Interstitial Lung Disease Cohort Research Articles

Triple-combination therapy did not improve prognosis in anti-MDA5 positive dermatomyositis: a multicentre longitudinal cohort study.

Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5+ DM) is frequently linked with interstitial lung disease (ILD), especially the rapidly progressive ILD (RP-ILD). We conduct this research to evaluate the efficacy and safety of triple-combination (triple-combo) therapy consisting of high-dose corticosteroids, tacrolimus and intravenous cyclophosphamide in treating MDA5+ DM patients with ILD. A multicentre longitudinal cohort study involving 115 MDA5+ DM patients from the Nanjing Medical University Myositis Associated ILD (NMMI) cohort was conducted between January 2019 and November 2022. Patients were categorised into triple-combo and non-triple therapy groups, and their outcomes were assessed. Contrary to expectations, triple-combo therapy did not improve the prognosis for MDA5+ DM patients but was linked to increased mortality rates, especially among those at high risk for RP-ILD. Our study suggests that triple-combo therapy might not be effective in improving prognosis in MDA5+ DM patients. Further research is needed to establish safer and more effective treatment modalities for this patient population.

Impact of a multidisciplinary interstitial lung disease clinic on healthcare utilization

RATIONALEA minimal amount is known of the impact that a multidisciplinary interstitial lung disease (ILD) clinic with dedicated nursing support may have on healthcare utilization. OBJECTIVES The objective of this study is to determine if there is a reduction in healthcare utilization including emergency room (ER) visits, hospitalizations, and hospitalization costs in the year after a patient is assessed in the ILD clinic. METHODS This retrospective study evaluated the number of ER visits and hospitalizations 1 year before and after being seen in an ILD clinic. For those with hospitalizations, length of stay (LOS) and cost of each stay were collected. Pre- and post-ILD clinic outcomes were compared using Mann-Whitney and Wilcoxon rank sum test. MEASUREMENTS AND MAIN RESULTSA total of 202 patients were screened and 140 included in the analysis. Mean age was 66 years (±12), and 47% were female. Mean forced vital capacity percentage predicted was 77% (±22). There was no significant difference in the pre- and post-ILD clinic mean number of ER visits per patient (p = 0.33) nor hospitalizations (p = 0.91). LOS was shorter in the post-ILD clinic period (10.8 ± 10.5 days) versus pre-ILD clinic visit (18.8 ± 25.4 days), although not statistically significant (p = 0.30). Pre-ILD clinic visit mean hospitalization cost was $24,881.89 (±35,817.48) and post-ILD clinic visit was $16,751.68 (±16,549.74) although not statistically different (p = 0.66). CONCLUSIONS We found no statistically significant difference in ER visits, hospitalizations or hospitalization costs post-ILD multidisciplinary clinic assessment in our ILD cohort. However, there was a trend toward lower overall healthcare utilization and cost in the year post-ILD clinic.

A Harmonised Approach to Curating Research-Ready Datasets for Asthma, Chronic Obstructive Pulmonary Disease (COPD) and Interstitial Lung Disease (ILD) in England, Wales and Scotland Using Clinical Practice Research Datalink (CPRD), Secure Anonymised Information Linkage (SAIL) Databank and DataLoch.

Electronic healthcare records (EHRs) are an important resource for health research that can be used to improve patient outcomes in chronic respiratory diseases. However, consistent approaches in the analysis of these datasets are needed for coherent messaging, and when undertaking comparative studies across different populations. We developed a harmonised curation approach to generate comparable patient cohorts for asthma, chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) using datasets from within Clinical Practice Research Datalink (CPRD; for England), Secure Anonymised Information Linkage (SAIL; for Wales) and DataLoch (for Scotland) by defining commonly derived variables consistently between the datasets. By working in parallel on the curation methodology used for CPRD, SAIL and DataLoch for asthma, COPD and ILD, we were able to highlight key differences in coding and recording between the databases and identify solutions to enable valid comparisons. Codelists and metadata generated have been made available to help re-create the asthma, COPD and ILD cohorts in CPRD, SAIL and DataLoch for different time periods, and provide a starting point for the curation of respiratory datasets in other EHR databases, expediting further comparable respiratory research.

Epidemiology and Prognostic Significance of Cough in Fibrotic Interstitial Lung Disease.

