Diagnosis Of Idiopathic Pulmonary Fibrosis Research Articles

Changes in physical activity in people with idiopathic pulmonary fibrosis before and after virtual pulmonary rehabilitation: a feasibility study

BackgroundPulmonary rehabilitation (PR) is recommended for the treatment of people with idiopathic pulmonary fibrosis (IPF). Physical activity is an important health behaviour, closely linked to survival in people with IPF. Little is known about the impact of virtual (V) PR on physical activity in people with IPF.ObjectiveTo explore the feasibility of conducting a trial to explore effect of virtual PR on objectively measured physical activity in people with IPF.MethodsAll patients with a diagnosis of IPF in a stable phase of the disease were invited to participate in VPR: a 10 week exercise programme delivered twice-weekly for one hour. Data were collected at baseline (BL) and post VPR (10 weeks): Kings Brief Interstitial Lung Disease (K-BILD), Exercise capacity (6-minute walk test (6MWT) or 1-minute sit-to-stand (STS)) and Physical Activity. Physical activity was measured with a triaxial accelerometer for seven days. Screening, recruitment, adherence and safety data were collected.Results68 people were screened for this study. N = 16 participants were recruited to the study. There was one dropout. N = 15 completed VPR. All results reported in mean (standard deviation) (SD). Participants attended 18.1(2.0) of the 20 sessions. No adverse events were detected. The mean age of participants was 71.5(11.5) years, range: 47–95 years; 7 M:9 F. Mean (SD) FEV1 2.3(0.3)L, FVC 2.8(0.7)L. No statistically significant changes were observed in outcome measures apart from exercise capacity. Light physical activity increased from 152(69.4) minutes per day (n = 16) to 161.9(88.7) minutes per day (n = 14), mean change (SD) (CI) p-value: 9.9 (39.8) [-12.3 to 30.9] p = 0.4. Moderate-to-vigorous physical activity increased from 19.1(18.6) minutes per day (n = 16) to 25.7(28.3) minutes per day (n = 14), mean change (SD) (CI) p-value: 6.7 (15.5) [-2.1 to 15.1] p = 0.1. Step count increased from 3838(2847) steps per day (n = 16) to 4537(3748) steps per day (n = 14), mean change (SD) (CI) p-value: 738 (1916) [-419.3 to 1734.6] p = 0.2. K-BILD (n = 15) increased from 55.1(7.4) at BL to 55.7(7.9) post VPR mean change (SD) [95% confidence interval] (CI) p-value: 1.7(6.5) [-1.7 to 5.3], p = 0.3. 6MWT (n = 5) increased from 361.5(127.1) to 452.2(136.1) meters, mean change (SD) (CI) p-value: 63.7 (48.2) [-3.8 to 123.6], p = 0.04 and 1-minute STS increased from 17.6(3.0) (n = 11) to 23.7(6.3) (n = 10), mean change (SD) (CI) p-value 5.8 (4.6) [2.6 to 9.1], p = 0.003.ConclusionVPR can improve physical activity in people with IPF. A number of important feasibility issues included recruitment, retention, adherence and safety have been reported which are crucial for future research in this area. A fully powered trial is needed to determine the response of people with IPF to PR with regard to physical activity.

[Inflammageing in patients with idiopathic pulmonary fibrosis (IPF)].

We took Peripheral blood samples from adult patients over 60 years of age with a confirmed diagnosis of IPF through biopsy or clinical criteria. Plasma separation was performed, and proinflammatory cytokines were measured using CBA. This study received approval from the ethics and research committee of the Colombian Pulmonological Foundation. Patients with IPF exhibited an increase in cytokines such as IL-4, INFy, and IL-6 compared to healthy older adults. Inflammatory disease has been associated with the development and coexistence of multiple chronic non-communicable diseases that have a higher incidence after 65 years of age. The involvement of adaptive immunity in the pathogenesis of IPF has been described as an imbalance in the Th1/Th2 lymphocyte response. Further studies are required to identify additional markers of immunosenescence that correlate with IPF.

A Machine Learning System to Indicate Diagnosis of Idiopathic Pulmonary Fibrosis Non-Invasively in Challenging Cases.

