Is it feasible to perform a continuous laryngoscopy exercise test with a cold air inhalate? A case report.

The continuous laryngoscopy exercise (CLE) test can be combined with breathing cold air. Combining the CLE test and cold air does not cause excessive discomfort. The indicated laryngeal responses with cold air support the need for more research. https://bit.ly/3AChJ7V.

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.

Effect of stimulating waveform and of data processing on respiratory impedance measurement.

OBJECTIVE: Several commercial and custom-made forced oscillation technique (FOT) devices are used to assess respiratory system impedance. The impulse oscillometry system (IOS) is a widespread device, which yields similar but not identical results to those provided by other FOT systems. Differences may be related to the forcing waveform, the device hardware, or the data processing algorithms. We evaluated the agreement between resistance (R rs) and reactance (X rs) measurements while alternating between different forcing waveforms and data processing algorithms. APPROACH: We performed pre- and post-bronchodilator measurements in 20 patients with respiratory complaints. We generated pulse waveforms using an IOS, and sinusoidal oscillations by replacing the IOS loudspeaker with customized loudspeaker providing a 5 Hz sinusoidal pressure signal. Pressure and flow were measured using the IOS sensors and breathing circuit. We developed a data processing algorithm compatible to both forcing signals. We also applied commercial IOS software during pulse waveform and a least mean square (lms) algorithm during sinusoidal waveform. MAIN RESULTS: The median (5th, 95th percentile) differences between R rs and X rs were (1) -0.35 (-2.49, 1.23) and 0.16 (-1.63, 3.07 cmH2O*s l-1, when the same algorithm was used during pulse vs sinusoidal stimulus; (2) 0.34 (-2.33, 5.98) and 0.57 (-2.64, 6.09) cmH2O*s l-1, when our algorithm and the IOS software were used during pulse waveform; and (3) 0.33 (-1.20, 6.05) and 0.25 (-4.94, 4.28) cmH2O*s l-1 when the IOS software was used during pulse and the lms algorithm during sinusoidal waveforms. SIGNIFICANCE: Both forcing signal and data processing contribute to differences in impedance values measured by different FOT devices.

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.

Risk factors for lung cancer in COPD - results from the Bergen COPD cohort study.

BACKGROUND: COPD patients have an increased risk of developing lung cancer, but the underlying mechanisms are poorly understood. We aimed to identify risk factors for lung cancer in patients from the Bergen COPD Cohort Study. METHODS: We compared 433 COPD patients with 279 healthy controls, all former or current smokers. All COPD patients had FEV1<80% and FEV1/FVC-ratio<0.7. Baseline predictors were sex, age, spirometry, body composition, smoking history, emphysema assessed by CT, chronic bronchitis, prior exacerbation frequency, Charlson Comorbidity Score, inhalation medication and 44 serum/plasma inflammatory biomarkers. Patients were followed up for 9 years recording incidence of lung cancer. Cox-regression models were fitted for the statistical analyses. The biomarkers were evaluated using principal component analysis. RESULTS: 28 COPD patients and 3 controls developed lung cancer, COPD patients had a significantly higher risk of developing lung cancer, (HR 5.0; 95% CI 1.5-17.1, p < 0.01, adjusted values). Among COPD patients, emphysema (HR 4.4; 1.7-10.8, p < 0.01) and obesity (HR 3.3; 1.3-8.5, p = 0.02) were associated with a higher cancer rate. Use of inhaled steroids was associated with a lower rate (HR 0.4; 0.2-0.9, p = 0.03). Smoking status, pack-years smoked or levels of systemic inflammatory markers, except for interferon gamma-induced protein 10, did not affect the lung cancer rate in patients with COPD. CONCLUSION: Patients with COPD have a higher lung cancer rate compared to healthy controls adjusted for smoking. The presence of emphysema and obesity in COPD predicted a higher lung cancer risk in COPD patients. Systemic inflammation was not associated with increased lung cancer risk.

Lung hyperinflation and functional exercise capacity in patients with COPD - a three-year longitudinal study.

