Search Results (145)

Background: Langerhans Cell Histiocytosis (LCH) is a rare histiocytic hematological disorder that frequently involves the lungs. Due to a lack of data about sex-related differences in LCH, the aim of this study is to evaluate sex-related differences in pulmonary function in a cohort of patients with LCH. Methods: We retrospectively analyzed data from 79 adult patients diagnosed with LCH. Demographic, clinical, and spirometric data were collected and compared by sex. Continuous variables were analyzed using the Mann–Whitney test and categorical variables were analyzed with the Chi-square test. Results: Out of 79 patients, 47 (59.5%) were females and 32 (40.5%) were males. Women showed significantly lower diffusing capacity of the lungs for carbon monoxide (DLCO%) and lower diffusing capacity of the lungs for carbon monoxide per unit of alveolar volume (DLCO/VA%) compared to men. Females showed a trend toward lower small airway indices, including maximal expiratory flow at 25 (MEF₂₅%) and forced expiratory flow at 25–75% (FEF_25–75%), though this was not statistically significant, while the residual volume-to-total lung capacity (RV/TLC) ratio was significantly higher in women. Among the functional parameters, DLCO% showed the highest accuracy (AUC 0.70) in the identification of lung involvement after multivariate regression analysis. Conclusions: Our findings suggest that the combination of lower gas exchange efficiency and increased peripheral air trapping secondary to small airway involvement in female patients may reflect the presence of a distinct functional LCH phenotype in women characterized by early small airway involvement and altered ventilation–perfusion dynamics, which may influence the clinical management of these patients. Furthermore, the moderate predictive value of DLCO% for lung involvement at baseline in LCH women suggests that DLCO may contribute to the detection of LCH women with lung involvement, although it should not be considered a definitive diagnostic test without a prospective and independent external validation. Full article

Background: Patients with mastocytosis may present with exacerbated respiratory symptoms and lung diseases resulting from mast cell mediator release. However, their prevalence and severity level remain under debate. The study aims to analyze the prevalence of respiratory symptoms and the usefulness of lung function tests like spirometry, diffusing capacity of the lung for carbon monoxide (DLCO), and high-resolution computed tomography (HRCT) of the chest in mastocytosis patients presenting with dyspnea, cough, and exercise intolerance. Methods: We included 104 patients with mastocytosis and 71 healthy controls. Data collection encompassed patient interview, clinical examination, spirometry, DLCO, and chest HRCT. Diagnosis of mastocytosis included bone marrow biopsies and serum tryptase measurements. Results: Compared to controls, patients with mastocytosis exhibited significantly lower values in FEV1/VC ratio, absolute DLCO/VA, predicted DLCO/VA, absolute DLCOcSB, and predicted DLCOcSB (p < 0.001). Commonly reported respiratory symptoms included dyspnea (36.5%), chest tightness (22.1%), and wheezing (9.6%). Airway obstruction was identified in 7.7% of patients; however, it appeared to be independent of the mastocytosis subtype. A decreased DLCO/VA ratio was observed in 4.8% of patients, but HRCT did not reveal any evidence of underlying lung disease. Conclusions: Mastocytosis appears to be a risk factor for the occurrence and exacerbation of respiratory symptoms. However, airway obstruction and impairment of the alveolar–capillary membrane seem to occur independently of the clinical subtype of mastocytosis. Additionally, the causal relationship between pulmonary involvement, mast cell infiltration of the alveolar–capillary membrane, and the systemic circulation of mast cell mediators remains unclear and requires further research. Full article

