Interstitial Lung Disease Group Research Articles

Risk Factors and Biomarkers for Interstitial Lung Disease and Pulmonary Arterial Hypertension in Systemic Sclerosis: Experience of Two Tertiary Centers in Turkey

Purpose: To define the clinical and laboratory characteristics of patients with systemic sclerosis (SSc), and to investigate the risk factors affecting the prevalence of interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), which are important causes of morbidity and mortality. Patients and methods: 88 patients with SSc were compared according to the presence of ILD and PAH. ILD was confirmed by chest computed tomography, and PAH was suspected and considered probable PAH when right ventricular systolic pressure was >40 mmHg according to echocardiography. Results: Of the 88 patients, 44.3% had diffuse-type and 55.7% had limited-type SSc. Diffuse type, percentages of positive anti-scleroderma-70 (anti-Scl70) antibody and anti-centromere antibody, white blood cell (WBC), platelet, erythrocyte sedimentation rate (ESR), smoking, and presence of the sclerodactyly and telangiectasia differed significantly in SSc with ILD group. The positive titer of anti-Scl70 antibody (odds ratio (OR)=6.124, p=0.004), platelet count (OR=0.138, p=0.002), ESR (OR=1.042, p=0.035) and presence of telangiectasia (OR=10.571, p=0.001) were associated with ILD in patients with SSc. Also, while diffuse-type (OR=0.223, p=0.010), the presence of sclerodactyly (OR=11.112, p=0.028) and telangiectasia (OR=3.861, p=0.020) were risk factors for the development of ILD in nonspecific interstitial pneumonia pattern, anti-Scl-70 antibody positivity (OR=12.921, p=0.019) and high ESR (OR=1.034, p=0.030) were found to be risk factors for the development of usual interstitial pneumonia pattern. Conclusion: Positive titer of the anti-Scl70 antibody, diffuse type, presence of telangiectasia, and high ESR were independently associated with ILD in SSc patients.

Osteopontin as a Biomarker in Interstitial Lung Diseases.

Osteopontin (OPN) is a glycoprotein involved in Th1 and Th17 differentiation, and inflammation and tissue remodeling. OPN is a biomarker of disease activity in patients with autoimmune inflammatory conditions. This study aimed to assess the diagnostic and prognostic value of OPN in interstitial lung diseases (ILDs). Between May 2016 and October 2019, 344 patients with ILD were recruited at the Hospital Universitario Marqués de Valdecilla (Spain) and were prospectively followed-up. This study involved the determination of OPN serum levels by ELISA and OPN RNA expression quantified using qPCR. Six genetic polymorphisms in OPN (rs28357094, rs2853749, rs2853750, rs11728697, rs7695531, and rs1126616) were genotyped using TaqMan assays. OPN serum levels were also assessed in 140 healthy controls. OPN serum levels (median [interquartile range]) were significantly higher in ILD patients than in controls (1.05 [0.75-1.51] ng/mL versus 0.81 [0.65-0.98] ng/mL in healthy controls; p < 0.01). OPN serum levels were inversely correlated with the forced vital capacity. OPN serum levels were also higher in ILD patients who died or underwent lung transplantation when compared with the remaining ILD patients (1.15 [0.80-1.72] ng/mL versus 0.99 [0.66-1.32] ng/mL; p = 0.05). Survival worsened in ILD patients with OPN > 1.03 ng/mL at 1, 3, and 5 years. No statistically significant differences in the genetic frequencies of OPN polymorphisms or the RNA expression were found among the different ILD groups. Elevated levels of OPN in the serum may be a useful indicator in identifying patients with ILD who are more likely to experience poor outcomes.

