Tofacitinib as a Steroid-Sparing Therapy in Pulmonary Sarcoidosis, an Open-Label Prospective Proof-of-Concept Study.

This is a prospective, open-label, proof-of-concept study of tofacitinib, a Janus kinase inhibitor, as a steroid-sparing therapy in corticosteroid-dependent pulmonary sarcoidosis. Five patients with corticosteroid-dependent pulmonary sarcoidosis were treated with tofacitinib 5 mg twice daily. The primary endpoint was a ≥ 50% reduction in corticosteroids at week 16 with no worsening in pulmonary function or respiratory symptoms. 60% of patients (3/5) met the primary endpoint. One patient was lost to follow up prior to steroid taper, and another was withdrawn due to worsening of known neurosarcoidosis. The three patients who met the primary endpoint each tapered to ≤ 5 mg/day prednisone, respiratory symptoms improved, and spirometry remained stable. In this proof-of-concept study, the addition of a JAK-inhibitor allowed 60% of patients with pulmonary sarcoidosis to successfully taper corticosteroids. JAK-inhibitors are a promising therapy for pulmonary sarcoidosis, which require further investigation in randomized trials.Trial Registration clinicaltrials.gov NCT03793439; registered Jan 4, 2019.

Diagnosis and Detection of Sarcoidosis. An Official American Thoracic Society Clinical Practice Guideline.

Background: The diagnosis of sarcoidosis is not standardized but is based on three major criteria: a compatible clinical presentation, finding nonnecrotizing granulomatous inflammation in one or more tissue samples, and the exclusion of alternative causes of granulomatous disease. There are no universally accepted measures to determine if each diagnostic criterion has been satisfied; therefore, the diagnosis of sarcoidosis is never fully secure.Methods: Systematic reviews and, when appropriate, meta-analyses were performed to summarize the best available evidence. The evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation approach and then discussed by a multidisciplinary panel. Recommendations for or against various diagnostic tests were formulated and graded after the expert panel weighed desirable and undesirable consequences, certainty of estimates, feasibility, and acceptability.Results: The clinical presentation, histopathology, and exclusion of alternative diagnoses were summarized. On the basis of the available evidence, the expert committee made 1 strong recommendation for baseline serum calcium testing, 13 conditional recommendations, and 1 best practice statement. All evidence was very low quality.Conclusions: The panel used systematic reviews of the evidence to inform clinical recommendations in favor of or against various diagnostic tests in patients with suspected or known sarcoidosis. The evidence and recommendations should be revisited as new evidence becomes available.

Physiological predictors of survival in patients with sarcoidosis-associated pulmonary hypertension: results from an international registry.

INTRODUCTION: Sarcoidosis-associated pulmonary hypertension (SAPH) is associated with reduced survival in single-centre studies. The international Registry for SAPH (ReSAPH) with long-term follow-up was established to enrich our knowledge of this complication of sarcoidosis. This analysis aims to elucidate factors associated with reduced transplant-free survival in SAPH patients. METHODS: ReSAPH contains prospectively collected outcomes of SAPH patients since the time of registry enrolment. Information analysed includes right heart catheterisation data, pulmonary function testing, chest radiography, Scadding stage and 6-min walk distance (6MWD), among others. Cox regression models were used to identify independent predictors of transplant-free survival. RESULTS: Data from 215 patients followed for a mean±sd 2.5±1.9 years were available for analysis. In the 159 precapillary patients, the Kaplan-Meier-adjusted 1-, 3- and 5-year transplant-free survival was 89.2%, 71.7% and 62.0%, respectively. Kaplan-Meier-adjusted 1-, 3- and 5-year transplant-free survival in the incident group was 83.5%, 70.3% and 58.3%, respectively, and in the prevalent group was 94.7%, 72.2% and 66.3%, respectively. Patients with reduced diffusing capacity of the lung for carbon monoxide (D LCO) (<35% predicted) and 6MWD <300 m in the precapillary cohort had significantly worse transplant-free survival. Reduced 6MWD and preserved forced expiratory volume (FEV1)/forced vital capacity (FVC) ratio were identified as independent risk factors for reduced transplant-free survival in the precapillary cohort. CONCLUSION: Reduced D LCO (<35% pred) and 6MWD (<300 m) at the time of registry enrolment were associated with reduced transplant-free survival in the overall precapillary cohort. Preserved FEV1/FVC ratio was identified as an independent risk factor for worsened outcomes.

