Hypo- and hypercapnia predict mortality in oxygen-dependent chronic obstructive pulmonary disease: a population-based prospective study

Background

The prognostic role of the arterial blood gas tension of carbon dioxide (PaCO₂) in severe Chronic Obstructive Pulmonary Disease (COPD) remains unknown. The aim of this study was to estimate the association between PaCO₂ and mortality in oxygen-dependent COPD.

Methods

National prospective study of patients starting long-term oxygen therapy (LTOT) for COPD in Sweden between October 1, 2005 and June 30, 2009, with all-cause mortality as endpoint. The association between PaCO₂ while breathing air, PaCO₂ (air), and mortality was estimated using Cox regression adjusted for age, sex, arterial blood gas tension of oxygen (PaO₂), World Health Organization performance status, body mass index, comorbidity, and medications.

Results

Of 2,249 patients included, 1,129 (50%) died during a median 1.1 years (IQR 0.6-2.0 years) of observation. No patient was lost to follow-up. PaCO₂ (air) independently predicted adjusted mortality (p < 0.001). The association with mortality was U-shaped, with the lowest mortality at approximately PaCO₂ (air) 6.5 kPa and increased mortality at PaCO₂ (air) below 5.0 kPa and above 7.0 kPa.

Conclusion

In oxygen-dependent COPD, PaCO₂ (air) is an independent prognostic factor with a U-shaped association with mortality.     

Reliability and Validity of the Multimedia Activity Recall in Children and Adults (MARCA) in People with Chronic Obstructive Pulmonary Disease

Objective

To determine the reliability and validity of the Multimedia Activity Recall for Children and Adults (MARCA) in people with chronic obstructive pulmonary disease (COPD).

Design

People with COPD and their carers completed the Multimedia Activity Recall for Children and Adults (MARCA) for four, 24-hour periods (including test-retest of 2 days) while wearing a triaxial accelerometer (Actigraph GT3X+®), a multi-sensor armband (Sensewear Pro3®) and a pedometer (New Lifestyles 1000®).

Setting

Self reported activity recalls (MARCA) and objective activity monitoring (Accelerometry) were recorded under free-living conditions.

Participants

24 couples were included in the analysis (COPD; age 74.4±7.9 yrs, FEV₁ 54±13% Carer; age 69.6±10.9 yrs, FEV₁ 99±24%).

Interventions

Not applicable.

Main Outcome Measure(s)

Test-retest reliability was compared for MARCA activity domains and different energy expenditure zones. Validity was assessed between MARCA-derived physical activity level (in metabolic equivalent of task (MET) per minute), duration of moderate to vigorous physical activity (min) and related data from the objective measurement devices. Analysis included intra-class correlation coefficients (ICC), Bland-Altman analyses, paired t-tests (p) and Spearman''s rank correlation coefficients (r_s).

Results

Reliability between occasions of recall for all activity domains was uniformly high, with test-retest correlations consistently >0.9. Validity correlations were moderate to strong (r_s = 0.43–0.80) across all comparisons. The MARCA yields comparable PAL estimates and slightly higher moderate to vigorous physical activity (MVPA) estimates.

Conclusion

In older adults with chronic illness, the MARCA is a valid and reliable tool for capturing not only the time and energy expenditure associated with physical and sedentary activities but also information on the types of activities.     

Long-term gas exchange characteristics as markers of deterioration in patients with cystic fibrosis

Background and Aim

In patients with cystic fibrosis (CF) the architecture of the developing lungs and the ventilation of lung units are progressively affected, influencing intrapulmonary gas mixing and gas exchange. We examined the long-term course of blood gas measurements in relation to characteristics of lung function and the influence of different CFTR genotype upon this process.

Methods

Serial annual measurements of PaO₂ and PaCO₂ assessed in relation to lung function, providing functional residual capacity (FRC_pleth), lung clearance index (LCI), trapped gas (V_TG), airway resistance (sR_eff), and forced expiratory indices (FEV₁, FEF₅₀), were collected in 178 children (88 males; 90 females) with CF, over an age range of 5 to 18 years. Linear mixed model analysis and binary logistic regression analysis were used to define predominant lung function parameters influencing oxygenation and carbon dioxide elimination.