Diagnostic Value of Krebs von den Lungen (KL-6) for Interstitial Lung Disease: A European Prospective Cohort

IntroductionKrebs von den Lungen 6 (KL-6) is a mucin-1 glycoprotein produced by type II pneumocytes. High levels of KL-6 in blood may be found in patients with lung fibrosis. In Asia this biomarker is used for diagnosis and prognosis in interstitial lung diseases (ILD). There is a lack of information regarding KL-6 cut-off point for diagnosis and prognosis in European population. The aim of this study was to establish the cut-off point for serum KL-6 associated with the presence of ILD in the Spanish population. MethodsProspective study including subjects who underwent chest HRCT, PFTs and autoimmune blood analysis. Two groups were created: non-ILD subjects and ILD patients. Serum KL-6 concentrations were measured using a Lumipulse KL-6 reagent assay and the optimal cut-off value was evaluated by a ROC analysis. Data on demographics and smoking history was also collected. ResultsOne hundred seventy-nine patients were included, 102 with ILD. Median serum KL-6 values overall were 762U/mL, 1080 (±787)U/mL for the ILD group vs 340 (±152)U/mL for the non-ILD group (p<0.0001). The main radiological pattern was NSIP (43%). ROC analysis showed greater specificity (86%) and sensitivity (82%) for KL-6 465U/mL for detecting ILD patients. The multivariate logistic regression model pointed to the male sex, higher KL-6 values, lower FVC and low DLCO values as independent factors associated with ILD. ConclusionSerum KL-6 values greater than 465U/mL have excellent sensitivity and specificity for detecting ILD in our Spanish cohort. Multicentre studies are needed to validate our results.

Evaluating the diagnostic and therapeutic significance of KL-6 in patients with interstitial lung diseases

BackgroundThis study aimed to assess the diagnostic value of Krebs von den Lungen-6 (KL-6), Surfactant protein-A (SP-A), SP-D and molecular matrixmetalloproteinase-7 (MMP-7) in discriminating patients with interstitial lung diseases (ILDs) from disease control subjects. MethodsSerum levels of KL-6, SP-A, SP-D and MMP-7 were measured in both the ILD and non-ILD (NILD) groups. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic potential of these markers and laboratory indices. High-resolution computed tomography (HRCT) fibrosis scores were determined, and their correlation with the serum markers was analyzed. ResultsSerum levels of KL-6 and MMP-7 were significantly elevated in the ILD group compared to the control group, while no significant differences were observed for SP-A and SP-D. ROC analysis of KL-6 demonstrated superior diagnostic accuracy, with a sensitivity of 76.36%, specificity of 91.07%, and an area under curve (AUC) of 0.902 (95%CI 0.866–0.945). These findings were consistent across an additional cohort. Correlation analysis revealed a link between KL-6 levels at initial diagnosis and HRCT fibrosis scores, indicating disease severity. Moreover, a negative correlation was found between KL-6 and pulmonary function indices, reflecting disease progression. Patients with increased 12-month HRCT fibrosis score showed higher lactate dehydrogenase (LDH) levels, with LDH exhibiting an AUC of 0.767 (95% CI: 0.520–0.927) as a predictor of progression. ConclusionsSerum KL-6 detection proves to be a valuable tool for accurately distinguishing ILDs from control subjects. While KL-6 shows a correlation with HRCT fibrosis scores and a negative association with pulmonary function indices, its predictive value for ILDs prognosis is limited. Trial registrationThis study received retrospective approval from the Ethical Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (institutional review board ID: TJ-IRB20210331, date: 2021.03.30).

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...

Efficacy and safety of local ablative therapy for patients with NSCLC and coexisting interstitial lung disease.

The effective therapeutic approach is still an unmet need for patients diagnosed with both lung cancer and interstitial lung disease (ILD). This is primarily due to the possible risk of ILD exacerbation caused by surgery or radiotherapy. The current study aimed to investigate the efficacy and safety of local ablative therapy (LAT) for this specific population. Consecutive patients with non-small cell lung cancer (NSCLC) and ILD who received LAT between January 2018 and August 2022 were enrolled, and propensity score matching (PSM) was utilized to match the non-ILD group. The primary endpoint was recurrence-free survival (RFS), and secondary endpoints included overall survival (OS), adverse events (AEs) and hospital length of stay (HLOS). The PSM algorithm yielded matched pairs in the ILD group (n = 25) and non-ILD group (n = 72) at a ratio of 1:3. There were no statistically significant differences in RFS (median 16.4 vs. 18 months; HR = 1.452, p = 0.259) and OS (median: not reached vs. 47.9 months; HR = 1.096, p = 0.884) between the two groups. Meanwhile, no acute exacerbation of ILD was observed in the ILD group. However, the incidence of pneumothorax, especially pneumothorax requiring chest tube drainage, was significantly higher (36.0% vs. 11.2%, p = 0.005) among patients with NSCLC and co-existing ILD, which resulted in longer HLOS (p = 0.045). Although ILD was associated with a higher incidence of pneumothorax, the efficacy of LAT for NSCLC patients with ILD was comparable to those without ILD, suggesting that LAT might be a reliable and effective treatment option for this population, particularly in the early stage.

