Diagnosis Of IPF Research Articles

Reliability of crackles in fibrotic interstitial lung disease: a prospective, longitudinal study

BackgroundAlthough crackles on chest auscultation represent a fundamental component of the diagnostic suspect for fibrotic interstitial lung disease (ILD), their reliability has not been properly studied. We assessed the agreement among respiratory physicians on the presence and changes over time of audible crackles collected in a prospective longitudinal cohort of patients with fibrotic ILD.MethodsLung sounds were digitally recorded at baseline and after 12 months at eight anatomical sites. Nine respiratory physicians blindly assessed randomized couples of recordings obtained from the same anatomical site at different timepoints. The physicians indicated the presence of crackles in individual recordings and which recording from each couple eventually had more intense crackles. Fleiss’ kappa coefficient was used to measure inter- and intra-rater agreement.ResultsFifty-two patients, mostly with a diagnosis of IPF (n = 40, 76.9%) were prospectively enrolled between October 2019 and May 2021. The final acoustic dataset included 702 single recordings, corresponding to 351 couples of recordings from baseline and 12-months timepoints. Kappa coefficient was 0.57 (95% CI 0.55–0.58) for the presence of crackles and 0.42 (95% CI 0.41–0.43) for acoustic change. Intra-rater agreement, measured for three respiratory physicians on three repeated assessments, ranged from good to excellent for the presence of crackles (κ = 0.87, κ = 0.86, κ = 0.79), and from moderate to good for acoustic change (κ = 0.75, κ = 0.76, κ = 0.57).ConclusionsAgreement between respiratory physicians for the presence of crackles and acoustic change was acceptable, suggesting that crackles represent a reliable acoustic finding in patients with fibrotic ILD. Their role as a lung-derived indicator of disease progression merits further studies.

Prevalence and prognostic value of malnutrition in patients with IPF using three scoring systems

BackgroundTo describe the nutritional status of IPF patients, report clinical associations and evaluate the prognostic value of them in IPF. Methods264 IPF patients diagnosed with IPF at the Second Xiangya Hospital of Central South University between January 2011 and January 2021 were recruited. Three different scoring systems, including nutritional risk index (NRI), controlling nutritional status (CONUT) score, and prognostic nutritional index (PNI) were used to describe the nutritional status of IPF patients. ResultThis study investigated the prevalence of malnutrition in 264 IPF patients, of which the percentage with malnutrition varied from 37.5 % with the NRI, to 47.4 % with the CONUT score, and to 6.4 % with the PNI. The moderate to severe malnutrition ranged from 10.2 % to 31.1 % across these indices, with PNI identifying only 4.9 % in this category. Worsening malnutrition status was associated with significantly higher incidence of all-cause mortality and IPF death regard of the malnutrition index as NRI (p < 0.05). When the normal nutrition of NRI was used as a reference, patients in the moderate to severe risk remained at a higher risk of all-cause death (HR = 2.06(1.25–3.41)) and IPF death(HR = 2.36(1.35–4.15)). The adjusted multivariate analysis, identified age(HR = 1.13(1.08–1.20)), DLCO <60, % predicted (HR = 3.31(1,24–9.42)) and the use of anti-fibrotic drugs (HR = 0.25(0.10–0.60)) as independent predictors of mortality. ConclusionsMalnutrition is common among patients with IPF and the baseline as diagnosis of IPF is strongly related to increased mortality.

