Diagnosis and management of hypersensitivity pneumonitis in adults: A position statement from the Thoracic Society of Australia and New Zealand.

Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) relating to specific occupational, environmental or medication exposures. Disease behaviour is influenced by the nature of exposure and the host response, with varying degrees of lung inflammation and fibrosis seen within individuals. The differentiation of HP from other ILDs is important due to distinct causes, pathophysiology, prognosis and management implications. This Thoracic Society of Australia and New Zealand (TSANZ) position statement aims to provide an up-to-date summary of the evidence for clinicians relating to the diagnosis and management of HP in adults, in the Australian and New Zealand context. This document highlights recent relevant findings and gaps in the literature for which further research is required.

The influence of defaecating proctograms on clinical decision-making in pelvic floor disorders.

AIM: Defaecating proctogram (DP) studies have become an integral part of the evaluation of patients with pelvic floor disorders. However, their impact on treatment decision-making remains unclear. The aim of this study was to assess the concordance of decision-making by colorectal surgeons and the role of the DP in this process. METHOD: Four colorectal surgeons were presented with online surveys containing the complete history, examination and investigations of 106 de-identified pelvic floor patients who had received one of three treatment options: physiotherapy only, anterior Delorme's procedure or anterior mesh rectopexy. The survey assessed the management decisions made by each of the surgeons for the three treatments both before and after the addition of the DP to the diagnostic work-up. RESULTS: After the addition of the DP results; treatment choice changed in 219 (52%) of 424 surgical decisions and interrater agreement improved significantly from κ = 0.26 to κ = 0.39. Three of the four surgeons reported a significant increase in confidence. Agreement with the actual treatments patients received increased from κ = 0.21 to κ = 0.28. Intra-anal rectal prolapse on DP was a significant predictor of a decision to perform anterior mesh rectopexy. CONCLUSION: The DP improves interclinician agreement in the management of pelvic floor disorders and enhances the confidence in treatment decisions. Intra-anal rectal prolapse was the most influential DP parameter in treatment decision-making.

Tiotropium treatment for bronchiectasis: a randomised, placebo-controlled, crossover trial.

BACKGROUND: Tiotropium via the HandiHaler device is an established long-acting, anticholinergic bronchodilator that prevents exacerbations and improves lung function in patients with chronic obstructive pulmonary disease. We hypothesised that tiotropium would reduce pulmonary exacerbations and improve lung function in patients with stable bronchiectasis and airflow limitation, and assessed the effect of tiotropium on these outcomes. METHODS: In a randomised, double-blind, two-period crossover trial, we recruited adult patients from three hospitals in New Zealand. Patients were excluded if they had a smoking history of >20 pack-years. Patients were assigned to either the tiotropium-placebo or placebo-tiotropium sequence in a 1:1 ratio, using randomly permuted blocks stratified by centre. Participants and investigators were masked to treatment allocation. Eligible patients received tiotropium 18 µg via HandiHaler daily for 6 months followed by 6 months of placebo, or vice versa, with a washout period of 4 weeks. The primary end-point was rate of event-based exacerbations during the 6-month period. Primary analyses were carried out in an intention-to-treat set. RESULTS: 90 patients were randomly assigned and 85 completed both treatment cycles. The rate of exacerbations was 2.17 per year under the tiotropium treatment and 2.27 per year under placebo (rate ratio 0.96, 95% CI 0.72-1.27; p=0.77). Tiotropium, compared with placebo, improved forced expiratory volume in 1 s by 58 mL (95% CI 23-92 mL; p=0.002). Adverse events were similar under both treatments. CONCLUSIONS: Tiotropium via HandiHaler over 6 months significantly improved lung function but not frequency of exacerbations. Further research is required to understand the clinical context and significance of these findings.

Preventing depression using a smartphone app: a randomized controlled trial.

