Presence Of Interstitial Lung Disease Research Articles

Incidence Rates of Infections in Rheumatoid Arthritis Patients Treated with Janus Kinase or Interleukin-6 Inhibitors: Results of a Retrospective, Multicenter Cohort Study.

Objective: This study aimed to compare the incidence rates (IRs) of infections, including herpes zoster (HZ), in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKis) or interleukin-6 inhibitors (IL-6is). Methods: We retrospectively analyzed 444 RA patients treated using IL-6is (n = 283) or JAKis (n = 161). After adjusting for clinical characteristic imbalances by propensity score matching (PSM), we compared the IRs of infections including HZ between the JAKi and IL-6i groups. Results: Observational period: 1423.93 patient years (PY); median observational period: 2.51 years. After PSM, incidence rate ratios comparing JAKi with IL-6i were 3.45 (95% confidence interval [CI]: 1.48-9.04) for serious infections other than HZ indicating that the JAKi-treated group was more likely to develop serious infection than the IL-6i-treated group. Multivariate Cox regression analyses revealed that the use of prednisolone > 5.0 mg/day, coexisting interstitial lung disease (ILD), and diabetes mellitus (DM) were independent risk factors for serious infections. The crude IR for HZ was significantly higher in the JAKi group, but the difference between groups was not significant (IRR: 2.83, 95% CI: 0.87-10.96) in PSM analysis. Unadjusted and PSM analyses performed in our study showed increased IRs of serious infections in patients with RA treated with JAKis compared with those treated with IL-6is. Conclusions: The presence of ILD or DM and the use of prednisolone were found to be independent risk factors for serious infection in RA patients treated using JAKis. Whereas the IRs for HZ after PSM were not significantly different between the JAKi and IL-6i groups.

P149 Association between nailfold videocapillaroscopy findings and sKL-6 levels in patients with idiopathic inflammatory myopathies-related interstitial lung disease

Abstract Background/Aims Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of acquired muscle diseases with distinct clinical, pathological and histological features. Interstitial lung disease (ILD) is a frequent pulmonary manifestation in IIM (IIM-ILD) and considerably influences morbidity and mortality. Krebs von den Lungen 6 (sKL-6) has been proposed as a potential biomarker reflecting the severity of ILD in connective tissue diseases. Raynaud’s phenomenon is very frequent and the presence of microvascular changes in IIM have been described however, the role of nailfold videocapillaroscopy (NVC) in diagnosis and prognosis in IIM is not clearly established. We aim to determine if there is any association between NVC findings, sKL-6 levels and pulmonary involvement in patients with inflammatory myopathies. Methods We performed a retrospective study of IIM patients followed in a reference center and compared them according to the presence of ILD. Epidemiological, clinical and immunological data, pulmonary function tests (forced vital capacity and diffusing capacity for carbon monoxide), sKL-6 levels and NVC finding were retrieved. Statistical analysis was performed by T-test and Fisher’s exact test to compare qualitative and/or quantitative variables and multiple logistic regression modelling to identify correlation between pulmonary function tests, NVC findings and sKL-6 levels. Results 95 patients were included, 47 patients (49%) with ILD. 34% were male with a median age at inclusion of 55.3±24 years. Avascular areas and capillary lossshowed a significant association with the presence of ILD (OR 2.43, 95% CI 1.3-5.7, p 0.004) and (OR 1.7, 95% CI 1.48-3.1, p 0.04). A negative correlation between capillary loss and enlarged capillaries was also found with FVC% (β=-0.46, p 0.001 and β=-0.57, p < 0.0001) and DLCO% (β=-0.32, p 0.04 and β=- 0.23, p 0.03), respectively. When we studied the correlation between sKL-6 levels, positive correlations with the presence of ILD (β = 0.77, p 0.0004), the presence of hemorrhages (β = 0.21, p 0.04) and avascular areas in NVC (β = 0.64, p 0.03) and negative correlations with FVC% (β=-0.47, p 0.001) and DLCO% (β=-0.59, p, 0.005) were found. Male sex, respiratory symptoms, %FVC and %DLCO, sKL-6 levels, anti-Jo1 positivity and the presence of avascular areas and enlarged capillaries in NVC were identified as IIM-ILD predictors (R2=0.974, p = 0.006). Conclusion Capillary loss and avascular areas showed a significant association with the presence of ILD, worse FVC and DLCO values and sKL-6 levels. We identified nine predictors for developing ILD in IIM. NVC assessment and sKL-6 levels can have a predictive role for studying pulmonary function and assessing the prognosis of IIM-ILD. Disclosure C. Sieiro Santos: None. J. Tandaipan: None. D. Castillo: None. L. Martínez Martínez: None. H. Codes: None. L. Sainz: None. B. Magallares: None. P. Moya: None. H. Corominas: None. E. Díez Álvarez: None. I. Castellvi: None.

