Dataset Information

Targeted lung denervation for moderate to severe COPD: a pilot study.

ABSTRACT: BACKGROUND:Parasympathetic pulmonary nerves release acetylcholine that induces smooth muscle constriction. Disruption of parasympathetic pulmonary nerves improves lung function and COPD symptoms. AIMS:To evaluate 'targeted lung denervation' (TLD), a novel bronchoscopic therapy based on ablation of parasympathetic pulmonary nerves surrounding the main bronchi, as a potential therapy for COPD. METHODS:This 1-year, prospective, multicentre study evaluated TLD in patients with COPD forced expiratory volume in 1?s (FEV1)/forced vital capacity (FVC) (FEV1/FVC <0.70; FEV1 30%-60% predicted). Patients underwent staged TLD at 20 watts (W) or 15?W following baseline assessment off bronchodilators. Assessments were repeated on tiotropium before treatment and off bronchodilators at 30, 90, 180, 270 and 365?days after TLD. The primary endpoint was freedom from documented and sustained worsening of COPD directly attributable to TLD to 1 year. Secondary endpoints included technical feasibility, change in pulmonary function, exercise capacity, and quality of life. RESULTS:Twenty-two patients were included (n=12 at 20?W, n=10 at 15?W). The procedures were technically feasible 93% of the time. Primary safety endpoint was achieved in 95%. Asymptomatic bronchial wall effects were observed in 3 patients at 20?W. The clinical safety profiles were similar between the two energy doses. At 1?year, changes from baseline in the 20 W dose compared to the 15 W dose were: FEV1 (+11.6%±32.3 vs +0.02%±15.1, p=0.324), submaximal cycle endurance (+6.8?min±12.8 vs 2.6?min±8.7, p=0.277), and St George's Respiratory Questionnaire (-11.1 points ±9.1 vs -0.9 points ±8.6, p=0.044). CONCLUSIONS:Bronchoscopic TLD, based on the concept of ablating parasympathetic pulmonary nerves, was feasible, safe, and well tolerated. Further investigation of this novel therapy is warranted. TRIAL REGISTRATION NUMBER:NCT01483534.

SUBMITTER: Slebos DJ

PROVIDER: S-EPMC4413833 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Targeted lung denervation for moderate to severe COPD: a pilot study.

Slebos Dirk-Jan DJ Klooster Karin K Koegelenberg Coenraad F N CF Theron Johan J Styen Dorothy D Valipour Arschang A Mayse Martin M Bolliger Chris T CT

Thorax 20150304 5

<h4>Background</h4>Parasympathetic pulmonary nerves release acetylcholine that induces smooth muscle constriction. Disruption of parasympathetic pulmonary nerves improves lung function and COPD symptoms.<h4>Aims</h4>To evaluate 'targeted lung denervation' (TLD), a novel bronchoscopic therapy based on ablation of parasympathetic pulmonary nerves surrounding the main bronchi, as a potential therapy for COPD.<h4>Methods</h4>This 1-year, prospective, multicentre study evaluated TLD in patients with ...[more]

PMID: 25739911

Similar Datasets

Project description:Rationale: Targeted lung denervation (TLD) is a bronchoscopic radiofrequency ablation therapy for chronic obstructive pulmonary disease (COPD), which durably disrupts parasympathetic pulmonary nerves to decrease airway resistance and mucus hypersecretion.Objectives: To determine the safety and impact of TLD on respiratory adverse events.Methods: We conducted a multicenter, randomized, sham bronchoscopy-controlled, double-blind trial in patients with symptomatic (modified Medical Research Council dyspnea scale score, ≥2; or COPD Assessment Test score, ≥10) COPD (FEV1, 30-60% predicted). The primary endpoint was the rate of respiratory adverse events between 3 and 6.5 months after randomization (defined as COPD exacerbation, tachypnea, wheezing, worsening bronchitis, worsening dyspnea, influenza, pneumonia, other respiratory infections, respiratory failure, or airway effects requiring therapeutic intervention). Blinding was maintained through 12.5 months.Measurements and Main Results: Eighty-two patients (50% female; mean ± SD: age, 63.7 ± 6.8 yr; FEV1, 41.6 ± 7.3% predicted; modified Medical Research Council dyspnea scale score, 2.2 ± 0.7; COPD Assessment Test score, 18.4 ± 6.1) were randomized 1:1. During the predefined 3- to 6.5-month window, patients in the TLD group experienced significantly fewer respiratory adverse events than those in the sham group (32% vs. 71%, P = 0.008; odds ratio, 0.19; 95% confidence interval, 0.0750-0.4923, P = 0.0006). Between 0 and 12.5 months, these findings were not different (83% vs. 90%; P = 0.52). The risk of COPD exacerbation requiring hospitalization in the 0- to 12.5-month window was significantly lower in the TLD group than in the sham group (hazard ratio, 0.35; 95% confidence interval, 0.13-0.99; P = 0.039). There was no statistical difference in the time to first moderate or severe COPD exacerbation, patient-reported symptoms, or other physiologic measures over the 12.5 months of follow-up.Conclusions: Patients with symptomatic COPD treated with TLD combined with optimal pharmacotherapy had fewer study-defined respiratory adverse events, including hospitalizations for COPD exacerbation.Clinical trial registered with www.clinicaltrials.gov (NCT02058459).