Forensic application of three interstitial pneumonia markers: search for new pneumonia markers in dead bodies.

In forensic cases, detailed identification of pneumonia is important. Our objective was to statistically determine the applicability of three interstitial lung disease (ILD) markers for forensic diagnosis using serum collected from dead bodies with various postmortem intervals (PMIs). We retrospectively analyzed the levels of postmortem serum Krebs von den Lungen-6 (KL-6) and pulmonary surfactant-associated proteins A and D (SP-A and SP-D) using 221 samples obtained during forensic autopsy at our facility from 2019 to 2023. We evaluated the diagnostic efficacy of ILD markers for various pneumonias against the pathological diagnosis, and examined the assessment of the severity of ILD. When comparing the ILD group with bacterial pneumonia (BP) versus the control group, there was a significant increase in KL-6 in the ILD group. When comparing the severe ILD (SILD) group with the mild ILD (MILD) group, there was a significant increase in KL-6 and SP-D in the SILD group. The optimal cutoff values for differentiating SILD were 607.0 U/mL for KL-6, 55.5ng/mL for SP-A, and 160.0ng/mL for SP-D, and the sensitivity/specificity (%) of KL-6, SP-A, and SP-D for SILD were 84.1/95.2, 55.6/85.7, and 66.7/74.6, respectively. This is the first study to examine KL-6 in postmortem serum in forensic medicine. By analyzing dead bodies with various PMIs, our results confirmed statistically that postmortem serum KL-6 specifically detects ILD, postmortem serum SP-A has high sensitivity to lung injury, and postmortem serum SP-D is potentially useful in assessing the severity of ILD.

Effect of pre-treatment with EGFR-TKIs on immune checkpoint inhibitor-associated interstitial lung disease in lung cancer patients: Analysis using a Japanese claims database.

Immune checkpoint inhibitors (ICI) and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) are key drugs for the treatment of EGFR mutation-positive lung cancer. While previous studies reported that the concomitant use of these drugs increases the risk of interstitial lung disease (ILD), the impact of sequential treatment on ILD risk is unknown. This study aimed to analyze the impact of EGFR-TKI pre-treatment on the risk of developing ILD after subsequent ICI administration. We conducted a retrospective study using a Japanese health insurance claims database. ILD-naive lung cancer patients who had first ICI administration during the screening period from July 2014 to February 2019 were selected. Patients who had ILD within 1 year of receiving the first ICI dose were included in the ILD group. Multivariate logistic regression analysis was conducted to evaluate the effect of pre-treatment with EGFR-TKI on the development of ICI-associated ILD. A total of 353 patients were included, of which 61 were included in the ILD group. The median time to onset of ILD after ICI administration was 3 months. Multivariate logistic regression analysis revealed that pre-treatment with EGFR-TKI was not associated with ICI-associated ILD (odds ratio: 0.26, 95% confidence interval: 0.033-2.01). Although further analyses are required to confirm our findings, this study indicated that pre-treatment with EGFR-TKI might not increase the ILD risk after ICI treatment.

Clinicopathological characteristics of everolimus-associated interstitial lung disease: A single-center consecutive analysis.