BACKGROUND: There is evidence that depression can be prevented; however, traditional approaches face significant scalability issues. Digital technologies provide a potential solution, although this has not been adequately tested. The aim of this study was to evaluate the effectiveness of a new smartphone app designed to reduce depression symptoms and subsequent incident depression amongst a large group of Australian workers. METHODS: A randomized controlled trial was conducted with follow-up assessments at 5 weeks and 3 and 12 months post-baseline. Participants were employed Australians reporting no clinically significant depression. The intervention group (N = 1128) was allocated to use HeadGear, a smartphone app which included a 30-day behavioural activation and mindfulness intervention. The attention-control group (N = 1143) used an app which included a 30-day mood monitoring component. The primary outcome was the level of depressive symptomatology (PHQ-9) at 3-month follow-up. Analyses were conducted within an intention-to-treat framework using mixed modelling. RESULTS: Those assigned to the HeadGear arm had fewer depressive symptoms over the course of the trial compared to those assigned to the control (F3,734.7 = 2.98, p = 0.031). Prevalence of depression over the 12-month period was 8.0% and 3.5% for controls and HeadGear recipients, respectively, with odds of depression caseness amongst the intervention group of 0.43 (p = 0.001, 95% CI 0.26-0.70). CONCLUSIONS: This trial demonstrates that a smartphone app can reduce depression symptoms and potentially prevent incident depression caseness and such interventions may have a role in improving working population mental health. Some caution in interpretation is needed regarding the clinical significance due to small effect size and trial attrition.Trial Registration Australian and New Zealand Clinical Trials Registry (www.anzctr.org.au/) ACTRN12617000548336.

Isolated Atrial Neutrophilic Myocarditis: A Rare Cause of Death and Potential "Blind Spot" for Postmortem Computed Tomography and Postmortem Examination.

ABSTRACT: Myocarditis can focally or diffusely involve the myocardium and is associated with arrhythmia, cardiac failure, and sudden death. The majority of cases of myocarditis are lymphocytic in etiology, and neutrophilic myocarditis is relatively uncommon. Although reported in lymphocytic myocarditis, isolated/focal neutrophilic myocarditis of the atrium causing death is not reported in the postmortem literature, and its postmortem computed tomography correlation is not documented. We report a fatal case of isolated neutrophilic atrial myocarditis affecting only the left atrium in a 33-year-old woman presenting as a sudden unexpected death. Microscopy of the left atrium, a not commonly sampled area of the heart, showed florid neutrophilic myocarditis with the remaining right atrium, conduction system, and both ventricles uninvolved. Similar to previously reported fatal isolated atrial lymphocytic myocarditis, postmortem computed tomography was unable to detect any atrial abnormalities. This case highlights a potential "blind spot" for both routine postmortem imaging and examination.

Cervical Epidural Abscess: A Blind Spot for Postmortem Computed Tomography.

ABSTRACT: Spinal epidural abscess is an uncommon condition, which may have serious complications, including neurological sequelae and death. Classical symptoms include spinal pain, fever, and neurological deficit; however, diagnosis is difficult and requires a high degree of clinical suspicion. Antemortem magnetic resonance imaging (MRI) scanning is the gold-standard diagnostic tool. Computed tomography (CT) is less sensitive and as such, postmortem CT may miss the diagnosis. We report a case of Staphylococcus aureus cervical epidural abscess presenting as neck pain and causing flaccid paralysis and subsequently death. Antemortem MRI showed a small epidural collection, spinal cord edema, and fluid in the adjacent cervical disc and facet joints; however, these findings could not be appreciated on postmortem CT. Postmortem examination, guided by the antemortem imaging, was able to confirm a cervical spinal epidural abscess; however, similar deaths may occur before medical presentation. This case demonstrates a limitation of postmortem imaging in diagnosing spinal epidural abscess and highlights that such cases may be missed.

Improving Moderator Responsiveness in Online Peer Support Through Automated Triage.

