Interstitial Lung Disease Research Articles

Polyhexamethylene Guanidine Phosphate Induces Restrictive Ventilation Defect and Alters Lung Resistance and Compliance in Mice

Polyhexamethylene guanidine phosphate (PHMG-p), a major ingredient of humidifier disinfectants, is known to induce inflammation, interstitial pneumonitis, and fibrosis in the lungs. While its histopathologic toxicities have been studied in rodents, research on pulmonary function test (PFT) changes following PHMG-p exposure is limited. This study aimed to investigate the acute and chronic effects, as well as the dose and time response, of PHMG-p on the lungs in mice using PFT and histopathologic examinations. In the single instillation model, mice received PHMG-p and were sacrificed at 2, 4, and 8 weeks. In the five-time instillation model, PHMG-p was administered five times at one-week intervals, and mice were sacrificed 10 weeks after the first instillation. Results showed that PHMG-p exposure reduced lung volume, increased resistance, and decreased compliance, indicating a restrictive ventilation defect. Histopathologic examination showed increases in lung inflammation and fibrosis scores. Changes in several lung volume and compliance parameters, as well as histopathology, were dose-dependent. Lung resistance and compliance parameters had significant correlations with lung inflammation and fibrosis scores. PHMG-p exposure in mice resulted in a restrictive ventilation defect with altered lung resistance and compliance, along with histopathologic lung inflammation and fibrosis.

Experimental infection of ringtail possums (Pseudocheirus peregrinus) with Mycobacterium ulcerans, the agent of Buruli ulcer

Buruli ulcer (BU) is a necrotizing disease of skin and soft tissue caused by the bacterium Mycobacterium ulcerans (MU). In Australia, where the disease is emerging in new geographic areas and human case numbers are increasing, native possum species act as reservoir hosts. To better understand the life history of MU in one of its natural hosts, we conducted intra-dermal challenge of six wild caught, MU-naïve common ringtail possums (Pseudocheirus peregrinus). All six animals developed BU disease consistent with that observed in naturally infected ringtail possums. Time to ulceration varied between 49 and 77 days (mean = 61.8 days). Molecular evidence of systemic infection was detected in five animals and was supported by consistent histopathological findings in four animals. Pathological findings included random, multifocal, granulomatous hepatitis in four possums, one of which also had a mild, multifocal, interstitial granulomatous pneumonia. Acid-fast bacilli were only evident in inflammatory foci beyond the primary inoculation site in one possum. The ringtail possum model of MU infection is an important tool for the investigation of bacterial transmission dynamics, pathogenesis and immune response in a natural host. Data from this model may improve disease risk modelling and help identify intervention points to stop zoonotic transmission and disease spread.

Newly diagnosed advanced HIV infection in an older female in Poland

This paper presents the diagnostic and therapeutic challenges encountered in an older woman with advanced HIV infection. Upon admission, the patient exhibited severe symptoms of interstitial pneumonia and cachexia. During hospitalization, the patient was diagnosed with SARS-CoV-2 infection and a wide spectrum of opportunistic pulmonary infections, including Pneumocystis jiroveci, Candida krusei, and Staphylococcus haemolyticus. Another major diagnostic challenge posed the patient’s prolonged fever, which persisted despite comprehensive treatment. This report underscores the importance of considering new HIV infections in older patients presenting complex clinical pictures, its significant mortality risk in older individuals, and the need for timely initiation and adjustment of antiretroviral therapy.

Capillaroscopic Insights: Exploring the Connection Between Microvascular Changes and Pulmonary Manifestations in Systemic Sclerosis.

