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Background Physiological functions with circadian rhythmicity are often disrupted during illness. Objective To assess the utility of circadian rhythmicity of vital signs in predicting outcome of traumatic brain injury (TBI). Methods A retrospective single-center cohort study of adult intensive care unit (ICU) patients with largely isolated TBI to explore the relationship between the circadian rhythmicity of vital signs during the last 24 hours before ICU discharge and clinical markers of TBI severity and score on the Glasgow Outcome Scale 6 months after injury (GOS-6). Results The 130 study participants had a median age of 39.0 years (IQR, 23.0-59.0 years), a median Glasgow Coma Scale score at the scene of 8.0 (IQR, 3.0-13.0), and a median Rotterdam score on computed tomography of the head of 3 (IQR, 3-3), with 105 patients (80.8%) surviving to hospital discharge. Rhythmicity was present for heart rate (30.8% of patients), systolic blood pressure (26.2%), diastolic blood pressure (20.0%), and body temperature (26.9%). Independent predictors of a dichotomized GOS-6 ≥4 were the Rotterdam score (odds ratio [OR], 0.38 [95% CI, 0.18-0.81]; P = .01), Glasgow Coma Scale score at the scene (OR, 1.22 [95% CI, 1.05-1.41]; P = .008), age (OR, 0.95 [95% CI, 0.92-0.98]; P = .003), oxygen saturation Conclusion Circadian rhythmicity of vital signs at ICU discharge is not predictive of GOS-6 in patients with TBI.

Objectives Fibrotic interstitial lung disease (ILD) includes a large group of conditions that lead to scarring of the lungs. The lack of available 5-level EuroQol 5D (EQ5D) data has limited the ability to conduct economic evaluations in ILD. The purpose of this study was to develop and validate a mapping algorithm that predicts EQ5D utilities from commonly collected pulmonary function measurements (forced vital capacity [FVC] and diffusing capacity of the lung for carbon monoxide [DLCO]) in fibrotic ILDs. Methods EQ5D utility and pulmonary function measurements from the Canadian Registry for Pulmonary Fibrosis were included. Ordinary least squares (OLS), beta regression, two-part, and tobit models were used to map EQ5D utilities from FVC or DLCO. Model performance was assessed by comparing the predicted and observed utilities. Subgroup analyses were also conducted to test how well models performed across different patient characteristics. The models were then externally validated in the Australian Idiopathic Pulmonary Fibrosis Registry. Results The OLS model performed as well as other more complex models (root mean squared error: 0.17 for FVC and 0.16 for DLCO). As with the other models, the OLS algorithm performed well across the different subgroups (except for EQ5D utilities < 0.5) and in the external validation cohort. Conclusion We developed a mapping algorithm that predicts EQ5D utilities from FVC and DLCO, with the intent that this algorithm can be applied to clinical trial populations and real-world cohorts that have not prioritized collection of health-related utilities. The mapping algorithm can be used in future economic evaluations of potential ILD therapies.

Core body temperature (CBT) patterns associated with sleep have not been described in the critically ill. This study aimed to characterise night-time sleep and its relationship to CBT in ICU patients. A prospective study was performed in a 27-bed tertiary adult intensive care unit of 20 mechanically ventilated patients in the weaning stage of their critical illness. The study assessed sleep by polysomnography (PSG) during the evening between 21:00-7:00 hours, nursing interventions using the Therapeutic Intervention Scoring System (TISS), illness severity using SOFA and APACHE II scores and CBT 24-hour pattern. Patients were awake for approximately half the study period (45.04%, IQR 13.81-77-17) with no REM (0%, IQR 0-0.04%) and median arousals of 19.5/hour (IQR 7.1-40.9). The 24-hour CBT had a rhythmic pattern in 13 (65%) patients with a highly variable phase of median peak time at 17:35 hours (IQR 12:40-19:39). No significant associations were found between CBT rhythmicity, sleep stages, sleep EEG frequency density, illness severity scores or TISS on the day of PSG. There was no relationship between time awake and CBT rhythmicity (P=0.48) or CBT peak time (P=0.82). The relationship between circadian rhythms and sleep patterns in the critically ill is complex. Patients recovering in ICU commonly have CBT loss of rhythmicity or a significant phase shift with loss of normal night-time patterns of sleep architecture. Appropriate care plans to promote sleep and circadian rhythm require further investigation of contributing factors such as environment, clinical care routines, illness type and severity.

