CT-defined emphysema in COPD patients and risk for change in desaturation status in 6-min walk test.

BACKGROUND: Emphysema and exercise induced desaturation (EID) are both related to poorer COPD prognosis. More knowledge of associations between emphysema and desaturation is needed for more efficient disease management. RESEARCH QUESTION: Is emphysema a risk factor for both new and repeated desaturation, and is emphysema of more or less importance than other known risk factors? METHODS: 283 COPD patients completed a 6-min walk test (6MWT) at baseline and one year later in the Bergen COPD cohort study 2006-2011. Degree of emphysema was assessed as percent of low attenuation areas (%LAA) under -950 Hounsfield units using high-resolution computed tomography at baseline. We performed multinomial logistic regression analysis, receiver operating curves (ROC) and area under the curve (AUC) estimations. Dominance analysis was used to rank emphysema and risk factors in terms of importance. RESULTS: A one percent increase in %LAA increases the relative risk (RR) of new desaturation by 10 % (RR 1.1 (95%CI 1.1, 1.2)) and for repeated desaturation by 20 % (RR 1.2 (95%CI 1.1, 1.3)). Compared with other important desaturation risk factors, %LAA ranked as number one in the dominance analysis, accounting for 50 % and 37 % of the predicted variance for new and repeated desaturators, respectively. FEV1% predicted accounted for 9 % and 24 %, and resting SpO2 accounted for 22 % and 21 % for new and repeated desaturation. CONCLUSION: Emphysema increases the risk of developing and repeatedly experiencing EID. Emphysema seems to be a more important risk factor for desaturation than FEV1% predicted and resting saturation.

One Year Change in 6-Minute Walk Test Outcomes is Associated with COPD Prognosis.

Six-minute walk test (6MWT) measures walking distance (6MWD) and desaturation status in chronic obstructive pulmonary disease (COPD) patients. This study aimed to examine whether change in 6MWD and desaturation in 1 year were risk factors for later mortality, lung function decline and number of exacerbations. A total of 295 COPD patients performed 6MWT at baseline and 1 year later in the Bergen COPD cohort study 2006-2011. They were clinically examined and interviewed at annual visits. Mortality information was collected from the Norwegian Cause of Death Registry in 2015. We performed cox regression for mortality outcomes, linear mixed effect models for lung function, and negative binomial regression for exacerbations. Patients who desaturated in both 6MWTs had increased risk of all-cause and respiratory mortality, hazard ratio (HR) 2.7 (95% confidence interval [CI] 1.5-5.0) and 3.6 (95% CI 1.7-7.6), respectively, compared to non-desaturators. Patients who desaturated only at second 6MWT were at risk for all-cause mortality (HR 2.0, 95% CI 1.0-3.8). There were no apparent association between 6MWD and mortality. Desaturation in second 6MWT was associated with later increased rate of decline in forced vital capacity (FVC) % predicted (after 1 year predicted mean 4.2% above non-desaturators, after 5 years 0.7% below). Decline in 6MWD ≥ 30m was borderline (p = 0.06) associated with later decline in forced expiratory volume in 1 second % predicted, and with exacerbations (p = 0.07). Repeated desaturation in the 6MWT over time in COPD patients is a risk factor for all-cause and respiratory mortality, while onset of desaturation is associated with future FVC decline.

Prevalence and prognostic ability of the GOLD 2017 classification compared to the GOLD 2011 classification in a Norwegian COPD cohort.

Rationale: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 is based on an ABCD assessment tool of symptoms and exacerbation history and grade 1-4 of airflow limitation severity, facilitating classification either into 4 groups (ABCD) or 16 groups (1A-4D). We aimed to compare the GOLD 2011, GOLD 2017 ABCD, and GOLD 2017 1A-4D classifications in terms of their distribution and prediction of mortality and hospitalizations. Methods: In the GenKOLS study, 912 COPD patients with FEV1 less than 80% of the predicted answered questionnaires and performed lung function testing in 2003-2005. The patients were recruited from a hospital patient registry (n=662) and from the general population (n=250), followed up until 2011 with respect to all-cause and respiratory mortality, and all-cause and respiratory hospitalizations. We performed logistic regression and receiver operating curve (ROC) analyses for the different classifications with estimations of area under the curve (AUC) for comparisons. Results: Mean age at baseline was 60 years (SD 11), 55% were male. Mean duration of follow-up was 91 months. By GOLD 2011, 21% were classified as group A, 29% group B, 6% group C, and 43% as group D, corresponding percentages for GOLD 2017 were: 25%, 52%, 3%, and 20%. The GOLD 2011 classification had higher AUC values than the GOLD 2017 group ABCD classification for respiratory mortality and hospitalization, but after inclusion of airflow limitation severity in GOLD 2017 groups 2A-4D, AUC values were significantly higher with GOLD 2017. Conclusion: In a clinically relevant sample of COPD patients, the GOLD 2017 classification doubles the prevalence of group B and halves the prevalence of groups C and D as compared to the GOLD 2011 classification. The prediction of respiratory mortality and respiratory hospitalization was better for GOLD 2017 2A-4D taking airflow limitation severity into account, as compared to GOLD 2017 ABCD and GOLD 2011.

