Indwelling pleural catheters: evidence for and management.

The incidence of pleural disease is increasing, and pleural medicine is increasingly recognised as a subspecialty within respiratory medicine. This often requires additional training time. Once underresearched, the last decade has seen an explosion in evidence related to the management of pleural disease. One of the cornerstones of pleural effusion management is the insertion of an indwelling pleural catheter. This allows patient-centred outpatient management and now has a robust evidence base. This article summarises evidence as well serves as a practical guide to the management of any complications related to an indwelling pleural catheter that might present on an acute take.

Lung ultrasound in the COVID-19 pandemic.

Lung ultrasound has been described for over a decade and international protocols exist for its application. It is a controversial area among pulmonologists and has had more uptake with emergency as well as intensive care physicians. We discuss the basics and evidence behind the use of lung ultrasound in respiratory failure, and what role we see it playing in the current 2019 novel coronavirus pandemic.

Radiological approach to cavitary lung lesions.

Cavitary lesions in the lung are not an uncommon imaging encounter and carry a broad differential diagnosis that includes a wide range of pathological conditions from cancers, infections/inflammatory processes to traumatic and congenital lung abnormalities. In this review article, we describe a comprehensive approach for evaluation of cavitary lung lesions and discuss the differential diagnosis in the light of radiological findings.

Use of zonal distribution of lung crackles during inspiration and expiration to assess disease severity in idiopathic pulmonary fibrosis.

PURPOSE OF THE STUDY: To measure the number and distribution of crackles in patients with idiopathic pulmonary fibrosis (IPF) and assess how this relates to measures of disease severity. STUDY DESIGN: Fourteen patients with IPF had both the number of crackles per litre of lung volume and lung function measured every 3 months for 1 year. Crackle counts were expressed according to position (upper and lower zones) and whether they occurred during inspiration and expiration. RESULTS: At baseline, crackle count per unit volume was higher at the bases than the apices and higher during inspiration than during expiration. There was a significant relationship between lung function and number of crackles per unit volume. Upper zone crackles during inspiration (crackle count vs forced vital capacity (FVC): r=0.69, p=0.007) and lower zone crackles during expiration (crackle count vs FVC: r=0.55, p=0.04) demonstrated the strongest relationship with lung function. CONCLUSIONS: Number and distribution of crackles in IPF relate to physiological measures of disease severity. Inspiratory lower zone crackles were universal and extensive but the presence, hence, development of inspiratory upper zone crackles and expiratory lower zone crackles correlated with measures of poorer lung function. The presence or appearance of these assessed using chest auscultation provides a clinician with simple measure of disease severity, and possibly progression, prompting further physiological assessment and review of treatment.

Serotype 3 Experimental Human Pneumococcal Challenge (EHPC) study protocol: dose ranging and reproducibility in a healthy volunteer population (challenge 3).

INTRODUCTION: Since the introduction of pneumococcal conjugate vaccines, pneumococcal disease rates have declined for many vaccine-type serotypes. However, serotype 3 (SPN3) continues to cause significant disease and is identified in colonisation epidemiological studies as one of the top circulating serotypes in adults in the UK. Consequently, new vaccines that provide greater protection against SPN3 colonisation/carriage are urgently needed. The Experimental Human Pneumococcal Challenge (EHPC) model is a unique method of determining pneumococcal colonisation rates, understanding acquired immunity, and testing vaccines in a cost-effective manner. To enhance the development of effective pneumococcal vaccines against SPN3, we aim to develop a new relevant and safe SPN3 EHPC model with high attack rates which could be used to test vaccines using small sample size. METHODS AND ANALYSIS: This is a human challenge study to establish a new SPN3 EHPC model, consisting of two parts. In the dose-ranging/safety study, cohorts of 10 healthy participants will be challenged with escalating doses of SPN3. If first challenge does not lead into colonisation, participants will receive a second challenge 2 weeks after. Experimental nasopharyngeal (NP) colonisation will be determined using nasal wash sampling. Using the dose that results in ≥50% of participants being colonised, with a high safety profile, we will complete the cohort with another 33 participants to check for reproducibility of the colonisation rate. The primary outcome of this study is to determine the optimal SPN3 dose and inoculation regime to establish the highest rates of NP colonisation in healthy adults. Secondary outcomes include determining density and duration of experimental SPN3 NP colonisation and characterising mucosal and systemic immune responses to SPN3 challenge. ETHICS AND DISSEMINATION: This study is approved by the NHS Research and Ethics Committee (reference 22/NW/0051). Findings will be published in peer-reviewed journals and reports will be made available to participants.

