non-IPF Interstitial Lung Disease Research Articles

Prognostic Impact of Pulmonary Diseases in 952 Patients with Thoracic and/or Abdominal Aortic Aneurysm

Background/Objectives: Pulmonary diseases are common in patients with thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA). Although high prevalences of chronic obstructive pulmonary disease and lung cancer (LC) are known, the prevalence of these and other pulmonary diseases regarding their relation to the outcome of TAA and/or AAA are not determined. Methods: Pulmonary diseases present at aortic aneurysm (AA) diagnosis and follow-up periods and cause of death of 952 patients with TAA, AAA, or TAA + AAA (including thoracoabdominal AA) treated at our institution in Japan were retrospectively analyzed. Cox regression analysis was used to investigate potential risk factors of mortality. Results: The mean patient age was 72.4 years, and the median follow-up was 4.92 years. At diagnosis, 528 (55.5%) patients had pulmonary diseases, including emphysema without interstitial lung disease (ILD) or LC, LC, idiopathic pulmonary fibrosis (IPF) without LC, non-IPF ILD without LC, and interstitial lung abnormalities (ILAs) without LC in 250, 85, 65, 15, and 58 patients, respectively. During follow-up, LC and acute exacerbation (AE) of IPF developed in 50 and 12 patients, respectively. In 213 patients who died, there were 45 (21.1%) aortic disease-related deaths. Other causes of death included LC (27.7%), cardiovascular events (9.4%), pneumonia (5.6%), and interstitial lung disease (4.7%). In a multivariate Cox regression hazard model, age; larger maximum aneurysm diameter; and coexisting LC, IPF, or concomitant cancer were associated with poor prognosis. Conclusions: In patients with AA, not only age and aneurysm diameter but also coexisting LC and IPF were prognostic factors for mortality.

Expanding horizons: lung transplantation for non-IPF interstitial lung diseases

ObjectiveInterstitial lung diseases (ILDs) are diverse pulmonary disorders marked by diffuse lung inflammation and fibrosis. The variability in characteristics and treatment approaches complicates diagnosis and management. In advanced cases requiring transplantation, determining indications and selecting suitable candidates presents additional challenges.MethodsOf all patients with non-IPF ILD between December 2016 to December 2022 were analyzed retrospectively. Patients were categorized into two groups: transplanted patients and deceased patients on the waiting list. Clinical data and survival outcomes were compared between groups.ResultsOf the 43 patients, 20 underwent lung transplantation while 23 died awaiting transplantation. Waiting list mortality was 53.4%, with median waiting times similar between groups (3 months for transplant patients and 6 months for those on the waiting list). There were no significant differences between groups in age, gender, height, BMI, 6-minute walk test (6MWT), or forced vital capacity (FVC). The prevalence of pulmonary hypertension (PH) was 76.7% in right heart catheterizations, similar in both groups. One single and 19 bilateral lung transplants were performed. Overall, 13 of the 20 patients survived to discharge from the hospital. One-year mortality was 7/20 (35%). The median follow-up was 34 months, with a 1-year conditional survival of 90.9% at 3 years and 70.7% at 5 years.ConclusionsThis study underscores the importance of further research into non-IPF ILDs. Lung transplantation remains a viable option that can significantly enhance both the quality and longevity of life for patients with advanced ILD.

A pilot metabolomics study across the continuum of interstitial lung disease fibrosis severity.

Interstitial lung diseases (ILDs) include a variety of inflammatory and fibrotic pulmonary conditions. This study employs high-resolution metabolomics (HRM) to explore plasma metabolites and pathways across ILD phenotypes, including non-fibrotic ILD, idiopathic pulmonary fibrosis (IPF), and non-IPF fibrotic ILD. The study used 80 plasma samples for HRM, and involved linear trend and group-wise analyses of metabolites altered in ILD phenotypes. We utilized limma one-way ANOVA and mummichog algorithms to identify differences in metabolites and pathways across ILD groups. Then, we focused on metabolites within critical pathways, indicated by high pathway overlap sizes and low p-values, for further analysis. Targeted HRM identified putrescine, hydroxyproline, prolyl-hydroxyproline, aspartate, and glutamate with significant linear increases in more fibrotic ILD phenotypes, suggesting their role in ILD fibrogenesis. Untargeted HRM highlighted pathway alterations in lysine, vitamin D3, tyrosine, and urea cycle metabolism, all associated with pulmonary fibrosis. In addition, methylparaben level had a significantly increasing linear trend and was higher in the IPF than fibrotic and non-ILD groups. This study highlights the importance of specific amino acids, metabolic pathways, and xenobiotics in the progression of pulmonary fibrosis.

