Integrating Clinical Probability into the Diagnostic Approach to Idiopathic Pulmonary Fibrosis: An International Working Group Perspective.

Background: When considering the diagnosis of idiopathic pulmonary fibrosis (IPF), experienced clinicians integrate clinical features that help to differentiate IPF from other fibrosing interstitial lung diseases, thus generating a "pre-test" probability of IPF. The aim of this international working group perspective was to summarize these features using a tabulated approach similar to chest HRCT and histopathologic patterns reported in the international guidelines for the diagnosis of IPF, and to help formally incorporate these clinical likelihoods into diagnostic reasoning to facilitate the diagnosis of IPF. Methods: The committee group identified factors that influence the clinical likelihood of a diagnosis of IPF, which was categorized as a pre-test clinical probability of IPF into "high" (70-100%), "intermediate" (30-70%), or "low" (0-30%). After integration of radiological and histopathological features, the post-test probability of diagnosis was categorized into "definite" (90-100%), "high confidence" (70-89%), "low confidence" (51-69%), or "low" (0-50%) probability of IPF. Findings: A conceptual Bayesian framework was created, integrating the clinical likelihood of IPF ("pre-test probability of IPF") with the HRCT pattern, the histopathology pattern when available, and/or the pattern of observed disease behavior, into a "post-test probability of IPF." The diagnostic probability of IPF was expressed using an adapted diagnostic ontology for fibrotic interstitial lung diseases. Interpretation: The present approach will help incorporate the clinical judgment into the diagnosis of IPF, thus facilitating the application of IPF diagnostic guidelines and, ultimately improving diagnostic confidence and reducing the need for invasive diagnostic techniques.

Syndrome of Combined Pulmonary Fibrosis and Emphysema: An Official ATS/ERS/JRS/ALAT Research Statement.

Background: The presence of emphysema is relatively common in patients with fibrotic interstitial lung disease. This has been designated combined pulmonary fibrosis and emphysema (CPFE). The lack of consensus over definitions and diagnostic criteria has limited CPFE research. Goals: The objectives of this task force were to review the terminology, definition, characteristics, pathophysiology, and research priorities of CPFE and to explore whether CPFE is a syndrome. Methods: This research statement was developed by a committee including 19 pulmonologists, 5 radiologists, 3 pathologists, 2 methodologists, and 2 patient representatives. The final document was supported by a focused systematic review that identified and summarized all recent publications related to CPFE. Results: This task force identified that patients with CPFE are predominantly male, with a history of smoking, severe dyspnea, relatively preserved airflow rates and lung volumes on spirometry, severely impaired DlCO, exertional hypoxemia, frequent pulmonary hypertension, and a dismal prognosis. The committee proposes to identify CPFE as a syndrome, given the clustering of pulmonary fibrosis and emphysema, shared pathogenetic pathways, unique considerations related to disease progression, increased risk of complications (pulmonary hypertension, lung cancer, and/or mortality), and implications for clinical trial design. There are varying features of interstitial lung disease and emphysema in CPFE. The committee offers a research definition and classification criteria and proposes that studies on CPFE include a comprehensive description of radiologic and, when available, pathological patterns, including some recently described patterns such as smoking-related interstitial fibrosis. Conclusions: This statement delineates the syndrome of CPFE and highlights research priorities.

Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline.