Radiologic usual interstitial pneumonia (UIP) patterns and concordant clinical characteristics define a diagnosis of idiopathic pulmonary fibrosis (IPF). However, limited expert access and high inter-clinician variability challenge early and pre-invasive diagnostic sensitivity and differentiation of IPF from other interstitial lung diseases (ILDs). We investigated a machine learning-driven software system, Fibresolve, to indicate IPF diagnosis in a heterogeneous group of 300 patients with interstitial lung disease work-up in a retrospective analysis of previously and prospectively collected registry data from two US clinical sites. Fibresolve analyzed cases at the initial pre-invasive assessment. An Expert Clinical Panel (ECP) and three panels of clinicians with varying experience analyzed the cases for comparison. Ground Truth was defined by separate multi-disciplinary discussion (MDD) with the benefit of surgical pathology results and follow-up. Fibresolve met both pre-specified co-primary endpoints of sensitivity superior to ECP and significantly greater specificity (p = 0.0007) than the non-inferior boundary of 80.0%. In the key subgroup of cases with thin-slice CT and atypical UIP patterns (n = 124), Fibresolve's diagnostic yield was 53.1% [CI: 41.3-64.9] (versus 0% pre-invasive clinician diagnostic yield in this group), and its specificity was 85.9% [CI: 76.7-92.6%]. Overall, Fibresolve was found to increase the sensitivity and diagnostic yield for IPF among cases of patients undergoing ILD work-up. These results demonstrate that in combination with standard clinical assessment, Fibresolve may serve as an adjunct in the diagnosis of IPF in a pre-invasive setting.

The effect of antifibrotic agents on acute respiratory failure in COVID-19 patients: a retrospective cohort study from TriNetX US collaborative networks

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on global health and economies, resulting in millions of infections and deaths. This retrospective cohort study aimed to investigate the effect of antifibrotic agents (nintedanib and pirfenidone) on 1-year mortality in COVID-19 patients with acute respiratory failure.MethodsData from 61 healthcare organizations in the TriNetX database were analyzed. Adult patients with COVID-19 and acute respiratory failure were included. Patients with a pre-existing diagnosis of idiopathic pulmonary fibrosis before their COVID-19 diagnosis were excluded. The study population was divided into an antifibrotic group and a control group. Propensity score matching was used to compare outcomes, and hazard ratios (HR) for 1-year mortality were calculated.ResultsThe antifibrotic group exhibited a significantly lower 1-year mortality rate compared to the control group. The survival probability at the end of the study was 84.42% in the antifibrotic group and 69.87% in the control group. The Log-Rank test yielded a p-value of less than 0.001. The hazard ratio was 0.434 (95% CI: 0.264–0.712), indicating a significant reduction in 1-year mortality in the antifibrotic group. Subgroup analysis demonstrated significantly improved 1-year survival in patients receiving nintedanib treatment and during periods when the Wuhan strain was predominant.DiscussionThis study is the first to demonstrate a survival benefit of antifibrotic agents in COVID-19 patients with acute respiratory failure. Further research and clinical trials are needed to confirm the efficacy of these antifibrotic agents in the context of COVID-19 and acute respiratory failure.

Eating and drinking experience in patients with idiopathic pulmonary fibrosis: a qualitative study

ObjectiveTo explore eating and drinking experiences of patients with idiopathic pulmonary fibrosis (IPF), the impact of any changes associated with their diagnosis and any coping mechanisms developed by patients.SettingPulmonary fibrosis...

Impact of surgical lung biopsy on lung function and survival in patients with idiopathic pulmonary fibrosis in a multi-centre registry cohort.