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

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

Assessing health-related quality of life in patients with interstitial lung diseases

BackgroundThe R-Scale-PF was proposed to evaluate the health-related quality of life (HRQoL) in patients with idiopathic pulmonary fibrosis (IPF). We generated a German version of the R-Scale-PF (GR-Scale), representing the first translation of the questionnaire into another language and assessed HRQoL longitudinally in various interstitial lung diseases (ILDs) using the R-Scale-PF scoring system at a specialized ILD centre.MethodsWe have translated the questionnaire in accordance with the WHO translation guidelines and applied it to 80 ILD patients of our department, with follow-ups after 3–6 months, assessing its internal consistency, floor and ceiling effects, concurrent validity, known-groups validity, and its responsiveness to changes over time.ResultsAt baseline, all 80 patients completed the GR-Scale. In 70 patients (87.5%), follow-up data could be obtained after 4.43 ± 1.2 months. The GR-Scale demonstrated acceptable internal consistency (Cronbach’s α 0.749) and slight floor effects. Concurrent validity analysis showed weak but significant correlations with forced vital capacity (FVC; r=-0.282 p = 0.011) and diffusion capacity for carbon monoxide (DLco; r=-0.254 p = 0.025). In the follow-up analysis, moderate correlations were found with FVC (r=-0.41 p < 0.001) and DLco (r=-0.445 p < 0.001). No significant difference in the total score was found between patients with IPF (n = 10) and with non-IPF ILDs (n = 70). The GR-Scale successfully discriminated between groups of varying disease severity based on lung function parameters and the need for long-term oxygen therapy (LTOT). Furthermore, it was able to distinguish between patients showing improvement, stability or decline of lung function parameters.ConclusionOur prospective observational pilot study suggests that the GR-Scales is a simple and quick tool to measure HRQoL in patients with ILDs, thus providing an important additional information for the clinical assessment of ILD patients.Trial registrationOur study was retrospectively registered in the German Clinical Trial Register (DRKS) on 02.11.2022 (DRKS-ID: DRKS00030599).

Serum metalloproteinase-7 as a biomarker of progressive pulmonary fibrosis

IntroductionProgressive pulmonary fibrosis (PPF) corresponds to any fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF) that presents clinical, physiological and/or radiological evidence of disease progression similar to IPF. Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of pulmonary fibrosis and are associated with disease progression and reduced survival in IPF and other fibrotic ILDs.AimThis study aimed to investigate the role of the serum levels of MMP-1 and MMP-7 in patients with fibrotic non-IPF ILD as possible biomarkers of patients at risk of developing PPF.MethodsNewly diagnosed patients with fibrotic non-IPF ILD were included in this study. Serum levels of MMP-1 and MMP-7 were quantified at baseline, and disease progression was monitored. PPF was defined according to the recent ATS/ERS/JRS/ALAT Clinical Practice Guidelines.ResultsSeventy-nine patients with fibrotic non-IPF ILDs were included and classified as having PPF or non-PPF. Significantly higher levels of MMP-7, but not MMP-1, were detected in the PPF group (p=0.01). MMP-7 was independently associated with PPF (aOR=1.263; 95% CI 1.029—1.551, p=0.026) after adjustment for sex, age and smoking history. A cut-off value of 3.53 ng·mL−1for serum MMP-7 levels had a sensitivity of 61% and a specificity of 74% for predicting PPF in non-IPF ILDs.ConclusionsIn patients with fibrotic non-IPF ILDs, serum MMP-7 levels were significantly greater in the subgroup of patients meeting the PPF criteria at follow-up. This can be considered and further investigated as a possible biomarker to identify fibrotic ILD patients at risk of PPF.

