Assessment of dyspnea in sarcoidosis using the Baseline Dyspnea Index (BDI) and the Transition Dyspnea Index (TDI).

INTRODUCTION: The Borg and Modified Medical Research Council (mMRC) dyspnea scales have been used to evaluate dyspnea in sarcoidosis. The Baseline Dyspnea Index (BDI) and Transitional Dyspnea Index (TDI) are useful for the assessment of dyspnea in COPD. It is not known if the BDI-TDI accurately assesses dyspnea in sarcoidosis patients. METHODS: Data was analyzed from the Registry for Advanced Sarcoidosis (ReAS), a multi-national database enrolling patients with advanced sarcoidosis and a comparison group of sarcoidosis patients with non-advanced disease. At baseline, patients completed a BDI questionnaire along with spirometry, 6-min walk distance (6MWD), mMRC, Borg score, fatigue assessment score (FAS) and HRQoL assessments using Kings Sarcoidosis Questionnaire (KSQ) and St Georges Respiratory Questionnaire (SGRQ). At 12-months, patients with advanced disease completed a TDI questionnaire along with the other measures. Correlations between BDI and baseline variables, and between TDI and changes in baseline variables were evaluated. RESULTS: There was significant correlation (p < 0.001 for all) between BDI and baseline 6MWD (rho = 0.336), FVC% (rho = 0.387), FEV1% (rho = 0.285), DLCO% (rho = 0.355), mMRC (rho = -0.721), Borg score (rho = -0.389), FAS (rho = -0.669), SGRQ (rho = -0.785), and KSQ (rho = 0.318 to 0.724). At follow-up, TDI correlated with BDI, but not with changes in pulmonary function or other dyspnea measures. CONCLUSION: BDI scores correlated with pulmonary function, 6MWD, and other dyspnea measures. TDI scores did not correlate with changes in pulmonary function or other dyspnea measures. BDI may be a useful independent measure of dyspnea in sarcoidosis patients. The role of TDI needs further evaluation in longitudinal studies associated with changes in clinical parameters.

Pleuroparenchymal fibroelastosis in idiopathic pulmonary fibrosis: Survival analysis using visual and computer-based computed tomography assessment.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) and pleuroparenchymal fibroelastosis (PPFE) are known to have poor outcomes but detailed examinations of prognostic significance of an association between these morphologic processes are lacking. METHODS: Retrospective observational study of independent derivation and validation cohorts of IPF populations. Upper-lobe PPFE extent was scored visually (vPPFE) as categories of absent, moderate, marked. Computerised upper-zone PPFE extent (cPPFE) was examined continuously and using a threshold of 2·5% pleural surface area. vPPFE and cPPFE were evaluated against 1-year FVC decline (estimated using mixed-effects models) and mortality. Multivariable models were adjusted for age, gender, smoking history, antifibrotic treatment and diffusion capacity for carbon monoxide. FINDINGS: PPFE prevalence was 49% (derivation cohort, n = 142) and 72% (validation cohort, n = 145). vPPFE marginally contributed 3-14% to variance in interstitial lung disease (ILD) severity across both cohorts.In multivariable models, marked vPPFE was independently associated with 1-year FVC decline (derivation: regression coefficient 18·3, 95 CI 8·47-28·2%; validation: 7·51, 1·85-13·2%) and mortality (derivation: hazard ratio [HR] 7·70, 95% CI 3·50-16·9; validation: HR 3·01, 1·33-6·81). Similarly, continuous and dichotomised cPPFE were associated with 1-year FVC decline and mortality (cPPFE ≥ 2·5% derivation: HR 5·26, 3·00-9·22; validation: HR 2·06, 1·28-3·31). Individuals with cPPFE ≥ 2·5% or marked vPPFE had the lowest median survival, the cPPFE threshold demonstrated greater discrimination of poor outcomes at two and three years than marked vPPFE. INTERPRETATION: PPFE quantification supports distinction of IPF patients with a worse outcome independent of established ILD severity measures. This has the potential to improve prognostic management and elucidate separate pathways of disease progression. FUNDING: This research was funded in whole or in part by the Wellcome Trust [209,553/Z/17/Z] and the NIHR UCLH Biomedical Research Centre, UK.

Psychometric validation of the needs assessment tool: progressive disease in interstitial lung disease.