Establishing an accurate and timely diagnosis of idiopathic pulmonary fibrosis (IPF) is essential for appropriate management and prognostication. In some cases, surgical lung biopsy (SLB) is performed but carries non-negligible risk. The objective of this retrospective study was to determine if SLB is associated with accelerated lung function decline in patients with IPF using the Canadian Registry for Pulmonary Fibrosis. Linear mixed models and Cox proportional hazards regression models were used to compare decline in forced vital capacity (FVC)%, diffusion capacity of the lung (DLCO%) and risk of death or lung transplantation between SLB and non-SLB patients. Adjustments were made for baseline age, sex, smoking history, antifibrotic use, and lung function. A similar analysis compared lung function changes 12 months pre- and post-SLB. A total of 81 SLB patients and 468 non-SLB patients were included. In the SLB group, the post-biopsy annual FVC% decline was 2.0% (±0.8) in unadjusted, and 2.1% (±0.8) in adjusted models. There was no difference in FVC% decline, DLCO% decline, or time to death or lung transplantation between the two groups, in adjusted or unadjusted models (all p-values >0.07). In the pre-post SLB group, no differences were identified in FVC% decline in unadjusted or adjusted models (p = 0.07 for both). No association between SLB and lung function decline or risk of death or lung transplantation was identified in this multi-centre study of patients with IPF.

Patients with idiopathic pulmonary fibrosis and refractory cough have traction bronchiectasis and distorted airway architecture: a retrospective case review study.

Cough is a common and important sign/symptom in patients with idiopathic pulmonary fibrosis (IPF). However, there have been few reports focusing on cough, and the exact mechanisms for cough in patients with IPF have remained unclear. The objective of this study was to investigate the clinical features of IPF patients with refractory cough and to clarify mechanisms for cough in these patients. We retrospectively reviewed the files of patients with the diagnosis of IPF at Kanazawa University Hospital and compared the clinical features of IPF patients with refractory cough with the clinical features of IPF patients without refractory cough. Among a total of 23 patients with IPF, 10 patients (43.5%) had chronic cough. Of the ten patients, seven patients had concomitant conditions that could lead to cough. Of these seven patients, the cough of four patients was resolved after treatment of their concomitant condition. Finally, among the 23 patients there were 6 (26.1%) with refractory cough associated with IPF. Significant differences were seen between the following clinical features of IPF patients with or without refractory cough, respectively, as follows: lower body mass index (BMI; 18.8±2.5 vs. 22.8±2.5 kg/m2, P<0.01), lower forced vital capacity (FVC; 77.5%±30.4% predicted vs. 99.9%±0.53% predicted, P=0.046), and presence of traction bronchiectasis and distorted airway architecture on high-resolution computed tomography (HRCT; 83.3% vs. 11.8%, P<0.01). The difference between the proportions of patients with or without refractory cough with capsaicin cough sensitivity was not significant. Mechanical stress on the airways due to traction bronchiectasis and distorted airway architecture is a possible mechanism for cough in IPF patients.

External validation of Fibresolve, a machine-learning algorithm, to non-invasively diagnose idiopathic pulmonary fibrosis

BackgroundPrevious work has shown the ability of Fibresolve, a machine learning system, to non-invasively classify idiopathic pulmonary fibrosis (IPF) with a sensitivity of 41% and specificity of 87% versus other types of interstitial lung disease. Further external validation for the use of Fibresolve to classify IPF in patients with non-definite usual interstitial pneumonia (UIP) is needed. The aim of this study is to assess the sensitivity for Fibresolve to positively classify IPF in an external cohort of patients with a non-definite UIP radiographic pattern. MethodsThis is a retrospective analysis of patients (n=193) enrolled in two prospective phase two clinical trials that enrolled patients with IPF. We retrospectively identified patients with non-definite UIP on HRCT (n=51), 47 of whom required surgical lung biopsy for diagnosis. Fibresolve was used to analyze the HRCT chest imaging which was obtained prior to invasive biopsy and sensitivity for final diagnosis of IPF was calculated. ResultsThe sensitivity of Fibresolve for the non-invasive classification of IPF in patients with a non-definite UIP radiographic pattern by HRCT was 76.5% (95% CI 66.5-83.7). For the subgroup of 47 patients who required surgical biopsy to aid in final diagnosis of IPF, Fibresolve had a sensitivity of 74.5% (95% CI 60.5-84.7). ConclusionIn patients with suspected IPF with non-definite UIP on HRCT, Fibresolve can positively identify cases of IPF with high sensitivity. These results suggest that in combination with standard clinical assessment, Fibresolve has the potential to serve as a low-cost adjunct in the non-invasive diagnosis of IPF.

