Interstitial Lung Disease in a 14-Year-Old Boy.

CASE PRESENTATION: A 14-year-old Chinese boy presented with a 7-year history of exertional dyspnea and reduced exercise tolerance. His perinatal and family histories were unremarkable. He was short and underweight for his age since childhood but had normal intellectual development. At 3 years of age, he was admitted to the ICU for severe pneumonia and anemia, and he received blood transfusion. He developed exertional dyspnea and reduced exercise tolerance at 7 years of age and became reluctant to run or jump, with poor appetite, abdominal distension, and refusal of protein-rich foods. At 13 years of age, he experienced a coma during school military training, and he was hospitalized for hyperammonemia (blood ammonia levels between 98 and 148 µmol/L; normal range, 18-72 µmol/L). Brain MRI showed no abnormalities. He improved after symptomatic treatment and was discharged, without taking any oral medication afterwards. However, his dyspnea and exercise tolerance worsened gradually. This patient was referred to Children's Hospital affiliated with Zhengzhou University for further investigation and management.

Biomarkers of tissue remodelling are elevated in serum of COVID-19 patients who develop interstitial lung disease - an exploratory biomarker study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a viral pneumonia that can result in serious respiratory illness. It is associated with extensive systemic inflammation, changes to the lung extracellular matrix, and long-term lung impairment such as interstitial lung disease (ILD). In this study, the aim was to investigate whether tissue remodelling, wound healing, and neutrophil activity is altered in patients with COVID-19 and how these relate to the development of post-COVID ILD. METHOD: Serum samples were collected from 63 patients three months after discharge as part of the Research Evaluation Alongside Clinical Treatment study in COVID-19 (REACT COVID-19), 10 of whom developed ILD, and 16 healthy controls. Samples were quantified using neo-epitope specific biomarkers reflecting tissue stiffness and formation (PC3X, PRO-C3, and PRO-C6), tissue degradation (C1M, C3M, and C6M), wound healing (PRO-FIB and X-FIB), and neutrophil activity (CPa9-HNE and ELP-3). RESULTS: Mean serum levels of PC3X (p < 0.0001), PRO-C3 (p = 0.002), C3M (p = 0.009), PRO-FIB (p < 0.0001), CPa9-HNE (p < 0.0001), and ELP-3 (p < 0.0001) were significantly elevated in patients with COVID-19 compared to healthy controls. Moreover, PC3X (p = 0.023) and PRO-C3 (p = 0.032) were significantly elevated in post-COVID ILD as compared to COVID-19. CONCLUSION: Serological biomarkers reflecting type III collagen remodelling, clot formation, and neutrophil activity were significantly elevated in COVID-19 and type III collagen formation markers were further elevated in post-COVID ILD. The findings suggest an increased type III collagen remodelling in COVID-19 and warrants further investigations to assess the potential of tissue remodelling biomarkers as a tool to identify COVID-19 patients at high risk of developing ILD.

Prognosis of Lung Transplantation in Patients with Acute Exacerbations of Interstitial Lung Disease: A Meta-Analysis Based on Cohort Studies.

PURPOSE: This meta-analysis aimed to examine the prognosis of patients with acute exacerbation of interstitial lung disease (AE-ILD) treated with lung transplantation compared to those with stable interstitial lung disease (ILD). METHODS: We conducted a detailed search in PubMed, Embase, Web of Science, and the Cochrane Library, with the primary outcomes being overall survival (OS), acute cellular rejection (ACR), primary graft dysfunction (PGD), and length of stay (LOS). RESULTS: Five cohort studies were included in this meta-analysis, with 183 patients enrolled in the AE-ILD group and 337 patients in the stable-ILD group. The results showed that in regard to perioperative outcomes, the AE-ILD group did not differ from the stable-ILD group in the incidence of ACR (relative risks [RR] = 0.34, p = 0.44) and the incidence of PGD Ⅲ (RR = 0.53, p = 0.43), but had a longer LOS (mean difference = 9.15, p = 0.02). Regarding prognosis, the two also did not differ in 90-day OS (RR = 0.97, p = 0.59), 1-year OS (RR = 1.05, p = 0.66), and 3-year OS (RR = 0.91, p = 0.76). CONCLUSION: Our study concluded that the efficacy of lung transplantation in patients with AE-ILD is not inferior to that of patients with stable ILD. Lung transplantation is one of the potential treatments for patients with AE-ILD.