The inter-rater/test-retest reliability and construct validity of a palliative care needs assessment tool in interstitial lung disease (NAT:PD-ILD) were tested using NAT:PD-ILD-guided video-recorded consultations, and NAT:PD-ILD-guided consultations, and patient and carer-report outcomes (St George's Respiratory Questionnaire (SGRQ)-ILD, Carer Strain Index (CSI)/Carer Support Needs Assessment Tool (CSNAT)). 11/16 items reached at least fair inter-rater agreement; 5 items reached at least moderate test-retest agreement. 4/6 patient constructs demonstrated agreement with SGRQ-I scores (Kendall's tau-b, 0.24-20.36; P<0.05). 4/7 carer constructs agreed with the CSI/CSNAT items (kappa, 0.23-20.53). The NAT:PD-ILD is reliable and valid. Clinical effectiveness and implementation are to be evaluated.

Palliative care in interstitial lung disease: living well.

Progressive fibrotic interstitial lung diseases (ILDs) are characterised by major reductions in quality of life and survival and have similarities to certain malignancies. However, palliative care expertise is conspicuously inaccessible to many patients with ILD. Unmet patient and caregiver needs include effective pharmacological and psychosocial interventions to improve quality of life throughout the disease course, sensitive advanced care planning, and timely patient-centred end-of-life care. The incorrect perception that palliative care is synonymous with end-of-life care, with no role earlier in the course of ILD, has created a culture of neglect. Interventions that aim to improve life expectancy are often prioritised without rigorous assessment of the individual's health and psychosocial needs, thereby inadvertently reducing quality of life. As in malignant disorders, radical interventions to slow disease progression and palliative measures to improve quality of life should both be prioritised. Efficient patient-centred models of palliative care must be validated, taking into account religious and cultural differences, as well as variability of resources. Effective implementation of palliative care for ILD will require multidisciplinary participation from clinicians, specialist nurses, psychologists, social workers, and, in some countries, non-governmental faith and community-based organisations with access to palliative care expertise.

The Adaptation, Face, and Content Validation of a Needs Assessment Tool: Progressive Disease for People with Interstitial Lung Disease.

BACKGROUND: Irrreversible interstitial lung disease (ILD) is associated with high morbidity and mortality. Palliative care needs of patients and caregivers are not routinely assessed; there is no tool to identify needs and triage support in clinical practice. OBJECTIVE: The study objective was to adapt and face/content validate a palliative needs assessment tool for people with ILD. METHODS: The Needs Assessment Tool: Progressive Disease-Cancer (NAT:PD-C) was adapted to reflect the palliative care needs identified from the ILD literature and patient/caregiver interviews. Face and content validity of the NAT:PD-ILD was tested using patient/caregiver focus groups and an expert consensus group. Participants in the study were two English tertiary health care trusts' outpatients clinics. There were four focus groups: two patient (n = 7; n = 4); one caregiver (n = 3); and one clinician (n = 8). There was a single caregiver interview, and an expert consensus group-academics (n = 3), clinicians (n = 9), patients (n = 4), and caregivers (n = 2). Each item in the tool was revised as agreed by the groups. Expert consensus was reached. RESULTS: Overall, the tool reflected participants' experience of ILD. Each domain was considered relevant. Adaptations were needed to represent the burden of ILD: respiratory symptoms (especially cough) and concerns about sexual activity were highlighted. All emphasized assessment of caregiver need as critical, and the role of caregivers in clinical consultations. CONCLUSIONS: The NAT:PD-ILD appears to have face and content validity. The inclusion of the family caregiver in the consultation as someone with their own needs as well as a source of information was welcomed. Reliability testing and construct validation of the tool are ongoing.

