Unravelling the lung cancer diagnostic pathway: identifying gaps and opportunities for improvement.

BACKGROUND: A fast and well-organized complex diagnostic process is important for better success in the treatment of lung cancer patients. The aim of our study was to reveal the gaps and inefficiencies in the diagnostic process and to suggest improvement strategies in a single tertiary centre in Slovenia. PATIENTS AND METHODS: We employed a comprehensive approach to carefully dissect all the steps in the diagnostic journey for individuals suspected of having lung cancer. We gathered and analysed information from employees and patients involved in the process by dedicated questionnaires. Further, we analysed the patients' data and calculated the diagnostic intervals for patients in two different periods. RESULTS: The major concerns among employees were stress and excessive administrative work. The important result of the visual journey and staff reports was the design of electronic diagnostic clinical pathway (eDCP), which could substantially increase safety and efficacy by diminishing the administrative burden of the employees. The patients were generally highly satisfied with diagnostic journey, but reported too long waiting times. By analysing two time periods, we revealed that diagnostic intervals exceeded the recommended timelines and got importantly shorter after two interventions - strengthening the diagnostic team and specially by purchase of additional PET-CT machine (the average time from general practitioner (GP) referral to the multidisciplinary treatment board (MDTB) decision was 50.8 [± 3.0] prior and 37.1 [± 2.3] days after the interventions). CONCLUSIONS: The study illuminated opportunities for refining the diagnostic journey for lung cancer patients, underscoring the importance of both administrative and capacity-related enhancements.

Investigation and outcomes in patients with nonspecific pleuritis: results from the International Collaborative Effusion database.

Introduction: We present findings from the International Collaborative Effusion database, a European Respiratory Society clinical research collaboration. Nonspecific pleuritis (NSP) is a broad term that describes chronic pleural inflammation. Various aetiologies lead to NSP, which poses a diagnostic challenge for clinicians. A significant proportion of patients with this finding eventually develop a malignant diagnosis. Methods: 12 sites across nine countries contributed anonymised data on 187 patients. 175 records were suitable for analysis. Results: The commonest aetiology for NSP was recorded as idiopathic (80 out of 175, 44%). This was followed by pleural infection (15%), benign asbestos disease (12%), malignancy (6%) and cardiac failure (6%). The malignant diagnoses were predominantly mesothelioma (six out of 175, 3.4%) and lung adenocarcinoma (four out of 175, 2.3%). The median time to malignant diagnosis was 12.2 months (range 0.8-32 months). There was a signal towards greater asbestos exposure in the malignant NSP group compared to the benign group (0.63 versus 0.27, p=0.07). Neither recurrence of effusion requiring further therapeutic intervention nor initial biopsy approach were associated with a false-negative biopsy. A computed tomography finding of a mass lesion was the only imaging feature to demonstrate a significant association (0.18 versus 0.01, p=0.02), although sonographic pleural thickening also suggested an association (0.27 versus 0.09, p=0.09). Discussion: This is the first multicentre study of NSP and its associated outcomes. While some of our findings are reflected by the established body of literature, other findings have highlighted important areas for future research, not previously studied in NSP.

Elevated eosinophils, IL5 and IL8 in induced sputum in asthma patients with accelerated FEV1 decline.