BACKGROUND: Online peer support forums require oversight to ensure they remain safe and therapeutic. As online communities grow, they place a greater burden on their human moderators, which increases the likelihood that people at risk may be overlooked. This study evaluated the potential for machine learning to assist online peer support by directing moderators' attention where it is most needed. OBJECTIVE: This study aimed to evaluate the accuracy of an automated triage system and the extent to which it influences moderator behavior. METHODS: A machine learning classifier was trained to prioritize forum messages as green, amber, red, or crisis depending on how urgently they require attention from a moderator. This was then launched as a set of widgets injected into a popular online peer support forum hosted by ReachOut.com, an Australian Web-based youth mental health service that aims to intervene early in the onset of mental health problems in young people. The accuracy of the system was evaluated using a holdout test set of manually prioritized messages. The impact on moderator behavior was measured as response ratio and response latency, that is, the proportion of messages that receive at least one reply from a moderator and how long it took for these replies to be made. These measures were compared across 3 periods: before launch, after an informal launch, and after a formal launch accompanied by training. RESULTS: The algorithm achieved 84% f-measure in identifying content that required a moderator response. Between prelaunch and post-training periods, response ratios increased by 0.9, 4.4, and 10.5 percentage points for messages labelled as crisis, red, and green, respectively, but decreased by 5.0 percentage points for amber messages. Logistic regression indicated that the triage system was a significant contributor to response ratios for green, amber, and red messages, but not for crisis messages. Response latency was significantly reduced (P<.001), between the same periods, by factors of 80%, 80%, 77%, and 12% for crisis, red, amber, and green messages, respectively. Regression analysis indicated that the triage system made a significant and unique contribution to reducing the time taken to respond to green, amber, and red messages, but not to crisis messages, after accounting for moderator and community activity. CONCLUSIONS: The triage system was generally accurate, and moderators were largely in agreement with how messages were prioritized. It had a modest effect on response ratios, primarily because moderators were already more likely to respond to high priority content before the introduction of triage. However, it significantly and substantially reduced the time taken for moderators to respond to prioritized content. Further evaluations are needed to assess the impact of mistakes made by the triage algorithm and how changes to moderator responsiveness impact the well-being of forum members.

Empty Delta Sign on Unenhanced Postmortem Computed Tomography Scan in Cerebral Venous Thrombosis.

Cerebral venous thrombosis is a rare condition which constitutes 0.5% to 2% of all types of stroke and carries a mortality of up to 20% to 50%. It leads to cerebral edema, infarction, hemorrhage and venous hypertension. Clinically the diagnosis is confirmed using enhanced computed tomography (CT) angiography which demonstrates an empty delta sign in cerebral veins, particularly in the superior sagittal sinus. However, postmortem CT (PMCT) findings on cerebral venous thrombosis have not been documented in the literature. We present a case report of a 69-year-old man who on unenhanced PMCT scan showed an empty delta sign in the cerebral veins. The empty delta sign was able to be demonstrated in unenhanced PMCT which can be explained by hyper attenuation of the dural veins at postmortem forming an internal contrast highlighting the thrombus.

A Rare Case of Isolated Atrial Myocarditis Causing Death With no Post Mortem Computed Tomography Scan Correlation.

Acute myocarditis is a potentially fatal cardiac pathology that is thought to cause sudden death through arrhythmia and cardiac failure. Of the different subtypes, lymphocytic myocarditis is the most common form. The pathophysiology of myocarditis can be generally diffuse or focally involve the ventricles, but less frequently affects the atria. Although the clinical literature reports isolated atrial myocarditis as a cause of atrial fibrillation and enlargement, there is scant postmortem literature on the findings of this pathology. We report a fatal case of isolated lymphocytic atrial myocarditis affecting only the left atrium in a 56-year-old man, where microscopy of the left atrium confirmed a florid lymphocytic myocarditis. Retrospective postmortem computed tomography scan review did not show any abnormalities on the left atrial wall.

Vitamin D3 supplementation in adults with bronchiectasis: A pilot study.