Background The difference in patient comfort with conscious sedation versus general anaesthesia for bronchoscopy has not been adequately assessed in a randomised trial. This study aimed to assess if patient comfort during bronchoscopy with conscious sedation is noninferior to general anaesthesia. Methods 96 subjects were randomised to receive conscious sedation or general anaesthesia for bronchoscopy. The primary outcome was subject comfort. Secondary outcomes included willingness to undergo a repeat procedure if necessary and level of sedation assessed clinically and by bispectral index (BIS) monitoring. Results There was no significant difference between subject comfort scores (difference −0.01, 95% CI −0.63–0.61 on a 10-point scale; p=0.97) or willingness to undergo a repeat procedure (97.7% versus 91.8%, 95% CI −4.8–15.5%; p=0.37). Deeper levels of sedation in the general anaesthesia cohort was confirmed with both clinical and BIS monitoring. There was no significant difference in diagnostic accuracy (conscious sedation 93.9%, 95% CI 80.4–98.3% versus general anaesthesia 86.5%, 95% CI 72.0–94.1%; p=0.43). There were more complications (29.6%, 95% CI 18.2–44.2% versus 6.1%, 95% CI 2.1–16.5%; p, Conscious sedation was noninferior to anaesthetist-controlled general anaesthesia for patient comfort during bronchoscopy in this randomised trial. Deeper sedation with general anaesthesia did not improve comfort and had increased complications. https://bit.ly/3sCDfEy

Background and objective Current guidelines for the diagnosis of idiopathic pulmonary fibrosis (IPF) provide specific criteria for diagnosis in the setting of multidisciplinary discussion (MDD). We evaluate the utility and reproducibility of these diagnostic guidelines, using clinical data from the Australian IPF Registry. Methods All patients enrolled in the registry undergo a diagnostic review whereby international IPF guidelines are applied via a registry MDD. We investigated the clinical applicability of these guidelines with regard to: (i) adherence to guidelines, (ii) Natural history of IPF diagnostic categories and (iii) Concordance for diagnostic features. Results A total of 417 participants (69% male, 70.6 ± 8.0 years) with a clinical diagnosis of IPF underwent MDD. The 23% of participants who did not meet IPF diagnostic criteria displayed identical disease behaviour to those with confirmed IPF. Honeycombing on radiology was associated with a worse prognosis and this translated into poorer prognosis in the ‘definite’ IPF group. While there was moderate agreement for IPF diagnostic categories, agreement for specific radiological features, other than honeycombing, was poor. Conclusion In clinical practice, physicians do not always follow IPF diagnostic guidelines. We demonstrate a cohort of IPF patients who do not meet IPF diagnostic guideline criteria, based largely on their radiology and lack of lung biopsy, but who have outcomes identical to those with IPF.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive lung disease in which circulatory biomarkers have the potential for guiding management in clinical practice. We assessed the prognostic role of serum biomarkers in three independent IPF cohorts: Australian Idiopathic Pulmonary Fibrosis Registry (AIPFR), Trent Lung Fibrosis (TLF) and Prospective Observation of Fibrosis in the Lung Clinical Endpoints (PROFILE).MethodsIn the AIPFR cohort, candidate proteins were assessed by ELISA as well as in an unbiased proteomic approach. LASSO (least absolute shrinkage and selection operator) regression was used to restrict the selection of markers that best accounted for the progressor phenotype at 1 year in the AIPFR cohort, and subsequently prospectively selected for replication in the validation TLF cohort and assessed retrospectively in the PROFILE cohort. Four significantly replicating biomarkers were aggregated into a progression index model based on tertiles of circulating concentrations.Results189 participants were included in the AIPFR cohort, 205 participants from the TLF cohort and 122 participants from the PROFILE cohort. Differential biomarker expression was observed by ELISA and replicated for osteopontin, matrix metallopeptidase-7, intercellular adhesion molecule-1 and periostin for those with a progressor phenotype at 1 year. Proteomic data did not replicate. The progression index in the AIPFR, TLF and PROFILE cohorts predicted risk of progression, mortality and progression-free survival. A statistical model incorporating the progression index demonstrated the capacity to distinguish disease progression at 12 months, which was increased beyond the clinical GAP (gender, age and physiology) score model alone in all cohorts, and significantly so within the incidence-based TLF and PROFILE cohorts.ConclusionA panel of circulatory biomarkers can provide potentially valuable clinical assistance in the prognosis of IPF patients.

