Value pluralism about sexual intimacy in residential care.

BACKGROUND: The existing literature on sexuality and intimacy in residential care tends to focus on either the question of rights, or the value of autonomy. Where the literature does reference values other than autonomy, such values are considered in the context of being a guide to whether or not a resident is autonomous, rather than being important values in their own right. OBJECTIVE: This paper draws on qualitative data gathered as part of a larger study in order to inform practice on how care workers respond to intimacy issues that arise with residents with dementia and to inform a general ethics of sex and sexuality, demonstrating that an approach which permits value pluralism can be appropriate in certain contexts. RESEARCH DESIGN: The qualitative data referred to in this paper was gathered from semi-structured interviews undertaken as part of a larger mixed-method research project. The interview text was analysed using Thorne's methodological approach, interpretive description. PARTICIPANTS AND RESEARCH CONTEXT: The qualitative arm of the project consisted of semi-structured interviews conducted between October 2018 and October 2019 with participants (staff, residents and family members) recruited from 35 residential care homes in Aotearoa New Zealand. ETHICAL CONSIDERATIONS: Participation was informed, voluntary and written consent was gained before interviews. The project was approved by the Massey University Human Ethics Committee (Northern), number NOR 18/25. FINDINGS: Analysis of the scenarios presented in this paper shows that decision-making around sexual intimacy involving people with dementia in a residential care setting is complex and requires recognizing and weighing the different values that may be a in play. CONCLUSION: A focus on safety and consent to the exclusion of other values which matter morally in this context is a mistake which prevents care workers from providing appropriately person-centred care to residents, as policies which focus on the goal of care allow space for critical examination of issues which are likely to be highly context-sensitive.

Incivility in practice - incidence and experiences of nursing students in eastern Canada: A descriptive quantitative study.

BACKGROUND: Incivility within nursing is professionally unacceptable. Little research exists regarding student nurses' experiences with incivility from healthcare professionals and others within the clinical environment and particularly within a Canadian context. AIM: To describe the incidence and perceptions of incivility experienced by undergraduate nursing students from healthcare professionals and others within clinical practice. METHOD: This descriptive study used an electronic survey and was conducted at an eastern Canadian university. Descriptive statistics were applied. RESULTS: Of 650 nursing students invited to participate in the study, 260 surveys were fully completed. Of these, 70% of respondents indicated experiencing incivility, mostly in acute care settings. Registered nurses and licensed practical nurses were the major offenders. Discourteous gestures and condescending remarks were the most frequently experienced uncivil acts, resulting in feelings of high anxiety and inadequacy. Participants coped by avoiding communication with the perpetrator. Incivility was rarely reported because of a belief it would be fruitless to do so, lack of awareness of policies and fear of retaliation. CONCLUSIONS: Nursing students experience incivility frequently in clinical practice with serious consequences. Recommendations arising from this study encourage educators and healthcare leaders to collaborate to review, implement and evaluate curricula, policies and processes to address incivility.

The 6-minute walk test predicts mortality in a pulmonary nontuberculous mycobacteria-predominant bronchiectasis cohort.

BACKGROUND: Bronchiectasis is a chronic lung condition frequently associated with nontuberculous mycobacteria pulmonary (NTM) disease. Persons with these conditions are at increased risk of mortality. Patient reported outcome (PRO) instruments and the 6-minute walk test (6MWT) have been shown to predict mortality for several lung conditions, but these measures have not been fully evaluated for bronchiectasis and NTM. METHODS: We conducted a retrospective cohort study among adult patients enrolled in a natural history study of bronchiectasis at the National Heart, Lung, and Blood Institute. Electronic medical records were queried for demographic, clinical, microbiologic, radiographic, and PRO instrument data: St. George's Respiratory Questionnaire (SGRQ), Medical Research Council Dyspnea Scale, and the Pulmonary Symptom Severity Score (PSSS). The study baseline date was defined as the patient's first visit after January 1st, 2015 with a SGRQ or 6MWT completed. Follow-up was defined as the interval between the study baseline visit and date of death or December 31st, 2019. Sex-stratified Cox proportional-hazards regression was conducted to identify predictors of mortality. Separate models were run for each PRO and 6MWT measure, controlling for age, body mass index (BMI), fibrocavitary disease status, and M. abscessus infection. RESULTS: In multivariable Cox proportional-hazards regression models, the PSSS-severity (aHR 1.29, 95% CI 1.04-1.59), the 6MWT total distance walked (aHR 0.938, 95% CI 0.896-0.981) and distance saturation product (aHR 0.930, 95% CI 0.887-0.974) independently predicted mortality. In addition, BMI was significantly predictive of mortality in all models. CONCLUSIONS: The 6MWT and a PRO instrument capturing symptom severity are independently predictive of mortality in our cohort of bronchiectasis patients.