Background and Objectives: Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive interstitial lung disease with an unknown etiology. It is often accompanied by skeletal muscle mass loss. Chest wall muscles play a crucial role in respiratory movements and form part of the skeletal muscles. The aim of this study is to evaluate the relationship between chest wall muscle thickness and pulmonary function test (PFT) results, as well as other prognostic markers, in patients with IPF. Materials and Methods: A retrospective analysis was conducted on 108 patients diagnosed with IPF and 53 control subjects. Chest wall muscle thickness was measured on thoracic computed tomography (CT) images at specific anatomical levels. PFT parameters, the Gender-Age-Physiology (GAP) index, number of acute exacerbations, and mortality data were evaluated in relation to muscle thickness. Results: IPF patients had significantly reduced thickness in the bilateral external scapular muscles at both the aortic and pulmonary trunk levels compared to controls. Bilateral pectoral muscle thickness at the aortic level was positively correlated with forced vital capacity (FVC) and negatively correlated with the number of exacerbations. Internal scapular muscle thickness at the aortic level showed a significant positive correlation with diffusion capacity of the lung for carbon monoxide (DLCO) and a negative correlation with both GAP scores and exacerbation frequency. External scapular muscle thickness at the pulmonary trunk level was positively associated with PFT parameters and inversely correlated with the GAP index, exacerbations, and mortality. Conclusions: In patients with IPF, the bilateral external scapular muscle thickness at the aortic and pulmonary trunk levels was significantly reduced compared to controls. Significant associations were found between some chest wall muscle thicknesses and the GAP index, pulmonary function, acute exacerbations, and mortality, underscoring the prognostic value of baseline muscle measurements. Measurement of chest wall muscle thickness using routine thoracic CT scans may offer additional prognostic value in IPF. Incorporating this parameter into clinical evaluation may help identify patients who could benefit from supportive interventions, such as nutritional therapy or pulmonary rehabilitation. Full article

Lung involvement is the most common extraglandular manifestation of primary Sjögren’s Disease (pSjD). There is an increasing interest in finding the clinical/serological risk predictors of this feature. A cross-sectional study evaluating anti-SSA/Ro antibodies, anti-SSB/La antibodies, rheumatoid factor, antinuclear antibodies, and the diffusing capacity of the lungs for carbon monoxide (DLCO) in 26 pSjD patients who presented interstitial changes on the chest CT scan was performed. The titres and positivity rates for anti-SSA/Ro (p = 0.02, p = 0.02) and anti-SSB/La antibodies (p = 0.01, p = 0.001) proved to be significantly increased in patients with abnormal DLCO. Anti-SSB/La antibodies’ titres seemed to be the best predictor for decreased DLCO–AUC 0.791 (0.587–0.994), p = 0.016. A close-to-significance decrease was found in the titres (p = 0.07) and positivity rates—p = 0.09 and OR of 0.15 (0.01–1.63)—of anti-SSB/La antibodies in patients with usual interstitial pneumonia (UIP), indicating their possible protective role against UIP. The lymphocytic interstitial pneumonitis (LIP) pattern on lung CT scan was significantly associated with the simultaneous positivity of the four examined serological markers (p = 0.03). The increase in anti-SSB/La antibody positivity rate in patients with LIP patterns was situated close to the significance level (p = 0.09). Quadruple positivity, as well as isolated anti-SSB/La positivity, could be risk factors for developing LIP in pSjD patients. Thus, anti-SSB/La antibodies might represent a marker of lung involvement in pSjD patients. Full article