Radiograph accelerated detection and identification of cancer in the lung (RADICAL): a mixed methods study to assess the clinical effectiveness and acceptability of Qure.ai artificial intelligence software to prioritise chest X-ray (CXR) interpretation.

INTRODUCTION: Diagnosing and treating lung cancer in early stages is essential for survival outcomes. The chest X-ray (CXR) remains the primary screening tool to identify lung cancers in the UK; however, there is a shortfall of radiologists, while demand continues to increase. Image analysis by machine-learning software has the potential to support radiology workflows with a focus on immediate triage of suspicious X-rays. The RADICAL study will evaluate Qure.ai's 'qXR' software in reducing reporting time for suspicious X-rays in NHS Greater Glasgow & Clyde. METHODS AND ANALYSIS: This is a stepped-wedge cluster-randomised study consisting of a retrospective technical evaluation and prospective clinical effectiveness study alongside the assessment of acceptability via qualitative work and evaluation of cost-effectiveness via a cost utility analysis. The primary objective is to assess the clinical effectiveness of qXR to prioritise patients suspected with lung cancer on CXR for follow-up CT. Secondary objectives will look at the utility, safety, technical performance, health economics and acceptability of the intervention. The study period is 24 months, consisting of an initial 12 month data collection period and a 12 month follow-up period. All the standard care CXRs from outpatient and primary care requests will be securely transmitted to Qure.ai software 'qXR' for interpretation. Images with features of cancer will be flagged as 'Urgent Suspicion of Cancer' and be prioritised for radiologist review within the existing reporting workflow. ETHICS AND DISSEMINATION: The study will follow the principles of Good Clinical Practice. The protocol was granted REC approval in August 2023 from North West-Greater Manchester West Research Ethics Committee (REC 23/NW/0211). This study was registered on clinicaltrials.gov (NCT06044454). An interim report will be produced for use by the Scottish Government. The results from this study will be presented at artificial intelligence, radiology and respiratory meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT06044454.

Association between obstructive sleep apnoea and cancer: a cross-sectional, population-based study of the DISCOVERY cohort.

OBJECTIVES: Nocturnal hypoxia in obstructive sleep apnoea (OSA) is a potential risk factor for cancer. We aimed to investigate the association between OSA measures and cancer prevalence in a large national patient cohort. DESIGN: Cross-sectional study. SETTINGS: 44 sleep centres in Sweden. PARTICIPANTS: 62 811 patients from the Swedish registry for positive airway pressure (PAP) treatment in OSA, linked to the national cancer registry and national socioeconomic data (the course of DIsease in patients reported to Swedish CPAP, Oxygen and VEntilator RegistrY cohort). OUTCOME MEASURES: After propensity score matching for relevant confounders (anthropometric data, comorbidities, socioeconomic status, smoking prevalence), sleep apnoea severity, measured as Apnoea-Hypopnoea Index (AHI) or Oxygen Desaturation Index (ODI), were compared between those with and without cancer diagnosis up to 5 years prior to PAP initiation. Subgroup analysis for cancer subtype was performed. RESULTS: OSA patients with cancer (n=2093) (29.8% females, age 65.3 (SD 10.1) years, body mass index 30 (IQR 27-34) kg/m2) had higher median AHI (n/hour) (32 (IQR 20-50) vs 30 (IQR 19-45), n/hour, p=0.002) and median ODI (n/hour) (28 (IQR 17-46) vs 26 (IQR 16-41), p<0.001) when compared with matched OSA patients without cancer. In subgroup analysis, ODI was significantly higher in OSA patients with lung cancer (N=57; 38 (21-61) vs 27 (16-43), p=0.012)), prostate cancer (N=617; 28 (17-46) vs 24, (16-39)p=0.005) and malignant melanoma (N=170; 32 (17-46) vs 25 (14-41),p=0.015). CONCLUSIONS: OSA mediated intermittent hypoxia was independently associated with cancer prevalence in this large, national cohort. Future longitudinal studies are warranted to study the potential protective influence of OSA treatment on cancer incidence.

