BTS Guideline for Pleural Disease.pdf

BTS Guideline British Thoracic Society Guideline for pleural disease Mark E Roberts,1 Najib M Rahman ‍ ‍,2,3,4 Nick A Maskell,5 Anna C Bibby,5 Kevin G Blyth,6,7 John P Corcoran ‍ ‍,8 Anthony Edey,9 Matthew Evison ‍ ‍,10 Duneesha de Fonseka ‍ ‍,11 Rob Hallifax,12 Susan Harden ‍ ‍,13 Iain Lawrie,14 E...

BTS Guideline British Thoracic Society Guideline for pleural disease Mark E Roberts,1 Najib M Rahman ‍ ‍,2,3,4 Nick A Maskell,5 Anna C Bibby,5 Kevin G Blyth,6,7 John P Corcoran ‍ ‍,8 Anthony Edey,9 Matthew Evison ‍ ‍,10 Duneesha de Fonseka ‍ ‍,11 Rob Hallifax,12 Susan Harden ‍ ‍,13 Iain Lawrie,14 Eric Lim,15 David J McCracken,16 Rachel Mercer,17 Eleanor K Mishra ‍ ‍,18 Andrew G Nicholson,19 Farinaz Noorzad,20 Kirstie Opstad,21 Maria Parsonage,22 Andrew E Stanton ‍ ‍,23 Steven Walker,5 On behalf of the BTS Pleural Guideline Development Group ►► Additional supplemental material is published online only. To view, please visit the journal online (http://​dx.​doi.​ org/​10.​1136/​thorax-​2022-​ 219784). For numbered affiliations see end of article. Correspondence to Dr Mark Roberts, Department Of Respiratory Medicine, King’s Mill Hospital, Sutton-in-Ashfield NG17 4JL, UK; [email protected] Summary of recommendations and good practice points Spontaneous pneumothorax Acute management for spontaneous pneumothorax Recommendations ►► Conservative management can be considered ►► ►► ►► ►► ►► http://​dx.​doi.​org/​10.​1136/​ thorax-​2022-​219371 for the treatment of minimally symptomatic (ie, no significant pain or breathlessness and no physiological compromise) or asymptomatic primary spontaneous pneumothorax in adults regardless of size. (Conditional—by consensus) Ambulatory management should be considered for the initial treatment of primary spontaneous pneumothorax in adults with good support, and in centres with available expertise and follow-­up facilities. (Conditional) In patients not deemed suitable for conservative or ambulatory management, needle aspiration or tube drainage should be considered for the initial treatment of primary spontaneous pneumothorax in adults. (Conditional) Chemical pleurodesis can be considered for the prevention of recurrent of secondary spontaneous pneumothorax in adults (eg, patients with severe chronic obstructive pulmonary disease who significantly decompensated in the presence of a pneumothorax, even during/after the first episode). (Conditional) Thoracic surgery can be considered for the treatment of pneumothorax in adults at initial presentation if recurrence prevention is deemed important (eg, patients presenting with tension pneumothorax, or those in high-­risk occupations). (Conditional) Good practice points © Author(s) (or their employer(s)) 2022. No commercial re-­use. See rights and permissions. Published by BMJ. To cite: Roberts ME, Rahman NM, Maskell NA, et al. Thorax Epub ahead of print: [please include Day Month Year]. doi:10.1136/ thorax-2022-219784 ✓✓ When establishing local ambulatory treatment pathways, planning and coordination between with the emergency department, general medicine and respiratory medicine is vital. ✓✓ When performing chemical pleurodesis for the treatment of pneumothorax in adults, adequate analgesia should be provided before and after treatment. ✓✓ All treatment options should be discussed with the patient to determine their main priority, with consideration for the least invasive option. Optimal management after the resolution of a first episode of pneumothorax Good practice points ✓✓ Elective surgery may be considered for patients in whom recurrence prevention is deemed important (eg, at-­ risk professionals (divers, airline pilots, military personnel), or those who developed a tension pneumothorax at first episode). ✓✓ Elective surgery should be considered for patients with a second ipsilateral or first contralateral pneumothorax. ✓✓ Discharge and activity advice should be given to all patients post pneumothorax. Optimal management for spontaneous pneumothorax and ongoing air leak Good practice point ✓✓ If a patient is not considered fit for surgery, autologous blood pleurodesis or endobronchial therapies should be considered for the treatment of pneumothorax with persistent air leak in adults. Optimal surgical approach and surgical operation for pneumothorax management Recommendations ►► Video-­ assisted thoracoscopy access can be considered for surgical pleurodesis in the general management of pneumothorax in adults. (Conditional) ►► Thoracotomy access and surgical pleurodesis should be considered for the lowest level of recurrence risk required for specific (eg, high-­ risk) occupations. (Conditional) ►► Surgical pleurodesis and/or bullectomy should be considered for the treatment of spontaneous pneumothorax in adults. (Conditional) Investigation of the undiagnosed unilateral pleural effusion Radiology for diagnosing unilateral pleural effusions of benign aetiology Good practice points ✓✓ Imaging findings of a unilateral pleural effu- sion should be interpreted in the context of clinical history and knowledge of pleural fluid characteristics. Roberts ME, et al. Thorax 2023;0:1–34. doi:10.1136/thorax-2022-219784    1 BTS Guideline ✓✓ CT follow-­up should be considered for patients presenting Good practice points Image-guided versus non-image-guided intervention for suspected unilateral pleural effusion Recommendation subtype, including diagnostic sensitivity and predictive value for response to subsequent cancer therapies. This should be taken into consideration when planning the most suitable diagnostic strategy (eg, direct biopsies in those with a likely low cytological yield can be considered). ✓✓ Pleural fluid N-­ terminal prohormone brain natriuretic peptide (NT-­ proBNP) is useful when considering heart failure as a cause in unilateral pleural effusions but not superior to serum NT-­proBNP and therefore should not be ordered routinely. with pleural infection to exclude occult malignancy if there are ongoing symptoms, or other clinically concerning features. ✓✓ Positron emission tomography-­CT (PET-­CT) should not be used in the assessment of pleural infection. ►► Image-­guided thoracentesis should always be used to reduce the risk of complications. (Strong—by consensus) Optimal volume and container for pleural aspiration samples Recommendations ►► 25–50 mL of pleural fluid should be submitted for cytolog- ical analysis in patients with suspected malignant pleural effusion (MPE). (Strong—by consensus) ►► Pleural fluid should be sent in both plain and blood culture bottle tubes in patients with suspected pleural infection. (Strong—by consensus) Good practice points ✓✓ At least 25 mL, and where possible 50 mL, of pleural fluid ✓✓ ✓✓ ✓✓ ✓✓ ✓✓ should be sent for initial cytological examination. If volumes of ≥25 mL cannot be achieved, smaller volumes should be sent, but clinicians should be aware of the reduced sensitivity. If small volume aspirate (<25 mL) has been non-­ diagnostic, a larger volume should be sent, if achievable, except when there is high suspicion of a tumour type associated with low pleural fluid cytology sensitivity (especially mesothelioma). Pleural fluid samples should be processed by direct smear and cell block preparation. In patients with an undiagnosed pleural effusion where pleural