BACKGROUND: Lung hyperinflation contributes to dyspnea, morbidity and mortality in chronic obstructive pulmonary disease (COPD). The inspiratory-to-total lung capacity (IC/TLC) ratio is a measure of lung hyperinflation and is associated with exercise intolerance. However, knowledge of its effect on longitudinal change in the 6-min walk distance (6MWD) in patients with COPD is scarce. We aimed to study whether the IC/TLC ratio predicts longitudinal change in 6MWD in patients with COPD. METHODS: This prospective cohort study included 389 patients aged 40-75 years with clinically stable COPD in Global Initiative for Chronic Obstructive Lung Disease stages II-IV. The 6MWD was measured at baseline, and after one and 3 years. We performed generalized estimating equation regression analyses to examine predictors for longitudinal change in 6MWD. Predictors at baseline were: IC/TLC ratio, age, gender, pack years, fat mass index (FMI), fat-free mass index (FFMI), number of exacerbations within 12 months prior to inclusion, Charlson index for comorbidities, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and light and hard self-reported physical activity. RESULTS: Reduced IC/TLC ratio (p < 0.001) was a statistically significant predictor for decline in 6MWD. With a 0.1-unit decrease in baseline IC/TLC ratio, the annual decline in 6MWD was 12.7 m (p < 0.001). Study participants with an IC/TLC ratio in the upper quartiles maintained their 6MWD from baseline to year 3, while it was significantly reduced for the patients with an IC/TLC ratio in the lower quartiles. Absence of light and hard physical activity, increased age and FMI, decreased FEV1 and FVC, more frequent exacerbations and higher Charlson comorbidity index were also predictors for lower 6MWD at any given time, but did not predict higher rate of decline over the timespan of the study. CONCLUSION: Our findings demonstrated that patients with less lung hyperinflation at baseline maintained their functional exercise capacity during the follow-up period, and that it was significantly reduced for patients with increased lung hyperinflation.

Median regression spline modeling of longitudinal FEV1 measurements in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) patients.

RATIONALE: Clinical phenotyping, therapeutic investigations as well as genomic, airway secretion metabolomic and metagenomic investigations can benefit from robust, nonlinear modeling of FEV1 in individual subjects. We demonstrate the utility of measuring FEV1 dynamics in representative cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) populations. METHODS: Individual FEV1 data from CF and COPD subjects were modeled by estimating median regression splines and their predicted first and second derivatives. Classes were created from variables that capture the dynamics of these curves in both cohorts. RESULTS: Nine FEV1 dynamic variables were identified from the splines and their predicted derivatives in individuals with CF (n = 177) and COPD (n = 374). Three FEV1 dynamic classes (i.e. stable, intermediate and hypervariable) were generated and described using these variables from both cohorts. In the CF cohort, the FEV1 hypervariable class (HV) was associated with a clinically unstable, female-dominated phenotypes while stable FEV1 class (S) individuals were highly associated with the male-dominated milder clinical phenotype. In the COPD cohort, associations were found between the FEV1 dynamic classes, the COPD GOLD grades, with exacerbation frequency and symptoms. CONCLUSION: Nonlinear modeling of FEV1 with splines provides new insights and is useful in characterizing CF and COPD clinical phenotypes.

The association of tidal EFL with exercise performance, exacerbations, and death in COPD.

BACKGROUND: Tidal expiratory flow limitation (EFLT) is frequently found in patients with COPD and can be detected by forced oscillations when within-breath reactance of a single-breath is ≥0.28 kPa·s·L-1. The present study explored the association of within-breath reactance measured over multiple breaths and EFLT with 6-minute walk distance (6MWD), exacerbations, and mortality. METHODS: In 425 patients, spirometry and forced oscillation technique measurements were obtained on eight occasions over 3 years. 6MWD was assessed at baseline and at the 3-year visit. Respiratory symptoms, exacerbations, and hospitalizations were recorded. A total of 5-year mortality statistics were retrieved retrospectively. We grouped patients according to the mean within-breath reactance [Formula: see text], measured over several breaths at baseline, calculated as mean inspiratory-mean expiratory reactance over the sampling period. In addition to the established threshold of EFLT, an upper limit of normal (ULN) was defined using the 97.5th percentile of [Formula: see text], of the healthy controls in the study; 6MWDs were compared according to [Formula: see text], as normal, ≥ ULN < EFLT, or ≥ EFLT. Annual exacerbation rates were analyzed using a negative binomial model in the three groups, supplemented by time to first exacerbation analysis, and dichotomizing patients at the ULN. RESULTS: In patients with COPD and baseline [Formula: see text] below the ULN (0.09 kPa·s·L-1), 6MWD was stable. 6MWD declined significantly in patients with [Formula: see text]. Worse lung function and more exacerbations were found in patients with COPD with [Formula: see text], and patients with [Formula: see text] had shorter time to first exacerbation and hospitalization. A significantly higher mortality was found in patients with [Formula: see text] and FEV1 >50%. CONCLUSION: Patients with baseline [Formula: see text] had a deterioration in exercise performance, more exacerbations, and greater hospitalizations, and, among those with moderate airway obstruction, a higher mortality. [Formula: see text] is a novel independent marker of outcome in COPD.