An update on sarcoidosis-associated pulmonary hypertension.

PURPOSE OF REVIEW: Pulmonary hypertension in sarcoidosis is a well known entity. Sarcoidosis-associated pulmonary hypertension (SAPH) incurs substantial morbidity and mortality. This review examines recent literatures published on epidemiology, prognosis and therapeutic management in SAPH. RECENT FINDINGS: Several registries have been published between 2017 and 2020. The consensus conclusion - SAPH is a harbinger for poor prognosis. Several factors were noted for predicting adverse outcome in SAPH like reduced 6-min walk distance and diffusing capacity for carbon monoxide. Given its adverse outcome, experts have now focused on methods for early screening of SAPH in sarcoid patients. The exploration of pulmonary vasodilator drugs in SAPH is ongoing. In recent times, trials have been published utilizing Macitentan and parenteral prostacyclin in severe SAPH. Although these trials show encouraging results, the evidence from these studies are limited to approve these agents as preferred drugs for treating SAPH. A large multicentric trial of drugs used for pulmonary arterial hypertension with meaningful, yet feasible, event driven endpoint is still lacking. Lately, interventional treatment by pulmonary artery balloon pulmonary angioplasty and stenting has gained traction for treating pulmonary artery stenosis and chronic thromboembolic pulmonary hypertension. However, the conclusion is still based on small cohorts or case series. SUMMARY: Several registries have highlighted SAPH portends an unfavorable consequence. On the contrary, no published guideline exists to treat SAPH. The precise role of immunosuppressive agents is unclear. The limited evidence favoring use of pulmonary vasodilators arise from small retrospective case series and/or single-center nonrandomized observational studies. Further multicenter randomized research is warranted to better define patient population to treat and how best to treat them.

Advanced pulmonary sarcoidosis.

PURPOSE OF REVIEW: Mortality in patients with sarcoidosis has primarily been attributed to advanced pulmonary sarcoidosis. This review aims to provide an update on recent clinical studies that help to better phenotype these patients, discuss new treatment options, and suggest areas where additional research is needed. RECENT FINDINGS: Diagnosis and management of advanced pulmonary sarcoidosis has changed as new technologies and treatment options have emerged. Clinical phenotypes of advanced disease have evolved to show overlap in presentation with other interstitial lung diseases. Assessment involves more advanced imaging modalities. New promising treatment options are being studied. Pulmonary rehabilitation and lung transplantation are being utilized to improve health-related quality of life and survival. SUMMARY: Patients with advanced pulmonary fibrosis can have variable clinical, radiographic, histopathologic presentation. Given the poor health-related quality of life and high rates of mortality, medical therapy and pulmonary rehabilitation may benefit these patients. Lung transplantation should be considered in those with end-stage disease.

Overlap Syndromes in Sarcoidosis: Clinical Features and Outcomes.

Sarcoidosis is a multisystem inflammatory disease characterized by noncaseating granulomatous inflammation. While pulmonary sarcoidosis is most common, extrapulmonary involvement occurs in 50 to 74% of patients and can be the presenting abnormality in some patients. The diagnosis of sarcoidosis is based on a compatible clinical presentation in combination with granulomas on histology and exclusion of other causes. However, the absence of a diagnostic biomarker for sarcoidosis, in addition to the overlap of granulomatous inflammation and nonspecific clinical findings with other diseases, often results in a delayed diagnosis. Sarcoidosis overlap syndromes are typically described when sarcoidosis is diagnosed in the presence of another disease (concurrently or sequentially) with shared clinical and histologic features, or when sarcoidosis presents with clinical features typically observed in, but not diagnostic of, other diseases. Awareness of overlap syndromes is important for clinicians to avoid diagnostic errors and evaluate for concomitant diagnoses that may impact the management and outcome of sarcoidosis. This article is intended to provide an overview of these presentations and the most commonly associated diseases, with attention to their prevalence, clinical features, and reciprocal impacts on disease outcomes.