Everolimus, a mammalian target of rapamycin inhibitor used as an antineoplastic drug, is associated with a remarkably high incidence of interstitial lung disease (ILD). The clinical and pathological characteristics of ILD caused by everolimus have not been thoroughly investigated; therefore, we aimed to elucidate the features of everolimus-associated ILD. We retrospectively reviewed the medical records of patients who received everolimus for cancer treatment at our hospital. Patient backgrounds were compared between the ILD and non-ILD groups. Chest computed tomography (CT), changes in biomarkers, and lung histopathological features were analyzed for ILD cases. Sixty-six patients were reviewed, and ILD developed in 19. There were no differences in patient demographics between the ILD and non-ILD groups. The severity of ILD was grade 1 (G1) in 9 and grade 2 (G2) in 10 cases. Chest CT showed organizing pneumonia (OP) or a hypersensitive pneumonia pattern. The levels of lactate dehydrogenase, C-reactive protein, Krebs von den lungen-6, and surfactant protein-D (SP-D) at the onset of ILD were significantly higher than those at baseline. Analysis of G1 and G2 ILD subgroups showed a higher SP-D levels in the G2 subgroup. Five patients underwent lung biopsies; all specimens demonstrated alveolitis with lymphocytic infiltration and granulomatous lesions, and some had OP findings. Everolimus-associated ILD is mild and has a favorable prognosis. Patients with symptomatic ILD were more likely to have higher SP-D levels than those with asymptomatic ILD. Granulomatous lesions are an important pathological feature of everolimus-associated ILD.

Reproducibility of pulmonary function tests in patients with systemic sclerosis

Systemic sclerosis (SSc) is a rare autoimmune disease in which interstitial lung disease (ILD) is the leading cause of morbidity and mortality. Clinical management of the lung disease is mainly based on pulmonary function testing (PFT) and their changes over time. Little is known about the reproducibility of PFT testing in SSc patients. The aim of this study was to assess the test–retest reliability and reproducibility of PFTs in SSc patients with or without ILD over 30 days in order determine the potential physiologic variation over the time. We performed prospective observational study of SSc patients. The FVC, FEV1/FVC ratio, DLCO and KCO parameters were assessed in this population at four different timepoints; T0 (time 0) and H3 (T0 + 3 h) defined test–retest reliability, D15 (T0 + 15 days) and D30 (T0 + 30 days) for reproducibility. A mixed linear model was used to test the effect of time (and therefore reproducibility) on patients and we looked for an interaction. We included 25 SSc patients divided in two groups, 14 with ILD and 11 non-ILD. Interactions between time and group were not significant and were not reported. Time and group did not significantly influence the different measures of the PFT: FVC [p values time and group effect respectively (0.33; 0.34)], FEV1/FVC ratio (0.093; 0.056) and DLCO (0.99; 0.13) in the ILD and non ILD group (Table S2). The analyse with interactions between time and group were not significant and are not reported. We also used a Bland Altman test to assess reproducibility for FVC (L) and DLCO (mMKpa/min/L), Figs. 1 and 2 respectively. The measurements were therefore reproducible over time and in each group. PFT parameters are reproducible over time in a clinically stable population of SSc (no significant effect of the time T0, H3, D15 and D30) and there is no significant distinction between patients with ILD and no ILD. These respiratory functional data can further underline their use in clinical practice.

Clinical characteristics and prognostic analysis of idiopathic inflammatory myopathy with positive anti-aminoacyl-tRNA synthetase antibodies: A single center experience.

