Previous research has yielded conflicting results regarding the association between ACE genotypes and both susceptibility to sarcoidosis and disease prognosis. While some studies have found no significant impact of the ACE genotype on sarcoidosis susceptibility, others have suggested that the DD genotype may be associated with an increased risk of developing the disease and a poor prognosis. This study aimed to evaluate the influence of ACE genotypes on the susceptibility to sarcoidosis, prognosis and treatment response in patients with pulmonary sarcoidosis in Denmark. Patients with sarcoidosis were consecutively enrolled and genotyped using allele-specific PCR and high-resolution melting methods. The distribution of ACE genotypes was then compared with that of 400 healthy Danish individuals. To assess the impact of ACE genotypes on sarcoidosis prognosis, their association with changes in pulmonary function tests, radiological staging over 24 months, the frequency of Löfgren's syndrome, and treatment response were analyzed. Among 148 patients with sarcoidosis, the frequency of the II, ID, and DD genotypes was 25%, 52%, and 23%, respectively. No significant difference was observed in the distribution of ACE genotypes between patients and controls. Prognostic factors and treatment response also did not vary among the genotypes. Conclusion:Our findings do not support an association between the ACE I/D genotypes and sarcoidosis susceptibility, prognosis or response to treatment in a Danish cohort.

Sarcoidosis is a systemic inflammatory disease of unknown etiology that can affect multiple organs including a known complication of hypercalcemia. Many therapies, both steroidal and nonsteroidal, have been employed. However, the optimal therapy for hypercalcemia in sarcoidosis is unknown, with most data from case reports and small case series. More information is needed to determine which nonsteroidal agents control hypercalcemia in sarcoidosis patients, particularly for populations in whom steroids should be avoided. We sought to answer the question, which pharmacological agents control hypercalcemia in patients diagnosed with sarcoidosis? We performed a retrospective chart review on all adult patients at our hospital a diagnosis of Sarcoidosis and Hypercalcemia and a recorded calcium level of greater than 10.4 mg/dL. We then determined which agents were able to control their calcium to a level of 10.4 mg/dL or less for at least 6 months and 12 months. The most common efficacious treatments were prednisone, methotrexate, hydroxychloroquine, and prednisone + methotrexate. A positive linear relationship was found between ACE and highest calcium levels. No significant relationship between organ involvement or race and highest calcium levels were noted. There is currently little data or guidelines to best guide the treatment of hypercalcemia in sarcoidosis. This study represents the first with the primary aim to compare treatment options for hypercalcemia in sarcoidosis across a large cohort. Several non-steroidal options were identified that controlled hypercalcemia as a single agent. In addition, this study further investigated potential biomarkers for abnormal calcium metabolism as well as the relationship between calcium levels and organ involvement/race. Further work is needed to determine the most effective steroid sparing therapy to control hypercalcemia in sarcoidosis.

The association between sarcoidosis and autonomic dysfunction is demonstrated but poorly known. Heart rate variability (HRV) studies can provide a simple, non-invasive analysis of sympathetic and vagal tone in sarcoidosis. To date, the burden of steroid treatment on HRV has not been investigated. We aim to compare the HRV in sarcoidosis with general population and to explorate the burden of steroid treatment in HRV. Prospective analysis of 30 patients enrolled in Sarcoidosis Clinic of Policlinico Gemelli Hospital compared to 72 healthy control subjects. Continuous EKG recording over 24 hours has been performed and HRV was assessed using time and frequency domain analysis. Results were evaluated using a propensity score matching 1:1. Patients affected by sarcoidosis presented a mean age of 59.7±10.1 y and female gender predominance (n=20, 71.4%) %) while the control group was 54.6±16.0 y. The HRV analysis outlined a remarkable difference when both time / frequency domain were compared to the general, healthy population (ΔSDNN: 89.4±6.7 p=0.0001; ΔrMSSD: 5.7±2.6 p=0.03; ΔLF: 497.0±142.3 p=0.0007; ΔHF: 325.0±159.5 p=0.0442) suggesting a significant impact of sarcoidosis in autonomic activation. Remarkably the lung function tests and scadding stage did not show any relationship with the HRV (p=NS). At the same time, steroid treatment of ≥10 mg/day of prednisone for the previous 3 months was associated with a significant reduction of HRV in time (SDNN: Δ17.2±6.9, p=0.020) and frequency domain (LF: Δ355.2±125.7, p=0.009 and HF: Δ116.2±65.2, p=0.087). Lastly, the propensity score matching did confirm the previous results regarding time/frequency domain analysis. HRV is an effective tool for the autonomic evaluation in patients affected by sarcoidosis. The time (r-MSSD, SDNN, pNN50%) and frequency domain (HF/LF mean) analysis in sarcoidosis suggested that autonomic dysfunction is not related to the lung function or scadding stage though steroid treatment may impact.