The clinical effectiveness and cost-effectiveness of treatments for idiopathic pulmonary fibrosis: a systematic review and economic evaluation.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a life-limiting lung disease that generally affects people over 60 years old. The main symptoms are shortness of breath and cough, and as the disease progresses there is a considerable impact on day-to-day life. Few treatments are currently available. OBJECTIVES: To conduct a systematic review of clinical effectiveness and an analysis of cost-effectiveness of treatments for IPF based on an economic model informed by systematic reviews of cost-effectiveness and quality of life. DATA SOURCES: Eleven electronic bibliographic databases, including MEDLINE, EMBASE, Web of Science, and The Cochrane Library and the Centre for Reviews and Dissemination databases, were searched from database inception to July 2013. Reference lists of relevant publications were also checked and experts consulted. METHODS: Two reviewers independently screened references for the systematic reviews, extracted and checked data from the included studies and appraised their risk of bias. An advisory group was consulted about the choice of interventions until consensus was reached about eligibility. A narrative review with meta-analysis was undertaken, and a network meta-analysis (NMA) was performed. A decision-analytic Markov model was developed to estimate cost-effectiveness of pharmacological treatments for IPF. Parameter values were obtained from NMA and systematic reviews. Univariate and probabilistic sensitivity analyses were undertaken. The model perspective is NHS and Personal Social Services, and discount rate is 3.5% for costs and health benefits. RESULTS: Fourteen studies were included in the review of clinical effectiveness, of which one evaluated azathioprine, three N-acetylcysteine (NAC) (alone or in combination), four pirfenidone, one BIBF 1120, one sildenafil, one thalidomide, two pulmonary rehabilitation, and one a disease management programme. Study quality was generally good, with a low risk of bias. The current evidence suggests that some treatments appear to be clinically effective. The model base-case results show increased survival for five pharmacological treatments, compared with best supportive care, at increased cost. General recommendations cannot be made of their cost-effectiveness owing to limitations in the evidence base. LIMITATIONS: Few direct comparisons of treatments were identified. An indirect comparison through a NMA was performed; however, caution is recommended in the interpretation of these results. In relation to the economic model, there is an assumption that pharmacological treatments have a constant effect on the relative rate of per cent predicted forced vital capacity decline. CONCLUSIONS: Few interventions have any statistically significant effect on IPF and a lack of studies on palliative care approaches was identified. Research is required into the effects of symptom control interventions, in particular pulmonary rehabilitation and thalidomide. Other research priorities include a well-conducted randomised controlled trial on inhaled NAC therapy and an updated evidence synthesis once the results of ongoing studies are reported. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012002116. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

The effectiveness and cost-effectiveness of treatments for idiopathic pulmonary fibrosis: systematic review, network meta-analysis and health economic evaluation.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a life-limiting lung disease with considerable impact on patients and carers as the disease progresses. Currently few treatments are available. We aimed to evaluate the clinical and cost-effectiveness of available treatments for IPF. METHODS: Systematic reviews of clinical effectiveness, quality of life and cost effectiveness were undertaken. Eleven bibliographic databases were searched from inception to July 2013 and studies were assessed for eligibility against a set of pre-defined criteria. Two reviewers screened references, extracted data from included studies and appraised their quality. An advisory group was consulted about the choice of interventions. A narrative review was undertaken and where feasible fixed effect and random effects meta-analysis were undertaken including a network meta-analysis (NMA). A decision-analytic Markov model was developed to estimate cost-effectiveness of pharmacological treatments for IPF. Following best practice recommendations, the model perspective was of the national health service and personal social services, a discount rate of 3.5% for costs and health benefits was applied and outcomes were expressed as cost per quality adjusted life-year gained. Parameter values were obtained from the NMA and systematic reviews. Sensitivity analyses were undertaken. RESULTS: Fourteen studies were included in the review of clinical effectiveness, of which one evaluated azathioprine, three N-acetylcysteine [NAC] (alone or in combination), four pirfenidone, one nintedanib, one sildenafil, one thalidomide, two pulmonary rehabilitation, and one a disease management programme. Study quality was generally good. Evidence suggests that some effective treatments are available. In NMA only nintedanib and pirfenidone show statistically significant improvements. The model results show increased survival for five pharmacological treatments (NAC triple therapy, inhaled NAC, nintedanib, pirfenidone, and sildenafil) compared with best supportive care, at increased cost. Only inhaled NAC was cost-effective at current willingness to pay thresholds but it may not be clinically effective. CONCLUSIONS: Few interventions have any statistically significant effect and the cost-effectiveness of treatments is uncertain. A lack of studies on palliative care approaches was identified and there is a need for further research into pulmonary rehabilitation and thalidomide in particular. A well conducted RCT on inhaled NAC therapy should also be considered.

The WASOG Sarcoidosis Organ Assessment Instrument: An update of a previous clinical tool.