Growth differentiation factor-15 is a predictor of important disease outcomes in patients with COPD.

Increased levels of growth differentiation factor-15 (GDF15) are associated with cachexia, cardiovascular disease and all-cause mortality. The role of GDF15 in chronic obstructive pulmonary disease (COPD) is unknown.The study included 413 patients with COPD from the Bergen COPD Cohort Study. All patients had a forced expiratory volume in 1 s (FEV1) <80% predicted, a FEV1 to forced vital capacity (FVC) ratio <0.7 and a history of smoking. Spirometry, fat free mass index, blood gases and plasma GDF15 were measured at baseline. Patients were followed for 3 years regarding exacerbations and changes in lung function, and 9 years for mortality. Yearly exacerbation rate, survival and yearly change in FEV1/FVC were evaluated with regression models.Median plasma GDF15 was 0.86 ng·mL-1 (interquartile range 0.64-1.12 ng·mL-1). The distribution was not normal and GDF15 was analysed as a categorical variable. High levels of GDF15 were associated with a higher exacerbation rate (incidence rate ratio 1.39, 95% CI 1.1-1.74, p=0.006, adjusted values). Furthermore, high levels of GDF15 were associated with higher mortality (hazard ratio 2.07, 95% CI 1.4-3.1, p<0.001) and an increased decline in both FEV1 (4.29% versus 3.25%) and FVC (2.63% versus 1.44%) in comparison to low levels (p<0.01 for both).In patients with COPD, high levels of GDF15 were independently associated with a higher yearly rate of exacerbations, higher mortality and increased decline in both FEV1 and FVC.

Antimicrobial peptide levels are linked to airway inflammation, bacterial colonisation and exacerbations in chronic obstructive pulmonary disease.

Antimicrobial peptides (AMPs) are effectors of host defence against infection, inflammation and wound repair. We aimed to study AMP levels in stable chronic obstructive pulmonary disease (COPD) and during acute exacerbations of COPD (AECOPD), and to examine their relation to clinical parameters and inflammatory markers.The 3-year Bergen COPD Cohort Study included 433 COPD patients and 325 controls. Induced sputum was obtained and analysed for levels of the AMPs human cathelicidin (hCAP18/LL-37) and secretory leukocyte protease inhibitor (SLPI), and for the inflammatory markers interleukin (IL)-8, IL-6 and tumour necrosis factor-α (TNF-α) using immunoassays. Systemic hCAP18/LL-37 and vitamin D levels were also studied. Treating AMPs as response variables, non-parametric tests were applied for univariate comparison, and linear regression to obtain adjusted estimates. The risk of AECOPD was assessed by Cox proportional-hazard regression.Sputum AMP levels were higher in patients with stable COPD (n=215) compared to controls (n=45), and further changed during AECOPD (n=56), with increased hCAP18/LL-37 and decreased SLPI levels. Plasma hCAP18/LL-37 levels showed a similar pattern. In stable COPD, high sputum hCAP18/LL-37 levels were associated with increased risk of AECOPD, non-typeable Haemophilus influenzae colonisation, higher age, ex-smoking and higher levels of inflammatory markers.Altered levels of selected AMPs are linked to airway inflammation, infection and AECOPD, suggesting a role for these peptides in airway defence mechanisms in COPD.

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.

Macrophage migration inhibitory factor, a role in COPD.