Not in the Brochure: Porneia and Residential Aged Care.

Introduction: Sexuality and intimacy in residential aged care (RAC) are receiving increased research attention. In this article, porneia refers to access to sex workers, as well as online pornography, and masturbation by residents in RAC. Sex work is legal and regulated in Aotearoa New Zealand. Methods: The present study was a two-arm mixed-method cross-sectional study using a concurrent triangulation design. A validated survey tool was developed. Data were collected in 2018-2019: 433 staff surveys were collected from 35 RAC across the country; 61 interviews were carried out with 77 staff, residents, and family members. Results: Staff opinions about sex work and pornography were inconclusive. Nevertheless, access to sex workers occurs in many RAC facilities across the country. Interviews demonstrated a diversity of responses among the three groups; staff attitudes are paramount. Conclusions: Some staff are prepared for resident requests for sex workers; others continue to look to policies and management for guidance, but such policies are often lacking. Most staff have adopted the language of needs vs. rights which dominates the literature. Policy Implications: Staff education on sexuality and facility policy is essential; education for residents and their families is also desirable. Facilities often over-notify third parties. Discourse about sexuality needs to move towards a person-centred, salutogenic approach.

Home before Hospital: a whole of system re-design project to improve rates of home-based dialysis therapy: Experience and outcomes over 8 years.

BACKGROUND: Despite evidence that clinical outcomes for patients treated with peritoneal dialysis (PD) or home haemodialysis are better than for patients treated with conventional satellite or hospital-based haemodialysis, rates of home-based dialysis therapies world-wide remain low. Home-based dialysis care is also cost-effective and indeed the favoured dialysis option for many patients. METHODS & OBJECTIVES: Using a lean-thinking framework and established change management methodology, a project embracing a system-wide approach at making a change where a 'Home before Hospital' philosophy underpinned all approaches to dialysis care was undertaken. Three multidisciplinary working groups (pathway, outreach and hybrid) were established for re-design and implementation. The primary aim was to improve home-based dialysis therapy prevalence rates from a baseline of 14.8% by ≥2.5%/year to meet a target of 35%, whilst not only maintaining but improving the quality of care provided to patients requiring maintenance dialysis. A 'future' state pathway was developed after review of the 'current' state (Pathway Working Group) and formed the basis on which a nurse-led outreach service (Outreach Working Group) was established. With the support of the multidisciplinary team, the outreach service model focussed on early, consistent, and frequent education, patient support in decision-making, and clinician engagement. RESULTS: A target prevalence of >30% for home-based therapies (mainly achieved with PD) was achieved within 2 years. This prevalence rate reached 35% within 3 years and was maintained at 8 years. In addition, selected patients already on maintenance satellite-based haemodialysis (Hybrid Working Group) were educated to achieve high levels of proficiencies in self-care. CONCLUSION: Having the system-wide approach to a Quality Improvement Process and using established principles and change management processes, the successful implementation of a new sustainable model of care focussed on home-based dialysis therapy was achieved. A key feature of the model (through outreach) was early nurse-led education and support of patients in decision-making and ongoing support through multidisciplinary care.