Background and objective Studies analysing the effect of worsening pulmonary physiological impairment in idiopathic pulmonary fibrosis (IPF) with respect to quality of life have been limited to single centres or highly selected trial populations. The aim of this study was to determine the principal determinants of baseline and longitudinal health-related quality of life (HRQoL) in a large unselected IPF population. Methods We used the Australian IPF Registry to examine the relationship between HRQoL, measured using the St George Respiratory Questionnaire (SGRQ), and demographic features, physiological features, co-morbidities and symptoms. Linear regression analysis was performed to identify predictors of baseline HRQoL, linear mixed model analysis to determine the effect of time and forced vital capacity (FVC) on SGRQ and Cox proportional hazards regression to examine the relationship between HRQoL and all-cause mortality. Results Baseline data from 516 patients were available (347 males; mean (SD) age: 71.3 ± 8.6 years). Univariate analysis showed significant associations between HRQoL and demographic, clinical and physiological features. However, multivariate analysis demonstrated independent associations only between SGRQ and dyspnoea (University of California San Diego Shortness of Breathlessness Questionnaire (UCSD-SOBQ); R2 = 0.71, P

Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterised by progressive decline in pulmonary function. The rate of decline can vary, with some patients remaining stable over longer periods of time and others rapidly progressing [1]. tThe variable progression of this disease makes it difficult to elucidate pathogenic pathways involved in the initiation and progression of IPF. Advances in high-throughput gene-expression analyses have led to improvements in our understanding of disease biology and prognostic gene signatures. We hypothesise that IPF has a unique circulatory transcriptional profile compared to healthy controls, with additional differences between stable and progressive disease likely related to disease pathogenesis. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Miss Clynick has nothing to disclose. Conflict of interest: Dr. Jo has nothing to disclose. Conflict of interest: Dr. Corte has nothing to disclose. Conflict of interest: Dr. Glaspole has nothing to disclose. Conflict of interest: Dr. Grainge has nothing to disclose. Conflict of interest: Dr. Hopkins has nothing to disclose. Conflict of interest: Dr. Reynolds has nothing to disclose. Conflict of interest: Dr. Chapman has nothing to disclose. Conflict of interest: Dr. Walters has nothing to disclose. Conflict of interest: Dr. Zappala has nothing to disclose. Conflict of interest: Dr. Keir has nothing to disclose. Conflict of interest: Dr. Cooper has nothing to disclose. Conflict of interest: Dr. Mahar has nothing to disclose. Conflict of interest: Dr. Ellis has nothing to disclose. Conflict of interest: Dr. Goh has nothing to disclose. Conflict of interest: Dr. Baltic has nothing to disclose. Conflict of interest: Miss Ryan has nothing to disclose. Conflict of interest: Dr. Tan has nothing to disclose. Conflict of interest: Dr. Moodley has nothing to disclose.

Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterised by an overall poor prognosis. The rate of disease decline and progression to death can vary, with some patients remaining stable over longer periods of time and others displaying rapid progression [1, 2]. The highly heterogeneous nature of this disease makes it difficult to elucidate the pathways involved in the initiation and progression of IPF and what determines the clinical trajectory of these patients. Advances in high-throughput gene expression analyses have led to improvements in our understanding of disease biology with insights into prognostic and predictive gene signatures [3]. This study sought to characterise differences in gene expression profiles found in the circulation between “stable” and “progressive” IPF patients, to help identify relevant biomarkers that may provide insights into the pathogenesis of progressive IPF. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Miss Clynick has nothing to disclose. Conflict of interest: Dr. Jo has nothing to disclose. Conflict of interest: Dr. Corte has nothing to disclose. Conflict of interest: Dr. Glaspole has nothing to disclose. Conflict of interest: Dr. Grainge has nothing to disclose. Conflict of interest: Dr. Hopkins has nothing to disclose. Conflict of interest: Dr. Reynolds has nothing to disclose. Conflict of interest: Dr. Chapman has nothing to disclose. Conflict of interest: Dr. Walters has nothing to disclose. Conflict of interest: Dr. Zappala has nothing to disclose. Conflict of interest: Dr. Keir has nothing to disclose. Conflict of interest: Dr. Cooper has nothing to disclose. Conflict of interest: Dr. Mahar has nothing to disclose. Conflict of interest: Dr. Ellis has nothing to disclose. Conflict of interest: Dr. Goh has nothing to disclose. Conflict of interest: Dr. Baltic has nothing to disclose. Conflict of interest: Miss Ryan has nothing to disclose. Conflict of interest: Dr. Tan has nothing to disclose. Conflict of interest: Dr. Moodley has nothing to disclose.

Background Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal fibrosing lung disease of unknown cause. The advent of anti-fibrotic medications known to slow disease progression has revolutionised IPF management in recent years. However, little is known about the natural history of IPF patients with mild physiological impairment. We aimed to assess the natural history of these patients using data from the Australian IPF Registry (AIPFR). Methods Using our cohort of real-world IPF patients, we compared FVC criteria for mild physiological impairment (FVC ≥ 80%) against other proposed criteria: DLco ≥ 55%; CPI ≤40 and GAP stage 1 with regards agreement in classification and relationship with disease outcomes. Within the mild cohort (FVC ≥ 80%), we also explored markers associated with poorer prognosis at 12 months. Results Of the 416 AIPFR patients (mean age 70.4 years, 70% male), 216 (52%) were classified as ‘mild’ using FVC ≥ 80%. There was only modest agreement between FVC and DLco (k = 0.30), with better agreement with GAP (k = 0.50) and CPI (k = 0.48). Patients who were mild had longer survival, regardless of how mild physiologic impairment was defined. There was, however, no difference in the annual decline in FVC% predicted between mild and moderate-severe groups (for all proposed criteria). For patients with mild impairment (n = 216, FVC ≥ 80%), the strongest predictor of outcomes at 12 months was oxygen desaturation on a 6 min walk test. Conclusion IPF patients with mild physiological impairment have better survival than patients with moderate-severe disease. Their overall rate of disease progression however, is comparable, suggesting that they are simply at different points in the natural history of IPF disease. Electronic supplementary material The online version of this article (10.1186/s12890-018-0575-y) contains supplementary material, which is available to authorized users.