Background: Interstitial lung disease (ILD) is a prominent complication in the course of rheumatoid arthritis (RA), with a prevalence ranging from 5% to 60% and several phenotypes. The existing knowledge on the impact of different pharmacological interventions in individuals with rheumatoid arthritis-related interstitial lung disease (RA-ILD) is inconclusive, and this variable response to treatment highlights the need for a personalized approach to the management of RA-associated ILD. Therefore, we aimed to evaluate the therapeutic effect and safety of different pharmacological agents, including conventional synthetic DMARDs (Cs DMARDs), biologic DMARDs (bDMARDs), targeted synthetic DMARDs (Ts DMARDs), and antifibrotic agents, in patients with RA-ILD. Method: This systematic review and meta-analysis searched for available randomized controlled trials (RCTs) and prospective cohort studies. A search was performed in the PubMed, Google Scholar, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Eligible studies comprised those involving hospitalized patients diagnosed with RA-ILD, regardless of concomitant medications, who were of adult age (≥18 years); the studies measured the effect of pharmacological interventions, including methotrexate, leflunomide, tumor necrosis factor inhibitors (anti-TNF), abatacept, rituximab, JAK inhibitors, and antifibrotic agents, compared to placebo or other therapies for RA. Results: Out of 446 studies from 2002 to 2024, only 16 were included in this systematic review, including 14 prospective cohort studies and 2 placebo-controlled studies. Unfortunately, no RCTs were found that address our research question. The most relevant studies (n = 4) were performed in different countries (mainly Spain and the UK), with sample sizes varying from 23 to 381 patients (total: 2199 patients). The current study reveals that non-anti-TNF biologics were associated with a decreased risk of radiologic progression, while advanced therapies improved disease-related outcomes in patients requiring oxygen therapy. Methotrexate and other DMARDs were found to have inconsistent effects on ILD progression and mortality. Conclusions: Our review supports the integration of personalized medicine into the management of RA-ILD. By considering patient-specific factors and therapeutic responses, clinicians can better tailor interventions. We confirmed the high methodological quality of the trials, yielding solid evidence for the clinical management of RA-ILD. This review adds to the existing literature by identifying nintedanib as a potential disease-modifying therapy with the potential to slow the progression of lung disease. Full article

Background: Children’s interstitial and diffuse lung diseases, commonly referred to as “chILDs”, include around 200 rare conditions that disrupt normal lung function. They are classified, based on etiopathogenesis, into several subgroups, having a varied and multifaceted clinical presentation depending on the type of genetic mutation present. Methods and Results: We describe the case of a late preterm newborn presenting soon after birth with respiratory distress syndrome poorly responsive to surfactant administration, in whom a targeted gene panel analysis for pulmonary congenital diseases, performed using next-generation sequencing (NGS), revealed a novel compound heterozygous variant of the ATP-Binding-Cassette-Subfamily-A-Member-3 (ABCA3) gene. A review of the literature on the subject completes our work. Conclusions: Molecular genetic analysis has become crucial for a more targeted therapeutic treatment, along with the only current curative treatment option that is lung transplantation. Full article

Background: It has yet to be determined whether the immunocytological profile of the bronchoalveolar lavage (BAL) in respiratory post-COVID syndrome (PCS) reflects the risk of persistent interstitial lung disease (ILD), including pulmonary fibrosis. In this study, we aimed to assess the prognostic value of the BAL cytoimmunologic profile in PCS-related ILD. Materials and Methods: We enrolled 58 non-smoking patients with a history of COVID-19 and new-onset ILD, divided into PCS remission and PCS persistence groups based on clinical data, including repeated computed tomography and pulmonary function tests. We phenotyped BAL major T cell subsets, immune checkpoints (including programmed cell death-1, PD1), and markers of Th1/Th2/Th17 polarization. Results: The PCS groups compared to the control showed increased total cell, lymphocyte, and neutrophil counts and a high BAL neutrophil:lymphocyte ratio (NLR). PCS persistence compared to the controls presented an increased neutrophil count (26 [17–36] vs. 2.6 [1.9–5.4] 10³/mL, median [Q1–Q3], p < 0.001) and percentage, BAL NLR (0.77 [0.26–1.63] vs. 0.21 [0.17–0.31], p < 0.0001), CD8+PD1+ cell percentage (43.5 [34–60.5] vs. 24.5 [22–44]%, p = 0.045), and a decreased CD4:CD8 ratio. A high percentage of CD4+CD196+CD183 cells (relevant to Th17 activity, 6.2 [2.0–9.4] vs. 1.2 [0.7–2.7]%, p = 0.02) and increased BAL supernatant elevated IL-8 levels (62.5 [16–243] vs. 10.9 [3.44–32] pg/mL, p = 0.002) were found in the PCS persistence vs. control groups. In the total PCS group, predicted values of Vital Capacity (VC) [16–243] and Diffusing Lung Capacity for CO (DLCO) correlated negatively with BAL NLR; VC correlated negatively with BAL CD8+PD1+; and DLCO correlated positively with the CD4:CD8 ratio. Conclusions: Worse prognosis in PCS is associated with higher BAL NLR, BAL neutrophilia, an elevated percentage of CD8+PD1+ lymphocytes, and a decline in the CD4:CD8 ratio. Th17 cells and IL-8 participate in lung PCS persistence. Full article