To identify the differences of clinical characteristics, laboratory findings, and the long-term outcomes in patients with anti-synthetase syndrome (ASS) of different anti-aminoacyl-transfer RNA synthetase antibodies. We retrospectively enrolled 119 patients with ASS, and the clinical characteristics and laboratory findings were collected. Additionally, multivariate COX regression analysis was performed to estimate the risk factors of prognosis in patients with ASS. The frequency of interstitial lung disease (ILD) reached 93.3% in our cohort, of 28 (23.5%) was classified as rapidly progressive (RP)-ILD. The highest incidence of RP-ILD was 36.4% in the PL12 group of ASS patients. The ILD group was characterized by an older age, a lower prevalence of V sign, and a higher prevalence of pulmonary symptoms when contrasted with the non-ILD group. There were statistical differences of clinical significance in arthritis, myositis, mechanic's hands, triad, shawl sign, V sign, and Raynaud's phenomenon among the four subgroups (all p < .05). Additionally, the prevalence rates of arthritis, myositis, mechanic's hands, triad, and V sign in the anti-Jo1 antibody-positive group were significantly higher than anti-Jo1 antibody-negative patients with ASS (all p < .05). Multivariate Cox regression analysis showed mechanic's hands (odds ratio [OR] = 6.47, p < .001), anti-nuclear antibodies (ANA) (OR = 2.13, p = .026), ILD (OR = 10.50, p < .001), and V sign (OR = 0.30, p = .007) were independent factors affecting the prognosis of patients with ASS. The incidences of RP-ILD, arthritis, myositis, triad, mechanic's hands, and shawl sign were more frequent in the anti-Ro52 antibody-positive group than the anti-Ro52 antibody-negative patients with ASS (all p < .05). Patients with ASS accompanied with ILD are highly prevalent. Mechanic's hands, ANA, and ILD may be a potential biomarker for predicting a poor prognosis in patients with ASS. Additionally, the detection of the anti-Ro52 antibody provides valuable insights for managing and predicting disease progression and long-term outcomes.

RETRACTED ARTICLE: Serum bilirubin levels in primary Sjögren’s syndrome: an association with interstitial lung disease

ObjectiveWe aimed to assess the association between serum bilirubin levels and interstitial lung disease (ILD) in patients with Primary Sjögren’s syndrome (pSS).Materials and methodsThe retrospectively analysis included 89 consecutive patients with pSS, we collected the clinical materials of pSS patients from the electronic medical records, and all pSS patients were divide into pSS with ILD group and pSS without ILD group.ResultsSerum bilirubin levels were significantly lower in pSS patients with ILD than those without ILD (p = 0.010). Serum bilirubin levels showed a significant negative correlation with erythrocyte sedimentation rate (ESR) (r = -0.321, p = 0.002) in patients with pSS. A multivariable logistic regression analysis confirmed that serum bilirubin presented an independent association with ILD in patients with pSS (OR = 0.841, 95%CI:0.728–0.972, p = 0.019).ConclusionSerum bilirubin is independently associated with ILD and therefore may be a promising marker of ILD in patients with pSS.

Efficacy and Safety of Nintedanib in Patients with Interstitial Lung Disease with or without Systemic Sclerosis: A Meta-Analysis.

Nintedanib is a potent intracellular inhibitor of tyrosine kinases and modulates the pathways involved in the development of fibrosis. We assessed nintedanib efficacy and safety in interstitial lung disease (ILD) patients. We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Register to identify available articles (up to April 2022). We conducted a meta-analysis of randomized controlled trials (RCTs) examining nintedanib efficacy and safety in patients with ILD with or without systemic sclerosis (SSc). Meta-analysis of five RCTs including 2,470 patients with ILD (1,343 nintedanib group and 1,127 controls) revealed that the annual rate of change in forced vital capacity (FVC) was significantly lower in the ILD group than in the control group (standardized mean difference [SMD] = 0.336; 95% confidence interval (CI) = 0.256-0.416, P<0.001). Stratification by disease type showed a low annual rate of change in FVC in patients with and without SSc (SMD = 0.389, 95% CI=0.294-0.478, P<0.001; SMD=0.177, 95% CI=0.013-0.340, P<0.00). The incidence of serious adverse events did not differ between the nintedanib and placebo groups; however, adverse events (AEs) and withdrawals due to AEs were significantly higher in the nintedanib group than in the placebo group (SMD =2.365, 95% CI=1.673-3.343, P<0.001; SMD =1.740, 95% CI= 1.385-2.185, P<0.001). Nintedanib is effective for ILD with or without SSc. However, it increased the incidence of AEs and withdrawals due to AEs.