Vitamin D supplementation prevents acute respiratory infections and, through modulating innate and adaptive immunity, could have a potential role in bronchiectasis management. The primary aims of this pilot study were to assess serum 25-hydroxyvitamin D (25(OH)D) levels in New Zealand adults with bronchiectasis, and their 25(OH)D levels after vitamin D3 supplementation. Adults with bronchiectasis received an initial 2.5 mg vitamin D3 oral loading dose and 0.625 mg vitamin D3 weekly for 24 weeks. The primary outcome was serum 25(OH)D levels before and after vitamin D3 supplementation. Secondary outcomes (time to first infective exacerbation, exacerbation frequency, spirometry, health-related quality of life measures, sputum bacteriology and cell counts and chronic rhinosinusitis) were also assessed. This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12612001222831). The initial, average 25(OH)D level was 71 nmol/L (95% confidence interval (CI): [58, 84]), rising to 218 nmol/L (95% CI: [199, 237]) at 12 weeks and 205 nmol/L (95% CI: [186, 224]) at 24 weeks. The initial serum cathelicidin level was 25 nmol/L (95% CI: [17, 33]), rising to 102 nmol/L (95% CI: [48, 156]) at 12 weeks and 151 nmol/L (95% CI: [97, 205]) at 24 weeks. Over the 24-week study period, we observed statistically significant changes of 1.11 (95% CI: [0.08, 2.14]) in the Leicester Cough Questionnaire and -1.97 (95% CI: [-3.71, -0.23]) in the Dartmouth COOP charts score. No significant adverse effects were recorded. Many New Zealand adults with bronchiectasis have adequate 25(OH)D levels. Weekly vitamin D3 supplementation significantly improved 25(OH)D levels.

Application of Synchronous Text-Based Dialogue Systems in Mental Health Interventions: Systematic Review.

BACKGROUND: Synchronous written conversations (or "chats") are becoming increasingly popular as Web-based mental health interventions. Therefore, it is of utmost importance to evaluate and summarize the quality of these interventions. OBJECTIVE: The aim of this study was to review the current evidence for the feasibility and effectiveness of online one-on-one mental health interventions that use text-based synchronous chat. METHODS: A systematic search was conducted of the databases relevant to this area of research (Medical Literature Analysis and Retrieval System Online [MEDLINE], PsycINFO, Central, Scopus, EMBASE, Web of Science, IEEE, and ACM). There were no specific selection criteria relating to the participant group. Studies were included if they reported interventions with individual text-based synchronous conversations (ie, chat or text messaging) and a psychological outcome measure. RESULTS: A total of 24 articles were included in this review. Interventions included a wide range of mental health targets (eg, anxiety, distress, depression, eating disorders, and addiction) and intervention design. Overall, compared with the waitlist (WL) condition, studies showed significant and sustained improvements in mental health outcomes following synchronous text-based intervention, and post treatment improvement equivalent but not superior to treatment as usual (TAU) (eg, face-to-face and telephone counseling). CONCLUSIONS: Feasibility studies indicate substantial innovation in this area of mental health intervention with studies utilizing trained volunteers and chatbot technologies to deliver interventions. While studies of efficacy show positive post-intervention gains, further research is needed to determine whether time requirements for this mode of intervention are feasible in clinical practice.

A chest radiograph scoring system in patients with severe acute respiratory infection: a validation study.