Trends in antineoplastic drug use, cost and prescribing patterns among patients with lung cancer in nine major cities of China, 2016-2020: a retrospective observational study based on inpatient and outpatient hospital data.

OBJECTIVES: It is unclear whether the use of antineoplastic drugs for patients with lung cancer in China has changed after the implementation of the national drug price negotiation in 2016 and continual update of clinical guidelines. This study aims to evaluate the trends in antineoplastic drug use, cost and prescribing patterns among patients with lung cancer in major cities of China. DESIGN: We conducted a retrospective observational study using data from January 2016 to December 2020. SETTING: This study used prescription records based on inpatient and outpatient hospital data from 97 hospitals in 9 major cities of China. PARTICIPANTS: A total of 218 325 antineoplastic drug prescriptions in patients with lung cancer were retrospectively collected from the Hospital Prescription Analysis Cooperative Project during the study period. OUTCOME MEASURES: Trends in antineoplastic drug use, cost and prescribing patterns among patients with lung cancer. RESULTS: The yearly antineoplastic prescriptions increased by 85.6% from 28 594 in 2016 to 53 063 in 2020 (Z=1.71, p=0.086). Significant increases were seen in the prescriptions for protein kinase inhibitors (PKIs) and monoclonal antibodies (mAbs), whereas significant decreases were observed in antimetabolites, plant alkaloids and platinum compounds. The yearly cost increased progressively by 145.0% from ¥113.6 million in 2016 to ¥278.3 million in 2020 (Z=2.20, p=0.027). The top three anticancer drug classes in terms of total cost were PKIs, antimetabolites and mAbs. In prescribing patterns of antineoplastic agents for lung cancer, monotherapy, and triple or more drug combinations gradually increased, while dual combinations decreased significantly from 30.8% to 19.6%. CONCLUSIONS: Prescription practices among patients with lung cancer in China underwent major changes during the study period. The observed trends can aid in understanding the present medication use status of patients with lung cancer in China and provide information for future drug management.

Effects of preoperative mildly elevated pulmonary artery systolic pressure on the incidence of perioperative adverse events undergoing thoracoscopic lobectomy: an observational cohort study protocol.

INTRODUCTION: Echocardiography provides a non-invasive estimation of pulmonary artery systolic pressure (PASP) and is the first diagnostic test for pulmonary hypertension. Recent studies have demonstrated that PASP of more than 30 mm Hg related to increased mortality and morbidity. However, perioperative risks and management for patients with mildly elevated PASP are not well established. This study aims to explore the association between mildly elevated PASP and perioperative adverse outcomes. METHODS AND ANALYSIS: This will be a retrospective cohort study conducted at Shanghai Pulmonary Hospital in Shanghai, China. Eligible patients are adults (≥18 years) who performed preoperative echocardiography and followed thoracoscopic lobectomy. Our primary objective is to determine the effect of preoperative mildly elevated PASP on the incidence of hypotension during surgery. Whether mildly elevated PASP is related to other perioperative adverse events (including hypoxaemia, myocardial injury, new-onset atrial fibrillation, postoperative pulmonary complications, 30-day readmission and 30-day mortality) will be also analysed. An estimated 2300 patients will be included. ETHICS AND DISSEMINATION: The study has been approved by the institutional review board of Shanghai Pulmonary Hospital (approval No: 2022LY1143). The research findings intend to be published in peer-reviewed scientific publications. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2200066679).

Observational cohort study to validate SEARCH, a novel hierarchical algorithm to define long-term outcomes after pulmonary embolism.