Systemic sclerosis (SSc) is a complex connective tissue disease characterized by microangiopathy, immune dysregulation, and fibrosis. Early detection of microvascular abnormalities using nailfold videocapillaroscopy (NVC) is crucial in assessing disease progression and associated disease's involvement such as interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). This study aims to explore the relationships correlation between NVC patterns, clinical manifestations, and systemic complications in SSc. We analyzed the data of 63 patients, predominantly female (95%), with a mean age of 49 years and an average disease duration of 42 months. Patients were categorized into early, active, and late patterns based on NVC findings. Clinical features, including digital ulcers (DU), ILD, and PAH, were assessed. Pearson correlation analyses were performed to evaluate the relationships between capillary loss, neoangiogenesis, ILD, and PAH. The early pattern group (mean mRSS 2.36) exhibited minimal microvascular damage and systemic involvement, with no DUs. In the active pattern group (mean mRSS 10.40), 34.38% had diffuse cutaneous SSc (dcSSc), with 15.63% presenting DUs, 65.63% ILD, and 37.5% PAH. The late pattern group (mean mRSS 18.00) showed the most severe disease, with 80% having DUs, 70% dcSSc, 90% ILD, and 70% PAH. Pearson correlation analyses revealed strong correlations between capillary loss and ILD (r = 0.7255) and PAH (r = 0.6369). A moderate correlation was found between neoangiogenesis and PAH (r = 0.5592). The study demonstrates that progressive microvascular damage in SSc, as visualized by NVC, correlates strongly with the severity of systemic complications. Early detection of capillary loss and neoangiogenesis using NVC is critical for timely interventions, which could improve patient outcomes by mitigating the progression of ILD and PAH.

Impact of Photon-counting Detector Computed Tomography on a Quantitative Interstitial Lung Disease Machine Learning Model.

Compare the impact of photon-counting detector computed tomography (PCD-CT) to conventional CT on an interstitial lung disease (ILD) quantitative machine learning (QML) model. A QML model analyzed 52 CT exams from patients who underwent same-day conventional and PCD-CT for suspected ILD. Lin's concordance correlation coefficient (CCC) assessed agreement between conventional and PCD-CT QML results. A CCC >0.90 was regarded as excellent, 0.9 to 0.8 as good, and <0.80 as a poor concordance. Spearman rank correlation evaluated the association between pulmonary function test results (PFT) and QML features (reticulation [R], honeycombing [HC], ground glass [GG], interstitial lung disease [ILD], and vessel-related structures [VRS]). Correlations were statistically significant if the 95% CI did not include 0.00 and P value <0.05. Conventional and PCD-CT QML results had good to excellent concordance (CCC ≥0.8) except for total HC (CCC <0.8), likely related to better PCD-CT honeycombing delineation. Overall, compared with conventional CT, PCD-CT had consistently more statistically significant correlation with PFT for HC (9 PCD vs. 2 conventional of 28 total and regional associations), similar correlation for R (20 PCD vs. 18 conventional of 28 associations) and VRS (19 PCD vs. 23 conventional of 28 associations), and less correlation for GG extent (12 PCD vs. 20 conventional associations). There is strong agreement between conventional and PCD-CT QML ILD features except for HC. PCD-CT improved HC but decreased GG extent correlation with PFT. Therefore, even though most quantitative features were not impacted by the newer PCD-CT technology, model adjustment is necessary.

A scoping review of the epidemiology of systemic sclerosis and its organ manifestations: 2018-2024.

Updates from large, observational cohorts and new statistical techniques have resulted in new data on the epidemiology of systemic sclerosis (SSc). This scoping review uses data from 2018 to 2024 to describe the current understanding of the epidemiology of SSc and several of its organ- manifestations. Our review identified new estimates for the global incidence and prevalence of SSc (1.4-8.6 per 100 000 person-years and 17.6-18.9 per 100 000 individuals, respectively). Mortality rates remain high, though mortality at younger ages has decreased. interstitial lung disease and pulmonary arterial hypertension remain the most common causes of death for patients with SSc. Literature on gastrointestinal (GI) manifestations of SSc was scarce, and we identified significant heterogeneity in results. Furthermore, data on the epidemiology of racial, ethnic and sex-based disparities was lacking. New techniques for the evaluation of the epidemiology of SSc highlight the high morbidity and mortality of SSc, and a growing prevalence rate compared with prior eras. Further research is needed to address notable heterogeneity in the reporting of epidemiological data and understudied disease manifestations, including GI disease and health disparities in disease outcomes.

Fatigue levels and associated factors in systemic sclerosis: a cross-sectional study of 2,385 SPIN Cohort participants.

