Frank J.J. van den Elshout

Sleep, hypnotics and chronic obstructive pulmonary disease

The quality of sleep is significantly compromised in many patients with chronic obstructive pulmonary disease (COPD) and may be further diminished when certain comorbidities are present. A reduced sleep quality is associated with daytime consequences like fatigue, psychiatric problems and an impaired quality of life. Sleep induces physiologic alterations in respiratory function, which can become pathologic and may provoke or worsen hypoxemia and hypercapnia in COPD. Dyspnea, cough and excessive mucus production should be optimised to minimise causes for sleep disturbance. Pharmacological therapy may be helpful; sedatives like benzodiazepines and non-benzodiazepine benzodiazepine-receptor agonists (NBBRAs) are (equally) effective in improving sleep quality. Whether or not these hypnotics produce serious adverse respiratory effects during sleep, remains unclear due to opposing studies. Therefore, their use should be as short as possible.

Temazepam 10mg does not affect breathing and gas exchange in patients with severe normocapnic COPD.

BACKGROUND Benzodiazepines can improve sleep quality, but are also thought to cause respiratory depression in patients with chronic obstructive pulmonary disease (COPD). The aims of this study were to assess the effects of temazepam on indices of circadian respiratory function, dyspnea, sleep quality, and sleepiness in patients with severe COPD and insomnia. METHODS In a double-blind, randomized, placebo-controlled, cross-over study in 14 stable patients with COPD (mean FEV(1) 0.99+/-0.3L) with insomnia, polysomnography with continuous transcutaneous capnography and oximetry, arterial gas sampling, hypercapnic ventilatory response, multiple sleep latency test, Epworth Sleepiness Scale, dyspnea and sleep visual analogue scales (VAS) were performed at baseline, after one week of temazepam 10mg at bedtime and after one week of placebo. RESULTS Temazepam did not cause statistically significant changes in mean transcutaneous carbon dioxide tension during sleep compared to placebo (5.9+/-1.0 kPa vs. 6.3+/-1.4 kPa, p-value 0.27), nor in mean oxygen saturation (92+/-3% vs. 92+/-2%, p-value 0.31), nor in any of the other investigated variables, except for the total sleep time and sleep latency VAS, which improved with temazepam. CONCLUSIONS One week usage of temazepam 10mg does not influence circadian respiratory function, dyspnea, and sleepiness in patients with stable, severe, normocapnic COPD and insomnia and it improves total sleep time and subjective sleep latency. However, this is a preliminary explorative study for assessing the feasibility to perform a larger study on this topic. The clinical implications of this study are very limited.

Accuracy of transcutaneous carbon dioxide tension measurements during cardiopulmonary exercise testing.

Background: Measurements of transcutaneous carbon dioxide tension (PtcCO₂) with current devices are proven to provide clinically acceptable agreement with measurements of partial arterial carbon dioxide tension (PaCO₂) in several settings but not during cardiopulmonary exercise testing (CPET). Objectives: The primary objective of this study was to investigate the agreement between PaCO₂ and PtcCO₂ measurements (using a Tosca 500 with a Tosca sensor 92) during CPET. A secondary objective was to investigate the agreement between arterial and transcutaneous oxygen saturation (SaO₂, SpO₂) as measured with this sensor during CPET. Methods: In patients with various pulmonary diseases, PtcCO₂ and SpO₂ were continuously measured and compared with arterial blood gas samples during CPET. A maximum bias of 0.5 kPa and 95% limits of agreement (LOA) of 1 kPa between carbon dioxide pressure (PCO₂) measurements were determined as clinically acceptable. Results: In total 101 ‘paired’ arterial and transcutaneous measurements were obtained from 21 patients. Bias between PaCO₂ and PtcCO₂ was –0.03 kPa with LOA from –0.78 to 0.71 kPa. Bias between SaO₂ and SpO₂ was –1.0% with LOA from –2.83 to 0.83%. Conclusions: Transcutaneous estimations of PCO₂ and SpO₂ are accurate and can be used in CPET, circumvening the need for arterial cannulation.

COPD in chronic heart failure: less common than previously thought?