Diffusion capacity and CT measures of emphysema and airway wall thickness - relation to arterial oxygen tension in COPD patients.

BACKGROUND: Decreased diffusing capacity of the lung for carbon monoxide (DLCO) is associated with emphysema. DLCO is also related to decreased arterial oxygen tension (PaO2), but there are limited data on associations between PaO2 and computed tomography (CT) derived measures of emphysema and airway wall thickness. OBJECTIVE: To examine whether CT measures of emphysema and airway wall thickness are associated with level of arterial oxygen tension beyond that provided by measurements of diffusion capacity and spirometry. METHODS: The study sample consisted of 271 smoking or ex-smoking COPD patients from the Bergen COPD Cohort Study examined in 2007-2008. Emphysema was assessed as percent of low-attenuation areas<-950 Hounsfield units (%LAA), and airway wall thickness as standardised measure at an internal perimeter of 10 mm (AWT-Pi10). Multiple linear regression models were fitted with PaO2 as the outcome variable, and %LAA, AWT-Pi10, DLCO and carbon monoxide transfer coefficient (KCO) as main explanatory variables. The models were adjusted for sex, age, smoking status, and haemoglobin concentration, as well as forced expiratory volume in one second (FEV1). RESULTS: Sixty two per cent of the subjects were men, mean (SD) age was 64 (7) years, mean (SD) FEV1 in percent predicted was 50 (15)%, and mean PaO2 (SD) was 9.3 (1.1) kPa. The adjusted regression coefficient (CI) for PaO2 was -0.32 (-0.04-(-0.019)) per 10% increase in %LAA (p<0.01). When diffusion capacity and FEV1 were added to the model, respectively, the association lost its statistical significance. No relationship between airway wall thickness and PaO2 was found. CONCLUSION: CT assessment of airway wall thickness is not associated with arterial oxygen tension in COPD patients. Emphysema score measured by chest CT, is related to decreased PaO2, but cannot replace measurements of diffusion capacity in the clinical evaluation of hypoxaemia.

Oxygen desaturation in 6-min walk test is a risk factor for adverse outcomes in COPD.

The 6-min walk test (6MWT) is an exercise test that measures functional status in chronic obstructive pulmonary disease (COPD) patients and provides information on oxygen desaturation. We investigated oxygen desaturation during 6MWT as a risk factor for important COPD outcomes: mortality, frequency of exacerbations, decline in lung function and decline in lean body mass.433 COPD patients were included in the Bergen COPD Cohort Study 2006-2009, and followed-up for 3 years. Patients were characterised using spirometry, bioelectrical impedance measurements, Charlson comorbidity score, exacerbation history, smoking and arterial blood gases. 370 patients completed the 6MWT at the baseline of the study. Information on all-cause mortality was collected in 2011.Patients who experienced oxygen desaturation during the 6MWT had an approximately twofold increased risk of death (hazard ratio 2.4, 95% CI 1.2-5.1), a 50% increased risk for experiencing later COPD exacerbations (incidence rate ratio 1.6, 95% CI 1.1-2.2), double the yearly rate of decline in both forced vital capacity and forced expiratory volume in 1 s (3.2% and 1.7% versus 1.7% and 0.9%, respectively) and manifold increased yearly rate of loss of lean body mass (0.18 kg·m(-2) versus 0.03 kg·m(-2) among those who did not desaturate).Desaturating COPD patients had a significantly worse prognosis than non-desaturating COPD patients, for multiple important disease outcomes.