Occupational and environmental risk factors for idiopathic pulmonary fibrosis: A case-control study

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease of unknown etiology. The aim of this study was to evaluate the environmental and occupational risk factors of IPF. MethodsThis hospital-based, case-control study included 206 patients with IPF selected from the Seoul National University Bundang Hospital Interstitial Lung Disease registry and 167 controls without lung disease. Data on occupation, lifestyle, transportation, and types of environmental and occupational dust exposure were obtained using a questionnaire. IPF diagnosis was confirmed based on the recent guidelines, and the possibility of hypersensitivity pneumonitis was excluded. Multiple logistic regression was performed to determine the risk factors for IPF. ResultsAfter adjusting for age and sex, ever-smokers (odds ratio [OR], 2.35; 95 % confidence interval [CI]: 1.51–3.68) and individuals who smoked more than 30 pack-years (OR, 2.79; 95%CI: 1.70–4.68) showed an increased risk for IPF. Any occupational dust exposure (adjusted OR, 2.08; 95%CI: 1.19–3.72), especially exposure to chemicals (adjusted OR, 3.52; 99%CI: 1.56–9.05), was associated with IPF after adjusting for age, sex, and smoking. ConclusionsSmoking and occupational dust exposure are associated with an increased risk for IPF. Both factors have dose and duration-dependent relationships with the risk for IPF.

The impact of antifibrotic use on long-term clinical outcomes in the pulmonary fibrosis foundation registry

BackgroundIdiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease (ILD) with a high mortality rate. The antifibrotic medications pirfenidone and nintedanib have been in use since 2014 for this disorder and are associated with improved rate of lung function decline. Less is known about their long-term outcomes outside of the clinical trial context.MethodsThe Pulmonary Fibrosis Foundation Patient Registry was used for this study. Patients with an IPF diagnosis made within a year of enrollment were included. The treated group was defined as patients receiving either pirfenidone or nintedanib for at least 180 days. The untreated group did not have any record of antifibrotic use. Demographic data, comorbidities, serial lung function, hospitalization, and vital status data were collected from the registry database. The primary outcomes were transplant-free survival, time to first respiratory hospitalization, and time to 10% absolute FVC decline. Time-to-event analyses were performed utilizing Cox proportional hazards models and the log-rank test. Model covariates included age, gender, smoking history, baseline lung function, comorbidities, and oxygen use.ResultsThe registry contained 1212 patients with IPF; ultimately 288 patients met inclusion criteria for the treated group, and 101 patients were designated as untreated. Patients treated with antifibrotics were significantly younger (69.8 vs. 72.6 years, p = 0.008) and less likely to have smoked (61.1% ever smokers vs. 72.3% never smokers, p = 0.04). No significant differences were seen in race, gender, comorbidities, or baseline pulmonary function between groups. The primary outcome of transplant-free survival was not significantly different between the two groups (adjusted HR 0.799, 95% CI 0.534–1.197, p = 0.28). Time to respiratory hospitalization was significantly shorter in the treated group (adjusted HR 2.12, 95% CI 1.05–4.30, p = 0.04). No significant difference in time to pulmonary function decline was seen between groups.ConclusionsThis multicenter study demonstrated 63% of newly diagnosed IPF patients had continuous antifibrotic usage. Antifibrotics were not associated with improved transplant-free survival or pulmonary function change but was associated with an increased hazard of respiratory hospitalization. Future studies should further investigate the role of antifibrotic therapy in clinically important outcomes in real-world patients with IPF and other progressive ILDs.

Predictors of Mortality in Pulmonary Hypertension-Associated Chronic Lung Disease.

Background/Objectives: Pulmonary hypertension (PH) often accompanies chronic lung diseases. Several chronic lung diseases with PH portends unfavorable outcomes. We investigated which variables in this cohort of patients with chronic lung disease and PH predicts mortality. Methods: This is a retrospective analysis of patients with chronic lung disease and PH at a single tertiary, academic center. The underlying lung disease included were COPD, IPF, other fibrotic ILD, non-fibrotic ILD, fibrotic sarcoidosis, and CPFE. All patients had right heart catheterization diagnostic of PH as well as pulmonary function testing data including 6 min walk testing. Univariable and multivariate Cox regression was performed to identify variables associated with mortality. Results: We identified 793 patients with chronic lung disease and PH. In total, 144 patients died prior to potential lung transplant. In multivariable Cox regression IPF, other fibrotic ILD, non-fibrotic ILD, and CPFE were significantly associated with an increased risk of mortality. Severe PH (PVR > 5 WU), FEV1 < 30% predicted, FVC < 40% predicted, 6 min walk distance < 150 m were also significantly associated with an increased risk of mortality. Conclusions: Carrying a diagnosis of IPF, CPFE, fibrotic ILD, or non-fibrotic ILD with PH has an increased risk of mortality as compared to COPD with PH. Hemodynamic, PVR > 5 WU, 6 min walk test less than 150 m, as well as spirometric data including FEV1 < 30% and FVC < 40% predicted were independently associated with an increased risk of death.

