Respiratory symptoms and cross-shift lung function in relation to cotton dust and endotoxin exposure in textile workers in Nepal: a cross-sectional study

Objectives: Inhalation of a cotton-based particulates has previously been associated with respiratory symptoms and impaired lung function. This study investigates the respiratory health of Nepalese textile workers in relation to dust and endotoxin exposure. Methods: A total of 938 individuals from four sectors (garment, carpet, weaving and recycling) of the textile industry in Kathmandu, Nepal completed a health questionnaire and performed spirometry. A subset (n=384) performed cross-shift spirometry. Personal exposure to inhalable dust and airborne endotoxin was measured during a full shift for 114 workers. Results: The overall prevalence of persistent cough, persistent phlegm, wheeze ever, breathlessness ever and chest tightness ever was 8.5%, 12.5%, 3.2%, 6.5% and 12.3%, respectively. Symptoms were most common among recyclers and least common among garment workers. Exposure to inhalable dust significantly predicted persistent cough and chest tightness. Exposure to endotoxin did not have any independent predictive effect. Significant cross-shift reduction in forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were found (p<0.001 for both) being largest for FEV1 in the recyclers (−143 mL), and least in the garment workers (−38 mL; p=0.012). Exposure to inhalable dust predicted a cross-shift reduction in FEV1. Conclusions: This study is the first to investigate the respiratory health of Nepalese cotton workers. The measured association between inhalable dust exposure and reporting of respiratory symptoms and across-shift decrement in FEV1 and FVC indicates that improved dust control measures should be instituted, particularly in the recycling and carpet sectors. The possible role of other biologically active agents of cotton dust beyond endotoxin should be further explored

A randomised controlled feasibility study of group cognitive behavioural therapy for people with severe asthma

Objectives: Evidence for the efficacy of Cognitive Behavioural Therapy (CBT) in asthma is developing but it is not known if this translates to benefits in severe asthma or if a group approach is acceptable to this patient group. This study aimed to assess the feasibility and acceptability of Group-CBT in severe asthma. Method: This was a two-centre, randomised controlled parallel group feasibility study. Eligible participants (patients with severe asthma and a clinically significant diagnosis of anxiety and/or depression – Hospital Anxiety and Depression Scale (HAD) score greater than 8 for the anxiety or depression sub-scale) received Group-CBT in weekly sessions for eight consecutive weeks and usual care or usual care only. Follow-up was for 16 weeks and end points were: Asthma Quality of Life Questionnaire, Asthma Control Questionnaire, HAD, Dyspnoea-12, EuroQual-5D and EuroQuol-VAS. Results: 51 patients were randomised: 36% (51 out of 140) consent rate and 25% (13/51) attrition at week 16. Screening logs indicated that study take-up was influenced by patients living long distances from the treatment centre and inability to commit to the weekly demands of the programme. Drop-out was higher in Group-CBT compared due to inability to commit to the weekly programme because of poor health. Participants who contributed to focus group discussions reported that Group-CBT contributed to a better understanding of their illness and related approaches to anxiety management and acceptance of their asthma condition. Although weekly face-to-face sessions were challenging, this was the preferred method of delivery for these participants. Conclusions: This feasibility study shows that Group-CBT warrants further investigation as a potentially promising treatment option for patients with severe asthma. It has been possible but not easy to recruit and retain the sample. Options for a less demanding intervention schedule, such as less frequent face-to-face visits and the use of web-based interventions, require careful consideration

A randomised controlled feasibility trial of Group Cognitive Behavioural Therapy for people with severe asthma

Evidence for the efficacy of Cognitive Behavioural Therapy (CBT) in asthma is developing but it is not known if this translates to benefits in severe asthma or if a group approach is acceptable to this patient group. This study aimed to assess the feasibility and acceptability of Group-CBT in severe asthma.This was a two-centre, randomised controlled parallel group feasibility study. Eligible participants (patients with severe asthma and a clinically significant diagnosis of anxiety and/or depression - Hospital Anxiety and Depression Scale (HAD) score greater than 8 for the anxiety or depression sub-scale) received Group-CBT in weekly sessions for eight consecutive weeks and usual care or usual care only. Follow-up was for 16 weeks and end points were: Asthma Quality of Life Questionnaire, Asthma Control Questionnaire, HAD, Dyspnoea-12, EuroQual-5D and EuroQuol-VAS.51 patients were randomised: 36% (51 out of 140) consent rate and attrition at week 16 was 12. Screening logs indicated that study take-up was influenced by patients living long distances from the treatment centre and inability to commit to the weekly demands of the programme. Drop-out was higher in Group-CBT compared due to inability to commit to the weekly programme because of poor health. Participants who contributed to focus group discussions reported that Group-CBT contributed to a better understanding of their illness and related approaches to anxiety management and acceptance of their asthma condition. Although weekly face-to-face sessions were challenging, this was the preferred method of delivery for these participants.This feasibility study shows that Group-CBT warrants further investigation as a potentially promising treatment option for patients with severe asthma. It has been possible but not easy to recruit and retain the sample. Options for a less demanding intervention schedule, such as less frequent face-to-face visits and the use of web-based interventions, require careful consideration