Nitrofurantoin, a commonly prescribed antibiotic for urinary tract infections, has been associated with rare but potentially serious pulmonary toxicity, which can present in acute, subacute, or chronic forms. Acute toxicity typically manifests in the form of hypersensitivity pneumonitis, which is characterized by fever, dyspnea, and eosinophilia, often resolving rapidly after drug discontinuation. However, chronic toxicity can lead to interstitial lung disease with progressive fibrosis, causing significant and sometimes irreversible pulmonary impairment. The pathophysiology of nitrofurantoin-induced lung injury is thought to involve oxidative stress, immune-mediated mechanisms, and direct cytotoxic effects; however, the exact pathways remain incompletely understood. Clinical diagnosis is challenging due to nonspecific symptoms that often resemble other respiratory conditions, leading to delays in recognition and treatment. Radiographic findings vary, with acute cases showing diffuse ground-glass opacities, while chronic cases may demonstrate reticular interstitial changes and fibrosis. The discontinuation of nitrofurantoin is the primary intervention, but corticosteroids may be beneficial, particularly in chronic cases with persistent inflammation or fibrosis, though their efficacy remains uncertain. Given the risk of long-term respiratory complications, heightened awareness among healthcare providers is essential for early diagnosis and intervention. Future research is needed to better define risk factors, improve diagnostic criteria, and explore alternative treatment strategies that mitigate the potential for pulmonary toxicity while maintaining effective antimicrobial therapy. This review explores the pathophysiology, clinical presentation, diagnostic challenges, and management strategies for nitrofurantoin-induced pulmonary toxicity. Full article

A monocentric cross-sectional study was performed to investigate the role of serum calprotectin as a biomarker for disease severity and activity in systemic sclerosis (SSc). Serum calprotectin was measured in 74 consecutive SSc patients admitted to a tertiary hospital in Rome, and in 50 healthy controls (HCs) who were healthcare workers, using Aptiva’s particle-based multianalyte technology. In SSc patients, a statistically significant correlation was found between calprotectin and the modified Rodnan skin score (mRSS) (r = 0.402, p < 0.001), disease activity index (DAI) (r = 0.420, p < 0.001), disease severity scale (DSS) (r = 0.365, p < 0.01), forced vital capacity (FVC) (r = −0.459, p < 0.001), and diffusion lung capacity for carbon monoxide (DLco) (r = −0.445, p < 0.001). Calprotectin was higher in SSc patients with digital ulcers (DUs) than in SSc patients without DUs [2.98 mcg/mL (IQR 2.07;4.29) vs. 2.08 mcg/mL (IQR 1.71;2.45), p < 0.01] and in SSc patients with interstitial lung disease (ILD) compared to SSc patients without ILD [2.56 mcg/mL (IQR 1.94;3.03) vs. 1.96 mcg/mL (IQR 1.7;2.35), p < 0.01]. The multivariable stepwise logistic regression analysis showed calprotectin to be independently associated with DUs [OR 2.531 (CI 95%: 1.074;5.961), p < 0.05] and ILD [OR 3.687 (CI 95%: 1.336;10.170), p < 0.05] in SSc patients. Serum calprotectin is associated with DUs and ILD in SSc patients. Full article