BACKGROUND: Chronic dyspnoea and exercise impairment are common after acute pulmonary embolism (PE) but are not defined and quantified sufficiently to serve as outcomes in clinical trials. The planned project will clinically validate a novel method to determine discrete, clinically meaningful diagnoses after acute PE. The method uses an algorithm entitled SEARCH, for symptom screen, exercise testing, arterial perfusion, resting echocardiography, confirmatory imaging and haemodynamic measurements. SEARCH is a stepwise algorithm that sorts patients by a hierarchical series of dichotomous tests into discreet categories of long-term outcomes after PE: asymptomatic, post-PE deconditioning, symptoms from other causes, chronic thromboembolism with ventilatory inefficiency, chronic thromboembolism with small stroke volume augmentation, chronic thromboembolic disease and chronic thromboembolic pulmonary hypertension. METHODS: The project will test the inter-rater reliability of the SEARCH algorithm by determining whether it will yield concordant post-PE diagnoses when six independent reviewers review the same diagnostic data on 150 patients evaluated at two time points after PE. The project will also determine whether the post-PE diagnoses are stable, according to the SEARCH algorithm, between the first evaluation and the subsequent one 6 months later. IMPLICATIONS: Validation of the SEARCH algorithm would offer clinicians a straightforward method to diagnose post-PE conditions that are rarely distinguished clinically. Their categorisation and definition will allow post-PE conditions to be used as endpoints in clinical trials of acute PE treatment. TRIAL REGISTRATION NUMBER: NCT05568927.

High versus low positive end-expiratory pressure setting in patients receiving veno-venous extracorporeal membrane oxygenation support for severe acute respiratory distress syndrome: study protocol for the multicentre, randomised ExPress SAVER Trial.

INTRODUCTION: While limiting the tidal volume to 6 mL/kg during veno-venous extracorporeal membrane oxygenation (V-V ECMO) to ameliorate lung injury in patients with acute respiratory distress syndrome (ARDS) is widely accepted, the best setting for positive end-expiratory pressure (PEEP) is still controversial. This study is being conducted to investigate whether a higher PEEP setting (15 cmH2O) during V-V ECMO can decrease the duration of ECMO support needed in patients with severe ARDS, as compared with a lower PEEP setting. METHODS AND ANALYSIS: The study is an investigator-initiated, multicentre, open-label, two-arm, randomised controlled trial conducted with the participation of 20 intensive care units (ICUs) at academic as well as non-academic hospitals in Japan. The subjects of the study are patients with severe ARDS who require V-V ECMO support. Eligible patients will be randomised equally to the high PEEP group or low PEEP group. Recruitment to the study will continue until a total of 210 patients with ARDS requiring V-V ECMO support have been randomised. In the high PEEP group, PEEP will be set at 15 cmH2O from the start of V-V ECMO until the trials for liberation from V-V ECMO (or until day 28 after the allocation), while in the low PEEP group, the PEEP will be set at 5 cmH2O. Other treatments will be the same in the two groups. The primary endpoint of the study is the number of ECMO-free days until day 28, defined as the length of time (in days) from successful libration from V-V ECMO to day 28. The secondary endpoints are mortality on day 28, in-hospital mortality on day 60, ventilator-free days during the first 60 days and length of ICU stay. ETHICS AND DISSEMINATION: Ethics approval for the trial at all the participating hospitals was obtained on 27 September 2022, by central ethics approval (IRB at Hiroshima University Hospital, C2022-0006). The results of this study will be presented at domestic and international medical congresses, and also published in scientific journals. TRIAL REGISTRATION NUMBER: The Japan Registry of Clinical Trials jRCT1062220062. Registered on 28 September 2022. PROTOCOL VERSION: 28 March 2023, version 4.0.

Argentine consensus recommendations for lung cancer screening programmes: a RAND/UCLA-modified Delphi study.

