Curated and harmonised transcriptomics datasets of interstitial lung diseases

PH-ILD: Identification, Evaluation, and Monitoring: A Diagnostic View From Both Sides

Year in review 2016: Interstitial lung disease, pulmonary vascular disease, pulmonary function, paediatric lung disease, cystic fibrosis and sleep.

Keywords: interstitial lung disease; lung function; paediatric lung disease; pulmonary vascular disease; sleep

Introduction Dashboards are considered an effective way to monitor key performance indicators (KPIs) in management practice. Publicly available NICE quality standards for the management of Idiopathic Pulmonary Fibrosis (IPF) and statutory requirements to submit quarterly specialised service quality dashboard information (SSQD) for commissioned ILD centres is driving the need to have readily available data on KPIs of service delivery. Our objective was to develop an electronic dashboard to capture ILD activity using recognised ‘model for improvement’ frameworks. Methods In conjunction with our business intelligence department we undertook a quality improvement project (QIP) using data stored in our ILD MDT database and patient administration system (Lorenzo), to develop an electronic ILD dashboard. The eMeasures were: 1) capture of outpatient ILD activity (something poorly assessed by HES data) 2) ILD population demographics 3) NICE quality standards for IPF and 4) the SSQD ’metric definition set’. Prototype electronic queries were built using numerator and denominator populations of ILD patients using standardised, ICD-10 coded terminology (inpatients) and named ILD clinics (outpatients) to enable automatic extraction of data. We adjusted clinical workflows, documentation and electronic queries through Plan-Do-Study-Act cycles to enable standardised information collection. Results The dashboard was conceptualised in June 2017, producing monthly reports to all our stakeholders. Between July 2017 to June 2018, 1200 patients were reviewed in outpatients. For the month of June 2018, 27 new(N) and 118 follow-up(F-up) ILD appointments were undertaken (N:F-up ratio of 1:4.4). The ‘did not attend’ rate was 3.3%. With regards to the NICE quality standards for IPF, data from the last quarter suggests that 100% ILD patients were discussed in our MDT, with 82.4% patients receiving lung function within 3 months of assessment. 90% of IPF patients had lung function testing on an annual basis. Emergency admission rate for respiratory deterioration of IPF patients was 2.2%, with an annual ILD mortality rate of 6.2%. Conclusion The development of an electronic dashboard has increased the accessibility of useful data to understand service quality and delivery. It enables us to fulfil statutory requirements for SSQD submission easily, providing a platform for future benchmarking of QIPs in service delivery.

Family History of Pulmonary Fibrosis Predicts Worse Survival in Patients With Interstitial Lung Disease

Interstitial lung diseases (ILDs) are a group of diffuse parenchymal lung disorders that can be idiopathic [idiopathic pulmonary fibrosis (IPF)] or associated with other diseases and are characterized by varying degrees of inflammation and fibrosis with poor prognosis. Several indicators are essential in diagnosing these individuals and differentiating between IPF and ILD. The study involved 44 IPF patients, 22 ILD (non-IPF) patients, and 24 healthy people. We aimed to compare ILD (non-IPF) and IPF patient groups with each other and with healthy people in terms of interleukin (IL)-1, tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase (MMP)-1, MMP-7, galectin (Gal)-3, IL-6, Krebs von den Lungen-6 (KL-6), total antioxidant status (TAS), total oxidant status (TOS), pyruvate kinase (PK), complete blood count (CBC), ferritin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) features. Furthermore, it was intended to assess the patient groups in terms of visual semi-quantitative score (VSQS) (IPF alone), respiratory function tests (RFT), and 6-minute walk test (6MWT), also potential correlations between these tests and the previously indicated parameters. MMP-1, MMP-7, Gal-3, IL-6, KL-6, forced vital capacity (FVC), % FVC, forced expiratory volume in 1 second (FEV1), % FEV1, TAS, TOS, and PK values significantly elevated in IPF and ILD. Weight, IL-1, MMP-1, MMP-7, Gal-3, IL-6, KL-6, % FVC, FEV1, % FEV1, eosinophil count, and % red blood cell distribution width (RDW) values differed between IPF and ILD. VSQS, 6MWT, and PK were substantially linked with MMP-1, MMP-7, Gal-3, IL-6, and KL-6 in IPF. The factors investigated can be helpful in the diagnosis and distinction of IPF and ILD. In addition to focusing on the inflammatory environment in IPF and ILD patients, oxidant and antioxidant interactions must be studied.

