Prevalence and progression rate of interstitial lung abnormalities detected on thoracic CT: a systematic review and meta-analysis.

OBJECTIVES: To estimate the pooled prevalence and progression rate of ILAs and identify the risk factors for radiological progression. MATERIALS AND METHODS: An EMBASE and PubMed search was undertaken, identifying all studies meeting the inclusion criteria performed before May 10, 2023. Random effect models were used to estimate pooled prevalence, ILA progression rates, and odds ratio for radiological progression based on radiological subtype. Subgroup analyses were performed to compare the general and high-risk populations for lung cancer. The quality of the included studies was evaluated using the risk of bias assessment tool for non-randomized studies. RESULTS: We analyzed 19 studies (241,541 patients) and 10 studies (1317 patients) for the pooled prevalence and progression rate of ILA, respectively. The pooled ILA prevalence was 9.7% (95% CI, 6.1-13.9%). The pooled prevalence was 6.8% (95% CI, 3.1-11.6%) and 7.1% (95% CI, 2.2-14.4%) in the general (six studies) and high-risk population for lung cancer (six studies), respectively. The pooled progression rate was 47.1% (95% CI, 29.1-65.5%). The pooled progression rate was 64.2% (95% CI, 45.0-81.2%, five studies) and 31.0% (95% CI, 8.2-60.5%, five studies) for longer (≥ 4.5 years) and shorter follow-up periods (< 4.5 years), respectively (p = 0.009). Fibrotic ILAs were significantly associated with a higher progression probability (combined OR, 5.55; 95% CI, 1.95-15.82). CONCLUSIONS: The prevalence of ILAs was approximately 9.7%. Approximately half of the patients exhibited radiological progression, with the rate increasing over a longer follow-up period. Fibrotic ILA was a significant risk factor for radiological progression. CLINICAL RELEVANCE STATEMENT: The prevalence of interstitial lung abnormalities (ILAs) is approximately 9.7%, with about half exhibiting progression; a longer follow-up duration and fibrotic ILAs are associated with a higher progression rate. KEY POINTS: ILAs are increasingly recognized as important, but few population data are available. ILAs exhibited a pooled prevalence of 9.7% with a progression rate of 47.1%. Fibrotic ILAs were associated with increased progression likelihood.

[Differential diagnosis of cystic and nodular lung diseases]. / Differenzialdiagnose zystischer und nodulärer Lungenkrankheiten.

BACKGROUND: Cystic and nodular lung diseases encompass a broad spectrum of diseases with different etiologies and clinicoradiological presentations. Their differentiation is crucial for patient management but can be complex due to diseases with features of both categories and overlapping radiological patterns. OBJECTIVE: This study aims to describe the imaging features of cystic and nodular lung diseases in high-resolution computed tomography (CT) in detail-primarily based on their etiology-in order to allow a more accurate differential diagnosis of these diseases. MATERIALS AND METHODS: A narrative review based on current literature on the topic was conducted from a clinicoradiological perspective. RESULTS: This paper systematically categorizes the differential diagnosis of cystic and nodular lung disease and provides insights into their radiological patterns and etiologies. It highlights the role of CT in the diagnosis of these diseases and emphasizes the importance of multidisciplinary panels combining expertise from radiology, pulmonology, rheumatology, and pathology. CONCLUSION: Reliable differential diagnosis of cystic and nodular lung diseases, particularly based on their radiological features alone, remains difficult due to their overlapping and dynamic nature. Multidisciplinary boards should be the clinical standard for accurate work-up of these diseases, as they combine the medical history, symptoms, radiological findings, and, if necessary, histopathological examinations, thus providing a more robust framework for diagnosis and management.

Occupational exposure to respirable crystalline silica and incident idiopathic interstitial pneumonias and pulmonary sarcoidosis: a national prospective follow-up study.