BACKGROUND: The term severe acute respiratory infection (SARI) encompasses a heterogeneous group of respiratory illnesses. Grading the severity of SARI is currently reliant on indirect disease severity measures such as respiratory and heart rate, and the need for oxygen or intensive care. With the lungs being the primary organ system involved in SARI, chest radiographs (CXRs) are potentially useful for describing disease severity. Our objective was to develop and validate a SARI CXR severity scoring system. METHODS: We completed validation within an active SARI surveillance project, with SARI defined using the World Health Organization case definition of an acute respiratory infection with a history of fever, or measured fever of ≥ 38 °C; and cough; and with onset within the last 10 days; and requiring hospital admission. We randomly selected 250 SARI cases. Admission CXR findings were categorized as: 1 = normal; 2 = patchy atelectasis and/or hyperinflation and/or bronchial wall thickening; 3 = focal consolidation; 4 = multifocal consolidation; and 5 = diffuse alveolar changes. Initially, four radiologists scored CXRs independently. Subsequently, a pediatrician, physician, two residents, two medical students, and a research nurse independently scored CXR reports. Inter-observer reliability was determined using a weighted Kappa (κ) for comparisons between radiologists; radiologists and clinicians; and clinicians. Agreement was defined as moderate (κ > 0.4-0.6), good (κ > 0.6-0.8) and very good (κ > 0.8-1.0). RESULTS: Agreement between the two pediatric radiologists was very good (κ = 0.83, 95% CI 0.65-1.00) and between the two adult radiologists was good (κ = 0.75, 95% CI 0.57-0. 93). Agreement of the clinicians with the radiologists was moderate-to-good (pediatrician:κ = 0.65; pediatric resident:κ = 0.69; physician:κ = 0.68; resident:κ = 0.67; research nurse:κ = 0.49, medical students: κ = 0.53 and κ = 0.56). Agreement between clinicians was good-to-very good (pediatrician vs. physician:κ = 0.85; vs. pediatric resident:κ = 0.81; vs. medicine resident:κ = 0.76; vs. research nurse:κ = 0.75; vs. medical students:κ = 0.63 and 0.66). Following review of discrepant CXR report scores by clinician pairs, κ values for radiologist-clinician agreement ranged from 0.59 to 0.70 and for clinician-clinician agreement from 0.97 to 0.99. CONCLUSIONS: This five-point CXR scoring tool, suitable for use in poorly- and well-resourced settings and by clinicians of varying experience levels, reliably describes SARI severity. The resulting numerical data enables epidemiological comparisons of SARI severity between different countries and settings.

Association between the appendix and the fecalith in adults.

BACKGROUND: We sought to determine the association between the presence of a fecalith and acute/nonperforated appendicitis, gangrenous/perforated appendicitis and the healthy appendix. METHODS: We retrospectively analyzed appendectomies performed between October 2003 and February 2012. We collected data on age, sex, appendix histology and the presence of a fecalith. RESULTS: During the study period, 1357 appendectomies were performed. Fecaliths were present in 186 patients (13.7%). There were 94 male (50.5%) and 92 female patients, and the mean age was 32 (range of 10-76) years. The fecalith rate was 13%- 16% and was nonexistant after age 80 years. The main groups with fecaliths were those with acute/nonperforated appendicitis (n = 121, 65.1%, p = 0.041) and those with a healthy appendix (n = 65, 34.9%, p = 0.003). The presence of fecaliths in the gangrenous/perforated appendicitis group was not significant (n = 19, 10.2%, p = 0.93). There were no fecaliths in patients with serositis, carcinoid or carcinoma. CONCLUSION: Our data confirm the theory of a statistical association between the presence of a fecalith and acute (nonperforated) appendicitis in adults. There was also a significant association between the healthy appendix and asymptomatic fecaliths. There was no correlation between a gangrenous/perforated appendix and the presence of a fecalith. The fecalith is an incidental finding and not always the primary cause of acute (nonperforated) appendictis or gangrenous (perforated) appendicitis. Further research on the topic is recommended.