Impact of Acute Exacerbation of Idiopathic Pulmonary Fibrosis on Lung Transplant Outcomes.

Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) are acute, significant respiratory deteriorations in patients with IPF and can lead to increased morbidity and mortality. It remains unclear how AE-IPF impacts lung transplant (LTX) outcomes. All adult patients who were listed for LTX between July 2005 and October 2020 at the Loyola University Medical Center with a diagnosis of IPF were included. Pretransplant characteristics and posttransplant outcomes were gathered via retrospective chart review. The primary outcome was short- and long-term survival for patients transplanted during stable IPF versus those with AE-IPF. One hundred fifty-nine patients were included in this study, 17.6% of whom were transplanted during AE-IPF. AE-IPF patients were more likely to have higher oxygen needs pretransplant, have higher lung allocation score, and were more likely to be intubated or be on extracorporeal membrane oxygenation as compared with stable IPF patients. Survival by AE status at transplant did not differ at 90 d or 1 y posttransplantation. There were also no significant differences in rates of severe primary graft dysfunction or acute rejection within 1 y. Patients with AE-IPF were more likely to have higher oxygenation requirements and higher lung allocation score at the time of LTX than those with stable IPF. Despite this, there were no differences in survival at 90 d, 1 y, or 3 y, or differences in incidence of severe primary graft dysfunction or acute cellular rejection. Transplantation of patients with AE-IPF has clinical outcomes comparable with transplantation of patients with stable IPF. This contrasts with previous studies examining LTX in patients with AE-IPF.

Association between statin use and the risk for idiopathic pulmonary fibrosis and its prognosis: a nationwide, population-based study

Given the pleiotropic effects of statins beyond their lipid-lowering effects, there have been attempts to evaluate the role of statin therapy in IPF, but they have shown inconclusive results. Data from the National Health Insurance Service (NHIS) database of South Korea were used to investigate the effects of statin therapy on IPF. The IPF cohort consisted of a total of 10,568 patients who were newly diagnosed with IPF between 2010 and 2017. These patients were then matched in a 1:3 ratio to 31,704 subjects from a control cohort without IPF, with matching based on age and sex. A case–control study was performed to evaluate the association between statin use and the risk for IPF, and the multivariable analysis revealed that statin use was associated with a lower risk for IPF (adjusted OR 0.847, 95% CI 0.800–0.898). Using the IPF cohort, we also evaluated whether statin use at the time of diagnosis was associated with future clinical outcomes. The statin use at the time of IPF diagnosis was associated with improved overall survival (adjusted HR 0.779, 95% CI 0.709–0.856). Further prospective studies are needed to clarify the role of statin therapy in IPF.