Rationale: Cough is a key symptom in patients with fibrotic interstitial lung disease (ILD). Objectives: This study evaluated the prevalence, longitudinal change, associations, and prognostic significance of cough severity in patients with fibrotic ILD. Methods: We included consecutive patients with idiopathic pulmonary fibrosis (IPF) and non-IPF fibrotic ILD who completed the 100-mm Cough Severity Visual Analog Scale from the prospective multicenter Canadian Registry for Pulmonary Fibrosis. Baseline cough severity and associations with patient demographics and clinical factors were determined. Relationships between baseline cough severity and health outcomes were evaluated. Measurements and Main Results: Patients with IPF (n = 1,061) had higher median baseline cough severity than those with non-IPF fibrotic ILD (n = 2,825) (24 vs. 20 mm; P < 0.001), with worse cough associated with gastroesophageal reflux disease for both cohorts. Worse cough severity was independently associated with worse health-related quality of life at baseline, larger annualized decline in DlCO, development of disease progression, and reduced transplant-free survival in both IPF and non-IPF fibrotic ILD cohorts. The IPF cohort (2.2 mm; 95% confidence interval, 1.6-2.9 mm) had larger annualized increments in cough severity than the non-IPF fibrotic ILD cohort (1.1 mm; 95% confidence interval, 0.8-1.4 mm; P = 0.004). There was no difference in worsening cough over time comparing those receiving and not receiving ILD-targeted therapy or with and without lung function decline. Conclusions: Cough is common in patients with IPF and non-IPF fibrotic ILD, with increasing cough severity over time irrespective of ILD-targeted therapy. Patient-reported cough severity has prognostic implications on health-related quality of life, disease progression, and survival in fibrotic ILD.

A multidimensional classifier to support lung transplant referral in patients with pulmonary fibrosis

BackgroundLung transplantation remains the sole curative option for patients with idiopathic pulmonary fibrosis (IPF), but donor organs remain scarce, and many eligible patients die prior to transplant. Tools to optimize the timing of transplant referral are urgently needed. MethodsLeast absolute shrinkage and selection operator (LASSO) was applied to clinical and proteomic data generated as part of a prospective cohort study of interstitial lung disease (ILD) to derive clinical, proteomic, and multi-dimensional logit models of near-term death or lung transplant within 18 months of blood draw. Model fitted values were dichotomized at the point of maximal sensitivity and specificity and decision curve analysis used to select the best performing classifier. We then applied this classifier to independent IPF and non-IPF ILD cohorts to determine test performance characteristics. Cohorts were restricted to patients aged ≤72 years with body mass index 18-32 to increase likelihood of transplant eligibility. ResultsIPF derivation, IPF validation and non-IPF ILD validation cohorts consisted of 314, 105 and 295 patients, respectively. A multi-dimensional model comprising two clinical variables and 20 proteins outperformed stand-alone clinical and proteomic models. Following dichotomization, the multi-dimensional classifier predicted near-term outcome with 70% sensitivity and 92% specificity in the IPF validation cohort and 70% sensitivity and 80% specificity in the non-IPF ILD validation cohort. ConclusionsA multi-dimensional classifier of near-term outcome accurately discriminated this endpoint with good test performance across independent IPF and non-IPF ILD cohorts. These findings support refinement and prospective validation of this classifier in transplant eligible individuals.

Health care costs and utilization of progressive fibrosing lung disease by underlying interstitial lung disease type.