Genetic Programs Between Steroid-Sensitive and Steroid-Insensitive Interstitial Lung Disease

The effectiveness of corticosteroids (GCs) varies greatly in interstitial lung diseases (ILDs). In this study, we aimed to compare the gene expression profiles of patients with cryptogenic organizing pneumonia (COP), idiopathic pulmonary fibrosis (IPF), and non-specific interstitial pneumonia (NSIP) and identify the molecules and pathways responsible for GCs sensitivity in ILDs. Three datasets (GSE21411, GSE47460, and GSE32537) were selected. Differentially expressed genes (DEGs) among COP, IPF, NSIP, and healthy control (CTRL) groups were identified. Functional enrichment analysis and protein–protein interaction network analysis were performed to examine the potential functions of DEGs. There were 128 DEGs when COP versus CTRL, 257 DEGs when IPF versus CTRL, 205 DEGs when NSIP versus CTRL, and 270 DEGs when COP versus IPF. The DEGs in different ILDs groups were mainly enriched in the inflammatory response. Further pathway analysis showed that “interleukin (IL)-17 signaling pathway” (hsa04657) and “tumor necrosis factor (TNF) signaling pathway” were associated with different types of ILDs. A total of 10 genes associated with inflammatory response were identified as hub genes and their expression levels in the IPF group were higher than those in the COP group. Finally, we identified two GCs’ response-related differently expressed genes (FOSL1 and DDIT4). Our bioinformatics analysis demonstrated that the inflammatory response played a pathogenic role in the progression of ILDs. We also illustrated that the inflammatory reaction was more severe in the IPF group compared to the COP group and identified two GCs’ response-related differently expressed genes (FOSL1 and DDIT4) in ILDs.

Clinical Characteristics and Risk Factors of Polymyositis and Dermatomyositis Combined with Interstitial Lung Disease in Patients Residing in the Northeast Sichuan Province of China.

Polymyositis (PM) and dermatomyositis (DM) are non-suppurative and autoimmune inflammatory diseases of striated muscle. Interstitial lung disease (ILD) is a group of heterogeneous diseases that mainly involve the pulmonary interstitium, alveoli, and/or bronchioles, also known as diffuse parenchymal lung disease (DPLD). A significant cause of death in persons with polymyositis (PM) and dermatomyositis (DM) is concurrent interstitial lung disease (ILD). However, research on the clinical characteristics and associated influencing factors of PM/DM combined with ILD (PM/DM-ILD) is currently scarce in China. The study aimed to probe the clinical features and risk factors of PM/DM-ILD. The data of 130 patients with PM/DM were gathered. General medical status, clinical symptoms, laboratory parameters, high-resolution CT, therapeutic outcomes, and prognoses were retrospectively reviewed in patients with PM/DM with (ILD group) and without (NILD) ILD. The age of the ILD group (n=65) was more than the NILD group (n=65), and the difference was statistically significant; there were no significant between-group variations in the PM/DM ratio, sex, or duration of the disease. The initial symptoms were arthritis and respiratory symptoms in the ILD group, and myasthenia symptoms in the NILD group. Incidences of Raynaud's phenomenon, dry cough, expectoration, dyspnea on exertion, arthritis, fever, total globulin (GLOB), erythrocyte sedimentation rate (ESR), and anti-Jo-1 antibody rate were higher for ILD; however, albumin (ALB), creatine kinase aspartate aminotransferase activity ratio (CK/AST) and CK levels were significantly lower in the ILD group. Bivariate logistic regression analysis showed age, dry cough, arthritis, dyspnea on exertion, anti-Jo-1 antibody, and elevated GLOB to be independent risk factors for ILD among patients with PM/DM. Advanced age, dry cough, arthritis, dyspnea on exertion, anti-Jo-1 antibody positivity, and elevated GLOB level are risk factors for PM/DM-ILD. This information could be utilized to carefully monitor changing lung function in these patients.

Treatment and Prognosis of Patients with Lung Cancer and Combined Interstitial Lung Disease.