CONTEXTE: Nous avons voulu examiner le lien entre la présence d'un fécalome et l'appendicite aiguë/non perforée, l'appendicite gangreneuse/perforée et un appendice sain. MÉTHODES: Nous avons analysé de manière rétrospective les appendicectomies effectuées entre octobre 2003 et février 2012. Nous avons recueilli des données sur l'âge, le sexe, l'histologie de l'appendice et la présence d'un fécalome. RÉSULTANTS: Durant la période de l'étude, 1357 appendicectomies ont été effectuées. Des fécalomes étaient présents chez 186 patients (13,7 %). L'étude regroupait 94 hommes (50,5 %) et 92 femmes; l'âge moyen était de 32 ans (entre 10 et 76 ans). Le taux de fécalome était de 13 % à 16 % et non existant après l'âge de 80 ans. Les principaux groupes porteurs de fécalomes étaient ceux qui présentaient une appendicite aiguë/non perforée (n = 121, 65,1 %, p = 0,041) et ceux dont l'appendice était sain (n = 65, 34,9 %, p = 0,003). La présence de fécalomes dans le groupe souffrant d'appendicite gangreneuse/perforée s'est révélée non significative (n = 19, 10,2 %, p = 0,93). Les patients qui souffraient de sérosite, de carcinoïde ou de carcinome ne présentaient pas de fécalomes. CONCLUSION: Nos données confirment la théorie d'un lien statistique entre la présence d'un fécalome et une appendicite aiguë (non perforée) chez l'adulte. On a également observé un lien significatif entre un appendice sain et des fécalomes asymptomatiques. On n'a observé aucune corrélation entre un appendice gangreneux/perforé et la présence de fécalomes. Le fécalome est une observation accessoire qui n'est pas toujours la principale cause de l'appendicite aiguë (non perforée) ou de l'appendicite gangreneuse (perforée). Une recherche plus approfondie à ce sujet est recommandée.

Declaration of a state of emergency in Trinidad and Tobago: effect on the trauma admissions at the National Referral Trauma Centre.

OBJECTIVE: To determine the effect of a State of Emergency (SOE) on penetrating injuries at the main trauma center in Trinidad and Tobago. METHODS: Emergency room registers were accessed in order to identify all patients treated for penetrating injuries from July 1, 2010 through December 30, 2012. This study period was chosen to include injuries one year before and one year after the SOE that spanned from August 21, 2011 to December 5, 2011. Data were analyzed using SPSS version 19 and a P value<.05 was considered statistically significant. RESULTS: There were 1,067 patients treated for penetrating injuries. There were significantly more injuries from gunshots compared to stab wounds (64.7% vs 35.3%; P<.001), and this pattern was maintained during the SOE (54.7% vs 45.3%; P=.37). There was a significant fall in mean monthly admissions for penetrating trauma during the SOE when compared to the 12-month period before its imposition (17.7, SD=4.0 vs 38.9, SD=12.3; CI, 5.6-36.8; P=.0108). One year later, mean monthly admissions for penetrating trauma were similar to those during the SOE (22.7, SD=2.1 vs 17.6, SD=4.0; CI, -2.3-12.3; P=.1295). The incidence of gunshot wounds remained low and stab wounds increased. CONCLUSION: This study has demonstrated that there was a reduction in the incidence of penetrating trauma at the national trauma center after the SOE, with a shift from gunshot to stab wounds.

Chronic obstructive pulmonary disease in non-smokers: a case-comparison study.

BACKGROUND: COPD is often regarded as a smoker's disease. In fact, up to 50% of COPD could be attributable to other causes. Relatively little is known about COPD among nonsmokers, and this group is usually excluded from studies of COPD. METHODS: In this cross-sectional case-comparison study, smokers and nonsmokers aged over 45 with COPD (post-bronchodilator FEV1 ≤ 70% predicted, FEV1/FVC ratio < 0.7) were recruited from specialist outpatient clinics and from primary care. Subjects completed a questionnaire and interview, and underwent spirometry, venesection, exhaled nitric oxide (ENO) measurement, allergen skinprick testing, formal lung function testing and high resolution CT. RESULTS: 48 nonsmokers and 45 smokers participated. Asthma was nearly universal among nonsmokers and was the commonest identifiable cause of COPD in that group. Nonsmokers also exhibited a high prevalence of objective eosinophilic inflammation (raised ENO and eosinophil counts, positive skinprick tests). Smokers had more severe airflow obstruction, but respiratory symptom prevalences were similar between groups. Nonsmokers reported greater lifetime burdens of respiratory disease. Nonsmokers' HRCT results showed functional small airways disease, with no significant emphysema in any subject. Previously undiagnosed bronchiectasis was common in both groups (31% and 42%). CONCLUSIONS: Asthma is a very common cause of COPD among nonsmokers. Radiological bronchiectasis is common in COPD; the clinical significance of this finding is unclear.

