Can an educational intervention in the context of inpatient pulmonary rehabilitation improve asthma self-management at work? A study protocol of a randomized controlled trial.

BACKGROUND: Asthma self-management (e.g., trigger avoidance or correct medication use) is a cornerstone of therapy. Its successful implementation in everyday working life is determined by psychosocial working conditions, in particular by support from superiors and colleagues and the job decision latitude (i.e., when and how to carry out which tasks). To empower individuals with asthma to modify their working conditions, employees need to use certain communication skills and acquire specific knowledge. Both could be taught as part of patient education during pulmonary rehabilitation. Therefore, the aim of the planned study is the development and multicentre implementation of an education module for individuals with asthma during their rehabilitation and to generate evidence on its effectiveness. METHODS: Participants (n ≥ 180) will be recruited, randomized into an intervention and a control group, trained and surveyed in two rehabilitation clinics. The intervention group will receive the supplementary patient education module "Asthma and Work" while the control group will participate in a program on " Eating behaviour" (both 2 × 50 min). The effectiveness of the intervention will be examined based on pre-post measurements (T1 and T2) and a 3-month follow-up (T3). We will consider behavioural intention (T2) and asthma self-management at work (T3) as primary outcomes. Secondary outcomes will include self-management-related knowledge, self-efficacy, number of sick days, number of exacerbations, asthma control (Asthma Control Test), asthma-related quality of life (Marks Asthma Quality of Life Questionnaire), and subjective employment prognosis (Brief Scale Measuring the Subjective Prognosis of Gainful Employment). The pre-post comparisons are to be evaluated using univariate analyses of covariance. DISCUSSION: Improving asthma self-management at work could increase the work ability and social participation of employees with asthma. This could reduce costs, e.g. in terms of asthma-related sick leave. TRIAL REGISTRATION: German Clinical Trials Register (ID: DRKS00031843).

Pirfenidone in patients with progressive fibrotic interstitial lung diseases other than idiopathic pulmonary fibrosis (RELIEF): a double-blind, randomised, placebo-controlled, phase 2b trial.