INTRODUCTION: A Case Control Etiology of Sarcoidosis Study (ACCESS) sarcoidosis organ assessment instrument has been used for more than a decade to establish uniform standards for the probability of sarcoidosis organ involvement. The ACCESS instrument has become increasingly outdated as new technologies have been developed. Furthermore, the ACCESS instrument failed to address all possible organs involved with sarcoidosis. For these reasons, the World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG) developed a new sarcoidosis organ assessment instrument. METHODS: Clinical sarcoidosis experts assessed various clinical manifestations for the probability of sarcoidosis organ involvement. Two criteria were required to apply this assessment: 1) histologic evidence of granulomatous inflammation of unknown cause in an organ that was not being assessed; 2) the clinical manifestation being addressed required that alternative causes other than sarcoidosis had been reasonably excluded. Clinical manifestations were assessed as either: a) highly probable: likelihood of sarcoidosis causing this manifestation of at least 90%.; b) probable: likelihood of sarcoidosis causing this manifestation of between 50 and 90%; c) possible: likelihood of sarcoidosis causing this manifestation of less than 50%. The sarcoidosis experts voted on the likelihood of sarcoidosis causing each manifestation using Delphi study methodology where at least 70% agreement of the experts was needed for consensus. RESULTS: Various clinical manifestations were classified as highly probable, at least probable, possible, or indeterminate when no consensus could be reached. CONCLUSION: An instrument was developed by expert opinion that may be useful for the clinician and researcher in establishing criteria for sarcoidosis organ involvement.

Palliative care for people with non-malignant lung disease: summary of current evidence and future direction.

BACKGROUND: The physical and psychosocial needs of patients with chronic non-malignant lung disease are comparable to those with lung cancer. This article will focus on chronic obstructive pulmonary disease, interstitial lung disease and cystic fibrosis as examples of life-limiting, non-curable and non-malignant lung diseases. THE NEED FOR SUPPORTIVE AND PALLIATIVE CARE: Recent national guidance has demanded that palliative care is inclusive of all patients with life-limiting disease, irrespective of diagnosis, and that specialist palliative care teams are involved in the management of patients on a basis of need rather than prognosis. WHAT IS KNOWN: Despite medical therapy, most patients with moderate to severe chronic obstructive pulmonary disease, interstitial lung disease and cystic fibrosis experience pain, fatigue and dyspnoea, with the majority not getting relief from dyspnoea towards the end of life. Furthermore, dyspnoea causes social isolation and difficulty performing activities of daily living and impairs quality of life. There is an increasing evidence base for the assessment of supportive and palliative care needs, symptom interventions, prognostication, models of service delivery and implications of these for clinical practice and research in non-malignant lung diseases. WHAT IS UNKNOWN: Despite advances, much still remains unknown regarding assessment, management and prognostication in individual chronic non-malignant lung diseases. Although different service models are being used in clinical practice, the optimal model(s) of service delivery remain unknown. IMPLICATION FOR FUTURE RESEARCH, POLICY AND PRACTICE: We describe key areas for further research, which include the need for large, high-quality trials of pharmacological and non-pharmacological interventions and their combinations as well as evaluation of the efficacy and cost-effectiveness of models of care. As access to palliative care is poor for these patients, the barriers to referral need to be understood and reduced, which along with effective working between palliative care teams, with respiratory services backup, should optimise delivery of care in patients with life-limiting non-malignant lung disease.

The palliative care needs for fibrotic interstitial lung disease: a qualitative study of patients, informal caregivers and health professionals.

BACKGROUND: While there have been some studies looking at the impact on quality of life of patients with idiopathic pulmonary fibrosis, to date no qualitative research looking at the specialist palliative needs of these patients has been conducted. AIM: This study aims to explore the specialist palliative care needs of people living with end-stage progressive idiopathic fibrotic interstitial lung disease. DESIGN AND SETTINGS/PARTICIPANTS: In total, 18 qualitative semi-structured in-depth interviews were conducted with patients, their informal caregivers and health professionals across two specialist interstitial lung disease centres in London and in the community. RESULTS: Many participants reported uncontrolled symptoms of shortness of breath, cough and insomnia, which profoundly impacted every part of patients' and informal caregivers' lives. Psychologically, patients were frustrated and angry at the way in which their illness severely limited their ability to engage in activities of daily living and compromised their independence. Furthermore, both patients and informal caregivers also reported that the disease seriously affected family relationships where strain was pronounced. There was varied knowledge and confidence among health professionals in managing symptoms, and psychosocial needs were often underestimated. CONCLUSION: This study is the first of its kind to examine in depth the impact of symptoms and psychosocial needs revealing the profound effect on every aspect of progressive idiopathic fibrotic interstitial lung disease patients' and informal caregivers' lives. Education and guidance of appropriate palliative care interventions to improve symptom control are needed. A case conference intervention with individualised care plans may help in addressing the substantial symptom control and psychosocial needs of these patients and informal caregivers.

