate whether changes in ILPs after use of these inhaler devices were similar to the changes in FEV1 and correlate with VAS (Visual Analogue Scale). METHODS: Forty-one stable COPD patients participated in a crossover trial. Spirometry was performed before and after two puffs Combivent (200 mcg salbutamol and 20 mcg ipratropium per puff) using an aerochamber or 2 mL of Combivent (2.5 mg salbutamol and 250 mcg ipratropium per mL) using a nebulizer. Differences in lung function parameters and changes in VAS were measured. RESULTS: ILP values improved significantly from baseline after Combivent administration using both devices (p ≤ 0.004). With both devices, the mean percent changes were significantly greater for FEV(1) than the ILPs (p ≤ 0.003), except for IC (p = 0.19). The mean VAS score did not differ significantly between the devices (p = 0.33), but significant correlations were found between the VAS and forced inspiratory flow at 50% of the vital capacity (FIF(50)) and peak inspiratory flow (PIF) when a nebulizer was used. With an aerochamber, no significant correlations between lung function parameters and VAS were found. CONCLUSIONS: The present study demonstrates that ILPs improved significantly after using either device. Although significant correlations were found between the VAS and FIF(50) and PIF for the nebulizer, in stable COPD patients, the pMDI plus spacer is a better route of administration than a nebulizer.

A method to study the effect of bronchodilators on smoke retention in COPD patients: study protocol for a randomized controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common disease, associated with cardiovascular disease. Many patients use (long-acting) bronchodilators, whilst they continue smoking alongside. We hypothesised an interaction between bronchodilators and smoking that enhances smoke exposure, and hence cardiovascular disease. In this paper, we report our study protocol that explores the fundamental interaction, i.e. smoke retention. METHOD: The design consists of a double-blinded, placebo-controlled, randomised crossover trial, in which 40 COPD patients smoke cigarettes during both undilated and maximal bronchodilated conditions. Our primary outcome is the retention of cigarette smoke, expressed as tar and nicotine weight. The inhaled tar weights are calculated from the correlated extracted nicotine weights in cigarette filters, whereas the exhaled weights are collected on Cambridge filters. We established the inhaled weight calculations by a pilot study, that included paired measurements from several smoking regimes. Our study protocol is approved by the local accredited medical review ethics committee. DISCUSSION: Our study is currently in progress. The pilot study revealed valid equations for inhaled tar and nicotine, with an R2 of 0.82 and 0.74 (p < 0.01), respectively. We developed a method to study pulmonary smoke retentions in COPD patients under the influence of bronchodilation which may affect smoking-related disease. This trial will provide fundamental knowledge about the (cardiovascular) safety of bronchodilators in patients with COPD who persist in their habit of cigarette smoking. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00981851.

Reversibility of inspiratory lung function parameters after short-term bronchodilators in COPD.

BACKGROUND: The responsiveness of short-term bronchodilator use on inspiratory lung function parameters (ILPs), including Forced Inspiratory Volume in one second (FIV(1)), Inspiratory Capacity (IC), Forced Inspiratory Flow at 50% of the vital capacity (FIF(50)), Peak Inspiratory Flow (PIF) and on the relationship between these values and dyspnea in COPD subjects has been examined only sparsely in past studies. The aim of this study was to assess the effects of inhaled salbutamol 400 mcg, ipratropium 80 mcg and a placebo on ILP and FEV(1) and their relationship to dyspnea, as measured with a Visual Analogue Scale (VAS). METHODS: A total of 85 subjects with stable COPD participated in a crossover, randomized, double-blind, placebo-controlled study. Spirometry was performed before and after inhalation of salbutamol, ipratropium or a placebo. The primary analysis was performed using 63 participants with absent reversibility. RESULTS: All ILP and FEV(1) values improved significantly after bronchodilator administration except for FIF(50) after ipratropium administration. After administration of both bronchodilators, the mean percent changes from initial values did not significantly differ between the various ILPs and FEV(1). The mean VAS score showed significant improvements after bronchodilator and placebo inhalation but did not significantly correlate with changes in lung function parameters. For each lung function parameter, patients were further classified as responders if the amount of change was greater than the coefficient of repeatability of the test. Response rates did not differ significantly between the various ILPs. Moreover, no significant differences were found between responders and non-responders with respect to dyspnea after bronchodilator inhalation. This finding applied to all ILP and FEV(1) values. CONCLUSIONS: In subjects with COPD, all ILP, FEV(1) values and VAS scores showed significant improvements after bronchodilator use as well as with placebo. However, ILPs were not more sensitive than FEV(1) for detecting responders after bronchodilator use or changes in the VAS score.

Maximal exercise capacity in chronic obstructive pulmonary disease: a limited indicator of the health status.