Radiological Findings in the Diagnosis of IPF, PPFE, and PPF

Radiological Findings in the Diagnosis of IPF, PPFE, and PPF

Exosomal circRNAs in the plasma serve as novel biomarkers for IPF diagnosis and progression prediction

BackgroundIdiopathic Pulmonary Fibrosis (IPF) is a type of chronic interstitial pneumonia, often fatal, with elusive causes and a bleak prognosis. Its treatment options are limited and largely ineffective. Early detection and precise diagnosis are pivotal in managing the disease effectively and enhancing patient survival rates. Recently, the quest for trustworthy biomarkers for IPF has gained momentum. Notably, emerging studies indicate that circular RNAs (circRNAs) found in exosomes may hold significant potential as valuable diagnostic markers.MethodsIn this study, we initially explored the expression profile of circRNAs in exosomes sourced from the blood of IPF patients and healthy volunteers, employing a human circRNA microarray. We then utilized RT-qPCR to corroborate the dysregulated circRNAs identified by the microarray during the training phase. Next, the circRNAs that displayed a significant increase during the training phase were selected for further validation in a larger cohort encompassing 113 IPF patients and 76 healthy volunteers. Ultimately, the expression level and function of hsa_circ_0044226 were substantiated through a series of in vivo and in vitro experiments.ResultsUtilizing a human circRNA microarray, we identified 11 dysregulated circRNAs in the exosomes derived from the blood of IPF patients and control volunteers. Subsequent RT-qPCR analysis revealed significant increases in three circRNAs (hsa_circ_0044226, hsa_circ_0004099, hsa_circ_0008898) within the IPF patients. Notably, hsa_circ_0044226 was markedly elevated in patients experiencing acute exacerbation of IPF (AE-IPF) compared to those with stable IPF (S-IPF). Additionally, an upregulation of hsa_circ_0044226 was observed in the blood exosomes derived from a bleomycin-induced IPF mouse model.ConclusionThe expression levels of hsa_circ_0044226, hsa_circ_0004099, and hsa_circ_0008898 in plasma exosomes introduce a new paradigm of biomarkers for the diagnosis and progression of IPF.

Prognostic factors associated with mortality in acute exacerbations of idiopathic pulmonary fibrosis: A systematic review and meta-analysis

BackgroundAcute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) increases mortality risk, but which factors increase mortality is unknown. We aimed to perform a prognostic review of factors associated with mortality in patients with IPF. Study designand methods: We searched MEDLINE, EMBASE, and CINAHL for studies that reported on the association between any prognostic factor and AE-IPF. We assessed risk of bias using the QUIPS tool. We conduced pairwise meta-analyses using REML heterogeneity estimator, and GRADE approach to assess the certainty of the evidence. ResultsWe included 35 studies in our analysis. We found that long-term supplemental oxygen at baseline (aHR 2.52 [95 % CI 1.68 to 3.80]; moderate certainty) and a diagnosis of IPF compared to non-IPF ILD (aHR 2.19 [95 % CI 1.22 to 3.92]; moderate certainty) is associated with a higher risk of death in patients with AE-IPF. A diffuse pattern on high resolution computed tomography (HRCT) compared to a non-diffuse pattern (aHR 2.61 [95 % CI 1.32 to 2.90]; moderate certainty) is associated with a higher risk of death in patients with AE-IPF. We found that using corticosteroids prior to hospital admission (aHR 2.19 [95 % CI 1.26 to 3.82]; moderate certainty) and those with increased neutrophils (by % increase) in bronchoalveolar lavage (BAL) during the exacerbation is associated with a higher risk of death (aHR 1.02 [1.01 to 1.04]; moderate certainty). InterpretationOur results have implications for healthcare providers in making treatment decisions and prognosticating the clinical trajectory of patients, for researchers to design future interventions to improve patient trajectory, and for guideline developers in making decisions about resource allocation.