infection is possible and volume of fluid sample available allows, microbiological samples should be sent in both white top containers and volumes of 5–10 mL inoculated into (aerobic and anaerobic) blood culture bottles. In cases where volume available does not allow 5–10 mL inoculation, volumes of 2–5 mL should be prioritised to blood culture bottles rather than a plain, sterile container. Pleural fluid tests (biomarkers) for diagnosing unilateral pleural effusion Recommendations ►► Pleural fluid cytology should be used as an initial diagnostic ►► ►► ►► ►► ►► 2 test in patients with suspected secondary pleural malignancy, accepting that a negative cytology should lead to consideration of further investigation. (Conditional) Pleural fluid biomarkers should not be used for diagnosing secondary pleural malignancy. (Conditional) In high prevalence populations, pleural fluid adenosine deaminase (ADA) and/or interferon gamma (IFN-­gamma) test(s) can be considered for diagnosing tuberculous pleural effusion. (Conditional) In low prevalence populations, pleural fluid ADA can be considered as an exclusion test for tuberculous pleural effusion. (Conditional) Tissue sampling for culture and sensitivity should be the preferred option for all patients with suspected tuberculous pleural effusion. (Strong—by consensus) Pleural fluid antinuclear antibody (ANA) should be considered to support a diagnosis of lupus pleuritis. (Conditional) ✓✓ The clinical utility of pleural fluid cytology varies by tumour Serum biomarkers for diagnosing unilateral pleural effusion Recommendation ►► Serum NT-­proBNP should be considered to support a diag- nosis of heart failure in patients with unilateral pleural effusion suspected of having heart failure. (Conditional) Good practice points ✓✓ Serum biomarkers should not currently be used to diagnose secondary pleural malignancy, pleural infection or autoimmune pleuritis. ✓✓ Serum biomarkers should not routinely be used to diagnose tuberculous pleural effusion, but may be considered in high prevalence areas. ✓✓ Serum biomarkers, including NT-­ proBNP, should not be used in isolation for diagnosing unilateral pleural effusion, as multiple conditions may co-­exist. Pleural biopsy for diagnosing unilateral pleural effusion Recommendations ►► Thoracoscopic or image-­guided pleural biopsy may be used depending on the clinical indication and local availability of techniques (including need for control of pleural fluid). (Strong) ►► Blind (non-­ image-­ guided) pleural biopsies should not be conducted. (Strong—by consensus) Pleural infection Predicting clinical outcomes of pleural infection Recommendation ►► Renal, age, purulence, infection source, dietary factors (RAPID) scoring should be considered for risk stratifying adults with pleural infection and can be used to inform discussions with patients regarding potential outcome from infection. (Conditional) Pleural fluid, or radiology parameters for determining which patients can be treated with intercostal drainage Recommendations ►► For patients with parapneumonic effusion (PPE) or suspected pleural infection, where diagnostic aspiration does not yield frank pus, immediate pH analysis should be performed. (Strong—by consensus) ►► For patients with suspected complex parapneumonic effusion (CPPE): – If pleural fluid pH is ≤7.2, this implies a high risk of CPPE or pleural infection and an intercostal drain (ICD) should be inserted if the volume of accessible pleural fluid on ultrasound makes it safe to do so. (Strong—by consensus) –– If pleural fluid pH is >7.2 and <7.4, this implies an intermediate risk of CPPE or pleural infection. Pleural Roberts ME, et al. Thorax 2023;0:1–34. doi:10.1136/thorax-2022-219784 BTS Guideline fluid lactate dehydrogenase should be measured and if >900 IU/L ICD should be considered, especially if other clinical parameters support CPPE (specifically ongoing temperature, high pleural fluid volume, low pleural fluid glucose (72 mg/dL ≤4.0 mmol/L), pleural contrast enhancement on CT or septation on ultrasound. (Strong— by consensus) –– If pleural fluid pH is ≥7.4, this implies a low risk of CPPE or pleural infection and there is no indication for immediate drainage. (Strong—by consensus) ►► In the absence of readily available immediate pleural fluid pH measurement, an initial pleural fluid glucose <3.3 mmol/L may be used as an indicator of high probability of CPPE/pleural infection and can be used to inform decision to insert ICD in the appropriate clinical context. (Strong— by consensus) Good practice points Good practice points Optimal surgical approach and surgical method for managing pleural infection Recommendation ✓✓ Clinicians should be mindful of alternative diagnoses that can mimic PPE with a low pH and potential for loculations (eg, rheumatoid effusion, effusions due to advanced malignancy/mesothelioma). ✓✓ Pleural fluid samples taken for pH measurement should not be contaminated with local anaesthetic or heparin (eg, by extruding all heparin from an arterial blood gas syringe) as this lowers pleural fluid pH. Delays in obtaining a pleural fluid pH or residual air in the sampling syringe will also increase pleural fluid pH. ✓✓ In patients where a clinical decision is made not to insert an ICD at initial diagnostic aspiration, regular clinical reviews should be performed and repeat thoracocentesis considered to ensure that CPPE is not missed. Optimal initial drainage strategy for established pleural infection Recommendation ►► Initial drainage of pleural infection should be undertaken using a small bore chest tube (14F or smaller). (Conditional—by consensus) Good practice points ✓✓ Due to the lack of supporting evidence, early surgical drainage under video-­assisted thoracoscopy surgery (VATS) or thoracotomy should not be considered over chest tube (‘medical’) drainage for the initial treatment of pleural infection. ✓✓ Due to lack of supporting evidence, medical thoracoscopy should not be considered as initial treatment for pleural infection. Intrapleural therapy for managing pleural infection Recommendations ►► Combination tissue plasminogen activator (TPA) and DNAse should be considered for the treatment of pleural infection, where initial chest tube drainage has ceased and leaves a residual pleural collection. (Conditional—by consensus) ►► Saline irrigation can be considered for the treatment of pleural infection when intrapleural TPA and DNase therapy or surgery is not suitable. (Conditional—by consensus) ►► Single agent TPA or DNAse should not be considered for treatment of pleural infection. (Conditional—by consensus) ►► Streptokinase should not be considered for treatment of pleural infection. (Conditional) Roberts ME, et al. Thorax 2023;0:1–34. doi:10.1136/thorax-2022-219784 ✓✓ Patient consent should be taken when using TPA and DNase as there is a potential risk of bleeding. ✓✓ When administering TPA plus DNase the regime should be 10 mg TPA twice daily (10 mg two times per day)+5 mg DNase two times per day for 3 days, based on randomised controlled trial data. Based on retrospective case series data, lower dose 5 mg TPA two times per day+5 mg DNase two times per day for 3 days may be as effective, and can be used if considered necessary. ✓✓ Reduced doses of TPA may be considered in those with a potentially higher