Background: This American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana de Tórax guideline updates prior idiopathic pulmonary fibrosis (IPF) guidelines and addresses the progression of pulmonary fibrosis in patients with interstitial lung diseases (ILDs) other than IPF. Methods: A committee was composed of multidisciplinary experts in ILD, methodologists, and patient representatives. 1) Update of IPF: Radiological and histopathological criteria for IPF were updated by consensus. Questions about transbronchial lung cryobiopsy, genomic classifier testing, antacid medication, and antireflux surgery were informed by systematic reviews and answered with evidence-based recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. 2) Progressive pulmonary fibrosis (PPF): PPF was defined, and then radiological and physiological criteria for PPF were determined by consensus. Questions about pirfenidone and nintedanib were informed by systematic reviews and answered with evidence-based recommendations using the GRADE approach. Results:1) Update of IPF: A conditional recommendation was made to regard transbronchial lung cryobiopsy as an acceptable alternative to surgical lung biopsy in centers with appropriate expertise. No recommendation was made for or against genomic classifier testing. Conditional recommendations were made against antacid medication and antireflux surgery for the treatment of IPF. 2) PPF: PPF was defined as at least two of three criteria (worsening symptoms, radiological progression, and physiological progression) occurring within the past year with no alternative explanation in a patient with an ILD other than IPF. A conditional recommendation was made for nintedanib, and additional research into pirfenidone was recommended. Conclusions: The conditional recommendations in this guideline are intended to provide the basis for rational, informed decisions by clinicians.

European Respiratory Society statement on long COVID follow-up.

Patients diagnosed with coronavirus disease 2019 (COVID-19) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently experience symptom burden post-acute infection or post-hospitalisation. We aimed to identify optimal strategies for follow-up care that may positively impact the patient's quality of life (QoL). A European Respiratory Society (ERS) Task Force convened and prioritised eight clinical questions. A targeted search of the literature defined the timeline of "long COVID" as 1-6 months post-infection and identified clinical evidence in the follow-up of patients. Studies meeting the inclusion criteria report an association of characteristics of acute infection with persistent symptoms, thromboembolic events in the follow-up period, and evaluations of pulmonary physiology and imaging. Importantly, this statement reviews QoL consequences, symptom burden, disability and home care follow-up. Overall, the evidence for follow-up care for patients with long COVID is limited.

Recent advances in the management of systemic sclerosis-associated interstitial lung disease.

PURPOSE OF REVIEW: Interstitial lung disease associated with systemic sclerosis (SSc-ILD) is a frequent organ manifestation leading to high morbidity and mortality. In 2020, the European management recommendations for SSc-ILD were published. Despite being comprehensive, several questions could not be answered or no consensus was reached. RECENT FINDINGS: We highlight recent advances in the screening and early diagnosis, including surveys emphasizing that still 30-40% of all experts do not order baseline HRCTs in their SSc patients. We discuss recent advances in the assessment of disease progression, risk prediction and monitoring of SSc-ILD including novel insights in the disease course of SSc-ILD, clinical predictive factors for disease progression, the role of increasing extent of ILD on serial HRCT and radiomics, PET/CT and home spirometry as sensitive future tools to monitor SSc-ILD patients. We describe recent advances in the treatment of SSc-ILD, including novel data and trials as well as post hoc analyses of clinical trials on mycophenolate, cyclophosmphamide, tocilizumab, rituximab, riociguat and nintedanib. Lastly, we elucidate on peripheral blood cell gene expression profiling as a novel way to identify patients with a better treatment response to mycophenolate. SUMMARY: In this review, we highlight recent advances in the management of SSc-ILD.

Performance of Lung Ultrasound for Monitoring Interstitial Lung Disease.

OBJECTIVES: In this study, we sought to assess the validity of lung ultrasound (LUS) during the follow-up of patients with a wide spectrum of interstitial lung diseases (ILDs). METHODS: Twenty-four patients (13 males, 11 females; mean age ± SD, 65.4 ± 14.3 years; age range, 40-84 years) with a diagnosis of ILDs who were admitted to the Interstitial Lung Disease Unit were prospectively enrolled. Patients were examined with a 56-lung intercostal space LUS protocol in lateral decubitus position, at baseline, 6-months, and 1-year. The LUS score was defined as the sum of B-lines counted in each intercostal space. All patients underwent complete pulmonary function tests at baseline and follow-up time-points. High-resolution computed tomography (HRCT) was performed at baseline and during follow-up, according to personalized patients' needs. All HRCT studies were graded according to the Warrick scoring system (WS). RESULTS: Pooled data analysis showed a significant correlation between WS and LUS scores (P < .001). For separate time-point analysis, a significant correlation between LUS scores and WS was found at baseline (P < .001) and 1 year (P = .005). LUS scores negatively correlated with alveolar volume (VA) (P < .046) and diffusing capacity for carbon monoxide (DLCO) (P < .001) at 6 months and with transfer coefficient of the lung for carbon monoxide (KCO) (P < .031) and DLCO (P = .002) at 12-months. A multivariate regression model showed DLCO to be an independent predictor of LUS score at 1 year (P = .026). CONCLUSIONS: Our results highlight the validity and potential applicability of LUS for disease monitoring in a wide spectrum of ILDs.