BACKGROUND: Lung cancer (LC) screening improves LC survival; the best screening method in terms of improving survival is low-dose CT (LDCT), outpacing chest X-ray and sputum cytology. METHODS: A consensus of experts in Argentina was carried out to review the literature and generate recommendations for LC screening programmes. A mixed-method study was used with three phases: (1) review of the literature; (2) modified Delphi consensus panel; and (3) development of the recommendations. The Evidence to Decision (EtD) framework was used to generate 13 evaluation criteria. Nineteen experts participated in four voting rounds. Consensus among participants was defined using the RAND/UCLA method. RESULTS: A total of 16 recommendations scored ≥7 points with no disagreement on any criteria. Screening for LC should be performed with LDCT annually in the population at high-risk, aged between 55 and 74 years, regardless of sex, without comorbidities with a risk of death higher than the risk of death from LC, smoking ≥30 pack-years or former smokers who quit smoking within 15 years. Screening will be considered positive when finding a solid nodule ≥6 mm in diameter (or ≥113 mm3) on baseline LDCT and 4 mm in diameter if a new nodule is identified on annual screening. A smoking cessation programme should be offered, and cardiovascular risk assessment should be performed. Institutions should have a multidisciplinary committee, have protocols for the management of symptomatic patients not included in the programme and distribute educational material. CONCLUSION: The recommendations provide a basis for minimum requirements from which local institutions can develop their own protocols adapted to their needs and resources.

Standard patient training versus Vik-Asthme chatbot-guided training: 'AsthmaTrain' - a protocol for a randomised controlled trial for patients with asthma.

INTRODUCTION: Therapeutic education for patients with asthma has been shown to reduce asthma morbidity. The high availability of smart phones provides the opportunity to furnish patient training via specifically designed chatbot applications. The goal of this protocol is to perform a first pilot comparison of traditional face to face versus chatbot-guided patient therapeutic education programmes for patients with asthma. METHODS AND ANALYSIS: Eighty adult patients with a physician-confirmed diagnosis of asthma will be enrolled in a two-parallel-arm, randomised (1:1) controlled pilot trial. A single-Zelen consent procedure is deployed to first enrol all participants in the comparator arm, that is, the standard patient therapeutic education programme at the University Hospitals of Montpellier, France. This means of patient therapeutic education is based on reoccurring interviews and discussion with qualified nursing staff as per usual care. Following baseline data acquisition, randomisation will be performed. Those patients randomised to the comparator arm will not be informed of the second arm. Those patients randomised to the experimental arm will be proposed access to a specifically designed chatbot (Vik-Asthme) as the second tested means of patient training (refusals continue with standard training, though analysed as intention to treat). The primary outcome is change in the total Asthma Quality of Life Questionnaire score at the end of follow-up (6 months). Secondary outcomes cover asthma control, spirometry, general health status, programme adherence and burden for medical staff, exacerbations and medical resource use (medications, consults, emergency visits, hospitalisation and intensive care). ETHICS AND DISSEMINATION: This study ('AsthmaTrain' protocol version 4-20220330) has been approved by the Committee for the Protection of Persons Ile-de-France VII on 28 March 2022 (reference number 21.03617.000059). Enrolment began on 24 May 2022. Results will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05248126.

Patient financial incentives to improve asthma management: a systematic review.

OBJECTIVES: The objectives of this systematic review are to identify studies that assess the effectiveness of patient-directed financial incentive interventions to improve asthma management behaviours, determine overall effectiveness of financial incentives, identify design characteristics of effective interventions and assess the impact on longer-term outcomes in the context of asthma. DESIGN: Systematic review with narrative synthesis. DATA SOURCES: Electronic databases (MEDLINE, Embase, Global Health, PsycINFO, CINAHL, PubMed and Web of Science) and grey literature sources (NHS Digital, CORE, ProQuest, Clinical Trials Register and EU Clinical Trials Register) were searched in November 2021 and updated March 2023. ELIGIBLITY CRITERIA: Eligible articles assessed financial incentives to improve asthma management behaviours (attendance at appointments, medication adherence, tobacco smoke/allergen exposure, inhaler technique and asthma education) for patients with asthma or parents/guardians of children with asthma. Eligible study design included randomised controlled, controlled or quasi-randomised trials and retrospective/prospective cohort, case-controlled or pilot/feasibility studies. SYNTHESIS: A narrative synthesis was conducted; eligible studies were grouped by asthma management behaviours and financial incentive framework domains. RESULTS: We identified 4268 articles; 8 met the inclusion criteria. The studies were from the USA (n=7) and the UK (n=1). Asthma management behaviours included attendance at appointments (n=4), reduction in smoke exposure (n=1) and medication adherence (n=3). Five studies demonstrated positive behaviour change, four of which were significant (attendance at appointments (n=3) showed significant differences between intervention and control: 73% and 49% in one study, 46.3% and 28.9% in another, and 35.7% and 18.9%, respectively; medication adherence (n=1) showed significant change from 80% during intervention to 33% post intervention). These four significant studies used 'positive gain', 'certain', 'fixed' financial incentives of smaller magnitude, given for 'all' instances of behaviour. CONCLUSION: There is some evidence that patient-directed financial incentives improve asthma management behaviours. However, in view of the wide heterogeneity in study design and measured outcomes, determining overall effectiveness was challenging. PROSPERO REGISTRATION NUMBER: CRD42021266679.