E062 Nailfold capillaroscopy: its application in routine clinical practice

Abstract Background/Aims Nailfold capillaroscopy (NFC) is a non-invasive tool to evaluate the structural microvascular abnormalities found in systemic sclerosis (SSc). NFC allows for the visualization of the capillary bed at the nailfold, providing valuable insights into the structure and function of these capillaries. NFC helps differentiate primary from secondary Raynaud’s phenomenon (RP). Abnormal NFC is included in the 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria and due to its predictive value of developing SSc is included in the Very Early Diagnosis of SSc (VEDOSS) criteria. Dudley Group NHS FT runs a consultant-led service supported by a specialty trainee where clinical review is carried out alongside NFC using video capillaroscopy. Patients can be referred to this clinic from rheumatology or respiratory colleagues. Methods We audited all patients who had attended a monthly NFC clinic between September 2021 and October 2023. We reviewed clinical letters and electronic patient record system and collected details of: demographics; immunology; clinical characteristics; reason for attending the clinic; NFC findings; and diagnosis. NFC findings were classified as normal or abnormal (to include scleroderma pattern and non-specific changes). Data was analysed using excel for individual variables and their comparison with nailfold capillaroscopy results. Results We identified 80 patients, of which 63 (79%) were females and median age was 54.5 years. ANA was positive in 64 (80%) patients, SSc and myositis immunology blots were positive in 41 (51%) and 4 (5%) respectively. Clinical characteristics included RP in 71 (89%) and interstitial lung disease (ILD) in 17 (21%). The reasons for attending the NFC clinic were categorised as: to exclude secondary causes of RP (52; 65%); to aid diagnosis of suspected SSc (23; 29%); surveillance of known SSc (5; 6%). NFC was normal in 42 patients. In the 38 patients where NFC was abnormal the clinical diagnosis was categorised as: primary RP (8; 10%); SSc spectrum of disease (17; 21%); and another CTD (20; 25%). Of patients with SSc spectrum of disease: 24% (4/17) had a diagnosis of VEDoSS; 47% (8/17) Limited Cutaneous SSc; and 29% (5/17) Diffuse SSc. The presence of RP and ANA was not significantly different in patients with abnormal NFC. There was a non-significant association between the presence of ILD and abnormal NFC. 9/17 (52%) patients with ILD had an abnormal NFC compared to 18/63 (29%) patients without ILD (p = 0.059). Conclusion NFC is a simple procedure in conjunction with a clinical review to enhance the early diagnosis of SSc and exclusion of secondary Raynaud’s. It supports education and training as a tool for learning as being part of the curriculum. Disclosure S.A. Tabassum: None. K.M.J. Douglas: None. E. Udeshika: None.

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.

Analyzing key elements of breathing patterns, deriving remaining variables, and identifying cutoff values in individuals with chronic respiratory disease and healthy subjects

BackgroundPulmonary physiology encompasses intricate breathing patterns (BPs), characterized by breathing frequency (Bf), volumes, and flows. The complexities intensify in the presence of interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD), especially during exercise. This study seeks to identify pivotal factors driving changes among these variables and establish cutoff values, comparing their efficacy in differentiating BPs to traditional methods, specifically a breathing reserve (BR) of 30% and a Bf of 50 bpm. MethodsScreening 267 subjects revealed 23 with ILD, 126 with COPD, 33 healthy individuals, and the exclusion of 85 subjects. Lung function tests and ramp-pattern cardiopulmonary exercise testing (CPET) were conducted, identifying crucial BP elements. Changes were compared between groups at peak exercise. The area under the receiver operating characteristic curve (AUC) analysis determined cutoff values. ResultsInspiratory time (TI) remained constant at peak exercise for all subjects (two-group comparisons, all p=NS). Given known differences in expiratory time (TE) and tidal volume (VT) among ILD, COPD, and healthy states, constant TI could infer patterns for Bf, total breathing cycle time (TTOT=60/Bf), I:E ratio, inspiratory duty cycle (IDC, TI/TTOT), rapid shallow breathing index (Bf/VT), tidal inspiratory and expiratory flows (VT/TI and VT/TE), and minute ventilation (V̇E=Bf×VT) across conditions. These inferences aligned with measurements, with potential type II errors causing inconsistencies. RSBI of 23 bpm/L and VT/TI of 104 L/min may differentiate ILD from control, while V̇E of 54 L/min, BR of 30%, and VT/TE of 108 may differentiate COPD from control. BR of 21%, TE of 0.99 s, and IDC of .45 may differentiate ILD from COPD. The algorithm outperformed traditional methods (AUC 0.84–0.91 versus 0.59–0.90). ConclusionThe quasi-fixed TI, in conjunction with TE and VT, proves effective in inferring time-related variables of BPs. The findings have the potential to significantly enhance medical education in interpreting cardiopulmonary exercise testing. Moreover, the study introduces a novel algorithm for distinguishing BPs among individuals with ILD, COPD, and those who are healthy.

