Diagnosis Of Idiopathic Pulmonary Fibrosis Research Articles

Hypnotics and Mortality in Idiopathic Pulmonary Fibrosis: Hospital and National Data-based Analysis

Patients with idiopathic pulmonary fibrosis (IPF) may suffer from insomnia and use hypnotics. However, the effect of the use of hypnotics on their clinical course remains unclear. Is the use of hypnotics associated with an increased risk of mortality in patients with IPF? This study included 99 and 123 patients with IPF from the Hamamatsu and Seirei hospital-based cohorts, respectively, and 30,218 patients with IPF from the national claims database of Japan (NDB cohort). To analyze the association of hypnotic use with outcomes avoiding immortal time bias, multivariable Cox models with time-dependent covariates and target trial emulation with a new user design were employed for the hospital- and NDB-based cohorts, respectively. In the cohorts studied, the 3-year cumulative incidence of new use of hypnotics after IPF diagnosis was 13.4%-24.1%. In both the hospital-based cohorts, the continuous use of hypnotics was associated with an increased risk of all-cause mortality and disease progression. In the NDB cohort, the continuous use of hypnotics was also associated with an increased risk of all-cause mortality. Subgroup analysis found associations between the continuous use of hypnotics and increased mortality regardless of sex and comorbidities, excluding certain subpopulations. This study found that continuous use of hypnotics was associated with an increased risk of mortality in patients with IPF. Given the relatively high cumulative incidence of hypnotic use in this population, there is an urgent need to reassess the appropriate use of hypnotics for patients with IPF.

Gene polymorphisms and risk of idiopathic pulmonary fibrosis: a systematic review and meta-analysis.

Idiopathic pulmonary fibrosis (IPF) has been widely hypothesized to occur as a result of an interplay between a nexus of environmental and genetic risk factors. However, not much is known about the genetic aspect of this disease. The objective of this review was to identify the genetic polymorphisms associated with the risk of developing IPF. We searched PubMed, EBSCO CINAHL Plus, Web of Science, and Wiley Cochrane Library databases for studies on risk factors of IPF published between March 2000 and November 2023. Studies with an IPF diagnosis based only on the American Thoracic Society and the European Respiratory Society guidelines were included. Thirty-one case-control studies were included with 3997 IPF and 20,925 non-IPF subjects. Two of the studies enrolled biopsy-proven IPF patients; 13 studies diagnosed IPF on the basis of clinical and high-resolution computed tomography (HRCT) findings; and 14 studies diagnosed based on both biopsy and clinical and HRCT findings. 16 studies with MUC5B rs35705950, IL-4 rs2243250, IL-4 rs2070874, and tumor necrosis factor α (TNFα)-308 were eligible for meta-analysis. The allele contrast model (T versus G) for MUC5B rs35705950 revealed statistically significant association of T allele with the risk of IPF [odds ratio (OR) 3.84, 95% confidence interval (CI) 3.20 to 4.61, adjusted p<0.0001), as was the allele contrast model for Asian (OR 2.83, 95% CI 1.51 to 5.32, adjusted p=0.009) and Caucasian (OR 4.11, 95% CI 3.56 to 4.75, adjusted p<0.0001). The allele contrast models for IL-4 rs2243250, IL-4 rs2070874, and TNFα-308 did not demonstrate any significant association with IPF. This review suggests an association of MUC5B rs35705950 T allele with the risk of developing IPF. To our knowledge, this study is the first to aggregate several genetic polymorphisms associated with IPF.

Exploring the Mechanisms and Preventive Strategies for the Progression from Idiopathic Pulmonary Fibrosis to Lung Cancer: Insights from Transcriptomics and Genetic Factors.