Results

PaO₂ decreased linearly from age 5 to 18 years, and was mainly associated with FRC_pleth, (p < 0.0001), FEV₁ (p < 0.001), FEF₅₀ (p < 0.002), and LCI (p < 0.002), indicating that oxygenation was associated with the degree of pulmonary hyperinflation, ventilation inhomogeneities and impeded airway function. PaCO₂ showed a transitory phase of low PaCO₂ values, mainly during the age range of 5 to 12 years. Both PaO₂ and PaCO₂ presented with different progression slopes within specific CFTR genotypes.

Conclusion

In the long-term evaluation of gas exchange characteristics, an association with different lung function patterns was found and was closely related to specific genotypes. Early examination of blood gases may reveal hypocarbia, presumably reflecting compensatory mechanisms to improve oxygenation.     

Mixed acid-base disorders, hydroelectrolyte imbalance and lactate production in hypercapnic respiratory failure: the role of noninvasive ventilation

Background

Hypercapnic Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with comorbidities and multidrug therapy is complicated by mixed acid-base, hydro-electrolyte and lactate disorders. Aim of this study was to determine the relationships of these disorders with the requirement for and duration of noninvasive ventilation (NIV) when treating hypercapnic respiratory failure.

Methods

Sixty-seven consecutive patients who were hospitalized for hypercapnic COPD exacerbation had their clinical condition, respiratory function, blood chemistry, arterial blood gases, blood lactate and volemic state assessed. Heart and respiratory rates, pH, PaO₂ and PaCO₂ and blood lactate were checked at the 1st, 2nd, 6th and 24th hours after starting NIV.

Results

Nine patients were transferred to the intensive care unit. NIV was performed in 11/17 (64.7%) mixed respiratory acidosis–metabolic alkalosis, 10/36 (27.8%) respiratory acidosis and 3/5 (60%) mixed respiratory-metabolic acidosis patients (p = 0.026), with durations of 45.1±9.8, 36.2±8.9 and 53.3±4.1 hours, respectively (p = 0.016). The duration of ventilation was associated with higher blood lactate (p<0.001), lower pH (p = 0.016), lower serum sodium (p = 0.014) and lower chloride (p = 0.038). Hyponatremia without hypervolemic hypochloremia occurred in 11 respiratory acidosis patients. Hypovolemic hyponatremia with hypochloremia and hypokalemia occurred in 10 mixed respiratory acidosis–metabolic alkalosis patients, and euvolemic hypochloremia occurred in the other 7 patients with this mixed acid-base disorder.

Conclusions

Mixed acid-base and lactate disorders during hypercapnic COPD exacerbations predict the need for and longer duration of NIV. The combination of mixed acid-base disorders and hydro-electrolyte disturbances should be further investigated.     

The Continuum of Physiological Impairment during Treadmill Walking in Patients with Mild-to-Moderate COPD: Patient Characterization Phase of a Randomized Clinical Trial

Background

To have a better understanding of the mechanisms of exercise limitation in mild-to-moderate chronic obstructive pulmonary disease (COPD), we compared detailed respiratory physiology in patients with COPD and healthy age- and sex-matched controls.

Methods

Data were collected during the pre-treatment, patient characterization phase of a multicenter, randomized, double-blind, crossover study. Patients with COPD met Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 or 2 spirometric criteria, were symptomatic, and had evidence of gas trapping during exercise. All participants completed pulmonary function and symptom-limited incremental treadmill exercise tests.

Results

Chronic activity-related dyspnea measured by Baseline Dyspnea Index was similarly increased in patients with GOLD 1 (n = 41) and 2 (n = 63) COPD compared with controls (n = 104). Plethysmographic lung volumes were increased and lung diffusing capacity was decreased in both GOLD groups. Peak oxygen uptake and work rate were reduced in both GOLD groups compared with controls (p<0.001). Submaximal ventilation, dyspnea, and leg discomfort ratings were higher for a given work rate in both GOLD groups compared with controls. Resting inspiratory capacity, peak ventilation, and tidal volume were reduced in patients with GOLD 2 COPD compared with patients with GOLD 1 COPD and controls (p<0.001).