Management of hospitalised adults with coronavirus disease 2019 (COVID-19): a European Respiratory Society living guideline.

INTRODUCTION: Hospitalised patients with coronavirus disease 2019 (COVID-19) as a result of SARS-CoV-2 infection have a high mortality rate and frequently require noninvasive respiratory support or invasive ventilation. Optimising and standardising management through evidence-based guidelines may improve quality of care and therefore patient outcomes. METHODS: A task force from the European Respiratory Society and endorsed by the Chinese Thoracic Society identified priority interventions (pharmacological and non-pharmacological) for the initial version of this "living guideline" using the PICO (population, intervention, comparator, outcome) format. The GRADE approach was used for assessing the quality of evidence and strength of recommendations. Systematic literature reviews were performed, and data pooled by meta-analysis where possible. Evidence tables were presented and evidence to decision frameworks were used to formulate recommendations. RESULTS: Based on the available evidence at the time of guideline development (20 February, 2021), the panel makes a strong recommendation in favour of the use of systemic corticosteroids in patients requiring supplementary oxygen or ventilatory support, and for the use of anticoagulation in hospitalised patients. The panel makes a conditional recommendation for interleukin (IL)-6 receptor antagonist monoclonal antibody treatment and high-flow nasal oxygen or continuous positive airway pressure in patients with hypoxaemic respiratory failure. The panel make strong recommendations against the use of hydroxychloroquine and lopinavir-ritonavir. Conditional recommendations are made against the use of azithromycin, hydroxychloroquine combined with azithromycin, colchicine, and remdesivir, in the latter case specifically in patients requiring invasive mechanical ventilation. No recommendation was made for remdesivir in patients requiring supplemental oxygen. Further recommendations for research are made. CONCLUSION: The evidence base for management of COVID-19 now supports strong recommendations in favour and against specific interventions. These guidelines will be regularly updated as further evidence becomes available.

Mepolizumab in Severe Eosinophilic Asthma: A 2-Year Follow-Up in Specialized Asthma Clinics in Greece: An Interim Analysis.

INTRODUCTION: Mepolizumab is a monoclonal antibody against IL-5 for the treatment of severe eosinophilic asthma. The aim of the current study was to present a predesigned interim analysis of the data of patients who have completed 1 year of therapy with mepolizumab. METHODS: This study is a prospective multicenter, noninterventional 2-year observational study and aims to describe the clinical benefit and safety profile of mepolizumab in patients with severe eosinophilic asthma. RESULTS: Compared to the year preceding the initiation of treatment, the annual rate of exacerbations decreased significantly, from 4.3 ± 2.3 to 1.3 ± 1.8; p < 0.0001. Forty-two patients received maintenance dose of oral corticosteroids (OCS) at baseline. From these patients at the end of 1 year of therapy with mepolizumab, 17 patients (40%) had achieved OCS discontinuation. A reduction in the median dose of OCS was also achieved. After 1 year of treatment with mepolizumab, the asthma control test score significantly increased from 16.3 ± 3.7 to 21.2 ± 3.8 (p < 0.0001). This marked clinical improvement was paralleled by a significant reduction of blood eosinophil count. All patients showed a considerable improvement of airflow limitation. In respect to adverse events of treatment with mepolizumab, 19 patients (27%) were recorded to have at least one such occurrence during their 1-year treatment. CONCLUSIONS: We have shown that in patients with severe eosinophilic asthma, 1 year of treatment with mepolizumab was safe, resulted in significant reduction of the annual exacerbation rate, reduction (or even discontinuation) of the needed dose of OCS, and improvements of asthma control and lung function.