The diagnosis and treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial lung disease (ILD) of unknown cause. The prognosis of IPF is poor, respiratory failure is the most common cause of mortality. Velcro rales are typical on respiratory system examination. Clubbing is seen in 30-60% of IPF cases. There is no laboratory test specific to IPF. Usual interstitial pneumonia (UIP) pattern is seen in IPF. UIP features in high-resolution computed tomography (HRCT); peripheral subpleural bibasilar reticular opacities, honeycombing, traction bronchiectasis and interseptal thickening. It shows craniocaudal localization. Diagnosis of IPF; It is diagnosed by the combination of HRCT findings and clinical findings. Antifibrotic drugs (Pirfenidone and Nintedanib) slow down the progression of IPF and reduce the number of annual attacks and reduce the frequency of hospitalization.

Identification of Idiopathic Pulmonary Fibrosis and Prediction of Disease Severity via Machine Learning Analysis of Comprehensive Metabolic Panel and Complete Blood Count Data.

Diagnosis of idiopathic pulmonary fibrosis (IPF) typically relies on high-resolution computed tomography imaging (HRCT) or histopathology, while monitoring disease severity is done via frequent pulmonary function testing (PFT). More reliable and convenient methods of diagnosing fibrotic interstitial lung disease (ILD) type and monitoring severity would allow for early identification and enhance current therapeutic interventions. This study tested the hypothesis that a machine learning (ML) ensemble analysis of comprehensive metabolic panel (CMP) and complete blood count (CBC) data can accurately distinguish IPF from connective tissue disease ILD (CTD-ILD) and predict disease severity as seen with PFT. Outpatient data with diagnosis of IPF or CTD-ILD (n = 103 visits by 53 patients) were analyzed via ML methodology to evaluate (1) IPF vs CTD-ILD diagnosis; (2) %predicted Diffusing Capacity of Lung for Carbon Monoxide (DLCO) moderate or mild vs severe; (3) %predicted Forced Vital Capacity (FVC) moderate or mild vs severe; and (4) %predicted FVC mild vs moderate or severe. ML methodology identified IPF from CTD-ILD with AUCTEST = 0.893, while PFT was classified as DLCO moderate or mild vs severe with AUCTEST = 0.749, FVC moderate or mild vs severe with AUCTEST = 0.741, and FVC mild vs moderate or severe with AUCTEST = 0.739. Key features included albumin, alanine transaminase, %lymphocytes, hemoglobin, %eosinophils, white blood cell count, %monocytes, and %neutrophils. Analysis of CMP and CBC data via proposed ML methodology offers the potential to distinguish IPF from CTD-ILD and predict severity on associated PFT with accuracy that meets or exceeds current clinical practice.

Thin-Section CT in the Categorization and Management of Pulmonary Fibrosis including Recently Defined Progressive Pulmonary Fibrosis.

While idiopathic pulmonary fibrosis (IPF) is the most common type of fibrotic lung disease, there are numerous other causes of pulmonary fibrosis that are often characterized by lung injury and inflammation. Although often gradually progressive and responsive to immune modulation, some cases may progress rapidly with reduced survival rates (similar to IPF) and with imaging features that overlap with IPF, including usual interstitial pneumonia (UIP)-pattern disease characterized by peripheral and basilar predominant reticulation, honeycombing, and traction bronchiectasis or bronchiolectasis. Recently, the term progressive pulmonary fibrosis has been used to describe non-IPF lung disease that over the course of a year demonstrates clinical, physiologic, and/or radiologic progression and may be treated with antifibrotic therapy. As such, appropriate categorization of the patient with fibrosis has implications for therapy and prognosis and may be facilitated by considering the following categories: (a) radiologic UIP pattern and IPF diagnosis, (b) radiologic UIP pattern and non-IPF diagnosis, and (c) radiologic non-UIP pattern and non-IPF diagnosis. By noting increasing fibrosis, the radiologist contributes to the selection of patients in which therapy with antifibrotics can improve survival. As the radiologist may be first to identify developing fibrosis and overall progression, this article reviews imaging features of pulmonary fibrosis and their significance in non-IPF-pattern fibrosis, progressive pulmonary fibrosis, and implications for therapy. Keywords: Idiopathic Pulmonary Fibrosis, Progressive Pulmonary Fibrosis, Thin-Section CT, Usual Interstitial Pneumonia © RSNA, 2024.