This systematic review aims to summarize and evaluate the diagnostic performance of chest X-ray (CXR) compared with high-resolution computed tomography (HRCT) for detecting interstitial lung disease (ILD). what is the diagnostic accuracy and radiological finding of CXR in ILD, using HRCT as a gold standard. We systematically searched electronic databases to find studies evaluating the diagnostic accuracy of CXR and HRCT for detecting ILD. We used StataMP/17 and R statistical software for the quantitative analysis. Values like pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio with their 95% confidence interval, and the SROC curve was performed. We included a total of 18 studies involving 1917 patients. Compared to HRCT, CXR had sensitivity of 0.62 (95% CI: 0.47-0.74), specificity of 0.90 (95% CI: 0.85 - 0.93), positive likelihood ratio of 5.9 (95% CI 4.5-7.7), negative likelihood ratio of 0.43 (95% CI 0.31, 0.59), diagnostic odds ratio of 14 (95% CI 9 - 21), and area under the ROC curve of 0.88 (95% CI 0.85-0.91). Deek's plot showed no publication bias (p= 0.44). CXR had lower sensitivity compared with HRCT in detecting specific radiologic findings. Subgroup analysis revealed that a patient sample surpassing 100 indicated significantly higher specificity. Chest radiography exhibits moderate sensitivity and high specificity for detecting ILD when HRCT is regarded as the gold standard test. Although CXR is recommended as an initial diagnostic tool, it should not be solely relied upon for a definitive diagnosis, as it might miss some cases.

Homocysteine (Hcy) has been implicated in inflammatory, oxidative stress (OS), and endoplasmic reticulum (ER) stress mechanisms, which are hypothesized to contribute to the pathogenesis of interstitial lung disease (ILD). Given the paucity of evidence regarding Hcy's role in ILD, a two-sample Mendelian randomization study was performed to investigate the causal association between Hcy and ILD. We sourced data for total plasma Hcy from genome-wide association studies (GWAS) involving 44,147 European individuals. Data for ILD, idiopathic pulmonary fibrosis (IPF), IPF-related respiratory insufficiency, and systemic autoimmune disease-associated IPF were derived from the FinnGen consortium. To evaluate the causal association of reduced total plasma Hcy with ILD and related conditions, a range of Mendelian randomization (MR) analytical techniques were utilized to analyze the data. The results are reported as odds ratios (ORs) with corresponding 95% confidence intervals (CIs). We conducted sensitivity analyses through leave-one-out procedures and Radial MR plots. Our IVW estimates suggested that total plasma Hcy had a potential causal association with IPF (OR=0.649, 95%CI: 0.495-0.851), indicating that along with total plasma Hcy depressed 1 µmol/L, odds of IPF decreased 0.351. Although it seemed that decreased total plasma Hcy level is associated with lower odds of IPF-related respiratory insufficiency (OR=0.672, 95%CI: 0.489-0.924), due to the existence of horizontal pleiotropy, this causal association was not robust. In addition, MR leave-one-out and Radial MR sensitivity analyses showed there is no outlier among the selected IVs that could affect the potential causal relationship between Hcy and IPF. The levels of total plasma Hcy may bear a significant association with the risk of developing IPF, a specific form of ILD. However, to definitively establish a causal relationship between elevated Hcy levels and the pathogenesis of ILD, additional well-controlled, prospective studies are indispensable.