PurposeTo compare imaging biomarkers from hyperpolarised 129Xe ventilation MRI and dynamic oxygen-enhanced MRI (OE-MRI) with standard pulmonary function tests (PFT) in interstitial lung disease (ILD) patients. To evaluate if biomarkers can separate ILD subtypes and detect early signs of disease resolution or progression. Study typeProspective longitudinal. PopulationForty-one ILD (fourteen idiopathic pulmonary fibrosis (IPF), eleven hypersensitivity pneumonitis (HP), eleven drug-induced ILD (DI-ILD), five connective tissue disease related-ILD (CTD-ILD)) patients and ten healthy volunteers imaged at visit 1. Thirty-four ILD patients completed visit 2 (eleven IPF, eight HP, ten DIILD, five CTD-ILD) after 6 or 26 weeks. Field strength/sequenceMRI was performed at 1.5 T, including inversion recovery T1 mapping, dynamic MRI acquisition with varying oxygen levels, and hyperpolarised 129Xe ventilation MRI. Subjects underwent standard spirometry and gas transfer testing. AssessmentFive 1H MRI and two 129Xe MRI ventilation metrics were compared with spirometry and gas transfer measurements. Statistical testTo evaluate differences at visit 1 among subgroups: ANOVA or Kruskal-Wallis rank tests with correction for multiple comparisons. To assess the relationships between imaging biomarkers, PFT, age and gender, at visit 1 and for the change between visit 1 and 2: Pearson correlations and multilinear regression models. ResultsThe global PFT tests could not distinguish ILD subtypes. Percentage ventilated volumes were lower in ILD patients than in HVs when measured with 129Xe MRI (HV 97.4 ± 2.6, CTD-ILD: 91.0 ± 4.8 p = 0.017, DI-ILD 90.1 ± 7.4 p = 0.003, HP 92.6 ± 4.0 p = 0.013, IPF 88.1 ± 6.5 p < 0.001), but not with OE-MRI. 129Xe reported more heterogeneous ventilation in DI-ILD and IPF than in HV, and OE-MRI reported more heterogeneous ventilation in DI-ILD and IPF than in HP or CTD-ILD. The longitudinal changes reported by the imaging biomarkers did not correlate with the PFT changes between visits. Data conclusionNeither 129Xe ventilation nor OE-MRI biomarkers investigated in this study were able to differentiate between ILD subtypes, suggesting that ventilation-only biomarkers are not indicated for this task. Limited but progressive loss of ventilated volume as measured by 129Xe-MRI may be present as the biomarker of focal disease progresses. OE-MRI biomarkers are feasible in ILD patients and do not correlate strongly with PFT. Both OE-MRI and 129Xe MRI revealed more spatially heterogeneous ventilation in DI-ILD and IPF.

Circulating Dickkof-1 as a potential biomarker associated with the prognosis of patients with rheumatoid arthritis-associated interstitial lung disease.

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Background Studies using public health records have reported an increased risk of developing lung cancer in patients with interstitial lung disease (ILD). However little information exists on the frequency of lung cancer in UK ILD practice. Method All cases discussed in the Royal Brompton Hospital Lung Cancer MDT meetings between May 2015 and April 2018 were interrogated for referring indication, patient attributes, staging and cancer confirmation. Results 74 ILD patients (45 male) and 223 COPD patients (132 male) were identified; median age at cancer diagnosis (70) was similar in both groups. ‘Ever’ smokers formed three-quarters (55/74) of the ILD group. 1 in 4 ILD patients had IPF. Cancer was pathologically proven in 25/74 (33.8%) of ILD patients, against 56/223 (25.1%) of those with COPD. Cancer that was suspected due to CT morphology or progression but were not amenable to sampling because of poor fitness, inaccessibility or metastatic disease occurred in 15/74 (20.3%) and 22/223 (9.9%) of ILD and COPD patients respectively (p Conclusion The risk of developing lung cancer is high amongst those with ILD especially in IPF and when there is evidence of suspicious ‘interval CT’ change. Stage IV NSCLC and aggressive (SCLC) are frequent in patients with IPF and scleroderma who develop lung malignancies. Delayed cancer diagnosis may result from decreased suspicion in patients who have progressive ILD or diffuse lung disease that complicates radiological interpretation.