Serum S1P level in interstitial lung disease (ILD) is a potential biomarker reflecting the severity of pulmonary function.

BACKGROUND: sphingosine-1-phosphate (S1P), a naturally occurring sphingolipid, has been involved in pulmonary interstitial remodeling signaling. However, no study has examined its clinical merits for interstitial lung disease (ILD). This study aimed to investigate the serum level of S1P in ILD patients and its clinical correlation with the severity of disease in the two main types of ILDs: the IPF and the CTD-ILD patients. METHODS: This retrospective observational pilot study included 67 ILD patients and 26 healthy controls. These patients were stratified into the IPF group (35) and the CTD-ILD group (32). The severity of ILD was evaluated through pulmonary function indicators and the length of hospital stay. RESULTS: Serum S1P level was statistically higher in ILD patients than in health control (p = 0.002), while the Serum S1P levels in CTD-ILD and IPF patients were comparable. Serum S1P level further showed statistically negative correlation with pulmonary function indexes (TLC% pred, FVC% pred and FEV1% pred) and positive correlation with length of hospital stay (r = -0.38, p = 0.04; r = -0.41, p = 0.02, r = -0.37, p = 0.04; r = 0.42, p = 0.02, respectively) in CTD-ILD patients, although serum S1P level was not significantly correlated with inflammatory indexes. The IPF patients failed to exhibit a significant correlation of serum S1P level with pulmonary function and length of hospital stay. CONCLUSIONS: Serum S1P level might be a clinically useful biomarker in evaluating the severity of CTD-ILD patients rather than IPF patients.

Stress-strain curve and elastic behavior of the fibrotic lung with usual interstitial pneumonia pattern during protective mechanical ventilation.

Patients with acute exacerbation of lung fibrosis with usual interstitial pneumonia (EUIP) pattern are at increased risk for ventilator-induced lung injury (VILI) and mortality when exposed to mechanical ventilation (MV). Yet, lack of a mechanical model describing UIP-lung deformation during MV represents a research gap. Aim of this study was to develop a constitutive mathematical model for UIP-lung deformation during lung protective MV based on the stress-strain behavior and the specific elastance of patients with EUIP as compared to that of acute respiratory distress syndrome (ARDS) and healthy lung. Partitioned lung and chest wall mechanics were assessed for patients with EUIP and primary ARDS (1:1 matched based on body mass index and PaO2/FiO2 ratio) during a PEEP trial performed within 24 h from intubation. Patient's stress-strain curve and the lung specific elastance were computed and compared with those of healthy lungs, derived from literature. Respiratory mechanics were used to fit a novel mathematical model of the lung describing mechanical-inflation-induced lung parenchyma deformation, differentiating the contributions of elastin and collagen, the main components of lung extracellular matrix. Five patients with EUIP and 5 matched with primary ARDS were included and analyzed. Global strain was not different at low PEEP between the groups. Overall specific elastance was significantly higher in EUIP as compared to ARDS (28.9 [22.8-33.2] cmH2O versus 11.4 [10.3-14.6] cmH2O, respectively). Compared to ARDS and healthy lung, the stress/strain curve of EUIP showed a steeper increase, crossing the VILI threshold stress risk for strain values greater than 0.55. The contribution of elastin was prevalent at lower strains, while the contribution of collagen was prevalent at large strains. The stress/strain curve for collagen showed an upward shift passing from ARDS and healthy lungs to EUIP lungs. During MV, patients with EUIP showed different respiratory mechanics, stress-strain curve and specific elastance as compared to ARDS patients and healthy subjects and may experience VILI even when protective MV is applied. According to our mathematical model of lung deformation during mechanical inflation, the elastic response of UIP-lung is peculiar and different from ARDS. Our data suggest that patients with EUIP experience VILI with ventilatory setting that are lung-protective for patients with ARDS.

Clinical profiles and treatment outcomes of outpatients with interstitial lung disease and mechanic's hands: A retrospective and observational cohort.