The aims of this study are (1) to investigate hypersensitivity pneumonitis (HP) related publications from Türkiye, (2) to discuss features of HP concerning our case series, and (3) to evaluate our patients in terms of diagnostic confidence according to guidelines. We conducted a comprehensive review of the literature to analyse cumulated data about HP publications originating from Türkiye. HP cases diagnosed and followed in last 5 year in our hospital were also evaluated. There are 34 Türkiye-originated HP-related publication. 13 articles were of pediatric origin and 19 of the articles included adult patients. Bird fancier's disease was the most frequent etiology of HP. A total of 138 patients were included in this study. 107 (77.5%) patients were female and 31 (22.5%) were male. A definite diagnosis has been made to 45 (33%) patients according to the ATS guideline and to 94 (68%) patients according to the ACCP guideline. 85 (62%) of the patients were in non-fibrotic form while 53 (38%) were in the fibrotic form. The most frequent etiology of our patient group was barn located under the houses in 58 (42%) patients. Barns under the houses in rural areas and moldy houses in urban areas are two main etiology of HP in our region. The presence of chronic form mostly in our patient group shows HP can not be diagnosed at an early stage. We propose chronic forms to classify as "chronic inflammatory" and "chronic fibrotic". Classifying patients according to two new HP guidelines results in a very high "definite diagnosis" according to ACCP compared to ATS.

Progressive pulmonary fibrosis (PPF) is an umbrella term for several interstitial lung diseases characterized by the progressive proliferation of fibrous tissue within the lung interstitium. This study aimed to assess the prevalence of depressive and anxiety symptoms among PPF patients and their repercussions on quality of life. Thirty-seven PPF patients undergoing treatment at the Institute for Pulmonary Diseases of Vojvodina, Serbia were enrolled. The SGRQ questionnaire assessed quality of life, while the DASS-21 questionnaire evaluated anxiety and depression symptoms. Sociodemographic and clinical factors were correlated with questionnaires outcomes, and the influence of anxiety and depression symptoms on quality of life was examined. Anxiety symptoms were detected in 56.75% of PPF patients and were more prevalent in patients previously diagnosed with depression and/or anxiety. Depression symptoms were detected in 45.95% of PPF patients and were more pronounced in the patients with longer duration of PPF, and positive history of malignancies. Stress symptoms were linked to lower PaO2 values and were detected in 37.84% of participants. HRQL was moderately to severely decreased and was lower in patients who, in addition to PPF, also suffered from other respiratory diseases, and was statistically significantly associated with lower DLCO values. A statistically significant correlation has been proven between the presence of anxiety, depression, and stress symptoms and HRQL, as measured through the "Symptoms" and "Impact" subscales of the SGRQ questionnaire. Anxiety and depression symptoms are highly prevalent among PPF patients, exerting substantial impacts on their quality of life.

The objective of this systematic review is to provide an overview of research that examined the relationship between pulmonary hypertension (PH) and the neutrophil-to-lymphocyte ratio (NLR). To identify the studies related to NLR, a search was done on PubMed, Scopus, and Web of Science with an end date of March 30th, 2023. A total of 25 studies were included in the review. These studies included a variety of pathologies that contribute to PH. We employed the Newcastle-Ottawa Scale to assess the quality of studies. For all studies, a significance level of P˂0.05 was used. In patients with sarcoidosis, chronic obstructive pulmonary disease, systemic sclerosis, chronic kidney disease, and congenital heart disease, NLR appears to be an independent predictor of PH. Also, it was frequently linked to the result, complications, and severity of the disease in PH patients. NLR may be utilized as a repeatable, inexpensive, and trustworthy proxy for the onset and severity of PH.

Pulmonary ossification is the histologic finding of mature bone with or without marrow elements within pulmonary tissue. The mechanism of formation is incompletely understood but thought to include metaplastic transformation of pulmonary fibroblasts to osteoblasts secondary to some form of chronic insult and the resulting inflammation from this insult. There are two classifications of pulmonary ossification, nodular and diffuse, based on histologic features. Management of pulmonary ossification is typically supportive, with treatment of the underlying process if one is identified. Here, we describe a man with known pulmonary sarcoidosis previously considered stable who presented with worsening dyspnea and was found to have pulmonary ossification and active cardiac and pulmonary sarcoidosis.