Purpose:Fibrosing interstitial lung diseases (F-ILD), which include idiopathic pulmonary fibrosis (IPF) and other ILDs conferring risk for progressive pulmonary fibrosis (PPF), are a heterogeneous group of diseases with multiple subtypes. A multidisciplinary team discussion (MDD) incorporating HRCT is considered the gold standard for diagnosing and quantifying pulmonary fibrosis. However, repeated HRCTs are associated with substantial costs and radiation exposure. Thoracic ultrasound (TUS) has emerged as a potential radiation-free method for diagnosing and monitoring disease severity in F-ILD. However, consistent knowledge regarding the use of TUS in patients with F-ILD remains limited. This systematic review aimed to evaluate existing literature on the applicability of TUS in patients with F-ILD. Materials and Methods:We performed a systematic review according to PRISMA guidelines. MEDLINE, Embase, CINAHL, and Cochrane library databases were searched. Prospective, cross-sectional, and retrospective studies were considered. Risk of bias was assessed using quality assessment of diagnostic accuracy studies 2 (QUADAS-2). Results:Six studies met the inclusion criteria. All examined patients had IPF, and two had other F-ILD subtypes. The most frequently evaluated TUS findings were B-lines and pleural line irregularities (PI). However, there was marked heterogeneity in TUS methodology and protocols, precluding meta-analysis. Conclusion:Although the preliminary findings in this review suggest TUS may have potential utility in this patient group, available data on TUS in F-ILD are sparse and heterogeneous, highlighting the need for further research.

Pulmonal hyalinizing granuloma (PHG) is a rare benign disease of unknown cause, first described by Engleman in 1977 (1). Fewer than 200 cases have been reported worldwide (2). We present the case of a middle-aged male referred to the respiratory clinic after a routine chest X-ray (CXR) and chest computed topography (CT) scan revealed multiple bilateral peripheral pulmonary lesions (PPL). Over a 10-year period, the patient´s PPLs increased in size and number, with heterogeneous hypermetabolism observed on fluorodeoxyglucose -positron emission tomography (FDG-PET) imaging. Initially, the PPLs were suspected to be metastases from a salivary gland cancer due to a hypermetabolic focus in the right parotid gland. However, a biopsy of the parotid gland revealed a benign Warthin’s tumour, and CT-guided fine needle biopsies from the lung lesions did not show malignant cells. A thoracoscopic resection of one PPL was consistent with a diagnosis of hyalinizing granuloma.

The evidence base supporting the use of thoracic ultrasound to assess the lung parenchyma has expanded and consolidated itself significantly within the last decade. Thoracic ultrasound for lung parenchyma assessment is now finding its way into statements and clinical practice guidelines for several conditions in various settings. Since assessment of patients with possible chest disease is a very common clinical scenario, knowledge of the various types of chest imaging is essential for any physician. The most common indication for thoracic ultrasound for lung parenchymal assessment is for screening and diagnostic purposes. Several new studies have, however, demonstrated a possible large potential for using thoracic lung ultrasound to monitor lung diseases. The recent COVID-19 pandemic has increased the scope of lung parenchymal ultrasound, from diagnosis to monitoring of the disease. Deep learning of contrast-enhanced thoracic ultrasound to aid diagnosis is a new developing area. Despite increasing use of thoracic ultrasound in respiratory medicine, a consensus on assessment of competencies, and education is lacking. The aim of this review is to provide the reader with a focus overview of the current use and diagnostic limitation of thoracic ultrasound for assessment of the lung parenchyma, and future development.