Evaluating Tissue Heterogeneity in the Radiologically Normal-Appearing Tissue in IPF Compared to Healthy Controls.

RATIONALE AND OBJECTIVES: Idiopathic Pulmonary Fibrosis (IPF) is a progressive interstitial lung disease characterised by heterogeneously distributed fibrotic lesions. The inter- and intra-patient heterogeneity of the disease has meant that useful biomarkers of severity and progression have been elusive. Previous quantitative computed tomography (CT) based studies have focussed on characterising the pathological tissue. However, we hypothesised that the remaining lung tissue, which appears radiologically normal, may show important differences from controls in tissue characteristics. MATERIALS AND METHODS: Quantitative metrics were derived from CT scans in IPF patients (N = 20) and healthy controls with a similar age (N = 59). An automated quantitative software (CALIPER, Computer-Aided Lung Informatics for Pathology Evaluation and Rating) was used to classify tissue as normal-appearing, fibrosis, or low attenuation area. Densitometry metrics were calculated for all lung tissue and for only the normal-appearing tissue. Heterogeneity of lung tissue density was quantified as coefficient of variation and by quadtree. Associations between measured lung function and quantitative metrics were assessed and compared between the two cohorts. RESULTS: All metrics were significantly different between controls and IPF (p < 0.05), including when only the normal tissue was evaluated (p < 0.04). Density in the normal tissue was 14% higher in the IPF participants than controls (p < 0.001). The normal-appearing tissue in IPF had heterogeneity metrics that exhibited significant positive relationships with the percent predicted diffusion capacity for carbon monoxide. CONCLUSION: We provide quantitative assessment of IPF lung tissue characteristics compared to a healthy control group of similar age. Tissue that appears visually normal in IPF exhibits subtle but quantifiable differences that are associated with lung function and gas exchange.

Quantitative Analysis of Lung Shape in Idiopathic Pulmonary Fibrosis: Insights Into Disease- and Age-Associated Patterns.

RATIONALE AND OBJECTIVES: Fibrotic scarring in idiopathic pulmonary fibrosis (IPF) typically develops first in the posterior-basal lung tissue before advancing to involve more of the lung. The complexity of lung shape in the costo-diaphragmatic region has been proposed as a potential factor in this regional development. Intrinsic and disease-related shape could therefore be important for understanding IPF risk and its staging. We hypothesized that lung and lobe shape in IPF would have important differences from controls. MATERIALS AND METHODS: A principal component (PC) analysis was used to derive a statistical shape model (SSM) of the lung for a control cohort aged > 50 years (N = 39), using segmented lung and fissure surface data from CT imaging. Individual patient shape models derived for baseline (N = 18) and follow-up (N = 16) CT scans in patients with IPF were projected to the SSM to describe shape as the sum of the SSM average and weighted PC modes. Associations between the first four PC shape modes, lung function, percentage of fibrosis (fibrosis%) and pulmonary vessel-related structures (PVRS%), and other tissue metrics were assessed and compared between the two cohorts. RESULTS: Shape was different between IPF and controls (P < 0.05 for all shape modes), with IPF shape forming a distinct shape cluster. Shape had a negative relationship with age in controls (P = 0.013), but a positive relationship with age in IPF (P = 0.026). Some features of shape changed on follow-up. Shape in IPF was associated with fibrosis% (P < 0.05) and PVRS% (P < 0.05). CONCLUSION: Quantitative comparison of lung and lobe shape in IPF with controls of a similar age reveals shape differences that are strongly associated with age and percent fibrosis. The clustering of IPF cohort shape suggests that it could be an important feature to describe disease.

High-resolution CT phenotypes in pulmonary sarcoidosis: a multinational Delphi consensus study.

