Ahmed Yousuf

Effectiveness of chemical pleurodesis in spontaneous pneumothorax recurrence prevention: a systematic review

Objectives Spontaneous pneumothorax is a common pathology. International guidelines suggest pleurodesis for non-resolving air leak or recurrence prevention at second occurrence. This study comprehensively reviews the existing literature regarding chemical pleurodesis efficacy. Design We systematically reviewed the literature to identify relevant randomised controlled trials (RCTs), case–control studies and case series. We described the findings of these studies and tabulated relative recurrence rates or ORs (in studies with control groups). Meta-analysis was not performed due to substantial clinical heterogeneity. Results Of 560 abstracts identified by our search strategy, 50 were included in our systematic review following screening. Recurrence rates in patients with chest tube drainage only were between 26.1% and 50.1%. Thoracoscopic talc poudrage (four studies (n=249)) provided recurrence rates of between 2.5% and 10.2% with the only RCT suggesting an OR of 0.10 compared with drainage alone. In comparison, talc administration during video-assisted thoracic surgery (VATS) from eight studies (n=2324) recurrence was between 0.0% and 3.2%, but the RCT did not demonstrate a significant difference compared with bleb/bullectomy alone. Minocycline appears similarly effective post-VATS (recurrence rates 0.0–2.9%). Prolonged air leak and recurrence prevention using tetracycline via chest drain (n=726) is likely to provide recurrence rates between 13.0% and 33.3% and autologous blood patch pleurodesis (n=270) between 15.6% and 18.2%. Conclusions Chemical pleurodesis postsurgical treatment or via thoracoscopy appears to be most effective. Evidence for definitive success rates of each agent is limited by the small number of randomised trials or other comparative studies.

Assessment of patient-reported outcome measures in pleural interventions

Introduction There is a lack of data evaluating the clinical effect on symptoms of pleural intervention procedures. This has led to the development of patient-reported outcome measures (PROMs) to define what constitutes patient benefit. The primary aim of this paper was to prospectively assess the effect of pleural procedures on PROMs and investigate the relationship between symptom change and clinical factors. Methods We prospectively collected data as part of routine clinical care from 158 patients with pleural effusion requiring interventions. Specific questionnaires included two patient-reported scores (a seven-point Likert scale and a 100 mm visual analogue scale (VAS) to assess symptoms). Results Excluding diagnostic aspiration, the majority of patients (108/126, 85.7%) experienced symptomatic benefit from fluid drainage (mean VAS improvement 42.6 mm, SD 24.7, 95% CI 37.9 to 47.3). There was a correlation between symptomatic benefit and volume of fluid removed post aspiration. A negative association was identified between the number of septations seen on ultrasound and improvement in dyspnoea VAS score in patients treated with intercostal chest drain. Conclusion The results of our study highlight the effect of pleural interventions from a patient’s perspective. The outcomes defined have the potential to form the basis of a clinical useful tool to appraise the effect, compare the efficiency and identify the importance of pleural interventions to the patients.

A Pilot Feasibility Study in Establishing the Role of Ultrasound-Guided Pleural Biopsies in Pleural Infection (The AUDIO Study)

Background Pleural infection is a common complication of pneumonia associated with high mortality and poor clinical outcome. Treatment of pleural infection relies on the use of broad‐spectrum antibiotics because reliable pathogen identification occurs infrequently. We performed a feasibility interventional clinical study assessing the safety and significance of ultrasound (US)‐guided pleural biopsy culture to increase microbiological yield. In an exploratory investigation, the 16S ribosomal RNA technique was applied to assess its utility on increasing speed and accuracy vs standard microbiological diagnosis. Methods Twenty patients with clinically established pleural infection were recruited. Participants underwent a detailed US scan and US‐guided pleural biopsies before chest drain insertion, alongside standard clinical management. Pleural biopsies and routine clinical samples (pleural fluid and blood) were submitted for microbiological analysis. Results US‐guided pleural biopsies were safe with no adverse events. US‐guided pleural biopsies increased microbiological yield by 25% in addition to pleural fluid and blood samples. The technique provided a substantially higher microbiological yield compared with pleural fluid and blood culture samples (45% compared with 20% and 10%, respectively). The 16S ribosomal RNA technique was successfully applied to pleural biopsy samples, demonstrating high sensitivity (93%) and specificity (89.5%). Conclusions Our findings demonstrate the safety of US‐guided pleural biopsies in patients with pleural infection and a substantial increase in microbiological diagnosis, suggesting potential niche of infection in this disease. Quantitative polymerase chain reaction primer assessment of pleural fluid and biopsy appears to have excellent sensitivity and specificity.