Protein profiling in systemic sclerosis patients with different pulmonary complications using proteomic antibody microarray

BackgroundPulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) are leading causes of systemic sclerosis (SSc)-related death. In this study, we aimed to identify biomarkers for detecting SSc pulmonary complications that are mild and in the early stages to improve the prognosis.MethodsWe screened for serum biomarkers using a proteomic antibody microarray that simultaneously assessed 1000 proteins. Differentially expressed proteins were further verified using ELISA. Finally, we performed a correlation analysis using clinical data.ResultsWe identified 125 differentially expressed proteins, of which calcitonin, sclerostin (SOST), CD40, and fibronectin were selected for further verification. Serum calcitonin and SOST levels were significantly elevated in all SSc pulmonary complication subgroups, whereas serum calcitonin levels were higher in the SSc with PAH subgroup than in the SSc without PAH and ILD subgroup. Serum SOST levels were possibly associated with the presence of ILD and positively related to the presence of cardiac and gastrointestinal involvement. Serum CD40 and calcitonin levels appeared to be positively related to the presence of renal involvement, and serum calcitonin was also positively related to the presence of gastrointestinal involvement.ConclusionsThis study indicated that serum calcitonin and SOST levels may be promising biomarkers for SSc-related PAH and ILD, respectively. Further research is needed to verify this result and understand the underlying mechanisms.

Lupus hands mimicking psoriatic arthritis.

We report a case of a 68-year-old woman with chronic and severely destructive arthritis for 8 years with imaging features mimicking psoriatic arthritis (PsA) but serological evidence of systemic lupus erythematosus. Both the lupus panniculitis-like rash and the presence of interstitial lung disease were considered manifestations of systemic involvement of SLE.

Clinical characteristics and prognostic factors of non-tuberculous mycobacterial disease in patients with rheumatoid arthritis.

This study aimed to identify the clinical characteristics of patients with concurrent rheumatoid arthritis (RA) and suspected non-tuberculous mycobacterial (NTM) infections as well as determine their prognostic factors. We retrospectively reviewed the medical records of 91 patients with RA whose computed tomography (CT) findings suggested NTM infection. Subsequently, we compared the clinical characteristics between patients with and without clinical or radiological exacerbation of NTM-pulmonary disease (PD) and investigated the risk factors for the exacerbation and associated mortality. The mean age of patients with RA and suspected NTM-PD was 65.0 ± 10.2 years. The nodular/bronchiectatic (NB) form of NTM-PD was the predominant radiographic feature (78.0%). During follow-up, 36 patients (41.9%) experienced a radiological or clinical exacerbation of NTM-PD, whereas 12 patients (13.2%) died. Combined interstitial lung disease (ILD), microbiologically confirmed NTM-PD, and NB with the fibrocavitary (FC) form on chest CT were identified as risk factors for the clinical or radiological exacerbation of NTM-PD. Hydroxychloroquine use was identified as a good prognostic factor. Conversely, history of tuberculosis, ILD, smoking, microbiologically confirmed NTM-PD, and NB with the FC form on chest CT were identified as poor prognostic factors for mortality in suspected NTM-PD. ILD and NB with the FC form on chest CT were associated with NTM-PD exacerbation and mortality. Hydroxychloroquine use may lower the risk of NTM-PD exacerbation. Therefore, radiographic features and presence of ILD should be considered when predicting the prognosis of patients with RA and suspected NTM-PD.