BACKGROUND: Respirable crystalline silica is a well-known cause of silicosis but may also be associated with other types of interstitial lung disease. We examined the associations between occupational exposure to respirable crystalline silica and the risk of idiopathic interstitial pneumonias, pulmonary sarcoidosis and silicosis. METHODS: The total Danish working population was followed 1977-2015. Annual individual exposure to respirable crystalline silica was estimated using a quantitative job exposure matrix. Cases were identified in the Danish National Patient Register. We conducted adjusted analyses of exposure-response relations between cumulative silica exposure and other exposure metrics and idiopathic interstitial pneumonias, pulmonary sarcoidosis and silicosis. RESULTS: Mean cumulative exposure was 125 µg/m3-years among exposed workers. We observed increasing incidence rate ratios with increasing cumulative silica exposure for idiopathic interstitial pneumonias, pulmonary sarcoidosis and silicosis. For idiopathic interstitial pneumonias and pulmonary sarcoidosis, trends per 50 µg/m3-years were 1.03 (95% CI 1.02 to 1.03) and 1.06 (95% CI 1.04 to 1.07), respectively. For silicosis, we observed the well-known exposure-response relation with a trend per 50 µg/m3-years of 1.20 (95% CI 1.17 to 1.23). CONCLUSION: This study suggests that silica inhalation may be related to pulmonary sarcoidosis and idiopathic interstitial pneumonias, though these findings may to some extent be explained by diagnostic misclassification. The observed exposure-response relations for silicosis at lower cumulative exposure levels than previously reported need to be corroborated in analyses that address the limitations of this study.

Thin seams and small mines are associated with higher exposures to respirable crystalline silica in US underground coal mines.

OBJECTIVES: Previous radiologic and histopathologic studies suggest respirable crystalline silica (RCS) overexposure has been driving the resurgence of pneumoconiosis among contemporary US coal miners, with a higher prevalence of severe disease in Central Appalachia. We sought to better understand RCS exposure among US underground coal miners. METHODS: We analysed RCS levels, as measured by respirable quartz, from coal mine dust compliance data from 1982 to 2021. RESULTS: We analysed 322 919 respirable quartz samples from 5064 US underground coal mines. Mean mine-level respirable quartz percentage and mass concentrations were consistently higher for Central Appalachian mines than the rest of the USA. Mean mine-level respirable quartz mass concentrations decreased significantly over time, from 0.116 mg/m3 in 1982 to as low as 0.017 mg/m3 for Central Appalachian mines, and from 0.089 mg/m3 in 1983 to 0.015 mg/m3 in 2020 for the rest of the USA. Smaller mine size, location in Central Appalachia, lack of mine safety committee and thinner coal seams were predictive of higher respirable quartz mass concentrations. CONCLUSIONS: These data substantially support the association between RCS overexposure and the resurgence of coal workers' pneumoconiosis in the USA, particularly in smaller mines in Central Appalachia.

Identification and management of interstitial lung disease associated with systemic sclerosis (SSc-ILD), rheumatoid arthritis (RA-ILD), and polymyositis/dermatomyositis (PM/DM-ILD): development of expert consensus-based clinical algorithms.

BACKGROUND: Clinical guidance on the identification and management of connective tissue disease-associated interstitial lung disease (CTD-ILD) is needed for optimal clinical practice. We aimed to develop clinical algorithms for identifying and managing three common CTD-ILDs: those associated with systemic sclerosis (SSc-ILD), rheumatoid arthritis (RA-ILD), and polymyositis/dermatomyositis (PM/DM-ILD). RESEARCH DESIGN AND METHODS: Meetings were held October-November 2023 to create consensus-based algorithms for identifying and managing SSc-ILD, RA-ILD, and PM/DM-ILD in clinical practice, based on expert consensus statements for identification and management of CTD-ILD previously derived from a Delphi process. RESULTS: We developed clinical algorithms for SSc-ILD, RA-ILD, and PM/DM-ILD that highlight both commonalities and differences in the identification and management of these CTD-ILDs. Importantly, ILD should be suspected in patients with SSc, RA, or PM/DM who have respiratory symptoms. Chest high-resolution computed tomography has utility for screening, diagnosis and assessment of severity. Furthermore, regular follow-up and multidisciplinary management are important. Disease-specific considerations include unique risk factors such as anti-topoisomerase I antibodies in SSc-ILD, high-titer cyclic citrullinated peptide antibodies in RA, anti-aminoacyl tRNA synthetase antibodies in PM/DM, and anti-melanoma differentiation-associated gene 5 antibody in DM. CONCLUSIONS: These algorithms may help physicians to identify and manage patients with SSc-ILD, RA-ILD, or PM/DM-ILD.