Idiopathic inflammatory myopathies, especially antisynthetase syndrome, often appear outside of the muscles as interstitial lung disease (ILD). Another typical finding is the presence of mechanic's hands. The aim of the present study was to describe the clinical, functional, tomographic, and serological data of patients with ILD and mechanic's hands and their response to treatment and survival rates. This is a retrospective study of ILD with concurrent myopathy. Among the 119 patients initially selected, 51 had mechanic's hands. All the patients were screened for anti-Jo-1 antibodies. An expanded panel of myopathy autoantibodies was also performed in 27 individuals. Of the 51 patients, 35 had 1 or more antibodies. The most common were anti-Jo-1, anti-PL-7, and anti-PL-12, while of the associated antibodies, anti-Ro52 was present in 70% of the 27 tested individuals. A significant response to treatment was characterized by an increase in predicted forced vital capacity (FVC) of at least 5% in the last evaluation done after 6 to 24 months of treatment. A decrease in predicted FVC of at least 5%, the need for oxygen therapy, or death were all considered treatment failures. All patients were treated with corticosteroids, and 71% with mycophenolate. After 24 months, 18 patients had an increase in FVC, 11 had a decrease, and 22 remained stable. After a median follow-up of 58 months, 48 patients remained alive and three died. Patients with honeycombing on high-resolution chest tomography (log-rank = 34.65; P < .001) and a decrease in FVC ≥5% (log-rank = 18.28, P < .001) had a poorer survival rate. Patients with ILD and mechanic's hands respond well to immunosuppressive treatment.

Prognostic value of serum oncomarkers for patients hospitalized with acute exacerbation of interstitial lung disease.

BACKGROUND: Different types of inflammatory processes and fibrosis have been implicated in the pathogenesis of interstitial lung disease (ILD), a heterogeneous, diffuse, parenchymal lung disease. Acute exacerbation (AE) of ILD is characterized by significant respiratory deterioration and is associated with high mortality rates. Several serum oncomarkers have been used to determine the prognosis of ILD; however, the prognostic value of serum oncomarker levels in patients with AE-ILD remains unclear. OBJECTIVE: To evaluate the prognostic value of serum oncomarker levels in patients with AE-ILD and its main subtypes. DESIGN: Retrospective study. METHODS: The serum levels of 8 oncomarkers in 281 patients hospitalized with AE-ILD at our institution between 2017 and 2022 were retrospectively reviewed. The baseline characteristics and serum oncomarker levels were compared between the survival and non-survival groups of AE-ILD and its main subtypes. Multivariate logistic regression analysis was performed to identify independent prognosis-related markers, and the best prognostic predictor was analyzed using receiver operating characteristic curve (ROC) analysis. RESULT: Idiopathic pulmonary fibrosis (IPF; n = 65), idiopathic nonspecific interstitial pneumonia (iNSIP; n = 26), and connective tissue disease-associated interstitial lung disease (CTD-ILD; n = 161) were the three main subtypes of ILD. The in-hospital mortality rate among patients with AE-ILD was 21%. The serum oncomarker levels of most patients with AE-ILD and its main subtypes in the non-survival group were higher than those in the survival group. Multivariate analysis revealed that ferritin and cytokeratin 19 fragments (CYFRA21-1) were independent prognostic risk factors for patients hospitalized with AE-ILD or AE-CTD-ILD. CYFRA21-1 was identified as an independent prognostic risk factor for patients hospitalized with AE-IPF or AE-iNSIP. CONCLUSION: CYFRA21-1 may be a viable biomarker for predicting the prognosis of patients with AE-ILD, regardless of the underlying subtype of ILD. Ferritin has a prognostic value in patients with AE-ILD or AE-CTD-ILD.

Untreated Obstructive Sleep Apnea in Interstitial Lung Disease and Impact on Interstitial Lung Disease Outcomes.

Subjects with interstitial lung disease (ILD) often suffer from nocturnal cough, insomnia, and poor sleep quality. Subjects with ILD and obstructive sleep apnea (OSA) seem to have relatively mild symptoms from sleep fragmentation compared to subjects with only ILD. The overlap of ILD, OSA, and sleeping hypoxemia may be associated with poor outcome, even though there is no agreement on which sleep parameter is mostly associated with worsening ILD prognosis. Randomized controlled trials are needed to understand when positive airway pressure (PAP) treatment is required in subjects with ILD and OSA and the impact of PAP treatment on ILD progression.

Review of Pulmonary Manifestations in Antisynthetase Syndrome.