Antisynthetase syndrome: a case report and review of the literature.

antisynthetase syndrome is a rare autoimmune disease characterized byinterstitial lung disease, non-erosive arthritis, myositis, Raynaud&amp;#39;s disease, and/or &amp;quot;mechanichand&amp;quot; when autoantibodies directed against aminoacyl-tRNA synthetases are detected.Antisynthetase syndrome belongs to the group of idiopathic inflammatory myopathies and isthe so-called overlap myositis. The article provides the latest literature data on the diagnosticvalue of myositis-specific autoantibodies based on a literature review for the period from2013 to 2023 using the scientometric databases MEDLINE/ PubMed, Wiley Online Library,and Scopus. Data from the literature show that certain myositis-specific autoantibodies,namely anti-PL-7 and anti-PL-12, can affect the risk of developing interstitial lung disease,and determine the course and prognosis of the disease. The presence of interstitial lungdisease in patients with myositis correlates with increased morbidity and mortality. Thearticle describes a clinical case of the debut of the antisynthetase syndrome from interstitiallung disease, which was falsely diagnosed as a coronavirus disease. The patient&amp;#39;s condition&#x0D; improved only because of using glucocorticoids, which the patient stopped taking over time,which led to the worsening of pulmonary symptoms, the appearance of new clinical signs ofdamage to the joints and skin, progressive decrease in muscle function, and dysphagia. Afteran examination in the rheumatology department, based on the presence of interstitial lungdisease in the patient - fibrotic alveolitis, which was confirmed by computer tomography,myositis, arthritis, characteristic skin changes, the presence of antinuclear antibodies, anti-SS-A/Ro52, specific antisynthetase antibodies (Jo-1, Pl-7, Pl-12), the diagnosis of theantisynthetase syndrome was established. A detailed laboratory and instrumental examinationmade it possible to rule out a paraneoplastic process at the time of examination. Theprescribed treatment included pulse therapy with methylprednisolone and cyclophosphamide,which led to improvement in the patient&amp;#39;s condition. The work carried out emphasizes theneed for interdisciplinary interaction of pulmonologists, rheumatologists, and infectiousdisease specialists at the stage of verification of the final diagnosis and the therapyappointment. Achieving clinical and laboratory remission of the disease requires long-termmonitoring by a rheumatologist.

Ways to predict interstitial lung disease in patients with systemic sclerosis: results of an observational study

In patients with systemic sclerosis (SSc), interstitial lung disease (ILD) is a factor in the decline of functional capacity up to disability and is also the leading cause of death. Therefore, one of the most important tasks in the treatment of this group of patients is not only to detect involvement of respiratory system, but also to predict the likelihood of its development.Objective: to study the possibility of predicting the development of ILD and advanced ILD in patients with SSc.Material and methods. The study included 79 patients with SSc (mean age 64.4±11.5 years; 94.9% women) from the Registry of myositis, SSc and Mixed Connective Tissue Diseases (РЕМИССиС) who underwent high-resolution computed tomography (HRCT) of the lungs. Classification trees (CTr) were constructed to predict the development of widespread ILD using the CHAID algorithm (exhaustive). All patients were tested for antibodies against Scl-70 (anti-Scl-70), CENP-B (anti-CENP-B), and PmScl (anti-PmScl).Results and discussion. ILD signs according to HRCT were detected in 53 patients. Fibrotic (34.2%) and cellular (15.2%) types of nonspecific interstitial pneumonia were the most common, and common interstitial pneumonia was less frequent (11.4%).The presence of ILD and advanced ILD (involvement of more than 20% of the lung parenchyma) were significantly associated with the detection of any autoantibodies, except anti-centromere antibodies, an increase in pulmonary artery systolic pressure, a decrease in forced vital capacity, diffusing capacity of the lungs, blood oxygen saturation at rest, and all parameters of six-minute walk test (6MWT), and complaints of shortness of breath. In addition, the presence of extensive ILD was also significantly associated with diffuse SSc and with SSc without skin manifestations.In establishing the CTr, it was found that the development of widespread ILD was unlikely in individuals who were able to walk more than 440 m in 6MWT and had neither anti-Scl-70 nor anti-PmScl.Significant associations were also found between the radiological pattern of ILD and the types of disease-specific antibodies.Conclusion. The 6MWT data in conjunction with the results of testing for SSc-specific autoantibodies provide a very accurate prediction of the presence and extent of ILD. It is advisable to include these indicators in the algorithm for screening and monitoring patients with SSc.

Lung Ultrasound in Diagnosis of Interstitial Lung Disease.