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

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

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

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

Can FDG-PET/CT imaging be used to predict decline in quality of life in interstitial lung disease? A prospective study of the relationship between FDG uptake and quality of life in a UK outpatient setting

Background18Fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) CT imaging has been used in many inflammatory and infectious conditions to differentiate areas of increased metabolic activity. FDG uptake differs between areas of...

Machine learning classifier is associated with mortality in interstitial lung disease: a retrospective validation study leveraging registry data

BackgroundMortality prediction in interstitial lung disease (ILD) poses a significant challenge to clinicians due to heterogeneity across disease subtypes. Currently, forced vital capacity (FVC) and Gender, Age, and Physiology (GAP) score are the two most utilized metrics in prognostication. Recently, a machine learning classifier system, Fibresolve, designed to identify a variety of computed tomography (CT) patterns associated with idiopathic pulmonary fibrosis (IPF), was demonstrated to have a significant association with mortality across multiple subtypes of ILD. The purpose of this follow-up study was to retrospectively validate these findings in a large, external cohort of patients with ILD.MethodsIn this multi-center validation study, Fibresolve was applied to chest CT scans of patients with confirmed ILD that had available follow-up data. Fibresolve scores categorized by tertile were analyzed using Cox regression analysis adjusted for tobacco use and modified GAP (mGAP) score.ResultsOf 643 patients included, 446 (69.3%) died over a median follow-up time of 144 [1-821] weeks. The median [range] mGAP score was 5 [3–7]. In multivariable analysis, Fibresolve score categorized by tertile was significantly associated with mortality (Tertile 2 HR 1.47, 95% CI 0.82–2.37, p = 0.11; Tertile 3 HR 3.12, 95% CI 1.98–4.90, p < 0.001). Subgroup analyses revealed significant associations amongst those with non-IPF ILDs (Tertile 2 HR 1.95, 95% CI 1.28–2.97, Tertile 3 HR 4.66, 95% CI 2.94–7.38) and severe disease, defined by a FVC ≤ 75% (Tertile 2 HR 2.29, 95% CI 1.43–3.67, Tertile 3 HR 4.80, 95% CI 2.93–7.86).ConclusionsFibresolve is independently associated with mortality in ILD, particularly amongst patients with non-IPF ILDs and in those with severe disease.

A comparative study to evaluate factors affecting adverse outcomes in interstitial lung diseases with Idiopathic pulmonary fibrosis (IPF) and other non-IPF interstitial lung diseases at 6 months in a tertiary care centre

A comparative study to evaluate factors affecting adverse outcomes in interstitial lung diseases with Idiopathic pulmonary fibrosis (IPF) and other non-IPF interstitial lung diseases at 6 months in a tertiary care centre

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.

Clinical characteristics and outcome of lung cancer in patients with fibrosing interstitial lung disease

BackgroundLung cancer (LC) is an important comorbidity of interstitial lung disease (ILD) and has a poor prognosis. The clinical characteristics and outcome of each ILD subtype in LC patients have not been sufficiently investigated. Therefore, this study aimed to evaluate the difference between idiopathic pulmonary fibrosis (IPF) and non-IPF ILD as well as prognostic factors in patients with ILD-LC.MethodsThe medical records of 163 patients diagnosed with ILD-LC at Asan Medical Center from January 2018 to May 2023 were retrospectively reviewed. Baseline characteristics and clinical outcomes were compared between the IPF-LC and non-IPF ILD-LC groups, and prognostic factors were analyzed using the Cox proportional-hazard model.ResultsThe median follow-up period was 11 months after the cancer diagnosis. No statistically significant differences were observed in clinical characteristics and mortality rates (median survival: 26 vs. 20 months, p = 0.530) between the groups. The independent prognostic factors in patients with ILD-LC were higher level of Krebs von den Lungen-6 (≥ 1000 U/mL, hazard ratio [HR] 1.970, 95% confidence interval [CI] 1.026-3.783, p = 0.025) and advanced clinical stage of LC (compared with stage I, HR 3.876 for stage II, p = 0.025, HR 5.092 for stage III, p = 0.002, and HR 5.626 for stage IV, p = 0.002). In terms of treatment, surgery was the significant factor for survival (HR 0.235; 95% CI 0.106-0.520; p < 0.001).ConclusionsNo survival difference was observed between IPF-LC and non-IPF ILD-LC patients. A higher level of Krebs von den Lungen-6 may act as a prognostic marker in ILD-LC patients.