Sarcoidosis-Associated Pulmonary Hypertension.

Pulmonary hypertension (PH) is a well-known complication of sarcoidosis, defined by a mean pulmonary artery pressure of ≥25 mm Hg. Since both PH and sarcoidosis are rare diseases, data on sarcoidosis-associated PH (SAPH) is retrieved mostly from small retrospective studies. Estimated prevalence of SAPH ranges from 3% in patients referred to a tertiary center up to 79% in patients awaiting lung transplant. Most patients with SAPH show advanced parenchymal disease as the underlying mechanism. However, some patients have disproportional elevated pulmonary artery pressure, and PH can occur in sarcoidosis patients without parenchymal disease. Other mechanisms such as vascular disease, pulmonary embolisms, postcapillary PH, extrinsic compression, and other sarcoidosis-related comorbidities might contribute to SAPH. The diagnosis of PH in sarcoidosis is challenging since symptoms and signs overlap. Suspicion can be raised based on symptoms or tests, such as pulmonary function tests, laboratory findings, electrocardiography, or chest CT. PH screening mainly relies on transthoracic echocardiography. Right heart catheterization should be considered on a case-by-case basis in patients with clinical suspicion of PH, taking into account clinical consequences. Treatment options are considered on patient level in a PH expert center, and might include oxygen therapy, immunosuppressive, or PH-specific therapy. However, qualitative evidence is scarce. Furthermore, in a subset of patients, interventional therapy or eventually lung transplant can be considered. SAPH is associated with high morbidity. Mortality is higher in sarcoidosis patients with PH compared with those without PH, and increases in patients with more advanced stages of sarcoidosis and/or PH.

Advanced Pulmonary Sarcoidosis.

At least 5% of sarcoidosis patients die from their disease, usually from advanced pulmonary sarcoidosis. The three major problems encountered in advanced pulmonary sarcoidosis are pulmonary fibrosis, pulmonary hypertension, and respiratory infections. Pulmonary fibrosis is the result of chronic inflammation, but other factors including abnormal wound healing may be important. Sarcoidosis-associated pulmonary hypertension (SAPH) is multifactorial including parenchymal fibrosis, vascular granulomas, and hypoxia. Respiratory infections can be cause by structural changes in the lung and impaired immunity due to sarcoidosis or therapy. Anti-inflammatory therapy alone is not effective in most forms of advanced pulmonary sarcoidosis. New techniques, including high-resolution computer tomography and 18F-fluorodeoxyglucose positron emission tomography (PET) have proved helpful in identifying the cause of advanced disease and directing specific therapy.

Pulmonary Rehabilitation in Patients with Pulmonary Sarcoidosis: Impact on Exercise Capacity and Fatigue.

