Hypersensitivity pneumonitis (HP) is an interstitial lung disease triggered by inhalation of a variety of environmental antigens. HP ranges from acute manifestations to progressive fibrosis and can be classified as nonfibrotic or fibrotic based on imaging and histopathological features. The pathophysiological mechanism of HP involves an exaggerated immune cell response and, in chronic stages, fibroblast activation leading to fibrosis. Diagnosis requires integrated assessment of exposure history, HRCT findings, BAL findings, and histopathological findings, as well as multidisciplinary discussion. In nonfibrotic HP patients, HRCT typically shows ground-glass opacities, centrilobular nodules, and mosaic attenuation, whereas, in fibrotic HP patients, HRCT often shows reticulation, traction bronchiectasis, and honeycombing. Typical histological features include cellular bronchiolitis, poorly formed granulomas, and interstitial fibrosis. Recent advances in imaging—including artificial intelligence–based pattern recognition—and investigation of biomarkers are improving precision and will likely contribute to the diagnostic investigation of HP. Management strategies depend on disease phenotype and severity, with antigen avoidance remaining the cornerstone of therapy. Immunomodulators such as corticosteroids, azathioprine, and mycophenolate may be used when there is evidence or suspicion of active inflammatory disease, whereas nintedanib is indicated for progressive fibrotic forms. Emerging phosphodiesterase 4B inhibitors have shown promise based on recent evidence. A greater number of comorbidities are observed in patients with fibrotic HP and are associated with worse survival, particularly pulmonary hypertension. Understanding genetic predisposition, comorbidities, and the transition from inflammation to fibrosis is essential to guide personalized treatment and improve outcomes. This review provides an update of pathophysiology, current diagnostic approaches, and therapeutic options, including emerging strategies.

To describe the demographic profile and risk factors for kidney stone formation in patients with sarcoidosis. 158 sarcoidosis patients were analyzed, comparing groups with and without kidney stones evaluating clinical and metabolic factors and medication use. Statistical analysis was carried out using R software (p < 0.05). The sample consisted of 138 patients (87.34

Background Lymphangioleiomyomatosis (LAM) is a rare disease that can occur sporadically (S-LAM) or associated with the tuberous sclerosis complex (TSC-LAM). The natural history of LAM is not completely understood, including whether there is a difference between the clinical courses of the two forms. This study aimed to compare the clinical, functional and tomographic features between S-LAM and TSC-LAM, and evaluate the annual rates of change in lung function. Methods This retrospective cohort study included patients with LAM followed up between 1994 and 2019. Clinical, functional and imaging variables were evaluated, and the lung cysts were automatically quantified. Quality of life and predictors of lung function impairment were accessed, and the annual rate of lung function decline was compared between S-LAM and TSC-LAM. Results Of the 107 patients included, 77 had S-LAM and 30 had TSC-LAM. Although patients with TSCLAM had a higher prevalence of renal angiomyolipomas and neurological and dermatological manifestations, pulmonary function tests were similar. Patients with S-LAM had a greater rate of forced expiratory volume in 1 s decline and a higher extent of cysts. Pneumothorax, desaturation in the 6-minute walking test and a higher extent of lung cysts were predictors of functional impairment. A greater impact on vitality and emotional health was observed in the TSC-LAM. Conclusion Greater functional decline and a higher cystic extension were found in patients with S-LAM. Our study provides a broad clinical, functional and tomographic characterisation of patients with LAM, adding valuable information to the existing evidence to better understand the two forms of the disease.