Conclusions

Lower exercise tolerance in patients with GOLD 1 and 2 COPD compared with controls was explained by greater mechanical abnormalities, greater ventilatory requirements, and increased subjective discomfort. Lower resting inspiratory capacity in patients with GOLD 2 COPD was associated with greater mechanical constraints and lower peak ventilation compared with patients with GOLD 1 COPD and controls.

Trial Registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01072396","term_id":"NCT01072396"}}NCT01072396     

Vibration response imaging: a novel noninvasive tool for evaluating the initial therapeutic effect of noninvasive positive pressure ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease

Background

The popular methods for evaluating the initial therapeutic effect (ITE) of noninvasive positive pressure ventilation (NPPV) can only roughly reflect the therapeutic outcome of a patient’s ventilation because they are subjective, invasive and time-delayed. In contrast, vibration response imaging (VRI) can monitor the function of a patient’s ventilation over the NPPV therapy in a non-invasive manner. This study aimed to investigate the value of VRI in evaluating the ITE of NPPV for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Methods

Thirty-six AECOPD patients received VRI at three time points: before NPPV treatment (T1), at 15 min of NPPV treatment (T2), and at 15 min after the end of NPPV treatment (T4). Blood gas analysis was also performed at T1 and at 2 hours of NPPV treatment (T3). Thirty-nine healthy volunteers also received VRI at T1 and T2. VRI examination at the time point T2 in either the patients or volunteers did not require any interruption of the on-going NPPV. The clinical indices at each time point were compared between the two groups. Moreover, correlations between the PaCO₂ changes (T3 vs T1) and abnormal VRI scores (AVRIS) changes (T2 vs T1) were analyzed.

Results

No significant AVRIS differences were found between T1 and T2 in the healthy controls (8.51 ± 3.36 vs. 8.53 ± 3.57, P > 0.05). The AVRIS, dynamic score, MEF score and EVP score showed a significant decrease in AECOPD patients at T2 compared with T1 (P < 0.05), but a significant increase at T4 compared with T2 (P < 0.05). We also found a positive correlation (R² = 0.6399) between the PaCO₂ changes (T3 vs T1) and AVRIS changes (T2 vs T1).

Conclusions

VRI is a promising noninvasive tool for evaluating the initial therapeutic effects of NPPV in AECOPD patients and predicting the success of NPPV in the early stage.     

Defective alterations in the collagen network to prostacyclin in COPD lung fibroblasts

Background

Prostacyclin analogs are potent vasodilators and possess anti-inflammatory properties. However, the effect of prostacyclin on extracellular matrix (ECM) in COPD is not well known. Collagen fibrils and proteoglycans are essential ECM components in the lung and fibroblasts are key players in regulating the homeostasis of ECM proteins. The aim was to study the synthesis of prostacyclin and its effect on fibroblast activity and ECM production, and in particular collagen I and the collagen-associated proteoglycans biglycan and decorin.

Methods

Parenchymal lung fibroblasts were isolated from lungs from COPD patients (GOLD stage IV) and from lungs and transbronchial biopsies from control subjects. The prostacyclin analog iloprost was used to study the effect of prostacyclin on ECM protein synthesis, migration, proliferation and contractile capacity of fibroblasts.

Results

TGF-β₁ stimulation significantly increased prostacyclin synthesis in fibroblasts from COPD patients (p < 0.01), but showed no effect on fibroblasts from control subjects. Collagen I synthesis was decreased by iloprost in both control and COPD fibroblasts (p < 0.05). Conversely, iloprost significantly altered biglycan and decorin synthesis in control fibroblasts, but iloprost displayed no effect on these proteoglycans in COPD fibroblasts. Proliferation rate was reduced (p < 0.05) and contractile capacity was increased in COPD fibroblasts (p < 0.05) compared to control fibroblasts. Iloprost decreased proliferative rate in control fibroblasts (p < 0.05), whereas iloprost attenuated contraction capacity in both COPD (p < 0.01) and control fibroblasts (p < 0.05).

Conclusions

Iloprost reduced collagen I synthesis and fibroblast contractility but did not affect the collagen-associated proteoglycans or proliferation rate in fibroblasts from COPD patients. Enhanced prostacyclin production could lead to improper collagen network fibrillogenesis and a more emphysematous lung structure in severe COPD patients.     