Macrophage migration inhibitor factor (MIF) is a pluripotent cytokine associated with several different inflammatory conditions, but its role within lung inflammation and chronic obstructive pulmonary disease (COPD) is unclear. This study aimed to examine MIF in both stable COPD and during acute exacerbations (AECOPD). The study included 433 patients with COPD aged 41-76 and 325 individuals from the Bergen COPD cohort study who served as controls. All patients had an FEV1 of <80% predicted, FEV1/FVC ratio of <0.7, and a smoking history >10 pack-years. Serum levels of MIF were compared between the two groups at baseline, and for 149 patients, measurements were also carried out during AECOPD. Linear regression models were fitted with MIF as the outcome variable and adjusted for sex, age, body composition, smoking, and Charlson Comorbidity Score (CCS). Median MIF (interquartile range) in patients with COPD was 20.1 ng/ml (13.5-30.9) compared with 14.9 ng/ml (11.1-21.6) in controls (P < 0.01). MIF was bivariately associated with sex, body composition, and CCS (P < 0.05 for all). In the regression analyses, MIF was significantly higher in patients with COPD, coefficient 1.32 (P < 0.01) and 1.30 (P < 0.01) unadjusted and adjusted, respectively. In addition, in 149 patients during episodes of AECOPD, MIF was significantly elevated, with a median of 23.2 ng/ml (14.1-42.3) compared with measurements at stable disease of 19.3 ng/ml (12.4-31.3, P < 0.01). Serum levels of MIF were significantly higher in patients with COPD compared with controls. We also identified an additional increase in MIF levels during episodes of AECOPD.

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.

Expert opinion of mediastinal lymph node positions from an intrabronchial view.

BACKGROUND: The knowledge of the mediastinal lymph node positions from an intrabronchial view was important for conventional transbronchial needle aspiration (TBNA). The introduction of endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) changed the focus from the intrabronchial landmarks to the real life ultrasound images. However when all EBUS reachable lymph nodes are evaluated (mapping), the knowledge of the intrabronchial positions is crucial. The objective of this study was to present a new expert opinion map from an intrabronchial perspective validated by an interobserver variation analysis. METHODS: Physicians who had performed more than 30 EBUS-TBNA were included. They marked areas for optimal TBNA sampling on standardized pictures from an intrabronchial perspective. Areas marked by more than 3 of the 14 experts who had performed more than 1000 EBUS provided the data for the map. The map was validated among the experts and the agreement was compared to the agreement among less experienced physicians. RESULTS: There was high agreement (>80%) among the experts in lymph node positions 4 L, 7, 10 L, 11R and 11 L. The agreement for 4R and 10R was low (<70%). The agreement among the most experienced physicians was significantly higher than the less experienced physicians in station 10 L (92% vs. 50%, p:0.01). CONCLUSIONS: It was possible to present a new map of expert opinion for optimal sampling positions in lymph node stations 4 L, 4R, 7, 10 L, 11R and 11 L. All positions except 4R had high agreement. No area was covered by more than 3 of the 14 experts in station 10R.

Peak oxygen uptake and breathing pattern in COPD patients--a four-year longitudinal study.

BACKGROUND: Activities of daily living in patients with chronic obstructive pulmonary disease (COPD) are limited by exertional dyspnea and reduced exercise capacity. The aims of the study were to examine longitudinal changes in peak oxygen uptake (V̇O2peak), peak minute ventilation (V̇Epeak) and breathing pattern over four years in a group of COPD patients, and to examine potential explanatory variables of change. METHODS: This longitudinal study included 63 COPD patients, aged 44-75 years, with a mean forced expiratory volume in one second (FEV1) at baseline of 51 % of predicted (SD = 14). The patients performed two cardiopulmonary exercise tests (CPETs) on treadmill 4.5 years apart. The relationship between changes in V̇O2peak and V̇Epeak and possible explanatory variables, including dynamic lung volumes and inspiratory capacity (IC), were analysed by multivariate linear regression analysis. The breathing pattern in terms of the relationship between minute ventilation (V̇E) and tidal volume (VT) was described by a quadratic equation, VT = a + b∙V̇E + c∙V̇E (2), for each test. The VTmax was calculated from the individual quadratic relationships, and was the point where the first derivative of the quadratic equation was zero. The mean changes in the curve parameters (CPET2 minus CPET1) and VTmax were analysed by bivariate and multivariate linear regression analyses with age, sex, height, changes in weight, lung function, IC and inspiratory reserve volume as possible explanatory variables. RESULTS: Significant reductions in V̇O2peak (p < 0.001) and V̇Epeak (p < 0.001) were related to a decrease in resting IC and in FEV1. Persistent smoking contributed to the reduction in V̇O2peak. The breathing pattern changed towards a lower VT at a given V̇E and was related to the reduction in FEV1. CONCLUSION: Increasing static hyperinflation and increasing airway obstruction were related to a reduction in exercise capacity. The breathing pattern changed towards more shallow breathing, and was related to increasing airway obstruction.