Background: Idiopathic pulmonary fibrosis (IPF) leads to excessive fibrous tissue in the lungs, increasing the risk of lung cancer (LC) due to heightened fibroblast activity. Advances in nucleotide point mutation studies offer insights into fibrosis-to-cancer transitions. Methods: A two-sample Mendelian randomization (TSMR) approach was used to explore the causal relationship between IPF and LC. A weighted gene co-expression network analysis (WGCNA) identified shared gene modules related to immunogenic cell death (ICD) from transcriptomic datasets. Machine learning selected key genes, and a multi-layer perceptron (MLP) model was developed for IPF prediction and diagnosis. SMR and PheWAS were used to assess the expression of key genes concerning IPF risk. The impact of core genes on immune cells in the IPF microenvironment was explored, and in vivo experiments were conducted to examine the progression from IPF to LC. Results: The TSMR approach indicated a genetic predisposition for IPF progressing to LC. The predictive model, which includes eight ICD key genes, demonstrated a strong predictive capability (AUC = 0.839). The SMR analysis revealed that the elevated expression of MS4A4A was associated with an increased risk of IPF (OR = 1.275, 95% CI: 1.029-1.579; p = 0.026). The PheWAS did not identify any significant traits linked to MS4A4A expression. The rs9265808 locus in MS4A4A was identified as a susceptibility site for the progression of IPF to LC, with mutations potentially reprogramming lung neutrophils and increasing the LC risk. In vivo studies suggested MS4A4A as a promising therapeutic target. Conclusions: A causal link between IPF and LC was established, an effective prediction model was developed, and MS4A4A was highlighted as a therapeutic target to prevent IPF from progressing to LC.

Quantitative CT-analysis of over aerated lung tissue and correlation with fibrosis extent in patients with idiopathic pulmonary fibrosis

IntroductionThe usual interstitial pneumonia (UIP) pattern, hallmark of idiopathic pulmonary fibrosis (IPF), may induce harmful local overdistension during mechanical ventilation given the juxtaposition of different tissue elasticities. Mechanotransduction, linking mechanical stress and strain to molecular pro-fibrotic pathways, likely contributes to fibrosis progression. Understanding the mechanical forces and aeration patterns in the lungs of IPF patients is crucial for unraveling potential mechanisms of disease progression. Quantitative lung computed tomography (CT) can accurately assess the air content of lung regions, thus informing on zonal distension. This study aims to investigate radiological evidence of lung over aeration in spontaneously breathing UIP patients compared to healthy controls during maximal inspiration.MethodsPatients with IPF diagnosis referred to the Center for Rare Lung Diseases of the University Hospital of Modena (Italy) in the period 2020–2023 who underwent High Resolution Computed Tomography (HRCT) scans at residual volume (RV) and total lung capacity (TLC) using standardized protocols were retrospectively considered eligible. Patients with no signs of lung disease at HRCT performed with the same image acquisition protocol nor at pulmonary function test (PFTs) served as controls. Lung segmentation and quantitative analysis were performed using 3D Slicer software. Lung volumes were measured, and specific density thresholds defined over aerated and fibrotic regions. Comparison between over aerated lung at RV and TLC in the two groups and according to lung lobes was sought. Further, the correlation between aerated lung and the extent of fibrosis was assessed and compared at RV and TLC.ResultsIPF patients (N = 20) exhibited higher over aerated lung proportions than controls (N = 15) both at RV and TLC (4.5% vs. 0.7%, p < 0.0001 and 13.8% vs. 7%, p < 0.0001 respectively). Over aeration increased significantly from RV to TLC in both groups, with no intergroup difference (p = 0.67). Sensitivity analysis revealed significant variations in over aerated lung areas among lobes when passing from RV to TLC with no difference within lobes (p = 0.28). Correlation between over aeration and fibrosis extent was moderate at RV (r = 0.62, p < 0.0001) and weak at TLC (r = 0.27, p = 0.01), being the two significantly different at interpolation analysis (p < 0.0001).ConclusionsThis study provides the first evidence of radiological signs of lung over aeration in patients with UIP-pattern patients when passing from RV to TLC. These findings offer new insights into the complex interplay between mechanical forces, lung structure, and fibrosis and warrant larger and longitudinal investigations.

A STUDY ON PIRFENIDONE VERSUS NINTEDANIB IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS IN A TERTIARY CARE HOSPITAL: A CROSS SECTIONAL STUDY