Fostering Undergraduate Medicine, Nursing, and Pharmacy Students' Readiness for Interprofessional Learning Using High Fidelity Simulation.

Background Interprofessional education is directly linked to high-quality patient care, however, it remains unclear whether senior undergraduate medicine, nursing, and pharmacy students are ready for interprofessional education using high fidelity human patient simulators. Purpose The purpose of this study was to explore student's readiness for interprofessional learning and determine whether participation in high fidelity interprofessional education resulted in higher levels of readiness for interprofessional learning. Methods An interventional program starting with a pre-test before the program and a post-test after the program ends were designed with 24 students. The students were assigned to seven interprofessional teams. Each team participated in a high fidelity interprofessional education module designed to teach the clinical management of an adult patient experiencing acute anaphylaxis. The Readiness for Interprofessional Learning Scale (RIPLS) was used as the pre and post-test instrument. Results Prior to participation, students reported a high level of readiness for interprofessional learning, but that readiness significantly improved after participation, including more positive attitudes towards teamwork, enhanced communication skills, and improved respect and trust for team members. Conclusions The findings from this study show a higher level of readiness for high fidelity interprofessional learning using human patient simulators among senior undergraduate medicine, nursing, and pharmacy students. These findings support the integration of high fidelity interprofessional education into undergraduate medicine, nursing, and pharmacy undergraduate education programs.

Antibacterial activity of high-dose nitric oxide against pulmonary Mycobacterium abscessus disease.

INTRODUCTION: Mycobacterium abscessus is an emerging pulmonary pathogen with limited treatment options. Nitric oxide (NO) demonstrates antibacterial activity against various bacterial species, including mycobacteria. In this study, we evaluated the effect of adjunctive inhaled NO therapy, using a novel NO generator, in a CF patient with pulmonary M. abscessus disease, and examined heterogeneity of response to NO in vitro. METHODS: In the compassionate-use treatment, a 24-year-old CF patient with pulmonary M. abscessus was treated with two courses of adjunctive intermittent NO, first at 160 p.p.m. for 21 days and subsequently by escalating the dose up to 240 p.p.m. for 8 days. Methemoglobin, pulmonary function, 6 min walk distance (6MWD), qualify of life and sputum microbiology were assessed. In vitro susceptibility tests were performed against patient's isolate and comparison clinical isolates and quantified by Hill's slopes calculated from time-kill curves. RESULTS: M. abscessus lung infection eradication was not achieved, but improvements in selected qualify of life domains, lung function and 6MWD were observed during the study. Inhaled NO was well tolerated at 160 p.p.m. Dosing at 240 p.p.m. was stopped due to adverse symptoms, although methemoglobin levels remained within safety thresholds. In vitro susceptibility tests showed a dose-dependent NO effect on M. abscessus susceptibility and significant heterogeneity in response between M. abscessus clinical isolates. The patient's isolate was found to be the least susceptible strain in vitro. CONCLUSION: These results demonstrate heterogeneity in M. abscessus susceptibility to NO and suggest that longer treatment regimens could be required to see the reduction or eradication of more resistant pulmonary strains.

Performance of models predicting residual lymph node disease in melanoma patients following sentinel lymph node biopsy.

BACKGROUND: Among melanoma patients with a tumor-positive sentinel node biopsy (SNB), approximately 20% harbor disease in non-sentinel nodes (nSN), as determined by a completion lymph node dissection (CLND). CLND lacks a survival benefit and has high morbidity. This study assesses predictive factors for nSN metastasis and validates five models predicting nSN metastasis. METHODS: Patients with invasive melanoma were identified from the BC Cancer Agency (2005-2015). Clinicopathological data were collected from 296 patients who underwent a CLND after a positive SNB. Multivariate analysis was completed to assess predictive variables in the study population. Five models were externally validated using overall model performance (Brier score [calibration and discrimination]) and discrimination (area under the ROC curve [AUC]). RESULTS: Seventy-three patients had nSN metastasis at the time of CLND. The variable most predictive of nSN involvement was lymphovascular invasion (odds ratio [OR] 3.99; 95% confidence interval [CI] 1.67-9.54; p = 0.002). The highest discrimination was Lee et al. (2004) (AUC 0.68 [95% CI 0.61-0.75]), Rossi et al. (2018) (AUC 0.68 [95% CI 0.57-0.77]), and Bertolli et al. (2019) (AUC 0.68 [95% CI 0.60-0.75]). Rossi et al. (2018) had the lowest overall model performance (Brier score 0.44). Rossi et al. (2018) and Bertolli et al. (2019) had the ability to stratify patients to a risk of nSN involvement up to 99% and 95%, respectively. CONCLUSION: Bertolli et al. (2019) had amongst the highest overall model performance, was the most clinically meaningful and is recommended as the preferred model for predicting nSN metastasis.

