Lars Christian Laursen

The Effect of Inhaled Corticosteroids on the Development of Emphysema in Smokers Assessed by Annual Computed Tomography

The objective was to evaluate the effect of inhaled corticosteroids on disease progression in smokers with moderate to severe chronic obstructive pulmonary disease (COPD), as assessed by annual computed tomography (CT) using lung density (LD) measurements. Two hundred and fifty-four current smokers with COPD were randomised to treatment with either an inhaled corticosteroids (ICS), budesonide 400 μ g bid, or placebo. COPD was defined as FEV1 ≤ 70% pred, FEV1/FVC ≤ 60% and no reversibility to β2-agonists and oral corticosteroids. The patients were followed for 2–4 years with biannual spirometry and annual CT and comprehensive lung function tests (LFT). CT images were analysed using Pulmo-CMS software. LD was derived from a pixel-density histogram of the whole lung as the 15thpercentile density (PD15) and the relative area of emphysema at a threshold of −910 Hounsfield units (RA-910), and both were volume-adjusted to predicted total lung capacity. At baseline, mean age was 64 years and 64 years; mean number of pack-years was 56 and 56; mean FEV1 was 1.53 L (51% pred) and 1.53 L (53% pred); mean PD15 was 103 g/L and 104 g/L; and mean RA-910 was 14% and 13%, respectively, for the budesonide and placebo groups. The annual fall in PD15 was −1.12 g/L in the budesonide group and −1.81 g/L in the placebo group (p = 0.09); the annual increase in RA–910 was 0.4% in the budesonide group and 1.1% in the placebo group (p = 0.02). There was no difference in annual decline in FEV1 between ICS (−54 mL) and placebo (−56 mL) (p = 0.89). Long-term budesonide inhalation shows a non-significant trend towards reducing the progression of emphysema as determined by the CT-derived 15th percentile lung density from annual CT scans in current smokers with moderate to severe COPD.

Rapid Fall in Lung Density Following Smoking Cessation in COPD

Introduction: Whether smoking-induced lung inflammation subsides after smoking cessation is currently a matter of debate. We used computed tomography (CT) to evaluate the effect of smoking cessation on lung density in patients with COPD. Material and methods: Thirty-six patients quit smoking out of 254 current smokers with COPD who were followed with annual CT and lung function tests (LFT) for 2–4 years as part of a randomised placebo-controlled trial of the effect of inhaled budesonide on CT-lung density. Lung density was expressed as the 15th percentile density (PD15) and relative area of emphysema below -910 HU (RA-910). From the time-trends in the budesonide and placebo groups the expected CT-lung densities at the first visit after smoking cessation were calculated by linear regression and compared to the observed densities. Results: Following smoking cessation RA-910 increased by 2.6% (p = 0.003) and PD15 decreased by −4.9 HU (p = 0.0002). Furthermore, changes were larger in the budesonide group than the placebo group (PD15: −7.1 vs −2.8 HU. RA-910 3.7% vs 1.7%). These differences were, however, not statistically significant. The LFT parameters (FEV1 and diffusion capacity) were not significantly influenced by smoking cessation. Conclusion: Inflammation partly masks the presence of emphysema on CT and smoking cessation results in a paradoxical fall in lung density, which resembles rapid progression of emphysema. This fall in density is probably due to an anti-inflammatory effect of smoking cessation.

Effect of tele health care on exacerbations and hospital admissions in patients with chronic obstructive pulmonary disease: a randomized clinical trial

Background and objective Tele monitoring (TM) of patients with chronic obstructive pulmonary disease (COPD) has gained much interest, but studies have produced conflicting results. Our aim was to investigate the effect of TM with the option of video consultations on exacerbations and hospital admissions in patients with severe COPD. Materials and methods Patients with severe COPD at high risk of exacerbations were eligible for the study. Of 560 eligible patients identified, 279 (50%) declined to participate. The remaining patients were equally randomized to either TM (n=141) or usual care (n=140) for the 6-month study period. TM comprised recording of symptoms, saturation, spirometry, and weekly video consultations. Algorithms generated alerts if readings breached thresholds. Both groups received standard care. The primary outcome was number of hospital admissions for exacerbation of COPD during the study period. Results Most of the enrolled patients had severe COPD (forced expiratory volume in 1 second <50%pred in 86% and ≥hospital admission for COPD in the year prior to enrollment in 45%, respectively, of the patients). No difference in drop-out rate and mortality was found between the groups. With regard to the primary outcome, no significant difference was found in hospital admissions for COPD between the groups (P=0.74), and likewise, no difference was found in time to first admission or all-cause hospital admissions. Compared with the control group, TM group patients had more moderate exacerbations (ie, treated with antibiotics/corticosteroid, but not requiring hospital admission; P<0.001), whereas the control group had more visits to outpatient clinics (P<0.001). Conclusion Our study of patients with severe COPD showed that TM including video consultations as add-on to standard care did not reduce hospital admissions for exacerbated COPD, but TM may be an alternative to visits at respiratory outpatient clinics. Further studies are needed to establish the optimal role of TM in the management of severe COPD.

