Petra J.E. Vos

An Integral assessment framework of health status in chronic obstructive pulmonary disease (COPD).

Background: To date, many health status instruments exist, but the validity of these instruments is questionable. This is caused by the fact that health status is poorly defined.Purpose: To develop a validated framework that improves conceptual insight into health status and its domains.Methods: Based on theoretical and clinical considerations, we defined the domains of health status into concrete sub-domains by formulating conceptual models. Guided by these conceptual models, for each sub-domain, existing instruments were selected. We validated the conceptual models in the data of 168 COPD patients. Using factor analysis, underlying concepts in the data were identified.Results: The resulting framework included physiological functioning, complaints, functional impairment, and quality of life. These main domains were shown to be subdivided into 15 sub-domains.Conclusions: The present study shows that health status consists of conceptually distinct sub-domains. Integral assessment of health status thus entails measuring all sub-domains. Existing instruments measure only few sub-domains. Integral assessment of health status thus requires the combination of different instruments. The present framework of health status can help in composing such a battery of instruments. Patient profiles obtained by the framework are essential in individualizing treatment.

Predictors for nocturnal hypoxaemia (mean Sao2 <90%) in normoxic and mildly hypoxic patients with COPD

Detection of nocturnal hypoxaemia, defined as a mean arterial oxygen saturation below 90%, in normoxic or mildly hypoxic chronic obstructive pulmonary disease (COPD) patients seems clinically relevant, since this feature may precede pulmonary hypertension. Nocturnal studies are expensive and time-consuming procedures. The current study investigates to what extent it is possible to predict nocturnal hypoxaemia from daytime parameters. Forty two COPD patients with a daytime arterial oxygen tension (PaO2) above 8 kPa participated. Nocturnal oxygenation, daytime blood gas values, and ventilatory responses to hypercapnia were measured. In 10 patients, enough desaturations occurred to qualify as nocturnal hypoxaemia. They had a significantly lower daytime PaO2 value, and a lower steady-state hypercapnic ventilatory response. They also smoked more often, and complained about daytime sleepiness. Multiple linear regression analysis demonstrated that daytime PaO2 (32%) was the best independent predictor. Sleepiness (12%), and number of cigarettes smoked (5%) also contributed independently, but in a minor way. Patients with a high daytime PaO2 (> 11 kPa) did not develop nocturnal hypoxaemia. The hypercapnic ventilatory response was used to distinguish nocturnal hypoxaemic from normoxaemic patients. Only patients with a low response (< 3.5 l.min-1.kPa-1) appeared to run a risk of developing nocturnal hypoxaemia. The sensitivity of this test was 80%, and the specificity 70%. It is concluded that daytime PaO2, hypercapnic ventilatory response and sleepiness are helpful in predicting nocturnal hypoxaemia.

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.

Visual attention in patients with chronic obstructive pulmonary disease.

The selective visual attention of 39 patients with chronic obstructive pulmonary disease (COPD) was measured by the Bourdon-Vos test and compared with the attention performance of 38 healthy controls of the same age range. The correlation between the attention of the COPD patients and day- and night-time parameters was determined. Furthermore, in 44 other COPD patients with daytime hypoxaemia, the effect of one night of oxygen supplementation and of a 7-day treatment with two respiratory stimulants (chlormadinone acetate) (CMA) or acetazolamide (ACET) on attention performance was studied. The results showed that the attention performance of COPD patients was lower than that of controls. Significant correlations were found between the mean line time (attention parameter) and the following parameters: age, inspiratory vital capacity (IVC), hypercapnic ventilatory response (HCVR), daytime arterial oxygen saturation (SaO2), daytime arterial oxygen pressure (PaO2), daytime arterial carbon dioxide pressure (PaCO2), mean nocturnal SaO2, lowest nocturnal SaO2 and the standard deviation of the mean nocturnal SaO2. Multiple linear regression analysis showed that, apart from age, only the nadir of the nocturnal SaO2 contributed to the prediction of the attention. No clinically important short-term effect of oxygen or respiratory stimulating therapy on the attention performance was found.

Combined treatment with acetazolamide and medroxyprogesterone in chronic obstructive pulmonary disease patients.

Medroxyprogesterone acetate (MPA) and acetazolamide (ACET) are two ventilatory stimulants which are used in hypoxic and hypercapnic patients with chronic obstructive pulmonary disease (COPD). In a double-blind randomised study, the effects of a 2-week treatment with MPA (30 mg b.i.d.) or ACET (250 mg b.i.d.), followed by a 2-week treatment with a combination of both drugs (MPA/ACET), on daytime and nocturnal ventilatory and blood gas parameters in 17 stable hypercapnic COPD patients were investigated. ACET, MPA and MPA/ACET treatment decreased mean daytime carbon dioxide tension in arterial blood by 0.4, 0.7 and 1.2 kPa, respectively. Minute ventilation was improved only with combined therapy, from 9.3 to 11.2 L·min−1. With MPA/ACET therapy, the hypercapnic and hypoxic ventilatory responses significantly increased, from 3.7 to 5.8 L·min−1·kPa−1 and from −0.13 to −0.40 L·min−1·%−1, respectively. The mouth exclusion pressure response to hypoxia increased during combination therapy, from −0.01 to −0.03 kPa·%−1. Nocturnal end-tidal carbon dioxide tension decreased with MPA and MPA/ACET treatment, by 0.9 and 1.4 kPa, respectively. MPA/ACET significantly increased mean nocturnal arterial oxygen saturation values, from 85.5 to 90.2%. The authors conclude that short-term combined treatment with medroxyprogesterone acetate and acetazolamide has a more favourable effect on day and night-time blood gas values and chemical drive than single drug treatment.

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.

Sufficient indication of nocturnal oxygen saturation and breathing pattern in COPD patients, from a single night's study

Introduction Overnight studies in patients with chronic obstructive pulmonary disease (COPD) and daytime hypoxia are performed to record the degree of nocturnal hypoxaemia and to prescribe the proper flow of oxygen supplementation needed for maintaining normoxia (0.5-5.0 1 min ‘). Nocturnal studies are also performed in COPD patients with daytime normoxia who are suspected to have nocturnal hypoxaemia, e.g. because of the presence of secondary polycythaemia or pulmonary hypertension. It is quite common to perform duplicate studies since a first-night effect in EEG variables has been shown in normal subjects (14). However, little is known about the impact of this first-night effect on nocturnal oxygen saturation (SaO,) and breathing in COPD patients (5,6). The aim of the present study is to determine if the study of a single night is representative and sufficient for clinical purposes.