IntroductionIn the general population elevated circulating inflammatory markers have been associated with impaired lung function in cross-sectional and longitudinal studies. No studies have investigated this association in liver transplant recipients, and we aimed to investigate if elevated inflammatory markers were associated with impaired lung function in this population.MethodsAdult liver transplant recipients from The Danish Comorbidity in Liver Transplant Recipients (DACOLT) study, with available spirometry, high sensitivity (hs)-CRP, interleukin (IL)-1β, IL-2, IL-6, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were included. Outcomes were forced expiratory volume in one second (FEV1), forced vital capacity (FVC), airflow limitation, and preserved ratio impaired spirometry (PRISm).ResultsWe included 335 liver transplant recipients. The prevalence of airflow limitation and PRISm was 11.6% and 24.5%, respectively. The median FEV1 was 2790 mL (IQR 2230–3505 mL) and the median FVC was 3680 mL (IQR 2980–3755 mL). When adjusted for age and sex, hs-CRP >3 mg/L was associated with increased odds of PRISm (aOR 2.08, 95% CI: 1.1; 3.9, p=0.02), lower FEV1 (-209 mL 95% CI -340; -77 mL, p<0.01), and lower FVC (-290 mL 95% CI -448 mL; -132 mL, p<0.01). For FEV1 and FVC, the associations were consistent when additionally adjusted for ethnicity, BMI, and smoking status. None of the remaining inflammatory markers were significantly associated with any of the outcomes across statistical models.ConclusionElevated hs-CRP was associated with impaired lung function indicating that systemic inflammation may be part of the pathophysiology of impaired lung function in liver transplant recipients.

Objective Our objective is to estimate the prevalence and incidence of interstitial lung diseases (ILDs) among adults with systemic lupus erythematosus (SLE) and to explore possible differences in reported prevalence and incidence of SLE-ILDs between clinical observational and register-based studies.Method EMBASE, MEDLINE, Cochrane Library and Scopus were searched for eligible studies investigating SLE-ILDs prevalence and/or incidence. Risk of bias was assessed using the Joanna Briggs Institute Prevalence Critical Appraisal Tool. Data were extracted in a predefined Excel spreadsheet by two reviewers independent and blinded to each other. Pooled weighted prevalences and incidences were calculated with corresponding 95% CIs, visualised in forest plots. Heterogeneity was assessed with I2 test.Results Ninety-eight studies comprising 155 964 participants were included in the systematic review and meta-analyses. The pooled weighted SLE-ILDs prevalence was 11.0% (9.0% to 13.0%), with substantial heterogeneity (I²=99.9%), and 18% when identifying SLE-ILDs with chest high-resolution CT (HRCT) scans. Clinical observational studies reported a higher prevalence of 25.0% (19.0% to 31.0%) compared with register-based studies 7.0% (5.0% to 8.0%). The incidence analysis was based on three registry-based studies and estimated an incidence of 4.9 per 1000 person-years (−0.5 to 10.3) with substantial heterogeneity (I² = 99.8%).Conclusion ILDs appear to be a prevalent manifestation in SLE with a pooled prevalence estimate of 11.0%, although this estimate should be interpreted with caution due to substantial heterogeneity across studies. HRCT-based studies reported a higher prevalence (18.0%), suggesting that diagnostic modality influences prevalence estimates. The incidence estimate (4.9 per 1000 person-years) should be interpreted as exploratory because it was based on only three registry-based studies. Overall, the findings suggest that ILD may be more common in SLE than previously assumed, highlighting the importance of awareness of pulmonary manifestations. We found the prevalence to be higher in clinical observational studies than register-based studies.PROSPERO registration number CRD420250642237.