Fibrosing interstitial lung disease (ILD) encompasses more than 200 diverse pulmonary disorders, of which up to 40% become progressive. The 4 underlying ILD types most likely to result in progression are unclassified ILD/idiopathic interstitial pneumonia (IIP), autoimmune ILDs, exposure-related ILD/hypersensitivity pneumonitis, and sarcoidosis. To compare health care resource utilization (HCRU) and costs among patients with fibrosing ILD that has progressed ("progressive" fibrosing cohort) vs patients whose fibrosis did not meet criteria set for progression ("not yet progressed" cohort). This was a noninterventional study of commercial enrollees and Medicare Advantage with Part D beneficiaries, which used administrative claims data for the period from October 1, 2015, through May 31, 2021. Adult patients (aged ≥18 years) with fibrosing ILD and 12 months of continuous health plan enrollment were included. Patients with idiopathic pulmonary fibrosis, baseline ILD diagnoses, or missing demographic data were excluded. Patients were first classified according to the underlying type of fibrosing ILD. For statistical analyses of outcomes, 2 cohorts were compared within each subtype: progressive fibrosing ILD vs not yet progressed ILD. The final study population included propensity score-matched (PSM) patients (1:1) based on pre-ILD baseline demographic and clinical characteristics. HCRU categories included inpatient hospitalization counts and the number of inpatient days and total costs (in 2021 US dollars), analyzed descriptively and weighted by the per-patient-per-month cost. Lin's regression was used to predict 12-month total cost estimates for comparison by cohort. The distribution by underlying conditions was as follows: autoimmune ILD (n = 4,156), HP (n = 8,181), sarcoidosis (n = 775), and unclassified ILD/IIP (n = 18,635). After PSM, pre-ILD baseline variables were generally well balanced between the progressive and not yet progressed fibrosing ILD cohorts. For all underlying subtypes of ILD, patients in the progressive cohort had significantly more utilization and higher costs compared with patients in the not yet progressed cohort. Progressive cohorts had significantly higher adjusted rates of inpatient days among patients with at least 1 inpatient stay compared with the not yet progressed cohorts (all P < 0.01). In addition, the progressive cohorts had significantly higher adjusted 12-month total costs, with the differences ranging from $24,493 to $55,072 (all comparisons P < 0.001). Irrespective of underlying ILD type, patients with progressive fibrosing ILD had significantly increased HCRU and cost relative to those whose fibrosing ILD had not yet progressed.

Epidemiology and clinical characteristics of interstitial lung disease in patients with rheumatoid arthritis from the JointMan database

Interstitial lung disease (ILD) is a progressive fibrotic disease associated with rheumatoid arthritis (RA); real-world data for evaluating RA–associated ILD (RA–ILD) are limited. We evaluated prevalence, time to onset, clinical characteristics and prognostic factors in patients diagnosed with RA (n = 8963) in the Discus Analytics JointMan database (2009–2019) with and without ILD. ILD prevalence was 4.1% (95% confidence interval 3.7–4.5); > 90% had an ILD diagnosis after RA diagnosis (mean time to onset 3.3 years). At baseline, a higher proportion of patients with RA–ILD were older (> 65 years), male, with history of chronic obstructive pulmonary disease (COPD) compared with patients in the RA cohort. Patients in the RA–ILD cohort were likely to have more severe RA characteristics and joint evaluation compared with patients without ILD, at baseline and before/after ILD diagnosis. In this large, real-world database patients with (vs without) ILD had a higher burden of RA characteristics. Previously established risk factors for RA–ILD were confirmed (age, baseline COPD, anti-cyclic citrullinated peptide positivity, C-reactive protein, Clinical Disease Activity Index score); thus, recognition of these factors and tracking routine disease activity metrics may help identify patients at higher risk of RA complications and lead to improved diagnosis and earlier treatment.

Extracting patient-level data from the electronic health record: Expanding opportunities for health system research.

Epidemiological studies of interstitial lung disease (ILD) are limited by small numbers and tertiary care bias. Investigators have leveraged the widespread use of electronic health records (EHRs) to overcome these limitations, but struggle to extract patient-level, longitudinal clinical data needed to address many important research questions. We hypothesized that we could automate longitudinal ILD cohort development using the EHR of a large, community-based healthcare system. We applied a previously validated algorithm to the EHR of a community-based healthcare system to identify ILD cases between 2012-2020. We then extracted disease-specific characteristics and outcomes using fully automated data-extraction algorithms and natural language processing of selected free-text. We identified a community cohort of 5,399 ILD patients (prevalence = 118 per 100,000). Pulmonary function tests (71%) and serologies (54%) were commonly used in the diagnostic evaluation, whereas lung biopsy was rare (5%). IPF was the most common ILD diagnosis (n = 972, 18%). Prednisone was the most commonly prescribed medication (911, 17%). Nintedanib and pirfenidone were rarely prescribed (n = 305, 5%). ILD patients were high-utilizers of inpatient (40%/year hospitalized) and outpatient care (80%/year with pulmonary visit), with sustained utilization throughout the post-diagnosis study period. We demonstrated the feasibility of robustly characterizing a variety of patient-level utilization and health services outcomes in a community-based EHR cohort. This represents a substantial methodological improvement by alleviating traditional constraints on the accuracy and clinical resolution of such ILD cohorts; we believe this approach will make community-based ILD research more efficient, effective, and scalable.