BACKGROUND: Pirfenidone has been shown to slow disease progression in patients with idiopathic pulmonary fibrosis (IPF). However, there are few treatment options for progressive fibrotic interstitial lung diseases (ILDs)) other than IPF. In view of the pathomechanistic and clinical similarities between IPF and other progressive fibrotic ILDs, we aimed to assess the efficacy and safety of pirfenidone in patients with four non-IPF progressive fibrotic ILDs. METHODS: We did a multicentre, double-blind, randomised, placebo-controlled, parallel phase 2b trial (RELIEF) in 17 centres with expertise in ILD in Germany. Eligible participants were patients aged 18-80 years with progressive fibrotic ILD due to four diagnoses: collagen or vascular diseases (ie, connective tissue disease-associated ILDs), fibrotic non-specific interstitial pneumonia, chronic hypersensitivity pneumonitis, or asbestos-induced lung fibrosis. Other eligibility criteria included a forced vital capacity (FVC) of 40-90% predicted, a diffusing capacity of the lung for carbon monoxide of 10-90% predicted, and an annual decline of FVC of at least 5% predicted despite conventional therapy, based on at least three measurements within 6-24 months before enrolment. Patients who had received any previous antifibrotic therapy were excluded. We randomly assigned patients (1:1) to either oral pirfenidone (267 mg three times per day in week 1, 534 mg three times per day in week 2, and 801 mg three times per day thereafter) or matched placebo, added to their ongoing medication. Randomisation was done centrally using permuted block randomisation with varying block sizes stratified by the four diagnostic groups. Patients, investigators, statisticians, monitors, and the study coordinator were masked to treatment assignment until database closure. The placebo-controlled study period was 48 weeks (including up-titration). The primary endpoint was absolute change in percentage of predicted FVC (FVC % predicted) from baseline to week 48 in the intention-to-treat population, with imputation of missing data by the smallest sum of squared differences and attribution of deceased patients to the lowest rank in a rank ANCOVA model. Additionally, we did linear mixed-model repeated measures slope analyses of FVC % predicted longitudinal data over the course of the study as a prespecified sensitivity analysis and post-hoc sensitivity analyses of the primary endpoint in the intention-to-treat population using imputation methods of last observation carried forward [LOCF] and a regression-based multiple imputation procedure. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered with EudraCT 2014-000861-32; DRKS00009822 and is no longer recruiting. FINDINGS: Between April 5, 2016, and Oct 4, 2018, we randomly assigned 127 patients to treatment: 64 to pirfenidone, 63 to placebo. After 127 patients had been randomised, the study was prematurely terminated on the basis of an interim analysis for futility triggered by slow recruitment. After 48 weeks and in the overall population of 127 patients, rank ANCOVA with diagnostic group included as a factor showed a significantly lower decline in FVC % predicted in the pirfenidone group compared with placebo (p=0·043); the result was similar when the model was stratified by diagnostic group (p=0·042). A significant treatment effect was also observed when applying the LOCF and multiple imputation methods to analyses of the primary endpoint. The median difference (Hodges-Lehmann estimate) between pirfenidone and placebo groups for the primary endpoint was 1·69 FVC % predicted (95% CI -0·65 to 4·03). In the linear mixed-model repeated measures slope analysis of FVC % predicted, the estimated difference between treatment and placebo groups from baseline to week 48 was 3·53 FVC % predicted (95% CI 0·21 to 6·86) with imputation of deaths as prespecified, or 2·79 FVC % predicted (95% CI 0·03 to 5·54) without imputation. One death (non-respiratory) occurred in the pirfenidone group (2%) and five deaths (three of which were respiratory) occurred in the placebo group (8%). The most frequent serious adverse events in both groups were infections and infestations (five [8%] in the pirfenidone group, ten [16%] in the placebo group); general disorders including disease worsening (two [3%] in the pirfenidone group, seven [11%] in the placebo group); and cardiac disorders (one ([2%] in the pirfenidone group, 5 [8%] in the placebo group). Adverse events (grade 3-4) of nausea (two patients on pirfenidone, two on placebo), dyspnoea (one patient on pirfenidone, one on placebo), and diarrhoea (one patient on pirfenidone) were also observed. INTERPRETATION: In view of the premature study termination, results should be interpreted with care. Nevertheless, our data suggest that in patients with fibrotic ILDs other than IPF who deteriorate despite conventional therapy, adding pirfenidone to existing treatment might attenuate disease progression as measured by decline in FVC. FUNDING: German Center for Lung Research, Roche Pharma.

Combined videothoracoscopic and videomediastinoscopic approach improves radicality of minimally invasive mediastinal lymphadenectomy for early stage lung carcinoma.

OBJECTIVES: To assess the feasibility and radicality of a combined thoracoscopic and mediastinoscopic approach to mediastinal lymphadenectomy compared to thoracoscopy only for minimally invasive management of early stage lung carcinoma. METHODS: Prospective observational study of patients undergoing anatomical thoracoscopic lung resection for lung carcinoma in our department in 2007. Mediastinal lymphadenectomy was performed either thoracoscopically (VATS group) or by a combination of video-assisted mediastinoscopic lymphadenectomy (VAMLA) and thoracoscopy (VAMLA+VATS group). Inclusion criteria for the study were: stage Ia on CT scan, no central tumor at bronchoscopy, and no contraindications against lobectomy or segmentectomy. RESULTS: Eighteen VAMLA+VATS and fourteen VATS patients were studied. For histology, pTNM stage, type of resection, semiquantitative assessment of the fissure and vascular dissection plane, conversions, blood loss, operation time, adverse events and drainage time, no differences between the two groups were observed. In the VATS group, there was a slight preponderance of women, and right-sided tumors. In the VAMLA+VATS group, both the number of dissected mediastinal lymph node stations (mean, 6.4 stations vs 3.6 stations) and the weight of the mediastinal specimen (median, 11.2 groups vs 5.5 groups), were significantly higher than in the VATS group (p<0.05). CONCLUSIONS: A combined approach by VATS and VAMLA improves radicality of minimally invasive mediastinal lymphadenectomy without increase in operation time, morbidity, and drainage time.

Does endoesophageal ultrasound-guided fine-needle aspiration replace mediastinoscopy in mediastinal staging of thoracic malignancies?