Antisynthetase syndrome (ASyS) is now a widely recognized entity within the spectrum of idiopathic inflammatory myopathies. Initially described in patients with a triad of myositis, arthritis, and interstitial lung disease (ILD), its presentation can be diverse. Additional common symptoms experienced by patients with ASyS include Raynaud's phenomenon, mechanic's hand, and fever. Although there is a significant overlap with polymyositis and dermatomyositis, the key distinction lies in the presence of antisynthetase antibodies (ASAs). Up to 10 ASAs have been identified to correlate with a presentation of ASyS, each having manifestations that may slightly differ from others. Despite the proposal of three classification criteria to aid diagnosis, the heterogeneous nature of patient presentations poses challenges. ILD confers a significant burden in patients with ASyS, sometimes manifesting in isolation. Notably, ILD is also often the initial presentation of ASyS, requiring pulmonologists to remain vigilant for an accurate diagnosis. This article will comprehensively review the various aspects of ASyS, including disease presentation, diagnosis, management, and clinical course, with a primary focus on its pulmonary manifestations.

The acute effect of inhaled nitric oxide on the exercise capacity of patients with advanced interstitial lung disease: a randomized controlled trial.

BACKGROUND: Inhaled nitric oxide (iNO) selectively acts on the pulmonary vasculature of ventilated lung tissue by reducing pulmonary vascular resistance and intrapulmonary shunt. This effect may reduce ventilation/perfusion mismatch and decrease pulmonary hypertension in patients with interstitial lung disease. METHODS: In a prospective, single-blinded, randomized, placebo-controlled trial, participants with advanced interstitial lung disease, underwent two separate six-minute walk tests (6MWT): one with iNO and the other with a placebo. The primary outcome measured the difference in meters between the distances covered in the two tests. Secondary outcomes included oxygen saturation levels, distance-saturation product, and Borg dyspnea score. A predefined subgroup analysis was conducted for patients with pulmonary hypertension. RESULTS: Overall, 44 patients were included in the final analysis. The 6MWT distance was similar for iNO treatment and placebo, median 362 m (IQR 265-409) vs 371 m (IQR 250-407), respectively (p = 0.29). Subgroup analysis for patients with pulmonary hypertension showed no difference in 6MWT distance with iNO and placebo, median 339 (256-402) vs 332 (238-403) for the iNO and placebo tests respectively (P=0.50). No correlation was observed between mean pulmonary artery pressure values and the change in 6MWT distance with iNO versus placebo (spearman correlation Coefficient 0.24, P=0.33). CONCLUSION: In patients with advanced interstitial lung disease, both with and without concurrent pulmonary hypertension, the administration of inhaled nitric oxide failed to elicit beneficial effects on the six-minute walk distance and oxygen saturation. The use of inhaled NO was found to be safe and did not lead to any serious side effects. TRIAL REGISTRATION: (NCT03873298, MOH_2018-04-24_002331).

Oxygen therapy for exercise capacity in fibrotic interstitial lung disease: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Fibrotic interstitial lung disease (fILD) is characterised primarily by impaired lung function and quality of life. The present study investigated whether oxygen therapy could improve exercise capacity among patients with fILD. METHODS: Previously published randomised controlled trials (RCTs) were surveyed. A systematic review and meta-analysis was conducted to evaluate the effectiveness of oxygen therapy in improving the exertional capacity of patients with fILD. The primary outcome was peripheral oxygen saturation (SpO2) during exercise. The effects of oxygen therapy on fatigue, dyspnoea, heart rate, and exercise duration or distance were also analysed. RESULTS: Fourteen RCTs involving 370 patients were included. Oxygen therapy improved SpO2 during exercise (mean difference, MD = 6.26 %), exercise duration (MD = 122.15 s), fatigue (standard mean difference, SMD = -0.30), and dyspnoea (MD = -0.75 Borg score units). High-flow oxygen systems tended to be more effective than low-flow systems in improving exercising SpO2, duration, fatigue, dyspnoea, and heart rate. High-flow nasal cannulas (HFNCs) yielded better outcomes regarding SpO2 and fatigue than did high-flow Venturi masks (MD = 1.60 % and MD = -1.19 Borg score units, respectively). No major adverse events were reported. CONCLUSION: The evidence from RCTs supports the short-term use of oxygen supplementation to improve SpO2, exercise capacity, fatigue, and dyspnoea among patients with fILD. Further analyses demonstrates that HFNCs yield more favourable outcomes, yet not reaching statistical significance except for improving SpO2 and fatigue. However, the long-term effects of oxygen therapy on quality of life and mortality remain unclear.