Relative incidence of interstitial lung diseases in Brazil / Incidência relativa de doenças pulmonares intersticiais no Brasil

ABSTRACT Objective: To assess the relative frequency of incident cases of interstitial lung diseases (ILDs) in Brazil. Methods: This was a retrospective survey of new cases of ILD in six referral centers between January of 2013 and January of 2020. The diagnosis of ILD followed the criteria suggested by international bodies or was made through multidisciplinary discussion (MDD). The condition was characterized as unclassifiable ILD when there was no specific final diagnosis following MDD or when there was disagreement between clinical, radiological, or histological data. Results: The sample comprised 1,406 patients (mean age = 61 ± 14 years), and 764 (54%) were female. Of the 747 cases exposed to hypersensitivity pneumonitis (HP)-related antigens, 327 (44%) had a final diagnosis of HP. A family history of ILD was reported in 8% of cases. HRCT findings were indicative of fibrosis in 74% of cases, including honeycombing, in 21%. Relevant autoantibodies were detected in 33% of cases. Transbronchial biopsy was performed in 23% of patients, and surgical lung biopsy, in 17%. The final diagnoses were: connective tissue disease-associated ILD (in 27%), HP (in 23%), idiopathic pulmonary fibrosis (in 14%), unclassifiable ILD (in 10%), and sarcoidosis (in 6%). Diagnoses varied significantly among centers (c2 = 312.4; p < 0.001). Conclusions: Our findings show that connective tissue disease-associated ILD is the most common ILD in Brazil, followed by HP. These results highlight the need for close collaboration between pulmonologists and rheumatologists, the importance of detailed questioning of patients in regard with potential exposure to antigens, and the need for public health campaigns to stress the importance of avoiding such exposure.

RESUMO Objetivo: Avaliar a frequência relativa de casos incidentes de doenças pulmonares intersticiais (DPI) no Brasil. Métodos: Levantamento retrospectivo de casos novos de DPI em seis centros de referência entre janeiro de 2013 e janeiro de 2020. O diagnóstico de DPI seguiu os critérios sugeridos por órgãos internacionais ou foi feito por meio de discussão multidisciplinar (DMD). A condição foi caracterizada como DPI não classificável quando não houve um diagnóstico final específico após a DMD ou houve discordância entre dados clínicos, radiológicos ou histológicos. Resultados: A amostra foi composta por 1.406 pacientes (média de idade = 61 ± 14 anos), sendo 764 (54%) do sexo feminino. Dos 747 casos expostos a antígenos para pneumonite de hipersensibilidade (PH), 327 (44%) tiveram diagnóstico final de PH. Houve relato de história familiar de DPI em 8% dos casos. Os achados de TCAR foram indicativos de fibrose em 74% dos casos, incluindo faveolamento, em 21%. Autoanticorpos relevantes foram detectados em 33% dos casos. Biópsia transbrônquica foi realizada em 23% dos pacientes, e biópsia pulmonar cirúrgica, em 17%. Os diagnósticos finais foram: DPI associada à doença do tecido conjuntivo (em 27%), PH (em 23%), fibrose pulmonar idiopática (em 14%), DPI não classificável (em 10%) e sarcoidose (em 6%). Os diagnósticos variaram significativamente entre os centros (c2 = 312,4; p < 0,001). Conclusões: Nossos achados mostram que DPI associada à doença do tecido conjuntivo é a DPI mais comum no Brasil, seguida pela PH. Esses resultados destacam a necessidade de uma estreita colaboração entre pneumologistas e reumatologistas, a importância de fazer perguntas detalhadas aos pacientes a respeito da potencial exposição a antígenos e a necessidade de campanhas de saúde pública destinadas a enfatizar a importância de evitar essa exposição.

Connective tissue disease-associated interstitial lung disease / Doença pulmonar intersticial associada a doença do tecido conjuntivo

ABSTRACT Connective tissue disease-associated interstitial lung disease (CTD-ILD) represents a group of systemic autoimmune disorders characterized by immune-mediated organ dysfunction. Systemic sclerosis, rheumatoid arthritis, idiopathic inflammatory myositis, and Sjögren's syndrome are the most common CTDs that present with pulmonary involvement, as well as with interstitial pneumonia with autoimmune features. The frequency of CTD-ILD varies according to the type of CTD, but the overall incidence is 15%, causing an important impact on morbidity and mortality. The decision of which CTD patient should be investigated for ILD is unclear for many CTDs. Besides that, the clinical spectrum can range from asymptomatic findings on imaging to respiratory failure and death. A significant proportion of patients will present with a more severe and progressive disease, and, for those, immunosuppression with corticosteroids and cytotoxic medications are the mainstay of pharmacological treatment. In this review, we summarized the approach to diagnosis and treatment of CTD-ILD, highlighting recent advances in therapeutics for the various forms of CTD.