BACKGROUND Using a fixed ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) < 0.70 instead of the lower limit of normal (LLN) to define chronic obstructive pulmonary disease (COPD) may lead to overdiagnosis of COPD in elderly patients with heart failure (HF) and consequently unnecessary treatment with possible adverse health effects. OBJECTIVE The aim of this study was to determine COPD prevalence in patients with chronic HF according to two definitions of airflow obstruction. METHODS Spirometry was performed in 187 outpatients with stable chronic HF without pulmonary congestion who had a left ventricular ejection fraction <40% (mean age 69 ± 10 years, 78% men). COPD diagnosis was confirmed 3 months after standard treatment with tiotropium in newly diagnosed COPD patients. RESULTS COPD prevalence varied substantially between 19.8% (LLN-COPD) and 32.1% (GOLD-COPD). Twenty-three of 60 patients (38.3%) with GOLD-COPD were potentially misclassified as having COPD (FEV1/FVC < 0.7 but > LLN). In contrast to patients with LLN-COPD, potentially misclassified patients did not differ significantly from those without COPD regarding respiratory symptoms and risk factors for COPD. CONCLUSIONS One fifth, rather than one third, of the patients with chronic HF had concomitant COPD using the LLN instead of the fixed ratio. LLN may identify clinically more important COPD than a fixed ratio of 0.7.

Effect of acute metabolic acid/base shifts on the human airway calibre

Acute metabolic alkalosis (NaHCO(3)), acidosis (NH(4)Cl), and placebo (NaCl) were induced in 15 healthy volunteers (12 females, median age 34 (range 24-56) years) in a double blind, placebo controlled study to evaluate the presence of the effects on airway calibre. Acid-base shifts were determined by capillary blood gas sampling. Measurements were performed at the maximal acid-base shift, 90 min after intervention. Airway resistance (R(aw)) and specific airway conductance (sG(aw)), were evaluated, as primary variables, pre and post intervention. Secondary variables, including bronchial responsiveness to histamine, maximal respiratory mouth pressures and grip strength, were evaluated post intervention. In alkalosis, base excess (BE) increased from -0.3 (-3.0-1.9) to 3.0 (1.0-4.8) mmol/l and pH increased from 7.41 (7.37-7.43) to 7.44 (7.39-7.47) (both P<0.01), accompanied by an increase in Pa(CO(2)): 4.7 (4.0-5.7) to 5.0 (4.7-6.1) kPa (P<0.05). R(aw) increased from 0.156 (0.134-0.263) to 0.169 (0.132-0.271) kPa s/L (P<0.05), sG(aw) decreased, but this was not statistically significantly. In acidosis, BE decreased from -0.2 (-2.0-2.2) to -3.5 (-6.3-1.1) mmol/l and pH decreased from 7.41 (7.39-7.45) to 7.36 (7.31-7.40) (both P<0.01), accompanied by a non-significant decrease in Pa(CO(2)). Changes in R(aw) and sG(aw) were contrary to those in alkalosis, but did not reach statistical significance. Acute metabolic acid-base shifts mildly influence the airway calibre in healthy human subjects.

Serial pulmonary function tests to diagnose COPD in chronic heart failure

BackgroundIt is unknown whether serial pulmonary function tests are necessary for the correct diagnosis of chronic obstructive pulmonary disease (COPD) in patients with stable non-congested chronic heart failure (CHF). The aim of this study was to determine the prevalence of COPD in outpatients with stable CHF without pulmonary congestion using initial as well as confirmatory spirometry three months after treatment for COPD.MethodsSpirometry was performed in 187 outpatients with stable CHF without pulmonary congestion on chest radiograph who had a left ventricular ejection fraction < 40% (mean age 69 ± 10 years, 78% men). COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease guidelines. The diagnosis of COPD was confirmed three months after treatment with tiotropium in newly diagnosed COPD patients.ResultsUsing a three month follow-up spirometry to confirm initial diagnosis of de novo COPD did not change COPD prevalence significantly: 32.6% initially versus 32.1% after three months of follow-up. Only 1 of 25 (4%) patients with newly diagnosed COPD was not reproducibly obstructed at follow-up. COPD was greatly under- (19%) and overdiagnosed (32%).ConclusionsSpirometry should be used under stable and euvolemic conditions to decrease the burden of undiagnosed or overdiagnosed COPD in patients with CHF. Under these conditions, a confirmatory spirometry is unnecessary, as it does not change a newly established diagnosis of COPD in the vast majority of patients with CHF.Trial registrationClinicalTrials.gov Identifier NCT01429376.