Interstitial lung disease (ILD) is associated with a higher lung cancer (LC) risk and may impact cancer's clinical characteristics, treatment strategies, and outcomes. This impact's extent is unclear, particularly in Caucasians. In this retrospective observational study, we reviewed the files of all LC patients diagnosed in a 38-month period. Expert radiologists reviewed the computed tomography scans performed at diagnosis. Patients with LC and ILD (n = 29, 7%) were compared to those without ILD (n = 363, 93%) for population and cancer characteristics, treatments, and clinical outcomes. Patients with LC and ILD were older (73 ± 8 vs. 65 ± 11 years; p < 0.001). There was no significant difference in LC histology, localization, stage, or treatment modalities. The respiratory complication rate after cancer treatment was significantly higher in the ILD group (39% vs. 6%; p < 0.01). Overall survival rates were similar at 12 (52% vs. 59%; p = 0.48) and 24 months (41% vs. 45%; p = 0.64) but poorer in the ILD group at 36 months, although not statistically significant (9% vs. 39%; p = 0.06). The ILD group had a higher probability of death (hazard ratio (HR) = 1.49 [0.96;2.27]), but this was not statistically significant (p = 0.06). In a Cox regression model, patients with ILD treated surgically had a significantly higher mortality risk (HR = 2.37 [1.1;5.09]; p = 0.03). Patients with combined LC and ILD have worse clinical outcomes even when similar treatment modalities are offered.

Usefulness and performance evaluation of serum KL-6 and SP-A assays in healthy individuals and patients with interstitial lung disease

BackgroundInterstitial lung abnormalities (ILAs) are associated with the risk of progression to interstitial lung diseases (ILDs). Krebs von den Lungen 6 (KL-6) and surfactant protein (SP)-A have been used as biomarkers of ILDs. In this study, we evaluated the levels of these biomarkers and identified their clinical correlations in healthy individuals to assess their usefulness in the diagnosis of ILAs. MethodsThe patient samples were categorized into three groups: healthy, disease, and ILD groups. We used the automated immunoassay HISCL KL-6 and SP-A assay kits. The analytical performance evaluation involved precision, linearity, comparison, establishment of reference intervals, and determination of the cutoff points. We also analyzed the correlations between presence of abnormalities on chest radiography and computed tomography (CT) or pulmonary function test (PFT) and serum levels in the healthy group. ResultsKL-6 and SP-A assays showed good analytical performance. The KL-6 and SP-A cutoff values were 304 U/mL and 43.5 ng/mL between the ILD and healthy groups, respectively, which were lower than the values recommended by the manufacturer. In the clinical correlations with radiological findings, SP-A values in subjects with lung abnormalities on CT scans were significantly higher than those in normal scans. There was no significant difference in KL-6 and SP-A levels among PFT patterns; however, both serum levels in the mixed pattern showed higher values than those in the other patterns. ConclusionsThe results revealed a positive association between increased serum levels of SP-A and KL-6 and clinical characteristics as incidental findings on chest imaging and reduced lung function.

Resting pulmonary function and artery pressure and cardiopulmonary exercise testing in chronic heart failure patients in Taiwan − a prospective observational cross-sectional study comparing healthy subjects and interstitial lung disease patients

Background Restrictive ventilatory defects and elevated pulmonary artery pressure (PAP) are common in patients with chronic heart failure (CHF) and those with interstitial lung disease (ILD). However, as oxyhemoglobin desaturation seldom occurs in stable CHF patients at peak exercise, we hypothesized that the pathophysiology may be different between them. This study aimed to investigate: (1) PAP and lung function at rest, (2) pulmonary gas exchange (PGX) and breathing patterns at peak exercise, (3) mechanisms of dyspnea at peak exercise in patients with CHF compared to healthy subjects and ILD patients. Methods We consecutively enrolled 83 participants (27 with CHF, 23 with ILD, and 33 healthy controls). The CHF and ILD groups had similar functional status. Lung function and cardiopulmonary exercise tests with Borg Dyspnea Score were performed. PAP was estimated using echocardiography. Resting lung function, PAP and peak exercise data in the CHF group were compared to the healthy and ILD groups. Correlation analysis was performed to elucidate the mechanisms of dyspnea in the CHF and ILD groups. Results Compared to the healthy group, the CHF group had normal lung function, PAP at rest, and normal dyspnea score and PGX at peak exercise, whereas the ILD group had abnormal values compared to the CHF group. Dyspnea score was positively correlated with pressure gradient, lung expansion capabilities, and expiratory tidal flow in the CHF group (all p < 0.05), but inversely correlated with inspiratory time-related variables in the ILD group (all p < 0.05). Conclusion Normal lung function and PAP at rest, and dyspnea scores and PGX at peak exercise indicated that pulmonary hypertension and fibrosis were insignificant in the patients with CHF. The factors affecting dyspnea at peak exercise were different between the CHF and ILD groups. As the sample size in this study was small, large-scale studies are warranted to confirm our findings.