To compare fatigue in a large multinational systemic sclerosis (SSc) cohort to general population data and identify associated sociodemographic, lifestyle and SSc disease factors. Scleroderma Patient-centered Intervention Network Cohort participants completed the Patient-Reported Outcomes Measurement Information System-29 v2.0 fatigue domain. T-scores were compared with the USA general population (mean = 50; SD = 10). Multivariable linear regression was used to assess associations with sociodemographic, lifestyle, and disease-related variables. Among 2,385 participants (mean age 54.9 (SD = 12.6) years, 87% female, 38% diffuse SSc), mean fatigue T-score was 54.6 (SD = 11.0); 438 (18%) reported mild fatigue, 641 (27%) moderate, and 180 (8%) severe fatigue. Fatigue was independently associated with sociodemographic factors age (-0.10 points per year, [95% CI -0.14;-0.07]), male sex (-1.67 points, [-2.96;-0.37]), non-married status (0.97 points [0.04; 1.89]), and country (reference USA; France -2.35 points [-3.48;-1.21] and UK 2.38 points [0.80; 3.97]), and lifestyle factors smoking (4.16 points [2.52; 5.80]), alcohol consumption (-0.18 points per drink per week [-0.28;-0.07]), and body-mass index (0.34 points per unit [0.27; 0.42]). Fatigue was associated with disease-related factors gastrointestinal involvement (4.21 points [2.99; 5.43]), digital ulcers (1.51 points, [0.25; 2.77]), moderate small joints contractures (1.41 points [0.13; 2.69]), rheumatoid arthritis (4.34 points [2.37-6.31]) and Sjögren's syndrome (1.89 points [0.23; 3.55]). When pain was included in the model, its association was large (2.19 points [2.03; 2.34]) and interstitial lung disease was also associated (1.21 points [0.42; 2.00]). In people with SSc, fatigue scores were substantially higher than the general population and associated with multiple disease factors including gastrointestinal involvement, several painful disease manifestations, and lung involvement.

The prevalence of respiratory symptoms and diseases and declined lung function among foundry workers.

Foundry workers are occupationally exposed to a variety of inhalable chemical substances. Occupational exposure to vapors, gases, dusts, and fumes can lead to adverse health effects on the respiratory system and cause chronic respiratory diseases, such as interstitial lung diseases (ILDs), chronic obstructive lung disease (COPD), chronic bronchitis, and emphysema. Research on respiratory symptoms, diseases, and lung function in foundry workers over the past few decades has been limited. The aim of this cross-sectional study was to assess the prevalence of respiratory symptoms and diseases and declined lung function of current foundry workers, ex-foundry workers, and unexposed controls. We assessed respiratory symptoms, diseases, and lung function among 335 current foundry workers, 64 ex-foundry workers, and 161 unexposed controls. The cumulative dust exposure (mg-y) of each participant was calculated, and the median cumulative dust exposure according to the main places of exposure was determined. A higher prevalence of chronic bronchitis, as reported in a questionnaire, was found among current and ex-foundry workers compared to unexposed controls, even after adjusting for pack-years of smoking (p = 0.009). Additionally, cough and wheezing in adulthood without respiratory infection, and chronic rhinitis symptoms were more common among current and ex-foundry workers compared to unexposed controls. These differences remained significant even after adjusting for pack-years of smoking and body mass index (BMI) (p = 0.007 and p < 0.001, respectively). Impaired lung function was more prevalent among both ex-foundry workers (29.7%) and current foundry workers (15.5%) compared to the unexposed controls (8.7%), with the difference remaining significant even after adjusting for the pack-years of smoking and BMI (p = 0.009). According to the questionnaire, the number of physician-diagnosed cases of chronic obstructive pulmonary disease (COPD) or chronic bronchitis was unexpectedly low compared to the indications from the symptom questionnaire and lung function test results, suggesting a potential underdiagnosis. The prevalence of silicosis was low (0.8%) among current and ex-foundry workers. Respiratory symptoms are common among foundry workers. Current and ex-foundry workers exhibited lower lung function in spirometry compared to unexposed controls. There is a potential underdiagnosis of COPD and chronic bronchitis among foundry workers.

Neutrophils and Lymphocytes: Yin and Yang of Lung Fibrosis and Patient Outcome in Diffuse Interstitial Lung Diseases

Neutrophils and Lymphocytes: Yin and Yang of Lung Fibrosis and Patient Outcome in Diffuse Interstitial Lung Diseases

Clinical characteristics and prognosis of interstitial lung disease in systemic juvenile idiopathic arthritis: a two-center retrospective observational cohort study