Interstitial lung disease denotes a group of disorders which mainly affects pulmonary interstitium consisting of connective tissue fibers that support the lungs. High-resolution computed tomography is currently the main imaging modality of diagnosis, however except for few major cities in the country, availability of computed tomography scan facility is sparse in remote areas; thus relevant use of lung ultrasound in patients with suspected interstitial lung disease could be rewarding. A single center cross-sectional clinical diagnostic study was carried out at department of Radiology and Imaging, Patan Academy of Health Sciences after approval from institutional review committee. Lung ultrasound was done prior to patients undergoing high-resolution computed tomography chest. Senstivity, specificity, positive predictive value , negative predictive value , and accuracy of different echographic criteria-positive chest area score, total B lines score 5 and total B lines score 10 were calculated. Association of non-homogeneity of B lines and pleural line abnormalities with presence of interstitial lung disease, and association between B3 and B7 lines with alveolar and interstitial pattern were derived. Sensitivity (97.4%) and negative predictive value (97.9%) of total B lines score 5 was the highest. Maximum specificity (70.7%), PPV (61.4%) and accuracy (77.2%) was ofpositive chest area score. Pleural line abnormalities showed highly significant association with interstitial lung disease(p=0.003). B3 and B7 lines illustrated very highly significant association with alveolar and interstitial pattern respectively (p<0.001). Lung ultrasound can be a valid and reliable additional imaging method in evaluation of ILD in appropriate clinical scenario.

Clinical and autoantibody profiles of systemic sclerosis patients: A cross-sectional study from North India.

Objectives This cross-sectional study was designed to assess the clinical profile and frequency of associated autoantibodies in all consecutive patients classified as systemic sclerosis (SSc) at Medanta-the Medicity Hospital, Gurgaon, India. Methods Between August 2017 and July 2019, we identified a total of 119 consecutive patients meeting the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2013 criteria for SSc and 106 patients consented to this study. Their clinical and serological data at the time of enrolment were analysed. Results Our cohort had a mean age at symptom onset of 40 ± 13 years with a median symptom duration of 6 years. We had 76 patients (71.7%) with interstitial lung disease (ILD), which was a higher proportion compared to European cohorts. 62 patients (58.5%) had diffuse cutaneous involvement which was significantly associated with anti-Scl70 antibodies (p < 0.001), digital ulcers (p = 0.039) and the presence of ILD (p = 0.004). 65 patients (61.3%) had anti-Scl70 and 15 patients (14.2%) had anti-centromere (anti-CENP) antibodies. Scl70 positivity was associated with the presence of ILD (p < 0.001) and digital ulcers (p = 0.01). Centromere antibodies had a negative association with ILD (p < 0.001), but was a risk factor for calcinosis (p < 0.001) and pulmonary arterial hypertension (PAH) (p = 0.01). The combination of diffuse cutaneous disease and Scl70 antibodies was the strongest predictor of ILD and digital ulcers (p = 0.015). sm/RMP, RNP68 and Ku antibodies correlated with musculoskeletal involvement (p < 0.01), while all seven of the patients with Pm/Scl antibodies had ILD. Renal involvement was noted in only two patients. Limitations A single-centre study may not capture the true prevalence of disease characteristics in the population. Referral bias for patients with diffuse cutaneous disease has been noted. Data on RNA-Polymerase antibodies have not been provided. Conclusion North Indian patients have some characteristic differences in disease phenotype as compared to their Caucasian counterparts with a larger proportion of patients presenting with ILD and Scl70 antibodies. Antibodies against Ku, RNP and Pm/Scl occur in a minority of patients, but may be associated with musculoskeletal features.

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.