Bone Marrow-Derived Mesenchymal Stromal Cells (MSCs) Modulate the Inflammatory Character of Alveolar Macrophages from Sarcoidosis Patients.

Sarcoidosis is a devastating inflammatory disease affecting many organs, especially the lungs and lymph nodes. Bone marrow-derived mesenchymal stromal cells (MSCs) can "reprogram" various types of macrophages towards an anti-inflammatory phenotype. We wanted to determine whether alveolar macrophages from sarcoidosis subjects behave similarly by mounting an anti-inflammatory response when co-cultured with MSCs. Fifteen sarcoidosis and eight control subjects underwent bronchoscopy and bronchoalveolar lavage (BAL). Unselected BAL cells (70-94% macrophages) were isolated and cultured with and without MSCs from healthy adults. Following stimulation of the cultured cells with lipopolysaccharide, the medium was removed to measure interleukin 10 and tumor necrosis factor alpha (IL-10 and TNF-α). In two additional sarcoidosis subjects, flow cytometry was used to study intracellular cytokines and surface markers associated with alveolar macrophages to confirm the results. Unselected BAL cells from sarcoidosis subjects co-cultured with MSCs showed a reduction in TNF-α (pro-inflammatory M1) and an increase in IL-10 (anti-inflammatory M2) in 9 of 11 samples studied. Control subject samples showed few, if any, differences in cytokine production. Unselected BAL cells from two additional patients analyzed by flow cytometry confirmed a switch towards an anti-inflammatory state (i.e., M1 to M2) after co-culture with MSCs. These results suggest that, similarly to other macrophages, alveolar macrophages also respond to MSC contacts by changing towards an anti-inflammatory phenotype. Based on our results, we hypothesize that mesenchymal stromal cells applied to the airways might alleviate lung inflammation and decrease steroid need in patients with sarcoidosis.

Early effects of roflumilast on insulin sensitivity in adults with prediabetes and overweight/obesity involve age-associated fat mass loss - results of an exploratory study.

PURPOSE: Roflumilast (Daliresp, Daxas) is a FDA-approved phosphodiesterase 4 (PDE4) inhibitor for the treatment of moderate-to-severe chronic obstructive pulmonary disease. In mice and in limited human studies, this oral medication can cause weight loss and improve insulin sensitivity. We set out to determine the mechanism of its effect on insulin sensitivity. PATIENTS AND METHODS: Eight adults with overweight/obesity and prediabetes received roflumilast for 6 weeks. Before and after roflumilast, subjects underwent tests of insulin sensitivity, mixed meal test, body composition, markers of inflammation, and mitochondria function. Dietary intake and physical activity were also assessed. Our primary outcome was the change in peripheral insulin sensitivity, as assessed by the hyper-insulinemic euglycemic clamp. RESULTS: This study was underpowered for the primary outcome. Pre- and post-roflumilast mean peripheral insulin sensitivity were 48.7 and 70.0 mg/g fat free mass/minute, respectively, (P-value=0.18), respectively. Among the mixed meal variables, roflumilast altered glucagon-like peptide 1 (GLP-1) hormone the most, although the average effect was not statistically significant (P=0.18). Roflumilast induced a trend toward significance in 1) decreased energy intake (from 11,095 KJ to 8,4555 KJ, P=0.07), 2) decreased fat mass (from 34.53 to 32.97 kg, P=0.06), 3) decreased total and LDL cholesterol (P=0.06 for both variables), and 4) increased plasma free fatty acids (from 0.40 to 0.50 mEq/L, P=0.09) The interval changes in adiposity and free fatty acid were significantly associated with the subject's age (P-value range= <0.001 to 0.02 for the correlations). Inflammatory and adhesion markers, though unchanged, significantly correlated with one another and with incretin hormones only after roflumilast. CONCLUSION: We demonstrate, for the first time in humans, increasing percentage of fat mass loss from roflumilast with increasing age in adults with prediabetes and overweight/obesity. We also demonstrate novel associations among roflumilast-induced changes in incretin hormones, inflammatory markers, peripheral insulin sensitivity, and adiposity. We conclude that roflumilast's early effects on insulin sensitivity is indirect and likely mediated through roflumilast's prioritization of lipid over glucose handling. CLINICAL TRIALS REGISTRATION: NCT01862029.