BACKGROUND: Some patients with asthma present with accelerated lung function decline. This phenomenon is mostly associated with severe exacerbations and with poor asthma control. OBJECTIVE: Our aim was to detect the extent of FEV1 decline in patients with mild asthma and to discriminate clinical, functional and inflammatory factors associated with accelerated FEV1 decline. METHODS: We recruited 50 patients with mild asthma for pulmonary function testing and induced sputum sampling 12-15 years after the initial diagnosis. In 33 patients, from whom sputum of a good quality was obtained, inflammatory cells were counted and concentrations of cytokines IL-2, IL-4, IL-5, IL-8, IL-10, IFN-γ, angiogenin and VEGF in the sputum were measured by cytometric bead array. RESULTS: Eighteen of 33 patients presented with accelerated FEV1 decline of more than 30 ml/year, with a mean (SEM) of 43.2 (3.9) ml/year, compared to 15 control patients with a FEV1 decline of 14.4 (2.1) ml/year. In the accelerated FEV1 decline group, we found elevated sputum levels of IL5 with a median (IQR) of 1.8 (0.4-3.2) pg/ml vs. 0.2 (0.1-1.2) pg/ml, p = 0.04; IL8 with a mean (SEM) of 1503 (194) pg/ml vs. 938 (177) pg/ml, p = 0.04; and eosinophils with a median (IQR) of 223 (41-1020) cells/µl vs. 39 (1-190) cells/µl, p = 0.03. No significant differences in other measured parameters were detected between the two groups. CONCLUSION: Elevated sputum eosinophils, IL5 and IL8, which have a potential to stimulate airway remodelling, might be a useful non-invasive biomarkers and therapeutic targets of accelerated FEV1 decline in asthma patients.

Telemonitoring in asthma control: a randomized controlled trial.

OBJECTIVE: Telemonitoring seems to be a useful tool for patients' management. The aim of our project was to test the applicability and potential effects of a 12-month telemonitoring of patients with asthma supported by information and communication technologies. METHODS: We included 100 patients with asthma followed in the outpatient pulmonary clinic in a randomized controlled clinical trial. The patients' data were collected by study questionnaires and lung function tests at the inclusion and at the end of interventional period. In the interventional group, asthma control test (ACT) and peak expiratory flow measurements (PEF) were stimulated to be regularly reported by Short Message Service (SMS). As a response to reported values, the patients automatically received a preformed text or a call from a study nurse in case of detected predefined critical values. RESULTS: The compliance of reporting PEF and ACT values was higher than 80% in 96% of patients. Although we did not detect significant differences in ACT score improvement between the two study groups, we found more prominent improvement of ACT score in the subgroup of patients with two or more exacerbations prior to inclusion in the interventional group, compared to the control group. 40 (78%) patients in the interventional group listed at least one positive effect of telemonitoring on management of asthma. CONCLUSIONS: The developed program for home monitoring of patients with asthma was applicable and offered the patients support in managing their disease. Further studies with more selected patients are needed to confirm its usefulness in improving asthma control.

8-isoprostane as Oxidative Stress Marker in Coal Mine Workers.

This study was to investigate whether working in conditions of elevated concentrations of mine gases (CO2, CO, CH4, DMS) and dust may result in oxidative stress. Coal miners (n=94) from the Velenje Coal mine who were arranged into control group and three groups according to a number of consecutive working days. 8-isoprostane as a biological marker of oxidative stress was measured in exhaled breath condensate (EBC). Miners who worked for three consecutive days had higher 8-isoprostane values in EBC compared to the control group. Gas/dust concentrations and exposure time of a single/two day shift seem too low to trigger immediate oxidative stress.

Polymorphisms and haplotypes of the chromosome locus 17q12-17q21.1 contribute to adult asthma susceptibility in Slovenian patients.

One of the major asthma susceptibility loci is 17q12-17q21.1, but the relationship between this locus and adult asthma is unclear. Association analysis of 13 single nucleotide polymorphisms (SNPs) and haplotypes from 17q12-17q21.1 was performed in 418 adult patients with asthma and 288 controls from Slovenia. Single SNP analysis revealed only marginal associations with adult asthma for SNPs located in GSDMA, GSDMB, ORMDL3 and ZPBP2 genes, and rs7219080 was the most highly associated. Analyses of asthma phenotypes found no association with atopy or lung function, but rs2305480 and rs8066582 were associated with childhood asthma and rs9916279 was associated with asthma in smokers. Notably, haplotypes consisting of rs9916279, rs8066582, rs1042658, and rs2302777 harbouring PSMD3, CSF3 and MED24 genes were highly associated with asthma. The four most common haplotypes, TCCG, TTTA, CCCA and TTCA, were more frequent in patients with asthma, whereas TTCG, TCCA, TCTA and TTTG were more frequent in controls. Only 3% of asthma patients belonged to haplotypes TTCG, TCCA, TCTA and TTTG compared with nearly one-third (31%) of controls. Associations confirmed that the 17q12-17q21.1 locus harbours a genetic determinant for asthma risk in adults and suggest that in addition to the previously known ORMDL3-GSDM locus, CSF3-PSMD3-MED24 also plays a role in asthma pathogenesis.