Introduction Idiopathic pulmonary fibrosis (IPF) is a progressive disease ultimately resulting in respiratory failure and death. While decline in FVC is often used as an endpoint in clinical trials, it is unclear whether this reflects longer term outcomes, especially given significant phenotypic heterogeneity of IPF. Methods Patients from the Australian IPF Registry with ≥ 2 lung function tests performed within 1 yr were included. Using regression modelling the trajectory of FVC %pred was obtained for each patient over 1yr. Patients were then categorised as: ‘decliners’ if annual slope change was ≥10% decline or ‘stable’. Baseline characteristics were compared and outcomes post 1 yr were assessed. Results 217 subjects (Age 70.2±8.2yrs, 74% male) with IPF were included: 148 stable; 69 decliners. Patients who declined had higher baseline FVC%pred (85.4% vs 79.1%; p= 0.034), but there was no other differences in demographics or other measures of lung function. There were 57 (26%) deaths recorded, with no difference found for mortality between the two groups using Cox analysis (p=0.376). There was also no difference in the post 1 yr annual FVC %pred decline using linear mixed models, with initial decliners falling 3.9% p.a. thereafter, while the initially stable patients fell 4.3% p.a. (p=0.827). The median post-first yr follow-up time was 1.1 yrs (IQR 0.64 to 1.88 yrs), amounting to a total of 280 patient years. Conclusion It is not possible to predict patient outcomes on the basis of the 1 yr decline in FVC. There is a need for improved biomarkers to predict disease behaviour in individual patients, and inform management decisions.

There is little Australian epidemiologic data on idiopathic pulmonary fibrosis (IPF), a relatively uncommon but devastating disease. The vast geographic distances in Australia have been a major impediment for collaborative research into IPF. A collaborative national effort, the Australian IPF Registry, has been formed, launched and is recruiting successfully (n = 359, January 2014). Our experience provides unique insights for others wishing to set up IPF registries and in time for a global IPF registry.

Objective.Biomarkers of progression of interstitial lung disease (ILD) are needed to allow early therapeutic intervention in patients with scleroderma-associated disease (SSc-ILD).Methods.A panel of 8 serum cytokines [interleukin 6 (IL-6), IL-8, IL-10, CCL2, CXCL10, vascular endothelial growth factor, fibroblast growth factor 2, and CX3CL1] was assessed by Luminex bead technology in exploratory cohorts of 74 patients with SSc and 58 patients with idiopathic pulmonary fibrosis (IPF). Mortality and significant lung function decline [forced vital capacity (FVC) ≥ 10%; DLCO ≥ 15%] from date of serum collection were evaluated by proportional hazards analysis. Based on these findings, the prognostic value of serum IL-6, evaluated by ELISA, was assessed in a larger test cohort of 212 patients with SSc-ILD.Results.In the exploratory cohort, only serum IL-6 was an independent predictor of DLCO decline in both IPF and SSc-ILD. The IL-6 threshold level most predictive of DLCO decline within a year was 7.67 pg/ml. In the larger test cohort, serum IL-6 > 7.67 pg/ml was predictive of decline in FVC (HR 2.58 ± 0.98, p = 0.01) and in DLCO (HR 3.2 ± 1.7, p = 0.02) within the first year, and predictive of death within the first 30 months (HR 2.69 ± 0.96, p = 0.005). When stratified according to severity (FVC < 70%), serum IL-6 > 7.67 pg/ml was predictive of functional decline or death within the first year in patients with milder disease (OR 3.1, 95% CI 1.4–7.2, p = 0.007), but not in those with severe ILD.Conclusion.In SSc-ILD, serum IL-6 levels appear to be predictive of early disease progression in patients with mild ILD, and could be used to target treatment in this group, if confirmed by prospective studies.

Idiopathic pulmonary fibrosis (IPF) is progressive with a median survival of 2-3yrs. The natural history is highly variable and difficult to predict for an individual presenting with early IPF. Aim: To identify markers associated with disease progression for IPF patients; especially those with early disease. Method: The Australian IPF Registry recruits IPF patients across Australia collating clinical, physiological and questionnaire data. Using this real-world longitudinal cohort we compared mild disease(FVC >80%) with FVC 10% or DLco>15% ± death). Result: Baseline data in 631 participants revealed: 433(69%) male, mean age 70.1±8.5yrs; mean FVC 81±22% and DLco 49±17%. Patients with mild disease(n=235) were older(p=0.001) and more often female(p Reduced PFS was associated with: male gender, impaired quality of life(SGRQ), depression, cough severity, and lower baseline FVC and DLco. Patients with mild disease had improved PFS compared to those with FVC In the subset of patients with mild disease, 41 (18%) had disease progression at 12mths. In mild IPF, disease progression at 12mths was associated with: 6MWT end SpO2 (OR 0.91, 95%CI 0.84-0.99; p=0.028), 6MWT distance and cough severity. On multivariate regression, the variable most closely associated with death at 12mths was 6MWT end SpO2. Conclusion: Impaired baseline lung function is associated with a worse PFS in IPF patients. However a significant proportion of patients with mild disease also show disease progression at 12mths.