RESUMO Doença pulmonar intersticial associada à doença do tecido conjuntivo (DPI-DTC) representa um grupo de distúrbios autoimunes sistêmicos caracterizados por disfunção de órgãos imunomediada. Esclerose sistêmica, artrite reumatoide, miosite inflamatória idiopática e síndrome de Sjögren são as DTC mais comuns que apresentam acometimento pulmonar, bem como pneumonia intersticial com achados autoimunes. A frequência de DPI-DTC varia de acordo com o tipo de DTC, mas a incidência total é de 15%, causando um impacto importante na morbidade e mortalidade. A decisão sobre qual paciente com DTC deve ser investigado para DPI não é clara para muitas DTC. Além disso, o espectro clínico pode variar desde achados assintomáticos em exames de imagem até insuficiência respiratória e morte. Parte significativa dos pacientes apresentará doença mais grave e progressiva, e, para esses pacientes, imunossupressão com corticosteroides e medicamentos citotóxicos são a base do tratamento farmacológico. Nesta revisão, resumimos a abordagem do diagnóstico e tratamento de DPI-DTC, destacando os recentes avanços na terapêutica para as diversas formas de DTC.

Value of CT quantification in progressive fibrosing interstitial lung disease: a deep learning approach.

OBJECTIVES: To evaluate the relationship of changes in the deep learning-based CT quantification of interstitial lung disease (ILD) with changes in forced vital capacity (FVC) and visual assessments of ILD progression, and to investigate their prognostic implications. METHODS: This study included ILD patients with CT scans at intervals of over 2 years between January 2015 and June 2021. Deep learning-based texture analysis software was used to segment ILD findings on CT images (fibrosis: reticular opacity + honeycombing cysts; total ILD extent: ground-glass opacity + fibrosis). Patients were grouped according to the absolute decline of predicted FVC (< 5%, 5-10%, and ≥ 10%) and ILD progression assessed by thoracic radiologists, and their quantification results were compared among these groups. The associations between quantification results and survival were evaluated using multivariable Cox regression analysis. RESULTS: In total, 468 patients (239 men; 64 ± 9.5 years) were included. Fibrosis and total ILD extents more increased in patients with larger FVC decline (p < .001 in both). Patients with ILD progression had higher fibrosis and total ILD extent increases than those without ILD progression (p < .001 in both). Increases in fibrosis and total ILD extent were significant prognostic factors when adjusted for absolute FVC declines of ≥ 5% (hazard ratio [HR] 1.844, p = .01 for fibrosis; HR 2.484, p < .001 for total ILD extent) and ≥ 10% (HR 2.918, p < .001 for fibrosis; HR 3.125, p < .001 for total ILD extent). CONCLUSION: Changes in ILD CT quantification correlated with changes in FVC and visual assessment of ILD progression, and they were independent prognostic factors in ILD patients. CLINICAL RELEVANCE STATEMENT: Quantifying the CT features of interstitial lung disease using deep learning techniques could play a key role in defining and predicting the prognosis of progressive fibrosing interstitial lung disease. KEY POINTS: • Radiologic findings on high-resolution CT are important in diagnosing progressive fibrosing interstitial lung disease. • Deep learning-based quantification results for fibrosis and total interstitial lung disease extents correlated with the decline in forced vital capacity and visual assessments of interstitial lung disease progression, and emerged as independent prognostic factors. • Deep learning-based interstitial lung disease CT quantification can play a key role in diagnosing and prognosticating progressive fibrosing interstitial lung disease.

Cumulative occupational exposure to gases and fumes is associated with impairment in lung function and disease-related quality of life in a German COPD patient cohort.