Health-related quality of life in a multiracial Asian interstitial lung disease cohort.

Understanding health-related quality of life (HRQL) in patients with interstitial lung disease (ILD) provides insight into disease burden and treatment effects on patients' well-being. We examined HRQL in a multiracial Asian ILD cohort using the King's brief ILD (K-BILD) and EuroQol 5-dimension-3-level (EQ5D-3L) questionnaires and their associations with several clinical variables. This was a single-centre cross-sectional study of ILD patients in a university-affiliated tertiary public hospital in Singapore. All patients completed two self-administered HRQL questionnaires upon study entry, and their clinical information was retrieved from electronic medical records. Ninety-nine patients (56% male, 75% Chinese) were included. The median (interquartile range) age was 63 (54-72) years. The most common ILD diagnosis was connective tissue disease-related ILD (n=51, 52%), followed by idiopathic pulmonary fibrosis (n=27, 27%). The mean (standard deviation) scores for the EQ5D-3L utility value, EQ5D Visual Analogue Scale (VAS) and K-BILD total were 0.806 (0.284), 75.1 (12.8) and 63.9 (14.3), respectively. A moderate correlation was found between the EQ5D-3L and K-BILD total and domain scores. The HRQL scores also correlate moderately with the modified Medical Research Council dyspnoea scale (mMRC) scores. There was a weak-to-moderate correlation between HRQL and forced vital capacity (FVC), carbon monoxide diffusing capacity (DLCO) and Charlson comorbidity index. Multiple linear regression showed a significant association of K-BILD total [beta coefficient 0.244, 95% confidence interval (CI): 0.075-0.414; P=0.005], K-BILD 'breathlessness and activities' (beta coefficient 0.448, 95% CI: 0.192-0.703; P=0.001), and the 'psychological' domain (beta coefficient 0.256, 95% CI: 0.024-0.488; P=0.031) with DLCO %pred after adjustment for age, sex, BMI, race, smoking history, comorbidities, FVC %pred and ILD diagnosis. Non-Chinese race was a predictor of better K-BILD 'psychological' domain (beta coefficient 8.680, 95% CI: 0.656-16.704; P=0.034) after adjustment. HRQL is significantly impaired in ILD patients, and low DLCO is a strong predictor of this impairment.

Colchicine Is a Weapon for Managing the Heart Disease Among Interstitial Lung Disease With Viral Infection: Have We Found the Holy Grail?

BackgroundThis study investigated the effect of colchicine use on the risks of heart disease (HD), pericarditis, endocarditis, myocarditis, cardiomyopathy, cardiac arrhythmia, and cardiac failure in patients having interstitial lung disease (ILD) with virus infection (ILD cohort).MethodsWe retrospectively enrolled ILD cohort between 2000 and 2013 from the Longitudinal Health Insurance Database and divided them into colchicine users (n = 12,253) and colchicine non-users (n = 12,253) through propensity score matching. The event of interest was the diagnosis of HD. The incidence of HD was analyzed using multivariate Cox proportional hazards models between colchicine users and the comparison cohort after adjustment for age, sex, medication, comorbidities, and index date based on the time-dependent analysis.ResultsColchicine users had a significantly lower risk of HD (aHR = 0.87, 95% confidence interval (CI]) = 0.82–0.92) than did the colchicine non-user. For colchicine non-users as the reference, the aHR (95% CI) of the patients who received colchicine of 2–7, 8–30, 31–150, and > 150 days were 0.89 (0.81–0.98), 0.84 (0.76–0.94), 090 (0.80–0.99), and 0.83 (0.74–0.93), respectively; regardless of duration use, the lower risk of HD persisted in colchicine users. The cumulative incidence of HD in colchicine users was significantly lower than that in the colchicine non-users (log-rank p < 0.001).ConclusionThe addition of short-term or long-term colchicine to standard medical therapy may have benefits to prevent the HD among the ILD patients concurrent with a virus infection or comorbidities even in elderly patients.

Identification and Prognosis of Patients With Interstitial Pneumonia With Autoimmune Features.