Zopiclone effects on breathing at sleep in stable chronic obstructive pulmonary disease.

PURPOSE: More than half of patients with chronic obstructive pulmonary disease (COPD) experiences sleep-related problems and about one fourth uses hypnotics regularly. We explored what the effect zopiclone, a commonly used hypnotic, had on nocturnal gas exchange and the apnea/hypopnea frequency in stable COPD. METHODS: Randomized crossover study of 31 (ten males) inpatients at a pulmonary rehabilitation hospital, median age 64 years, of which 20 had a forced expiratory volume first second <50% of predicted. Subjects investigated in randomized order of either baseline sleep or intervention with 5 mg zopiclone by polysomnography including transcutaneous measurement of carbon dioxide pressure increased (ΔPtcCO2). RESULTS: Zopiclone increased the mean ΔPtcCO2 from baseline both in rapid eye movement (REM) sleep, non-REM sleep, and even in stage N0 (awake after sleep onset) with a mean (SD) of 0.25 (0.40) kPa, 0.22 (0.32) kPa, and 0.14 (0.27) kPa, respectively. Subjects with sleep hypoventilation as defined by the American Academy of Sleep Medicine increased from 6 subjects (19%) to 13 subjects (42%) (P = 0.020). REM sleep minimum oxygen saturation (minSpO2) did not change significantly from baseline median (interquartile range [IQR]) minSpO2 81.8 (12.1) % to zopiclone sleep median (IQR) minSpO2 80.0 (12.0) % (P = 0.766). Interestingly, zopiclone reduced the number of apneas/hypopneas per hour (AHI) in subjects with overlap (AHI ≥ 15) with a median difference (IQR) of -8.5 (7.8) (N = 11, P = 0.016). CONCLUSIONS: In stable COPD, zopiclone moderately increases the mean ΔPtcCO2 without changing minSpO2 at night and reduces AHI in overlap (COPD and obstructive sleep apnea) subjects.

Alcohol at bedtime induces minor changes in sleep stages and blood gases in stable chronic obstructive pulmonary disease.

PURPOSE/BACKGROUND: The purpose of this study is to explore the effect of a moderate dose of alcohol on sleep architecture and respiration in chronic obstructive pulmonary disease (COPD). Alcohol depresses both hypercapnic and hypoxic ventilatory drives in awake, normal individuals and reduces the amount of rapid eye movement (REM) sleep and oxygen saturation (SpO2) in sleeping COPD subjects. METHODS: Prospectively designed, open-label interventional study in a pulmonary rehabilitation hospital. Twenty-six (nine males) stable inpatients, median forced expiratory volume first second (FEV1) 40.5 % of predicted, median age 65 years, investigated by polysomnography including transcutaneous measurement of carbon dioxide pressure increase (ΔPtcCO2) in randomized order of either control sleep or intervention with 0.5 g of ethanol/kilogram bodyweight, taken orally immediately before lights off. RESULTS: Alcohol induced a mean increase (95 % confidence interval, [CI]) in the mean ΔPtcCO2 of 0.10 kPa (0.002-0.206, P = 0.047) and a mean decrease (CI) in the REM-sleep percentage of total sleep time (REM % of TST) of 3.1 % (0.2-6.0), (P = 0.020). Six subjects with apnea/hypopnea index (AHI) ≥15 had fewer apneas/hypopneas during alcohol versus control sleep (mean reduction of AHI 11 (1-20), P = 0.046). Alcohol-sleep changes in SpO2, but not in ΔPtcCO2, correlated with daytime arterial pressures of carbon dioxide (PaCO2) and oxygen (PaO2). CONCLUSION: Occasional use of a moderate, bedtime dose of alcohol has only minor respiratory depressant effects on the majority of COPD subjects, and in a minority even slightly improves respiration during sleep. However, caution is appropriate as this study is small and higher doses of alcohol may result in major respiratory depressive and additional negative health effects.

Sleep hypoventilation and daytime hypercapnia in stable chronic obstructive pulmonary disease.