Vitamin D, vitamin D binding protein, and longitudinal outcomes in COPD.

BACKGROUND: Associations between Vitamin D3 [25(OH)D], vitamin D binding protein (VDBP) and chronic obstructive pulmonary disease (COPD) are previously reported. We aimed to further investigate these associations on longitudinal outcomes. METHODS: 426 COPD patients from western Norway, GOLD stage II-IV, aged 40-76, were followed every six-month from 2006 through 2009 with spirometry, bioelectrical impedance measurements and registration of exacerbation frequency. Serum 25(OH)D and VDBP levels were determined at study-entry by high-performance liquid chromatography coupled with mass spectrometry and enzyme immunoassays respectively. Yearly change in lung function and body composition was assessed by generalized estimating equations (GEE), yearly exacerbation rate by negative binomial regression models, and 5 years all-cause mortality by Cox proportional-hazard regression. RESULTS: 1/3 of the patients had vitamin D deficiency (<20ng/mL) and a greater decline in both FEV1 and FVC, compared to patients with normal levels; for FEV1 this difference only reached statistical significance in the 28 patients with the lowest levels (<10ng/mL, p = 0.01). Neither 25(OH)D nor VDBP levels predicted exacerbation rate, change in fat free mass index or risk of death. CONCLUSION: Severe vitamin D deficiency may affect decline in lung function parameters in COPD. Neither 25(OH)D nor VDBP levels did otherwise predict markers of disease progression.

Serial Measurements of Arterial Oxygen Tension are Associated with Mortality in COPD.

BACKGROUND: Knowledge on factors associated with mortality can help identify patients with COPD that might benefit from close monitoring and intervention. Arterial blood gases (ABGs) are related to mortality, but both arterial tension of oxygen (PaO2) and arterial tension of carbon dioxide (PaCO2) vary over time. The aim of our study was to investigate the association between repeatedly measured ABGs and mortality in men and women with COPD. METHODS: A cohort of 419 Norwegian subjects with COPD, GOLD stage II-IV, aged 40-75, was followed up with up to seven ABGs, measured during stable phase for three years. Cox proportional hazard models were used to quantify the relationship between both single and repeatedly measured ABGs and all-cause mortality after five years, adjusting for age, sex, and the updated BODE index. RESULTS: A total of 64 subjects died during follow-up. Mean initial arterial oxygen tension (standard deviation) was significantly higher in survivors compared to deceased, with PaO2 (in kPa) 9.4 (1.1) versus 8.8 (1.2), p<0.001. Corresponding numbers for PaCO2 were 5.3 (0.5) and 5.5 (0.7), p < 0.001. In analyses adjusting for age, sex, and the updated BODE index hazard ratios - HR(95% confidence intervals) - for all-cause mortality were 0.73 (0.55, 0.97) and 1.58 (0.90, 2.76) for repeated measures of PaO2 and PaCO2, respectively. CONCLUSION: Both arterial oxygen and carbon dioxide tension were related to mortality in this study, and arterial oxygen tension added prognostic information to the updated BODE index in COPD.

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.

Variability of within-breath reactance in COPD patients and its association with dyspnoea.

The forced oscillation technique can identify expiratory flow limitation (EFL) when a large difference in inspiratory and expiratory reactance (ΔXrs) occurs. However, flow limitation can vary from breath to breath, and so we compared a multiple-breath ΔXrs approach to the traditional breath-by-breath assessment of EFL. We investigated the within- and between-day reproducibility and the factors that affect the size of ΔXrs when used as a continuous measurement over multiple breaths. In addition, we examined how multiple-breath ΔXrs relates to the sensation of breathlessness. 425 moderate to very severe chronic obstructive pulmonary disease (COPD) patients and 229 controls were included. Spirometry and impedance measurements were performed on a MasterScope CT Impulse Oscillation System. Median ΔXrs approached zero in healthy controls with little variation between measurements. COPD patients generally had higher ΔXrs and higher variability. The COPD patients with ΔXrs >0.1 kPa · L(-1) · s(-1) were prone to be more breathless and had a higher modified Medical Research Council dyspnoea scale score. In controls, the 95th percentile of ΔXrs was as low as 0.07 kPa · L(-1) · s(-1). We describe a new method to assess EFL at a patient level and propose a cut-off, mean ΔXrs >0.1 kPa · L(-1) · s(-1), as a way to identify COPD patients who are more likely to report dyspnoea.