Obstructive sleep apnea in pulmonary fibrosis.

PURPOSE OF REVIEW: In previous years, there was limited research related to the role of sleep in interstitial lung diseases (ILDs). Physicians treating ILD patients tended to focus mainly on the daily disabling symptoms overlooking the possible significant role of coexisting sleep disorders, such as obstructive sleep apnea (OSA). However, recently, there has been a growing interest in OSA in ILDs, as well as OSA effect on sleep, life quality and outcome in these patients with emphasis on idiopathic pulmonary fibrosis (IPF). RECENT FINDINGS: OSA has been recognized as an important, high-prevalence comorbidity for the diagnosis and management of IPF. This publication provides a summary of the most relevant recent evidence with regard to OSA in various ILDs and especially IPF, including prevalence, clinical presentation, complications, screening and diagnosis. It also provides updated evidence on the role of OSA therapy in improving sleep, quality of life and disease outcome. SUMMARY: It is too early to characterize OSA and ILDs association as an 'overlap' syndrome. In depth research is needed, including studies with large numbers of ILDs and IPF patients. The main priority is to increase the awareness among physicians for early diagnosis of OSA in ILDs patients.

Combined Pulmonary Fibrosis and Emphysema.

Combined pulmonary fibrosis and emphysema (CPFE) is a clinical entity characterized by the combination of upper lobe emphysema and lower lobe fibrosis, the latter owing to various interstitial lung diseases. These patients have a characteristic lung function profile, with relatively preserved dynamic and static lung volumes, contrasting with a significant reduction of carbon monoxide transfer. The pathogenic mechanisms leading to the coexistence of emphysema with fibrosis remain unclear and different theories have been proposed. CPFE is frequently complicated by pulmonary hypertension, acute exacerbations, and lung cancer leading to poor natural history and prognosis. The syndrome of CPFE represents a distinct pulmonary manifestation in the spectrum of lung diseases associated with connective tissue diseases. Currently, there are no established recommendations regarding the management of patients with CPFE. We provide a review on the existing knowledge of CPFE regarding the epidemiology, pathogenesis, clinical manifestations, radiologic appearance, complications, prognosis, and possible treatment options.

Diagnostic Likelihood Thresholds That Define a Working Diagnosis of Idiopathic Pulmonary Fibrosis.

Rationale: The level of diagnostic likelihood at which physicians prescribe antifibrotic therapy without requesting surgical lung biopsy (SLB) in patients suspected of idiopathic pulmonary fibrosis (IPF) is unknown.Objectives: To determine how often physicians advocate SLB in patient subgroups defined by IPF likelihood and risk associated with SLB, and to identify the level of diagnostic likelihood at which physicians prescribe antifibrotic therapy with requesting SLB.Methods: An international cohort of respiratory physicians evaluated 60 cases of interstitial lung disease, giving: 1) differential diagnoses with diagnostic likelihood; 2) a decision on the need for SLB; and 3) initial management. Diagnoses were stratified according to diagnostic likelihood bands described by Ryerson and colleagues.Measurements and Main Results: A total of 404 physicians evaluated the 60 cases (24,240 physician-patient evaluations). IPF was part of the differential diagnosis in 9,958/24,240 (41.1%) of all physician-patient evaluations. SLB was requested in 8.1%, 29.6%, and 48.4% of definite, provisional high-confidence and provisional low-confidence diagnoses of IPF, respectively. In 63.0% of provisional high-confidence IPF diagnoses, antifibrotic therapy was prescribed without requesting SLB. No significant mortality difference was observed between cases given a definite diagnosis of IPF (90-100% diagnostic likelihood) and cases given a provisional high-confidence IPF diagnosis (hazard ratio, 0.97; P = 0.65; 95% confidence interval, 0.90-1.04).Conclusions: Most respiratory physicians prescribe antifibrotic therapy without requesting an SLB if a provisional high-confidence diagnosis or "working diagnosis" of IPF can be made (likelihood ≥ 70%). SLB is recommended in only a minority of patients with suspected, but not definite, IPF.