BackgroundInterstitial lung disease (ILD) is a serious complication in systemic juvenile idiopathic arthritis (SJIA). This study aimed to identify the clinical characteristics and prognosis of SJIA-ILD.MethodsA two-center retrospective cohort study was conducted on patients newly diagnosed with SJIA in China from October 2010 to December 2021. Clinical characteristics, laboratory parameters, outcomes, and relapse rates were compared between ILD and non-ILD groups.ResultsA total of 176 children with SJIA were included, including 35 in ILD group and 141 in non-ILD group. The median age at onset of SJIA was 5.8 years (range 4.4–9.5) in patients with SJIA-ILD. It exhibited higher incidences of cervical spine (28.6%) and hip involvement (40.0%) in ILD group (P = 0.031 and P = 0.029, respectively). The incidence of macrophage activation syndrome (MAS) in ILD group reached up to 40%, significantly elevated than that in non-ILD group (P = 0.047). Children with ILD demonstrated a stronger inflammatory response and were more prone to developing lymphopenia (P = 0.009), requiring more combination therapy (P = 0.006) to control disease activity. 54.3% of patients received biologic therapies, with only three patient receiving biologics (one with IL-6 blockade, two with TNF inhibitor) prior to ILD onset and none receiving IL-1 blockade. The median follow-up duration was 6.0 years (range 3.9–9.5). The proportions of patients with SJIA-ILD achieving clinical inactive disease without glucocorticoids within 6 to 12 months of the treatment were significantly lower than control group (45.7% vs. 70.2%, P = 0.006). In ILD group, only 54.3% of patients achieved complete remission, and 17.1% were in a non-remission state, among whom two deaths from respiratory failure. There was no significant difference in disease relapse rates between the two groups (P > 0.05).ConclusionsPatients with SJIA-ILD exhibited heightened inflammation, increased hip joint and cervical spine involvement, and were more susceptible to developing lymphopenia and MAS, suggesting a relatively poor prognosis. They required a prolonged time to control inflammation and more aggressive treatment strategies to achieve inactive status. The unsatisfactory rate of complete remission highlighted an urgent need for focused clinical strategies.

Risk profiles for rheumatoid arthritis-associated interstitial lung disease in a cohort of patients with five-year follow-up

Objectives Early identification of interstitial lung disease (ILD) among patients with rheumatoid arthritis (RA) is a challenge for clinicians. The aim of this study was to evaluate screening algorithms for ILD by comparing the proportion of patients assigned a high-risk profile by three recently proposed models. Method We used the four-factor risk score, categorizing patients into high and low risk; the ILD screening criteria, categorizing patients into high, intermediate, and low risk; and the risk score for detection of subclinical RA-ILD, with four different risk categories, on patients with RA followed for 5 years after the RA diagnosis with pulmonary function tests, dyspnoea score, and pulmonary imaging. Results The four-factor risk score identified 22% of the cohort (25/115) as eligible for further ILD investigations, while the ILD screening criteria identified 37% as high risk (43/115) and 34% as intermediate risk (39/115). The risk score for detection of subclinical RA-ILD identified 44% of the cohort as being at increased risk, with 7% in the highest risk group. The agreement between high-risk groups in the two clinical ILD screening models was moderate (kappa 0.43). Three patients in the cohort had clinical or subclinical ILD, and they were identified as high risk in the two clinical models. Conclusion The three algorithms identified approximately one-third of the cohort as being at increased risk of ILD. Further development and validation of these algorithms are needed to reduce false positives and balance the potential benefit of earlier ILD diagnosis and healthcare resources used for respiratory assessment.

Nerandomilast Improves Bleomycin-Induced Systemic Sclerosis-Associated Interstitial Lung Disease in Mice by Regulating the TGF-β1 Pathway.

Systemic sclerosis (SSc) is a rare connective tissue disease with a heterogeneous clinical course. Interstitial lung disease (ILD) is a common complication of SSc and a major contributor to SSc-related deaths. Besides nintedanib and tocilizumab, there are currently no clinically approved drugs for SSc-ILD, highlighting the urgent need for new treatment strategies. Previous studies have shown that cyclic adenosine monophosphate (cAMP) plays a crucial role in the pathogenesis of SSc and lung fibrosis. Phosphodiesterases (PDEs) are enzymes that specifically hydrolyze cAMP, making PDE inhibitors promising candidates for SSc-ILD treatment. Nerandomilast, a preferential phosphodiesterase 4B (PDE4B) inhibitor currently undergoing phase III clinical trials for idiopathic pulmonary fibrosis and progressive fibrosing interstitial lung diseases (PF-ILD), has good preference for PDE4B but lacks studies for SSc-ILD. Our research demonstrates that nerandomilast effectively inhibits skin and lung fibrosis in a bleomycin-induced mouse model of SSc-ILD. For lung fibrosis, we found that nerandomilast could improve bleomycin-induced SSc-ILD through inhibiting PDE4B and the TGF-β1-Smads/non-Smads signaling pathways, which provides a theoretical basis for potential therapeutic drug development for SSc-ILD.

