Six-minute walking-induced systemic inflammation and oxidative stress in muscle-wasted COPD patients

BACKGROUND: Systemic inflammation and oxidative stress are potential mechanisms for muscle wasting in COPD patients. Six-minute walking testing (6MWT) has been suggested as simple and valid exercise test in COPD that is well tolerated, and reflective of activities of daily living. The present study investigated physiologic and systemic immunologic responses to a 6MWT in muscle-wasted patients with COPD and compared them with maximal cardiopulmonary exercise testing (CPET). METHODS: Ten patients with muscle-wasted COPD were included (fat-free mass index [FFMI]: men, < 16 kg/m2; women, < 15 kg/m2). 6MWT and CPET were performed in random order. The physiologic response was followed by a mobile oxycon. Arterial blood was obtained at rest and after exercise to measure blood gases and markers of systemic inflammation and oxidative stress. RESULTS: In these patients (FEV1 55 +/- 4% of predicted [mean +/- SE]), the 6MWT was a submaximal, albeit intense, exercise as reflected by oxygen uptake (VO2), minute ventilation, heart rate, and lactate values. Leukocytosis was less intense after 6MWT compared to CPET. Contrary, the increase in interleukin-6, free radical release by neutrophils, oxidation of proteins and lipids, and the reduction in antioxidant capacity were similar after both exercises. FFMI was inversely related to 6MWT-induced increases in protein and lipid peroxidation. CONCLUSIONS: This study shows that a 6MWT induces a systemic immunologic response in muscle-wasted patients with COPD, which is comparable to CPET-induced responses. The correlation between systemic oxidative stress and the degree of muscle wasting supports a possible causal relation between systemic inflammation, oxidative stress, and muscle wasting.     

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 (FIV₁), Inspiratory Capacity (IC), Forced Inspiratory Flow at 50% of the vital capacity (FIF₅₀), 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 FEV₁ 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 FEV₁ values improved significantly after bronchodilator administration except for FIF₅₀ after ipratropium administration. After administration of both bronchodilators, the mean percent changes from initial values did not significantly differ between the various ILPs and FEV₁. 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 FEV₁ values.

Conclusions

In subjects with COPD, all ILP, FEV₁ values and VAS scores showed significant improvements after bronchodilator use as well as with placebo. However, ILPs were not more sensitive than FEV₁ for detecting responders after bronchodilator use or changes in the VAS score.     

Development of a battery of instruments for detailed measurement of health status in patients with COPD in routine care: the Nijmegen Clinical Screening Instrument

Purpose  To compose a battery of instruments that provides a detailed assessment of health status (HS) in COPD but that is applicable and clinically meaningful in routine care. Methods  In a previous study, we developed the Nijmegen Integral Assessment Framework (NIAF) that organizes existing tests and instruments by the sub-domains of HS they measure. Based on clinical and statistical criteria (correlation coefficients and Cronbach alpha’s) we selected for each sub-domain instruments from the NIAF. A COPD-study group was used to determine c-scores, and two control groups were used to determine the score ranges indicating normal functioning versus clinically relevant problems for each sub-domain. Existing questionnaire completion software (TestOrganiser) was adapted to enhance clinical applicability. Results  The NCSI measures eleven sub-domains of physiological functioning, symptoms, functional impairment, and quality of life. The TestOrganiser automatically processes the data and produces the graphical PatientProfileChart, which helps to easily interpret results. This envisages the problem areas and discrepancies between the different sub-domains. Conclusion  The NCSI provides a valid and detailed picture of a patient’s HS within 15–25 min. In combination with the PatientProfileChart, the NCSI can be used perfectly in routine care as screening instrument and as a guide in patient-tailored treatment.     

Pleural small cell carcinoma in pre-existent asbestos related pleural disease.

Extrapulmonary small cell carcinoma (SCC) is a very rare disease, and a primary pleural manifestation is extremely rare. A case of SCC of the pleura in a 66-year-old man with pre-existent asbestos-related pleural plaques is presented. This is the first case of pleural SCC in a patient with asbestos-induced pleural disease and the third reported case of a pleural SCC. The SCC developed in an area with pre-existent pleural thickening, underlining the need for careful analysis of alterations in the manifestation of pleural disease in patients with asbestos exposition.     