Serum metabolomic profiling reveals potential biomarkers in systemic sclerosis

BackgroundSystemic sclerosis (SSc) is a chronic and systemic autoimmune disease marked by the skin and visceral fibrosis. Metabolic alterations have been found in SSc patients; however, serum metabolomic profiling has not been thoroughly conducted. Our study aimed to identify alterations in the metabolic profile in both SSc patients before and during treatment, as well as in mouse models of fibrosis. Furthermore, the associations between metabolites and clinical parameters and disease progression were explored. MethodsHigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS)/MS was performed in the serum of 326 human samples and 33 mouse samples. Human samples were collected from 142 healthy controls (HC), 127 newly diagnosed SSc patients without treatment (SSc baseline), and 57 treated SSc patients (SSc treatment). Mouse serum samples were collected from 11 control mice (NaCl), 11 mice with bleomycin (BLM)-induced fibrosis and 11 mice with hypochlorous acid (HOCl)-induced fibrosis. Both univariate analysis and multivariate analysis (orthogonal partial least-squares discriminate analysis (OPLS-DA)) were conducted to unravel differently expressed metabolites. KEGG pathway enrichment analysis was performed to characterize the dysregulated metabolic pathways in SSc. Associations between metabolites and clinical parameters of SSc patients were identified by Pearson's or Spearman's correlation analysis. Machine learning (ML) algorithms were applied to identify the important metabolites that have the potential to predict the progression of skin fibrosis. ResultsThe newly diagnosed SSc patients without treatment showed a unique serum metabolic profile compared to HC. Treatment partially corrected the metabolic changes in SSc. Some metabolites (phloretin 2’-O-glucuronide, retinoyl b-glucuronide, all-trans-retinoic acid, and betaine) and metabolic pathways (starch and sucrose metabolism, proline metabolism, androgen and estrogen metabolism, and tryptophan metabolism) were dysregulated in new-onset SSc, but restored upon treatment. Some metabolic changes were associated with treatment response in SSc patients. Metabolic changes observed in SSc patients were mimicked in murine models of SSc, indicating that they may reflect general metabolic changes associated with fibrotic tissue remodeling. Several metabolic changes were associated with SSc clinical parameters. The levels of allysine and all-trans-retinoic acid were negatively correlated, while D-glucuronic acid and hexanoyl carnitine were positively correlated with modified Rodnan skin score (mRSS). In addition, a panel of metabolites including proline betaine, phloretin 2’-O-glucuronide, gamma-linolenic acid and L-cystathionine were associated with the presence of interstitial lung disease (ILD) in SSc. Specific metabolites identified by ML algorithms, such as medicagenic acid 3-O-b-D-glucuronide, 4’-O-methyl-(−)-epicatechin-3’-O-beta-glucuronide, valproic acid glucuronide, have the potential to predict the progression of skin fibrosis. ConclusionsSerum of SSc patients demonstrates profound metabolic changes. Treatment partially restored the metabolic changes in SSc. Moreover, certain metabolic changes were associated with clinical manifestations such as skin fibrosis and ILD, and could predict the progression of skin fibrosis.

Outcomes following cryoablation of stage IA non-small cell lung cancer in patients with and without interstitial lung disease: A retrospective single-center cohort study

ObjectiveTo compare the safety and efficacy of cryoablation of treatment-naïve stage IA non-small cell lung cancer (NSCLC) in patients with and without interstitial lung disease (ILD). Materials and MethodsThis retrospective single-center cohort study evaluated 33 consecutive patients (24 females, median age 75 years, Eastern Cooperative Oncology Group performance score 0–3) with ILD (9 patients) and without ILD (24 patients) who underwent 39 percutaneous cryoablations to treat 42 stage IA (8th IASLC edition) NSCLC measuring 1.2 cm (range 0.5–2.6 cm) from 2018 to 2022. Presence of ILD was determined according to 2018 American Thoracic Society Criteria on pre-ablation CT scans. The primary outcome was 90-day adverse events graded by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Secondary outcomes were hospital length of stay (LOS), local recurrence-free survival, overall survival, and the cumulative incidence of local recurrence with death as a competing risk. ResultsAdverse events ranged from grade 1–3 and occurred more often in the non-ILD group (p <.001). No acute exacerbation of ILD or death occurred within 90 days after cryoablation. The median LOS was 1 day (interquartile range 1–2 days) and did not differ between groups. One patient with ILD and two patients without ILD died after 22, 26, and 27 months from causes unrelated to cryoablation. Median imaging follow-up was 11 months (range, 0–47 months) and three tumors (7%) showed local recurrence after 4, 17, and 22 months. No difference in the cumulative incidence of local recurrence (p =.56) was found. Among all patients, local recurrence-free survival on a per-tumor basis and overall survival were 97% and 100% at 1 year, respectively. ConclusionAdverse events and local recurrence following percutaneous cryoablation of stage IA NSCLC did not differ between patients with and without ILD. No acute exacerbation of ILD or death within 90 days were observed.

Prevalence of myositis specific and associated antibodies in a cohort of patients affected by idiopathic NSIP and no hint of inflammatory myopathies.

