Effects of Active Chronic Cigarette-Smoke Exposure on Circulating Fibrocytes.

PURPOSE: This study aimed to evaluate the hypothesis that active smoking impacts upon mediators and abundance of circulating fibrocyte cells in smoking-related disease characterised by fibrosis. METHODS: Flow cytometry and enzyme-linked immunosorbent assays were used to investigate blood from five patient groups: healthy never-smokers, healthy current smokers, stable chronic obstructive pulmonary disease (COPD) active smokers, idiopathic pulmonary fibrosis (IPF) never-smokers, and IPF active smokers. RESULTS: A significant inverse dose-response relationship was observed in healthy smokers among cumulative smoking burden (pack-years) and fibrocyte abundance (p = 0.006, r = -0.86). Among serum profibrotic fibrocyte chemokines measured, CCL18 rose significantly alongside fibrocyte numbers in all five subject groups, while having an inverse dose-response relationship with pack-year burden in healthy smokers (p = 0.003, r = -0.89). In IPF, CCL2 rose in direct proportion to fibrocyte abundance irrespective of smoking status but had lower serum levels in those currently smoking (p = < 0.001). For the study population, CXCL12 was decreased in pooled current smokers versus never-smokers (p = 0.03). CONCLUSION: The suppressive effect of current, as distinct from former, chronic smoking on circulating fibrocyte abundance in healthy smokers, and modulation of regulatory chemokine levels by active smoking may have implications for future studies of fibrocytes in smoking-related lung diseases as a potential confounding variable.

Analysis of tissue lipidomics and computed tomography pulmonary fat attenuation volume (CTPFAV ) in idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: There is increasing interest in the role of lipids in processes that modulate lung fibrosis with evidence of lipid deposition in idiopathic pulmonary fibrosis (IPF) histological specimens. The aim of this study was to identify measurable markers of pulmonary lipid that may have utility as IPF biomarkers. STUDY DESIGN AND METHODS: IPF and control lung biopsy specimens were analysed using a unbiased lipidomic approach. Pulmonary fat attenuation volume (PFAV) was assessed on chest CT images (CTPFAV ) with 3D semi-automated lung density software. Aerated lung was semi-automatically segmented and CTPFAV calculated using a Hounsfield-unit (-40 to -200HU) threshold range expressed as a percentage of total lung volume. CTPFAV was compared to pulmonary function, serum lipids and qualitative CT fibrosis scores. RESULTS: There was a significant increase in total lipid content on histological analysis of IPF lung tissue (23.16 nmol/mg) compared to controls (18.66 mol/mg, p = 0.0317). The median CTPFAV in IPF was higher than controls (1.34% vs. 0.72%, p < 0.001) and CTPFAV correlated significantly with DLCO% predicted (R2 = 0.356, p < 0.0001) and FVC% predicted (R2 = 0.407, p < 0.0001) in patients with IPF. CTPFAV correlated with CT features of fibrosis; higher CTPFAV was associated with >10% reticulation (1.6% vs. 0.94%, p = 0.0017) and >10% honeycombing (1.87% vs. 1.12%, p = 0.0003). CTPFAV showed no correlation with serum lipids. CONCLUSION: CTPFAV is an easily quantifiable non-invasive measure of pulmonary lipids. In this pilot study, CTPFAV correlates with pulmonary function and radiological features of IPF and could function as a potential biomarker for IPF disease severity assessment.

Cleaning up the paper trail - our clinical notes in open view.

