Thrombelastography and Conventional Coagulation Markers in Chronic Obstructive Pulmonary Disease: A Prospective Paired-Measurements Study Comparing Exacerbation and Stable Phases.

Chronic Obstructive Pulmonary Disease (COPD) exacerbation is known for its substantial impact on morbidity and mortality among affected patients, creating a significant healthcare burden worldwide. Coagulation abnormalities have emerged as potential contributors to exacerbation pathogenesis, raising concerns about increased thrombotic events during exacerbation. The aim of this study was to explore the differences in thrombelastography (TEG) parameters and coagulation markers in COPD patients during admission with exacerbation and at a follow-up after discharge. This was a multi-center cohort study. COPD patients were enrolled within 72 h of hospitalization. The baseline assessments were Kaolin-TEG and blood samples. Statistical analysis involved using descriptive statistics; the main analysis was a paired t-test comparing coagulation parameters between exacerbation and follow-up. One hundred patients participated, 66% of whom were female, with a median age of 78.5 years and comorbidities including atrial fibrillation (18%) and essential arterial hypertension (45%), and sixty-five individuals completed a follow-up after discharge. No significant variations were observed in Kaolin-TEG or conventional coagulation markers between exacerbation and follow-up. The Activated Partial Thromboplastin Clotting Time (APTT) results were near-significant, with p = 0.08. In conclusion, TEG parameters displayed no significant alterations between exacerbation and follow-up.

Long-term non-invasive ventilation for COPD patients following an exacerbation with acute hypercapnic respiratory failure: a randomized controlled trial.

Introduction: It remains unclear whether long-term non-invasive ventilation (LT-NIV) for patients with chronic obstructive pulmonary disease (COPD) improves survival and reduces admissions as results from randomized trials are inconsistent. We aim to determine whether LT-NIV initiated after an admission with acute hypercapnic respiratory failure (AHRF) can affect survival and admission rate in COPD patients. Methods: A randomized controlled open-label trial, allocating patients with COPD to LT-NIV or standard of care immediately after an admission with AHRF treated with acute NIV. LT-NIV was aimed to normalize PaCO2 using high-pressure NIV. Results: The study was discontinued before full sample size due to slow recruitment. 28 patients were randomized to LT-NIV and 27 patients to standard of care. 42% of patients had a history of ≥ 2 admissions with AHRF. Median IPAP was 24 cmH2O (IQR 20-28). The primary outcome, time to readmission with AHRF or death within 12 months, did not reach significance, hazard ratio 0.53 (95% CI 0.25-1.12) p = 0.097. In a competing risk analysis, adjusted for history of AHRF, the odds ratio for AHRF within 12 months was 0.30 (95% CI 0.11-0.87) p = 0.024. The LT-NIV group had less exacerbations (median 1 (0-1) vs 2 (1-4) p = 0.021) and readmissions with AHRF (median 0 (0-1) vs 1 (0-1) p = 0.016). Conclusion: The risk of the primary outcome, time to readmission with AHRF or death within 12 months was numerically smaller in the LT-NIV group, however, did not reach significance. Nevertheless, several secondary outcome analyses like risk of AHRF, number of episodes of AHRF and exacerbations were all significantly reduced in favour of high-pressure LT-NIV, especially in patients with frequent AHRF.

Renin-angiotensin-system inhibitors and the risk of exacerbations in chronic obstructive pulmonary disease: a nationwide registry study.

OBJECTIVE: The renin-angiotensin system (RAS) has been shown to play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD) because of the inflammatory properties of the system. Many patients with COPD use RAS-inhibiting (RASi) treatment. The aim was to determine the association between treatment with RASi and the risk of acute exacerbations and mortality in patients with severe COPD. METHODS: Active comparator analysis by propensity-score matching. Data were collected in Danish national registries, containing complete information on health data, prescriptions, hospital admissions and outpatient clinic visits. Patients with COPD (n=38 862) were matched by propensity score on known predictors of the outcome. One group was exposed to RASi treatment (cases) and the other was exposed to bendroflumethiazide as an active comparator in the primary analysis. RESULTS: The use of RASi was associated with a reduced risk of exacerbations or death in the active comparator analysis at 12 months follow-up (HR 0.86, 95% CI 0.78 to 0.95). Similar results were evident in a sensitivity analysis of the propensity-score-matched population (HR 0.89, 95% CI 0.83 to 0.94) and in an adjusted Cox proportional hazards model (HR 0.93, 95% CI 0.89 to 0.98). CONCLUSION: In the current study, we found that the use of RASi treatment was associated with a consistently lower risk of acute exacerbations and death in patients with COPD. Explanations to these findings include real effect, uncontrolled biases, and-less likely-chance findings.