bleeding risk (eg, those on therapeutic anticoagulation which cannot be temporarily ceased). ✓✓ For details on administration of intrapleural treatments, please refer to the British Thoracic Society (BTS) Clinical Statement on Pleural Procedures.1 ►► VATS access should be considered over thoracotomy for adults in the surgical management of pleural infection. (Conditional) Good practice points ✓✓ When selecting a surgical access for the treatment of pleural infection in adults, it is important to ensure the technique can facilitate optimal clearance of infected material and achieve lung re-­expansion where appropriate. ✓✓ Extent of surgery should be tailored according to patient and empyema stage when the lung is not completely trapped (drainage vs debridement). ✓✓ Decortication should be a decision that is individualised to the patient with a trapped lung based on assessment of patient fitness and empyema stage. Pleural malignancy Optimal imaging modality for diagnosing pleural malignancy Recommendations ►► Ultrasound may be a useful tool at presentation to support a diagnosis of pleural malignancy, particularly in the context of a pleural effusion, where appropriate sonographic skills are present. (Conditional) ►► CT allows assessment of the entire thorax, and positive findings may support a clinical diagnosis of pleural malignancy when biopsy is not an option (Conditional); however, a negative CT does not exclude malignancy. (Strong—by consensus) ►► PET-­CT can be considered to support a diagnosis of pleural malignancy in adults when there are suspicious CT or clinical features and negative histological results, or when invasive sampling is not an option. (Conditional) Good practice points ✓✓ Imaging can play an important role in the assessment of pleural malignancy, but results should be interpreted in the context of clinical, histological and biochemical markers. ✓✓ Features of malignancy may not be present on imaging at presentation. Unless a clear diagnosis is reached by other means (eg, biopsy), monitoring with follow-­up imaging of patients presenting with pleural thickening and unexplained unilateral pleural effusion should be considered to exclude occult malignancy. 3 BTS Guideline ✓✓ MRI has potential as a diagnostic tool in pleural malignancy. Its clinical value has yet to be determined and its use should be limited to highly selected cases and research studies at the present time. Systemic therapy for reducing the need for definitive pleural intervention for malignant pleural effusion Recommendation ►► Definitive pleural intervention should not be deferred until after systemic anticancer therapy (SACT). (Conditional—by consensus) Managing malignant pleural effusion Pleural aspiration with no pleurodesis agent versus talc slurry pleurodesis Recommendation ►► Management of MPE using talc pleurodesis (or another method) is recommended in preference to repeated aspiration especially in those with a better prognosis, but the relative risks and benefits should be discussed with the patient. (Conditional—by consensus) Good practice points ✓✓ Decisions on the best treatment modality should be based on patient choice. ✓✓ Informed decision-­making should include the role of inpa- tient versus ambulatory management and the potential risk of requiring further pleural interventions. Indwelling pleural catheter versus talc slurry pleurodesis Recommendation Good practice point ✓✓ Where a diagnostic procedure is being conducted at thora- coscopy (pleural biopsies), if talc pleurodesis is reasonable, this should be conducted during the same procedure via poudrage. Surgical pleurodesis, or surgical decortication versus talc slurry pleurodesis Recommendation ►► In selected patients considered fit enough for surgery, either surgical talc pleurodesis or medical talc slurry can be considered for the management of patients with MPE. The relative risks, benefits and availability of both techniques should be discussed with patients to individualise treatment choice. (Conditional—by consensus) Good practice points ✓✓ Informed decision-­making should include the role of surgery versus ambulatory management with an IPC for the management of MPE in selected patients. ✓✓ Decortication surgery may improve pleurodesis success in patients wih MPE with non-­ expandable lung, but the risks and benefits of IPC and surgical treatment should be discussed with patients, and treatment individualised according to circumstances (eg, fitness to undergo thoracic surgery). Managing malignant pleural effusion and non-expandable lung Pleural aspiration, talc slurry pleurodesis, talc poudrage pleurodesis, decortication surgery or indwelling pleural catheter Good practice points ✓✓ Decisions on treatment modality for MPE and non-­ ►► Patients without known non-­ expandable lung should be offered a choice of indwelling pleural catheter (IPC) or pleurodesis as first-­ line intervention in the management of MPE. The relative risks and benefits should be discussed with patients to individualise treatment choice. (Conditional) ✓✓ Good practice points ✓✓ The psychological implications and potential altered body image aspects of having a semi-­permanent tube drain in situ should not be underestimated and must be considered prior to insertion. ✓✓ All patients who have had an IPC inserted should be referred to the community nursing team on discharge for an early assessment of the wound site, symptom control, support with IPC drainage and removal of sutures. ✓✓ Patients and their relatives should be supported to perform community drainage and complete a drainage diary if they feel able to do so, to promote independence and self-­management. ✓✓ Complications such as infection refractory to community management, suspected drain fracture, loculations or blockage with persistent breathlessness should be referred back to the primary pleural team for further assessment. Thoracoscopy and talc poudrage pleurodesis versus chest drain and talc slurry pleurodesis Recommendation ►► Talc slurry or talc poudrage may be offered to patients with MPE to control fluid and reduce the need for repeated procedures. (Conditional) 4 ✓✓ ✓✓ ✓✓ ✓✓ expanded lung should be based on patient choice, with the relative risks and benefits of each modality discussed with the patient, but patients should be made aware of the limited evidence base regarding treatment options for non-­ expandable lung. IPCs are effective at controlling symptoms in non-­expandable lung and should be considered, but it may be appropriate to undertake pleural aspiration first to assess symptomatic response. Pleural aspiration may result in a need for multiple procedures so alternatives should be discussed with the patient. In patients with radiologically significant (>25%) non-­ expandable lung requiring intervention for a symptomatic MPE, current evidence suggests the use of an IPC rather than talc pleurodesis. In patients with MPE and <25% non-­expandable lung, talc slurry pleurodesis may improve quality of life, chest pain, breathlessness and pleurodesis rates. Decortication surgery may improve pleurodesis success in selected patients with MPE and non-­ expandable lung, but the risks and benefits of IPC and surgical treatment should be discussed with patients, and treatment individualised according to circumstances (eg, fitness to undergo thoracic surgery). Managing malignant pleural effusion and septated effusion (on radiology) Intrapleural enzymes versus surgery, or no treatment Good practice points ✓✓ Intrapleural fibrinolytics can be considered in highly selected symptomatic patients with MPE and septated effusion to try to improve breathlessness. Roberts ME, et al. Thorax 2023;0:1–34. doi:10.1136/thorax-2022-219784 BTS Guideline ✓✓ Intrapleural fibrinolytics may be used in patients with MPE and septated effusion and an IPC to improve drainage if flushing the IPC with normal saline or heparin saline does not improve drainage. ✓✓ Surgery can be considered for palliation of symptoms in a minority of patients with significantly septated MPE and associated symptoms and otherwise good prognosis and performance status. Managing malignant pleural effusion treated with an indwelling pleural catheter Symptom-based/conservative drainage versus daily drainage Recommendations ►► Where IPC removal is a priority, daily IPC drainages are recommended to offer increased rates of pleurodesis when compared with less frequent drainages of symptom-­guided or alternate drainage regimes. (Conditional) ►► Patients should be advised that they do not require daily drainage to control symptoms of breathlessness and chest pain if they wish to opt for a less intensive regime. (Strong— by consensus) Good practice points ✓✓ Decisions on the optimal drainage frequency should be based on patient choice. ✓✓ Informed decision-­making should include the explanation of the effect of drainage regimes on the patient-­centre outcomes such as breathlessness and the possibility of autopleurodesis during the disease course. ✓✓ Although daily drainage may result in earlier removal of IPC, there may be an associated cost associated with the increased number of drainage events (both to the healthcare system and to the patient). This has been addressed in a modelling study2 and should be considered. Intrapleural agents (talc or other pleurodesis agents) Recommendation ►► Instillation of talc via an IPC should be offered to patients with expandable lung where the clinician or patient deems achieving pleurodesis and IPC removal to be important. (Conditional—by consensus) Intrapleural chemotherapy versus systemic treatment for treating pleural malignancy Recommendation ►► Intrapleural chemotherapy should not be routinely used for the treatment of MPE. (Conditional—by consensus) Good practice point ✓✓ All patients of good performance status with metastatic malignancy should be considered for SACT as standard of care as per national guidelines. Using prognostic or predictive scores to provide prognostic information for patients with malignant pleural effusion Good practice points ✓✓ Clinicians may consider using a validated risk score for MPE, if the information is of use in planning treatments or in discussion with patients. ✓✓ Patients with pleural malignancy should be managed in a multidisciplinary way, including referral to specialist palliative care services where appropriate. Roberts ME, et al. Thorax 2023;0:1–34. doi:10.1136/thorax-2022-219784 Introduction Aim of the guideline This guideline aims to provide evidence-­based guidance on the investigation and management of: a. Spontaneous pneumothorax (SP) b. Undiagnosed unilateral pleural effusion c. Pleural infection d. Pleural malignancy Pleural disease is common and represents a major and rapidly developing subspecialty that presents to many different hospital services. Since the last British Thoracic Society (BTS) Guideline for pleural disease published in 2010,3–9 many high-­quality and practice changing studies, using patient-­centred outcomes, have been published. The paradigms for the investigation and management of pleural disease have therefore shifted. For example, ambulatory treatments have become much more prominent in the management of pleural disease. This guideline aims to capture this evidence and use it to answer the most important questions relevant to today’s practice. Intended users of the guideline and target patient populations The guideline will be of interest to UK-­based clinicians caring for adults with pleural disease, including chest physicians, respiratory trainees, specialist respiratory nurses, specialist lung cancer nurses, specialist pleural disease nurses, pathologists, thoracic surgeons, thoracic surgeon trainees, acute physicians, oncologists, emergency physicians, hospital practitioners, intensive care physicians, palliative care physicians, radiologists, other allied health professional and patients and carers. Guideline group members were selected to offer a broad geographical coverage of the UK and to include specialists with backgrounds in respiratory medicine, thoracic surgery, oncology, palliative care, nursing and pathology. The group included specialists from tertiary centres as well as district general hospitals. Scope of the guideline The guideline is specifically designed to answer important questions in the investigation and management of pleural disease in adults. Questions have been agreed by the whole guideline group. While as many important questions as possible have been included, there are areas that have not been covered. As this guideline covers four broad areas of pleural disease, the number of questions is limited by the practicalities of writing a guideline with a large scope that remains relevant and up to date at the point of publication and a workload manageable by the guideline group. This guideline covers adult patients in both inpatient and ambulatory settings, and questions from investigation to management in the inpatient and outpatient settings and by specialists of all disciplines involved in the care of patients with pleural disease. Areas not covered by the guideline Mesothelioma has been excluded from this guideline as this is already covered in the BTS Guideline for the investigation and management of pleural mesothelioma.10 Benign (non-­infectious, non-­pneumothorax) pleural disease and rare pleural diseases are also excluded. Guidance on pleural interventions are covered in the BTS Clinical Statement on Pleural Procedures.1 5 BTS Guideline Limitations of the guideline Healthcare providers need to use clinical judgement, knowledge and expertise when deciding whether it is appropriate to apply recommendations for the management of patients. The recommendations cited here are a guide and may not be appropriate for use in all situations. The guidance provided does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of each patient, in consultation with the patient and/or their guardian or carer. Members of the Guideline Development Group The Guideline Development Group (GDG) was chaired by three respiratory consultants—Professor Nick Maskell, Professor Najib Rahman and Dr Mark Roberts. The GDG had a wide membership and included colleagues from respiratory medicine, oncology, radiology, pathology and palliative medicine. Two patient representatives were recruited to the group, but due to personal circumstances both had to withdraw before completion of the guideline (August 2019 and July 2021). However, two further patient representatives were recruited at the end of the guideline process to review the final guideline and provide the patients’ perspective. Those on the group were not required to be BTS members and a full list of members can be seen in Appendix 2. Acknowledgements The co-­chairs would like to acknowledge the huge contributions of all guideline group members both to robust discussions during the meetings and sourcing, critically reviewing papers and formulating judgements. They would also like to specifically thank Dr Kirstie Opstad at BTS Head Office who has coordinated the whole process, performed searches and initial abstract filtering, supported the evidence review process and ensured consistency of presentation of the whole guideline. The GDG would like to thank Mr Richard Bremner, Mr Yannick Mouchilli, Mr Chris Smith and Dr Tim Wallington (patient representatives) for their helpful contributions during development of this guideline. Methodology of guideline production Establishment of Guideline Development Group The GDG was convened in July 2018, with the first meeting taking place in November 2018. The full GDG met 10 times during the development of the guideline and kept in close contact by teleconference and email throughout the process. Methodology This BTS Guideline uses Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology in the guideline development process. Full details are provided in the BTS Guideline production manual (https://www.brit-thoracic.​org.uk/quality-improvement/guidelines/). Table 1 6 Summary of key questions, outcomes and literature search Clinical questions were defined from the scope of the guideline and formulated into systematic review type questions (diagnostic accuracy, intervention or prognostic) according to the nature of the question. A full list of clinical questions for each section of the guideline is provided in Appendix 3. Patient-­centred outcomes were agreed by the group for each question. The Population, Intervention, Comparator and Outcome (PICO) framework, or equivalent for the diagnostic accuracy and prognostic review questions, formed the basis of the literature search. The initial searches were completed by the University of York (and latterly by BTS Head Office). Systematic electronic database searches were conducted to identify all papers that may be relevant to the guideline. For each question, the following databases were searched: Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE. The search strategy is available for review in online supplemental appendix 1. Literature review Two literature searches were conducted for the guideline, with the number of resulting abstracts from each search shown in table 1. Letters, conference papers and news articles were removed and criteria for initial screening of the abstracts were: • Does the study type match the study type criteria in the clinical question protocols? • Does the population match the clinical question population(s)? • Is the abstract in English? The remaining abstracts were screened by Professor Maskell, Professor Rahman and Dr Roberts and potentially relevant abstracts allocated to the relevant clinical questions. Abstracts were not rejected on the basis of the journal of publication, authorship or country of origin. GDG members were allocated to work on individual questions in small groups. Each abstract was read and at least two members agreed whether the abstract was ‘potentially relevant’ or ‘not relevant’ to the clinical question of interest. Abstracts were excluded if they were deemed ‘not relevant’ to the clinical question. Full papers were obtained for all abstracts assigned as ‘potentially relevant’. Each full paper was reviewed to assess if it addressed: i. The clinical question population; ii. The index test and reference standard (for diagnostic accuracy questions), the intervention and comparator (for intervention questions) or the exposure and referent (for prognostic questions); iii. The study type(s) defined in the clinical question protocol; iv. The clinical question outcome(s). Literature searches were conducted for each section of the guideline as follows Section  Search 1 date Spontaneous pneumothorax  20 March 2020   Number of abstracts 6325  18 May 2021  Search 2 date Number of abstracts 1260 Investigation of the undiagnosed unilateral pleural effusion  18 March 2019   6773  13 May 2021 2199 Pleural infection  17 December 2019   4138  20 May 2021 822 Pleural malignancy  03 April 2019 14 276  11 May 2021 3641 Roberts ME, et al. Thorax 2023;0:1–34. doi:10.1136/thorax-2022-219784 BTS Guideline Table 2 Evidence statement (GRADE) score definitions GRADE High Moderate Low Very low Definition ‍ ‍ High confidence that the true effect is close to the estimated effect. ‍ ‍ Moderate confidence that the true effect is close to the estimated effect. ‍ ‍ Low confidence that the true effect is close to the estimated effect. ‍ ‍ Very low confidence that the true effect is close to the estimated effect. Ungraded GRADE analysis not possible, but evidence deemed important by the GDG. GDG, Guideline Development Group; GRADE, Grading of Recommendations, Assessment, Development and Evaluation. GRADE analysis of the evidence Having generated evidence profiles for each of the clinical question, GDG question groups assessed the quality of the evidence using the GRADE methodology.12 Where meta-­analysis was not possible, but studies had used comparable methodologies and data reporting methods to allow an assessment of the quality of the data, a prognostic review GRADE analysis approach was used.13 14 Where GRADE analysis was not possible, but GDG members felt the evidence was important to be included in the evidence statements, these have been listed as (Ungraded). Definitions of the evidence statement (GRADE) scores are shown in table 2. Each clinical question review was reviewed by the full GDG during the regular meetings and consensus was reached in relation to the evidence summary. Development of recommendations Each full paper fulfilling the above criteria, and agreed by at least two members of the GDG, was ‘accepted’ for meta-­analysis and subsequent critical appraisal. In circumstances where there was little, or no supporting evidence that fulfilled the above criteria, the full paper inclusion strategy was widened to include evidence that partially addressed the clinical question. The second literature search (Search 2, table 1) was undertaken in May 2021 to capture additional published evidence while the guideline was in development prior to finalising the draft document. The additional abstracts were reviewed and allocated to the clinical questions as above. The full list of abstracts has been retained and is kept in an archive. The GDG proceeded to decide on the direction and strength of recommendations considering the quality of the evidence, the balance of desirable and undesirable outcomes and the values and preferences of patients and others. GRADE specifies two categories of strength for a recommendation, as shown in table 3. From the outset, it was acknowledged that there would be little high-­quality evidence for some of the clinical questions identified. In this instance, low-­ grade evidence was considered, along with the expert opinion of the GDG via informal consensus at the meetings. Good practice points (GPPs) were developed by informal consensus in areas where there was no quality evidence, but the GDG felt