The presence of interstitial lung disease (ILD) is a common and fearsome feature of idiopathic inflammatory myopathies (IIM). Such patients show radiological pattern of non-specific interstitial pneumonia (NSIP). The present study aimed to assess the prevalence of myositis-specific and myositis-associated antibodies (MSA and MAA) in a cohort of patients with a previous diagnosis of NSIP and no sign or symptom of IIM. Secondly, it will be assessed whether patients displaying MSA and/or MAA positivity have a worse or a better outcome than idiopathic NSIP. All patients affected by idiopathic NSIP were enrolled. MSA and MAA were detected using EUROLINE Autoimmune Inflammatory Myopathies 20 Ag (Euroimmun Lubeck, Germany), line immunoassay. A total of 16 patients (mean age 72 ± 6.1years old) were enrolled. Six out of 16 patients (37.5%) had significant MSA and/or MAA positivity: one displayed positivity of anti-PL-7 (+ +), one of anti-Zo (+ +), anti-TIF1γ (+ + +) and anti-Pm-Scl 75 (+ + +), one of anti-Ro52 (+ +), one of anti-Mi2β (+ + +), one of anti-Pm-Scl 75 (+ + +) and the latter of both anti-EJ (+ + +) and anti-Ro52 (+ + +).Two out of 7 seropositive patients showed a significant impairment of FVC (relative risk 4.8, 95% CI 0.78-29.5; p = 0.0350). Accordingly, among the 5 patients that started antifibrotic treatment during the observation time, 4 were seronegative. Our findings highlighted a potential autoimmune or inflammatory in idiopathic NSIP patients and also in those without significant rheumatological symptoms. A more accurate diagnostic assessment may ameliorate diagnostic accuracy as well as may provide new therapeutic strategy (antifibrotic + immunosuppressive). A cautious assessment of NSIP patients with a progressive and non-responsive to glucocorticoids disease course should therefore include an autoimmunity panel comprising MSA and MAA.

Pulmonary Ultrasonography in Systemic Sclerosis-Induced Interstitial Lung Disease—A Systematic Review and Meta-Analysis

Background: The aim of the current systematic review was to summarize and evaluate the overall advantages of lung ultrasonography (LUS) examination using high-resolution computed tomography (HRCT) as a reference standard in assessing the presence of interstitial lung disease (ILD) in systemic sclerosis (SSc) patients. Methods: Databases PubMed, Scopus, and Web of Science were searched for studies evaluating LUSs in ILD assessments including SSc patients on 1 February 2023. In assessing risk of bias and applicability, the Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used. A meta-analysis was performed and the mean specificity, sensitivity, and diagnostic odds ratio (DOR) with a 95% confidence interval (CI) were obtained. In addition, in a bivariate meta-analysis, the summary receiver operating characteristic (SROC) curve area was additionally calculated. Results: Nine studies with a total of 888 participants entered the meta-analysis. A meta-analysis was also performed without one study that used pleural irregularity to assess the diagnostic accuracy of LUSs using B-lines (with a total of 868 participants). Overall sensitivity and specificity did not differ significantly, with only the analysis of the B-lines having a specificity of 0.61 (95% CI 0.44–0.85) and a sensitivity of 0.93 (95% CI 0.89–0.98). The diagnostic odds ratio of univariate analysis of the eight studies using the B-lines as a criterion for ILD diagnosis was 45.32 (95% CI 17.88–114.89). The AUC value of the SROC curve was 0.912 (and 0.917 in consideration of all nine studies), which indicates high sensitivity and a low false-positive rate for the majority of the included studies. Conclusions: LUS examination proved to be a valuable tool in discerning which SSc patients should receive additional HRCT scans to detect ILD and therefore reduces the doses of ionizing radiation exposure in SSc patients. However, further studies are needed to achieve consensus in scoring and the evaluation methodology of LUS examination.

Serum cold-inducible RNA-binding protein levels as a potential biomarker for systemic sclerosis-associated interstitial lung disease

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by fibrotic, inflammatory, and vascular dysfunction. Danger-associated molecular patterns (DAMPs)-mediated inflammasome activation has been reported to be involved in the pathogenesis of SSc. Cold-inducible RNA-binding protein (CIRP) is newly identified as a DAMP. Here we examined the clinical significance of serum levels of CIRP in 60 patients with SSc and 20 healthy control patients (HCs) using an enzyme-linked immunosorbent assay. Serum CIRP levels in diffuse cutaneous SSc (dcSSc) patients were significantly increased compared with limited cutaneous SSc (lcSSc) patients or HCs. When examining the relationship with SSc-specific parameters, serum CIRP levels with the presence of interstitial lung disease (ILD) were higher than those without ILD. In detail, serum CIRP levels correlated negatively with the percent predicted diffusing capacity for carbon monoxide and positively with levels of Krebs von den Lungen-6. In addition, elevated serum CIRP levels declined along with decreased SSc-ILD activity in patients who received immunosuppressive therapy. These results suggest that CIRP may play a role in the development of ILD in SSc. Moreover, CIRP could serve as a useful serological marker of SSc-ILD in terms of disease activity and therapeutic effects.