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.

Use of 6-minute walk distance to predict lung transplant-free survival in fibrosing non-IPF interstitial lung diseases.

The identification of progression in patients with fibrosing non-idiopathic pulmonary fibrosis (IPF) interstitial lung diseases (ILDs) represents an ongoing clinical challenge. Lung function decline alone may have significant limitations in the detection of clinically significant progression. We hypothesized that longitudinal changes of 6-min walk distance (6MWD) from baseline, simultaneously considered with measures of lung function, may independently predict survival and identifying clinically significant progression of disease. Forced vital capacity (FVC), diffusing lung capacity (DLCO) and 6MWD were considered both at baseline and at 1 year in a discovery cohort (n = 105) and in a validation cohort (n = 138) from different centres. The primary endpoint was lung transplant (LTx)-free survival. Average follow-up was 3 years in both cohorts. Combined incidence of deaths and LTx was 29% and 21%, respectively. No collinearity and no strong correlations were observed among FVC, DLCO and 6MWD longitudinal changes. While age, gender and BMI were not significant, 6MWD decline ≥24 m predicted LTx-free-survival significantly and independently from FVC and DLCO declines, with high sensitivity and specificity, in both the discovery and the validation cohorts. Although FVC and DLCO declines remained significant predictors of LTx-free survival, 6MWD decline was more accurate than the proposed ATS/ERS/JRS/ALAT functional criteria. Results were confirmed after stratifying patients by baseline FVC. Longitudinal declines of 6MWD are associated with poor survival in fibrosing ILDs across a wide range of baseline severity, with high accuracy. 6MWD longitudinal decline is largely independent from lung function decline and may be integrated into the routine assessment of progression.

Clinical manifestations and prognostic factors analysis of patients hospitalised with acute exacerbation of idiopathic pulmonary fibrosis and other interstitial lung diseases

BackgroundAcute exacerbation (AE) is a life-threatening condition taking place not only in idiopathic pulmonary fibrosis (IPF) but also in interstitial lung diseases (ILD) other than IPF (non-IPF ILD). This study...

Advances in the identification and management of progressive pulmonary fibrosis: perspective from Chinese experts.

Fibrosing interstitial lung diseases (FILDs) other than idiopathic pulmonary fibrosis (IPF) can develop into progressive pulmonary fibrosis (PPF) despite initial management. A substantial proportion of patients with non-IPF interstitial lung diseases (ILDs) progress to PPF, including connective tissue disease-associated ILD (such as rheumatoid arthritis-associated ILD, systemic sclerosis-associated ILD, and idiopathic inflammatory myositis-associated ILD), fibrosing hypersensitivity pneumonitis, and fibrosing occupational ILD. The concept of PPF emerged only recently and several studies have confirmed the impact of PPF on mortality. In addition to poor prognosis among patients with PPF, there remains a lack of consensus in the diagnosis and treatment of PPF across different types of ILDs. There is a need to raise awareness of PPF in FILDs and to explore measures to improve PPF diagnosis and treatment, which in turn could potentially reduce the progression from FILD to PPF. This review discusses the disease burden of PPF and recent advances in the management of PPF among patients with ILDs, including antifibrotic medications that have emerged as promising treatment options. Additionally, this review highlights the perspectives of expert Chinese physicians with regard to their experience in managing PPF in clinical practice.

Telomere length and immunosuppression in non-idiopathic pulmonary fibrosis interstitial lung disease.