Patients classified as interstitial pneumonia with autoimmune features (IPAF) have interstitial lung disease (ILD) and features of autoimmunity but do not fulfill criteria for connective tissue diseases (CTDs). Our goal was to identify patients classifiable as IPAF, CTD-ILD, and idiopathic pulmonary fibrosis (IPF) from a preexisting pulmonary cohort and evaluate the prognosis of patients with IPAF. We reviewed the medical records of 456 patients from a single-center pulmonary ILD cohort whose diagnoses were previously established by a multidisciplinary panel that did not include rheumatologists. We reclassified patients as IPAF, CTD-ILD, or IPF. We compared transplant-free survival using Kaplan-Meier methods and identified prognostic factors using Cox models. We identified 60 patients with IPAF, 113 with CTD-ILD, and 126 with IPF. Transplant-free survival of IPAF was not statistically significantly different from that of CTD-ILD or IPF. Among IPAF patients, male sex (hazard ratio, 4.58 [1.77-11.87]) was independently associated with worse transplant-free survival. During follow-up, only 10% of IPAF patients were diagnosed with CTD-ILD, most commonly antisynthetase syndrome. Despite similar clinical characteristics, most patients with IPAF did not progress to CTD-ILD; those who did often developed antisynthetase syndrome, highlighting the critical importance of comprehensive myositis autoantibody testing in this population. As in other types of ILD, male sex may portend a worse prognosis in IPAF. The routine engagement of rheumatologists in the multidisciplinary evaluation of ILD will help ensure the accurate classification of these patients and help clarify prognostic factors.

Hydroxychloroquine on the Pulmonary Vascular Diseases in Interstitial Lung Disease: Immunologic Effects, and Virus Interplay.

To investigate the effects of hydroxychloroquine (HCQ) drug use on the risk of pulmonary vascular disease (PVD) in an interstitial lung disease cohort (ILD cohort, ILD+ virus infection), we retrospectively enrolled the ILD cohort with HCQ (HCQ users, N = 4703) and the ILD cohort without HCQ (non-HCQ users, N = 4703) by time-dependence after propensity score matching. Cox models were used to analyze the risk of PVD. We calculated the adjusted hazard ratios (aHRs) and their 95% confidence intervals (CIs) for PVD after adjusting for sex, age, comorbidities, index date and immunosuppressants, such as steroids, etc. Compared with the HCQ nonusers, in HCQ users, the aHRs (95% CIs) for PVD were (2.24 (1.42, 3.54)), and the women’s aHRs for PVD were (2.54, (1.49, 4.35)). The aHRs based on the days of HCQ use for PVD of 28–30 days, 31–120 days, and >120 days were (1.27 (0.81, 1.99)), (3.00 (1.81, 4.87)) and (3.83 (2.46, 5.97)), respectively. The medium or long-term use of HCQ or young women receiving HCQ were associated with a higher aHR for PVD in the ILD cohort. These findings indicated interplay of the primary immunologic effect of ILD, comorbidities, women, age and virus in the HCQ users.

The Effect of Borderline Pulmonary Hypertension on Survival in Chronic Lung Disease

Background: The impact of the new “borderline” hemodynamic class for pulmonary hypertension (PH) (mean pulmonary artery pressure [mPAP], 21–24 mm Hg and pulmonary vascular resistance, [PVR], ≥3 wood units, [WU]) in chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) is unclear. Objectives: The aim of this study was to assess the effect of borderline PH (BLPH) on survival in COPD and ILD patients. Method: Survival was analyzed from retrospective data from 317 patients in 12 centers (Italy, Spain, UK) comparing four hemodynamic groups: the absence of PH (NoPH; mPAP <21 mm Hg or 21–24 mm Hg and PVR <3 WU), BLPH (mPAP 21–24 mm Hg and PVR ≥3 WU), mild-moderate PH (MPH; mPAP 25–35 mm Hg and cardiac index [CI] ≥2 L/min/m²), and severe PH (SPH; mPAP ≥35 mm Hg or mPAP ≥25 mm Hg and CI <2 L/min/m²). Results: BLPH affected 14% of patients; hemodynamic severity did not predict survival when COPD and ILD patients were analyzed together. However, survival in the ILD cohort for any PH level was worse than in NoPH (3-year survival: NoPH 58%, BLPH 32%, MPH 28%, SPH 33%, p = 0.002). In the COPD cohort, only SPH had reduced survival compared to the other groups (3-year survival: NoPH 82%, BLPH 86%, MPH 87%, SPH 57%, p = 0.005). The mortality risk correlated significantly with mPAP in ILD (hazard ratio [HR]: 2.776, 95% CI: 2.057–3.748, p < 0.001) and notably less in COPD patients (HR: 1.015, 95% CI: 1.003–1.027, p = 0.0146). Conclusions: In ILD, any level of PH portends worse survival, while in COPD, only SPH presents a worse outcome.