Interstitial lung disease (ILD) is a group of diffuse parenchymal disorders, which are diagnosed in many cases by multidisciplinary discussion (MDD). In some cases, diagnosis can be challenging, and the addition of histopathology can increase diagnostic confidence. The tools to obtain a histopathological sample to diagnose ILD are expanding. In this review, we will discuss the various modalities, their sensitivities and specificities, and procedural complication rates. In this review, we conducted a comprehensive review of literature focusing on emerging and established diagnostic tools for ILD. A systematic search of peer-reviewed publications was performed using PubMed with a focus on clinical trials, retrospective and prospective cohort studies, and systematic reviews. The key diagnostic modalities in focus were genomic classifier (GC), transbronchial cryobiopsy (TBLC), surgical lung biopsy (SLB), endobronchial ultrasound cryobiopsy (EBUS-C), genetic testing, and speckled transthoracic echocardiography (STE). Data extracted from these studies focused on diagnostic yield, specificity, sensitivity, and procedural complication rate. Genomic classifier, a gene-based molecular diagnostic tool, has a high specificity for histological usual interstitial pneumonia (UIP). However, in cases of a negative result, it often results in a need for further invasive sampling by TBLC or SLB. TBLC results in a larger histological sample, which can increase diagnostic yield and increase diagnostic confidence at MDD. Recent prospective trials have compared this modality with SLB and found 63–77% interobserver agreement between pathologists. SLB remains the gold standard with diagnostic yields reported to be more than 90%. EBUS-C has shown promising results increasing diagnostic yield in patients with suspected sarcoidosis or lymphoma. All diagnostic modalities have procedural complications with most common being pneumothorax, bleeding and, rarely, death. Advancements in diagnostic tools for interstitial lung disease (ILD) have significantly improved accuracy. Even though surgical lung biopsy remains the gold standard, the alternative modalities are promising and provide a promising yield with a lower procedural risk. Full article

Background/Objectives: Rapid skin thickness progression assessed using the modified Rodnan skin score (mRSS) is associated with poor outcomes in systemic sclerosis (SSc). However, the correlation between patterns of skin thickness and the onset of internal organ involvement remains unclear. This study aimed to determine the correlation between peak skin thickness progression rate (pSTPR) and the onset of internal organ involvement, particularly interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) among Thai SSc patients. Method: A prospective cohort study with retrospective analysis was conducted on adult SSc patients who experienced the onset of their first non-Raynaud phenomenon symptoms between January 2013 and December 2020 and had at least a 2-year follow-up. Patients with an overlap syndrome were excluded from this study. The pSTPR was calculated by dividing the peak of the mRSS by the duration of disease at the peak of the mRSS. Result: A total of 509 patients were included in this study. The majority of cases were female (351; 69.0%) and comprised diffuse cutaneous SSc subsets (353 cases; 69.4%). The respective mean age and median pSTPR was 48.2 ± 11.6 years and 1.63 points/year (interquartile range 0.5–4.4). The respective median durations of disease at the onset of significant ILD (>20% extent), ILD, and mean duration of disease at the onset of PAH were 3.4 (Q1–Q3 1.4–7.7), 5.4 (Q1–Q3 2.4–9.2), and 8.0 ± 4.9 years. pSTPR was negatively correlated with disease duration at the onset of significant ILD (Rho −0.509, p < 0.001), ILD (Rho −0.480, p < 0.001), PAH (Rho −0.372, p = 0.03), and disease duration from onset to death (Rho −0.367, p = 0.03) after adjusting for age, sex, and anti-topoisomerase I. Conclusion: SSc patients with a high skin thickness progression rate reaching the maximum point of mRSS were at risk of developing early ILD, PAH, and death. The pSTPR may be used to assess individuals at risk of experiencing early onset cardiopulmonary involvement in SSc. Full article