High-pressure NIV for acute hypercapnic respiratory failure in COPD: improved survival in a retrospective cohort study.

INTRODUCTION: Updated treatment guidelines for acute hypercapnic respiratory failure (AHRF) in chronic obstructive pulmonary disease (COPD) with non-invasive ventilation (NIV) in 2016 recommended a rapid increase in inspiratory positive airway pressure (IPAP) to 20 cm H2O with possible further increase for patients not responding. Previous guidelines from 2006 suggested a more conservative algorithm and maximum IPAP of 20 cm H2O. AIM: To determine whether updated guidelines recommending higher IPAP during NIV were related with improved outcome in patients with COPD admitted with AHRF, compared with NIV with lower IPAP. METHODS: A retrospective cohort study comparing patients with COPD admitted with AHRF requiring NIV in 2012-2013 and 2017-2018. RESULTS: 101 patients were included in the 2012-2013 cohort with low IPAP regime and 80 patients in the 2017-2018 cohort with high IPAP regime. Baseline characteristics, including age, forced expiratory volume in 1 s (FEV1), pH and PaCO2 at initiation of NIV, were comparable. Median IPAP in the 2012-2013 cohort was 12 cm H2O (IQR 10-14) and 20 cm H2O (IQR 18-24) in the 2017-2018 cohort (p<0.001). In-hospital mortality was 40.5% in the 2012-2013 cohort and 13.8% in the 2017-2018 cohort (p<0.001). The 30-days and 1-year mortality were significantly lower in the 2017-2018 cohort. With a Cox model 1 year survival analysis, adjusted for age, sex, FEV1 and pH at NIV initiation, the HR was 0.45 (95% CI 0.27 to 0.74, p=0.002). CONCLUSION: Short-term and long-term survival rates were substantially higher in the cohort treated with higher IPAP. Our data support the current strategy of rapid increase and higher pressure.

Prognostic impact of ventilation-perfusion defects and pulmonary diffusing capacity after single lung transplantation.

BACKGROUND: Ventilation-perfusion (VQ) scintigraphy and lung function testing are often used to assess allograft function after single lung transplantation (SLTX). However, it is unknown whether allograft defects on VQ scintigraphy presage all-cause mortality after SLTX. OBJECTIVE: To investigate whether allograft defects on VQ scintigraphy portend poorer lung function and increased mortality after SLTX. METHODS: We retrospectively identified 45 consecutive patients in which a VQ scintigraphy was performed as part of the routine workup 12 weeks after SLTX. VQ scintigraphies were scored for matched and mismatched perfusion defects in the allograft. Lung function testing was performed according to established guidelines six months after SLTX. Time to all-cause mortality was the endpoint. RESULTS: 19 (42%) patients had matched VQ defects. After a median follow-up of 4.1 (IQR 1.5-7.9) years since SLTX, 35 (78%) had died. Those with matched defects in the allograft had lower diffusing capacity (mean 42 [SD 14] versus mean 54 [SD 18] % of predicted, p < .05) and increased mortality (univariable HR 2.06, 95% CI: 1.05-4.06, p = .04). However, in multivariate analysis, only lower post-transplantation diffusing capacity remained associated with mortality (HR 1.08, 95% CI: 1.02-1.30 per % lower diffusing capacity of predicted, p = .003). CONCLUSION: In SLTX patients, a lower diffusing capacity appeared to explain the increased mortality among those with matched VQ defects in the allograft.

NIV for acute respiratory failure in COPD: high in-hospital mortality is determined by patient selection.