4541 Harnessing the Power of the Electronic Medical Record in Interstitial Lung Disease

OBJECTIVES/GOALS: Harnessing the EHR to support clinical research is critical for the study of rare diseases such as interstitial lung disease (ILD). However no studies have compared EHR and research-quality data in the ILD population. Our objectives were to (1) identify ILD patients and extract clinical data from an EHR system and (2) assess the performance of ILD data capture. METHODS/STUDY POPULATION: Case validated algorithms were implemented to identify patients from the University of California San Francisco EHR and extract key ILD clinical information including, demographic variables, process measures and patient outcomes. Key clinical information were defined based on consensus statements and ILD clinical trials. A subset of ILD patients, had variables recorded in both the EHR and a separate ILD longitudinal research database. The completeness of EHR data capture and level of agreement were compared between three data collection methods: (1) data manually and systematically collected for an ILD research database (gold standard), (2) data automatically extracted from structured fields in the EHR, and (3) data extracted from unstructured data sources. RESULTS/ANTICIPATED RESULTS: We identified 5857 ILD patients in the EHR, of which 2100 patients had data available in the both the EHR and research database. Baseline demographic variables, co-morbidities, use of diagnostic testing, pharmacotherapy were accurately extracted from structured fields. Outcome measures, including lung physiology, radiographic patterns, pathology results, and health related quality of life (HRQoL) were unevenly extracted from structured fields alone. With the exception of HRQoL, these measures were accurately captured in unstructured EHR sources. Notably, certain metrics were better defined in the EHR, including health care resource utilization metrics, acute exacerbations, medication side effects, supplemental oxygen use and specialty care referrals (rheumatology, lung transplant, palliative care, etc). DISCUSSION/SIGNIFICANCE OF IMPACT: A large real-world ILD cohort can be algorithmically extracted from the EHR along with key clinical variables with accuracy comparable to protocol-driven research databases. Rigorous assessment of the types of disease-specific variables that are present in EHR-derived data will inform future interventions to improve the fidelity, accessibility and use of the EHR in clinical research.

Sleep and interstitial lung disease.

There is an increasing recognition of the impact of sleep and sleep disorders on respiratory disease. Recent years have seen a new focus on the relationship between sleep and outcomes in patients interstitial lung disease (ILD). Recent studies suggest a high prevalence of sleep issues in ILD cohorts, which seem to have a meaningful negative impact on quality of life, disease progression, and survival. Sleep disordered breathing is common in ILD patients: obstructive sleep apnoea (OSA) is found in 44-72% of ILD patients, and nocturnal hypoxemia is relatively common even in the absence of OSA. Sleep disorders are associated with worse quality of life in ILD, and may also predict more rapid disease progression and increased mortality. It remains unknown if nocturnal hypoxemia may itself cause progression of ILD. Uncontrolled and retrospective studies have suggested that treating OSA may improve ILD-related outcomes, but prospective studies are lacking in this field.

Significance of Interstitial Lung Disease on Outcomes Following Cardiac Surgery

Interstitial lung disease (ILD) is a known risk factor for noncardiac surgery due to acute pulmonary exacerbations but its impact after cardiac surgery is not known. We examined perioperative outcomes and risk factors for long-term survival in ILD patients who underwent cardiac surgery. From January 2002 to June 2017, 294 cardiac surgery patients with a previous ILD diagnosis, including 75 patients with idiopathic pulmonary fibrosis (IPF), were identified. A comparison cohort of 1,481 non-ILD patients was selected based on a priori variables. Long-term survival was evaluated using Cox proportional hazard modeling. Median follow-up was 6.4 years. ILD patients had higher postoperative mortality, reintubation rates, longer intensive care unit stay, and higher 30-day readmission rates (all p <0.05). Kaplan-Meier estimates of survival at 1, 5, and 10 years were 89%, 62%, and 37% for the non-IPF ILD cohort, 89%, 50%, and 13% for the IPF cohort, and 95%, 82%, and 67% for the comparison cohort, respectively (overall p <0.001). These significant differences in survival persisted in our risk-adjusted survival analysis. Adjusted survival analysis identified IPF (hazard ratio 3.04) and ILD (non-IPF; hazard ratio 1.78) as significant contributors to all-cause mortality. However, there were no changes in pulmonary function tests after 48 months postprocedure. In conclusion, ILD patients who underwent cardiac surgery have increased operative mortality, reintubation rates, longer intensive care unit, and higher 30-day readmissions compared with non-ILD patients. Moreover, severity of ILD, especially in IPF, appears to be associated with shorter long-term survival. In these patients, pulmonary risk stratification and multidisciplinary team approach are crucial.