A microdroplet SERS-RCA biosensor with enhanced specificity and reproducibility for profiling dual miRNAs in idiopathic pulmonary fibrosis diagnosis and monitoring

Accurate detection of low-abundance, highly homologous miRNAs is crucial for the precise diagnosis and monitoring of idiopathic pulmonary fibrosis (IPF). In this study, a fully integrated microdroplet analysis platform based on rolling circle amplification (RCA) technology and surface-enhanced Raman spectroscopy (SERS) has been developed to precisely detect miRNA-21 and miRNA-155 in the serum of IPF patients. By utilizing the RCA strategy, the constructed sensor is able to realize single nucleotide variation detection with prominent specificity. The integration of microfluidics provides satisfactory directions to the reproducibility issue in SERS, thereby improving detecting sensitivity. With this sophisticated biosensing platform, low detection limits of 0.398 fM and 0.215 fM have been achieved for miRNA-21 and miRNA-155, respectively. Moreover, the combined determination of these two miRNAs demonstrates a more substantial diagnostic potential, with an AUC value of 0.884, higher than their evaluations. When used in conjunction with high-resolution chest computed tomography, this innovative SERS-RCA microfluidic biosensor can serve as an auxiliary diagnostic tool for IPF risk assessment, particularly for real-time monitoring of miRNA levels in patients undergoing chemotherapy. This sensing technique holds promise to extend into versatile platforms for diverse miRNA detection in the rapid and accurate diagnosis of various diseases beyond IPF.

Disease diagnosis and severity classification in pulmonary fibrosis using carbonyl volatile organic compounds in exhaled breath

BackgroundPathophysiological conditions underlying pulmonary fibrosis remain poorly understood. Exhaled breath volatile organic compounds (VOCs) have shown promise for lung disease diagnosis and classification. In particular, carbonyls are a byproduct of oxidative stress, associated with fibrosis in the lungs. To explore the potential of exhaled carbonyl VOCs to reflect underlying pathophysiological conditions in pulmonary fibrosis, this proof-of-concept study tested the hypothesis that volatile and low abundance carbonyl compounds could be linked to diagnosis and associated disease severity. MethodsExhaled breath samples were collected from outpatients with a diagnosis of Idiopathic Pulmonary Fibrosis (IPF) or Connective Tissue related Interstitial Lung Disease (CTD-ILD) with stable lung function for 3 months before enrollment, as measured by pulmonary function testing (PFT) DLCO (%), FVC (%) and FEV1 (%). A novel microreactor was used to capture carbonyl compounds in the breath as direct output products. A machine learning workflow was implemented with the captured carbonyl compounds as input features for classification of diagnosis and disease severity based on PFT (DLCO and FVC normal/mild vs. moderate/severe; FEV1 normal/mild/moderate vs. moderately severe/severe). ResultsThe proposed approach classified diagnosis with AUROC=0.877 ± 0.047 in the validation subsets. The AUROC was 0.820 ± 0.064, 0.898 ± 0.040, and 0.873 ± 0.051 for disease severity based on DLCO, FEV1, and FVC measurements, respectively. Eleven key carbonyl VOCs were identified with the potential to differentiate diagnosis and to classify severity. ConclusionsExhaled breath carbonyl compounds can be linked to pulmonary function and fibrotic ILD diagnosis, moving towards improved pathophysiological understanding of pulmonary fibrosis.