Accumulation of damaged mitochondria in alveolar macrophages with reduced OXPHOS related gene expression in IPF.

BACKGROUND: Impaired mitochondria homeostasis and function are established hallmarks of aging and increasing evidence suggests a link with lung fibrosis. Mitochondria homeostasis may be also affected in alveolar macrophages (AMs) in idiopathic pulmonary fibrosis (IPF). In this study, we used bronchoalveolar lavage (BAL), a tool for both clinical and research purposes, and a rich source of AMs. METHODS: BAL samples were examined from 52 patients with IPF and 19 healthy individuals. Measurements of mitochondria reactive oxygen species (mtROS), mitochondria morphology and related gene expression were performed. Additionally, autophagy and mitophagy levels were analysed. RESULTS: Mitochondria in AMs from IPF patients had prominent morphological defects and impaired transcription paralleled to a significant reduction of mitochondria homeostasis regulators PINK1, PARK2 and NRF1. mtROS, was significantly higher in IPF and associated with reduced expression of mitochondria-encoded oxidative phosphorylation (OXPHOS) genes. Age and decline in lung function correlated with higher mtROS levels. Augmentation of damaged, oxidised mitochondria in IPF AMs however was not coupled to increased macroautophagy and mitophagy, central processes in the maintenance of healthy mitochondria levels. CONCLUSION: Our results suggest a perturbation of mitochondria homeostasis in alveolar macrophages in IPF.

Design, Rationale, Methodology, and Aims of a Greek Prospective Idiopathic Pulmonary Fibrosis Registry: Investigating Idiopathic Pulmonary Fibrosis in Greece (INDULGE IPF).

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing interstitial pneumonia of unknown origin. Despite the fact that the guidelines on the diagnosis and management of the disease were updated in 2015, incorporating novel agents recently introduced in the therapeutic approach of IPF, there is a lack of data on the epidemiology, disease status, and treatment in clinical practice. Contemporary data provided by national registries in IPF provide valuable information to guide clinical management of the disease in the real-world setting, adjusted to the local needs. OBJECTIVE: Investigating Idiopathic Pulmonary Fibrosis in Greece (INDULGE IPF) is a Greek observational registry aiming at gaining further knowledge on the characteristics, management, progression, and outcomes of patients with IPF treated under real-world, clinical practice conditions in Greece. METHODS: Approximately 300 patients will be enrolled consecutively in seven reference centers, constituting the largest IPF registry ever established in Greece. CONCLUSION: This registry is expected to provide data on the characteristics of IPF patients in Greece and the entire clinical management during the course of the disease.

Effect of Emphysema Extent on Serial Lung Function in Patients with Idiopathic Pulmonary Fibrosis.

RATIONALE: Patients with idiopathic pulmonary fibrosis and emphysema may have artificially preserved lung volumes. OBJECTIVES: In this post hoc analysis, we investigated the relationship between baseline emphysema and fibrosis extents, as well as pulmonary function changes, over 48 weeks. METHODS: Data were pooled from two phase III, randomized, double-blind, placebo-controlled trials of IFN-γ-1b in idiopathic pulmonary fibrosis (GIPF-001 [NCT00047645] and GIPF-007 [NCT00075998]). Patients with Week 48 data, baseline high-resolution computed tomographic images, and FEV1/FVC ratios less than 0.8 or greater than 0.9 (<0.7 or >0.9 in GIPF-007), as well as randomly selected patients with ratios of 0.8-0.9 and 0.7-0.8, were included. Changes from baseline in pulmonary function at Week 48 were analyzed by emphysema extent. The relationship between emphysema and fibrosis extents and change in pulmonary function was assessed using multivariate linear regression. MEASUREMENTS AND MAIN RESULTS: Emphysema was identified in 38% of patients. A negative correlation was observed between fibrosis and emphysema extents (r = -0.232; P < 0.001). In quartile analysis, patients with the greatest emphysema extent (28 to 65%) showed the smallest FVC decline, with a difference of 3.32% at Week 48 versus patients with no emphysema (P = 0.047). In multivariate analyses, emphysema extent greater than or equal to 15% was associated with significantly reduced FVC decline over 48 weeks versus no emphysema or emphysema less than 15%. No such association was observed for diffusing capacity of the lung for carbon monoxide or composite physiologic index. CONCLUSIONS: FVC measurements may not be appropriate for monitoring disease progression in patients with idiopathic pulmonary fibrosis and emphysema extent greater than or equal to 15%.