Interstitial pneumonia with autoimmune features show better survival and less exacerbations compared to idiopathic pulmonary fibrosis

BackgroundPatients with interstitial lung disease (ILD) who show features related to autoimmunity without meeting criteria for a defined connective tissue disease are categorized as interstitial pneumonia with autoimmune features (IPAF). The present study compared clinical characteristics and clinical outcomes of patients with IPAF to patients with connective tissue disease related-interstitial lung disease (CTD-ILD) and patients with idiopathic pulmonary fibrosis (IPF).MethodsILD patients who were consecutively enrolled in a single institution ILD cohort between 2008 and 2015 were evaluated for the study. Clinical data had been prospectively collected, while radiologic imaging and pathologic findings were re-reviewed for the present study.ResultsOut of 305 patients with ILD, 54 (17.7%) patients met the classification of IPAF, 175 (57.4%) patients had IPF, and 76 (24.9%) patients were diagnosed with CTD-ILD. Compared to IPF, incidences of acute exacerbations in 1,3 and 5 years were significantly less in the IPAF group (p = 0.022, p = 0.026 and p = 0.007, respectively). From multivariate analysis for mortality, age (p = 0.034, HR 1.022, 95% CI: 1.002–1.044), FVC (p < 0.001, HR 0.970, 95% CI: 0.955–0.984), ILD exacerbation (p = 0.001, HR 2.074, 95% CI: 1.366–3.148), and ILD type (p = 0.047, HR 0.436, 95% CI: 0.192–0.984 (IPAF vs IPF), respectively) showed significant association.ConclusionsCompared to the other ILD groups, IPAF showed distinct clinical characteristics. The IPAF group showed better survival and less episodes of exacerbation when compared to the IPF group.

Prognosticating Outcomes in Interstitial Lung Disease by Mediastinal Lymph Node Assessment. An Observational Cohort Study with Independent Validation.

Mediastinal lymph node (MLN) enlargement on chest computed tomography (CT) is prevalent in patients with interstitial lung disease (ILD) and may reflect immunologic activation and subsequent cytokine-mediated immune cell trafficking. We aimed to determine whether MLN enlargement on chest CT predicts clinical outcomes and circulating cytokine levels in ILD. MLN measurements were obtained from chest CT scans of patients with ILD at baseline evaluation over a 10-year period. Patients with sarcoidosis and drug toxicity-related ILD were excluded. MLN diameter and location were assessed. Plasma cytokine levels were analyzed in a subset of patients. The primary outcome was transplant-free survival (TFS). Secondary outcomes included all-cause and respiratory hospitalizations, lung function, and plasma cytokine concentrations. Cox regression was used to assess mortality risk. Outcomes were assessed in three independent ILD cohorts. Chest CT scans were assessed in 1,094 patients (mean age, 64 yr; 52% male). MLN enlargement (≥10 mm) was present in 66% (n = 726) and strongly predicted TFS (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.12-2.10; P = 0.008) and risk of all-cause and respiratory hospitalizations (internal rate of return [IRR], 1.52; 95% CI, 1.17-1.98; P = 0.002; and IRR, 1.71; 95% CI, 1.15-2.53; P = 0.008, respectively) when compared with subjects with MLN <10 mm. Patients with MLN enlargement had lower lung function and decreased plasma concentrations of soluble CD40L (376 pg/ml vs. 505 pg/ml, P = 0.001) compared with those without MLN enlargement. Plasma IL-10 concentration >45 pg/ml predicted mortality (HR, 4.21; 95% CI, 1.21-14.68; P = 0.024). Independent analysis of external datasets confirmed these findings. MLN enlargement predicts TFS and hospitalization risk in ILD and is associated with decreased levels of a key circulating cytokine, soluble CD40L. Incorporating MLN and cytokine findings into current prediction models might improve ILD prognostication.