Morphine for treatment of cough in idiopathic pulmonary fibrosis (PACIFY COUGH): a prospective, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial

Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease, with most patients reporting cough. Currently, there are no proven treatments. We examined the use of low dose controlled-release morphine compared with placebo as an antitussive therapy in individuals with idiopathic pulmonary fibrosis. The PACIFY COUGH study is a phase 2, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial done in three specialist centres in the UK. Eligible patients aged 40-90 years had a diagnosis of idiopathic pulmonary fibrosis within 5 years, self-reported cough (lasting >8 weeks), and a cough visual analogue scale (VAS) score of 30 mm or higher. Patients were randomly assigned (1:1) to placebo twice daily or controlled-release morphine 5 mg orally twice daily for 14 days followed by crossover after a 7-day washout period. Patients were randomised sequentially to a sequence group defining the order in which morphine and placebo were to be given, according to a computer-generated schedule. Patients, investigators, study nurses, and pharmacy personnel were masked to treatment allocation. The primary endpoint was percentage change in objective awake cough frequency (coughs per h) from baseline as assessed by objective digital cough monitoring at day 14 of treatment in the intention-to-treat population, which included all randomised participants. Safety data were summarised for all patients who took at least one study drug and did not withdraw consent. This study was registered at ClinicalTrials.gov, NCT04429516, and has been completed. Between Dec 17, 2020, and March 21, 2023, 47 participants were assessed for eligibility and 44 were enrolled and randomly allocated to treatment. Mean age was 71 (SD 7·4) years, and 31 (70%) of 44 participants were male and 13 (30%) were female. Lung function was moderately impaired; mean forced vital capacity (FVC) was 2·7 L (SD 0·76), mean predicted FVC was 82% (17·3), and mean predicted diffusion capacity of carbon monoxide was 48% (10·9). Of the 44 patients who were randomised, 43 completed morphine treatment and 41 completed placebo treatment. In the intention-to-treat analysis, morphine reduced objective awake cough frequency by 39·4% (95% CI -54·4 to -19·4; p=0·0005) compared with placebo. Mean daytime cough frequency reduced from 21·6 (SE 1·2) coughs per h at baseline to 12·8 (1·2) coughs per h with morphine, whereas cough rates did not change with placebo (21·5 [SE 1·2] coughs per h to 20·6 [1·2] coughs per h). Overall treatment adherence was 98% in the morphine group and 98% in the placebo group. Adverse events were observed in 17 (40%) of 43 participants in the morphine group and six (14%) of 42 patients in the placebo group. The main side-effects of morphine were nausea (six [14%] of 43 participants) and constipation (nine [21%] of 43). One serious adverse event (death) occurred in the placebo group. In patients with cough related to idiopathic pulmonary fibrosis, low dose controlled-release morphine significantly reduced objective cough counts over 14 days compared with placebo. Morphine shows promise as an effective treatment to palliate cough in patients with idiopathic pulmonary fibrosis, and longer term studies should be the focus of future research. The Jon Moulton Charity Trust.

Identification of cuproptosis-related diagnostic biomarkers in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with clinical and pathological heterogeneity. Recent studies have identified cuproptosis as a novel cell death mechanism. However, the role of cuproptosis-related genes in the pathogenesis of IPF is still unclear. Two IPF datasets of the Gene Expression Omnibus database were studied. Mann-Whitney U test, correlation analysis, functional enrichment analyses, single-sample gene set enrichment analysis, CIBERSORT, unsupervised clustering, weighted gene co-expression network analysis, and receiver operating characteristic curve analysis were used to conduct our research. The dysregulated cuproptosis-related genes and immune responses were identified between IPF patients and controls. Two cuproptosis-related molecular clusters were established in IPF, the high immune score group (C1) and the low immune score group (C2). Significant heterogeneity in immunity between clusters was revealed by functional analyses results. The module genes with the strongest correlation to the 2 clusters were identified by weighted gene co-expression network analysis results. Seven hub genes were found using the Cytoscape software. Ultimately, 2 validated diagnostic biomarkers of IPF, CDKN2A and NEDD4, were obtained. Subsequently, the results were validated in GSE47460. Our investigation illustrates that CDKN2A and NEDD4 may be valid biomarkers that were useful for IPF diagnosis and copper-related clustering.

The preventative effects of statin on lung cancer development in patients with idiopathic pulmonary fibrosis using the National Health Insurance Service Database in Korea.