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic condition with a poor prognosis and have an average life expectancy of 3-4 years. Two antifibrotic treatments have been approved to treat IPF: nintedanib and pirfenidone. These medications lower the decline in lung function and lower the risk of acute respiratory deterioration, which is linked with a high morbidity and death.Individual clinical trials have not been powered to demonstrate mortality decreases, however analysis of pooled data from clinical trials and observational research imply that anti-fibrotic drugs increase life expectancy. This study describes the utility of anti-fibrotic drugs and compare their efficacy. Methods and Materials: This 6 month cross-sectional study conducted at Santhiram Medical College and General Hospital in Nandyal.In patients with IPF , Clinical, functional and radiological data were gathered at baseline and during the follow-up, as per our Center procedure.This study compares and evaluates the efficacy of nintedanib and pirfenidone. A total of 40 patients over the age of 18 with IPF diagnosis were included. Patients under 18 years , those with known fibrosing lung diseases, bronchial asthma, COPD, HIV, Tuberculosis, or other organ failures were excluded. Results: At baseline, IPF patients treated with Pirfenidone had Forced vital capacity(FVC) and Forced expiratory volume at 1 second(FEV1) predicted percentages of 63.57 ± 8.34% and 72.31 ± 4.91%, respectively. In IPF patients treated with Nintedanib, at baseline(time 0), FVC and FEV1 percentages were 60.15±8.82% and 72.31±4.91% respectively. There were no significant variations in FVC and FEV1 percentages at time 0 between patients treated with the two medications (p=0.23,p=0.7,respectively). At 3-month follow-up, patients treated with Pirfenidone had predicted FVC and FEV1 values of 65.73 ± 7.84% and 72.94 ± 4.45%, respectively, whereas patients treated with Nintedanib had predicted valuesof 65.75 ± 7.67% and 72.42 ± 4.45%. At 6-month follow-up, patients on Pirfenidone had predicted FVC and FEV1 values of 66.9 ± 8.72% and 73.5 ± 4.50%, respectively. Nintedanib treatment resulted in 67.7±8.46% and 72.94±4.51% outcomes. Conclusion: our study shown that pirfenidone and nintedanib are equally effective at reducing FVC decline over a 6-month time frame.While nintedanib was slightly more beneficial in lowering FVC decline during the 6-month period. Both drugs were well tolerated, while nintedanib showing good tolerance in the majority of IPF patients.

Diagnostic Performance of CLEIA Versus FEIA for KL-6 Peripheral and Alveolar Concentrations in Fibrotic Interstitial Lung Diseases: A Multicentre Study.

Interstitial lung diseases (ILD) is a group of lung disorders characterized by interstitial lung thickening due to inflammatory and fibrotic processes. Krebs von den Lungen-6 (KL-6) is a molecule secreted by damaged type II alveolar pneumocytes in the alveolar space. The goal of the present study was to compare two detection methods of KL-6 in both bronchoalveolar lavage (BAL) and serum from ILD patients at the moment of diagnosis. Patients with suspicious of ILD and followed at two Italian referral centres for rare lung diseases were included in the study. BAL fluid and serum were collected and analysed by chemiluminescent enzyme immunoassay (CLEIA) and fluorescent enzyme immunoassay (FEIA) methods provided by Tosoh Biosciences. A total of 158 (mean age ± standard deviation, 61.5 ± 13.7, 65 females) patients were enrolled. A total of, 36 had diagnosis of idiopathic pulmonary fibrosis (IPF), 74 sarcoidosis, 15 connective tissue disease-ILD (CTD-ILD) and 33 other ILD. Diagnostic agreement between two methods was demonstrated for both BAL (r = 0.707, p < 0.0001) and serum (r = 0.816, p < 0.0001). BAL KL-6 values were lower than serum (p < 0.0001). IPF patients had higher serum KL-6 concentration than other ILDs (p = 0.0294), while BAL KL-6 values were lower in IPF than in non-IPF (p = 0.0023). This study explored KL-6 concentrations through the CLEIA method in serum and BAL of patients with various ILDs, showing significant differences of biomarkers concentrations between IPF and other non-IPF ILDs. Our findings are promising as they provided further knowledge concerning KL-6 expression across different ILDs and may suggest its utility in differential diagnosis.

The incidence of acute exacerbation of idiopathic pulmonary fibrosis: a systematic review and meta-analysis