Target renal damage: the microvascular associations of increased aortic stiffness in patients with COPD

Background

Although renal impairment has been described in COPD, there is opportunity to evaluate further to determine nature and consider optimal management. Increased aortic stiffness, as seen in COPD, leads to reduced buffering of pulsatile flow. We hypothesised that urinary albumin creatinine ratio (UACR) would reflect glomerular damage related to aortic stiffness.

Methods

Patients with COPD and controls underwent spirometry, blood pressure, arterial stiffness - aortic pulse wave velocity (PWV) and provided a spot urine sample for UACR, with other renal biomarkers measured.

Results

The UACR was increased in patients (n = 52): 0.80 mg/mmol compared to controls (n = 34): 0.46 mg/mmol, p < 0.05. Aortic PWV was related to log₁₀ UACR in all subjects (r = 0.426, p < 0.001) and COPD patients alone. Aortic PWV was a significant variable for UACR with oxygen saturations, after accounting for potential confounders. Eight subjects (7 patients) reached a defined clinical microalbuminuria threshold, with aortic PWV greater in these patients compared to those patients without, although albuminuria is a continuum. Proximal tubular damage biomarkers, unlike the glomerular marker, were not different between patients and controls.

Conclusions

There is glomerular damage in patients with COPD evidenced by increased UACR, related to increased aortic stiffness. Besides the macrovascular prognostic implications of increased aortic stiffness, the microvascular state in COPD management should be considered.     

Feasibility and Safety of Fiber Optic Micro-Imaging in Canine Peripheral Airways

Purpose

To assess the feasibility and safety of imaging canine peripheral airways (<1 mm) with an experimental micro-imaging fiber optic bronchoscope.

Methods

Twenty healthy dogs were scoped with a micro-imaging fiber optic bronchoscope (0.8 mm outer diameter). Images at various levels of the bronchioles, mucosal color, and tracheal secretions were recorded. The apparatus was stopped once it was difficult to insert. CT imaging was performed simultaneously to monitor progression. The safety of the device was evaluated by monitoring heart rate (HR), respiratory rate (RR), mean artery pressure (MAP), peripheral oxygen saturation (SpO₂) and arterial blood gases (partial pressure of arterial carbon-dioxide, PaCO₂, partial pressure of arterial oxygen, PaO₂, and blood pH).

Results

(1) According to the CT scan, the micro-imaging fiber was able to access the peripheral airways (<1 mm) in canines. (2) There was no significant change in the values of HR, MAP, pH and PaCO₂ during the procedure (P>0.05). Comparing pre-manipulation and post-manipulation values, SpO₂ (F = 13.06, P<0.05) and PaO₂ (F = 3.01, P = 0.01) were decreased, whereas RR (F = 3.85, P<0.05) was elevated during the manipulation. (3) Self-limited bleeding was observed in one dog; severe bleeding or other complications did not occur.

Conclusion

Although the new apparatus had little effect on SpO₂, PaO₂ and RR, it can probe into small peripheral airways (<1 mm), which may provide a new platform for the early diagnosis of bronchiolar diseases.     

A Non Invasive Estimate of Dead Space Ventilation from Exercise Measurements

Rationale

During exercise, heart failure patients (HF) show an out-of-proportion ventilation increase, which in patients with COPD is blunted. When HF and COPD coexist, the ventilatory response to exercise is unpredictable.

Objectives

We evaluated a human model of respiratory impairment in 10 COPD-free HF patients and in 10 healthy subjects, tested with a progressive workload exercise with different added dead space. We hypothesized that increased serial dead space upshifts the VE vs. VCO₂ relationship and that the VE-axis intercept might be an index of dead space ventilation.

Measurements

All participants performed a cardiopulmonary exercise test with 0, 250 and 500 mL of additional dead space. Since DS does not contribute to gas exchange, ventilation relative to dead space is ventilation at VCO₂ = 0, i.e. VE-axis intercept. We compared dead space volume, estimated dividing VE-axis intercept by the intercept on respiratory rate axis of the respiratory rate vs. VCO₂ relationship with standard method measured DS.