Background/Objectives: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) significantly affects disease prognosis and patient survival. The impact of conventional synthetic DMARDs (csDMARDs) and biologic/targeted synthetic DMARDs (b/tsDMARDs) on RA-ILD prognoses remains unclear. This study aimed to investigate the effects of csDMARDs and b/tsDMARDs on RA-ILD progression and prognosis based on pulmonary function tests (PFTs), high-resolution computed tomography (HRCT), and symptom changes. Methods: This multicenter, retrospective, observational study included patients with RA-ILD at 13 referral hospitals in South Korea. The participants were categorized into csDMARD-only and b/tsDMARD-exposed groups. RA-ILD prognosis was assessed over a 24-month follow-up period using serial PFTs (the forced vital capacity [FVC] and diffusing capacity of the lungs for carbon monoxide [DLCO]), HRCT findings, and clinical symptom changes. Kaplan–Meier survival analyses and Cox proportional hazards models were used to compare disease progression risk while adjusting for baseline lung function, RA disease activity, and glucocorticoid use. Results: Among 127 eligible patients, 22 (17.3%) were exposed to b/tsDMARDs, predominantly abatacept and tocilizumab. During a mean follow-up of 2.8 years, 65 (51.2%) patients experienced RA-ILD progression. A higher baseline Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28-ESR) (adjusted hazard ratio [aHR]: 1.344, 95% confidence interval [CI]: 1.136–1.590, p = 0.001) and initially prescribed prednisone dose (aHR: 1.078, 95% CI: 1.011–1.151, p = 0.023) were significant prognostic factors for ILD progression. No statistically significant difference in progression risk was observed between the csDMARD-only and b/tsDMARD-exposed groups (aHR: 0.937, p = 0.851). Conclusions: The RA-ILD prognosis was more strongly influenced by disease activity, rather than the type of DMARD used. These findings emphasize the importance of maintaining low RA disease activity to improve RA-ILD prognosis. Full article

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by the disruption of the alveolar and interstitial architecture due to extracellular matrix deposition. Emerging evidence suggests that genetic susceptibility plays a crucial role in IPF development. This study explores the role of human leukocyte antigen (HLA) alleles and haplotypes in IPF susceptibility and progression within the genetically distinct Sardinian population. Genotypic data were analyzed for associations with disease onset and progression, focusing on allele and haplotype frequencies in patients exhibiting slow (S) or rapid (R) progression. While no significant differences in HLA allele frequencies were observed between IPF patients and controls, the HLA-DRB1*04:05 allele and the extended haplotype (HLA-A*30:02, B*18:01, C*05:01, DQA1*05:01, DQB1*02:01, DRB1*03:01) were associated with a slower disease progression and improved survival (log-rank = 0.032 and 0.01, respectively). At 36 months, carriers of these variants demonstrated significantly better pulmonary function, measured with single-breath carbon monoxide diffusing capacity (DLCO%p) (p = 0.005 and 0.02, respectively). Multivariate analysis confirmed these findings as being independent of confounding factors. These results highlight the impact of HLA alleles and haplotypes on IPF outcomes and underscore the potential of the Sardinian genetic landscape to illuminate immunological mechanisms, paving the way for predictive biomarkers and personalized therapies. Full article

Background: Systemic sclerosis (SSc) is a multisystem autoimmune disease characterised by fibrosis, vasculopathy, and immune dysfunction. Silica exposure has been associated with a more aggressive phenotype of the disease, including diffuse cutaneous involvement and interstitial lung disease. This study aims to identify proteomic differences between SSc patients exposed to silica and those not exposed to silica. Methods: An observational study of 32 SSc patients (11 silica-exposed and 21 non-exposed) was performed, with occupational history and quantitative proteomic analysis using SWATH-MS mass spectrometry. Differentially expressed proteins were analysed, and functional pathway enrichment was performed. Results: Eight proteins showed significant differences between groups, all with reduced levels in silica-exposed patients: adiponectin, immunoglobulins (IGLV3-19, IGLV2-18), complement C2, alpha-2-macroglobulin, vitronectin, cytoplasmic actin 2, and pigment epithelium-derived factor. Alterations in pathways related to fibrinolysis, complement activation, and inflammation were highlighted, suggesting that silica exposure may influence the pathogenesis of SSc and worsen its clinical course. Conclusions: This study supports the hypothesis that silica exposure is not only a triggering factor for SSc, but is also modulating its progression through inflammatory, procoagulant, and fibrotic pathways. The identification of proteomic biomarkers could contribute to the phenotypic classification of patients and the development of personalised therapies. Future studies should expand the cohort and further investigate the functional mechanisms of these proteins in SSc. Full article