The prevalence of idiopathic pulmonary fibrosis (IPF), a fatal and progressive lung disease, is estimated at 1.25–63 out of 100 000, making large population studies difficult. Recently, the need for large longitudinal registries to study IPF has been recognised.The Australian IPF Registry (AIPFR) is a national registry collating comprehensive longitudinal data of IPF patients across Australia. We explored the characteristics of this IPF cohort and the effect of demographic and physiological parameters and specific management on mortality.Participants in the AIPFR (n=647, mean age 70.9±8.5 years, 67.7% male, median follow up 2 years, range 6 months–4.5 years) displayed a wide range of age, disease severity and co-morbidities that is not present in clinical trial cohorts. The cumulative mortality rate in year one, two, three and four was 5%, 24%, 37% and 44% respectively. Baseline lung function (forced vital capacity, diffusing capacity of the lung for carbon monoxide, composite physiological index) and GAP (gender, age, physiology) stage (hazard ratio 4.64, 95% CI 3.33–6.47, pThe AIPFR provides important insights into the understanding of the natural history and clinical management of IPF.

Background: IPF is a progressive, fibrosing lung disease causing diminished health related quality of life (HRQoL). Aims: We sort to determine the principal determinants of HRQoL in IPF. Methods: Data from the Australian IPF Registry included demographic features, comorbidities, St George Respiratory Questionnaire (SGRQ), Hospital Anxiety & Depression (HAD-A & D) scale, UCSD Shortness of BreathQuestionnaire (UCSD), cough, oxygen use, spirometry, DLCO & 6MWT parameters. Linear regression analysis was performed to identify predictors of HRQoL. Results: Data from 516 patients was available (347 male; mean (SD) age 71.3±8.6 yrs). Mean FVC 81.3±22.5%pr, DLco 46.7±17.4%pr, 6MWD 434±135m, resting SpO 2 95.1±3.3%, end-exercise SpO 2 84.8±6.9%. SGRQ: Symptom 47.2±23.5; Activity 61.9±23.9; Impact 37.3±22.9; Total 46.6±20.9. Symptom scores: UCSD median (IQR) 38 (17-67); HAD-A Score 4 (2-7), 20.3% > 8, HAD-D Score 4 (2-7), 17.7% > 8; cough presence 88.5%; cough severity (visual analogue scale 0-100mm): 40.3±25.8. Significant associations with HRQoL on univariate analysis included: GAP index, smoking, cardiorespiratory comorbidity, oxygen therapy, UCSDSOBQ, HAD-A, HAD-D, cough presence & severity, FEV1, FVC, DLCO, 6MWD, baseline & end test oxygen saturation, & end 6MWT dyspnea score. Multivariate analysis of 109 subjects with complete data demonstrated independent association between SGRQ and UCSDSOBQ (R 2 = 0.76, p 2 = 0.07, p 2 = 0.02, p=0.003) & age (R 2 = 0.01, p=0.015). Conclusions: Cough, dyspnoea & depression, are major determinants of HRQoL in IPF. Their treatment may improve HRQoL, & should be a focus of future clinical trials.