that some guidance, based on the clinical experience of the GDG, might be helpful to the reader. These are indicated as shown below. Systematic review of the evidence ✓✓ Advised best practice based on the clinical experience of the GDG. Each ‘accepted’ full paper underwent a systematic review. Data were extracted and meta-­analyses were performed for each clinical question on an outcome-­by-­outcome basis for intervention reviews, or an index test basis for diagnostic accuracy reviews. If meta-­analysis was not possible, for example, if there was insufficient evidence to perform a meta-­analysis, if data could not be extracted to input into a meta-­analysis, or data across studies had been published in different formats, all relevant supporting data were tabulated where possible. All full papers contributing towards a meta-­analysis underwent critical appraisal. For all non-­meta-­analysed data included in an evidence review, contributing papers also underwent critical appraisal where possible. Meta-­analyses and risk of bias assessments (critical appraisal) were performed in Review Manager V.5.3 and agreed by at least two members of the GDG. Diagnostic accuracy meta-­analyses involved an additional step which was performed by BTS Head Office using the MetaDTA app.11 Papers no longer deemed relevant were removed from the systematic review, with the decision to ‘exclude’ a paper solely based on it not fulfilling the clinical question criteria. Table 3 In some instances where evidence was limited, but GDG members felt that it was important to include a recommendation rather than a GPP, recommendations were agreed by informal consensus and categorised as (Strong—by consensus) or (Conditional—by consensus), based on the same criteria detailed in table 3. Cost-­effectiveness was not considered in detail as in-­depth economic analysis of recommendations falls outside of the scope of the BTS Guideline production process. However, the GDG were asked to be mindful of any potential economic barriers to the implementation of recommendations and GPPs. Research recommendations were also identified and are detailed in online supplemental appendix 2. Drafting the guideline The guideline group corresponded regularly by email and meetings of the full group were also held in the period between November 2018 and late 2020. A revised draft guideline document was circulated to all the relevant stakeholders for consultation in May 2022 followed by a period of online consultation. Explanation of the terminology used in BTS recommendations Strength Benefits and risks Implications Strong Recommended, so ‘offer’ Benefits appear to outweigh the risks (or vice versa) for the majority of the target group. Most service users would want to, or should receive this intervention. Conditional Suggested, so ‘consider’ Risks and benefits are more closely balanced, or there is more uncertainty in likely service users’ values and preferences. Service users should be supported to arrive at a decision based on their values and preferences. Roberts ME, et al. Thorax 2023;0:1–34. doi:10.1136/thorax-2022-219784 7 BTS Guideline The BTS Standards of Care Committee reviewed the ‘Investigation of the undiagnosed unilateral pleural effusion’ and ‘Pleural malignancy’ sections of the draft guideline in March 2020 and the full guideline in March 2022. Review of the guideline The guideline will be reviewed 5 years after the date of publication. Declarations of interests BTS declarations of interest forms have been completed by all members for each year they were part of the GDG. Details of these forms can be obtained from BTS Head Office. ‘Declarations of interests’ was a standing item at each GDG meeting. Stakeholders Stakeholders were identified at the start of the process. All stakeholder organisations were notified when the guideline was available for public consultation and a list is published in Appendix 4. Spontaneous pneumothorax Introduction The term pneumothorax describes air in the pleural space and is characterised as spontaneous in the absence of trauma or causative medical intervention. It is an increasing problem, with annual hospital admission rates rising from 9.1 to 14.1 per 100 000 population in the last 50 years, leading to substantial symptom burden and healthcare utilisation.15 16 Since the last version of the BTS pneumothorax guideline, published in 2010,5 there have been several large high-­quality clinical trials examining the management of SP.17–20 This guideline seeks to consolidate and update the pneumothorax guidelines in the light of this subsequent research using GRADE methodology and addresses the following clinical questions addressing adults with pneumothorax: • What is the best acute management for SP? (Question A1) • What is the optimal management of patients after resolution of first episode of pneumothorax? (Question A2) • What is the optimal management of patients with ongoing air leak? (Question A3) • What is the optimal surgical approach when performing surgery? (Question A4) • What is the optimal operation when performing surgery? (Question A5) Other areas of clinical importance that are not covered by the guideline questions are discussed in the ‘Other areas of clinical importance not covered by the clinical questions’ section, including traumatic and iatrogenic pneumothorax which are not specifically covered in the evidence review. Definitions and treatment principles Spontaneous pneumothoraces can be subclassified into primary spontaneous pneumothorax (PSP) in the absence of suspected lung disease or SSP in patients with established underlying lung disease. This distinction does not imply that patients with PSP have normal underlying lung parenchyma, with the majority demonstrating emphysema-­ like pulmonary changes on CT imaging, but instead reflects that current management and outcomes differ between the two patient groups. Patients can also be characterised as SSP if they are older than 50 years of age and have a smoking history. This categorisation reflects case 8 series data that this cohort may respond differently to needle aspiration (NA) than younger patients or non-­smokers. There have been substantial changes in recommendation in this BTS guideline compared with the 2010 guidelines. Size of pneumothorax is no longer an indication for invasive management (although does dictate the safety of conducting an intervention) and the use of chest drains is mainly centred around patients with high-­risk characteristics (Appendix 1, Pneumothorax pathway). The expanded evidence base now allows for a more personalised approach and greater patient choice. For details of interventions and how these are best conducted, please refer to the BTS Clinical Statement on Pleural Procedures for further details.1 What is the best acute management for spontaneous pneumothorax? Drainage of symptomatic pneumothorax, either with NA or intercostal chest drain (ICD) attached to an underwater seal is the current standard of care for PSP. There is ongoing debate over the respective benefits of NA over ICD, with multiple recent randomised trials comparing NA with ICD. Conservative management (ie, no active intervention) is often undertaken in patients with small or incidental PSP, but could be an alternative to NA or chest drain in patients with