BACKGROUND: Dyspnoea and diminished functional status are pivotal features of the health status (HS) in chronic obstructive pulmonary disease (COPD). However, it is still not fully understood how pulmonary function tests and cardiopulmonary exercise testing relate to these aspects. This may be due to incomplete assessment and/or deficient definitions of HS. Especially regarding peak oxygen consumption, inconsistent results have been reported. OBJECTIVES: To determine the value of maximal cycle ergometry in relation to a broad spectrum of HS aspects. METHODS: 129 patients with COPD, stage II and III according to the GOLD classification, performed a cardiopulmonary exercise test. Sixteen independent sub-domains of HS were assessed according to the Nijmegen Integral Assessment Framework, covering physiological functioning, complaints, functional impairments and quality of life as main domains. VO(2)(max) and HS sub-domains were correlated by bivariate analysis. RESULTS: Weak correlations of VO(2)(max) with most sub-domains were found, except for exercise capacity; the other 5 sub-domains of physiological functioning did not correlate. Between different types of exercise limitation (5 types were differentiated), no significant differences were noted in the scores of 13/16 HS sub-domains. CONCLUSIONS: VO(2)(max) is indeed correlated with most aspects of HS, except for physiological variables, but associations are weak. No single exercise limitation type is associated with specific HS problems. Thus separate assessment of all HS sub-domains is advocated to ensure adequate planning of therapeutic interventions.

Physiologic limitations during daily life activities in COPD patients.

INTRODUCTION: Patients with COPD are known to be limited in their performance of activities of daily life (ADL). This observational study aims to investigate the ventilatory and metabolic demand of ADL in home settings of patients and evaluate possible mechanisms involved in physiological limitation during ADL in COPD. METHODS: In their home settings, 21 stable patients with COPD (GOLD II-IV, mean FEV(1) 43% predicted) were asked to perform their most dyspnea causing activities at their usual pace until symptoms discouraged further performance. Ten healthy control subjects, matched for age and gender, performed comparable activities. Ventilatory and metabolic demands of the ADL were studied using a portable breath-by-breath system. RESULTS: Compared with healthy controls, ADL time was shorter in patients (530 +/- 38 s vs. 318 +/- 37 s respectively) and activities resulted in important complaints of dyspnea. Oxygen consumption (V O(2)) during the activities was higher in patients compared to healthy subjects (957 +/- 51 vs. 768 +/- 63 mL/min resp.). Ventilatory demand (V E) for comparable activity (at isoV O(2)) was higher in patients and went together with complaints of dyspnea in patients, but not in healthy subjects. Ventilatory constraints like low ventilatory reserve and inspiratory reserve volume and dynamic hyperinflation occurred in more than 80% of the patients, especially in (very) severe patients. CONCLUSION: Patients with COPD experience limitations in the performance of ADL, which lead to reductions in ADL time and dyspnea complaints. There appears to be an important role for ventilatory limitations, which become more prominent as disease progresses.

Exercise in systemic sclerosis intensifies systemic inflammation and oxidative stress.

OBJECTIVE: Exercise testing can be used (i) to evaluate functional limitations of systemic sclerosis (SSc) and (ii) to study whether the inflammatory and oxidative systems are activated after a physical stimulus. The aim of this study was to determine exercise-induced inflammatory and oxidative responses in SSc compared with healthy subjects. METHODS: Eleven patients with SSc and pulmonary involvement and 10 healthy subjects underwent maximal cardiopulmonary exercise testing (CPET). Physiological responses were followed continuously during cycling. Blood samples were taken at rest, during and after maximal exercise to measure inflammatory and oxidative markers. RESULTS: In nine of the 11 SSc patients, cardiocirculatory limitation and gas exchange impairment limited exercise capacity. Basal inflammatory cells, interleukin (IL)-6, and oxidative stress were increased in SSc compared to healthy subjects and intensified after exercise. Basal and exercise-induced inflammation and oxidative stress were correlated with the modified Rodnan skin score. CONCLUSIONS: Although exercise capacity is impaired in patients with SSc, physical activity intensifies the already increased basal levels of systemic inflammation and oxidative stress. These data support the concept of a role for systemic inflammation and oxidative stress in the ongoing systemic effects of SSc.

Is physician-diagnosed allergic rhinitis a risk factor for the development of asthma?