We have recently shown that anxiety and depression are common comorbidities for people with interstitial lung disease (ILD). In a cross-sectional single-centre study, the prevalence of anxiety was 31% and the prevalence of depression was 23% [1]. Anxiety and depression were not related to physiological parameters; however, dyspnoea and number of comorbidities were important contributors. The aims of this study were to determine the frequency of prolonged anxiety and depression among sufferers of idiopathic pulmonary fibrosis (IPF), and factors contributing to their persistence., Prolonged anxiety and depression occur frequently in IPF and strongly relate to dyspnoea and cough http://ow.ly/iWxV30cLCfl

Geometry is quantized in loop quantum gravity. As a step toward building a detailed phenomenology of this discrete geometry a model of an atom of geometry is reviewed. The model, which preserves local Lorentz invariance, exhibits a lever arm that raises the scale at which the granularity in angle becomes apparent. The signature of this effect is a systematic shift of observed angles in processes such as high energy particle scattering experiments. To check assumptions in the model, coherent states of a simple atom of spatial geometry are explored using information intrinsic to the quantum state.

Background The clinical course of idiopathic pulmonary fibrosis (IPF) is characterized by progressive decline in lung function and eventual mortality. We sought to determine if future declines in pulmonary function, mortality, or both can be predicted from prior trends in pulmonary function tests (PFTs). Methods Data from 1981 to 2008 on 4,431 PFTs and mortality were analyzed from 734 subjects with IPF. The Kaplan-Meier method was used for mortality analyses. Mixed models were used to describe longitudinal pulmonary function dynamics, since PFTs were observed at varying time points from baseline. Results During the first year of follow-up, 135 subjects (73%) had stable FVC while 50 subjects (37%) showed a decline in FVC. During months 12 to 24 (1-2 years after diagnosis), a stable FVC occurred with the same frequency among both subjects whose FVC had declined during year 1 and whose FVC had remained stable (84.0% and 80.7%, respectively; P = .59). Among subjects alive at the end of year 1, those with a stable FVC were more likely to be alive at the end of year 2 than those whose FVC declined (hazard ratio [HR], 0.91 [95% CI, 0.87-0.94] and HR, 0.71 [95% CI, 0.62-0.78], respectively). Conclusions PFT decline predicts early mortality, but not future declines in physiology, regardless of time since diagnosis.

Dear Editor, We read with interest the article by Wells et al 1 in which the problematic selection of primary end-points for treatment studies in idiopathic pulmonary fibrosis (IPF) patients is addressed. In this document endorsed by respiratory physicians across Europe, the authors explore the implications of using all-cause mortality as a primary end-point in response to a recent statement by a working group on this topic.2 In a rather controversial statement by this working group, Raghu et al suggested that all-cause mortality and all-cause non-elective hospitalisation are the strongest and cleanest clinically meaningful end-points for use in Phase 3 clinical …

The mucolytic, anticoagulative, anti-inflammatory and neo-angiogenic properties of inhaled heparin may benefit patients with burns and cystic fibrosis. We assessed the antibacterial effects of unfractionated heparin.Stored clinical isolates of Acinetobacter baumannii (n =4), Candida albicans (n = 5), Haemophilus influenzae (n =5), Klebsiella pneumoniae (n =4), methicillin-resistant Staphylococcus aureus (n=3), Pseudomonas aeruginosa (n = 2), and Streptococcus pneumoniae (n = 7) were subcultured on horse blood agar, incubated at 35 degrees C overnight, then inoculated into trypticase soy broth to a density of 1 McFarland standard. Dilutions of unfractionated heparin (containing 250- 7500 U) and 100 microL of the 1.0 McFarland standard broth were incubated at 35 degrees C overnight in microtitre plates and then subcultured on horse blood agar using 1 microL standard loops. Colonies (representing viable organisms) were counted.Heparin produced dose-dependent growth inhibition of three of seven S. pneumoniae isolates (complete inhibition at 2500U dose per 200 microL) and one of five H. influenzae isolates (complete inhibition at 7500 U dose per 200 microL), but no inhibition of other isolates.Unfractionated heparin is unlikely to have antibacterial effects because of its unpredictable inhibition of growth of common respiratory pathogens.