Impact of GAP score on surgical prognosis of non-small-cell lung cancer with usual interstitial pneumonia.

Post-surgical survival outcomes in patients with non-small-cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF) are expected to be worse than those in patients with other idiopathic interstitial pneumonias (IIPs). However, these remain unclear regarding patients with NSCLC and IPF histologically diagnosed as usual interstitial pneumonia [IPF(UIP)]. We aimed to assess the surgical and survival outcomes and identify prognostic factors in patients with NSCLC and IPF(UIP). This retrospective cohort study included patients with pathological stage I-III NSCLC and UIP. Prognostic factors and their association with lung cancer deaths (LCDs) and non-LCDs (NLCDs) were investigated. The overall survival of patients with UIP was significantly poorer than that of others with IIPs. The main causes of death were lung cancer (36%) and respiratory disease (44%). Multivariate analyses revealed the pathological stage of NSCLC ≥ II (hazard ratio [HR], 2.196; p = 0.009) and GAP stage ≥ II (HR, 2.821; p = 0.016) to be significant prognostic factors. NLCD incidence was significantly high in patients with GAP stage ≥ II. Recurrence occurred in 26 patients (36.1%); the period from recurrence to death was shorter in patients with IPF(UIP) than in patients without IPF(UIP). Patients with NSCLC and IPF(UIP) had poor prognosis after surgery. However, the prognosis varied greatly depending on the GAP stage. Considering the difficulty in managing post-surgical recurrence and high incidence of LCDs in patients with IPF(UIP), pursuing a radical resection is recommended in patients with GAP stage I. For patients with GAP stage ≥ II, comprehensive management of UIP is also necessary.

Chronic acid sphingomyelinase deficiency diagnosed in infancy/childhood in Polish patients: 2024 update.

Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive lysosomal storage disease (LSD) associated with biallelic pathogenic variants in the sphingomyelin phosphodiesterase 1 (SMPD1) gene. The aim of this study was to provide the 2024 update on chronic visceral and neurovisceral ASMD diagnosed in the infancy/childhood in Polish patients. All the patients diagnosed in the pediatric age (0-18 years) with ASMD, both chronic neurovisceral and visceral type, and then systematically followed up, were enrolled into the study. A total number of 7 patients were enrolled into the study. Four patients were previously reported. Two patients were newly recognized with ASMD - 1 with chronic visceral and 1 with chronic neurovisceral ASMD. Splenomegaly was noted in all the patients while a mild liver enlargement was observed in 4 of 7 patients. All patients presented with decreased high-density lipoprotein cholesterol (HDL-C) and decreased serum 25-hydroxy-vitamin D concentration while almost all (6 of 7) with hypercholesterolemia. Cherry-red spot was observed in 5 of 7 patients, including 1 patient with neurovisceral type. Seven various SMPD1 gene variants were identified and missense variants were the most common types of genetic lesions, comprising 71% of all alleles. In all the screened patients, lyso-sphingomyelin (lyso-SM) in dried blood spot (DBS) was found elevated; however, the greater values were observed for patients with chronic neurovisceral type. Chronic acid sphingomyelinase deficiency (ASMD) is a slowly progressive disease. Pediatric ASMD is characterized by spleno-hepatomegaly, dyslipidemia (with decreased HDL-C as the most characteristic) and infiltrative (interstitial) lung disease. Both visceral and neurovisceral chronic ASMD patients could present with cherry-red spot. Both acid spingomyelinase activity and lyso-spingomyelin concentration in DBS should be regarded as a first-tier screening method into ASMD.