Interventions to improve symptoms and quality of life of patients with fibrotic interstitial lung disease: a systematic review of the literature.

BACKGROUND: Patients with fibrotic interstitial lung disease have symptom control and quality of life (QoL) needs. This review aims to evaluate the evidence for the use of interventions in improving dyspnoea, other symptoms and QoL. METHODS: Eleven databases, relevant websites and key journals were hand-searched. Studies were assessed and data extracted independently by two researchers using standardised proformas. Meta-analyses were performed where possible with 95% CI. RESULTS: 34 papers with 19 interventions in 3635 patients were included. Meta-analyses showed no significant effect of interferon γ-1b or sildenafil on 6-minute walking distance (6MWD) or dyspnoea. Pulmonary rehabilitation and pirfenidone had a positive effect on 6MWD (mean difference (95% CI) 27.4 (4.1 to 50.7)) and 24.0 (4.3 to 43.7), respectively), and pulmonary rehabilitation had a mixed effect on dyspnoea. Both pulmonary rehabilitation and sildenafil showed a trend towards significance in improving QoL. There was weak evidence for the improvement of 6MWD using oxygen; dyspnoea using prednisolone, diamorphine, D-pencillamine and colchicine; cough using interferon α and thalidomide; anxiety using diamorphine; fatigue using pulmonary rehabilitation; and QoL using thalidomide and doxycycline. A wide range of outcome scales was used and there were no studies with economic evaluation. CONCLUSIONS: There is strong evidence for the use of pulmonary rehabilitation and pirfenidone to improve 6MWD and moderate evidence for the use of sildenafil and pulmonary rehabilitation to improve QoL. Future recommendations for research would include careful consideration of the dichotomy of radical and palliative treatments when deciding on how symptom and QoL outcome measures are used and data presented.

'I wish I knew more ...' the end-of-life planning and information needs for end-stage fibrotic interstitial lung disease: views of patients, carers and health professionals.

The importance at the end of life of developing effective communication and meeting information needs is recognised as being central to enhance patient and family centred experience. This qualitative study aimed to explore understanding of the disease, preferences regarding end-of-life planning, and views on communication and coordination of care in patients with Progressive Idiopathic Fibrotic Interstitial Lung Disease (PIF-ILD). Twelve semistructured in-depth qualitative interviews were conducted among PIF-ILD patients and carers attending two London hospitals. Six Interviews were also conducted among health professionals from one London Hospital, a palliative care service and primary care. There was good understanding of the terminal nature of the disease among both patients and carers, but a poor understanding of prognosis, and how the disease would manifest at the end stages. Both patients and carers expressed a wish to receive more information from clinicians. Health professionals recognised the difficulty of balancing information needs with maintaining hope. No participants were aware of any palliative care input, and no participants had considered important end-of-life issues, such as preferred place of care and preferred place of death. Our work shows that palliative interventions need to be developed for this group of patients which should aim to improve communication and coordination of care, while facilitating discussions surrounding information needs and important end-of-life preferences.

The development and validation of the King's Sarcoidosis Questionnaire for the assessment of health status.