Introduction: Hospital mortality among chronic obstructive pulmonary disease (COPD) patients receiving NIV for acute respiratory failure has shown to be significantly higher in clinical settings than in the randomized trials (RCTs) which clinical guidelines are based on. This may be due to the quality of care of NIV or patient selection. In daily clinical practice, we include patients with terminal pulmonary disease with a do-not-intubate (DNI) or a do-not-resuscitate (DNR) order with a high mortality risk compared to highly selected patients in RCTs. The aim of this study was to determine the role of patient selection for in-hospital mortality among patients receiving NIV for acute respiratory failure of COPD. Methods: We conducted a retrospective study including all patients receiving acute NIV due to acute respiratory failure at the respiratory wards in 2012-2013 at two hospitals in Greater Copenhagen. Results: Overall in-hospital mortality rate was 30%. In patients with a DNI/DNR order, mortality was 59% and in patients with no limitations in treatment 2%. Patients who fulfilled the exclusion criteria of the RCT by Plant et al. had a mortality of 41% compared to 25% in the remaining population. Conclusions: High overall in-hospital mortality reflects that patient selection in clinical practice is very different from RCT. Quality of acute NIV treatment seems acceptable in clinical practice for patients with less severe COPD and no limitations in treatment. Higher mortality in patients with DNI/DNR order may be due to inefficient NIV treatment for these patients with more severe COPD.

Magnet tracking allows assessment of regional gastrointestinal transit times in children.

BACKGROUND: Data on small intestinal transit time in healthy children are lacking, and normal values for gastric emptying and colonic transit time are sparse. Conventional methods, including radiopaque markers, scintigraphy, and PillCam™ involve radiation or require the child to swallow a large pill. The minimally invasive, radiation-free Motility Tracking System-1 (MTS-1) has been introduced for description of gastrointestinal motility in adults. The aim of the study was to evaluate the MTS-1 for assessment of gastrointestinal transit times and motility patterns in healthy children. METHODS: Twenty-one healthy children (nine girls), median age 10 (range 7-12) years were included. For evaluation with MTS-1, a small magnetic pill was ingested and tracked through the gastrointestinal tract by a matrix of 16 magnetic sensors placed behind a nonmagnetic bed. The children were investigated for 8 hours after swallowing the magnetic pill and again for 4 hours the following morning. After leaving the unit, each child came back after every bowel movement to determine if the pill had been expelled. RESULTS: Nineteen children could swallow the pill. Characteristic contraction patterns were identified for the stomach (three per minute), small intestine (9-11 per minute), and colon (4-5 per minute). Median total gastrointestinal transit time was 37.7 (range 9.5-95.8) hours, median gastric emptying time was 37 (range 2-142) minutes, median small intestinal transit time was 302 (range 164 to >454) minutes, and median colorectal transit time was 38.1 (range 5.6-90.0) hours. CONCLUSION: MTS-1 allows minimally invasive evaluation of gastrointestinal motility in children. Use of the method is, however, restricted by the nonambulatory setup.

Gastrointestinal transit times and motility in patients with cystic fibrosis.

OBJECTIVE: Patients with cystic fibrosis (CF) often suffer from gastrointestinal (GI) dysfunction including obstructive symptoms, malabsorption and pain, but the underlying pathophysiology remains obscure. AIM: To compare GI motility and transit times in CF patients and healthy controls. MATERIAL AND METHODS: Ten CF patients (five women, median age 23) with pancreatic insufficiency were studied. Total gastrointestinal transit time (GITT) and segmental colonic transit times (SCTT) were assessed by radiopaque markers. Gastric emptying and small intestinal transit were evaluated using the magnet-based motility tracking system (MTS-1). With each method patients were compared with 16 healthy controls. RESULTS: Basic contraction frequencies of the stomach and small intestine were normal, but the pill reached the cecum after 7 h in only 20% of CF patients while in 88% of controls (p = 0.001). Paradoxically, velocity of the magnetic pill through the upper small intestine tended to be faster in CF patients (median 1.1 cm/min, range 0.7-1.7) compared with controls (median 1.0 cm/min, range 0.6-1.7) (p = 0.09). No statistically significant differences were found in median gastric emptying time (CF: 58 min, range 6-107 vs. healthy: 41 min, range 4-125 (p = 0.24)), GITT (CF: 2 days, range 0.5-3.3 vs. healthy: 1.5 days, range 0.7-2.5 (p = 0.10)), right SCTT (CF: 0.5 day, range 0-1.1 vs. healthy: 0.4 day, range 0-1.0 (p = 0.85)), or left SCTT (CF: 1.0 day, range 0-2.2 vs. healthy 0.6 day, range 0.2-1.2 (p = 0.10)). CONCLUSIONS: In spite of normal contraction patterns, overall passage through the small intestine is significantly delayed in CF patients while upper small intestinal transit may be abnormally fast.