Background/Objectives: Even today, interstitial lung disease (ILD) is diagnosed by chest high-resolution computed tomography (lung HR-CT). Large amounts of data are available about the usefulness of transthoracic lung ultrasound (LUS) in ILD. This study aimed to evaluate the transthoracic LUS capacity to discriminate different ILD patterns in systemic sclerosis (SSc) patients, such as usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP) with ground glass opacification/opacity (GGO), and NSIP with GGO and reticulations, as well as the possibility of identifying progressive fibrosing ILD. Methods: We enrolled SSc-patients attending the outpatient Clinic of the Rheumatology Unit of Policlinico of Foggia and the Rheumatology Unit of Policlinico of Bari who satisfied these inclusion criteria: age older than 18 years; the satisfaction of ACR/EULAR 2013 classification criteria for SSc; chest HR-CT scan within three months before or three months after transthoracic LUS evaluation; and availability of recent and complete pulmonary function test. The exclusion criteria were as follows: history or recent reactivation of chronic obstructive pulmonary disease, lung cancer, lung infection, heart failure, pulmonary oedema, pulmonary arterial hypertension, acute respiratory distress syndrome and diffuse alveolar haemorrhage and thoracic surgery. All enrolled SSc-patients underwent transthoracic LUS, performed by an experienced sonographer. The ILD diagnosis and the respective patterns were assessed by chest HR-CT, which still represents the best diagnostic tool. Results: ILD was observed in 99 (63.5%) patients. Of these, 25% had the UIP pattern and 75% the NSIP pattern (46 with GGO, 28 with GGO and reticulations). By receiver operating characteristic (ROC) curve analysis, higher values of accuracy, sensitivity, specificity, and negative clinical utility index (CUI) were found for pleural line irregularity (0.84 (95% CI: 0.75–0.91), 96%, and 73.6%, p = 0.0001; 0.72), and pleural line thickness (0.84 (95% CI: 0.74–0.91), 72%, and 96.4%, p = 0.0001; 0.85) for detecting the UIP pattern. The best performance among transthoracic LUS signs for NSIP with the GGO pattern was observed for B-lines (accuracy: 0.88 (95% CI: 0.80–0.93), sensitivity: 93.4% and specificity: 82.4, p = 0.0001; CUI+: 0.75, CUI−: 0.77). LUS signs with higher accuracy, sensitivity, and specificity for NSIP with GGO and reticulations were pleural line irregularity (0.89 (95% CI: 0.80–0.95), 96.4%, and 82.4%, p = 0.0001) with CUI−: 0.72, and B-lines (0.89 (95% CI: 0.80–0.95), 96.4%, 82.4%, p = 0.0001), with CUI+: 0.80 and CUI−: 0.70. Furthermore, a total number of B-lines > 10 maximises LUS performance with 92.3% sensitivity, and an accuracy of 0.83 (p = 0.0001) for detecting the NSIP pattern, particularly GGO. A sample-restricted analysis (66 SSc patients) evidenced the presence of progressive fibrosing ILD in 77% of these patients. By binary regression analysis, the unique LUS sign associated with progressive fibrosing ILD was the presence of pleural line irregularity (OR: 3.6; 95% CI 1.08–11.9; p = 0.036). Conclusions: Our study demonstrated that transthoracic LUS presented a high capacity to discriminate the different patterns of SSc-ILD. Therefore, the hypothesis that transthoracic LUS is an effective screening method for the evaluation of the presence of SSc-ILD and establishing the correct timing of chest HR-CT, in order to avoid patients receiving excessive exposure to ionising radiation, is supported. Full article