BACKGROUND: There is limited evidence regarding the impact of multidisciplinary pulmonary rehabilitation (PR) on exercise capacity and fatigue in patients with pulmonary sarcoidosis. The aim of this study was to evaluate the impact on exercise capacity and fatigue following PR, and to examine whether baseline fatigue was related to change in peak oxygen uptake (ΔV̇O2peak). METHODS: Forty-one patients with pulmonary sarcoidosis attending a 4-week inpatient PR program were recruited to this pre-post study. Both maximal exercise capacity, defined as V̇O2peak and measured with a cardiopulmonary exercise test, and fatigue, assessed with the Fatigue Assessment Scale (score 10-50 points), were measured before and after PR. RESULTS: There was a statistically significant improvement in V̇O2peak (1.2 ± 2.3 mL/kg/min, p = 0.002), and fatigue decreased significantly (-1.7 ± 3.9 points, p = 0.009) following PR. Unadjusted linear regression analyses demonstrated that age (B = -0.076, p = 0.017) and baseline fatigue (B = 0.196, p = 0.001) were predictors for change in V̇O2peak, while in adjusted analyses (age, sex, baseline V̇O2peak, baseline fatigue, and diffusion capacity of the lung for carbon monoxide), only baseline fatigue predicted change in V̇O2peak following PR (B = 0.165, p = 0.026). CONCLUSION: A 4-week multidisciplinary PR program improves maximal exercise capacity and reduces fatigue in patients with pulmonary sarcoidosis. Baseline fatigue only partly predicted change in V̇O2peak following PR.

The Role of Urinary Calcium and Chitotriosidase in a Cohort of Chronic Sarcoidosis Patients.

BACKGROUND: Calcium metabolism alterations are quite common in sarcoidosis and have been correlated with disease activity. OBJECTIVES: The aim of the study was to investigate the clinical significance of calcium metabolism alterations in patients with chronic sarcoidosis. We paid particular attention to associations with specific disease phenotypes and chitotriosidase (CTO) expression. METHODS: 212 chronic sarcoidosis patients (mean age 56.07 ± 12 years; 97 males) were retrospectively recruited. Demographic, clinical, functional, and radiological data, and serum-urinary calcium metabolism were entered into an electronical database for analysis. Levels of CTO and angiotensin-converting enzyme (ACE) were measured and bone mineral density and lung function tests were conducted. RESULTS: Hypercalciuria and hypercalcemia were observed in 18.8 and 1.8% of patients, respectively. Urinary calcium levels correlated with CTO activity (r = 0.33, p = 0.0042). Patients with worsening persistent disease showed the highest levels of urinary calcium. Diffusing capacity of the lung for carbon monoxide (DLCO) percentage correlated inversely with urinary calcium (r = 0.1482; p = 0.0397). CONCLUSIONS: Calcium metabolism alteration, particularly hypercalciuria, was observed in a significant percentage of patients of sarcoidosis. Urinary calcium was correlated with clinical status, DLCO, and serum CTO activity, suggesting its potential role as a biomarker of the activity and severity of sarcoidosis.

Moderate or Severe Impairment in Pulmonary Function is Associated with Mortality in Sarcoidosis Patients Infected with SARS­CoV­2.

PURPOSE: To investigate whether sarcoidosis patients infected with SARS-CoV-2 are at risk for adverse disease outcomes. STUDY DESIGN AND METHODS: This retrospective study was conducted in five hospitals within the Mount Sinai Health System during March 1, 2020 to July 29, 2020. All patients diagnosed with COVID-19 were included in the study. We identified sarcoidosis patients who met diagnostic criteria for sarcoidosis according to accepted guidelines. An adverse disease outcome was defined as the presence of intubation and mechanical ventilation or in-hospital mortality. In sarcoidosis patients, we reported (when available) the results of pulmonary function testing measured within 3 years prior to the time of SARS­CoV­2 infection. A multivariable logistic regression model was used to generate an adjusted odds ratio (aOR) to evaluate sarcoidosis as a risk factor for an adverse outcome. The same model was used to analyze sarcoidosis patients with moderate and/or severe impairment in pulmonary function. RESULTS: The study included 7337 patients, 37 of whom (0.5%) had sarcoidosis. The crude rate of developing an adverse outcome was significantly higher in patients with moderately and/or severely impaired pulmonary function (9/14 vs. 3/23, p = 0.003). While the diagnosis of sarcoidosis was not independently associated with risk of an adverse event, (aOR 1.8, 95% CI 0.9-3.6), the diagnosis of sarcoidosis in patients with moderately and/or severely impaired pulmonary function was associated with an adverse outcome (aOR 7.8, 95% CI 2.4-25.8). CONCLUSION: Moderate or severe impairment in pulmonary function is associated with mortality in sarcoidosis patients infected with SARS­CoV­2.