OBJECTIVES: The impact of occupational exposures on lung function impairments and quality of life (QoL) in patients with chronic obstructive pulmonary disease (COPD) was analysed and compared with that of smoking. METHODS: Data from 1283 men and 759 women (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-4 or former grade 0, without alpha-1-antitrypsin deficiency) of the COPD and Systemic Consequences Comorbidities Network cohort were analysed. Cumulative exposure to gases/fumes, biological dust, mineral dust or the combination vapours/gases/dusts/fumes was assessed using the ALOHA job exposure matrix. The effect of both occupational and smoking exposure on lung function and disease-specific QoL (St George's Respiratory Questionnaire) was analysed using linear regression analysis adjusting for age, body mass index, diabetes, hypertension and coronary artery disease, stratified by sex. RESULTS: In men, exposure to gases/fumes showed the strongest effects among occupational exposures, being significantly associated with all lung function parameters and QoL; the effects were partially stronger than of smoking. Smoking had a larger effect than occupational exposure on lung diffusing capacity (transfer factor for carbon monoxide) but not on air trapping (residual volume/total lung capacity). In women, occupational exposures were not significantly associated with QoL or lung function, while the relationships between lung function parameters and smoking were comparable to men. CONCLUSIONS: In patients with COPD, cumulative occupational exposure, particularly to gases/fumes, showed effects on airway obstruction, air trapping, gas uptake capacity and disease-related QoL, some of which were larger than those of smoking. These findings suggest that lung air trapping and QoL should be considered as outcomes of occupational exposure to gases and fumes in patients with COPD. TRIAL REGISTRATION NUMBER: NCT01245933.

[Characteristics of patients with systemic sclerosis who develop interstitial lung disease]. / Características de los pacientes con esclerosis sistémica que desarrollan enfermedad pulmonar intersticial.

Background: Systemic sclerosis associated-interstitial lung disease (SSc-ILD) show a high mortality. The factors associated SSc-ILD have shown variability in different populations. There are few studies in Mexican mestizos. Objective: To analyze the epidemiological, clinical and paraclinical factors associated with SSc-ILD. Material and methods: Cross-sectional study, where patients > 18 years of age with a diagnosis of SSc according to EULAR/ACR 2013 criteria and diagnosis of ILD by forced vital capacity (FVC) < 70% and > 5% of affected lung area on tomography were included. The strength of association of the factors for ILD was measured by odds ratio (OR) with 95% confidence intervals (95% CI). The significant variables were analyzed by multiple logistic regression with adjustment. Results: Of the 80 patients with SSc, 38 (47.5%) had ILD. Risk factors such as smoking, higher activity index, lower FVC, anti-topoisomerase I antibodies, and protective factors such as a limited SSc, early capillaroscopic pattern, and anti-centromere antibodies (ACA) were associated with ILD. In the multivariate analysis, a higher activity index with OR 4.17, (95% CI 2.01-8.65) persisted as a risk factor, while ACA with OR 0.17, (95% CI 0.03-0.85) persisted as a protective factor associated with SSc-ILD. Conclusions: A higher index of activity and ACA persisted as factors associated with SSc-ILD.

Introducción: la enfermedad pulmonar intersticial (EPI) está relacionada a una mayor mortalidad en esclerosis sistémica (ES). Los factores asociados a su presentación han mostrado variabilidad en diferentes poblaciones. Pocos estudios se han realizado en mestizos mexicanos. Objetivo: analizar los factores clínicos y paraclínicos asociados a EPI en pacientes con ES. Material y métodos: estudio retrospectivo de casos y controles en el que se incluyeron pacientes > 18 años con diagnóstico de ES, según criterios EULAR/ACR 2013 y EPI por capacidad vital forzada (CVF) < 70% y > 5% de área pulmonar efectada en tomografía. La fuerza de asociación de los factores para EPI se midió por razón de momios (RM) con intervalos de confianza del 95% (IC95%). Las variables significativas se analizaron por regresión logística múltiple con ajuste. Resultados: de los 80 pacientes con ES, 38 (47.5%) tenían EPI. Factores de riesgo como tabaquismo, mayor índice de actividad, menor CVF, anticuerpos antitopoisomerasa I y factores protectores como variedad limitada de ES, patrón capilaroscópico temprano y anticuerpos anticentrómero estuvieron asociados a EPI. En el análisis multivariado un mayor índice de actividad con RM 4.17, (IC95%: 2.01-8.65) persistió como un factor de riesgo; en cambio, los anticuerpos anticentrómero con RM 0.17, (IC95%: 0.03-0.85) persistieron como un factor protector asociado a EPI. Conclusiones: un mayor índice de actividad y la presencia anticuerpos anticentrómero persistieron como factores asociados a la presencia de EPI en ES.

Plasma metabolomics and quantitative interstitial abnormalities in ever-smokers.