larger pneumothoraces. Ambulatory treatment using a purpose-­made device containing a one-­way valve, or Heimlich valve attached to chest drain has the potential to allow outpatient management of pneumothorax. A proportion of pneumothoraces will recur and both chemical pleurodesis via chest tube and thoracic surgery have the potential to reduce this risk. Thoracic surgery is often the treatment of choice for ongoing air leak, or for those with recurrent pneumothorax. However due to the risk of recurrence, trials have been performed to establish whether thoracic surgery could be offered as first presentation of pneumothorax. Conservative management, in which no intervention is undertaken and the patient is observed or reviewed repeatedly, is also a further alternate initial potential treatment strategy. Hence, the first clinical question is: A1 For adults with spontaneous pneumothorax, is conservative management, needle aspiration, ambulatory management, chemical pleurodesis or thoracic surgery better than intercostal drainage at improving clinical outcomes? A summary of the evidence review is shown in table 4 and the evidence statements (conclusions from the evidence review), recommendations and GPPs are presented below. The full evidence review is available in online supplemental appendix A1. Evidence statements Conservative management –– –– –– Length of hospital stay appears to be shorter following conservative management for the treatment of PSP in adults when compared with ICD. (Ungraded) Risk of pneumothorax recurrence appears to be greater following ICD when compared with conservative management for the treatment of PSP in adults. (Very low) There may be more complications experienced following ICD when compared with conservative management for the treatment of PSP in adults. (Ungraded) Needle aspiration –– Length of hospital stay appears to be shorter following NA for the treatment of PSP in adults when compared with ICD. (Low) Roberts ME, et al. Thorax 2023;0:1–34. doi:10.1136/thorax-2022-219784 BTS Guideline Table 4 Evidence review summary for ‘What is the best acute management for spontaneous pneumothorax?’ Clinical outcomes Summary of evidence review (treatment vs ICD) (95% CI) (Treatment) Conservative management NA Ambulatory management Chemical pleurodesis Thoracic surgery LOS Shortened LOS with conservative management* 2.55 days shorter (2.24 to 2.87) with NA (PSP)† 3.47 days shorter (2.20 to 4.73) with ambulatory management† No difference No difference Pneumothorax recurrence Lesser risk with conservative management (111/1000 (80 to 155)) compared with (179/1000)† No difference No difference Lesser risk with chemical pleurodesis (179/1000 (138 to 227)) compared with 320/100 (PSP and SSP)† Lesser risk with thoracic surgery (54/1000 (36 to 80)) compared with 298/1000 (PSP and SSP)† Re-­admission Not enough evidence Not reported No difference Not reported Not reported Need for further pleural procedures Not enough evidence Greater need with NA (626/1000 (544 to 719) compared with 240/1000 No difference Not reported Not reported Complications Reduced post-­treatment complications with conservative management* No overall difference in complications, but may be an reduction in subcutaneous emphysema following NA (9/1000 (1 to 70) compared with 92/1000) No difference Not enough evidence No difference Pain and breathlessness Not enough evidence Not enough evidence Not enough evidence Greater need for opioids Not reported with chemical pleurodesis* Quality of life Not enough evidence Not reported Not reported Not reported Not reported Mortality Not reported Not reported Not reported Not reported No difference *Meta-­analysis not possible, data reported in different formats. †Meta-­analysis results reported as per 1000 patients. ICD, intercostal drainage; LOS, length of stay; NA, needle aspiration; PSP, primary spontaneous pneumothorax; SSP, secondary spontaneous pneumothorax. –– –– –– There appears to be no difference in the rate of recurrence between NA or ICD for the treatment of PSP in adults. (Very low) There appears to be a greater need for further pleural procedures following NA when compared with ICD for the treatment of PSP in adults. (Very low) The risk of overall complications following NA or ICD appear to be the same for the treatment of PSP in adults (Very low), but there may an increased risk of subcutaneous emphysema following ICD. (Low) Ambulatory management –– –– There appears to be a reduction in the length of hospital stay following ambulatory management when compared with standard care for the treatment of PSP in adults. (Moderate) There appears to be no difference in the rate of pneumothorax recurrence, the rate of hospital re-­ admission, the need for pleural procedures or complications following ambulatory management or standard care for the treatment of PSP in adults. (Very low) pleurodesis may cause greater post-­ treatment mortality when compared with ICD alone for the treatment of pneumothorax in adults. (Very low) Thoracic surgery –– –– –– –– Length of hospital stay appears to be shorter following thoracic surgery, when compared with ICD, for the treatment of PSP in adults. (Very low) The rate of pneumothorax recurrence appears to be reduced following thoracic surgery, when compared with ICD, for the treatment of PSP in adults. (Very low) Pneumonia and persistent air leak complications appear to be greater following video-­assisted thoracic surgery (VATS), when compared with ICD, for the treatment of PSP in adults. (Very low) There appears to be no difference in the rate of mortality following thoracic surgery or ICD, for the treatment of pneumothorax in adults, with the mortality rate being very low for both treatments. (Very low) Recommendations Chemical pleurodesis –– –– –– –– There appears to be no difference in the length of hospital stay following chemical pleurodesis or ICD alone for the treatment of PSP in adults. (Low) The risk of pneumothorax recurrence appears to be lower following chemical pleurodesis when compared with ICD alone for the treatment of PSP or SSP in adults. (Very low) There appears to be a greater need for opioid pain relief following chemical pleurodesis when compared with ICD alone for the treatment of PSP in adults. (Moderate) Although there appears to be no difference in mortality rate at time of treatment (Very low), tetracycline chemical Roberts ME, et al. Thorax 2023;0:1–34. doi:10.1136/thorax-2022-219784 ►► Conservative management can be considered for the treatment of minimally symptomatic (ie, no significant pain or breathlessness and no physiological compromise) or asymptomatic PSP in adults regardless of size. (Conditional—by consensus) ►► Ambulatory management should be considered for the initial treatment of PSP in adults with good support, and in centres with available expertise and follow-­up facilities. (Conditional) ►► In patients not deemed suitable for conservative or ambulatory management, NA or tube drainage should be considered for the initial treatment of PSP in adults. (Conditional) 9 BTS Guideline ►► Chemical pleurodesis can be considered for the prevention of recurrent SSP in adults (eg, patients with severe chronic obstructive pulmonary disease who significantly decompensated in the presence of a pneumothorax, even during/after