PURPOSE: To explore the associations between sleep hypoventilation (SH) and daytime arterial pressures of carbon dioxide (PaCO2), sleep stages, and sleep apneas/hypopneas (AHI) in subjects with chronic obstructive pulmonary disease (COPD). SH has previously been found in COPD-subjects with chronic hypercapnic respiratory failure (CHRF) using supplementary oxygen (LTOT), and has been proposed as a possible predictor for CHRF. PATIENTS AND METHODS: A prospectively designed observational study in a pulmonary rehabilitation hospital of 100 (39 male) stable COPD inpatients with a mean forced expiratory volume in 1 second (FEV1) of 1.1 L (42% of predicted) and a mean age of 64 years, using polysomnography with transcutaneous measurement of carbon dioxide pressure increase (ΔPtcCO2). RESULTS: SH as defined by the American Academy of Sleep Medicine (AASM) was found in 15 of the subjects, seven of whom used LTOT. However, six had SH despite being normocapnic during the daytime (only one on LTOT). Subjects with SH had a greater ΔPtcCO2 increase from nonrapid eye movement (NREM) to rapid eye movement (REM) sleep stages compared to non-SH subjects (mean [standard deviation] between-groups difference =0.23(0.20) kPa, P<0.0005). Subjects with apnea/hypopnea index ≥15 (overlap, N=27) did not differ from those with COPD alone (AHI <5, N=25) in sleep ΔPtcCO2 or daytime PaCO2. A regression model with the variables FEV1, LTOT, and sleep maximum ΔPtcCO2 explained 56% of the variance in daytime PaCO2 (F(3, 94) =40.37, P<0.001). CONCLUSION: In stable COPD, SH as defined by the AASM was found both in normocapnic, non-LTOT subjects and in hypercapnic, LTOT-using subjects. Between-sleep-stage increase in ΔPtcCO2 was higher in subjects with SH. Overlap subjects did not differ from simple COPD subjects in sleep ΔPtcCO2 or daytime PaCO2.

Reference values for within-breath pulmonary impedance parameters in asymptomatic elderly.

INTRODUCTION: A new application for the forced oscillation technique (FOT) has been described by Dellaca et al. using sinusoidal pressure variations at 5 Hz to detect expiratory flow limitation by measuring the within-breath reactance [termed difference between inspiratory and expiratory X5 (DX5)]. Few studies have been performed on respiratory phase differences in the elderly. OBJECTIVE: Our aim was to present reference values for within-breath impedance measurements and to examine how the earlier mentioned method performs in a study population of asymptomatic elderly. METHODS: An age- and sex-stratified random sample was drawn from the elderly population of Bergen, Norway. Among the healthy non-smoking responders from a postal questionnaire study, 148 were selected to perform FOT measurements using an impulse oscillometry system (IOS). Seventy five of these participants had a normal spirometry and were able to perform at least two valid FOT measurements. Predictive equations for men and women were created for FOT parameters by linear multiple regression analysis. DX5 was calculated from the within-breath variation of reactance at 5 Hz. RESULTS/CONCLUSION: This study presents reference values for whole-breath and within-breath impedance parameters in asymptomatic elderly aged >70 years using the IOS method. We found higher resistance measurements than what is reported in previous studies and significantly larger frequency dependence.

Chronic obstructive pulmonary disease is associated with low levels of vitamin D.

INTRODUCTION: COPD patients may be at increased risk for vitamin D (25(OH)D) deficiency, but risk factors for deficiency among COPD patients have not been extensively reported. METHODS: Serum 25(OH)D levels were measured by liquid chromatography double mass spectrometry in subjects aged 40-76 years from Western Norway, including 433 COPD patients (GOLD stage II-IV) and 325 controls. Levels <20 ng/mL defined deficiency. Season, sex, age, body mass index (BMI), smoking, GOLD stage, exacerbation frequency, arterial oxygen tension (PaO(2)), respiratory symptoms, depression (CES-D score≥16), comorbidities (Charlson score), treatment for osteoporosis, use of inhaled steroids, and total white blood count were examined for associations with 25(OH)D in both linear and logistic regression models. RESULTS: COPD patients had an increased risk for vitamin D deficiency compared to controls after adjustment for seasonality, age, smoking and BMI. Variables associated with lower 25(OH)D levels in COPD patients were obesity ( = -6.63), current smoking ( = -4.02), GOLD stage III- IV ( = -4.71, = -5.64), and depression ( = -3.29). Summertime decreased the risk of vitamin D deficiency (OR = 0.22). CONCLUSION: COPD was associated with an increased risk of vitamin D deficiency, and important disease characteristics were significantly related to 25(OH)D levels.