Neutrophil extracellular traps as immunofibrotic mediators in RA-ILD; pilot evaluation of the nintedanib therapy

ObjectiveRheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a significant pulmonary complication of RA. This study tried to elucidate the mechanisms enhancing inflammation and causing lung injury in RA-ILD, focusing on the role of neutrophil extracellular traps (NETs). The study also investigated the potential benefits of nintedanib in advanced disease.MethodsNine RA-ILD patients and nine healthy controls were included in the study. Inflammatory markers in patients’ circulation were evaluated with immunoassays. The formation of NETs was examined using a citrullinated histone H3 (CitH3) ELISA and cell immunofluorescence. Inflammatory proteins expressed in neutrophils/NETs were studied with real-time qPCR and NET ELISA. To assess the effect of nintedanib, an intracellular tyrosine kinase inhibitor with antifibrotic properties, in RA-ILD a paired study was conducted in five patients before treatment administration and 16 weeks later.ResultsThe soluble terminal complement complex sC5b-9 and the levels of CitH3 were significantly elevated in patients with RA-ILD, compared to healthy controls. In addition, neutrophils isolated from RA-ILD patients released NETs enriched with tissue factor and interleukin-17A. Inflammatory NETs had a dynamic role, increasing the fibrotic potential of human pulmonary fibroblasts (HPFs). On the other hand, nintedanib treatment decreased NETs and sC5b-9 levels in RA-ILD patients.ConclusionThe findings propose an interplay between circulating NETs and HPFs, establishing the immunofibrotic aspects of RA-ILD. They also support the effectiveness of nintedanib in reducing key pathological processes of the disease. Further research is needed to fully understand these mechanisms and optimize treatment strategies for RA-ILD.

Assessment of health-related quality of life in individuals with interstitial lung diseases in a tertiary care hospital in south India

Background &amp; objectives Interstitial lung diseases (ILD) cause progressive symptoms and decline in lung functions which impact health-related quality of life (HRQoL). Although HRQoL is gaining wider acceptance as an endpoint for disease perception, limited data is available regarding the same in Indians with ILD. Hence, this study was undertaken to assess HRQoL and its correlation with lung function parameters in individuals with ILD in a tertiary care setting in south India. Methods A hundred and fifty-nine consecutive patients with ILD were recruited between June 2022 to December 2023. HRQoL was assessed using the ILD specific K-BILD, generic EQ-5D-5L and an adapted version of the validated PESaM questionnaires. Correlation between various domains of the three questionnaires and lung function parameters was analyzed followed by linear regression analysis. Results The study population consisted predominantly of females (64.1%), with CTD-ILD being the most common ILD (40.8%). HRQoL impairment was noted, predominantly affecting the ‘breathlessness and activity’ domain and significant correlation was noted between K-BILD and EQ-5D-5L across domains. On regression analysis, FVC, 6-minute walk distance and desaturation were independent predictors of HRQoL. Type of ILD and disease duration did not have a significant association with HRQoL measures. Interpretation &amp; conclusions ‘Breathlessness and activity’ domain of HRQoL was affected the most in participants with ILD. Forced vital capacity, six-minute walk distance and exercise induced desaturation were independent predictors of HRQoL among individuals with ILD.

Predictive factors for interstitial lung disease progression in a Singapore systemic sclerosis cohort: a multicentre study.

Interstitial lung disease (ILD) in systemic sclerosis (SSc) is heterogeneous with varied progression rate. This study aimed to identify the baseline clinical characteristics associated with ILD progression within 1, 3 and 5 years of the diagnosis of ILD. This was a prospective, multicentre study - Systematic Sclerosis Cohort Singapore - conducted from January 2008 to February 2021, which included SSc patients with ILD diagnosed by high-resolution computed tomography. Progression of ILD was defined by forced vital capacity (FVC) decline ≥10% predicted or FVC decline 5%-9% predicted, with diffusing lung capacity of carbon monoxide decline ≥15% from the time of ILD diagnosis. Multivariable logistic and Cox regression analyses, adjusting for malignancy and treatment, were performed to determine independent risk factors of ILD progression. Of 124 SSc patients with ILD, 47.6% had limited cutaneous SSc, 33.9% had diffuse SSc and 18.5% had SSc-overlap. Progression of ILD was seen in 6%, 15% and 23% of patients within 1, 3 and 5 years, respectively. After adjusting for malignancy and treatment, anti-La was associated with ILD progression within 1 year (odds ratio [OR] 6.94, 95% confidence interval [CI]: 1.14-42.2; P = 0.04) and 3 years (OR 5.98, 95% CI: 1.31-27.4; P = 0.02), and anti-Scl-70 was associated with ILD progression within 5 years (OR 2.54, 95% CI: 1.05-6.12; P = 0.04). Analysing time to ILD progression as an outcome, anti-La was significantly associated with higher risk of ILD progression (hazard ratio 3.47, 95% CI: 1.18-10.2; P = 0.02). Time to ILD progression was 1.4 years in patients with anti-La versus 6.9 years in patients without anti-La (P = 0.02), and 4.7 years in patients with anti-Scl-70 versus 8.9 years in patients without anti-Scl-70 (P = 0.12). In this Asian cohort of SSc patients, autoantibodies may help to predict ILD progression rates.