Indications for the use of bronchial thermoplasty in severe asthma

Approximately 5% of the ~3 million asthmatics in South Africa have severe asthma that is associated with substantial morbidity, cost, absenteeism, preventable mortality, and the requirement for costly chronic medication that may be associated with significant adverse events. There is an unmet need for alternative safer and more effective interventions for severe asthma. A recently introduced option, bronchial thermoplasty (BT), imparts radiofrequency-generated heat energy to the airways to cause regression of airway smooth muscle. The effectiveness of this technique has been confirmed in randomised control trials and is now endorsed by several international guidelines, including the Global Initiative for Asthma (GINA) guideline, the British Asthma Guideline, and the UK National Institute of Clinical Excellence (NICE) guideline. We recommend BT as a potential therapeutic intervention for severe uncontrolled asthma, provided that it is performed by an experienced pulmonologist at an accredited centre and done within the broader context of appropriate management of the disease by doctors experienced in treating difficult-to-control asthma

Determining the contribution of IL33 and IL1RL1 polymorphisms to clinical and immunological features of asthma

Rationale: IL33 (9p24.1) and the IL33 receptor (IL1RL, 2q12) have been reproducibly identified as asthma susceptibility genes. However, the variants driving genetic associations are not yet fully defined. Using a population based birth cohort of 1059 children (Manchester Asthma and Allergy Study-(MAAS)) and 2536 adults with asthma (Genetics of Asthma Severity and Phenotypes- (GASP)) cohort we aimed to define genetic variants associated with clinical and immunological features of asthma. Methods: MAAS samples were genotyped using the Illumina 610 Quad array and imputed using 1000G reference panel. GASP samples were genotyped using two custom designed Affymetrix arrays (UK BiLEVE/UK Biobank array). Datasets were quality controlled for gender mismatches, outliers and relatedness. Data was generated for the IL33/IL1RL1 regions consisting of the genes and surrounding regions (chr9:5715785−6757983 & chr2:102427961−103468497) on the following traits: asthma diagnosis (MAAS), atopy, FEV1 (GASP) and FEV1/FVC (MAAS and GASP) as well as total blood eosinophil counts and serum total IgE levels (GASP). Variables for blood eosinophils and total IgE were log10 transformed. Analysis was carried out in PLINK using linear or logistic regression modelling including appropriate covariates for each trait. Results: In the MAAS cohort, we replicated the association of the IL33 locus with asthma diagnosis, identifying potentially two independent novel signals in that locus (rs10975398; P=1.70E-05; B= -1.519; MAF=0.32 and rs2890697; P=1.10E-04; B= -1.573; MAF=0.43). This association survived a Bonferroni correction for multiple testing. Although not surviving correction, an association was also identified for atopy in the IL1RL1 locus for MAAS (P=1.08E-04; MAF=0.48). In GASP we identified modest associations not in known LD with published loci (P-value range: 5.00E-02 – 7.60E-04) for FEV1, FEV1/FVC, atopy, blood eosinophils and total IgE in both the IL33 and IL1RL1 loci. Multiple SNPs presented nominal association (P<0.01) with more than one trait such as atopy & total IgE, providing supporting evidence for association. Conclusion: We replicated the association of IL33 region SNPs with asthma diagnosis in MAAS, highlighting the role of this locus in childhood asthma. Although trait association signals did not survive correction for multiple testing, nominal association across multiple phenotypes in GASP provides suggestive evidence of the role of the IL33/IL1RL1 genetic polymorphisms in determining clinical and immunological features of asthma

Management of patients with advanced prostate cancer—metastatic and/or castration-resistant prostate cancer: report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022