BACKGROUND: There is strong evidence that there is a relationship between allergic rhinitis (AR) and asthma, but it is unclear whether there is a causal relation between AR and asthma. The aim of this study was to assess prospectively whether AR is a risk factor for the diagnosis of asthma in a large primary care population. METHODS: We performed a historic cohort study of life-time morbidity that had been recorded prospectively since 1967 in four general practices. Two groups of subjects were selected: (i) patients with diagnosis of AR, (ii) a control group matched using propensity scores. We assessed the risk of physician-diagnosed asthma in patients with physician-diagnosed AR compared to subjects without a diagnosis of AR (controls). RESULTS: The study population consisted of 6491 subjects (n = 2081 patients with AR). Average study follow-up was 8.4 years. In patients with AR, the frequency of newly diagnosed asthma was 7.6% (n = 158) compared to 1.6% (n = 70) in controls (P < 0.001). After adjusting the effect of AR on asthma diagnosis for registration time, age, gender, eczema and socioeconomic status, having AR was a statistically significant risk factor for asthma (hazard ratio: 4.86, P < 0.001, 95% confidence interval: 3.50-6.73, controls as reference). CONCLUSION: A diagnosis of AR was an independent risk factor for asthma in our primary care study population. Having physician-diagnosed AR increased the risk almost fivefold for a future asthma diagnosis.

Interaction in COPD experiment (ICE): a hazardous combination of cigarette smoking and bronchodilation in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease, characterised by poorly reversible, obstructive airflow limitation. Alongside other comorbidities, COPD is associated with increased morbidity and mortality resulting from cardiovascular disease - mainly heart failure and ischemic heart disease. Both diseases share an important risk factor, namely, smoking. About 50% of COPD patients are active cigarette smokers. Bronchodilation is the cornerstone of pharmaceutical treatment for COPD symptoms, and half of all COPD patients use long-acting bronchodilating agents. Discussion about these agents is currently focusing on the association with overall mortality and morbidity in COPD patients, of cardiovascular origin in particular. Bronchodilation diminishes the hyperinflated state of the lung and facilitates the pulmonary deposition of cigarette smoke by deeper inhalation into the smaller airways. Smaller particles, as in smoke, tend to penetrate and depose more in these small airways. In addition, bronchodilation indeed increases carbon monoxide uptake in the lungs, an important gaseous compound of cigarette smoke. Since the number of cigarettes smoked is positively correlated to mortality from cardiac events, we therefore hypothesise that chronic bronchodilation increases cardiovascular disease and mortality in COPD patients who continue smoking by increasing pulmonary retention of pathogenic smoke constituents. Indeed, a recent meta-analysis is suggestive that long-acting anticholinergics might increase cardiovascular disease if patients exceed a certain number of cigarettes smoked. To demonstrate the fundamental mechanism of this pathogenic interaction we will perform a randomised placebo-controlled cross-over trial to investigate the effect of maximum bronchodilation on the retention of cigarette smoke constituents. In 40 moderate to severe COPD patients we measure the inhaled and exhaled amount of tar and nicotine, as well during maximum bronchodilation as during administration of placebo. The fraction of retention of tar and nicotine is subsequently calculated for both circumstances and analysed for association with bronchodilation. Further observational cohort studies or randomised clinical trials designed to monitor cardiovascular events may well evaluate the interaction. Since many patients are at risk for this possibly hazardous interaction, its relevance to our society and healthcare is potentially great. The implication will be that the urgency to quit smoking is intensified. Besides, chronic bronchodilation - specifically long-acting bronchodilators - needs to be discouraged in smoking COPD patients that refuse to quit.

Metabolic acidosis improves airway conductance in patients with asthma.

The objective was to investigate whether acute metabolic acidosis could cause bronchodilation in patients with asthma. Twelve patients with asthma (8 females, mean age 39 (+/- SD 12) years, forced expiratory volume in 1 second [FEV(1)] 93 [+/-9] % predicted, PC(20) 1.9 (+/-1.0) mg/mL) participated in a double-blind, placebo-controlled trial. Subjects ingested calculated amounts of ammonium chloride to induce acidosis or saline as placebo, in random order, each on a separate day. Airway resistance (R(aw)), specific airway conductance (sG(aw)), FEV(1), and PEF were measured as primary variables. To evaluate the consequences of alterations in bronchial contractility on the airway responsiveness, the histamine provocation test (PC(20)) was measured as secondary variable. The intervention resulted in a mean (SD) decrease in base excess from -0.5 (+/-1.4) to -3.9 (+/-1.1) mmol/L (p < 0.01) and a decrease in pH from 7.41 (+/-0.02) to 7.36 (+/-0.02) (p < 0.01). This caused a statistically significant increase in sG(aw) from 1.15 (+/-0.16) to 1.26 (+/-0.13) 1/kPa.s) (p < 0.05). Tendencies towards increase were found in PEF (7.79 (+/-2.2) versus 8.09 (+/-1.9) (NS, p = 0.10) and in FEV(1) (2.98 (+/-0.9) versus 3.06 (+/-0.9) (NS, p = 0.15). PC(20) did not change significantly. It was concluded that acute metabolic acidosis has a modest bronchodilating effect in patients with asthma.