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with a high incidence of acute exacerbation and an increasing mortality rate. Currently, treatment methods and effects are limited. Therefore, we conducted a meta-analysis of the incidence of acute exacerbation in patients with IPF, hoping to provide reference for the prevention and management of IPF. We systematically searched the PubMed, Embase, Cochrane Library and Web of Science databases. From the creation of the database to the cohort study on April 3, 2023, we collected studies on the incidence of acute exacerbation of IPF patients, and used Stata software (version 16.0) for meta analysis. We used the Newcastle Ottawa Quality Assessment Scale (NOS) to assess the risk of bias for each study. We calculated the incidence of acute exacerbation in IPF patients and analyzed the risk factors for acute exacerbation in IPF patients and prognostic factors for overall survival from the initial IPF diagnosis. A total of ten cohort studies on the incidence of AE-IPF were included, including 11,855 IPF patients. The results showed that the incidence of acute exacerbation within one year was 9%; the incidence of acute exacerbation within 2 years is 13%; the incidence of acute exacerbation within 3 years is 19%; the incidence of acute exacerbation within 4 years is 11%. In addition, one study reported an acute exacerbation rate of 1.9% within 30 days. The incidence of acute exacerbation within ten years reported in one study was 9.8%. Mura et al.'s article included a retrospective cohort study and a prospective cohort study. The prospective cohort study showed that the incidence of acute exacerbation within 3 years was 18.6%, similar to the results of the retrospective cohort study meta-analysis. Our system evaluation and meta-analysis results show that the incidence of AE-IPF is relatively high. Therefore, sufficient attention should be paid to the research results, including the management and prevention of the disease, in order to reduce the risk of AE.Trial registration: PROSPERO, identifier CRD42022341323.

Pathological features of connective tissue disease-associated interstitial lung disease in transbronchial cryobiopsies.

Transbronchial cryobiopsies are increasingly used for the diagnosis of interstitial lung disease (ILD), but there is a lack of published information on the features of specific ILD in cryobiopsies. Here we attempt to provide pathological guidelines for separating usual interstitial pneumonia (UIP) of idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (FHP) and connective tissue disease-associated ILD (CTD-ILD) in cryobiopsies. We examined 120 cryobiopsies from patients with multidisciplinary discussion (MDD)-established CTD-ILD and compared them to a prior series of 121 biopsies from patients with MDD-established IPF or FHP. A non-specific interstitial pneumonia (NSIP) pattern alone was seen in 36 of 120 (30%) CTD-ILD, three of 83 (3.6%) FHP and two of 38 (5.2%) IPF cases, statistically favouring a diagnosis of CTD-ILD. The combination of NSIP + OP was present in 29 of 120 (24%) CTD-ILD, two of 83 (2.4%) FHP and none of 38 (0%) IPF cases, favouring a diagnosis of CTD-ILD. A UIP pattern, defined as fibroblast foci plus any of patchy old fibrosis/fibrosis with architectural distortion/honeycombing, was identified in 28 of 120 (23%) CTD-ILD, 45 of 83 (54%) FHP and 27 of 38 (71%) IPF cases and supported a diagnosis of FHP or IPF. The number of lymphoid aggregates/mm2 and fibroblast foci/mm2 was not different in IPF, CTD-ILD or FHP cases with a UIP pattern. Interstitial giant cells supported a diagnosis of FHP or CTD-ILD over IPF, but were infrequent. In the correct clinical/radiological context the pathological findings of NSIP, and particularly NSIP plus OP, favour a diagnosis of CTD-ILD in a cryobiopsy, but CTD-ILD with a UIP pattern, FHP with a UIP pattern and IPF generally cannot be distinguished.

A nitroreductase responsive probe for early diagnosis of pulmonary fibrosis disease

Idiopathic pulmonary fibrosis (IPF) is a serious interstitial lung disease. However, the definitive diagnosis of IPF is impeded by the limited capabilities of current diagnostic methods, which may fail to capture the optimal timing for treatment. The main goal of this study is to determine the feasibility of a nitroreductase (NTR) responsive probe, 18F-NCRP, for early detection and deterioration monitoring of IPF. 18F-NCRP was obtained with high radiochemical purity (>95 %). BLM-injured mice were established by intratracheal instillation with bleomycin (BLM) and characterized through histological analysis. Longitudinal PET/CT imaging, biodistribution study and in vitro autoradiography were performed. The correlations between the uptake of 18F-NCRP and mean lung density (tested by CT), as well as histopathological characteristics were analyzed. In PET imaging study, 18F-NCRP exhibited promising efficacy in monitoring the progression of IPF, which was earlier than CT. The ratio of uptake in BLM-injured lung to control lung increased from 1.4-fold on D15 to 2.2-fold on D22. Biodistribution data showed a significant lung uptake of 18F-NCRP in BLM-injured mice. There was a strong positive correlation between the 18F-NCRP uptake in the BLM-injured lungs and the histopathological characteristics. Given that, 18F-NCRP PET imaging of NTR, a promising biomarker for investigating the underlying pathogenic mechanism of IPF, is attainable as well as desirable, which might lay the foundation for establishing an NTR-targeted imaging evaluation system of IPF.