Little is known about the effect of statin use in lung cancer development in idiopathic pulmonary fibrosis (IPF). We analyzed the database of the National Health Insurance Service to further investigate the clinical impacts of statin on lung cancer development and overall survival (OS) in IPF patients. The analysis included 9,182 individuals diagnosed with IPF, of which 3,372 (36.7%) were statin users. Compared to statin non-users, the time from diagnosis of IPF to lung cancer development and OS were longer in statin users in IPF patients. In Cox proportional hazard regression models, higher statin compliance, statin use, and being female had an inverse association with lung cancer risk, while older age at diagnosis of IPF and smoking history were associated with higher risk of lung cancer in IPF patients. For OS, statin use, female sex, higher physical activity frequency, and diabetes were associated with longer survival. In contrast, older age at diagnosis of IPF and smoking history were associated with shorter OS in IPF patients. These data from a large population indicate that statin had an independent protective association with lung cancer development and mortality in IPF patients.

Changes in the physical and affective dimensions of dyspnoea after a home-based pulmonary rehabilitation in fibrotic idiopathic interstitial pneumonias.

Our objective was to evaluate the short-, medium- and long-term benefits of home-based pulmonary rehabilitation (PR) on the physical and affective components of dyspnoea in people with fibrotic idiopathic interstitial pneumonias (f-IIPs). Anxiety and depressive symptoms, fatigue, health-related quality of life and exercise tolerance were also assessed. Data on 166 individuals with f-IIPs who enrolled in an 8-week home-based PR programme (weekly supervised 90-min session) were retrospectively analysed. Assessments included the Dyspnoea-12 (D-12) questionnaire, Hospital Anxiety and Depression Scale, Fatigue Assessment Scale, Visual Simplified Respiratory Questionnaire and 6-min stepper test, and were performed at home at short, medium (6 months) and long (12 months) term. Among the 166 individuals with f-IIPs who enrolled in PR, 75 (45%) and 91 (55%) participants had a diagnosis of idiopathic pulmonary fibrosis and fibrosing non-specific interstitial pneumonia, respectively, and 87 (52%) participants concluded a full year of follow-up. In the total group, both physical and affective components of dyspnoea were improved, at short, medium and long term, after PR. Overall, half of the participants reached the minimally important difference of 3 points of the D-12 questionnaire at the end of PR, and at the 6- and 12-month follow-ups. Anxiety and depressive symptoms, fatigue and health-related quality of life were also improved, while the short-term benefits in exercise tolerance were not maintained 1 year after PR. An individualised home-based PR programme resulted in short-, medium- and long-term improvements in both physical and affective components of dyspnoea assessed by the D-12 questionnaire.

S100 Calcium-Binding Protein A9, a Potential Novel Diagnostic Biomarker for Idiopathic Pulmonary Fibrosis.

Neutrophilic inflammation is a characteristic feature of idiopathic pulmonary fibrosis (IPF). S100 calcium-binding protein A9 (S100A9) is a neutrophil-derived protein involved in the development of neutrophil-related chronic inflammatory disorders. However, the role of S100A9 in IPF remains unclear. We used enzyme-linked immunosorbent assays to measure S100A9 levels in bronchoalveolar lavage fluid (BALF) and serum obtained from healthy controls (HCs) and patients with IPF, non-specific interstitial pneumonia, hypersensitivity pneumonitis, and sarcoidosis. Compared with HCs, BALF S100A9 levels were significantly higher in IPF patients (P < 0.001), patients with hypersensitivity pneumonitis (P = 0.043), and patients with nonspecific interstitial pneumonia (P < 0.001). The S100A9 level in BALF of 0.093 ng/mL could distinguish IPF patients from HCs, with a specificity of 78.8% and a sensitivity of 81.6%. Similarly, the S100A9 level in BALF of 0.239 ng/mL had a specificity of 64.7% and a sensitivity of 66.7% for distinguishing IPF patients from patients with other interstitial lung diseases. Additionally, BALF S100A9 levels were significantly correlated with neutrophil counts (r = 0.356, P < 0.001) in BALF. IPF patients with S100A9 levels in BALF > 0.533 ng/mL had lower survival rates, compared with patients who had levels ≤ 0.553 ng/mL (n = 49; hazard ratio [HR], 3.62; P = 0.021). Combination analysis revealed that IPF patients with S100A9 levels in BALF> 0.553 ng/mL or neutrophil percentages > 49.1% (n = 43) had significantly lower survival rates than patients with S100A9 levels in BALF ≤ 0.553 ng/mL and neutrophil percentages ≤ 49.1% (n = 41) (HR, 3.91; P = 0.014). Additionally, patients with serum S100A9 levels > 0.077 ng/mL (n = 29) had significantly lower survival rates than patients with levels ≤ 0.077 ng/mL (n = 53, HR, 2.52; P = 0.013). S100A9 was expressed on neutrophils and macrophages in BALF from IPF patients as well as α-smooth muscle actin positive cells in the lung tissues. S100A9 is involved in the development and progression of IPF. Moreover, S100A9 levels in BALF and serum may be surrogate markers for IPF diagnosis and survival prediction, particularly when analyzed in combination with neutrophil percentages.