BACKGROUND: Quantitative interstitial abnormalities (QIA) are an automated computed tomography (CT) finding of early parenchymal lung disease, associated with worse lung function, reduced exercise capacity, increased respiratory symptoms, and death. The metabolomic perturbations associated with QIA are not well known. We sought to identify plasma metabolites associated with QIA in smokers. We also sought to identify shared and differentiating metabolomics features between QIA and emphysema, another smoking-related advanced radiographic abnormality. METHODS: In 928 former and current smokers in the Genetic Epidemiology of COPD cohort, we measured QIA and emphysema using an automated local density histogram method and generated metabolite profiles from plasma samples using liquid chromatography-mass spectrometry (Metabolon). We assessed the associations between metabolite levels and QIA using multivariable linear regression models adjusted for age, sex, body mass index, smoking status, pack-years, and inhaled corticosteroid use, at a Benjamini-Hochberg False Discovery Rate p-value of ≤ 0.05. Using multinomial regression models adjusted for these covariates, we assessed the associations between metabolite levels and the following CT phenotypes: QIA-predominant, emphysema-predominant, combined-predominant, and neither- predominant. Pathway enrichment analyses were performed using MetaboAnalyst. RESULTS: We found 85 metabolites significantly associated with QIA, with overrepresentation of the nicotinate and nicotinamide, histidine, starch and sucrose, pyrimidine, phosphatidylcholine, lysophospholipid, and sphingomyelin pathways. These included metabolites involved in inflammation and immune response, extracellular matrix remodeling, surfactant, and muscle cachexia. There were 75 metabolites significantly different between QIA-predominant and emphysema-predominant phenotypes, with overrepresentation of the phosphatidylethanolamine, nicotinate and nicotinamide, aminoacyl-tRNA, arginine, proline, alanine, aspartate, and glutamate pathways. CONCLUSIONS: Metabolomic correlates may lend insight to the biologic perturbations and pathways that underlie clinically meaningful quantitative CT measurements like QIA in smokers.

Successful Trastuzumab-Deruxtecan Rechallenge After Interstitial Lung Disease: A Case Report.

Trastuzumab deruxtecan (T-DXd) is used to treat human epidermal growth factor receptor 2-positive advanced breast cancer. Interstitial lung disease (ILD) is a severe adverse event associated with T-DXd. Current guidelines recommend permanent discontinuation of T-DXd after Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2 ILD. Here, we describe a case of successful rechallenge with T-DXd after CTCAE grade 2 treatment-induced ILD. After discontinuation of T-DXd, ILD was treated with steroids until complete resolution. Given the initial beneficial antitumor response, retreatment was discussed during disease progression. In a shared decision with the patient, T-DXd was restarted at the lowest registered dose, along with low-dose steroids. ILD did not reoccur. Importantly, both clinical and radiological responses to the treatment were observed, with an improvement in the patient's quality of life. This case demonstrates that retreatment with T-DXd after a grade 2 ILD event is feasible and yields clinical benefit.

Airborne occupational exposures associated with pulmonary sarcoidosis: a systematic review and meta-analysis.

The aetiology and pathophysiology of sarcoidosis is ill defined-current hypotheses centre on complex genetic-immune-environmental interactions in an individual, triggering a granulomatous process. The aim of this systematic review is to define and describe which airborne occupational exposures (aOE) are associated with and precede a diagnosis of pulmonary sarcoidosis. The methodology adopted for the purpose was systematic review and meta-analyses of ORs for specified aOE associated with pulmonary sarcoidosis (DerSimonian Laird random effects model (pooled log estimate of OR)). Standard search terms and dual review at each stage occurred. A compendium of aOE associated with pulmonary sarcoidosis was assembled, including mineralogical studies of sarcoidosis granulomas. N=81 aOE were associated with pulmonary sarcoidosis across all study designs. Occupational silica, pesticide and mould or mildew exposures were associated with increased odds of pulmonary sarcoidosis. Occupational nickel and aluminium exposure were associated with a non-statistically significant increase in the odds of pulmonary sarcoidosis. Silica exposure associated with pulmonary sarcoidosis was reported most frequently in the compendium (n=33 studies) and was the most common mineral identified in granulomas. It was concluded that aOE to silica, pesticides and mould or mildew are associated with increased odds of pulmonary sarcoidosis. Equipoise remains concerning the association and relationship of metal dusts with pulmonary sarcoidosis.