Emergency Management of Anaphylaxis: A High Fidelity Interprofessional Simulation Scenario to Foster Teamwork Among Senior Nursing, Medicine, and Pharmacy Undergraduate Students.

Nursing, medicine, and pharmacy students have limited opportunities during their undergraduate programs to learn and practice together as an interprofessional team. This has prompted faculty at Memorial University of Newfoundland to explore the use of high fidelity simulated interprofessional education (HF-IPE) to help nursing, medicine, and pharmacy students learn about their roles, develop communication and collaboration skills, and foster teamwork. Research has shown that high fidelity simulated education can promote critical thinking, engage learners, improve confidence, and enhance psychomotor skills; however, there is limited data on the impact of HF-IPE on fostering teamwork. This technical report describes one HF-IPE scenario designed to foster teamwork among senior undergraduate nursing, medicine, and pharmacy students. The scenario is designed to promote an understanding of the roles of nursing, medical, and pharmaceutical professionals in an interprofessional team during the emergency management of an adult patient experiencing acute anaphylaxis. Teamwork and communication skills are emphasized, and students are provided with the opportunity to communicate and collaborate within an interprofessional healthcare team.

Translating Heart Health Knowledge into Action: A Vascular and Risk Reduction Program for Women Aged 35 to 65 Years.

BACKGROUND: Globally, about 8.6 million women die each year due to cardiovascular disease with cerebral vascular disease being the third leading cause of death in women. The province of New-foundland and Labrador has one of the highest rates of vascular disease in comparison to the rest of Canada. Women in New-foundland and Labrador have higher rates of vascular disease than their female cohorts across Canada. A vascular risk reduction programfor women aged 35 to 65 years was developed and implemented in a rural and an urban setting. PURPOSE: An evaluation of the program was conducted to assess the impact of the program on participants' satisfaction and to assess how women were able to apply acquired knowledge into their everyday lives to improve their vascular health. PROCEDURE: A thematic analysis of qualitative data collected during tvo focus groups (N=19) was completed. FINDINGS: Three core themes were identified that captured the experiences of the women who participated in the program including Solidifying One's Risk, Translating Knowledge into Action, and Making a Change. IMPLICATIONS: Implementation of community-based vascular education programs must consider the context in which the program is delivered, the population's unique needs, and existing resources if they are to be successful in sustaining healthy lifestyle behaviours known to decrease one's riskfor vascular disease.

Serum apolipoprotein A-I and large high-density lipoprotein particles are positively correlated with FEV1 in atopic asthma.