Main results

In HF, adding dead space increased VE-axis intercept (+0 mL = 4.98±1.63 L; +250 mL = 9.69±2.91 L; +500 mL = 13.26±3.18 L; p<0.001) and upshifted the VE vs.VCO₂ relationship, with a minor slope rise (+0 mL = 27±4 L; +250 = 28±5; +500 = 29±4; p<0.05). In healthy, adding dead space increased VE-axis intercept (+0 mL = 4.9±1.4 L; +250 = 9.3±2.4; +500 = 13.1±3.04; p<0.001) without slope changes. Measured and estimated dead space volumes were similar both in HF and healthy subjects.

Conclusions

VE-axis intercept is related to dead space ventilation and dead space volume can be non-invasively estimated.     

The prevalence of increased serum IgE and Aspergillus sensitization in patients with COPD and their association with symptoms and lung function

Background

Allergy and Aspergillus hypersensitivity (AH) were shown to be associated with severe symptoms or worse lung function in COPD patients. The prevalence of elevated total IgE (T-IgE) and its association with clinical symptoms and lung function in COPD have not been studied. The prevalence of AH and its correlation with clinical characteristics in a COPD cohort of larger sample size is also lacking.

Methods

273 patients with COPD were evaluated by respiratory symptoms, blood test, chest HRCT, lung function, serum detection of T-IgE and Aspergillus specific IgE. Patients with T-IgE ≥ 1000 KU/L were further investigated for allergic bronchopulmonary aspergillosis (ABPA).

Results

The prevalence of elevated T-IgE and AH in patients with COPD was 47.3% and 15.0%, respectively. Eight patients (2.9%) met the diagnostic criteria for ABPA. Compared with the normal T-IgE group, patients with elevated T-IgE had a longer history of dyspnea (p < 0.01), an earlier onset of dyspnea after chronic cough/expectoration (p < 0.01), and were more likely to wheeze (p < 0.01). They also showed worse lung functions and more severe GOLD staging (p < 0.01). Analysis of the clinical data in male patients with smoking as the risk factor showed the same results. To evaluate the clinical characteristics of COPD with AH, patients with elevated T-IgE were further divided into subgroups with and without AH. When compared with the normal T-IgE group, both the two subgroups showed longer history of dyspnea (p < 0.01), an earlier onset of dyspnea (p < 0.01) and a worse status of lung function (p < 0.05). Correlation analysis demonstrated that T-IgE was correlated positively with the time length of dyspnea (r = 0.401, p < 0.001), and the ratio of duration of dyspnea to that of chronic cough/expectoration (r = 0.59, p < 0.001), but negatively with FEV1/FVC% (r = −0.194, p = 0.001), and FEV1%predicted (r = −0.219, p < 0.001).

Conclusions

There was a high prevalence of elevated serum T-IgE and AH in patients with COPD. Serum T-IgE level was correlated with symptoms such as dyspnea and impairment of lung function. Allergens other than Aspergillus may have similar effects on disease expression or progression of COPD.     

Inhibition of breathing after surfactant depletion is achieved at a higher arterial PCO2 during ventilation with liquid than with gas

Background

Inhibition of phrenic nerve activity (PNA) can be achieved when alveolar ventilation is adequate and when stretching of lung tissue stimulates mechanoreceptors to inhibit inspiratory activity. During mechanical ventilation under different lung conditions, inhibition of PNA can provide a physiological setting at which ventilatory parameters can be compared and related to arterial blood gases and pH.

Objective

To study lung mechanics and gas exchange at inhibition of PNA during controlled gas ventilation (GV) and during partial liquid ventilation (PLV) before and after lung lavage.

Methods

Nine anaesthetised, mechanically ventilated young cats (age 3.8 ± 0.5 months, weight 2.3 ± 0.1 kg) (mean ± SD) were studied with stepwise increases in peak inspiratory pressure (PIP) until total inhibition of PNA was attained before lavage (with GV) and after lavage (GV and PLV). Tidal volume (V_t), PIP, oesophageal pressure and arterial blood gases were measured at inhibition of PNA. One way repeated measures analysis of variance and Student Newman Keuls-tests were used for statistical analysis.