Explained variance for blood gases in a population with COPD.

INTRODUCTION: Variation of blood gas levels in chronic obstructive pulmonary disease (COPD) patients has not been extensively reported and there is limited knowledge about predictors of chronic respiratory failure in COPD patients. OBJECTIVES: The aim of this study was to identify predictors of hypoxemia, hypercapnia and increased alveolar-arterial oxygen difference in COPD patients. We hypothesized that prediction of arterial blood gases will be improved in multivariate models including measurements of lung function, anthropometry and systemic inflammation. METHODS: A cross-sectional sample of 382 Norwegian COPD patients, age 40-76, Global Initiative for Chronic Obstructive Lung Disease stage II-IV, with a smoking history of at least 10 pack-years, underwent extensive measurements, including medical examination, arterial blood gases, systemic inflammatory markers, spirometry, plethysmography, respiratory impedance and bioelectrical impedance. Possible predictors of arterial oxygen (PaO(2)), arterial carbon dioxide (PaCO(2)) and alveolar-arterial oxygen difference (AaO(2)) were analyzed with both bivariate and multiple regression methods. RESULTS: We found that various lung function measurements were significantly associated with PaO2, PaCO(2) and AaO(2). In addition, heart rate and Fat Mass Index were predictors of PaO(2) and AaO(2), while heart failure and current smoking status were associated with PaCO(2). The explained variance (R(2)) in the final multivariate regression models was 0.14-0.20. CONCLUSIONS: With a wide assortment of possible clinical predictors, we could explain 14-20% of the variation in blood gas measurements in COPD patients.

A randomised trial of endobronchial ultrasound guided sampling in peripheral lung lesions.

AIM: The aim of the study was to evaluate endobronchial ultrasound (EBUS) for peripheral lung lesions and to find the most cost effective combination of sampling techniques. MATERIALS: 264 patients with lesions suspicious of malignancy were recruited in Bergen and Aalesund, Norway from 2005 to 2008. METHODS: The study was a prospective randomised cohort study. EBUS was performed with a 1.7 mm rotating probe. X-ray fluoroscopy was used in both arms. The different sampling techniques were evaluated in a cost-effectiveness analysis. RESULTS: The detection rate for cancer was 36% in the EBUS group, 44% in the non-EBUS group (ns). Lesions below 3 cm and lesions assumed difficult to reach had significant lower detection rates in the EBUS group. Lesions visualised by EBUS had a higher detection rate for cancer than lesions not visualised by EBUS (62% vs. 19%, p<0.01). The cost of one additional positive sample was 1211 euro when brushing was added to biopsy. It was not cost effective to add washing or TBNA. CONCLUSION: EBUS did not increase the detection rate for cancer in peripheral lung lesions when bronchoscopy was performed by bronchoscopists at all levels of expertise. Biopsy and brushing was the most cost effective combination of sampling techniques.

Cost minimization analysis for combinations of sampling techniques in bronchoscopy of endobronchial lesions.

BACKGROUND: The choice of sampling techniques in bronchoscopy with sampling from a visible lesion will depend on the expected diagnostic yields and the costs of the sampling techniques. AIMS: The aim of this study was to determine the most economical combination of sampling techniques when approaching endobronchial visible lesions. METHODS: A cost minimization analysis was performed. All bronchoscopies from 2003 and 2004 at Haukeland university hospital, Bergen, Norway, were reviewed retrospectively for diagnostic yields. 162 patients with endobronchial disease were included. Potential sampling techniques used were biopsy, brushing, endobronchial needle aspiration (EBNA) and washings. Costs were estimated based on registration of equipment costs and personnel costs. Sensitivity analyses were performed to determine threshold values. RESULTS: The combination of biopsy, brushing and EBNA was the most economical strategy with an average cost of Euro 893 (95% CI: 657, 1336). The cost of brushing had to be below Euro 83 and it had to increase the diagnostic yield more than 2.2%, for biopsy and brushing to be more economical than biopsy alone. The combination of biopsy, brushing and EBNA was more economical than biopsy and brushing when the cost of EBNA was below Euro 205 and the increase in diagnostic yield was above 5.2%. CONCLUSION: In the current study setting, biopsy, brushing and EBNA was the most economical combination of sampling techniques for endobronchial visible lesions.