Increased expression of OPN contributes to idiopathic pulmonary fibrosis and indicates a poor prognosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is fibrotic lung disease with no effective treatment. It is characterized by destruction of alveolar structure and pulmonary interstitial fibrosis, leading to dyspnea and even asphyxia death of patients. Epithelial-mesenchymal transition (EMT) is considered to be a driving factor in the pathogenesis of IPF. Osteopontin (OPN) is a secreted protein widely present in the extracellular matrix and involved in the occurrence and development of a variety of diseases.MethodsThe original datasets were obtained from NCBI GEO databases analyzed with the online tool GEO2R and EasyGEO. Bleomycin induced mouse pulmonary fibrosis model and OPN/OPN-biotin treated mouse model were established to investigate the role of OPN in mouse pulmonary fibrosis and the target cells of OPN. A549 cells and HBE cells were used to explore the mechanism of OPN-induced epithelial-mesenchymal transition (EMT) in epithelial cells and mass spectrometry was used to detect OPN downstream receptors. Precision-cut lung slices and lentivirus-treated mice with pulmonary fibrosis were used to examine the therapeutic effect of OPN and its downstream pathways on pulmonary fibrosis.ResultsWe demonstrate that the content of OPN in IPF bronchoalveolar lavage fluid (BALF) is high compared to the normal groups, and its expression level is correlated with prognosis. At the animal level, OPN was highly expressed at all stages of pulmonary fibrosis in mice, and the bronchoalveolar lavage fluid (BALF) could accurately reflect its expression in the lung. Next, we reveal that OPN was mainly expressed by macrophages and the main target cells of OPN were epithelial cells. Mice developed pulmonary fibrosis accompanied after treating the mice with OPN. Both in vitro and in vivo experiments confirmed that OPN could induce EMT of alveolar epithelial cells. Mechanistically, OPN binding triggered phosphorylation of FAK by CD44, thus activating snail1-mediated profibrotic protein synthesis. Inhibition of FAK phosphorylation and its downstream pathways can effectively alleviate pulmonary fibrosis in precision sections of lung tissue (PCLS) assay. OPN knockdown in bleomycin-induced lung fibrosis mice led to significantly less fibrosis.ConclusionOur data suggest that OPN mediates lung fibrosis through EMT, implicating its potential therapeutic target and prognostic indicator role for IPF. OPN may be a target for the diagnosis and treatment of IPF.

Identification and immunological characterization of PLA2G2A and cell death-associated molecular clusters in idiopathic pulmonary fibrosis

AimsIdiopathic pulmonary fibrosis (IPF) is a severe pulmonary interstitial pneumonia. Our study focuses on the role of PLA2 enzyme in the IPF to explore a more effective diagnosis and treatment mechanism of IPF. Main methodsTranscriptome data of IPF from GEO database and bleomycin-induced pulmonary fibrosis mice were analyzed to identify PLA2 enzyme and their metabolite, lysophosphatidylcholines 18:0, in IPF. Based on PLA2G2A and PLA2G2D / PLA2G2A-associated cell death genes (PCDs), the consensus clustering analysis was used to identify the subtypes of IPF and the correlation between PLA2G2A and prognosis was analyzed. The machine learning (ML) models and artificial neural network (ANN) model was used to validate the diagnostic accuracy of PLA2s and PCDs in diagnosing IPF. The gene and protein expression of NLRP3, GSDMD, and CASP-1 was estimated in recombinant PLA2G2A protein induced MLE-12 cells. Key findingsThe expression of PLA2G2D, PLA2G2A, and LPC18 significantly changed in IPF. Furtherly, PLA2G2A has a significant correlation with poor patient prognosis, which could predict the 2 or 3-years mortality rates of IPF. Two subtypes of IPF patients, identified based on PCDs, showed significant different immunoinfiltration. Recombinant PLA2G2A protein could induce the pyrotosis in the MLE-12 cell. The generalized linear model and ANN model of PLA2s or PCDs accurate diagnosis IPF. SignificancePLA2G2A is the most robustly associated gene with IPF among the PLA2s, which demonstrates a potential in diagnosing and prognostic value in IPF, and provides a foundation for further understanding and breakthroughs in IPF diagnosis and treatment.