Results

During GV, inhibition of PNA occurred at lower PIP, transpulmonary pressure (Ptp) and Vt before than after lung lavage. After lavage, inhibition of inspiratory activity was achieved at the same PIP, Ptp and Vt during GV and PLV, but occurred at a higher PaCO₂ during PLV. After lavage compliance at inhibition was almost the same during GV and PLV and resistance was lower during GV than during PLV.

Conclusion

Inhibition of inspiratory activity occurs at a higher PaCO₂ during PLV than during GV in cats with surfactant-depleted lungs. This could indicate that PLV induces better recruitment of mechanoreceptors than GV.     

Effects of Anabolic Steroids on Chronic Obstructive Pulmonary Disease: A Meta-Analysis of Randomised Controlled Trials

Background

Anabolic steroids are known to improve body composition and muscle strength in healthy people. However, whether anabolic steroids improve the physical condition and function in patients with chronic obstructive pulmonary disease (COPD) remains undetermined. A meta-analysis was conducted to review the current evidence regarding the effects of anabolic steroids on COPD patients.

Methods

A comprehensive literature search of PubMed and EMBASE was performed to identify randomised controlled trials that examine the effects of anabolic steroids on COPD patients. Weighted mean differences (WMDs) with 95% confidence intervals were calculated to determine differences between anabolic steroid administration and control conditions.

Results

Eight eligible studies involving 273 COPD patients were identified in this meta-analysis. Significant improvements were found in body weight (0.956 kg), fat-free mass (1.606 kg), St. George''s Respiratory Questionnaire total score (−6.336) and symptom score (−12.148). The apparent improvements in maximal inspiratory pressure (2.740 cmH₂O) and maximal expiratory pressure (12.679 cmH₂O) were not significant. The effects on handgrip strength, forced expiratory volume in one second (FEV₁), predicted FEV₁ percent, PaO₂, PaCO₂ and six-min walk distance were negative, with WMDs of −0.245 kg, −0.096 L/sec, −1.996% of predicted, −1.648 cmHg, −0.039 cmHg and −16.102 meters, respectively.

Conclusions

Limited evidence available from the published literature suggests that the benefit of anabolic steroids on COPD patients cannot be denied. However, further studies are needed to identify the specific benefits and adverse effects of anabolic steroids on COPD patients and to determine the optimal populations and regimes of anabolic steroids in COPD patients.     

DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease

Background

Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in subjects with moderate-to-severe airflow obstruction. The aim of our study was to identify genetic variants associated with TLC in COPD.

Methods

We performed genome-wide association studies (GWASs) in white subjects from three cohorts: the COPDGene Study; the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); and GenKOLS (Bergen, Norway). All subjects were current or ex-smokers with at least moderate airflow obstruction, defined by a ratio of forced expiratory volume in 1 second to forced vital capacity (FEV₁/FVC) <0.7 and FEV₁ < 80% predicted on post-bronchodilator spirometry. TLC was calculated by using volumetric computed tomography scans at full inspiration (TLC_CT). Genotyping in each cohort was completed, with statistical imputation of additional markers. To find genetic variants associated with TLC_CT, linear regression models were used, with adjustment for age, sex, pack-years of smoking, height, and principal components for genetic ancestry. Results were summarized using fixed-effect meta-analysis.

Results

Analysis of a total of 4,543 COPD subjects identified one genome-wide significant locus on chromosome 5p15.2 (rs114929486, β = 0.42L, P = 4.66 × 10⁻⁸).

Conclusions

In COPD, TLC_CT was associated with a SNP in dynein, axonemal, heavy chain 5 (DNAH5), a gene in which genetic variants can cause primary ciliary dyskinesia. DNAH5 could have an effect on hyperinflation in COPD.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0097-y) contains supplementary material, which is available to authorized users.     

The Administration of 100% Oxygen and Respiratory Drive in Very Preterm Infants at Birth

Aim

To retrospectively investigate the changes of SpO₂ and respiratory drive in preterm infants at birth after administration of 100% oxygen.

Methods

Respiratory parameters, FiO₂ and oximetry of infants <32 weeks gestation before and after receiving FiO₂ 1.0 were reviewed during continuous positive airway pressure (CPAP) or positive pressure ventilation (PPV).