Purpose Ireland's physicians have a legal and an ethical duty to protect confidential patient information. Most healthcare records in Ireland remain paper based, so the purpose of this paper is to: assess the protection afforded to paper records; log highest risk records; note the variations that occurred during the working week; and observe the varying protection that occurred when staff, students and public members were present. Design/methodology/approach A customised audit tool was created using Sphinx software. Data were collected for three months. All wards included in the study were visited once during four discrete time periods across the working week. The medical records trolley's location was noted and total unattended medical records, total unattended nursing records, total unattended patient lists and when nursing personnel, medical students, public and a ward secretary were visibly present were recorded. Findings During 84 occasions when the authors visited wards, unattended medical records were identified on 33 per cent of occasions, 49 per cent were found during weekend visiting hours and just 4 per cent were found during morning rounds. The unattended medical records belonged to patients admitted to a medical specialty in 73 per cent of cases and a surgical specialty in 27 per cent. Medical records were found unattended in the nurses' station with much greater frequency when the ward secretary was off duty. Unattended nursing records were identified on 67 per cent of occasions the authors visited the ward and were most commonly found unattended in groups of six or more. Practical implications This study is a timely reminder that confidential patient information is at risk from inappropriate disclosure in the hospital. There are few context-specific standards for data protection to guide healthcare professionals, particularly paper records. Nursing records are left unattended with twice the frequency of medical records and are found unattended in greater numbers than medical records. Protection is strongest when ward secretaries are on duty. Over-reliance on vigilant ward secretaries could represent a threat to confidential patient information. Originality/value While other studies identified data protection as an issue, this study assesses how data security varies inside and outside conventional working hours. It provides a rationale and an impetus for specific changes across the whole working week. By identifying the on-duty ward secretary's favourable effect on medical record security, it highlights the need for alternative arrangements when the ward secretary is off duty. Data were collected prospectively in real time, giving a more accurate healthcare record security snapshot in each data collection point.

Smoking-Related Interstitial Fibrosis: Evidence of Radiologic Regression with Advancing Age and Smoking Cessation.

More data are needed regarding the radiology, co-morbidities and natural history of smoking-related interstitial fibrosis (SRIF), a common pathological finding, mainly described heretofore in association with lung cancer, where respiratory bronchiolitis (RB) usually co-exists. We prospectively acquired high resolution CT scan data (edge-enhancing lung reconstructions) to detect any radiologic interstitial lung abnormality (ILA) in individuals who ultimately underwent surgical lobectomy for lung cancer (n = 20), for radiologic/pathologic correlation. We also re-examined other smoking-related benign histologic cases: chronic obstructive pulmonary disease (COPD lung explants, n = 20), alpha 1-antitrypsin deficiency (A1AT, explanted lungs n = 20), combined pulmonary fibrosis and emphysema (CPFE, n = 8) and idiopathic pulmonary fibrosis (IPF, n = 10). Finally, we pooled our data with all peer-reviewed published data describing histologic SRIF of known ILA status. SRIF was observed in 40% of cancer lobectomies, mean (±SD) age 65.8 ± 8.7 years, none of whom had ILA. SRIF was observed in other smoking-related benign diseases (COPD 35%, A1AT 20%, CPFE 25%, and IPF 10%). 71.4% of benign SRIF cases had no RB (nearly all ex-smokers) versus 0% of cancer-associated SRIF cases (P = 1.7 × 10-3). Pooled data showed that those SRIF subjects without ILA were 15.05 years older than those with ILA (95% confidence interval 8.99 to 21.11, P = 2.5 × 10-5) and more likely to be former smokers (P = 7.2 × 10-3). SRIF is frequently found without lung cancer, and mostly without RB in former smokers. SRIF is less likely to have ILA in older subjects and with smoking cessation, which could represent RB+/-SRIF regression.

Why is your patient sedated?

PURPOSE: The purpose of this paper is to examine the recording of clinical indication for prescribed sedative/hypnotic (SH) medications in a large, acute tertiary referral hospital. DESIGN/METHODOLOGY/APPROACH: All hospital inpatients' medications (n = 367) were audited for prescription details regarding SH medications. Medical notes were then examined for evidence of a recorded indication for such medications. FINDINGS: SH medications were prescribed to many hospital inpatients (42.5 per cent) during admission. An indication was documented in the nursing or medical records for 24.4 per cent of patients who were prescribed such medications. Nurses rather than by doctors prescribed most SH medications (74 vs 26 per cent, respectively, p = 0.003). Some patients receiving SH medications were both over 65 and impaired in their mobility (19.2 per cent). The treatment indication was documented in 47 per cent. PRACTICAL IMPLICATIONS: Most patients prescribed SH medications have nothing in their medical record explaining why these drugs are being used, including half of the elderly, less mobile patients. All health professionals dealing with SH medications and doctors in particular need to justify the use of such medications in the medical record. For the particularly high-risk groups where SH medications are potentially more dangerous, explicit guidance on why and how such medications are to be used must be provided by prescribers. ORIGINALITY/VALUE: For the first time, data are presented on documentation rates for clinical indication of prescribed SH medications across a large acute hospital, and highlights significant shortcomings in practice. This study should inform other organisations of the need to be mindful of facilitating greater compliance with good prescribing practice.