OBJECTIVE: To determine the impact of endoesophageal ultrasound-guided fine-needle aspiration (EUS-FNA) on management of thoracic malignancies. METHODS: One hundred and twenty patients referred for invasive diagnostic and resection of thoracic malignancies were studied prospectively. Negative and inconclusive EUS-FNA findings were assessed by video-assisted mediastinoscopic lymphadenectomy (VAMLA) or open lymphadenectomy. RESULTS: One hundred and twenty patients, aged 64.1 years (range 38-85) underwent 120 EUS-FNA, 53 video-assisted mediastinoscopic and 48 open lymphadenectomies for diagnosis and treatment of 99 lung carcinoma, six lung metastases, five mesothelioma, three lymphoma, and eight other conditions. EUS-FNA showed T4 in 15/120 and adrenal or hepatic metastases in 9/120 cases. Prevalence of mediastinal lymph node metastases was 51.7%. EUS-FNA false-negative rate was 25.3%. EUS-FNA sensitivity was 91.7%, 78.1% and 43.8% for bulky disease, enlarged mediastinal nodes or normal nodes on CT scan, 50% and 96.6% for right- and left-sided tumours, and 80.6%, 78.9%, 23.8% and 25.0% for the lymph node stations 7, 5/6, 4R, and 4L. A 38.3% respectively 100% cut-down of mediastinoscopies leads in 7.5% respectively 20.8% to incorrect treatment decisions. CONCLUSIONS: EUS-FNA sensitivity depends on the localisation of the primary tumour, and extent and location of mediastinal disease. For left-sided tumours, EUS-FNA improves mediastinal staging by assessing stations 5 and 6 inaccessible to conventional mediastinoscopy. For extended mediastinal disease, mediastinoscopy can be avoided or spared for restaging after neoadjuvant therapy. Exclusion of mediastinal involvement requires mediastinoscopy or open lymphadenectomy. Beyond mediastinal nodal staging, EUS-FNA may detect T4 and M1 situations. Thus, EUS-FNA is a useful supplement to and not the replacement of mediastinoscopy.

[Prognosis, staging and therapy of malignant pleural mesothelioma]. / Prognose, Staging und Therapie des malignen Pleuramesothelioms.

PROGNOSIS: Prognosis of pleural mesothelioma remains dismal. Regardless of the modality employed median survival ranges between 6 and 12 months, only 20% of patients survive 1 year. In 1996 the International Mesothelioma Interest Group (IMIG) published a widely accepted staging system. So far there is no effective standard therapy. Even very aggressive therapies do not basically influence the course of the disease. THERAPEUTICAL STUDIES: Despite numerous single-agent and combination chemotherapy trials no standard regimen could be found. Few agents yield reproducible response rates above 20%. The majority of the trials are inconclusive according to statistical criteria, as subject numbers are insufficient to prove or deny effectiveness. It also remains obscure in which stage of the disease patients may benefit from chemotherapy because of a lack of analysis of response rates within different stages. Striking is the lack of sufficient studies analyzing patients' quality of life treated with often very toxic regimens. DRUG TREATMENT: Systemic administration of interferons alone or in combination with chemotherapeutic agents did not result in higher response rates or prolonged median survival. In very early stages of the disease patients may have limited benefit from intracavitary, local administration of gamma-interferon. MULTIMODALITY APPROACHES: Mere surgical procedures as extrapleural pneumonectomy or pleurectomy/decortication have been left in favor of multimodality approaches. Due to careful patient selection and improved operation techniques mortality could be reduced. Neither chemotherapy, radiotherapy nor photodynamic therapy can prevent local relapse which occurs in the majority of patients. RADIOTHERAPY: The effectiveness of primary radiation therapy remains controversial. Even very high doses of radiation cannot control tumor growth. It remains unclear whether radiation therapy may palliate tumor associated symptoms. Prophylactic radiation of puncture channels and thoracotomy scars is effective to prevent tumor growth caused by seeding of mesothelioma cells. PERSPECTIVES: Research of the biological behavior of mesothelioma resulted in first phase I gene therapy trials. The results of the few promising approaches tested in phase II and III trials with sufficient patient numbers have to be awaited until we have learned whether and in which stage of the disease patients may benefit from therapy.