RATIONALE: Health status is impaired in patients with sarcoidosis. There is a paucity of tools that assess health status in sarcoidosis. The objective of this study was to develop and validate the King's Sarcoidosis Questionnaire (KSQ), a new modular health status measure. METHODS: Patients with sarcoidosis were recruited from outpatient clinics. The development of the questionnaire consisted of three phases: item generation; item reduction, Rasch analysis to create unidimensional scales and validation; repeatability testing. RESULTS: 207 patients with sarcoidosis (organ involvement: 184 lung, 54 skin, 45 eye disease) completed a 65-item preliminary questionnaire. 36 items were removed due to redundancy or poor fit to the Rasch model. The final version of the KSQ consisted of five modules (General health status, Lung, Skin, Eye, Medications). Internal consistency assessed with Cronbach's α coefficient was 0.70-0.93 for KSQ modules. Concurrent validity of the Lung module was high compared with St George's Respiratory Questionnaire (r=-0.83) and moderate when compared to forced vital capacity (r=0.49). Concurrent validity with skin-specific and eye-specific measures ranged from r=-0.4 to 0.8. The KSQ was repeatable over 2 weeks (n=39), intraclass correlation coefficients for modules were 0.90-0.96. CONCLUSIONS: The KSQ is a brief, valid, self-completed health status measure for sarcoidosis. It can be used in the clinic to assess sarcoidosis from the patients' perspective.

Effect of aging on lung structure in vivo: assessment with densitometric and fractal analysis of high-resolution computed tomography data.

PURPOSE: To test the hypothesis that there is a difference between the lung computed tomography (CT) microstructure of asymptomatic older individuals and that of young individuals as evaluated by objective indices of complexity and density. MATERIALS AND METHODS: Two study groups of nonsmoking urban-dwelling individuals over 75 years and under 55 years were prospectively identified. Thirty-three consecutive volunteers (21 older than 75 y and 12 less than 55 y) were included, and CTs were performed with concurrent pulmonary function testing. Pulmonary regions of interest (ROIs) were evaluated with fractal dimension (FD) analysis (an index of complexity), mean lung density (MLD), and percentage of pixels with lung density (LD) less than thresholds of -910 HU and -950 HU. The Student t test and the Mann-Whitney test were used to evaluate for differences in mean values between groups. The Pearson correlation coefficient was used to correlate mean FD value and LD data with pulmonary function. RESULTS: Significant correlations of ROI MLD, LD -910 HU, and LD -950 HU with age and sex were shown (P = 0.029-0.003). The ROI mean FD value was greater in younger individuals compared with older individuals (76.5 ± 1.7 vs. 70.3 ± 1.2; P = 0.004). There was a correlation between Kco (gas-diffusing capacity adjusted for alveolar volume) and mean FD value (P = 0.006) and MLD (P = 0.015). CONCLUSION: The lung parenchyma of nonsmoking older urban-dwelling asymptomatic individuals has significantly different CT density and complexity compared with younger individuals.

Non-invasive assessment of pulmonary blood flow using an inert gas rebreathing device in fibrotic lung disease.

BACKGROUND AND AIMS: Pulmonary hypertension (PH) is increasingly recognised in patients with diffuse lung disease, and is associated with increased mortality. Cardiac output (CO) is a prognostic marker in PH. Non-invasive assessment of pulmonary blood flow (PBF(INNOCOR)) with the inert gas rebreathing Innocor device has been validated against CO in PH, but not in PH associated with parenchymal lung disease. PBF(INNOCOR) may be less accurate in patients with lung disease because of intrapulmonary shunting and/or incomplete gas mixing. Our aim was to determine the variability of PBF(INNOCOR) in normal subjects, before evaluating PBF(INNOCOR) in diffuse lung disease against CO measured by the indirect Fick method (CO(FICK)) at right heart catheterisation (RHC). METHODS AND RESULTS: 23 normal subjects had lung volume measurements by a constant-volume body plethysmograph and three consecutive PBF(INNOCOR) measurements on the same day. 20 subjects returned for repeat assessment. PBF(INNOCOR) had good intrasession repeatability (coefficient of variation (CV)=6.57%) and intersession reproducibility (mean CO difference=0.13; single determinant SD=0.49; CV=9.7%). 28 consecutive patients with lung fibrosis referred for RHC had PBF(INNOCOR) measured within 24 h of RHC. There was good agreement between CO(FICK) and PBF(INNOCOR), with no evidence of systematic bias (mean CO(FICK) 4.3+/-1.0; PBF(INNOCOR) 4.0+/-1.2l/ min; p=0.07). Bland-Altman analysis revealed a mean difference of -0.32 and limits of agreement of -2.10 to +1.45. CONCLUSION: Non-invasive PBF measured by the inert gas rebreathing Innocor device has good intrasession repeatability and intersession reproducibility. In diffuse lung disease, CO can be accurately and non-invasively measured by the Innocor device.