Results

Results are given as median (IQR) or percentages where appropriate. Suitable recordings were made in 50 infants (GA 27 (26–29) weeks), 17 received CPAP and 33 PPV. SpO₂ increased rapidly in the first minute after FiO₂ 1.0 and remained stable. The duration of FiO₂ 1.0 tended to be shorter in the CPAP group than in the PPV group (CPAP vs. PPV: 65 (33–105) vs. 100 (40–280) s; p = 0.05), SpO₂ >95% occurred more often in PPV group (53% vs. 69%) and lasted longer (70(40–95) vs. 120(50–202) s). In CPAP group, minute volume increased from 134 (76–265) mL/kg/min 1 minute before to 240 (157–370) mL/kg/min (p<0.01) 1 minute after start FiO₂ 1.0 and remained stable at 2 minutes (252 (135–376) mL/kg/min; ns). The rate of rise to maximum tidal volume increased (from 13.8 (8.0–22.4) mL/kg/s to 18.2 (11.0–27.5) mL/kg/s; p<0.0001) to 18.8 (11.8–27.8) mL/kg/s; ns). In the PPV group respiratory rate increased from 0(0–4) to 9(0–20) at 1 minute (p<0.001) to 23 (0–34) breaths per minute at 2 minutes (p<0.01).

Conclusion

In preterm infants at birth, a rapid increase in oxygenation, resulting from a transient increase to 100% oxygen might improve respiratory drive, but increases the risk for hyperoxia.     

Three-year follow-up of Interleukin 6 and C-reactive protein in chronic obstructive pulmonary disease

Background

Past studies have shown that mean values of Interleukin-6 (IL-6) and C-reactive protein (CRP) do not change significantly in COPD patients over a one-year period. However, longer period follow-up studies are still lacking. Thus, the aim of this study is to evaluate plasma CRP and IL-6 concentration over three years in COPD patients and to test the association between these inflammatory mediators and disease outcome markers.

Methods

A cohort of 77 outpatients with stable COPD was evaluated at baseline, and 53 (mean FEV₁, 56% predicted) were included in the prospective study. We evaluated Interleukin-6 (IL-6), C-reactive protein (CRP), six-minute walking distance (6MWD), and body mass index (BMI) at baseline and after three years. Plasma concentration of IL-6 was measured by high sensitivity ELISA, and CRP was obtained by high sensitivity particle-enhanced immunonephelometry.

Results

IL-6 increased significantly after 3 years compared to baseline measurements [0.8 (0.5-1.3) vs 2.4 (1.3-4.4) pg/ml; p < 0.001] and was associated with worse 6MWD performance. In the Cox regression, increased IL-6 at baseline was associated with mortality [Hazard Ratio (95% CI) = 2.68 (0.13, 1.84); p = 0.02]. CRP mean values did not change [5 (1.6-7.9) vs 4.7 (1.7-10) pg/L; p = 0.84], although eleven patients (21%) presented with changes >3 mg/L in CRP after 3 years.

Conclusions

The systemic inflammatory process, evaluated by IL-6, seems to be persistent, progressive and associated with mortality and worse physical performance in COPD patients.

Trial registration

No.:{"type":"clinical-trial","attrs":{"text":"NCT00605540","term_id":"NCT00605540"}}NCT00605540     

Impact of Acetazolamide and CPAP on Cortical Activity in Obstructive Sleep Apnea Patients

Study Objectives

1) To investigate the impact of acetazolamide, a drug commonly prescribed for altitude sickness, on cortical oscillations in patients with obstructive sleep apnea syndrome (OSAS). 2) To examine alterations in the sleep EEG after short-term discontinuation of continuous positive airway pressure (CPAP) therapy.

Design

Data from two double-blind, placebo-controlled randomized cross-over design studies were analyzed.

Setting

Polysomnographic recordings in sleep laboratory at 490 m and at moderate altitudes in the Swiss Alps: 1630 or 1860 m and 2590 m.

Patients

Study 1: 39 OSAS patients. Study 2: 41 OSAS patients.

Interventions

Study 1: OSAS patients withdrawn from treatment with CPAP. Study 2: OSAS patients treated with autoCPAP. Treatment with acetazolamide (500–750 mg) or placebo at moderate altitudes.