Population genetic structure of the people of Qatar.

People of the Qatar peninsula represent a relatively recent founding by a small number of families from three tribes of the Arabian Peninsula, Persia, and Oman, with indications of African admixture. To assess the roles of both this founding effect and the customary first-cousin marriages among the ancestral Islamic populations in Qatar's population genetic structure, we obtained and genotyped with Affymetrix 500k SNP arrays DNA samples from 168 self-reported Qatari nationals sampled from Doha, Qatar. Principal components analysis was performed along with samples from the Human Genetic Diversity Project data set, revealing three clear clusters of genotypes whose proximity to other human population samples is consistent with Arabian origin, a more eastern or Persian origin, and individuals with African admixture. The extent of linkage disequilibrium (LD) is greater than that of African populations, and runs of homozygosity in some individuals reflect substantial consanguinity. However, the variance in runs of homozygosity is exceptionally high, and the degree of identity-by-descent sharing generally appears to be lower than expected for a population in which nearly half of marriages are between first cousins. Despite the fact that the SNPs of the Affymetrix 500k chip were ascertained with a bias toward SNPs common in Europeans, the data strongly support the notion that the Qatari population could provide a valuable resource for the mapping of genes associated with complex disorders and that tests of pairwise interactions are particularly empowered by populations with elevated LD like the Qatari.

Management of comorbidities in difficult and severe asthma.

Difficult-to-treat and severe asthma are challenging clinical entities. In the face of suboptimal asthma control, the temptation for clinicians is to reflexively escalate asthma-directed therapy, including increasing exposure to corticosteroids and commencement of costly but potent biologic therapies. However, asthma control is objectively and subjectively assessed based on measurable parameters (such as exacerbations or variability in pulmonary physiology), symptoms and patient histories. Crucially, these features can be confounded by common untreated comorbidities, affecting clinicians' assessment of asthma treatment efficacy.

RNA-Seq quantification of the human small airway epithelium transcriptome.

BACKGROUND: The small airway epithelium (SAE), the cell population that covers the human airway surface from the 6th generation of airway branching to the alveoli, is the major site of lung disease caused by smoking. The focus of this study is to provide quantitative assessment of the SAE transcriptome in the resting state and in response to chronic cigarette smoking using massive parallel mRNA sequencing (RNA-Seq). RESULTS: The data demonstrate that 48% of SAE expressed genes are ubiquitous, shared with many tissues, with 52% enriched in this cell population. The most highly expressed gene, SCGB1A1, is characteristic of Clara cells, the cell type unique to the human SAE. Among other genes expressed by the SAE are those related to Clara cell differentiation, secretory mucosal defense, and mucociliary differentiation. The high sensitivity of RNA-Seq permitted quantification of gene expression related to infrequent cell populations such as neuroendocrine cells and epithelial stem/progenitor cells. Quantification of the absolute smoking-induced changes in SAE gene expression revealed that, compared to ubiquitous genes, more SAE-enriched genes responded to smoking with up-regulation, and those with the highest basal expression levels showed most dramatic changes. Smoking had no effect on SAE gene splicing, but was associated with a shift in molecular pattern from Clara cell-associated towards the mucus-secreting cell differentiation pathway with multiple features of cancer-associated molecular phenotype. CONCLUSIONS: These observations provide insights into the unique biology of human SAE by providing quantitative assessment of the global transcriptome under physiological conditions and in response to the stress of chronic cigarette smoking.