IntroductionLiver transplant recipients have an increased risk of pulmonary complications, yet the pathogenesis remains poorly elucidated. The pulmonary endothelium is central in maintaining lung function, and endothelial dysfunction may contribute to airflow obstruction. Soluble thrombomodulin (TM) and syndecan-1 (SDC-1) are markers of endothelial damage, but whether TM and SDC-1 are related to lung function in liver transplant recipients remain unknown. This study investigated whether TM and SDC-1 are associated with forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and airflow obstruction in liver transplant recipients.MethodsWe included liver transplant recipients from The Danish Comorbidity in Liver Transplant Recipients (DACOLT) study. Airflow obstruction was defined as FEV1/FVC <0.7. TM and SDC-1 were dichotomized, and an elevated concentration was defined as above the 3rd quartile. Outcomes were analyzed using linear and logistic regression.Results340 liver transplant recipients were included. Liver transplant recipients with elevated TM had 39.5 mL lower FEV1 than liver transplant recipients with low TM (95% CI: -173.7;94.7, p=0.564), and 72.2 mL lower FVC (95% CI: -227.2;82.8, p=0.362), adjusted for confounders. The odds ratio (OR) for airflow obstruction was 1.01 (95% CI: 0.43;2.38, p=0.984). Liver transplant recipients with elevated SDC-1 had 93.4 mL lower FEV1 than liver transplant recipients with low SDC-1 (95% CI: -223.1;36.3, p=0.159) and 31.2 mL lower FVC (95% CI: -181.6;119.2, p=0.684), adjusted for confounders. The OR for airflow obstruction was 0.97 (95% CI: 0.42;2.27, p=0.950).ConclusionIn this study, we found no significant associations between TM or SDC-1 and FEV1, FVC, and airflow obstruction in liver transplant recipients. Further research is warranted to elucidate the mechanisms underlying pulmonary complications in liver transplant recipients.

Background The efficacy of endobronchial valve (EBV) treatment has been demonstrated in randomized controlled trials. However, real-life nationwide data from more heterogeneous patient populations remains limited. Therefore, this study aims to evaluate the one-year outcome of EBV treatment in a nationwide cohort study. Method In this nationwide cohort study, Danish patients treated with endobronchial valves from 2017-2024 were included. Outcomes, such as lung function, exercise capacity, and dyspnea, were assessed at 3 and 12 months, together with data on complications and mortality. Data was obtained from electronic medical records. Results A total of 232 patients were included in the study. Follow-up visits at 3 (1-5) and 12 (9-18) months were available for 189 and 165 patients, respectively. Nine patients died within the first year, and 37 patients underwent valve removal. Significant improvements from baseline were observed at both follow-up points in lung function (forced expiratory volume in 1 second +4.75%points & +3.43 %points, residual volume -30.5%points & -27.7 %points, total lung capacity -7.0%points & -5.7%points), physical ability (6-minute walk distance +30.6 m & +20.8 m), and dyspnea (Medical Research Council dyspnea scale -0.73 & -0.47). Responder rates declined over time, but 40-50% of patients maintained a clinically meaningful benefit at the 12-month visit. Revision bronchoscopies were performed in 44% of the patients. Conclusions Endobronchial valve treatment is associated with statistically significant improvements in lung function, exercise capacity, and dyspnea at both 3 and 12 months, with considerable inter-individual variability.

Background Granulomatous lymphocytic interstitial lung disease (GLILD) is a non-infectious complication of common variable immunodeficiency (CVID) entailing increased morbidity and mortality. The pathogenesis of GLILD remain unclear, and optimal treatment strategies are lacking. We aimed to highlight GLILD pathogenesis and identify biomarkers by proteomics and immunoassays in two independent CVID cohorts. Methods We measured 183 proteins by plasma proteomics in a Norwegian discovery cohort . The most significantly upregulated proteins in GLILD were selected for enzyme immunoassays (EIA) or MesoScale analysis in a Nordic validation cohort , and again in the discovery cohort . Findings were correlated to pulmonary function, computed tomography findings and treatment data. Results The discovery cohort included 68 CVID patients (GLILD, n=23; other complications , n=24; infection only , n=21) and 20 healthy controls, and the validation cohort 189 patients (GLILD n=32; other complications , n=82; infection only, n=75). Fifty-seven proteins measured by proteomics in the discovery cohort were significantly higher in GLILD compared to the other groups. These proteins were functionally linked to T cell activation, and the proteomic signature of GLILD was distinct from other CVID related organ complications. Twenty-three proteins were selected for EIA/MesoScale measurement, confirming elevated CXCL13, soluble CD27, IL-10, CD25, IL18BPa, CD5, PD-1, Granzyme A and B in GLILD versus other complications and infection only in both cohorts. Eight of nine proteins correlated to CT score, and CXCL13 was higher in patients that subsequently needed treatment. Conclusions Circulating proteins in GLILD reflect T cell activation, and the germinal centre activity marker CXCL13 shows promise as prognostic biomarker.