One view of sarcoidosis is that the term covers many different diseases. However, no classification framework exists for the future exploration of pathogenetic pathways, genetic or trigger predilections, patterns of lung function impairment, or treatment separations, or for the development of diagnostic algorithms or relevant outcome measures. We aimed to establish agreement on high-resolution CT (HRCT) phenotypic separations in sarcoidosis to anchor future CT research through a multinational two-round Delphi consensus process. Delphi participants included members of the Fleischner Society and the World Association of Sarcoidosis and other Granulomatous Disorders, as well as members' nominees. 146 individuals (98 chest physicians, 48 thoracic radiologists) from 28 countries took part, 144 of whom completed both Delphi rounds. After rating of 35 Delphi statements on a five-point Likert scale, consensus was achieved for 22 (63%) statements. There was 97% agreement on the existence of distinct HRCT phenotypes, with seven HRCT phenotypes that were categorised by participants as non-fibrotic or likely to be fibrotic. The international consensus reached in this Delphi exercise justifies the formulation of a CT classification as a basis for the possible definition of separate diseases. Further refinement of phenotypes with rapidly achievable CT studies is now needed to underpin the development of a formal classification of sarcoidosis.

Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulatory properties. We tested the hypothesis that azithromycin would decrease the frequency of exacerbations, increase lung function, and improve health-related quality of life in patients with non-cystic fibrosis bronchiectasis. METHODS: We undertook a randomised, double-blind, placebo-controlled trial at three centres in New Zealand. Between Feb 12, 2008, and Oct 15, 2009, we enrolled patients who were 18 years or older, had had at least one pulmonary exacerbation requiring antibiotic treatment in the past year, and had a diagnosis of bronchiectasis defined by high-resolution CT scan. We randomly assigned patients to receive 500 mg azithromycin or placebo three times a week for 6 months in a 1:1 ratio, with a permuted block size of six and sequential assignment stratified by centre. Participants, research assistants, and investigators were masked to treatment allocation. The coprimary endpoints were rate of event-based exacerbations in the 6-month treatment period, change in forced expiratory volume in 1 s (FEV(1)) before bronchodilation, and change in total score on St George's respiratory questionnaire (SGRQ). Analyses were by intention to treat. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12607000641493. FINDINGS: 71 patients were in the azithromycin group and 70 in the placebo group. The rate of event-based exacerbations was 0·59 per patient in the azithromycin group and 1·57 per patient in the placebo group in the 6-month treatment period (rate ratio 0·38, 95% CI 0·26-0·54; p<0·0001). Prebronchodilator FEV(1) did not change from baseline in the azithromycin group and decreased by 0·04 L in the placebo group, but the difference was not significant (0·04 L, 95% CI -0·03 to 0·12; p=0·251). Additionally, change in SGRQ total score did not differ between the azithromycin (-5·17 units) and placebo groups (-1·92 units; difference -3·25, 95% CI -7·21 to 0·72; p=0·108). INTERPRETATION: Azithromycin is a new option for prevention of exacerbations in patients with non-cystic fibrosis bronchiectasis with a history of at least one exacerbation in the past year. FUNDING: Health Research Council of New Zealand and Auckland District Health Board Charitable Trust.

Pulmonary vessel volume in idiopathic pulmonary fibrosis compared with healthy controls aged > 50 years.

Idiopathic pulmonary fibrosis (IPF) is characterised by progressive fibrosing interstitial pneumonia with an associated irreversible decline in lung function and quality of life. IPF prevalence increases with age, appearing most frequently in patients aged > 50 years. Pulmonary vessel-like volume (PVV) has been found to be an independent predictor of mortality in IPF and other interstitial lung diseases, however its estimation can be impacted by artefacts associated with image segmentation methods and can be confounded by adjacent fibrosis. This study compares PVV in IPF patients (N = 21) with PVV from a healthy cohort aged > 50 years (N = 59). The analysis includes a connected graph-based approach that aims to minimise artefacts contributing to calculation of PVV. We show that despite a relatively low extent of fibrosis in the IPF cohort (20% of the lung volume), PVV is 2-3 times higher than in controls. This suggests that a standardised method to calculate PVV that accounts for tree connectivity could provide a promising tool to provide early diagnostic or prognostic information in IPF patients and other interstitial lung disease.