Unravelling the health and economic burden of interstitial lung diseases in adults in Australia.

BACKGROUND: Interstitial lung diseases (ILD) are a heterogenous group of over 200 disorders affecting the pulmonary interstitium. Although there have been advances in knowledge on ILDs in Australia, the characterisation of the health and economic burden of disease remained largely undetermined until recently. OBJECTIVE: The main objective of this review is to provide a synopsis of health and economic burden of ILDs in Australia, based on recently completed research. DISCUSSION: Recent research has demonstrated that idiopathic pulmonary fibrosis (IPF) is the most frequent ILD in Australia. Incidence and prevalence of IPF have demonstrated an increasing trend over the past decades. Mortality has also increased over the past decades, but has shown a slight decreasing trend recently, since the introduction of antifibrotic medication. Health-related quality of life is poor in patients with IPF, and care is estimated to cost approximately AU$299 million per year in Australia. Early diagnosis and referral to tertiary care is crucial for favourable outcomes, and general practitioners are considerably important to this as the first interface to identify patients at risk and detect early symptoms of ILDs.

Interstitial Lung Disease and Progressive Pulmonary Fibrosis: a World Trade Center Cohort 20-Year Longitudinal Study.

PURPOSE: World Trade Center (WTC) exposure is associated with obstructive airway diseases and sarcoidosis. There is limited research regarding the incidence and progression of non-sarcoidosis interstitial lung diseases (ILD) after WTC-exposure. ILD encompasses parenchymal diseases which may lead to progressive pulmonary fibrosis (PPF). We used the Fire Department of the City of New York's (FDNY's) WTC Health Program cohort to estimate ILD incidence and progression. METHODS: This longitudinal study included 14,525 responders without ILD prior to 9/11/2001. ILD incidence and prevalence were estimated and standardized to the US 2014 population. Poisson regression modeled risk factors, including WTC-exposure and forced vital capacity (FVC), associated with ILD. Follow-up time ended at the earliest of incident diagnosis, end of study period/case ascertainment, transplant or death. RESULTS: ILD developed in 80/14,525 FDNY WTC responders. Age, smoking, and gastroesophageal reflux disease (GERD) prior to diagnosis were associated with incident ILD, though FVC was not. PPF developed in 40/80 ILD cases. Among the 80 cases, the average follow-up time after ILD diagnosis was 8.5 years with the majority of deaths occurring among those with PPF (PPF: n = 13; ILD without PPF: n = 6). CONCLUSIONS: The prevalence of post-9/11 ILD was more than two-fold greater than the general population. An exposure-response gradient could not be demonstrated. Half the ILD cases developed PPF, higher than previously reported. Age, smoking, and GERD were risk factors for ILD and PPF, while lung function was not. This may indicate that lung function measured after respirable exposures would not identify those at risk for ILD or PPF.

Pursuing Clinical Predictors and Biomarkers for Progression in ILD: Analysis of the Pulmonary Fibrosis Foundation (PFF) Registry.

INTRODUCTION: Pulmonary fibrosis is a characteristic of various interstitial lung diseases (ILDs) with differing etiologies. Clinical trials in progressive pulmonary fibrosis (PPF) enroll patients based on previously described clinical criteria for past progression, which include a clinical practice guideline for PPF classification and inclusion criteria from the INBUILD trial. In this study, we compared the ability of past FVC (forced vital capacity) progression and baseline biomarker levels to predict future progression in a cohort of patients from the PFF Patient Registry. METHODS: Biomarkers previously associated with pathobiology and/or progression in pulmonary fibrosis were selected to reflect cellular senescence (telomere length), pulmonary epithelium (SP-D, RAGE), myeloid activation (CXCL13, YKL40, CCL18, OPN) and fibroblast activation (POSTN, COMP, PROC3). RESULTS: PFF or INBUILD-like clinical criteria was used to separate patients into past progressor and non-past progressor groups, and neither clinical criterion appeared to enrich for patients with greater future lung function decline. All baseline biomarkers measured were differentially expressed in patient groups compared to healthy controls. Baseline levels of SP-D and POSTN showed the highest correlations with FVC slope over one year, though correlations were low. CONCLUSIONS: Our findings provide further evidence that prior decline in lung function may not predict future disease progression for ILD patients, and elevate the need for molecular definitions of a progressive phenotype. Across ILD subtypes, certain shared pathobiologies may be present based on the molecular profile of certain biomarker groups observed. In particular, SP-D may be a common marker of pulmonary injury and future lung function decline across ILDs.