Impact of interstitial lung disease on clinical remission and unfavourable events of rheumatoid arthritis: results from the IORRA cohort.

We aimed to examine the impact of concomitant interstitial lung disease (ILD) on achieving clinical remission and the occurrence of unfavourable clinical events in patients with RA. Among the participants in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort from 2011 to 2012, patients not achieving remission of 28-joint disease activity score (DAS28) at baseline and those with chest CT images were enrolled. Based on the chest CT images, the patients were divided into two groups: the ILD group and non-ILD group. The associations among the presence of ILD with time to achieving DAS28 remission and development of death, hospitalized infection, major adverse cardiac events (MACE), or malignancy within 5 years were evaluated using time-dependent Cox regression models. We enrolled 287 patients in the ILD group and 1235 in the non-ILD group. DAS28 remission was achieved at least once in 55.7% and 75.0% of the ILD and non-ILD groups within 5 years, respectively. Presence of ILD was significantly associated with failure to achieve DAS28 remission (adjusted hazard ratio [aHR]: 0.71; 95% CI: 0.58, 0.89). ILD was also a significant factor associated with death (aHR: 3.24; 95% CI: 2.08, 5.03), hospitalized infection (aHR 2.60; 95% CI: 1.77, 3.83), MACE (aHR: 3.40; 95% CI: 1.76, 6.58), and lung cancer (aHR: 16.0; 95% CI: 3.22, 79.2), but not with malignant lymphoma (aHR: 2.27; 95% CI: 0.59, 8.81). Concomitant ILD was a significant factor associated with failure to achieve clinical remission and the occurrence of the unfavourable clinical events in patients with RA.

A meta-analysis of the clinical significance of neutrophil-to-lymphocyte ratios in interstitial lung disease.

Interstitial lung disease (ILD) is a group of diffuse parenchymal infiltrating diseases of different etiologies. The neutrophil-to-lymphocyte ratio (NLR) can reflect ILD's existence, progression, and prognosis and is currently regarded as a promising biological marker. This meta-analysis assessed elevated NLR levels in ILD for their predictive value. From inception to July 27, 2022, the Scopus, Cochrane Library, Web of Science, Embase, and PubMed databases were checked thoroughly. We used the weighted mean difference (WMD) and 95% confidence interval (CI) to compare blood NLR values between groups. We examined the relationship between poor prognoses and elevated NLR concentrations in ILD patients using odds ratios (ORs) and 95% CI. After initially including 443 studies, 24 were ultimately analyzed. Fifteen studies(ILD:n = 2,912, Non-ILD: n = 2,868) revealed that the NLR values in the ILD group were relatively high (WMD = 0.61, 95% CI 0.43-0.79, p = 0.001). Eight articles (with poor prognoses: n = 407, without poor prognoses: n = 340) indicated that ILD patients with poor prognoses had higher NLR values (WMD = 1.33, 95% CI 0.32-2.33, p = 0.01). This distinction was especially noticeable in patients with the connective tissue disease (CTD)associated with ILD subgroup (WMD = 3.53, 95% CI 1.54-5.51, p = 0.0005). The pooled OR for increased NLR levels forecasting poor prognoses of ILD was 1.09 (95% CI 1.03-1.15, p = 0.0008). Increasing blood NLR values have clinical significance and application value for detecting ILD and predicting its poor prognosis, especially in CTD patients.