Contemporary Concise Review 2023: Interstitial lung disease.

In this review, we have discussed several important developments in 2023 in Interstitial Lung Disease (ILD). The association of pollution with genetic predispositions increased the risk of Idiopathic Pulmonary Fibrosis (IPF). An interesting comorbidity of malnutrition was not adequately recognized in ILD. Novel genes have been identified in IPF involving predominantly short telomere length and surfactant protein production leading to alveolar epithelial cell dysfunction. Genetics also predicted progression in IPF. Crosstalk between vascular endothelial cells and fibroblasts in IPF mediated by bone morphogenic protein signalling may be important for remodelling of the lung. A novel modality for monitoring of disease included the 4-min gait speed. New treatment modalities include inhaled pirfenidone, efzofitimod, for sarcoidosis, and earlier use of immunosuppression in connective tissue disease-ILD.

Giant cell interstitial pneumonia: case series with comprehensive ultrastructural analyses of "not only" hard metal pneumoconiosis.

Giant cell interstitial pneumonia (GIP) is a fibrosing lung disease histologically characterized by centrilobular pulmonary fibrosis and cannibalistic intra-alveolar multinucleated giant cells. It is considered a form of pneumoconiosis caused particularly by secondary exposure to hard metals (cemented carbide or tungsten carbide). Hard metals are commonly used in various industrial applications, such as cutting tools, drilling tools, machine inserts, and other wear-resistant components. However, cases with unknown exposure that recurred in transplanted lungs have been described. This has led to the hypothesis of a complex etiopathogenesis, likely multifactorial, involving the coparticipation of immune mechanisms. We aimed to identify all the elements present in a series of GIP lung samples to better understand the pathogenic mechanisms of the disease. We describe five cases of histologically diagnosed GIP in patients with occupational exposure to metallic dust using ultrastructural characterization to identify metal dust and to quantify asbestos fibres. We found that tungsten was present in three cases, albeit in trace amounts in two of them. Numerous elements were identified in all samples, including asbestos fibres in patients with endstage pulmonary fibrosis. Furthermore, in one of the described cases the recurrence of the disease was also observed in transplanted lungs. These findings support the hypothesis that GIP may be due to elements other than hard metals, with asbestos possibly representing a contributory factor in the expression of a more severe fibrotic disease. The recurrence of GIP observed in transplanted organs strengthens the hypothesis of the existence of a not yet fully understood etiopathogenic immune mechanism.

Fibroblast activation protein inhibitor PET/CT as an emerging diagnostic modality in interstitial lung disease and other fibrotic conditions.

Interstitial lung diseases (ILD) encompass a wide range of disorders characterized by alveolar inflammation and fibrotic tissue remodeling, marked by significant morbidity and mortality. Systemic sclerosis (SSc), among other connective tissue diseases, is a frequent cause of ILD. Assessment of pulmonary fibrosis is frequently constrained by the delayed manifestations of profibrotic activation of fibroblasts, which results in late macroscopic alterations detectable by standard imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) scans. 68Ga-labeled fibroblast activation protein inhibitors (68Ga-FAPI [fibroblast activation protein inhibitor]) are novel radionuclides used in the selective positron emission tomography/computed tomography (PET/CT) detection of profibrotic fibroblasts, a key player in fibrotic tissue remodeling. Application of 68Ga-FAPI in different target organs undergoing fibrosis, such as lung and heart, highlights its efficacy in detecting ongoing fibrotic processes, since FAPI tracer uptake has been correlated with clinical disease progression markers in SSc-ILD. This feature could enable physicians to detect subclinical fibrotic activity and tailor an individualised therapy plan on a case by case basis. The use of 68Ga-FAPI in ILD and other fibrotic conditions may emerge as a novel tool in future clinical practice for both activity monitoring and treatment optimisation. Other tracers tested in ILD of different etiologies have shown promising results and may in future also be considered for potential application in SSc-ILD.