A qualitative study of clinician perceptions regarding the potential role for digital health interventions for the management of COPD.

Effective self-management of chronic obstructive pulmonary disease (COPD) can lead to increased patient control and reduced health care costs. However, both patients and healthcare professionals encounter significant challenges. Digital health interventions, such as smart oximeters and COPD self-management applications, promise to enhance the management of COPD, yet, there is little evidence to support their use and user-experience issues are still common. Understanding the needs of healthcare professionals is central for increasing adoption and engagement with digital health interventions but little is known about their perceptions of digital health interventions in COPD. This paper explored the perceptions of healthcare professionals regarding the potential role for DHI in the management of COPD. Snowball sampling was used to recruit the participants (n = 32). Each participant underwent a semi-structured interview. Using NVivo 12 software, thematic analysis was completed. Healthcare professionals perceive digital health interventions providing several potential benefits to the management of COPD including the capture of patient status indicators during the interappointment period, providing new patient data to support the consultation process and perceived digital health interventions as a potential means to improve patient engagement. The findings offer new insights regarding potential future use-cases for digital health interventions in COPD, which can help ease user-experience issues as they align with the needs of healthcare professionals.

Functional study of elafin cleaved by Pseudomonas aeruginosa metalloproteinases.

Elafin is a 6-kDa innate immune protein present at several epithelial surfaces including the pulmonary epithelium. It is a canonical protease inhibitor of two neutrophil serine proteases [neutrophil elastase (NE) and proteinase 3] with the capacity to covalently bind extracellular matrix proteins by transglutamination. In addition to these properties, elafin also possesses antimicrobial and immunomodulatory activities. The aim of the present study was to investigate the effect of Pseudomonas aeruginosa proteases on elafin function. We found that P. aeruginosa PAO1-conditioned medium and two purified Pseudomonas metalloproteases, pseudolysin (elastase) and aeruginolysin (alkaline protease), are able to cleave recombinant elafin. Pseudolysin was shown to inactivate the anti-NE activity of elafin by cleaving its protease-binding loop. Interestingly, antibacterial properties of elafin against PAO1 were found to be unaffected after pseudolysin treatment. In contrast to pseudolysin, aeruginolysin failed to inactivate the inhibitory properties of elafin against NE. Aeruginolysin cleaves elafin at the amino-terminal Lys6-Gly7 peptide bond, resulting in a decreased ability to covalently bind purified fibronectin following transglutaminase activity. In conclusion, this study provides evidence that elafin is susceptible to proteolytic cleavage at alternative sites by P. aeruginosa metalloproteinases, which can affect different biological functions of elafin.

Predictive validity of measurements of clinical competence using the team objective structured bedside assessment (TOSBA): assessing the clinical competence of final year medical students.

BACKGROUND: The importance of valid and reliable assessment of student competence and performance is gaining increased recognition. Provision of valid patient-based formative assessment is an increasing challenge for clinical teachers in a busy hospital setting. A formative assessment tool that reliably predicts performance in the summative setting would be of value to both students and teachers. AIM: This study explores the utility of the team objective structured bedside assessment (TOSBA), a novel ward-based formative assessment tool, in predicting student performance in the final clinical examination. METHODS: The performance of a cohort of final year students (n = 191) in the TOSBA was compared with their subsequent performance in the final examination. A comparison was also made between student performance in the existing formative assessment tool, the objective structured long examination record (OSLER) and the final examination. We also examined the relationship between the TOSBA and the components of the final examination using clustering around latent variables analysis. RESULTS: There was a clear relationship between student performance in the TOSBA and performance in the final examination (r(2) = 0.35). Student performance in the OSLER showed a poor relationship with performance in the final examination (r(2) = 0.15) compared with the TOSBA. The TOSBA results showed particular correlation with specific components of the final examination which were clinically based. CONCLUSION: TOSBA performance is a strong predictor of subsequent performance in the final examination. The clustering of the TOSBA with other assessments of clinical skills underlines its utility. Further research is required to determine whether performance in the TOSBA is predictive of subsequent performance during internship.