Clinical characteristics of rheumatoid arthritis patients with interstitial lung disease: baseline data of a single-center prospective cohort

BackgroundTo introduce a prospective cohort for rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) and to identify their clinical features in comparison with RA patients without ILD.MethodsUsing a multidisciplinary collaborative approach, a single-center cohort for RA patients with ILD (RA-ILD) was established in May 2017, and enrolment data from May 2017 to March 2021 were used to compare the clinical features of RA patients without ILD (RA-non ILD). Multivariable logistic regression analysis was used to identify factors associated with ILD in RA patients.ResultsAmong 148 RA-ILD and 410 RA-non ILD patients, participants in the RA-ILD group were older (65.8 ± 9.9 vs. 58.0 ± 10.4 years, P < 0.001) and included more males (35.8% vs. 14.6%, P < 0.001) than in the RA-non ILD group. The RA-ILD group had a higher proportion of late-onset RA patients (age ≥ 60 years) than in the comparator group (43.9% vs. 14.2%, P < 0.001). Multivariable logistic regression analysis showed that higher age at RA onset (OR 1.056, 95% CI 1.021–1.091), higher body mass index (BMI; OR 1.65, 95% CI 1.036–2.629), smoking history (OR 2.484, 95% CI 1.071–5.764), and oral glucocorticoid use (OR 3.562, 95% CI 2.160–5.874) were associated with ILD in RA patients, whereas methotrexate use was less likely to be associated with ILD (OR 0.253, 95% CI 0.155–0.412).ConclusionsHigher age at RA onset, smoking history, and higher BMI were associated with the presence of ILD among RA patients. Oral glucocorticoids were more frequently used whereas methotrexate was less likely to be used in RA-ILD patients.

Peripheral Macrovascular Involvement in Systemic Sclerosis: A Cohort Study by Color and Spectral Doppler Ultrasonography.

Systemic sclerosis (SSc) is a disease characterized by diffuse sclerosis of skin and organs and small vessel vasculopathy. Despite it, large vessels can also be involved with ulnar artery vasculopathy, revealing as a more frequent feature of SSc. The aim of this paper is to assess the macrovascular involvement of SSc patients through an ultrasound (US) evaluation of radial and ulnar arteries. Radial and ulnar resistance indices (RIs) and peak systolic velocity (PV) (cm/s) together with clinical features of SSc patients were evaluated. Raynaud phenomenon (RP) and healthy control (HC) groups were used for comparison. Forty-three SSc patients were evaluated. Twelve patients (28%) had ulnar artery occlusions (UAOs). In nine cases (75%), UAOs were bilateral. A high UAO prevalence (42%) was found in SSc patients with late nailfold-video-capillaroscopy (NVC) pattern (p = 0.0264). Patients with UAOs had digital ulcers (DUs) in 10 cases (83.3%). Radial and ulnar PVs were lower in SSc and RP patients than the HC group. Radial and ulnar RIs were higher in SSc and RP patients than the HC group. A decision tree analysis led to the classification of 70% of SSc patients with an ulnar RI > 0.82 and ulnar PV > 2.8 cm/s. The most influential variables on UAO development were interstitial lung disease (ILD) (p = 0.002) and NVC pattern (p = 0.002). A positive correlation was shown between modified Rodnan skin score (mRSS) and ILD (p = 0.283; r = 0.033), mRSS and DU (r = 0.344; p = 0.012) and DU and ILD (r = 0.303; p = 0.024). Male sex was associated with increased UAO frequency (p = 0.042). UAO is a peculiar feature of severe SSc present in 28% of the cases, particularly associated with the presence of ILD and late NVC pattern. In 75% of the cases, UAOs are bilateral. DUs are very frequent in patients with UAOs (83%). The RI evaluated by US could be useful to distinguish SSc from HC patients. US could be a useful tool for assessing high-risk DU development in patients.