RATIONALE: Although lipids, apolipoproteins, and lipoprotein particles are important modulators of inflammation, varying relationships exist between these parameters and asthma. OBJECTIVES: To determine whether serum lipids and apolipoproteins correlate with the severity of airflow obstruction in subjects with atopy and asthma. METHODS: Serum samples were obtained from 154 atopic and nonatopic subjects without asthma, and 159 subjects with atopy and asthma. Serum lipid and lipoprotein levels were quantified using standard diagnostic assays and nuclear magnetic resonance (NMR) spectroscopy. Airflow obstruction was assessed by FEV1% predicted. MEASUREMENTS AND MAIN RESULTS: Serum lipid levels correlated with FEV1 only in the subjects with atopy and asthma. Serum levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apoA-I) were positively correlated with FEV1 in subjects with atopy and asthma, whereas a negative correlation existed between FEV1 and serum levels of triglycerides, low-density lipoprotein (LDL) cholesterol, apolipoprotein B (apoB), and the apoB/apoA-I ratio. NMR spectroscopy identified a positive correlation between FEV1 and HDLNMR particle size, as well as the concentrations of large HDLNMR particles and total IDLNMR (intermediate-density lipoprotein) particles in subjects with atopy and asthma. In contrast, LDLNMR particle size and concentrations of LDLNMR and VLDLNMR (very-low-density lipoprotein) particles were negatively correlated with FEV1 in subjects with atopy and asthma. CONCLUSIONS: In subjects with atopy and asthma, serum levels of apoA-I and large HDLNMR particles are positively correlated with FEV1, whereas serum triglycerides, LDL cholesterol, and apoB are associated with more severe airflow obstruction. These results may facilitate future studies to assess whether apoA-I and large HDLNMR particles can reduce airflow obstruction and disease severity in asthma.

Satellite hemodialysis services for patients with end stage renal disease.

More than 40,000 Canadians are living with end stage renal disease and approximately 22,400 of those are currently being treated with hemodialysis (The Kidney Foundation of Canada, 2013). Long distance travel to access hemodialysis services can be a serious burden for patients, and travelling more than 60 minutes can mean a 20% greater risk for death, as compared with those who travel 15 minutes or less (Moist et al., 2008). Satellite hemodialysis units are seen as one solution to this problem. This study assessed the impact of services provided by one satellite hemodialysis unit on patients' satisfaction, access to care and quality of life using a qualitative interview research design. Seven patients were interviewed and three themes emerged including the burden of long distance travel before satellite services (safety, time and cost), satisfaction with satellite services (pleasant environment and continuity of care), and improved quality of life. This study showed that a satellite hemodialysis unit improved access to services and enhanced the quality of life of those patients who participated in the study.

Caring for patients receiving therapeutic hypothermia post cardiac arrest in the intensive care unit.

Survivors of ventricular fibrillation cardiac arrest have poor and often devastating neurological outcomes despite advances in resuscitation techniques and services (Bernard et al., 2002; Collins & Samworth, 2008). In an effort to increase survival rates, improve neurological outcomes and reduce mortality for surviving patients, clinical trials have shown that a mild state of therapeutic hypothermia (32 degrees C to 34 degrees C) has been linked to improved patient outcomes post cardiac arrest (Koran, 2008; Lee & Asare, 2010). Many hospitals in Canada currently use therapeutic hypothermia (TH), but the nursing care requires advanced nursing knowledge and skills. In an effort to prepare registered nurses to care for patients receiving TH, a specially designed education program was implemented at the Rouge Valley Health System Hospital (RVHS) in Ontario. Busy nurses need flexibility in the delivery of programs in the clinical setting, and this program was designed to meet that need with a combination of self-paced modules, lectures, discussions and a return demonstration. In this article, the authors discuss the nursing care of post cardiac arrest patients receiving TH, and the design and implementation of the education program.

Organ donation experiences of family members.

The objective of this qualitative research study was to describe and interpret what life is like for individuals who have consented to donate the organs of a deceased relative for transplantation. This study captures the meaning of this phenomenon in a way to help nurses develop new insights into the lives of these individuals, enable them to implement strategies to better assist and support the family, and perhaps decrease barriers to organ donation. Thematic analysis of the participants' narrative descriptions identified five essential themes: the struggle to acknowledge the death, the need for a positive outcome of the death, creating a living memory, buying time, and the significance of support networks in the organ donation decision. The integration of these themes revealed the essence of the experience as creating of a sense of peace. These five themes and the essence of the experience are discussed in relation to the literature, followed by recommendations for future nursing practice, education, and research.