Research Progress of Idiopathic Pulmonary Fibrosis Complicated with Lung Cancer

Context: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic interstitial disease with unknown cause and pathogenesis. Idiopathic pulmonary fibrosis patients are more likely to be concomitant with lung cancer (LC) than normal older smoking men. Currently, there is no unified expert consensus on the diagnosis and treatment of IPF combined with lung cancer (IPF-LC) patients. Evidence Acquisition: We performed a computerized search of PubMed database with keywords: idiopathic pulmonary fibrosis complicated with LC and therapy. Results: Idiopathic pulmonary fibrosis is an independent risk factor for LC, and there are similar genetic mutations, epigenetic changes, and signaling pathways between IPF and LC. acute exacerbation of IPF (AE-IPF) poses a significant challenge in the treatment of IPF-LC patients, as surgery, chemotherapy, and targeted therapy may all trigger AE-IPF leading to patient death. The clinical benefits of anti-fibrotic therapy drugs such as nintedanib or combined therapy targeting lung fibrosis and LC are expected to outweigh adverse reactions. Conclusions: Combination therapy may be an effective strategy for treating IPF-LC in the future, and there is an urgent need to develop appropriate preclinical animal models and conduct more clinical studies to find safe and effective new strategies for treating IPF-LC.

Demographic and Clinical Factors Associated With Diagnostic Confidence in Interstitial Lung Disease: Findings From the Pulmonary Fibrosis Foundation Patient Registry

BACKGROUNDAccurate diagnosis of interstitial lung disease (ILD) can be challenging. Accordingly, clinicians may attribute a diagnostic certainty based on guideline criteria and clinical judgment. However, further research is needed to refine this approach and improve diagnostic clarity. RESEARCH QUESTIONWhat are the real-world factors associated with diagnostic confidence in fibrotic ILD? STUDY DESIGN AND METHODSData were included from all patients enrolled in the Pulmonary Fibrosis Foundation Patient Registry from March 2016 to August 2018. Baseline demographic and clinical characteristics were collected at enrollment, or at the test date closest to the date of consent for longitudinal measures. Descriptive analyses were performed separately for all participants, as well as for subgroup participants with idiopathic pulmonary fibrosis (IPF) and participants with non-IPF ILD, stratified by the level of investigator diagnostic confidence (High vs Medium/Low) assigned at registry enrollment. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable logistic regression, with the aforementioned characteristics as predictors. RESULTSData up to April 2022 from 1,992 participants were included. In adjusted logistic regression analyses among all participants, antifibrotic use (OR [95% CI], 1.51 [1.09-2.07]), longer time since diagnosis (0.94 [0.89-0.98]) at the research unit of 365 days, and diabetes (2.56 [1.01-6.44]) were significantly associated with higher diagnostic confidence, and non-IPF idiopathic interstitial pneumonia (vs IPF; 0.36 [0.24-0.55]), insurance - others (0.65 [0.43-0.97]), and Hispanic ethnicity (0.54 [0.31-0.94]) were significantly associated with lower diagnostic confidence. Factors associated with diagnostic confidence in the IPF and/or non-IPF ILD groups included age, male sex, region, immunomodulatory medication, multidisciplinary team discussion, surgical lung biopsy, and definite high-resolution computed tomography pattern. INTERPRETATIONThese findings suggest that certain demographic and clinical factors may influence physicians’ confidence in diagnosis of IPF and non-IPF ILD. Tailored physician education may help to reduce biases and improve consistency in diagnosis.