Thoracic Ultrasound as an Early Predictor of Pleurodesis Success in Malignant Pleural Effusion

BACKGROUND: Malignant pleural effusion (MPE) is common and imposes a significant burden on patients and health‐care providers. Most patients require definitive treatment, usually drainage and chemical pleurodesis, to relieve symptoms and prevent fluid recurrence. Thoracic ultrasound (TUS) can identify the presence of pleural adhesions in other clinical scenarios, and could therefore have a role in predicting long‐term pleurodesis success or failure in MPE. METHODS: Patients undergoing chest tube drainage and talc slurry pleurodesis for symptomatic MPE were recruited to a prospective observational cohort pilot study assessing whether TUS findings pre‐talc and post‐talc instillation predicted treatment outcome. Participants underwent TUS examination immediately before, and 24 h after talc slurry administration to derive pleural adherence scores for the affected hemithorax. The recorded TUS scans were additionally scored by two independent assessors blinded to the patients clinical status. The primary outcome was pleurodesis success at 1‐month and 3‐month follow‐up. RESULTS: Eighteen participants were recruited to the pilot study. Participants who suffered pleurodesis failure had a lower pleural adherence score at 24 h post‐talc instillation than those who were successful (difference of 6.27; 95% CI, 3.94‐8.59). TUS examination was acceptable to patients, while TUS scoring was highly consistent across all assessors (intraclass correlation coefficient, 0.762; 95% CI, 0.605‐0.872). CONCLUSION: A TUS‐derived pleural adherence score may facilitate early prediction of long‐term outcomes following chemical pleurodesis, with implications for personalized care and decision making in MPE. Further research is needed to evaluate this novel finding. TRIAL REGISTRY: ClinicalTrials.gov; No. NCT02625675; URL: www.clinicaltrials.gov.

P233 Thoracic ultrasonography as a predictor of pleurodesis success in malignant pleural effusion

Background Over 50 000 patients with malignant pleural effusion (MPE) are seen annually in the UK. The majority develop recurrent symptomatic disease requiring definitive treatment. MPE is most frequently managed with talc slurry pleurodesis via intercostal chest drain. This involves a lengthy inpatient stay and has a success rate of around 70%, with no means of predicting which patients will suffer pleurodesis failure. Thoracic ultrasound (TUS) is widely used by respiratory physicians, and data from animal and human studies suggest it can identify pleural adhesions (through the absence of normal lung sliding) in a range of conditions. By extension, TUS may allow clinicians to diagnose the presence or absence of adhesions post-pleurodesis in MPE, identifying patients suitable for discharge or needing further intervention. Abstract P233 Table 1 Ultrasonographic pleurodesis score at day 0 (pre-pleurodesis) and day 1 (24 hours post-pleurodesis) in patients being treated for malignant pleural effusion Successful pleurodesis n=11/15 (73.3%) patients Failed pleurodesis n=4/15 (26.7%) patients p value unpaired t-test Day 0 pleurodesis score (mean±SD, total out of 18) 10.89±3.98 6.50±1.29 0.054 Difference=4.39 (95% CI −0.09 to 8.86) Day 1 pleurodesis score (mean±SD, total out of 18) 13.45±2.63 6.75±2.94 0.002 Difference=6.70 (95% CI 3.08 to 10.33) Change from day 0 to 1 (mean±SD) 2.57±3.98 0.25±3.59 0.326 Difference=2.32 (95% CI −2.59 to 7.23) Method We recruited 18 adult patients with MPE undergoing drainage and talc slurry pleurodesis to a prospective single-centre cohort study. Patients underwent standardised TUS assessment pre- and post-pleurodesis, evaluating pleural sliding and adhesions at nine points (three anterior, three lateral, three posterior) across the affected hemithorax. Lung sliding was graded as per Zhu et al.,1 creating a total pleurodesis score out of 18. Pleurodesis failure was defined as radiological and symptomatic fluid recurrence in the same hemithorax requiring further intervention at any point up to 3 months post-pleurodesis. Patients also completed a questionnaire addressing satisfaction with TUS assessment. Results 3/18 patients (16.7%) died before 1 month follow-up. Of 15 patients seen at one month, 11 (73.3%) had successful pleurodesis and 4 (26.7%) had failed. No patient had delayed pleurodesis failure between 1 and 3 month follow-up. There was a significant difference observed in the day 1 TUS pleurodesis score between patients who went on to have successful pleurodesis and those who failed during follow-up (table 1). TUS assessment was acceptable to patients, with none considering it either time-consuming or unwilling to have it again if needed. Conclusion Our data suggest TUS assessment 24 hours post-pleurodesis for MPE predicts success or failure of this intervention, with significant implications for clinical care. A larger randomised study is now underway to further evaluate this hypothesis. Reference Chest2005;128(2):934–9.