Abstract Background The diagnosis of cardiac involvement in sarcoidosis is challenging and often expensive. Purpose The aim of this study is to assess whether a new strain index proposed by the authors has incremental value in the evaluation of cardiac involvement, compared to the use of left ventricular (LV) global longitudinal strain (GLS). Methods This is a single-center, non-blinded, pilot cross-sectional study. Patients of both genders, >18 years old, with confirmed diagnosis of cardiac sarcoidosis according to the Heart Rhythm Society criteria, and controls consisting of individuals diagnosed with systemic sarcoidosis without cardiac involvement, were included. Patients with obesity grade 2 or higher , moderate or severe primary heart valve disease, myocardial diseases of other etiologies, established coronary artery disease, and inadequate acoustic window were excluded. All patients underwent transthoracic echocardiography, with subsequent measurements performed on a workstation. The following LV indexes were evaluated: GLS and the new proposed index, calculated by the ratio between LVEF and the sum of the two segments with the lowest absolute strain values. ROC curves were calculated for both parameters using an online dedicated software, with determination of the optimal cutoff point for both variables, corresponding to the point of highest sensitivity and specificity. Confidence intervals were established by the DeLong method, and curves were compared using the Bonferroni method. A two-tailed p value of 0.05 was considered significant. Results Twenty patients with cardiac involvement and twenty patients without cardiac involvement were evaluated. The results of the variables are presented in table 1. Conclusions The new index showed a larger area under the curve compared to isolated GLS, as well as higher sensitivity and specificity for the identified cutoff point, although without statistical significance, possibly due to the small sample size. Further studies are needed for subsequent validation of this innovative index.

Abstract Background Cardiac involvement is associated with worse prognosis and mortality in sarcoidosis. Diagnosis often requires expensive and less available tests. Purpose The aim of this study is to evaluate whether non-invasive measurement of myocardial work by transthoracic echocardiogram has incremental value in the diagnosis of cardiac involvement compared to left ventricular (LV) global longitudinal strain (GLS). Methods This is a cross-sectional, non-blinded, single-center pilot study. Patients of both genders > 18 years old, with confirmed diagnosis of cardiac sarcoidosis according to the Heart Rhythm Society criteria, and controls consisting of individuals diagnosed with systemic sarcoidosis without cardiac involvement, were included. Patients with obesity grade 2 or higher , moderate or severe primary heart valve disease, myocardial diseases of other etiologies, established coronary artery disease, and inadequate acoustic window were excluded. All patients underwent transthoracic echocardiography and non-invasive blood pressure measurement, followed by subsequent analysis involving the construction of a pression-strain curve. The following LV indexes were calculated: GLS, global work index, global constructive work, global wasted work, and global work efficiency. ROC curves were calculated for all variables using the EasyROC online tool (v 1.3.1), and these were later compared to GLS. Confidence intervals were established by the DeLong method, and curves were compared by the Bonferroni method. A two-tailed p value of 0.05 was considered significant. Results Twenty patients with cardiac involvement and twenty patients without cardiac involvement were evaluated. The results of the variables are presented in table 1. Conclusions With exception of wasted work, all other LV myocardial work variables showed statistical correlation with cardiac involvement in sarcoidosis patients. However, there was no incremental value of myocardial work indexes compared to the isolated use of GLS.

BACKGROUND:Interstitial lung abnormalities (ILA) and interstitial lung disease (ILD) are seen in up to 60% of individuals with rheumatoid arthritis (RA), some of which will progress to have a significant impact on morbidity and mortality rates. Better characterization of progressive interstitial changes and identification of risk factors that are associated with progression may enable earlier intervention and improved outcomes. RESEARCH QUESTION:What are baseline characteristics associated with RA-ILD progression? STUDY DESIGN AND METHODS:We performed a retrospective study in which all clinically indicated CT chest scans in adult individuals with RA from 2014 to 2016 were evaluated for interstitial changes, and the data were further subdivided into ILA and ILD based on clinical record review. Progression was determined visually and subsequently semiquantified. RESULTS:Those individuals with a spectrum of interstitial changes (64 of 293) were older male smokers and less likely to be receiving biologics/small molecule disease-modifying antirheumatic drugs. Of 44% of the individuals with ILA, 46% had had chest CT scans performed for nonpulmonary indications. Of the 56 individuals with ILA/ILD with sequential CT scans, 38% had evidence of radiologic progression over 4.4 years; 29% of of individuals with ILA progressed. Risk factors for progressive ILA/ILD included a subpleural distribution and higher baseline involvement. INTERPRETATION:Of 293 individuals with RA with clinically indicated CT scans, interstitial changes were observed in 22%, one-half of whom had had a respiratory complaint at the time of imaging; radiologic progression was seen in 38%. Of individuals with progressive ILA, one-half had had baseline CT scans performed for nonpulmonary indications. Subpleural distribution and higher baseline ILA/ILD extent were risk factors associated with progression. Prospective longitudinal studies of RA-ILA are necessary.