Hospital-admitted COPD patients treated at home using telemedicine technology in The Virtual Hospital Trial: methods of a randomized effectiveness trial

BackgroundRecent reviews suggest that telemedicine solutions for patients with chronic obstructive pulmonary disease (COPD) may prevent hospital readmissions and emergency room visits and improve health-related quality of life. However, the studies are few and only involve COPD patients who are in a stable phase or in-patients who are ready for discharge. COPD patients hospitalized with an acute exacerbation may also benefit from telemedicine solutions. The overall aim is to investigate a telemedicine-based treatment solution for patients with acute exacerbation of COPD at home as compared to conventional hospital treatment measured according to first treatment failure, which is defined as readmission due to COPD within 30 days after discharge.MethodsCOPD patients with acute exacerbation who fulfilled the eligibility criteria and were from two university hospitals in Denmark were randomized (1:1) by computer-generated tables that allocated treatments in blocks of four to receive either standard treatment at the hospital or the same standard treatment at home using telemedicine technology (that is, a video conference system with a touch screen and webcam and monitoring equipment (spirometer, thermometer, and pulse oximeter)). Patients treated in the telemedicine group were backed up by an organizational setting securing 24/7/365 online access to the hospital, as well as access to oxygen, nebulizer therapy, oral medical therapy and surveillance of vital parameters from home monitoring devices. Patients in both groups were discharged when clinically stable and when fulfilling five pre-specified discharge criteria. Follow-up was performed at 1, 3 and 6 months after discharge.The primary outcome was treatment failure defined as readmission due to exacerbation in COPD within 30 days. Secondary outcomes were death from any cause, prescription of additional antibiotics or steroids, need of intubation or non-invasive ventilation, emergency room visits, visits to the general practitioner, lung function, bed days, health-related quality of life, healthcare costs and user satisfaction.ResultsEnrollment of patients started in June 2010 and ended in December 2011. Follow-up ended in May 2012. Results were analyzed in 2013.ConclusionsThe results may have implications on future hospital treatment modalities for patients with severe exacerbations in COPD where telemedicine may be used as an alternative to conventional admission.Trial registrationClinical Trials NCT01155856

Home-Based Telehealth Hospitalization for Exacerbation of Chronic Obstructive Pulmonary Disease: Findings from ‘‘The Virtual Hospital’’ Trial

BACKGROUNDnTelehealth interventions for patients with chronic obstructive pulmonary disease (COPD) have focused primarily on stable outpatients. Telehealth designed to handle the acute exacerbation that normally requires hospitalization could also be of interest. The aim of this study was to compare the effect of home-based telehealth hospitalization with conventional hospitalization for exacerbation in severe COPD.nnnMATERIALS AND METHODSnA two-center, noninferiority, randomized, controlled effectiveness trial was conducted between June 2010 and December 2011. Patients with severe COPD admitted because of exacerbation were randomized 1:1 either to home-based telehealth hospitalization or to continue standard treatment and care at the hospital. The primary outcome was treatment failure defined as re-admission due to exacerbation in COPD within 30 days after initial discharge. The noninferiority margin was set at 20% of the control groups risk of re-admission. Secondary outcomes were mortality, need for manual or mechanical ventilation or noninvasive ventilation, length of hospitalization, physiological parameters, health-related quality of life, user satisfaction, healthcare costs, and adverse events.nnnRESULTSnIn total, 57 patients were randomized: 29 participants in the telehealth group and 28 participants in the control group. Testing the incidence of re-admission within 30 days after discharge could not confirm noninferiority (lower 95% confidence limit [CL], -24.8%; p=0.35). Results were also nonsignificant at 90 days (lower 95% CL, -16.2%; p=0.33) and 180 days (lower 95% CL, -16.6%; p =0.33) after discharge. Superiority testing on secondary outcomes showed nonsignificant differences between groups. Healthcare costs have not yet been evaluated.nnnCONCLUSIONSnWhether home-based telehealth hospitalization is noninferior to conventional hospitalization requires further investigation. The results indicate that a subgroup of patients with severe COPD can be treated for acute exacerbation at home using telehealth, without the physical presence of health professionals and with a proper organizational back-up.

Home Non Invasive Ventilation (NIV) treatment for COPD patients with a history of NIV-treated exacerbation; a randomized, controlled, multi-center study

BackgroundIn chronic obstructive pulmonary disease, the prognosis for patients who have survived an episode of acute hypercapnic respiratory failure due to an exacerbation is poor. Despite being shown to improve survival and quality-of-life in stable patients with chronic hypercapnic respiratory failure, long-term noninvasive ventilation is controversial in unstable patients with frequent exacerbations, complicated by acute hypercapnic respiratory failure. In an uncontrolled group of patients with previous episodes of acute hypercapnic respiratory failure, treated with noninvasive ventilation, we have been able to reduce mortality and the number of repeat respiratory failure and readmissions by continuing the acute noninvasive ventilatory therapy as a long-term therapy.MethodsMulti-center open label randomized controlled trial of 150 patients having survived an admission with noninvasive ventilatory treatment of acute hypercapnic respiratory failure due chronic obstructive pulmonary disease. The included patients are randomized to usual care or to continuing the acute noninvasive ventilation as a long-term therapy, both with a one-year follow-up period. The primary endpoint is time to death or repeat acute hypercapnic respiratory failure; secondary endpoints are one-year mortality, number of readmissions and repeat acute hypercapnic respiratory failure, exacerbations, dyspnea, quality of life, sleep quality, lung function, and arterial gases.DiscussionThough previous studies of long-term noninvasive ventilation have shown conflicting results, we believe the treatment can reduce mortality and readmissions when applied in patients with previous need of acute ventilatory support, regardless of persistent hypercapnia.Trial registrationclinicaltrials.org: NCT01513655 16-Jan-2012.