P179 The Effectiveness of Chemical Pleurodesis Agents in Spontaneous Pneumothorax: A Systematic Review

Introduction and objectives Spontaneous Pneumothorax (SP) is a common pathology. Recurrence rates (RR) for Primary SP (PSP) are often quoted as approximately 30% (individual studies reporting anywhere between 17 and 49%), with less data available on Secondary SP (SSP) recurrence rates. Recurrence prevention at first episode remains controversial. International guidelines suggest pleurodesis for non-resolving air leak or recurrence prevention at second episode. There are numerous candidate agents for chemical pleurodesis. This study aimed to comprehensively review the existing literature regarding chemical pleurodesis as a treatment modality. Methods The systematic review methodology was based on the PRISMA approach and principles. Literature searches of multiple databases (PubMed, Embase, Medline, Web of Science, Cochrane Library) used combinations of terms including “spontaneous”, “pneumothor*”, “chemical”, “talc”, “tetracycline”, “minocycline”, “iodopovidine”, and “blood”. Abstracts were reviewed for relevance by two authors, who subsequently assessed and extracted data from the full articles. Results Of 522 abstracts reviewed; 427 were excluded (e.g. case reports, letters, reviews, animal models or basic science articles); an additional 4 papers included via back-referencing. 99 full text papers were reviewed; 58 were excluded for the following reasons: foreign language only, not available, or inadequate data/follow-up information. The remaining 41 papers’ data were extracted, showing variation in size, quality and type of studies. Eight randomised trials across differing patient groups (both medical and surgical) report markedly varying recurrence rates (Table 1). Six prospective series (n = 398) found thoracoscopic talc insufflation (RR: 3 to 7%) and tetracycline (9% via chest drain or poudrage) to be effective; with iodopovidone less so (13%). Of 27 retrospective case series (n = 4,990), seven were reasonable quality, finding good efficacy of adding talc or silver nitrate post-bullectomy (RR: 1 to 2%); better than minocycline or acromycin post-bullectomy (3 and 4%) or talc post-electrocoagulation (5%). The remaining 20 were poorer quality with high risk of bias, assessing 7 different agents.Abstract P179 Table 1 Detail of 8 randomised trials assessing efficacy of chemical pleurodesis Study Medical/Surgical Intervention agent (# cases) Control (# cases) PSP/SSP (# cases) Co-Intervention Recurrence rate (agent/control) Light (1990) M Tetracycline (113) Drainage only (116) 46/183 Nil 25%/41% Almind* (1989) M Talc (29) vs tetracycline (33) Drainage only (34) 71/25 Thoracoscopy (no intervention) 8%/13%/36% Tschopp (2002) M Talc (61) Drainage only (47) 108/0 Thoracoscopy (no intervention) 5%/34% Chen (2006) S Minocycline (103) Saline (99) 202/0 VATS - bullectomy 2%/8% Chung* (2007) S Talc and Dextrose (42) vs Dextrose alone (49) Drainage only (50) 141/0 Thoraco-scopic bleb resection/cautery 2%/2%/6% Agarwal (2011) M Iodopovidone (20) Talc (15) 10/25 Nil 0%/0% Alayouty (2011) S Minocycline (42) Abrasion (40) 82/0 VATS -bullectomy 0%/5% Chen (2013) M Minocycline (106) Drainage only (108) 214/0 Nil 29%/49% *Three arms of trial. Conclusions Numerous agents have been used for chemical pleurodesis for spontaneous pneumothorax. Chemical pleurodesis post-surgical treatment or via thoracoscopy appears most effective. Evidence for definitive success rates of each agent is limited by the small number of randomised and comparative trials.