Background: Little is known about subclinical right ventricle(RV) involvement in interstitial lung disease (ILD)patients. Our study aimed at evaluating early RV dysfunction by standard and advanced echocardiography in this clinical scenario. Methods: Sixty fibrotic ILD patients, including 30 cases affected by idiopathic pulmonary fibrosis(IPF), without heart failure and 20 age- and sex-matched healthy subjects underwent standard, speckle tracking and real time 3D echocardiography of the right ventricle. All patients also performed complete lung function testing. Results: Systolic pulmonary arterial pressure (sPAP) was significantly higher in ILD patients (with no differences between IPF and no-IPF) than in controls (p Conclusions: A subclinical RV dysfunction is detectable by speckle tracking in ILD patients. The impairment of RV GLS, RV SLS and RV LLS is more prominent in IPF patients and inversely correlates with gas transfer, despite comparable sPAP and 3D RVEF in no-IPF cases.

Prognostic value of transbronchial lung cryobiopsy for the multidisciplinary diagnosis of idiopathic pulmonary fibrosis: a retrospective validation study

Rationale: Hospital readmission within 30 days poses challenges for healthcare providers, policymakers, and patients because of its impact on care quality, costs, and outcomes. Patients with interstitial lung disease (ILD) are particularly affected by readmission, which is associated with increased morbidity and mortality and reduced quality of life. Because small sample sizes have hindered previous studies, this study seeks to address this gap in knowledge by examining a large-scale dataset. Objective: To determine the rate and probability of 30-day all-cause readmission and secondary outcomes in patients with coronavirus disease (COVID-19) or ILD admitted to the hospital. Methods: This study is a nested cohort study that used the PearlDiver patient records database. Adult patients (age ⩾18 yr) who were admitted to hospitals in 28 states in the United States with COVID-19 or ILD diagnoses were included. We defined and analyzed two separate cohorts in this study. The first cohort consisted of patients with COVID-19 and was later divided into two groups with or without a history of ILD. The second cohort consisted of patients with ILD and was later divided into groups with COVID-19 or with a non-COVID-19 pneumonia diagnosis at admission. We also studied two other subcohorts of patients with and without idiopathic pulmonary fibrosis within the second cohort. Propensity score matching was employed to match confounders between groups. The Kaplan-Meier log rank test was applied to compare the probabilities of outcomes. Results: We assessed the data of 2,286,775 patients with COVID-19 and 118,892 patients with ILD. We found that patients with COVID-19 with preexisting ILD had an odds ratio of 1.6 for 30-day all-cause readmission. Similarly, an odds ratio of 2.42 in readmission rates was observed among hospitalized individuals with ILD who contracted COVID-19 compared with those who were hospitalized for non-COVID-19 pneumonia. Our study also found a significantly higher probability of intensive care admission among patients in both cohorts. Conclusions: Patients with ILD face heightened rates of hospital readmissions, particularly when ILD is combined with COVID-19, resulting in adverse outcomes such as decreased quality of life and increased healthcare expenses. It is imperative to prioritize preventive measures against COVID-19 and establish effective postdischarge care strategies for patients with ILD.

ABSTRACTA disintegrin and metalloproteinases (ADAMs) are believed to be involved in the pathogenesis of many fibrosis-related diseases. However, little is known regarding the significance of ADAM17 as a biomarker for interstitial lung disease (ILD). In this study, by using the RT-PCR, western blotting and ELISA, we detected the expression level of ADAM17 in peripheral blood mononuclear cells and serum from idiopathic pulmonary fibrosis (IPF) patients, connective tissue disease associated ILD (CTD-ILD) patients and healthy controls, and correlations between clinical and laboratory parameters were also analyzed. We found that IPF patients and CTD-ILD patients showed higher levels of ADAM17 than healthy controls. Moreover, ADAM17 in IPF patients with acute exacerbation (AE-IPF) was significantly higher than that in stable IPF (S-IPF) patients. Expression of ADAM17 was positively correlated with disease duration and CRP but negatively correlated with diffusing capacity of carbon monoxide (DLCO) and total lung capacity (TLC). Among the CTD-ILD patients, SSc-ILD patients had the highest serum levels of ADAM17 compared with the RA-ILD, SS-ILD and IIM-ILD groups and ADAM17 expression levels were correlated with image grading. In conclusion, this study showed that ADAM17 is highly expressed in ILD patients and is associated with disease activity and severity. Additionally, ADAM17 expression is not only related to the primary CTDs, but also to image grading. ADAM17 may serve as a new biomarker for ILD.

Physiological predictors of Hypoxic Challenge Testing (HCT) outcomes in Interstitial Lung Disease (ILD).