Serum vascular endothelial growth factor-D (VEGF-D) is a lymphangiogenic growth factor that is considered a valuable tool in the diagnosis of lymphangioleiomyomatosis (LAM). Previous studies have reported a wide variability in VEGF-D serum levels in LAM patients and it seems to be associated with pulmonary impairment and lymphatic involvement. We conducted a cross-sectional study from 2009 to 2017 that evaluated VEGF-D serum levels in a cohort of LAM patients who were never treated with mTOR inhibitors and compared them to healthy age-matched volunteers. Clinical and functional parameters were assessed and correlated with their respective serum VEGF-D levels. One hundred and four patients were included in the analysis. Serum VEGF-D levels were higher in LAM patients compared to healthy controls: 796 (404–1588) versus 162 (117–232) pg/mL, respectively (p < 0.001). Patients with tuberous sclerosis complex–LAM, TSC–LAM (20%), had higher levels of VEGF-D when compared to patients with sporadic LAM (80%) [1005 (641–2732) vs. 772 (370–1383), p = 0.05]. Serum VEGF-D levels were weakly correlated with DLCO (r = − 0.26, p = 0.001) and lymphatic involvement was more frequent in those with serum VEGF-D levels equal or above 800 pg/mL (35% vs. 13%, p = 0.02). In LAM, serum VEGF-D is weakly associated with lung function impairment and strongly associated with lymphatic involvement. VEGF-D is validated for use in Brazilian patients with LAM whose characteristics must be accounted for when evaluating their serum VEGF-D levels.

Abstract Introduction Sarcoidosis is a multi-systemic granulomatous disease of unknown etiology. Cardiac sarcoidosis (CS) has proven to be a clinically significant cause of unexplained ventricular dysfunction, atrioventricular block (AVB) and ventricular tachyarrhythmias (VT). Studies have suggested that clinically manifest cardiac involvement occurs in only 5% of patients with sarcoidosis. However, recent imaging studies have shown that cardiac involvement can be observed in up to 54.9% of patients with extracardiac sarcoidosis, mostly clinically silent, but that can eventually manifest into life-threatening arrhythmias. Purpose The purpose of this study was to evaluate the routine use of cardiac testing in patients with sarcoidosis. We aimed to evaluate the frequency with which clinical evaluation and cardiac testing are routinely utilized, the results of these tests, and how these results impacted downstream management. Methods This study was carried out in a tertiary hospital, assessing referred patients with suspected cardiac sarcoidosis. Clinically manifest CS was defined as the presence of ventricular systolic dysfunction, AVB or sustained VT. The cardiac involvement was evaluated with Late gadolinium-enhanced MRI and PET-CT with FDG. The diagnosis of cardiac sarcoidosis was performed using the criteria of the HRS. All patients had a biopsy with a histopathology suggestive of Sarcoidosis. Results Forty-one patients with sarcoidosis were evaluated. CS was confirmed in 46% (N=19), with exclusive cardiac involvement in 10% (N=2). The mean age was 53±9.6 years old and 53% (N=10) were female. Clinically manifest CS was present in 63% (N=12). The most prevalent initial cardiac manifestation was left ventricular dysfunction, in 58% (N=7), usually in the silent form (71%), with VT in 25% (N=3) and AVB in 17% (N=2). All patients with cardiac silent form had PET-CT with FDG or MRI suggestive of CS. The sensitivity of the MRI and PET-CT with FDG was 75% and 82%, respectively, while the concomitant performance of the two methods had a sensitivity of 100%, considering the HRS criteria as gold standard. Conclusion Cardiac involvement in patients with sarcoidosis is high and has important prognostic implications. With the enhancement of imaging tests, diagnosis of CS has significantly increased. PET-CT with FDG and MRI are very useful and effective in the evaluation of patients with CS.