Abnormal lymphangiogenesis in idiopathic pulmonary fibrosis with insights into cellular and molecular mechanisms.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, debilitating respiratory disease whose pathogenesis is poorly understood. In IPF, the lung parenchyma undergoes extensive remodeling. We hypothesized that lymphangiogenesis is part of lung remodeling and sought to characterize pathways leading to lymphangiogenesis in IPF. We found that the diameter of lymphatic vessels in alveolar spaces in IPF lung tissue correlated with disease severity, suggesting that the alveolar microenvironment plays a role in the lymphangiogenic process. In bronchoalveolar lavage fluid (BALF) from subjects with IPF, we found short-fragment hyaluronic acid, which induced migration and proliferation of lymphatic endothelial cells (LECs), processes required for lymphatic vessel formation. To determine the origin of LECs in IPF, we isolated macrophages from the alveolar spaces; CD11b(+) macrophages from subjects with IPF, but not those from healthy volunteers, formed lymphatic-like vessels in vitro. Our findings demonstrate that in the alveolar microenvironment of IPF, soluble factors such as short-fragment hyaluronic acid and cells such as CD11b(+) macrophages contribute to lymphangiogenesis. These results improve our understanding of lymphangiogenesis and tissue remodeling in IPF and perhaps other fibrotic diseases as well.

MMP1 and MMP7 as potential peripheral blood biomarkers in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic lung disease associated with substantial morbidity and mortality. The objective of this study was to determine whether there is a peripheral blood protein signature in IPF and whether components of this signature may serve as biomarkers for disease presence and progression. METHODS AND FINDINGS: We analyzed the concentrations of 49 proteins in the plasma of 74 patients with IPF and in the plasma of 53 control individuals. We identified a combinatorial signature of five proteins-MMP7, MMP1, MMP8, IGFBP1, and TNFRSF1A-that was sufficient to distinguish patients from controls with a sensitivity of 98.6% (95% confidence interval [CI] 92.7%-100%) and specificity of 98.1% (95% CI 89.9%-100%). Increases in MMP1 and MMP7 were also observed in lung tissue and bronchoalveolar lavage fluid obtained from IPF patients. MMP7 and MMP1 plasma concentrations were not increased in patients with chronic obstructive pulmonary disease or sarcoidosis and distinguished IPF compared to subacute/chronic hypersensitivity pneumonitis, a disease that may mimic IPF, with a sensitivity of 96.3% (95% CI 81.0%-100%) and specificity of 87.2% (95% CI 72.6%-95.7%). We verified our results in an independent validation cohort composed of patients with IPF, familial pulmonary fibrosis, subclinical interstitial lung disease (ILD), as well as with control individuals. MMP7 and MMP1 concentrations were significantly higher in IPF patients compared to controls in this cohort. Furthermore, MMP7 concentrations were elevated in patients with subclinical ILD and negatively correlated with percent predicted forced vital capacity (FVC%) and percent predicted carbon monoxide diffusing capacity (DLCO%). CONCLUSIONS: Our experiments provide the first evidence for a peripheral blood protein signature in IPF to our knowledge. The two main components of this signature, MMP7 and MMP1, are overexpressed in the lung microenvironment and distinguish IPF from other chronic lung diseases. Additionally, increased MMP7 concentration may be indicative of asymptomatic ILD and reflect disease progression.

Progressive preclinical interstitial lung disease in rheumatoid arthritis.