Genome-wide DNA methylation analysis of Astragalus and Danshen on the intervention of myofibroblast activation in idiopathic pulmonary fibrosis

BackgroundIdiopathic pulmonary fibrosis (IPF), a chronic progressive interstitial lung disease of unknown etiology, is characterized by continuous damage to alveolar epithelial cells, abnormal repair of alveolar tissue, and alveolar wall scar formation. Currently, the recommended treatment for IPF in Western medicine is relatively limited. In contrast, traditional Chinese medicine and compound prescriptions show advantages in the diagnosis and treatment of IPF, which can be attributed to their multi-channel and multi-target characteristics and minimal side-effects. The purpose of this study was to further corroborate the effectiveness and significance of the traditional Chinese medications Astragalus and Danshen in IPF treatment.MethodsWe performed whole-genome methylation analysis on nine rat lung tissue samples to determine the epigenetic variation between IPF and non-fibrotic lungs using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and quantitative reverse transcription polymerase chain reactions.ResultsWe identified differentially methylated regions and 105 associated key functional genes in samples related to IPF and Chinese medicine treatment. Based on the methylation levels and gene expression profiles between the Chinese medicine intervention and pulmonary fibrosis model groups, we speculated that Astragalus and Salvia miltiorrhiza (traditionally known as Danshen) act on the Isl1, forkhead box O3, and Sonic hedgehog genes via regulation at transcriptional and epigenetic levels during IPF.ConclusionsThese findings provide novel insights into the epigenetic regulation of IPF, indicate the effectiveness of Astragalus and Danshen in treating IPF, and suggest several promising therapeutic targets for preventing and treating IPF.

The Reliability of Ultrasound in Diagnosis of Idiopathic Pulmonary Fibrosis

Abstract Background Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause. IPF is the most common and severe form of idiopathic interstitial pneumonia, with an unpredictable and variable clinical course, and is associated with an extremely poor prognosis. Objective To determine role of Ultrasound in diagnosis of idiopathic pulmonary fibrosis. Patients and Methods This cross-sectional study was conducted at tertiary care hospital at Ain Shams University hospitals from May 2021 till November 2021 and performed on total 60 patients diagnosed with idiopathic pulmonary fibrosis and had previous clinical features, documented high-resolution computed tomography (HRCT) scan findings and comparing it with lung ultrasound findings. Results Consequently, B-lines number and Pleural lines thickness statistically had significant high diagnostic performance in the diagnosis of IPF with cut-off of ≥ 3.0 which indicates that B-lines number ≥3.0 and Pleural lines thickness ≥3.0 mm had perfect sensitivity and LR+, while Pleural lines interruption had perfect specificity. B-lines number ≥3.0 had highest diagnostic accuracy, Youden’s index and kappa. Our research study revealed that B-lines number and Pleural lines thickness statistically were significantly higher in multiple zones spread cases (p value&amp;lt;0.001). Pleural lines interruption statistically was significantly more frequent in multiple zones spread cases. Conclusion As evident from the current study, this study introduced and thoroughly evaluated lung US features, which showed a high correlation with the high-resolution CT findings. Chest ultrasound could constitute an additional monitoring tool for IPF, which is a rapidly progressive disease, usable by the pulmonologist at the patient’s bedside or during a consultation, easily available, non-irradiating, achievable in a short time and immediately informative, for a trained sonographer.

Idiopathic pulmonary fibrosis in the United States: time to diagnosis and treatment