Project description:Chronic obstructive pulmonary disease (COPD) impairs physical status and impacts on mental health. This prospective study was designed to assess associations between mental health and systemic biomarkers, and their combined relationship with long-term survival in stable severe COPD.Forty-five patients with severe but stable COPD (forced expiratory volume in 1 s of 29.8 (quartiles: 22.6; 41.4) %predicted) were assessed using the Hospital Anxiety and Depression Scale (HADS), the Patient Health Questionnaire (PHQ), St. George's Respiratory Questionnaire and the State-Trait Anxiety Inventory (STAI). The following serum biomarkers were measured: 25-OH-cholecalciferol, C-reactive protein, erythrocyte sedimentation rate, leucocyte number, serum amyloid-A (SA-A), N-terminal pro-brain natriuretic peptide, troponin I, glycosylated haemoglobin, haemoglobin (Hb), haematocrit (Hc), creatinine and thyroid-stimulating hormone. Patients were followed-up for 36 months. Associations between aspects of mental health and biomarkers, and their utility as predictors of 3-year survival were evaluated by regression analyses.The prevalence of anxiety (HADS-A: 89.9 %), depression (HADS-D: 58.8 %; PHQ: 60.6 %), somatisation (PHQ-15: 81.8 %) and psychosocial stress (PHQ-stress: 60.6 %) was high. There was a significant positive association between the leucocyte count and SA-A level with STAI-trait anxiety (p = 0.03 and p = 0.005, respectively), and between leucocytes and PHQ-stress (p = 0.043). Hb and Hc were significantly negatively associated with HADS-depression (p = 0.041 and p = 0.031, respectively). Univariate Cox regression analyses revealed that leucocyte count (hazard ratio (HR) 2.976, 95 % CI 1.059-8.358; p = 0.038), and stress (HR 4.922, 95 % CI 1.06-22.848; p = 0.042) were linked to long-term survival. In multivariate Cox regression analyses, including known risk factors for survival in COPD, PHQ-stress (HR 45.63, 95 % CI 1.72-1,208.48; p = 0.022) remained significantly associated with survival.In this pilot study different dimensions of mental health were correlated to serum biomarkers, probably reflecting systemic effects of COPD. While leucocyte number and PHQ-stress were associated with long-term survival in univariate analyses, PHQ-stress remained in multivariate analyses as independent prognostic factor.

Project description:BackgroundPhysical and psychological symptoms are the hallmark of patients' subjective perception of their illness. The purpose of this analysis was to determine if patients with COPD have distinctive symptom profiles and to examine the association of symptom profiles with systemic biomarkers of inflammation.MethodsWe conducted latent class analyses of three physical (dyspnea, fatigue, and pain) and two psychological symptoms (depression and anxiety) in 302 patients with moderate to severe COPD using baseline data from a longitudinal observational study of depression in COPD. Systemic inflammatory markers included IL1, IL8, IL10, IL12, IL13, INF, GM-CSF, TNF-α (levels >75thcentile was considered high); and CRP (levels >3 mg/L was considered high). Multinominal logistic regression models were used to examine the association between symptom classes and inflammation while adjusting for key socio-demographic and disease characteristics.ResultsWe found that a 4-class model best fit the data: 1) low physical and psychological symptoms (26%, Low-Phys/Low-Psych), 2) low physical but moderate psychological symptoms (18%, Low-Phys/Mod Psych), 3) high physical but moderate psychological symptoms (25%, High-Phys/Mod Psych), and 4) high physical and psychological symptoms (30%, High-Phys/High Psych). Unadjusted analyses showed associations between symptom class with high levels of IL7, IL-8 (p ≤ .10) and CRP (p < .01). In the adjusted model, those with a high CRP level were less likely to be in the High-Phys/Mod-Psych class compared to the Low-Phys/Low-Psych (OR: 0.41, 95%CI 0.19, 0.90) and Low-Phys/Mod-Psych classes (OR: 0.35, 95%CI 0.16, 0.78); elevated CRP was associated with in increased odds of being in the High-Phys/High-Psych compared to the High-Phys/Mod-Psych class (OR: 2.22, 95%CI 1.08, 4.58). Younger age, having at least a college education, oxygen use and depression history were more prominent predictors of membership in the higher symptom classes.ConclusionsPatients with COPD can be classified into four distinct symptom classes based on five commonly co-occurring physical and psychological symptoms. Systemic biomarkers of inflammation were not associated with symptom class. Additional work to test the reliability of these symptom classes, their biological drivers and their validity for prognostication and tailoring therapy in larger and more diverse samples is needed.Trial registrationClinicaltrials.gov, NCT01074515 .

Dataset Information

Targeted lung denervation for moderate to severe COPD: a pilot study.

Publications

Targeted lung denervation for moderate to severe COPD: a pilot study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets