BACKGROUND:Hispanic/Latino individuals are the fastest growing subset of the US population. Although racial and ethnic differences in outcomes following lung transplantation have been recognized, they are not entirely understood. We compared long-term post-lung transplant outcomes in Hispanic/Latino and White non-Hispanic recipients and aimed to determine whether any differences are attributable to a specific racial-ethnic effect. METHODS:We performed a retrospective cohort study of first-time lung transplant recipients using UNOS/OPTN data from June 2005 through September 2020. We compared all-cause mortality post-transplantation in Hispanic/Latino and White non-Hispanic recipients using Kaplan-Meier curves, matched comparisons, and semiparametric (Cox) proportional hazards models, which were adjusted for relevant covariates and extended to account for time-varying effects and center random effects, and modeled graft failure against the competing risk of other-cause mortality. RESULTS:Of 18 915 transplant recipients for whom all study variables were available, 93% self-reported as White non-Hispanic, and 7.3% as Hispanic/Latino. Hispanics had similar short- and long-term survival compared to White non-Hispanics (1-year: 90% vs. 88%, p = 0.121; 5-year: 61% vs. 58%, p = 0.190; 10-year: 37% vs. 32%, p = 0.543). Nevertheless, overall survival curves (p = 0.037) and the fully adjusted model (aHR = 0.90, p = 0.047) suggested better outcomes among Hispanic/Latino recipients (p = 0.037). CONCLUSIONS:Despite several pre-transplantation indicators of worse health, Hispanic/Latino lung transplant recipients have similar long-term post-lung transplantation outcomes when compared to White non-Hispanic recipients.

We evaluated relationships between changes in lung function and changes in patient-reported outcomes (PROs) in 736 patients with idiopathic pulmonary fibrosis (IPF) enrolled in the IPF-PRO Registry. Weak correlations were observed between changes in percent predicted values for forced vital capacity or diffusing capacity of the lungs (DLco) and changes in St George’s Respiratory Questionnaire (SGRQ) total and activity scores and the 12-item Short Form Survey (SF-12) physical component summary score over 12-month periods. Patients who had a deterioration in SGRQ activity score or SF-12 PCS score of ≥ 5 units had numerically larger declines in lung function than other patients, but the differences were small. The weak relationships observed between changes in lung function and changes in PROs underscore the importance of evaluating both changes in lung function and changes in HRQL in clinical practice and clinical trials.

BACKGROUND:Pulmonary manifestations of inflammatory bowel disease (IBD) have been considered a rare extraintestinal manifestation, however recent evidence suggests otherwise. Previous work has focused on individual aspects of pulmonary manifestations between Crohn's disease (CD) and ulcerative colitis (UC). As such, we compared patients with CD and UC with respect to symptoms, imaging findings, lung function, treatments, and outcomes. METHODS:A single-center, retrospective, observational study was conducted that included patients aged 18 years and older with a confirmed diagnosis of either UC or CD, who had either a Chest Computed Tomography (CT) and/or Pulmonary Function Tests (PFTs) performed between 2014 and 2019. Data was collected from chart review. Comparisons were made between UC and CD groups. RESULTS:319 patients, with 221 diagnosed with CD and 98 with UC were included. Patients with UC exhibited a higher prevalence of coronary artery disease (p < 0.05) and a concomitant autoimmune disease (p < 0.05). 21/319 (6.6 %) patients exhibited IBD-related pulmonary disease. No differences in symptoms between patients with UC and CD were found. Common CT findings included ground glass opacities/consolidations (43.2 %), nodules (39.2 %), and emphysema (14.7 %), however these were not different between groups. The most common lung function abnormality was a presumed mixed ventilatory defect. In our cohort, patients with ulcerative colitis had a higher all cause mortality. CONCLUSION:Pulmonary abnormalities in patients with IBD are common and carry significant morbidity and mortality. We found no notable differences in clinical, physiologic, or radiographic manifestations between UC and CD patients despite differences in pathophysiology.

BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease associated with lung function decline and high mortality. RESEARCH QUESTION:What are the associations between thresholds of lung function decline and the risk of mortality in patients with IPF? STUDY DESIGN AND METHODS:The Idiopathic Pulmonary Fibrosis Prospective Outcomes Registry enrolled patients with IPF that was diagnosed or confirmed at the enrolling center within the prior 6 months. Associations between time to first decline in FVC or diffusing capacity of the lungs for carbon monoxide (Dlco) of ≥ 2% predicted, ≥ 5% predicted, and ≥ 10% predicted (and ≥ 15% predicted for Dlco) and risk of subsequent death or lung transplantation was assessed using Cox proportional hazards models with a time-dependent covariate. Models were unadjusted or adjusted for FVC and Dlco % predicted, age, sex, smoking status, BMI, antifibrotic treatment (yes or no), and oxygen use at enrollment. RESULTS:Among 1,001 patients, median follow-up time was 38.4 months. Significant associations were observed between all thresholds of decline in FVC and Dlco % predicted and the risk of death or lung transplantation in unadjusted and adjusted analyses. In adjusted analyses, absolute declines in FVC of ≥ 2% predicted, ≥ 5% predicted, and ≥ 10% predicted were associated with 1.8-fold, 2.3-fold, and 2.7-fold increases in the risk of subsequent death or lung transplantation, whereas absolute declines in Dlco of ≥ 2% predicted, ≥ 5% predicted, ≥ 10% predicted, and ≥ 15% predicted were associated with 2.0-fold, 1.4-fold, 1.5-fold, and 1.9-fold increases in the risk of subsequent death or lung transplantation, respectively. For Dlco, but not FVC, the increase in risk generally was greater for patients meeting a threshold based on a relative rather than an absolute decline. INTERPRETATION:Our results show that even small declines in FVC and Dlco % predicted inform prognosis in patients with IPF. CLINICAL TRIAL REGISTRY:ClinicalTrials.gov; No.: NCT01915511; URL: www. CLINICALTRIALS:gov.

BACKGROUND:Psoriasis is a chronic systemic autoimmune disease primarily affecting the skin and joints. Growing evidence suggests an association with pulmonary comorbidities, though lung involvement remains under characterized. We reviewed the literature and conducted a retrospective analysis to define pulmonary manifestations in psoriasis patients, termed Psoriasis-Associated Lung Disease (Psoriasis-LD). METHODS:We identified 251 adult psoriasis patients at our academic center (2012-2022) who had chest CT scans and/or pulmonary function tests (PFTs). Data included demographics, psoriasis phenotype/treatment, respiratory symptoms, PFTs, radiographic features, and outcomes. Psoriasis-LD was defined by symptoms and/or CT abnormalities and/or abnormal PFTs. CT findings were categorized as: fibrotic (traction bronchiectasis/honeycombing), airway disease (bronchial wall thickening/bronchiectasis), or ground-glass opacities (GGO)/consolidation. Statistical analyses included descriptive statistics, group comparisons, Kaplan-Meier, and Cox proportional hazards models. RESULTS:The mean patient age was 64.6 ± 14.7 years, with an equal gender distribution (50 % female). Common comorbidities included obesity, gastroesophageal reflux disease (GERD), and sleep apnea. CT abnormalities included pulmonary ground-glass opacification or consolidation (25.1 %), airway disease (8-9 %), and interstitial fibrosis (3-7 %), with over half of the patients displaying any one of these features. Airway disease and GGO were strongly linked to death or transplant (HR 2.07, 2.50, respectively). Follow-up showed that 39 % of patients died or received lung transplants. Interstitial lung disease (ILD) was confirmed in 8.8 %, mainly NSIP and UIP patterns and most patients with ILD had additional risk factors. CONCLUSION:Pulmonary abnormalities frequently occur in psoriasis patients and correlate with poorer outcomes, suggesting that psoriasis may be a significant risk factor for pulmonary complications. Earlier detection and multidisciplinary management are essential to improving patient outcomes.

Sarcoidosis is an inflammatory condition that can affect any part of the body, but most commonly affects the lungs. Many people with lung (pulmonary) sarcoidosis have manageable disease that does not impact them in the long term. However, some patients with pulmonary sarcoidosis develop complications that cause long-term (chronic) symptoms, such as shortness of breath and cough. These symptoms impair quality of life and may impair a person's ability to complete everyday activities at work and at home. Complications of pulmonary sarcoidosis also worsen the outcome of the disease (prognosis). It is important for patients with sarcoidosis to be aware of the journey that they may face with the disease so that they can better understand their condition and be part of decisions about their care. This article, co-authored by an experienced clinician and a patient, provides information for patients living with pulmonary sarcoidosis.

Sarcoidosis is a complex systemic disease. Our study aimed to (1) identify novel alleles associated with sarcoidosis susceptibility; (2) provide an in-depth evaluation of HLA alleles and sarcoidosis susceptibility and (3) integrate genetic and transcription data to identify risk loci that may more directly impact disease pathogenesis. We report a genome-wide association study of 1335 sarcoidosis cases and 1264 controls of European descent (EA) and investigate associated alleles in a study of African Americans (AA: 1487 cases and 1504 controls). The EA and AA cohort was recruited from multiple United States sites. HLA alleles were imputed and tested for association with sarcoidosis susceptibility. Expression quantitative locus and colocalization analysis were performed using a subset of subjects with transcriptome data. Forty-nine SNPs in the HLA region in HLA-DRA, -DRB9, -DRB5, -DQA1 and BRD2 genes were significantly associated with sarcoidosis susceptibility in EA, rs3129888 was also a risk variant for sarcoidosis in AA. Classical HLA alleles DRB1*0101, DQA1*0101 and DQB1*0501, which are highly correlated, were also associated with sarcoidosis. rs3135287 near HLA-DRA was associated with HLA-DRA expression in peripheral blood mononuclear cells and bronchoalveolar lavage from subjects and lung tissue and whole blood from GTEx. We identified six novel SNPs (out of the seven SNPs representing the 49 significant SNPs) and nine HLA alleles associated with sarcoidosis susceptibility in the largest EA population. We also replicated our findings in an AA population. Our study reiterates the potential role of antigen recognition and/or presentation HLA class II genes in sarcoidosis pathogenesis.

PURPOSE: While the role of IgE has been extensively studied in conditions such as asthma and allergic bronchopulmonary aspergillosis (ABPA), its role in interstitial lung disease (ILD) has not been elucidated.This study aims to describe the clinical and radiological manifestations as well as outcomes of patients with ILD and elevated IgE levels. METHODS:A retrospective review of adult patients with ILD with an elevated IgE level (>500 UI/ml), between 1/2011 and 12/ 2022, was performed.The diagnosis of ILD was confirmed by a multidisciplinary meeting.We report baseline characteristics and mortality.RESULTS: A total of 40 patients were included in the study.The median age was 61 years (IQR 49-70).Thirty patients (75%) were male.Twenty-seven patients (67%) carried the diagnosis of asthma.The median IgE level was 933 (IQR 628-1891).Eighteen patients (45%) had an eosinophil count >500 cells/mcl.Only four patients (10%) met criteria for ABPA.The most common abnormality detected on pulmonary function tests was intrinsic restrictive defect in (n¼16, 40%) followed by obstructive ventilatory defect (n¼15, 38%), and isolated reduction in DLCO (n¼3, 7.5%).Amongst radiological findings described, ground glass opacities were most common (n¼32, 80%) followed by traction bronchiectasis (n¼23, 58%), honeycombing (n¼12, 30%), micronodules (n¼5, 13%) and macronodules (n¼1, 3%).The most common ILD pattern recognized was non-specific interstitial pneumonia (NSIP: n¼17, 43%) followed by usual interstitial pneumonia (UIP: n¼11, 28%) and organizing pneumonia (OP: n¼5, 13%).Bronchoalveolar lavage was performed in 22 patients: mixed cellularity (n¼7), neutrophil predominant (n¼7), eosinophil predominant (n¼4) and lymphocyte-predominant (n¼4).Most patients were on systemic steroids (n¼37, 93%) and/ or inhaled steroids (n¼33, 83%).The most common cytotoxic agents used include mycophenolate mofetil (n¼10, 25%) and azathioprine (n¼5, 13%).Eleven patients died (28%) and one was transplanted during the study period.After controlling for IgE levels, age, eosinophil count, presence of asthma and oxygen requirement, a UIP pattern was associated with increased odds of mortality (OR: 8.9, 95% CI: 1.0-77.3,p¼0.04). CONCLUSIONS:The most common radiographic pattern in patients with elevated IgE levels was NSIP.Most patients were prescribed steroids and steroid sparing agents for disease control.ILD in patients with elevated IgE levels is associated with high mortality in patients with a UIP pattern. CLINICAL IMPLICATIONS:The disease process in patients with ILD and elevated IgE tends to be aggressive, especially in patients with a UIP pattern.Further investigation is required to identify the role of anti-IgE therapy in this patient population.

Background and aim: Inhalational exposures have been hypothesized to play a role in the pathogenesis of sarcoidosis. Herein, we describe a cohort of US Military personnel diagnosed with sarcoidosis during or after deployment to Southwest Asia and Afghanistan, who experienced complex inhalational exposures to burn pits and desert dust. Methods: Consecutive military personnel at four sub-specialty clinics across the United States were screened for deployment to Southwest Asia and Afghanistan and diagnosis of sarcoidosis based on 1999 ATS/ERS/WASOG Statement on Sarcoidosis. Detailed demographic, deployment and exposure data was collected. The data combined was analyzed after de-identification and local IRB approval. Results: Twenty-one patients met our case definition. Seventeen patients were male and 62% had extrapulmonary involvement, including 38% with musculoskeletal involvement. Conclusions: Our study suggests that the sarcoidosis in military personnel to Southwest Asia can be diagnosed many years after deployment. To our knowledge, this is the first case series to describe a group of military personnel diagnosed with sarcoidosis and exposures specific to military deployment to Southwest Asia.

BACKGROUND AND AIM:Cardiac sarcoidosis (CS) is the second most common cause of death in patients with sarcoidosis and data pertaining to its diagnosis and management is limited. We sought to describe diagnostic modalities and management of patients with CS in the United States, based on a national registry questionnaire. METHODS:We conducted a retrospective study based on a national registry investigating 3,835 respondents to the Foundation for Sarcoidosis Research Questionnaire. The registry includes patient surveys completed between June 2014 and August 2019. Summary and univariate analyses were performed. RESULTS:A total of 394 patients (10.3%) with CS were identified; 57% (n=223) were women and 81% (n=317) were white. The mean (±SD) age at diagnosis was 45 years (±13). CS was the initial presentation of sarcoidosis in 30%. Multiorgan involvement (≥3 organs) was present in 68%. Two-thirds of patients were admitted at least once to the hospital. Cardiac magnetic resonance imaging (74.4%) was the most common diagnostic modality used followed by positron emission tomography (PET) scan (59.3%) and cardiac biopsy (n=52, 13%).  Most patients received corticosteroids (86%) and steroid-sparing medications (61%) including methotrexate (26%) and tumor necrosis factor (TNF) inhibitors (19%). A combined cardioverter defibrillator and pacemaker (39%) was the most common cardiac device implanted. CONCLUSIONS:The prevalence of CS in this cohort was higher than previously described. CS was a common initial presentation of sarcoidosis. The diagnosis was most likely made using cMRI. Steroids, methotrexate and infliximab are the most common medications used. Conduction abnormalities and arrhythmias often occurred.

BACKGROUND Fibrocytes are BM-derived circulating cells that traffic to the injured lungs and contribute to fibrogenesis. The mTOR inhibitor, sirolimus, inhibits fibrocyte CXCR4 expression, reducing fibrocyte traffic and attenuating lung fibrosis in animal models. We sought to test the hypothesis that short-term treatment with sirolimus reduces the concentration of CXCR4+ circulating fibrocytes in patients with idiopathic pulmonary fibrosis (IPF).METHODS We conducted a short-term randomized double-blind placebo-controlled crossover pilot trial to assess the safety and tolerability of sirolimus in IPF. Participants were randomly assigned to sirolimus or placebo for approximately 6 weeks, and after a 4-week washout, they were assigned to the alternate treatment. Toxicity, lung function, and the concentration of circulating fibrocytes were measured before and after each treatment.RESULTS In the 28 study participants, sirolimus resulted in a statistically significant 35% decline in the concentration of total fibrocytes, 34% decline in CXCR4+ fibrocytes, and 42% decline in fibrocytes expressing α-smooth muscle actin, but no significant change in these populations occurred on placebo. Respiratory adverse events occurred more frequently during treatment with placebo than sirolimus; the incidence of adverse events and drug tolerability did not otherwise differ during therapy with drug and placebo. Lung function was unaffected by either treatment, with the exception of a small decline in gas transfer during treatment with placebo.CONCLUSION As compared with placebo, short-term treatment with sirolimus resulted in reduction of circulating fibrocyte concentrations in participants with IPF, with an acceptable safety profile.TRIAL REGISTRATION ClinicalTrials.gov, accession no. NCT01462006.FUNDING NIH R01HL098329 and American Heart Association 18TPA34170486.

PURPOSE:Sarcoidosis is a granulomatous disease affecting multiple organ systems characterized by noncaseating granulomas.It has a great predilection for the lungs manifesting as a variety of disorders ranging from sub-centimeter nodules to cavitary lung lesions and sometimes causing extensive structural lung damage thereby increasing the risk for lung infection particularly pneumonia.Our study was done to determine outcomes following hospitalization for pneumonia in sarcoidosis patients and the impact of sarcoidosis on mortality, length of stay and costs in patients admitted for pneumonia. METHODS:We used weighted data from National Inpatient Sample (NIS) database years 2018-2019 to analyze hospital admissions with a principal diagnosis of pneumonia, including all ICD codes with identifiable causes of pneumonia and ICD codes for unspecified causes of pneumonia and compared outcomes of patients with a secondary diagnosis of sarcoidosis.Primary outcomes were in-patient mortality due to any cause and need for mechanical ventilation.Secondary outcomes included length of stay and total hospital charges.We matched baseline characteristics and used multivariate logistic and linear regression to adjust for cofounders such as age, gender and other comorbidities.RESULTS: There was a total of 1,405,699 weighted admission with a principal diagnosis of pneumonia.17% of which were attributable to bacterial pneumonia, 7.1% with pneumonia related to influenza virus, 3% with pneumonia from other viral causes and 72.9% with unspecified pneumonia.Prevalence of sarcoidosis was 0.2% of all cases of pneumonia and pooled mortality was 0.02%.After adjusting for cofounders, we found that patients with sarcoidosis had a slightly higher chance of dying, although this was not statistically significant, adjusted odds ratio (aOR) 1.01, 95% CI: 0.12 -8.39, p¼0.99.There was no difference in the need for mechanical ventilation with patients with sarcoidosis having same risk as patients without.Patients with sarcoidosis spent 1.7 days less in the hospital compared to patients without sarcoidosis p¼0.003.Total charges for sarcoidosis patients on average was 16,411$ less than patients without sarcoidosis but this difference was not statistically significant p¼0.13. CONCLUSIONS:The presence of sarcoidosis does not seem to have a negative impact on patients admitted and treated for pneumonia.Patients with sarcoidosis had shorter length of stay compared to patients without sarcoidosis, there was a trend towards less total hospital charges, although this difference was not significant.CLINICAL IMPLICATIONS: Sarcoidosis is not an independent risk factor for mortality in patients admitted for pneumonia, patients with sarcoidosis do not have higher risk of needing mechanical ventilation when admitted to the hospital for pneumonia.

Introduction Respiratory infections are ubiquitous. The COVID-19 pandemic has refocused our attention on how morbid and potentially fatal they can be, and how host factors have an impact on the clinical course and outcomes. Due to a range of vulnerabilities, patients with sarcoidosis may be at higher risk of poor outcomes from respiratory infections. The objective of the SARCoidosis Outcomes in all respiratory Viral Infectious Diseases (SARCOVID) Study is to determine the short-term and long-term impacts of respiratory viral illnesses (COVID-19 and non-COVID-19) in sarcoidosis. Methods and analysis Up to 20 clinical sites across the USA are participating in the recruitment of 2000 patients for this observational, prospective study. To ensure that the study cohort is representative of the general population with sarcoidosis, participating sites include those dedicated to reaching under-represented minorities or patients from non-urban areas. Baseline data on demographic features, comorbidities, sarcoidosis characteristics and pre-enrolment lung function will be captured at study entry. During this 3-year study, all acute respiratory infectious events (from SARS-CoV-2 and any other respiratory pathogen) will be assessed and recorded at quarterly intervals. The level of required medical care and survival outcomes determine infection severity, and the impact of infection on quality of life measures will be recorded. Post-infection lung function and imaging results will measure the long-term impact on the trajectory of sarcoidosis. Patients will be analysed according to the clinical phenotypes of cardiac and fibrotic pulmonary sarcoidosis. Control groups include non-infected patients with sarcoidosis and patients with non-sarcoidosis interstitial lung disease. Ethics and dissemination Each site received local institutional review board approval prior to enrolling patients, with the consent process determined by local institution standards. Data will be published in a timely manner (goal <12 months) at the conclusion of the 3-year follow-up period and will be made available upon request.

CASE PRESENTATION:A 43-year-old woman with a medical history of hypothyroidism, psoriasis, and tobacco abuse (30-pack year history) who had quit smoking several months prior to presentation presented with pleuritic chest pain. She also noted a 2-year history of progressive numbness and weakness in her bilateral upper and lower extremities that now prevented her from completing her activities of daily living. She had worsening exertional dyspnea and a subjective 50-lb weight loss over the past year.

Allergic bronchopulmonary aspergillosis (ABPA) is a condition that most often occurs in patients with asthma or cystic fibrosis. The diagnosis is usually confirmed by the combination of clinical, radiographic, and immunologic criteria as there is not individual test to establish the diagnosis. We describe the case of a 64-year-old male with a prior medical history of moderate persistent asthma who presented with worsening cough and was found to have IgE positive for Aspergillus fumigatus with findings of diffuse bilateral pulmonary calcifications on HRCT.

OBJECTIVE:We aimed to determine the prevalence and clinical characteristics of self-reported hyperthyroidism in patients with sarcoidosis.METHODS:A national registry-based study investigating 3836 respondents to the Sarcoidosis Advanced Registry for Cures questionnaire in the period between June 2014 and August 2019 was conducted. This registry is generated from a web-based questionnaire that is self-reported by patients with sarcoidosis. We compared patients with sarcoidosis who had hyperthyroidism with those who did not. We used multivariate logistic regression analysis to study the association between hyperthyroidism and different cardiac manifestations in patients with sarcoidosis.RESULTS:Three percent of the study respondents self-reported having hyperthyroidism and were generally middle-aged Caucasian women. Compared with patients without hyperthyroidism, patients with hyperthyroidism had more sarcoidosis-related comorbidities (59% vs 43%, P = .001) and more steroid-related comorbidities (56% vs 44%, P = .01), but there was no difference in the sarcoidosis-specific treatments they received, which included corticosteroids. Patients with hyperthyroidism reported sarcoidosis involvement of the heart (26.6% vs 14.9%, P = .005), kidneys (14.9% vs 8%, P = .033) and sinuses (17.7% vs 10.2%, P = .030) more frequently. Cardiac manifestations that were more frequently reported in patients with hyperthyroidism included atrial arrhythmias (11.3% vs 6.3%, P = .046), ventricular arrhythmias (17.2% vs 7.5%, P < .001), congestive heart failure (10.4% vs 5%, P = .017), and heart block (9.4% vs 4.7%, P = .036).CONCLUSION:Hyperthyroidism is infrequent in patients with sarcoidosis but is potentially associated with different cardiac manifestations. We suggest considering routine screening for hyperthyroidism in patients with sarcoidosis, especially in those with cardiac involvement. Further studies are needed to investigate the impact of identifying and treating hyperthyroidism in patients with sarcoidosis.