the first episode). (Conditional) ►► Thoracic surgery can be considered for the treatment of pneumothorax in adults at initial presentation if recurrence prevention is deemed important (eg, patients presenting with tension pneumothorax, or those in high-­risk occupations). (Conditional) Good practice points ✓✓ When establishing local ambulatory treatment pathways, planning and coordination between with the emergency department, general medicine and respiratory medicine is vital. ✓✓ When performing chemical pleurodesis for the treatment of pneumothorax in adults, adequate analgesia should be provided before and after treatment. ✓✓ All treatment options should be discussed with the patient to determine their main priority, with consideration for the least invasive option. What is the optimal management of patients after resolution of a first episode of pneumothorax? Recurrence following SP is a frequent concern and overall occurs in 32% of patients after a single episode of PSP21 and 13%–39% after a first episode of SSP.16 Current usual practice in the UK is to consider surgical intervention after the second episode of an SP to reduce subsequent further recurrences. The aim of the next question was to assess if there was evidence to support the use of surgical intervention (surgical pleurodesis or bullectomy) at an earlier stage in an elective context, prior to the first recurrence, comparing against non-­surgical techniques (non-­surgical talc or conservative management): A2 What is the optimal management of patients after resolution of a first episode of pneumothorax? The evidence statement and GPPs are presented below; and the full evidence review is presented in online supplemental appendix A2. Evidence statement emergency department immediately should they develop further breathlessness. It is recommended that all patients should be followed up by a respiratory physician to ensure resolution of the pneumothorax, to institute optimal care of any underlying lung disease, to explain the risk of recurrence and the possible later need for surgical intervention and to reinforce lifestyle advice on issues such as smoking and air travel. Those managed by observation alone or by NA should be advised to return for a follow-­up chest X-­ray (CXR) after 2–4 weeks to monitor resolution. Patients managed with an ambulatory device may need to be seen more frequently to monitor for complications and prompt removal at resolution. Patients with a persistent closed pneumothorax (ie, no pleural breach or communication across the chest wall, and incompletely resolved on CXR) should not travel on commercial flights until complete radiological resolution. An exception to this is the very rare case of a loculated or chronic localised air collection which has been very carefully evaluated. In those with resolved pneumothorax confirmed radiologically (ie, at least CXR), patients can fly 7 days after the X-­ray demonstrates full resolution (the rationale for waiting 7 days is to exclude early recurrence). The BTS Clinical Statement on air travel for passengers with respiratory disease (2022) addresses this with greater detail.22 After a pneumothorax, scuba diving (ie, with pressurised gas tanks) should be discouraged permanently unless a very secure definitive prevention strategy has been performed such as surgical pleurectomy. The BTS Guidelines on respiratory aspects of fitness for diving deal with this in greater detail.23 Smoking influences the risk of recurrence so cessation should be advised. What is the optimal management of patients with ongoing air leak? Most spontaneous pneumothoraces will resolve once the air leak has ceased. However, some patients will have persistent/ prolonged air leak and/or failure of the lung to re-­expand on CXR. There are several treatment options available including application of thoracic suction, converting to larger-­bore chest drain, blood patch or chemical pleurodesis, endobronchial valves or thoracic surgery and the next clinical question asked if any of these treatment options give better clinical outcomes than ongoing chest tube drainage alone: A3 In adults with spontaneous pneumothorax and ongoing air leak (excluding postsurgical patients), which treatments are better than ongoing chest tube drainage alone at improving clinical outcomes? There was no evidence relevant to the review. Recommendations Due to the lack of supporting evidence, no recommendations can be made on the role of elective surgery at an earlier stage to prevent recurrence. Good practice points ✓✓ Elective surgery may be considered for patients in whom recurrence prevention is deemed important (eg, at-­risk professionals (divers, airline pilots, military personnel), or those who developed a tension pneumothorax at first episode). ✓✓ Elective surgery should be considered for patients with a second ipsilateral or first contralateral pneumothorax. ✓✓ Discharge and activity advice should be given to all patients post pneumothorax. Discharge advice, flying and activity All patients discharged after active treatment or otherwise should be given verbal and written advice to return to the accident and 10 Due to a lack of evidence, not all treatment strategies were reviewed, but the evidence statements and GPPs are presented below and the full evidence review is available in online supplemental appendix A3. Evidence statements –– –– –– Length of hospital stay appears to be shorter following autologous blood pleurodesis treatment, regardless of delivery method, for pneumothorax and persistent air leak in adults when compared with chest drainage alone. (Ungraded) There was no evidence to suggest that the application of suction is beneficial to treat pneumothorax and persistent air leak in adults. Limited evidence suggests that endobronchial therapies may have the potential to treat pneumothorax and persistent air leak. (Ungraded) Roberts ME, et al. Thorax 2023;0:1–34. doi:10.1136/thorax-2022-219784 BTS Guideline Table 5 Evidence review summary for ‘What is the optimal surgical approach when performing surgery?’ Clinical outcome Summary of evidence review (VATS vs thoracotomy) (95% CI) Length of hospital stay 3.66 days shorter (3.40 to 3.91) with VATS* Pneumothorax recurrence Slightly higher with VATS (31/1000 (23 to 41) compared with 15/1000) but low with both surgical techniques* Need for further treatment Slightly higher with VATS (59/1000 (37 to 94) compared with 31/1000)* Complications Reduced with VATS (99/1000 (88 to 112) compared with 138/1000)* Pain and breathlessness Reduced need for postoperative analgesia with VATS† Duration of air leak Not reported in any study Quality of life Not reported in any study Mortality No difference *Meta-­analysis results reported as per 1000 patients. †Meta-­analysis not possible, data reported in different formats. VATS, video-­assisted thoracoscopy surgery. Recommendations There is insufficient evidence to make any recommendations on the best treatment method for pneumothorax and persistent air leak in adults. Good practice point ✓✓ If a patient is not considered fit for surgery, autologous blood pleurodesis or endobronchial therapies should be considered for the treatment of pneumothorax with persistent air leak in adults (please refer to the BTS Clinical Statement on Pleural Procedures).1 Wha