Background/Objectives: Fibrosing interstitial lung disease (F-ILD) is associated with progressive respiratory impairment and substantial symptom burden. Diaphragmatic ultrasound (DUS) is a non-invasive method for assessing diaphragmatic structure and function, but its clinical role in F-ILD remains uncertain. This systematic review evaluated the available evidence on DUS in adults with F-ILD. Methods: This systematic review was conducted and reported according to the PRISMA guidelines. MEDLINE, Embase, CINAHL, and the Cochrane Library were searched and observational studies evaluating DUS in adults with F-ILD were included. Risk of bias was assessed using the QUADAS-2, and outcome-level certainty of evidence was evaluated by GRADE framework. Results: Six cross-sectional observational studies involving 232 participants were included. Diaphragmatic excursion (DE) was assessed in all six studies, while diaphragm thickness (DT) and thickening fraction (TF) were evaluated in four. Some studies reported abnormalities in DUS parameters during deep breathing and cross-sectional associations with pulmonary function, exercise capacity, dyspnoea, or radiological severity. Substantial heterogeneity in study populations, ultrasound protocols, and outcome reporting precluded meta-analysis. The certainty of evidence was very low. Conclusions: Current evidence suggests that DUS may detect diaphragmatic abnormalities in patients with F-ILD and may have future complementary value alongside established clinical assessments. However, the evidence is limited, heterogeneous, and of very low certainty and does not establish diagnostic accuracy, prognostic value, or usefulness for longitudinal monitoring. Accordingly, DUS cannot currently be recommended for routine clinical implementation in F-ILD, and prospective longitudinal validation is required.

Introduction Fibrosing interstitial lung disease (F-ILD) are a heterogeneous group of diseases with multiple subtypes. Both idiopathic pulmonary fibrosis and other ILDs associated with a risk of developing progressive pulmonary fibrosis (PPF) are subtypes of this category. A multidisciplinary team discussion, including a chest high-resolution CT (HRCT), is usually considered the gold standard for diagnosis of F-ILD. Repeated HRCT is one of several established methods to assess progression and thus development of PPF, but it is associated with substantial costs and radiation exposure. Thoracic ultrasound (TUS) and other ultrasound (US) methods have emerged as radiation-free methods for both diagnosing and monitoring disease severity in F-ILD. Yet, consistent knowledge on the use of different TUS- and US methods in patients with F-ILD is limited.Methods The LORD study is a prospective cohort study conducted in participants with F-ILD at a tertiary ILD centre in Denmark. Physiological testing and patient-related outcome measures, together with TUS- and US examinations, will be performed at inclusion, after 6 and 12 months. The correlations between these assessments will be evaluated. HRCT will be conducted between 3 months prior to and 1 month after baseline, and after 1 year. At least 34 participants will be included.Ethics and dissemination The protocol was approved by the Danish Data Protection Agency (journal number: 22/45135) and the Science Ethics Committee for the Region of Southern Denmark (journal number: S-20220036). Results will be published in peer-reviewed international journals and will be presented at an international congress.Trial registration number NCT06844331.