Measurements and Results

An evening dose of 500 mg acetazolamide reduced slow-wave activity (SWA; approximately 10%) and increased spindle activity (approximately 10%) during non-REM sleep. In addition, alpha activity during wake after lights out was increased. An evening dose of 250 mg did not affect these cortical oscillations. Discontinuation of CPAP therapy revealed a reduction in SWA (5–10%) and increase in beta activity (approximately 25%).

Conclusions

The higher evening dose of 500 mg acetazolamide showed the “spectral fingerprint” of Benzodiazepines, while 250 mg acetazolamide had no impact on cortical oscillations. However, both doses had beneficial effects on oxygen saturation and sleep quality.     

Changes in the endurance shuttle walk test in COPD patients with chronic respiratory failure after pulmonary rehabilitation: the minimal important difference obtained with anchor- and distribution-based method

Background

Although the endurance shuttle walk test (ESWT) has proven to be responsive to change in exercise capacity after pulmonary rehabilitation (PR) for COPD, the minimally important difference (MID) has not yet been established. We aimed to establish the MID of the ESWT in patients with severe COPD and chronic hypercapnic respiratory failure following PR.

Methods

Data were derived from a randomized controlled trial, investigating the value of noninvasive positive pressure ventilation added to PR. Fifty-five patients with stable COPD, GOLD stage IV, with chronic respiratory failure were included (mean (SD) FEV₁ 31.1 (12.0) % pred, age 62 (9) y). MID estimates of the ESWT in seconds, percentage and meters change were calculated with anchor based and distribution based methods. Six minute walking distance (6MWD), peak work rate on bicycle ergometry (Wpeak) and Chronic Respiratory Questionnaire (CRQ) were used as anchors and Cohen’s effect size was used as distribution based method.

Results

The estimated MID of the ESWT with the different anchors ranged from 186–199 s, 76–82% and 154–164 m. Using the distribution based method the MID was 144 s, 61% and 137 m.

Conclusions

Estimates of the MID for the ESWT after PR showed only small differences using different anchors in patients with COPD and chronic respiratory failure. Therefore we recommend using a range of 186–199 s, 76–82% or 154–164 m as MID of the ESWT in COPD patients with chronic respiratory failure. Further research in larger populations should elucidate whether this cut-off value is also valid in other COPD populations and with other interventions.

Trial registration

ClinicalTrials.Gov (ID {"type":"clinical-trial","attrs":{"text":"NCT00135538","term_id":"NCT00135538"}}NCT00135538).

Electronic supplementary material

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High Prevalence of Left Ventricle Diastolic Dysfunction in Severe COPD Associated with A Low Exercise Capacity: A Cross-Sectional Study

Background

A subclinical left ventricle diastolic dysfunction (LVDD) has been described in patients with chronic obstructive pulmonary disease (COPD).

Objectives

To evaluate the prevalence of LVDD in stable severe COPD patients, to analyze its relationship with exercise capacity and to look for its possible causes (lung hyperinflation, ventricular interdependence or inflammatory mechanisms).

Methods

We evaluated 106 consecutive outpatients with severe COPD (FEV₁ between 30–50%). Thirty-three (31%) were excluded because of previous heart disease. A pulmonary function test, a 6-minute walking test (6MWT), a Doppler echocardiography test, including diastolic dysfunction parameters, and an analysis of arterial blood gases, NT-proBNP and serum inflammatory markers (CRP, leucocytes), were performed in all patients.

Results

The prevalence of LVDD in severe stable COPD patients was 90% (80% type I, n=57, and 10% type II, n=7). A significant association between a lower E/A ratio (higher LVDD type I) and a lower exercise tolerance (6-minute walked distance (6MWD)) was found (r=0.29, p<0.05). The fully adjusted multivariable linear regression model demonstrated that a lower E/A ratio, a DLCO in the quartile 4^th and a higher tobacco consumption were associated with a lower 6MWD (76, 57 and 0.7 metres, respectively, p<0.05). A significant correlation between E/A ratio and PaO₂ was observed (r=0.26, p<0.05), but not with static lung hyperinflation, inflammation or right ventricle overload parameters.

Conclusion

In stable severe COPD patients, the prevalence of LVDD is high and this condition might contribute in their lower exercise tolerance. Hypoxemia could have a concomitant role in their pathogenesis.