Protocol for a mixed-method study to assess chronic cough in patients with renal cell carcinoma: the prevalence, impact on quality of life, trigger and potential clinical application of chronic cough as an early screening tool in patients with kidney cancer.

INTRODUCTION: Cough as a symptom of renal cell carcinoma (RCC) was first described by Creevy in 1935, and despite one (unpublished) study suggesting it may affect 31% of these patients, as well as cough being discussed in forums for patients with kidney cancer, few clinicians are aware of this association. The cough has been described as unusual in nature, resolving rapidly after treatment with nephrectomy/embolisation but returning if the tumour recurs. METHODS AND ANALYSIS: A prospective study using a questionnaire will identify the prevalence of cough in patients with suspected or confirmed RCC attending the Specialist Centre for Kidney Cancer (London, UK). A longitudinal study in a representative sample of these patients, using EQ-5D-5L and Leicester Cough Questionnaires, together with the use of semi-structured interviews with patients, will identify the impact of cough in addition to having a diagnosis of suspected or confirmed RCC on quality of life. To investigate cough mechanisms, a pilot study using cough hypersensitivity testing will be performed on patients with RCC, with and without a cough. Clinical samples (urine, blood, phlegm and breath condensate) from patients with RCC, with and without a cough, will be collected and analysed for the presence of substances known to trigger or enhance cough and compared with the results obtained from healthy volunteers. ETHICS AND DISSEMINATION: Ethical approval has been granted (UK HR REC 22/PR/0791 dated 25/08/2022). Study outputs will be presented and published nationally and internationally at relevant conferences. This study will establish the prevalence of cough in patients with suspected or confirmed kidney cancer and support the education of clinicians to consider this diagnosis in patients with chronic cough (eg, recommending protocols to include both kidneys when investigating respiratory symptoms with chest CT scans). If substances known to trigger or enhance cough are identified and elevated in clinical samples, this research could offer potential targets for treatment for this distressing symptom. TRIAL REGISTRATION NUMBER: NIHR CRN portfolio CPMS ID:53 372.

Prevalence and impact of exercise-induced laryngeal obstruction in asthma: a study protocol for a cross-sectional and longitudinal study.

INTRODUCTION: Exercise-induced laryngeal obstruction (EILO) and exercise-induced asthma can cause troublesome respiratory symptoms that can be difficult to distinguish between. Further, there is now a growing appreciation that the two conditions may coexist, complicating the interpretation of symptoms. The primary aim of this study is to investigate the prevalence of EILO in patients with asthma. Secondary aims include evaluation of EILO treatment effects and investigation of comorbid conditions other than EILO in patients with asthma. METHODS AND ANALYSIS: The study will be conducted at Haukeland University Hospital and Voss Hospital in Western Norway, and enrol 80-120 patients with asthma and a control group of 40 patients without asthma. Recruitment started in November 2020, and data sampling will continue until March 2024. Laryngeal function will be assessed at baseline and at a 1-year follow-up, using continuous laryngoscopy during high-intensity exercise (CLE). Immediately after the EILO diagnosis is verified, patients will be treated with standardised breathing advice guided by visual biofeedback from the laryngoscope video screen. The primary outcome will be the prevalence of EILO in patients with asthma and control participants. Secondary outcomes include changes in CLE scores, asthma-related quality of life, asthma control and number of the asthma exacerbations, as assessed between baseline and the 1-year follow-up. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Regional Committee for Medical and Health Research Ethics, Western Norway, (ID number 97615). All participants will provide signed informed consent before enrolment. The results will be presented in international journals and conferences. TRIAL REGISTRATION NUMBER: NCT04593394.