A qualitative study of chronic obstructive pulmonary disease patient perceptions of the barriers and facilitators to adopting digital health technology.

OBJECTIVE: Non-adherence to self-management plans in chronic obstructive pulmonary disease (COPD) results in poorer outcomes for patients. Digital health technology (DHT) promises to support self-management by enhancing the sense of control patients possess over their disease. COPD digital health studies have yet to show significant evidence of improved outcomes for patients, with many user-adoption issues still present in the literature. To help better address the adoption needs of COPD patients, this paper explores their perceived barriers and facilitators to the adoption of DHT. METHODS: A sample of convenience was chosen and patients (n = 30) were recruited from two Dublin university hospitals. Each patient completed a qualitative semi-structured interview. Thematic analysis of the data was performed using NVivo 12 software. RESULTS: Barrier sub-themes included lack of perceived usefulness, digital literacy, illness perception, and social context; facilitator sub-themes included existing digital self-efficacy, personalised education, and community-based support. CONCLUSION: The findings represent a set of key considerations for researchers and clinicians to inform the design of patient-centred study protocols that aim to account for the needs and preferences of patients in the development of implementation and adoption strategies for DHT in COPD.

Exploring the potential benefits of digital health technology for the management of COPD: a qualitative study of patient perceptions.

Engaging chronic obstructive pulmonary disease (COPD) patients to actively participate in self-management has proven difficult. Digital health technology (DHT) promises to facilitate a patient-centred care model for the management of COPD by empowering patients to self-manage effectively. However, digital health studies in COPD have yet to demonstrate significant patient outcomes, suggesting that this research has still to adequately address the needs of patients in the intervention development process. The current study explored COPD patients' perceptions of the potential benefits of DHT in the self-management and treatment of their disease. A sample of convenience was chosen and participants (n=30) were recruited from two Dublin university hospitals and each underwent a qualitative semi-structured interview. Thematic analysis of the data was completed using NVivo 12 software. Six themes were identified: symptom management, anxiety management, interaction with physician, care management, personalising care and preventative intervention. In our findings, patients reported a willingness to take a more active role in self-management using DHT. They perceived DHT potentially enhancing their self-management by improving self-efficacy and engagement and by supporting healthcare professionals to practise preventative care provision. The findings can be used to inform patient-centred COPD digital interventions for researchers and clinicians who wish to develop study aims that align with the needs and preferences of patients.

Variability in small airway epithelial gene expression among normal smokers.

BACKGROUND: Despite overwhelming data that cigarette smoking causes COPD, only a minority of long-term smokers are affected, strongly suggesting that genetic factors modify susceptibility to this disease. We hypothesized that individual variations exist in the response to cigarette smoking, with variability among smokers in expression levels of protective/susceptibility genes. METHODS: Affymetrix arrays and quantitative polymerase chain reaction were used to assess the variability of gene expression in the small airway epithelium obtained by fiberoptic bronchoscopy of 18 normal nonsmokers, 18 normal smokers, and 18 smokers with COPD. RESULTS: We identified 201 probe sets representing 152 smoking-responsive genes that were significantly up-regulated or down-regulated, and assessed the coefficient of variation in expression levels among the study population. Variation was a reproducible property of each gene as assessed by different microarray probe sets and real-time polymerase chain reaction, and was observed in both normal smokers and smokers with COPD. Greater individual variability was found in smokers with COPD than in normal smokers. The majority of these highly variable smoking-responsive genes were in the functional categories of signal transduction, xenobiotic degradation, metabolism, transport, oxidant related, and transcription. A similar pattern of the same highly variable genes was observed in an independent data set. CONCLUSIONS: We propose that genetic diversity is likely within this subset of genes, with highly variable individual-to-individual responses of the small airway epithelium to smoking, and that this subset of genes represents putative candidates for assessment of susceptibility/protection from disease in future gene-based epidemiologic studies of smokers' risk for COPD.