Pirfenidone improves survival in IPF: results from a real-life study.

BACKGROUND: Pirfenidone is an antifibrotic compound approved for the treatment of idiopathic pulmonary fibrosis (IPF). We present our real-world experience in terms of Pirfenidone's effect on mortality and adverse events profile outside the restrictions of a clinical trial. METHODS: This is a retrospective observational intention to treat study of 82 consecutive IPF patients (UHH cohort). RESULTS: We observed a high 3-years survival rate of 73% without excluding patients who discontinued treatment for different reasons. The survival was compared to the survival of an IPF cohort from a tertiary referral center (RBH cohort). After exclusion of severe cases (DLco< 30%), in unadjusted analysis, the survival in the UHH cohort was better than in the RBH cohort (HR:0.32, 95% CI: 0.19-0.53, p < 0.0001). After adjustment for age, gender and FVC, the survival remained higher in the UHH cohort (HR:0.28, 95% CI: 0.16-0.48, p < 0.0001). We observed a similar safety profile compared to previously published data and a lower rate of drug discontinuation due to photosensitivity reactions. CONCLUSION: Pirfenidone provides a survival benefit in a real-life IPF cohort compared to previously used medications. Counselling patients and proactively managing possible adverse effects can reduce the necessity to discontinue pirfenidone.

Lung Ultrasonography in Patients With Idiopathic Pulmonary Fibrosis: Evaluation of a Simplified Protocol With High-Resolution Computed Tomographic Correlation.

OBJECTIVES: To compare a simplified ultrasonographic (US) protocol in 2 patient positions with the same-positioned comprehensive US assessments and high-resolution computed tomographic (CT) findings in patients with idiopathic pulmonary fibrosis. METHODS: Twenty-five consecutive patients with idiopathic pulmonary fibrosis were prospectively enrolled and examined in 2 sessions. During session 1, patients were examined with a US protocol including 56 lung intercostal spaces in supine/sitting (supine/sitting comprehensive protocol) and lateral decubitus (decubitus comprehensive protocol) positions. During session 2, patients were evaluated with a 16-intercostal space US protocol in sitting (sitting simplified protocol) and left/right decubitus (decubitus simplified protocol) positions. The 16 intercostal spaces were chosen according to the prevalence of idiopathic pulmonary fibrosis-related changes on high-resolution CT. The sum of B-lines counted in each intercostal space formed the US scores for all 4 US protocols: supine/sitting and decubitus comprehensive US scores and sitting and decubitus simplified US scores. High-resolution CT-related Warrick scores (J Rheumatol 1991; 18:1520-1528) were compared to US scores. The duration of each protocol was recorded. RESULTS: A significant correlation was found between all US scores and Warrick scores and between simplified and corresponding comprehensive scores (P < .0001). Decubitus simplified US scores showed a slightly higher correlation with Warrick scores compared to sitting simplified US scores. Mean durations of decubitus and sitting simplified protocols were 4.76 and 6.20 minutes, respectively (P < .005). CONCLUSIONS: Simplified 16-intercostal space protocols correlated with comprehensive protocols and high-resolution CT findings in patients with idiopathic pulmonary fibrosis. The 16-intercostal space simplified protocol in the lateral decubitus position correlated better with high-resolution CT findings and was less time-consuming compared to the sitting position.

Diagnostic accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis: an international case-cohort study.