Objectives Pulmonary diseases (PDs) in SLE are thought to be common and of clinical importance but can be difficult to diagnose. Prior studies report divergent estimates of the prevalence of PD in SLE ranging from 30% to 98%. Therefore, our primary objective was to determine the prevalence of PD in patients with SLE, through a population-based cross-sectional study. Our secondary objectives were to investigate in patients with SLE: (1) the prevalence of specific subtypes of PD, (2) pulmonary function and (3) associations between selected patient characteristics and presence of PD and subtypes of PD.Methods We invited adult patients with SLE who met the classification criteria and lived in Region Southern Denmark. Each participant underwent a clinical assessment, pulmonary function tests (PFTs) and a chest high-resolution CT scan (HRCT). Subsequently, participants were assessed and diagnosed according to the presence of PD and subtypes of PD at a multidisciplinary discussion.Results We found PDs were prevalent in 109 (59%) of the 185 included participants, among whom interstitial lung diseases were prevalent in 22 (12%), pleural diseases in 35 (19%) and airway diseases in 70 (38%). PD and subtypes of PD were associated with decreased pulmonary function, but the PFT measures showed a low combined sensitivity and specificity for detecting PD and subtypes of PD. We found no strong associations between selected patient characteristics and the presence of PD or subtypes of PD.Conclusion 59% of patients with SLE have PD, and PD was associated with decreased pulmonary function. Diagnosing PD in SLE remains challenging because clinical assessment and PFTs have limited utility. Accurate diagnosis often requires HRCT or other specialised investigations.Trial registration number NCT06087523.

Background Pulmonary diseases (PD) in systemic lupus erythematosus (SLE) are common and cover several entities. Diagnosing PD in SLE is often challenging, why reliable biomarkers are warranted. Several studies have explored the relationship between circulating biomarkers (CB) and detection of PD in SLE, but with conflicting results. Objective To investigate evidence supporting associations between CB and PD in SLE through a systematic literature review of observational studies. Method We searched MEDLINE and EMBASE for studies addressing potential associations between CB and PD in SLE. Afterwards forward- and backward citation search was performed. Internal validity and risk of bias were addressed with Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Outcome Reporting Bias in Trials (ORBIT). Association between CB and PD across studies were investigated through meta-analyses and individual studies were summarized in tables. Results We identified 13,504 references; of these, 24 studies were eligible, including 1,883 patients and 43 different CB. In individual studies 21 different CB were significantly associated with PD. Meta-analyses resulted in 10 associations of potential clinical significance between PD or PD-related outcomes and five CB (anti-double stranded DNA antibodies, anti-Ribonucleoprotein antibodies, anti-Smith antibodies, C-C motif Ligand 21, and Interferon Gamma Inducible Protein 10). Conclusion Through meta-analyses we identified CB that were significantly associated with PD in SLE including anti-dsDNA. Furthermore, anti-dsDNA, anti-Sm, anti-RNP, and CCL21 were associated with reduced pulmonary function in SLE. The results were rated with very low certainty of evidence, why they are hypothesis generating. Further studies addressing associations are needed.

BackgroundBirt-Hogg-Dub & eacute; syndrome (BHD), a rare genetic disease characterized by multiple pulmonary cysts, can lead to spontaneous pneumothorax, cutaneous hamartomas, renal cysts, and renal cell cancer. The overall aim of this study was to assess clinical characteristics of patients with BHD-emphasizing on trends in pulmonary function patterns.MethodsBy use of data from electronic patient journals, we conducted a retrospective cohort study on clinical characteristics and pulmonary function tests (PFT) from patients with BHD, who were clinically followed-up in a Danish tertiary referral center for rare and interstitial lung diseases.ResultsA total of 101 patients (44 men (43.6%); mean age 48.4 years (SD +/- 15.9 years)) with BHD were included. Chest HRCT scans revealed pulmonary cysts in 82.2% of whom 38.6% had experienced at least one pneumothorax (median 2; IQR1-4). Baseline PFT showed FEV1/FVC ratio and RV% within normal values of predicted. In 28.7% of the patients, a slight decrease in DLco below 80% of predicted was observed (mean 86.9% +/- SD 15.8%). At two years follow-up, there were no significant declines in FEV1 and FVC, nor after accounting for age, gender, and smoking. At baseline cutaneous manifestations were found in 58.4% of the patients, 47.5% had benign renal cysts, and 11.9% had renal tumours.ConclusionMore than 80% of patients with BHD presented with pulmonary cysts, but consistent with other studies all had normal PFTs at two years follow-up. We conclude that routine monitoring of pulmonary function and pulmonary follow-up may not be necessary in patients with BHD.