ObjectiveCreate a timeline of diagnosis and treatment for IPF in the US.Design, setting, and participantsA retrospective analysis was performed in collaboration with the OptumLabs Data Warehouse using an administrative claims database of Medicare Fee for Service beneficiaries. Adults 50 and over with IPF were included (2014 to 2019).ExposureTo focus on IPF, the following diagnoses were excluded: post-inflammatory fibrosis, hypersensitivity pneumonitis, rheumatoid arthritis, sarcoidosis, scleroderma, and connective tissue disease.Main outcomes and measuresData were collected from periods prior, during, and following initial clinical diagnosis of IPF. This included prior respiratory diagnoses, number of respiratory-related hospitalizations, anti-fibrotic and oxygen use, and survival.ResultsA total of 44,891 with IPF were identified. The most common diagnoses prior to diagnosis of IPF were upper respiratory infections (47%), acute bronchitis (13%), other respiratory disease (10%), chronic obstructive pulmonary disease and bronchiectasis (7%), and pneumonia (6%). The average time to a diagnosis of IPF was 2.7 years after initial respiratory diagnosis. Half of patients had two or more respiratory-related hospitalizations prior to IPF diagnosis. Also, 37% of patients were prescribed oxygen prior to diagnosis of IPF. These observations suggest delayed diagnosis. We also observed only 10.4% were treated with anti-fibrotics. Overall survival declined each year after diagnosis with median survival of 2.80 years.Conclusions and relevanceOur retrospective cohort demonstrates that IPF is often diagnosed late, usually preceded by other respiratory diagnoses and hospitalizations. Use of available therapies is low and outcomes remain poor.

Pathologic Criteria for the Diagnosis of Usual Interstitial Pneumonia vs Fibrotic Hypersensitivity Pneumonitis in Transbronchial Cryobiopsies

Transbronchial cryobiopsy (TBCB) is increasingly used for the diagnosis of fibrosing interstitial pneumonias, but there are few detailed descriptions of the pathologic findings in such cases. It has been proposed that a combination of patchy fibrosis and fibroblast foci with an absence of alternative features is diagnostic of usual interstitial pneumonia (UIP; ie, idiopathic pulmonary fibrosis [IPF]) in TBCB. In this study, we reviewed 121 TBCB in which a diagnosis of fibrotic hypersensitivity pneumonitis (FHP; n = 83) or IPF (n = 38) was made by multidisciplinary discussion and evaluated a range of pathologic features. Patchy fibrosis was found in 65 of 83 (78%) biopsies from FHP and 32of 38 (84%) biopsies from UIP/IPF cases. Fibroblast foci were present in 47 of 83 (57%) FHP and 27 of 38 (71%) UIP/IPF cases. Fibroblast foci/patchy fibrosis combined did not favor either diagnosis. Architectural distortion was seen in 54 of 83 (65%) FHP and 32 of 38 (84%) UIP/IPF cases (odds ratio [OR] for FHP, 0.35; P = .036) and honeycombing in 18 of 83 (22%) and 17 of 38 (45%), respectively (OR, 0.37; P = .014). Airspace giant cells/granulomas were present in 13 of 83 (20%) FHP and 1 of 38 (2.6%) UIP/IPF cases (OR for FHP, 6.87; P = .068), and interstitial giant cells/granulomas in 20 of 83 (24%) FHP and 0 of 38 (0%) UIP/IPF (OR, 6.7 x 106; P = .000). We conclude that patchy fibrosis plus fibroblast foci can be found in TBCB from both FHP and UIP/IPF. The complete absence of architectural distortion/honeycombing favors a diagnosis of FHP, as does the presence of airspace or interstitial giant cells/granulomas, but these measures are insensitive, and many cases of FHP cannot be separated from UIP/IPF on TBCB.

Russian Registry of Idiopathic Pulmonary Fibrosis: Clinical Features, Treatment Management, and Outcomes.

This was a prospective multicenter, observational, non-interventional study. Patients' risk factors, demographics, clinical data, results of high-resolution computed tomography (HRCT) of the chest and pulmonary function testing, and lung tissue biopsy findings were analyzed. We also analyzed the exercise tolerance (6-min walking test) of patients, serological markers of systemic connective tissue diseases, treatment, clinical course, and outcomes of the disease. Multidisciplinary discussion (MDD) was used as needed. One thousand three hundred and fifty-three patients were included in the registry from 2016 to 2020. The mean age was 64.4 ± 10.7 years, most patients were active smokers or ex-smokers. Antifibrotic therapy was administered to 90 of 948 patients (9.5%). Since starting the registry in 2016, the incidences of IPF have increased and the time period from manifestation of the disease to making the diagnosis has shortened, the number of patients on antifibrotic therapy has increased and the number of patients taking systemic steroids decreased. The registry of patients with IPF was helpful to improve IPF diagnosis and to implement antifibrotic agents in clinical practice. Further analysis of the clinical course and prognostic markers of IPF in the Russian population is needed. An analysis of the long-term efficacy of antifibrotic therapy in this population is also important.