Verapamil causes decreased diaphragm endurance but no decrease of nocturnal O2 saturation in patients with chronic obstructive pulmonary disease

Objective: In animal studies, it has been shown that verapamil reduces strength and endurance of the diaphragm and inhibits the beneficial effects of theophylline. We examined whether the use of verapamil in patients with severe chronic obstructive pulmonary disease (COPD) who use theophylline leads to a deterioration of diaphragmatic function resulting in a decrease of nocturnal O₂ saturation. Methods: A double-blind, placebo-controlled crossover study was designed in eight stabile severe COPD patients [forced expiratory volume in 1 s (FEV₁) 0.9 ± 0.1 l] taking theophylline. The doses of theophylline ranged from 600 mg daily to 1200 mg daily (7.0 mg/kg daily to 16.9 mg/kg daily). Nocturnal recordings, maximal respiratory muscle strength and endurance tests, lung function, blood pressure, electrocardiogram and arterial blood gas analysis were performed after 6 days of verapamil and after placebo. Results: A significant decrease of the endurance time from 7.7 min to 6.4 min was found in the threshold loading test. However, the mean nocturnal saturation values did not change significantly: 89.8% and 89.6%, respectively. Results of pulmonary function tests, arterial blood gas analysis and routine blood samples also did not change. Conclusion: The decrease of the respiratory muscle endurance after the use of verapamil is in line with experiments in animal diaphragms. However, the nocturnal saturation did not change. This finding suggests that the effect found on diaphragm endurance is of no clinical significance and that verapamil can be given to COPD patients without risk of worsening nocturnal saturation. However, this must be confirmed by future larger scale studies. Received: 20 April 1999 / Accepted in revised form: 4 October 1999     

Underestimation of nocturnal hypoxemia due to monitoring conditions in patients with COPD

STUDY OBJECTIVES: COPD patients run a risk of developing nocturnal oxygen desaturation. When evaluating patients with nocturnal hypoxemia, an unfamiliar hospital environment and the monitoring equipment may cause sleep disturbances. It was hypothesized that increased sleep disruption will lead to fewer instances of desaturation during a night of monitoring. DESIGN:The following forms of monitoring were evaluated prospectively on 3 nights for each patient: oximetry at home; polysomnography (PSG) at home; and PSG in the hospital. SETTING: Department of Pulmonology, Rijnstate Hospital Arnhem, The Netherlands. PATIENTS: Fourteen stable COPD patients (7 men; median age, 71.5 years; age range, 59 to 81 years; FEV(1), 32.5% predicted; FEV(1) range, 19 to 70% predicted) participated in the study. All subjects had significant instances of nocturnal arterial oxygen desaturation. Those patients with a sleep-related breathing disorder or cardiac failure were excluded from the study. MEASUREMENTS AND RESULTS: The mean nocturnal arterial oxygen saturation (SaO(2)) level was higher during PSG monitoring at home (89.7%; range, 77 to 93%) than during oximetry monitoring (88.5%; range, 80 to 92%) [p < 0.025]. The fraction of time spent in hypoxemia (ie, SaO(2) < 90%) was lower during PSG monitoring at home (40.8%; range, 5 to 100%) than during oximetry monitoring (59.9%; range, 6 to 100%) [p < 0.01]. Desaturation time (DeltaSaO(2) > 4%) was lower during PSG monitoring at home (22.1%; range, 3 to 63%) during PSG monitoring at home than during oximetry monitoring (50.4%; range, 4 to 91%) [p < 0.01]. A correction for actual sleep during PSG monitoring reduced the differences between PSG monitoring at home and oximetry monitoring, although a difference in the desaturation time remained (PSG monitoring at home, 31.9% [range, 2 to 75%]; oximetry monitoring, 50.4% [range, 4 to 91%]) [p = 0.041]. A comparison of sleep architectures for nights when PSG was being monitored showed a higher arousal index in the hospital than at home (PSG monitoring in the hospital, 5.6 arousals per hour [range, 2 to 16 arousals per hour]; PSG monitoring at home, 2.5 arousals per hour [range, 1 to 6 arousals per hour]) [p < 0.025], but no differences in SaO(2) levels were found between PSG monitoring at home and PSG monitoring in the hospital. CONCLUSION: The artifacts due to sleep-monitoring equipment may cause an underestimation of the degree of nocturnal hypoxemia in COPD patients. The addition of an unfamiliar environment causes more sleep disruption, but this does not affect nocturnal SaO(2) levels further.