Heterogeneity in Unclassifiable Interstitial Lung Disease. A Systematic Review and Meta-Analysis.

Accurate diagnosis of interstitial lung disease is necessary to identify the most appropriate management strategy and to inform prognosis. Many patients cannot be provided a confident diagnosis, despite an exhaustive search for potential etiologies and review in a multidisciplinary conference, and are consequently labeled with unclassifiable interstitial lung disease. To systematically review and meta-analyze previous studies reporting on the diagnostic criteria, prevalence, clinical features, and outcome of unclassifiable interstitial lung disease. MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials databases were systematically searched for all studies related to unclassifiable interstitial lung disease published before September 1, 2017. Two authors independently screened each citation for eligibility criteria, serially reviewing the title, abstract, and full-text manuscript, and then abstracted data pertaining to the study objectives from eligible studies. Articles were stratified by risk of selection bias, whether the publication stated that patients were reviewed in a multidisciplinary discussion, and by the frequency of surgical lung biopsy. Meta-analyses and meta-regression were performed to calculate the pooled prevalence of unclassifiable interstitial lung disease within an interstitial lung disease population and within specific subgroups to identify reasons for across-study heterogeneity. The search identified 10,130 unique citations, 313 articles underwent full-text review, and eligibility criteria were met in 88 articles. Twenty-two studies were deemed low risk of selection bias, including 1,060 patients with unclassifiable interstitial lung disease from a total of 10,174 patients with interstitial lung disease. The terminology and definition of unclassifiable interstitial lung disease varied substantially across publications, with inconsistent diagnostic criteria and evaluation processes. The prevalence of unclassifiable interstitial lung disease was 11.9% (95% confidence interval, 8.5-15.6%), with lower prevalence in centers that reported use of a formal multidisciplinary discussion of cases (9.5% vs. 14.5%). Four articles reported survival of unclassifiable interstitial lung disease, with 1-year, 2-year, and 5-year survival of 84% to 89%, 70% to 76%, and 46% to 70%, respectively. This systematic review and meta-analysis shows that unclassifiable interstitial lung disease is common but has substantial heterogeneity and inconsistent definitions across interstitial lung disease cohorts. These findings highlight important limitations in multicenter studies of fibrotic interstitial lung disease and the need for a standardized approach to interstitial lung disease diagnostic classification.

Pulmonary hypertension in interstitial lung disease: Limitations of echocardiography compared to cardiac catheterization.

In interstitial lung disease (ILD), pulmonary hypertension (PH) is a major adverse prognostic determinant. Transthoracic echocardiography (TTE) is the most widely used tool when screening for PH, although discordance between TTE and right heart catheter (RHC) measured pulmonary haemodynamics is increasingly recognized. We evaluated the predictive utility of the updated European Society of Cardiology/European Respiratory Society (ESC/ERS) TTE screening recommendations against RHC testing in a large, well-characterized ILD cohort. Two hundred and sixty-five consecutive patients with ILD and suspected PH underwent comprehensive assessment, including RHC, between 2006 and 2012. ESC/ERS recommended tricuspid regurgitation (TR) velocity thresholds for assigning high (>3.4 m/s), intermediate (2.9-3.4 m/s) and low (<2.8 m/s) probabilities of PH were evaluated against RHC testing. RHC testing confirmed PH in 86% of subjects with a peak TR velocity >3.4 m/s, and excluded PH in 60% of ILD subjects with a TR velocity <2.8 m/s. Thus, the ESC/ERS guidelines misclassified 40% of subjects as 'low probability' of PH, when PH was confirmed on subsequent RHC. Evaluating alternative TR velocity thresholds for assigning a low probability of PH did not significantly improve the ability of TR velocity to exclude a diagnosis of PH. In patients with ILD and suspected PH, currently recommended ESC/ERS TR velocity screening thresholds were associated with a high positive predictive value (86%) for confirming PH, but were of limited value in excluding PH, with 40% of patients misclassified as low probability when PH was confirmed at subsequent RHC.