Association between weight loss and mortality in idiopathic pulmonary fibrosis

RationaleIdiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease that has no cure. Many current research efforts center on diagnostic and therapeutic modalities for IPF while other risk factors affecting disease pathogenesis receive less attention. Emerging data support the clinical importance of weight loss in patients with IPF. However, factors associated with weight loss and the impact of weight loss on mortality remain incompletely explored.ObjectivesExplore the association between weight loss and transplant-free survival in patients with IPF and identify clinical variables associated with weight loss in this population.MethodsKaplan–Meier and Cox proportional hazard regression analyses were generated and stratified by weight loss or use of antifibrotic medications. Conditional logistic regression was used to evaluate for factors associated with weight loss.ResultsThere was a significant increase in mortality in patients who lost ≥ 5% of their body weight loss (HR 2.21, [1.29, 4.43] p = .021). The use of supplemental oxygen (adjusted OR 13.16), and ≥ 200 mL loss of FVC over 1 year (adjusted OR 5.44) were both associated with a ≥ 5% weight loss in the year following a diagnosis of IPF. The use of antifibrotic medication did not significantly change median transplant-free survival in patients who lost more than ≥ 5% of their body mass.ConclusionsWeight loss over the first year following a diagnosis of IPF is strongly associated with decreased transplant-free survival. More research is needed to determine the mechanisms surrounding weight loss in patients with IPF.

Diagnostic and prognostic value of secreted phosphoprotein 1 for idiopathic pulmonary fibrosis: a systematic review and meta-analysis

Background There is an increasing number of studies on the diagnostic and prognostic biomarkers associated with IPF. The purpose of this study was to explore the diagnostic and prognostic value of secreted phosphoprotein 1 (SPP1) in IPF. Methods Using five database, appropriate studies were included. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and 95% confidence intervals (CIs) were calculated. Pooled hazard ratios (HRs) and 95% CIs related to prognosis were calculated. Results Thirteen studies were included in the meta-analyses. The pooled sensitivity, specificity, PLR, NLR and DOR were 0.84 (95% CI 0.72–0.91), 0.89 (95% CI 0.83–0.94), 7.94 (95% CI 4.63–13.62), 0.18 (95% CI 0.10–0.33), 43.08 (95% CI 15.88–116.84) for SPP1 in the differential diagnosis of IPF and healthy people. The pooled sensitivity, specificity, PLR, NLR and DOR were 0.97 (95% CI 0.57–1.00), 0.93 (95% CI 0.73–0.98), 13.87 (95% CI 3.26–58.99), 0.03 (95% CI 0–0.68), 446.91 (95% CI 21.02–9504.41) for SPP1 to differentiate IPF and lung cancer patients. High SPP1 expression predicts poor prognosis for IPF patients (HR= 1.42, 95% CI = 1.27 and 1.58, P < 0.001). Conclusions SPP1 is a potential diagnostic and prognostic biomarker for IPF patients.

PRIOR SPECIALIST CONSULTATIONS AND TREATMENTS IN A REFRACTORY CHRONIC COUGH POPULATION ENROLLED IN A PHASE 2B STUDY OF THE P2X3 ANTAGONIST BLU-5937

PRIOR SPECIALIST CONSULTATIONS AND TREATMENTS IN A REFRACTORY CHRONIC COUGH POPULATION ENROLLED IN A PHASE 2B STUDY OF THE P2X3 ANTAGONIST BLU-5937