Serum heme oxygenase-1 as a prognostic biomarker in patients with acute exacerbation of interstitial lung disease

Serum heme oxygenase (HO)-1 level has been reported as a clinically reliable diagnostic biomarker for acute exacerbation of interstitial lung disease (ILD); however, its utility for predicting mortality among these patients is unclear. Serum HO-1 levels of patients newly diagnosed with acute exacerbation of ILD were measured at the time of initiating steroid pulse therapy. The relationship between serum HO-1 and various other serum biomarkers, change in HRCT findings, and disease prognosis at 12 weeks after diagnosis of acute exacerbation was evaluated in 51 patients, of whom 17 (33%) had idiopathic pulmonary fibrosis (IPF). Serum HO-1 was higher in patients with acute exacerbation of IPF than in patients with acute exacerbation of other ILDs. Serum HO-1 levels were higher in patients who died within these 12 weeks than in survivors. Among age, sex, comorbidities, IPF diagnosis, HRCT findings, and blood biomarkers, serum HO-1 was a primary predictor of 12-week mortality. In 41 patients who underwent repeat HRCT, serum HO-1 was higher in patients with honeycomb progression than in those without. Serum HO-1 measurement could be useful for evaluating disease mortality and morbidity of patients with acute exacerbation of ILDs.

Anti-mutated citrullinated vimentin antibodies are increased in IPF patients

IntroAn increased prevalence of serum anti-MCV antibody is observed in the serum of patients with idiopathic pulmonary fibrosis (IPF) but the clinical relevance of these antibodies is unknown. MethodsPatients from our center with a diagnosis of IPF according to the 2018 ATS/ERS/JRS/ALAT guidelines and at least one anti-MCV assay available were selected. All patients were part of the prospective cohort European IPF registry and selected between 03/2010 and 03/2018. We constituted two groups of patients according to the anti-MCV status at baseline to compare their characteristics at baseline and the evolution of lung function, survival and/or transplantation status. ResultsAnti-MCV data were available for 101 patients, of whom 86 had complete clinical data available. Twenty-nine (34 %) patients had a positive anti-MCV assay (MCV+), at a low level in most patients (29 UI/mL [IQR 25—40]), and 57 (66 %) patients a negative assay (MCV-). MCV+ patients were 20 men and 9 women, with a median age of 73 years [IQR 67—78]. MCV- patients were 49 men and 8 women with a median age of 72 years [IQR 64—77]. Sixty-two (75 %) patients were ex-smokers and 5 (6 %) were active smokers. Median cumulative tobacco smoke exposure was 22.5 (15.0–38.6) and was similar in both groups. Lung function test results and HRCT pattern distribution was similar in both groups at baseline. The median duration of follow-up was 3.5 years [IQR 2.1—5.0]. Lung function decline was similar in both groups. During the study period, 31 (36 %) patients died or have been transplanted with no difference in transplant-free survival status between the two groups. ConclusionLow level anti-MCV autoimmunity was prevalent in IPF patients