A computed tomography-based radiomics nomogram for predicting overall survival in patients with connective tissue disease-associated interstitial lung disease.

OBJECTIVES: Accurate prognostic prediction is beneficial for the management of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). The purpose of the present study was to develop and validate a nomogram using clinical features and computed tomography (CT) based radiomics features to predict overall survival (OS) in patients with CTD-ILD, and to assess the incremental prognostic value the radiomics might add to clinical risk factors. MATERIALS & METHODS: Patients from two clinical centers with CTD-ILD were enrolled in the present retrospective study. A radiomics signature, a clinical model and a combined nomogram were developed and assessed in the cohorts. The incremental value of radiomics signature to the clinical independent risk factors in survival prediction was evaluated. The models were externally validated to evaluate the model generalization ability. RESULTS: A total of 215 patients (mean age, 53 years ± 14 [standard deviation], 45 men) were evaluated. Patients with higher radiomics scores had higher mortality risk than those with lower radiomics scores (Hazard ratio, 12.396; 95% CI, 3.364-45.680; P < 0.001). The combined nomogram showed better predictive capability than the clinical model did with higher C-indices (0.800, 0.738, 0.742 vs. 0.747, 0.631, 0.587 in the training, internal- and external-validation cohort, respectively), time-AUCs and overall net-benefit. CONCLUSION: The radiomics signature is a potential prognostic biomarker of CTD-ILD and add incremental value to the clinical independent risk factors. The combined nomogram can provide a more accurate estimation of OS than the clinical model for CTD-ILD patients. CLINICAL RELEVANCE STATEMENT: The developed combined nomogram showed accurate prognostic prediction performance, which is beneficial for the management of CTD-ILD patients. It also proved radiomics could extract prognostic information from CT images.

Prevalence and risk factors for silicosis among a large cohort of stone benchtop industry workers.

OBJECTIVES: High silica content artificial stone has been found to be associated with silicosis among stone benchtop industry (SBI) workers. The objectives of this study were to determine the prevalence of and risk factors for silicosis among a large cohort of screened SBI workers, and determine the reliability of respiratory function testing (RFT) and chest x-ray (CXR) as screening tests in this industry. METHODS: Subjects were recruited from a health screening programme available to all SBI workers in Victoria, Australia. Workers undertook primary screening, including an International Labour Office (ILO) classified CXR, and subject to prespecified criteria, also underwent secondary screening including high-resolution CT (HRCT) chest and respiratory physician assessment. RESULTS: Among 544 SBI workers screened, 95% worked with artificial stone and 86.2% were exposed to dry processing of stone. Seventy-six per cent (414) required secondary screening, among whom 117 (28.2%) were diagnosed with silicosis (median age at diagnosis 42.1 years (IQR 34.8-49.7)), and all were male. In secondary screening, silicosis was associated with longer SBI career duration (12 vs 8 years), older age, lower body mass index and smoking. In those with silicosis, forced vital capacity was below the lower limit of normal in only 14% and diffusion capacity for carbon monoxide in 13%. Thirty-six (39.6%) of those with simple silicosis on chest HRCT had an ILO category 0 CXR. CONCLUSION: Screening this large cohort of SBI workers identified exposure to dry processing of stone was common and the prevalence of silicosis was high. Compared with HRCT chest, CXR and RFTs had limited value in screening this high-risk population.

Historical shift in pathological type of progressive massive fibrosis among coal miners in the USA.

BACKGROUND: Pneumoconiosis among coal miners in the USA has been resurgent over the past two decades, despite modern dust controls and regulatory standards. Previously published studies have suggested that respirable crystalline silica (RCS) is a contributor to this disease resurgence. However, evidence has been primarily indirect, in the form of radiographic features. METHODS: We obtained lung tissue specimens and data from the National Coal Workers' Autopsy Study. We evaluated specimens for the presence of progressive massive fibrosis (PMF) and used histopathological classifications to type these specimens into coal-type, mixed-type and silica-type PMF. Rates of each were compared by birth cohort. Logistic regression was used to assess demographic and mining characteristics associated with silica-type PMF. RESULTS: Of 322 cases found to have PMF, study pathologists characterised 138 (43%) as coal-type, 129 (40%) as mixed-type and 55 (17%) as silica-type PMF. Among earlier birth cohorts, coal-type and mixed-type PMF were more common than silica-type PMF, but their rates declined in later birth cohorts. In contrast, the rate of silica-type PMF did not decline in cases from more recent birth cohorts. More recent year of birth was significantly associated with silica-type PMF. CONCLUSIONS: Our findings demonstrate a shift in PMF types among US coal miners, from a predominance of coal- and mixed-type PMF to a more commonly encountered silica-type PMF. These results are further evidence of the prominent role of RCS in the pathogenesis of pneumoconiosis among contemporary US coal miners.