Feasibility and safety of parietal pleural cryobiopsy during semi-rigid thoracoscopy.

BACKGROUND AND AIMS: Performing pleural biopsies during semi-rigid thoracoscopy is sometimes a difficult and time-consuming task because of the lack of mechanical power of dedicated flexible forceps in patients with thickened pleura. The purpose of this first ever pilot study was to test the feasibility of taking biopsy specimens by cryoprobe from the parietal pleura during semi-rigid thoracoscopy. Our aim was also to assess the diagnostic value and quality of specimens obtained, morphological features, feasibility of immunohistochemistry staining and possibility of DNA isolation. The secondary aim was to evaluate safety, tolerability and duration of the procedure. METHODS: Fifteen patients with pleural effusion of unknown origin that underwent semi-rigid thoracoscopy were included. Biopsies were obtained using a flexible autoclavable cryoprobe 20416-032 (Erbokryo CA, ERBE, Tübingen, Germany) 2.4 mm in diameter and a semi-rigid autoclavable Olympus LTF-160 (Olympus, Tokyo, Japan) thoracoscope. RESULTS: Tissue samples were obtained from 14 patients (93.3%), three from each. Of the samples, 81% were easily interpretable and 19% were interpretable with some difficulty by the pathologist. The samples were of good quality, with the level of artifacts below 25%. The specimens were adequate for histological diagnosis, immunohistochemical staining and DNA isolation. There were no moderate or major bleeding problems after the biopsies; two patients experienced pain. The median duration of three cryobiopsies (per patient) was 4 min (range 3-6 min). CONCLUSIONS: Cryobiopsy during semi-rigid thoracoscopy appears worth to be evaluated in a larger prospective multicenter trial as our preliminary data were promising for efficacy and safety.

Rigid versus semi-rigid thoracoscopy for the diagnosis of pleural disease: a randomized pilot study.

BACKGROUND AND OBJECTIVE: Thoracoscopy with a semi-rigid instrument is a recent technique successfully used for diagnosing pleural diseases. However, there are concerns about the diagnostic adequacy of biopsy samples obtained by semi-rigid procedures when compared with rigid thoracoscopy. The purpose of this study was to compare the size, quality and diagnostic adequacy of biopsy specimens obtained at semi-rigid and rigid thoracoscopy in a prospective, randomized fashion. METHODS: Patients with pleural effusion of unknown origin and/or pleural irregularities suspicious for pleural malignancy were included after less invasive means of diagnosis had failed. All procedures were performed under local anaesthesia with intravenous sedation/analgesia with a single point of entry. Patients were randomly assigned to a rigid instrument procedure (Olympus EndoEYE WA50120A, forceps) or semi-rigid instrument procedure (Olympus LTF-160, FB-55CR-1 forceps). RESULTS: Eighty-four patients were randomized. Five of them were excluded because of lack of pleural space. Thirty-eight patients were assigned to a rigid and 41 to a semi-rigid procedure, with mean follow up 24.1 (±8.1) months after the procedure. The average size of the sample obtained by rigid thoracoscopy was 24.7 mm(2) (±12.9), and 11.7 mm(2) (±7.6) by semi-rigid thoracoscopy. There were no differences in the quality and interpretability of the specimens assessed by the pathologist. The diagnostic accuracy was 100% for the rigid procedure and 97.6% for the semi-rigid procedure. CONCLUSIONS: The samples obtained by semi-rigid thoracoscopy were smaller, but of adequate quality. The diagnostic accuracy was comparable with that of rigid thoracoscopy in the evaluation of pleural disease.