A study on the prevalence and prognosis of progressive pulmonary fibrosis: A retrospective observational study.

Interstitial lung disease (ILD) encompasses a heterogeneous group of more than 200 diffuse parenchymal lung diseases with various clinical courses. Disease progression is one of the most important prognostic factors, and, the definition of progressive pulmonary fibrosis (PPF) has recently been established. This study aimed to estimate the prevalence, risk factors, and prognosis of PPF among patients with non-idiopathic pulmonary fibrosis (IPF) in real-world practice. A total of 215 patients were retrospectively analyzed between January 2010 and June 2023 at the Haeundae Paik Hospital in the Republic of Korea. According to the criteria proposed in 2022 by Raghu et al, PPF defined as a condition that satisfies 2 or more of the following in the past year: worsening of respiratory symptoms, physiological evidence of disease progression, and radiological evidence of disease progression. The median age of the subjects was 67 years and 63.7% were female. A total of 40% was diagnosed with PPF and connective tissue disease-associated ILD (52.3%) was the most common type, followed by nonspecific interstitial pneumonitis (NSIP) (25.6%) and cryptogenic organizing pneumonitis (16.3%). In multivariate logistic regression for predicting PPF, both the use of steroids and immunosuppressants (OR: 2.57, 95% CI: 1.41-4.67, P = .002) and home oxygen use (OR: 25.17, 95% CI: 3.21-197.24, P = .002) were independent risk factors. During the follow-up period, the mortality rate was significantly higher in the PPF group than in the non-PPF group (24.4% vs 2.3%, P < .001). In the survival analysis using the Cox proportional hazard regression model, disease progression, older age and lower forced vital capacity (FVC) were independent risk factors for mortality. Our study demonstrated that the prevalence of PPF was 40%. Concomitant therapy of steroids with an immunosuppressants and home oxygen use are risk factors for PPF. PPF itself was significantly associated with high mortality rates. Risk factors for mortality were disease progression, older age, and lower FVC.

Interstitial Lung Abnormalities: Current Understanding.

Interstitial lung abnormalities (ILAs) are incidental findings on computed tomography scans, characterized by nondependent abnormalities affecting more than 5% of any lung zone. They are associated with factors such as age, smoking, genetic variants, worsened clinical outcomes, and increased mortality. Risk stratification based on clinical and radiological features of ILAs is crucial in clinical practice, particularly for identifying cases at high risk of progression to pulmonary fibrosis. Traction bronchiectasis/bronchiolectasis index has emerged as a promising imaging biomarker for prognostic risk stratification in ILAs. These findings suggest a spectrum of fibrosing interstitial lung diseases, encompassing from ILAs to pulmonary fibrosis.

Proportion and predictors of FVC decline in patients with interstitial lung disease.

RATIONALE: The proportion of patients who develop progressive pulmonary fibrosis (PPF), along with risk factors for progression remain poorly understood. OBJECTIVES: To examine factors associated with an increased risk of developing PPF among patients at a referral center. METHODS: We identified patients with a diagnosis of interstitial lung disease (ILD) seen within the Cleveland Clinic Health System. Utilizing a retrospective observational approach we estimated the risk of developing progression by diagnosis group and identified key clinical predictors using the FVC component of both the original progressive fibrotic interstitial lung disease (PFILD) and the proposed PPF (ATS) criteria. RESULTS: We identified 5934 patients with a diagnosis of ILD. The cumulative incidence of progression over the 24 months was similar when assessed with the PFILD and PPF criteria (33.1 % and 37.9 % respectively). Of those who met the ATS criteria, 9.5 % did not meet the PFILD criteria. Conversely, 4.3 % of patients who met PFILD thresholds did not achieve the 5 % absolute FVC decline criteria. Significant differences in the rate of progression were seen based on underlying diagnosis. Steroid therapy (HR 1.46, CI 1.31-1.62) was associated with an increased risk of progressive fibrosis by both PFILD and PPF criteria. CONCLUSION: Regardless of the definition used, the cumulative incidence of progressive disease is high in patients with ILD in the 24 months following diagnosis. Some differences are seen in the risk of progression when assessed by PFILD and PPF criteria. Further work is needed to identify modifiable risk factors for the development of progressive fibrosis.