We conducted an international study of idiopathic pulmonary fibrosis (IPF) diagnosis among a large group of physicians and compared their diagnostic performance to a panel of IPF experts.A total of 1141 respiratory physicians and 34 IPF experts participated. Participants evaluated 60 cases of interstitial lung disease (ILD) without interdisciplinary consultation. Diagnostic agreement was measured using the weighted kappa coefficient (κw). Prognostic discrimination between IPF and other ILDs was used to validate diagnostic accuracy for first-choice diagnoses of IPF and were compared using the C-index.A total of 404 physicians completed the study. Agreement for IPF diagnosis was higher among expert physicians (κw=0.65, IQR 0.53-0.72, p<0.0001) than academic physicians (κw=0.56, IQR 0.45-0.65, p<0.0001) or physicians with access to multidisciplinary team (MDT) meetings (κw=0.54, IQR 0.45-0.64, p<0.0001). The prognostic accuracy of academic physicians with >20 years of experience (C-index=0.72, IQR 0.0-0.73, p=0.229) and non-university hospital physicians with more than 20 years of experience, attending weekly MDT meetings (C-index=0.72, IQR 0.70-0.72, p=0.052), did not differ significantly (p=0.229 and p=0.052 respectively) from the expert panel (C-index=0.74 IQR 0.72-0.75).Experienced respiratory physicians at university-based institutions diagnose IPF with similar prognostic accuracy to IPF experts. Regular MDT meeting attendance improves the prognostic accuracy of experienced non-university practitioners to levels achieved by IPF experts.

Upregulation of citrullination pathway: From Autoimmune to Idiopathic Lung Fibrosis.

BACKGROUND: Increased protein citrullination and peptidylarginine deiminases (PADIs), which catalyze the citrullination process, are central in Rheumatoid arthritis pathogenesis and probably involved in the initial steps towards autoimmunity. Approximately, 10% of RA patients develop clinically significantly ILD. A possible shared role of protein citrullination in rheumatoid arthritis associated interstitial lung disease (RA-ILD), and idiopathic pulmonary fibrosis (IPF) pathogenesis remains unclear. METHODS: We evaluated PADI2 and PADI4 mRNA expression in bronchoalveolar lavage fluid (BALF) cells of 59 patients with IPF, 27 patients RA-ILD and 10 healthy controls. PADI 2 and 4 expression was analyzed by western blot and immunohistochemistry. Citrullinated protein levels were also quantified. RESULTS: PADI4 mRNA and protein levels were higher in RA-ILD and IPF than controls. Furthermore, PADI4 mRNA levels showed an increase among smokers in RA-ILD. PADI4 expression was detected in granulocytes and macrophages in all groups, with the strongest cytoplasmic expression observed in granulocytes in RA-ILD and IPF. PADI2 mRNA and immunostaining of BAL cells, were similar in all groups among smokers. Overall, stronger staining was observed in current smokers. Citrullinated peptides were significantly increased in IPF compared to RA-ILD and controls. In RA-ILD, protein citrullination strongly correlated with PADI4 expression and anti-citrullinated protein antibodies (ACPAs). CONCLUSIONS: These results suggest that the citrullination pathway is upregulated in IPF and in RA-ILD.

Acute Exacerbation of Idiopathic Pulmonary Fibrosis. An International Working Group Report.

Acute exacerbation of idiopathic pulmonary fibrosis has been defined as an acute, clinically significant, respiratory deterioration of unidentifiable cause. The objective of this international working group report on acute exacerbation of idiopathic pulmonary fibrosis was to provide a comprehensive update on the topic. A literature review was conducted to identify all relevant English text publications and abstracts. Evidence-based updates on the epidemiology, etiology, risk factors, prognosis, and management of acute exacerbations of idiopathic pulmonary fibrosis are provided. Finally, to better reflect the current state of knowledge and improve the feasibility of future research into its etiology and treatment, the working group proposes a new conceptual framework for acute respiratory deterioration in idiopathic pulmonary fibrosis and a revised definition and diagnostic criteria for acute exacerbation of idiopathic pulmonary fibrosis.