Respiratory muscle strength and muscle endurance are not affected by acute metabolic acidemia.

Respiratory muscle fatigue in asthma and chronic obstructive lung disease (COPD) contributes to respiratory failure with hypercapnia, and subsequent respiratory acidosis. Therapeutic induction of acute metabolic acidosis further increases the respiratory drive and, therefore, may diminish ventilatory failure and hypercapnia. On the other hand, it is known that acute metabolic acidosis can also negatively affect (respiratory) muscle function and, therefore, could lead to a deterioration of respiratory failure. Moreover, we reasoned that the impact of metabolic acidosis on respiratory muscle strength and respiratory muscle endurance could be more pronounced in COPD patients as compared to asthma patients and healthy subjects, due to already impaired respiratory muscle function. In this study, the effect of metabolic acidosis was studied on peripheral muscle strength, peripheral muscle endurance, airway resistance, and on arterial carbon dioxide tension (PaCO2). Acute metabolic acidosis was induced by administration of ammonium chloride (NH4Cl). The effect of metabolic acidosis was studied on inspiratory and expiratory muscle strength and on respiratory muscle endurance. Effects were studied in a randomized, placebo‐controlled cross‐over design in 15 healthy subjects (4 male; age 33·2 ± 11·5 years; FEV1 108·3 ± 16·2% predicted), 14 asthma patients (5 male; age 48·1 ± 16·1 years; FEV1 101·6 ± 15·3% predicted), and 15 moderate to severe COPD patients (9 male; age 62·8 ± 6·8 years; FEV1 50·0 ± 11·8% predicted). An acute metabolic acidemia of BE –3·1 mmol.L−1 was induced. Acute metabolic acidemia did not significantly affect strength or endurance of respiratory and peripheral muscles, respectively. In all subjects airway resistance was significantly decreased after induction of metabolic acidemia (mean difference –0·1 kPa.sec.L−1 [95%‐CI: −0·1 –−0·02]. In COPD patients PaCO2 was significantly lowered during metabolic acidemia (mean difference –1·73 mmHg [−3·0 –−0·08]. In healthy subjects and in asthma patients no such effect was found. Acute metabolic acidemia did not significantly decrease respiratory or peripheral muscle strength, respectively muscle endurance in nomal subjects, asthma, or COPD patients. Metabolic acidemia significantly decreased airway resistance in asthma and COPD patients, as well as in healthy subjects. Moreover, acute metabolic acidemia slightly improved blood gas values in COPD patients. The results suggest that stimulation of ventilation in respiratory failure, by induction of metabolic acidemia will not lead to deterioration of the respiratory failure.

Manual vs. automated analysis of polysomnographic recordings in patients with chronic obstructive pulmonary disease.

PurposeThe sleep quality, as assessed by polysomnography (PSG), of patients with chronic obstructive pulmonary disease (COPD) can be severely disturbed. The manual analysis of PSGs is time-consuming, and computer systems have been developed to automatically analyze PSGs. Studies on the reliability of automated analyses in healthy subjects show varying results, and the purpose of this study was to assess whether automated analysis of PSG by one certain automatic system in patients with COPD provide accurate outcomes when compared to manual analysis.MethodsIn a retrospective study, the full-night polysomnographic recordings of patients with and without COPD were analyzed automatically by Matrix Sleep Analysis software and manually. The outcomes of manual and automated analyses in both groups were compared using Bland–Altman plots and Students’ paired t tests.ResultsFifty PSGs from patients with COPD and 57 PSGs from patients without COPD were included. In both study groups, agreement between manual and automated analysis was poor in nearly all sleep and respiratory parameters, like total sleep time, sleep efficiency, sleep latency, amount of rapid eye movement sleep and other sleep stages, number of arousals, apnea–hypopnea index, and desaturation index.ConclusionAutomated analysis of PSGs by the studied automated system in patients with COPD has poor agreement with manual analysis when looking at sleep and respiratory parameters and should, therefore, not replace the manual analysis of PSG recordings in patients with COPD.