Studies suggest a harmful pharmacogenomic interaction exists between short leukocyte telomere length (LTL) and immunosuppressants in idiopathic pulmonary fibrosis (IPF). It remains unknown if a similar interaction exists in non-IPF interstitial lung disease (ILD). A retrospective, multicentre cohort analysis was performed in fibrotic hypersensitivity pneumonitis (fHP), unclassifiable ILD (uILD) and connective tissue disease (CTD)-ILD patients from five centres. LTL was measured by quantitative PCR for discovery and replication cohorts and expressed as age-adjusted percentiles of normal. Inverse probability of treatment weights based on propensity scores were used to assess the association between mycophenolate or azathioprine exposure and age-adjusted LTL on 2-year transplant-free survival using weighted Cox proportional hazards regression incorporating time-dependent immunosuppressant exposure. The discovery and replication cohorts included 613 and 325 patients, respectively. In total, 40% of patients were exposed to immunosuppression and 22% had LTL <10th percentile of normal. fHP and uILD patients with LTL <10th percentile experienced reduced survival when exposed to either mycophenolate or azathioprine in the discovery cohort (mortality hazard ratio (HR) 4.97, 95% CI 2.26-10.92; p<0.001) and replication cohort (mortality HR 4.90, 95% CI 1.74-13.77; p=0.003). Immunosuppressant exposure was not associated with differential survival in patients with LTL ≥10th percentile. There was a significant interaction between LTL <10th percentile and immunosuppressant exposure (discovery pinteraction=0.013; replication pinteraction=0.011). Low event rate and prevalence of LTL <10th percentile precluded subgroup analyses for CTD-ILD. Similar to IPF, fHP and uILD patients with age-adjusted LTL <10th percentile may experience reduced survival when exposed to immunosuppression.

Clinical Impact of Physical Activity and Cough on Disease Progression in Fibrotic Interstitial Lung Disease.

Physical activity limitations and cough are common in patients with interstitial lung disease (ILD), potentially leading to reduced health-related quality of life. We aimed to compare physical activity and cough between patients with subjective, progressive idiopathic pulmonary fibrosis (IPF) and fibrotic non-IPF ILD. In this prospective observational study, wrist accelerometers were worn for seven consecutive days to track steps per day (SPD). Cough was evaluated using a visual analog scale (VAScough) at baseline and weekly for six months. We included 35 patients (IPF: n = 13; non-IPF: n = 22; mean ± SD age 61.8 ± 10.8 years; FVC 65.3 ± 21.7% predicted). Baseline mean ± SD SPD was 5008 ± 4234, with no differences between IPF and non-IPF ILD. At baseline, cough was reported by 94.3% patients (mean ± SD VAScough 3.3 ± 2.6). Compared to non-IPF ILD, patients with IPF had significantly higher burden of cough (p = 0.020), and experienced a greater increase in cough over six months (p = 0.009). Patients who died or underwent lung transplantation (n = 5), had significantly lower SPD (p = 0.007) and higher VAScough (p = 0.047). Long-term follow up identified VAScough (HR: 1.387; 95%-CI 1.081-1.781; p = 0.010) and SPD (per 1000 SPD: HR 0.606; 95%-CI: 0.412-0.892; p = 0.011) as significant predictors for transplant-free survival. In conclusion, although activity didn't differ between IPF and non-IPF ILD, cough burden was significantly greater in IPF. SPD and VAScough differed significantly in patients who subsequently experienced disease progression and were associated with long-term transplant-free survival, calling for better acknowledgement of both parameters in disease management.

Serum Progranulin Level Might Differentiate Non-IPF ILD from IPF.

Diagnosing interstitial lung disease (ILD) can be a challenging process. New biomarkers may support diagnostic decisions. Elevated serum progranulin (PGRN) levels have been reported in liver fibrosis and dermatomyositis-associated acute interstitial pneumonia. Our aim was to assess the role of PGRN in the differential diagnosis of idiopathic pulmonary fibrosis (IPF) and other ILDs. Serum levels of PGRN were measured by enzyme-linked immunosorbent assay in stable IPF (n = 40), non-IPF ILD (n = 48) and healthy controls (n = 17). Patient characteristics, lung function, CO diffusion (DLCO), arterial blood gases, 6-min walk test, laboratory parameters and high-resolution (HR)CT pattern were assessed. In stable IPF, PGRN levels did not differ from healthy controls; however, serum PGRN levels were significantly higher in non-IPF ILD patients compared to healthy subjects and IPF (53.47 ± 15.38 vs. 40.99 ± 5.33 vs. 44.66 ± 7.77 ng/mL respectively; p < 0.01). The HRCT pattern of usual interstitial pneumonia (UIP) was associated with normal PGRN level, while for non-UIP patterns, significantly elevated PGRN level was measured. Elevated serum PGRN levels may be associated with non-IPF ILD, especially non-UIP patterns and might be helpful in cases of unclear radiological patterns in the differentiation between IPF and other ILDs.