The role of biomarkers in the diagnosis and treatment follow-up of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease of unknown cause with a poor prognosis. The aim of our study is to determine the role of Krebs von den Lungen-6(KL-6),Matrix metalloproteinase (MMP)-7, Surfactant protein A (SP-A), Surfactant protein D(SP-D), vascular endothelial growth factor (VEGF) and periostin in the diagnosis of IPF and in the response monitoring of patients treated. 47 IPF patients, 27 non-IPF interstitial lung disease (ILD) patients and 21 healthy individuals were included in the study. Demographic data, pulmonary function test- Diffusing capacity of the lung for carbon monoxide (PFT-DLCO) measurements, High-resolution computed tomography (HRCT) findings of the patients were recorded, and serum samples were taken. While periostin and SP-A levels were not significantly different between IPF and non-IPF ILD, they were significantly higher in both IPF and non-IPF ILD compared to healthy control group (p=0.002,p=0.006 for periostin and p=0.002,p<0.001 for SP-A, respectively).By receiver operating characteristic (ROC) analysis, the cut-off point for periostin to distinguish IPF is >594.5 pg/ml (sensitivity 72%, specificity 76%), while the cut-off point for SP-A is found >6.62 ng/ml (sensitivity 87.2%,specificity 57.1%). In the combined ROC analysis based on SP-A=6.62 ng/ml and periostin >634.6 pg/ml values, sensitivity was found to be 85% and specificity was 57%.Considering the correlation of forced expiratory volumein the first second (FEV1)(%), forced vital capacity (FVC)(%), restriction and diffusion severities with biomarker levels in the 6th month of IPF patients treated, a correlation was detected between MMP-7 levels and restriction severities (p=0.020), between KL-6 levels and restriction and diffusion severities (p=0.002), and between SP-A levels and FVC(%)(p=0.006). It is thought that biomarkers SP-A and periostin may contribute significantly to the diagnosis of patients with IPF, and SP-A, MMP-7 and KL-6 levels may contribute significantly to treatment follow-up.

Succinate promotes pulmonary fibrosis through GPR91 and predicts death in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is believed to be associated with a notable disruption of cellular energy metabolism. By detecting the changes of energy metabolites in the serum of patients with pulmonary fibrosis, we aimed to investigate the diagnostic and prognostic value of energy metabolites in IPF, and further elucidated the mechanism of their involvement in pulmonary fibrosis. Through metabolomics research, it was discovered that the TCA cycle intermediates changed dramatically in IPF patients. In another validation cohort of 55 patients with IPF compared to 19 healthy controls, it was found that succinate, an intermediate product of TCA cycle, has diagnostic and prognostic value in IPF. The cut-off levels of serum succinate were 98.36 μM for distinguishing IPF from healthy controls (sensitivity, 83.64%; specificity, 63.16%; likelihood ratio, 2.27, respectively). Moreover, a high serum succinate level was independently associated with higher rates of disease progression (OR 13.087, 95%CI (2.819–60.761)) and mortality (HR 3.418, 95% CI (1.308–8.927)). In addition, accumulation of succinate and increased expression of the succinate receptor GPR91 were found in both IPF patients and BLM mouse models of pulmonary fibrosis. Reducing succinate accumulation in BLM mice alleviated pulmonary fibrosis and 21d mortality, while exogenous administration of succinate can aggravate pulmonary fibrosis in BLM mice. Furthermore, GPR91 deficiency protected against lung fibrosis caused by BLM. In vitro, succinate promoted the activation of lung fibroblasts by activating ERK pathway through GPR91. In summary, succinate is a promising biomarker for diagnosis and prognosis of IPF. The accumulation of succinate may promote fibroblast activation through GPR91 and pulmonary fibrosis.

Progress in the radiologic diagnosis of idiopathic pulmonary fibrosis.

To discuss the most recent applications of radiological imaging, from conventional to quantitative, in the setting of idiopathic pulmonary fibrosis (IPF) diagnosis. In this article, current concepts on radiological diagnosis of IPF, from high-resolution computed tomography (CT) to other imaging modalities, are reviewed. In a separate section, advances in quantitative CT and development of novel imaging biomarkers, as well as current limitations and future research trends, are described. Radiological imaging in IPF, particularly quantitative CT, is an evolving field which holds promise in the future to allow for an increasingly accurate disease assessment and prognostication of IPF patients. However, further standardization and validation studies of alternative imaging applications and quantitative biomarkers are needed.

Central Role of CT in Management of Pulmonary Fibrosis.