BACKGROUND: Early detection and treatment for interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) may ameliorate disease progression. The objective of this study was to identify asymptomatic lung disease and potential therapeutic targets in patients having RA and preclinical ILD (RA-ILD). METHODS: Sixty-four adults with RA and 10 adults with RA and pulmonary fibrosis (RAPF) were referred to the National Institutes of Health, Bethesda, Maryland, and underwent high-resolution computed tomography (HRCT) and pulmonary physiology testing. Proteins capable of modulating fibrosis were quantified in alveolar fluid. RESULTS: Twenty-one of 64 patients (33%) having RA without dyspnea or cough had preclinical ILD identified by HRCT. Compared with patients without lung disease, patients with RA-ILD had statistically significantly longer histories of cigarette smoking (P< .001), increased frequencies of crackles (P= .02), higher alveolar-arterial oxygen gradients (P= .004), and higher HRCT scores (P< .001). The HRCT abnormalities progressed in 12 of 21 patients (57%) with RA-ILD. The alveolar concentrations of platelet-derived growth factor-AB and platelet-derived growth factor-BB were statistically significantly higher in patients having RA-ILD (mean [SE], 497.3 [78.6] and 1473 [264] pg/mL, respectively) than in patients having RA without ILD (mean [SE], 24.9 [42.4] and 792.7 [195.0] pg/mL, respectively) (P< .001 and P=.047, respectively). The concentrations of interferon gamma and transforming growth factor beta(2) were statistically significantly lower in patients having RAPF (mean [SE], 5.59 [1.11] pg/mL and 0.94 [0.46] ng/mL, respectively) than in patients having RA without ILD (mean [SE], 14.1 [1.9] pg/mL and 2.30 [0.39] ng/mL, respectively) (P=.001 and P=.006, respectively) or with preclinical ILD (mean [SD], 11.4 [2.6] pg/mL and 3.63 [0.66] ng/mL, respectively) (P=.04 and P=.007, respectively). Compared with patients having stable RA-ILD, patients having progressive RA-ILD had statistically significantly higher frequencies of treatment using methotrexate and higher alveolar concentrations of interferon gamma and transforming growth factor beta(1) (P=.046, P=.04, and P=.04, respectively). CONCLUSIONS: Asymptomatic preclinical ILD, which is detectable by HRCT, may be prevalent and progressive among patients having RA. Cigarette smoking seems to be associated with preclinical ILD in patients having RA, and treatment using methotrexate may be a risk factor for progression of preclinical ILD. Quantification of alveolar proteins indicates that potential pathogenic mechanisms seem to differ in patients having RA-ILD and symptomatic RAPF.

Early interstitial lung disease in familial pulmonary fibrosis.

RATIONALE: Identification of early, asymptomatic interstitial lung disease (ILD) in populations at risk of developing idiopathic pulmonary fibrosis (IPF) may improve the understanding of the natural history of IPF. OBJECTIVES: To determine clinical, radiographic, physiologic, and pathologic features of asymptomatic ILD in family members of patients with familial IPF. METHODS: One hundred sixty-four subjects from 18 kindreds affected with familial IPF were evaluated for ILD. Bronchoalveolar lavage fluid cells were analyzed using flow cytometry. Lung biopsies were performed in six subjects with asymptomatic ILD. MEASUREMENTS AND MAIN RESULTS: High-resolution computed tomography abnormalities suggesting ILD were identified in 31 (22%) of 143 asymptomatic subjects. Subjects with asymptomatic ILD were significantly younger than subjects with known familial IPF (P < 0.001) and significantly older than related subjects without lung disease (P < 0.001). A history of smoking was identified in 45% of subjects with asymptomatic ILD and in 67% of subjects with familial IPF; these percentages were significantly higher than that of related subjects without lung disease (23%) (P = 0.02 and P < 0.001, respectively). Percentages of activated CD4(+) lymphocytes were significantly higher in bronchoalveolar lavage fluid cells from subjects with asymptomatic ILD compared with related subjects without lung disease (P < 0.001). Lung biopsies performed in subjects with asymptomatic ILD revealed diverse histologic subtypes. CONCLUSIONS: Asymptomatic ILD in individuals at risk of developing familial IPF can be identified using high-resolution computed tomography scan of the chest, especially in those with a history of smoking. Lung biopsies from individuals in this cohort with early asymptomatic lung disease demonstrate various histologic subtypes of ILD.