Background: Innovations in imaging and molecular characterisation together with novel treatment options have improved outcomes in advanced prostate cancer. However, we still lack high-level evidence in many areas relevant to making management decisions in daily clinical practise. The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) addressed some questions in these areas to supplement guidelines that mostly are based on level 1 evidence. Objective: To present the voting results of the APCCC 2022. Design, setting, and participants: The experts voted on controversial questions where high- level evidence is mostly lacking: locally advanced prostate cancer; biochemical recurrence after local treatment; metastatic hormone-sensitive, non-metastatic, and metastatic castration- resistant prostate cancer; oligometastatic prostate cancer; and managing side effects of hormonal therapy. A panel of 105 international prostate cancer experts voted on the consensus questions. Outcome measurements and statistical analysis: The panel voted on 198 pre-defined questions, which were developed by 117 voting and non-voting panel members prior to the conference following a modified Delphi process. A total of 116 questions on metastatic and/or castration- resistant prostate cancer are discussed in this manuscript. In 2022, the voting was done by a web-based survey because of COVID-19 restrictions. Results and limitations: The voting reflects the expert opinion of these panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results are reported in the supplementary material. We report here on topics in metastatic, hormone-sensitive prostate cancer (mHSPC), non-metastatic, castration-resistant prostate cancer (nmCRPC), metastatic castration-resistant prostate cancer (mCRPC), and oligometastatic and oligoprogressive prostate cancer. Conclusions: These voting results in four specific areas from a panel of experts in advanced prostate cancer can help clinicians and patients navigate controversial areas of management for which high-level evidence is scant or conflicting and can help research funders and policy makers identify information gaps and consider what areas to explore further. However, diagnostic and treatment decisions always have to be individualised based on patient characteristics, including the extent and location of disease, prior treatment(s), co-morbidities, patient preferences, and treatment recommendations and should also incorporate current and emerging clinical evidence and logistic and economic factors. Enrolment in clinical trials is strongly encouraged. Importantly, APCCC 2022 once again identified important gaps where there is non-consensus and that merit evaluation in specifically designed trials. Patient summary: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with healthcare providers worldwide. At each APCCC, an expert panel votes on pre-defined questions that target the most clinically relevant areas of advanced prostate cancer treatment for which there are gaps in knowledge. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients and their relatives as part of shared and multidisciplinary decision-making. This report focuses on the advanced setting, covering metastatic hormone-sensitive prostate cancer and both non-metastatic and metastatic castration-resistant prostate cancer. Twitter summary: Report of the results of APCCC 2022 for the following topics: mHSPC, nmCRPC, mCRPC, and oligometastatic prostate cancer. Take-home message: At APCCC 2022, clinically important questions in the management of advanced prostate cancer management were identified and discussed, and experts voted on pre-defined consensus questions. The report of the results for metastatic and/or castration- resistant prostate cancer is summarised here

Management of Patients with Advanced Prostate Cancer. Part I : Intermediate-/High-risk and Locally Advanced Disease, Biochemical Relapse, and Side Effects of Hormonal Treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022

Background: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. Objective: To present consensus voting results for select questions from APCCC 2022. Design, setting, and participants: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members (“panellists”) who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1–3. Outcome measurements and statistical analysis: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. Results and limitations: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. Conclusions: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials. Patient summary: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with health care providers and patients worldwide. At each APCCC, a panel of physician experts vote in response to multiple-choice questions about their clinical opinions and approaches to managing advanced prostate cancer. This report presents voting results for the subset of questions pertaining to intermediate- and high-risk and locally advanced prostate cancer, biochemical relapse after definitive treatment, advanced (next-generation) imaging, and management of side effects caused by hormonal therapies. The results provide a practical guide to help clinicians and patients discuss treatment options as part of shared multidisciplinary decision-making. The findings may be especially useful when there is little or no high-level evidence to guide treatment decisions.publishedVersionPeer reviewe

Management of patients with advanced prostate cancer. Part I: Intermediate-/high-risk and locally advanced disease, biochemical relapse, and side effects of hormonal treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022

© 2023 The Authors. Published by Elsevier on behalf of European Association of Urology. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1016/j.eururo.2022.11.002Background: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. Objective: To present consensus voting results for select questions from APCCC 2022. Design, setting, and participants: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members (“panellists”) who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1–3. Outcome measurements and statistical analysis: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. Results and limitations: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. Conclusions: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials. Patient summary: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with health care providers and patients worldwide. At each APCCC, a panel of physician experts vote in response to multiple-choice questions about their clinical opinions and approaches to managing advanced prostate cancer. This report presents voting results for the subset of questions pertaining to intermediate- and high-risk and locally advanced prostate cancer, biochemical relapse after definitive treatment, advanced (next-generation) imaging, and management of side effects caused by hormonal therapies. The results provide a practical guide to help clinicians and patients discuss treatment options as part of shared multidisciplinary decision-making. The findings may be especially useful when there is little or no high-level evidence to guide treatment decisions.We gratefully acknowledge the following organisations for providing financial support for the APCCC 2022: The City of Lugano and Movember Foundation. Ros Eeles is supported by a National Institute of Health Research grant to the Biomedical Research Centre at The Institute of Cancer Research and Royal Marsden NHS Foundation Trust. We also acknowledge sponsorship from several for-profit organisations for APCCC 2022, including Advanced Accelerator Applications, Amgen, Astellas, AstraZeneca, Bayer Health Care, Debiopharm, MSD, Janssen Oncology, Myovant Sciences, Orion Pharma, Pfizer Oncology, Roche, Telix Innovations SA, Ferring Pharmaceuticals, Lantheus, and Tolmar. These for-profit organisations supported the conference financially but had no input on the scientific content or the final publication.Accepted versio