Deep learning diagnostic and severity-stratification for interstitial lung diseases and chronic obstructive pulmonary disease in digital lung auscultations and ultrasonography: clinical protocol for an observational case-control study.

BACKGROUND: Interstitial lung diseases (ILD), such as idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP), and chronic obstructive pulmonary disease (COPD) are severe, progressive pulmonary disorders with a poor prognosis. Prompt and accurate diagnosis is important to enable patients to receive appropriate care at the earliest possible stage to delay disease progression and prolong survival. Artificial intelligence-assisted lung auscultation and ultrasound (LUS) could constitute an alternative to conventional, subjective, operator-related methods for the accurate and earlier diagnosis of these diseases. This protocol describes the standardised collection of digitally-acquired lung sounds and LUS images of adult outpatients with IPF, NSIP or COPD and a deep learning diagnostic and severity-stratification approach. METHODS: A total of 120 consecutive patients (≥ 18 years) meeting international criteria for IPF, NSIP or COPD and 40 age-matched controls will be recruited in a Swiss pulmonology outpatient clinic, starting from August 2022. At inclusion, demographic and clinical data will be collected. Lung auscultation will be recorded with a digital stethoscope at 10 thoracic sites in each patient and LUS images using a standard point-of-care device will be acquired at the same sites. A deep learning algorithm (DeepBreath) using convolutional neural networks, long short-term memory models, and transformer architectures will be trained on these audio recordings and LUS images to derive an automated diagnostic tool. The primary outcome is the diagnosis of ILD versus control subjects or COPD. Secondary outcomes are the clinical, functional and radiological characteristics of IPF, NSIP and COPD diagnosis. Quality of life will be measured with dedicated questionnaires. Based on previous work to distinguish normal and pathological lung sounds, we estimate to achieve convergence with an area under the receiver operating characteristic curve of > 80% using 40 patients in each category, yielding a sample size calculation of 80 ILD (40 IPF, 40 NSIP), 40 COPD, and 40 controls. DISCUSSION: This approach has a broad potential to better guide care management by exploring the synergistic value of several point-of-care-tests for the automated detection and differential diagnosis of ILD and COPD and to estimate severity. Trial registration Registration: August 8, 2022. CLINICALTRIALS: gov Identifier: NCT05318599.

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.

OBJECTIVE: To 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 METHODS: This 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. RESULTS: Adverse 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. CONCLUSION: Adverse 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.

Submission of mandatory respiratory health examinations among US coal miners participating in the Coal Workers' Health Surveillance Program.

BACKGROUND: Mandatory examination requirements for US coal miners newly entering the workforce have been in place since the 1969 Coal Act mandated chest radiographs and were updated to include spirometry with promulgation of the 2014 Mine Safety and Health Administration Dust Rule. Compliance with the mandatory respiratory screening series is described using data from the National Institute for Occupational Safety and Health Coal Workers' Health Surveillance Program (CWHSP). METHODS: Among all radiographic and spirometry submissions to the CWHSP during 30 June 1971-15 March 2022, new underground coal miners who began work in the industry after 30 June 1971, and new underground, surface miners and contractors who began work after new regulations were implemented 1 August 2014, were identified and included in analysis. RESULTS: Of the 115 093 unique miners who participated in the CWHSP and whose estimated entry into mining occurred during 30 June 1971-15 March 2019, 50 487 (43.9%) received their initial mandatory radiograph, and 15 452 (13.4%) submitted their initial and 3-year mandatory radiographs. Since new regulations were implemented, compliance with initial radiographs appeared to improve (80%) but compliance with 3-year radiographs remained low (11.6%). Compliance with spirometry testing was also low for initial (17.1%) and follow-up screenings (2.7%). CONCLUSIONS: The majority of new coal miners eligible for health surveillance did not receive a baseline radiograph or spirometry test through the CWHSP even though coal mine operators are required by law to provide these. Ensuring coal miners' regular participation in health surveillance from early in their careers is an important way to monitor and protect their respiratory health.