With the approval of antifibrotic medications to treat patients with idiopathic pulmonary fibrosis and progressive pulmonary fibrosis, radiologists have an integral role in diagnosing these entities and guiding treatment decisions. CT features of early pulmonary fibrosis include irregular thickening of interlobular septa, pleura, and intralobular linear structures, with subsequent progression to reticular abnormality, traction bronchiectasis or bronchiolectasis, and honeycombing. CT patterns of fibrotic lung disease can often be reliably classified on the basis of the CT features and distribution of the condition. Accurate identification of usual interstitial pneumonia (UIP) or probable UIP patterns by radiologists can obviate the need for a tissue sample-based diagnosis. Other entities that can appear as a UIP pattern must be excluded in multidisciplinary discussion before a diagnosis of idiopathic pulmonary fibrosis is made. Although the imaging findings of nonspecific interstitial pneumonia and fibrotic hypersensitivity pneumonitis can overlap with those of a radiologic UIP pattern, these entities can often be distinguished by paying careful attention to the radiologic signs. Diagnostic challenges may include misdiagnosis of fibrotic lung disease due to pitfalls such as airspace enlargement with fibrosis, paraseptal emphysema, recurrent aspiration, and postinfectious fibrosis. The radiologist also plays an important role in identifying complications of pulmonary fibrosis-pulmonary hypertension, acute exacerbation, infection, and lung cancer in particular. In cases in which there is uncertainty regarding the clinical and radiologic diagnoses, surgical biopsy is recommended, and a multidisciplinary discussion among clinicians, radiologists, and pathologists can be used to address diagnosis and management strategies. This review is intended to help radiologists diagnose and manage pulmonary fibrosis more accurately, ultimately aiding in the clinical management of affected patients. ©RSNA, 2024 Supplemental material is available for this article.

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.

Efficacy and Mechanism of Fuyang Yiyin Method in Pulmonary Fibrosis Based on the Theory of Yang Transforming into Qi, Yin Constituting Form

Idiopathic pulmonary fibrosis (IPF) is a common pathological manifestation of various pulmonary diseases, characterized by insidious onset and progression to irreversible organ failure. Currently, there are still inadequacies in the diagnosis and treatment of IPF. Traditional Chinese medicine (TCM) can intervene in IPF at multiple levels, targets, and pathways, possessing significant advantages in the treatment of IPF. The underlying mechanisms deserve further exploration. The theory of Yang Transforming into Qi, Yin Constituting Form in Huangdi Neijing embodies the specific meanings of yin and yang, containing profound views on life and disease. The pathological changes of IPF conform to the theory of yin and yang in Yang Transforming into Qi, Yin Constituting Form, where deficiency of yang transforming into qi and excessive formation of yin constitute the core pathogenesis of IPF. This paper proposes the principle of Fuyang Yiyin for IPF, aiming to nourish the source of fire and dispel yin turbidity, in order to broaden the clinical treatment strategies for IPF.

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.

Automatic breathing phase identification based on the second derivative of the recorded lung sounds

This paper presents a new method for automatic identification of the inspiratory and expiratory breathing phases in lung sound recordings. Adventitious lung sounds (wheezes and crackles), superimposed on the breath sounds, are generally an early indication of the disease, and their timing in the breathing cycle (early/mid/late inspiratory or expiratory) has clinical significance for monitoring or diagnosing disease. Therefore, the identification of the phases of the breathing cycle is an essential step for clinical interpretation of pulmonary auscultation. The proposed algorithm is designed to be robust in the presence of adventitious lung sounds or where the breath sounds may be noisy compared to healthy lung sounds. The algorithm uses the Savitzky & Golay (SG) filter to estimate the second derivative of the lung sound signal then calculates its normalized absolute value. A threshold value is used to clip any large amplitude peaks and, following low-pas filtering, the breathing phases are visible in the plotted signal. A rule-based approach to locating peaks and troughs is then used to identify inspirations and expirations. The performance of the method is evaluated using four different datasets: (a) a longitudinal dataset recorded from 19 subjects with a diagnosis of idiopathic pulmonary fibrosis (IPF), (b) a cross-sectional dataset recorded from 55 subjects who were referred for high-resolution computed tomography (HRCT) scan of the chest for various clinical indications, (c) a longitudinal dataset recorded from 10 healthy subjects, and (d) an open access lung sounds dataset containing recordings from 41 subjects with wheeze (9 with chronic obstructive pulmonary fibrosis and 32 with asthma). On average for inspiratory phase identification the algorithm had a sensitivity of (mean (standard deviation)) 92.84 (12.88)%, positive predictive value of 90.64(15.96)%, and F1-score of 90.67 (12.53)%. For identification of the expiratory phase, the algorithm had an average sensitivity of 92.19 (13.44)%, an average positive predictive value of 91.55 (15.23)%, and an average F1-score of 90.89 (12.45)%. The method shows good potential for automatic identification of breathing phases in recorded lung sounds.