Design of a randomized controlled trial to evaluate effectiveness of methotrexate versus prednisone as first-line treatment for pulmonary sarcoidosis: the PREDMETH study.

BACKGROUND: Treatment of pulmonary sarcoidosis is recommended in case of significant symptoms, impaired or deteriorating lung function. Evidence-based treatment recommendations are limited and largely based on expert opinion. Prednisone is currently the first-choice therapy and leads to short-term improvement of lung function. Unfortunately, prednisone often has side-effects and may be associated with impaired quality of life. Methotrexate is presently considered second-line therapy, and appears to have fewer side-effects. OBJECTIVE: The primary objective of this trial is to investigate the effectiveness and tolerability of methotrexate as first-line therapy in patients with pulmonary sarcoidosis compared with prednisone. The primary endpoint of this study will be the change in hospital-measured Forced Vital Capacity (FVC) between baseline and 24 weeks. Secondary objectives are to gain more insights in response to therapy in individual patients by home spirometry and patient-reported outcomes. Blood biomarkers will be examined to find predictors of response to therapy, disease progression and chronicity, and to improve our understanding of the underlying disease mechanism. METHODS/DESIGN: In this prospective, randomized, non-blinded, multi-center, non-inferiority trial, we plan to randomize 138 treatment-naïve patients with pulmonary sarcoidosis who are about to start treatment. Patients will be randomized in a 1:1 ratio to receive either prednisone or methotrexate in a predefined schedule for 24 weeks, after which they will be followed up in regular care for up to 2 years. Regular hospital visits will include pulmonary function assessment, completion of patient-reported outcomes, and blood withdrawal. Additionally, patients will be asked to perform weekly home spirometry, and record symptoms and side-effects via a home monitoring application for 24 weeks. DISCUSSION: This study will be the first randomized controlled trial comparing first-line treatment of prednisone and methotrexate and provide valuable data on efficacy, safety, quality of life and biomarkers. If this study confirms the hypothesis that methotrexate is as effective as prednisone as first-line treatment for sarcoidosis but with fewer side-effects, this will lead to improvement in care and initiate a change in practice. Furthermore, insights into the immunological mechanisms underlying sarcoidosis pathology might reveal new therapeutic targets. TRIAL REGISTRATION: The study was registered on the 19th of March 2020 in the International Clinical Trial Registry, www.clinicaltrials.gov; ID NCT04314193 .

Plasma mitochondrial DNA is associated with extrapulmonary sarcoidosis.

Sarcoidosis is an unpredictable granulomatous disease in which African Americans disproportionately experience aggressive phenotypes. Mitochondrial DNA (mtDNA) released by cells in response to various stressors contributes to tissue remodelling and inflammation. While extracellular mtDNA has emerged as a biomarker in multiple diseases, its relevance to sarcoidosis remains unknown. We aimed to define an association between extracellular mtDNA and clinical features of sarcoidosis.Extracellular mtDNA concentrations were measured using quantitative PCR for the human MT-ATP6 gene in bronchoalveolar (BAL) and plasma samples from healthy controls and patients with sarcoidosis from The Yale Lung Repository; associations between MT-ATP6 concentrations and Scadding stage, extrapulmonary disease and demographics were sought. Results were validated in the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis cohort.Relative to controls, MT-ATP6 concentrations in sarcoidosis subjects were robustly elevated in the BAL fluid and plasma, particularly in the plasma of patients with extrapulmonary disease. Relative to Caucasians, African Americans displayed excessive MT-ATP6 concentrations in the BAL fluid and plasma, for which the latter compartment correlated with significantly higher odds of extrapulmonary disease.Enrichments in extracellular mtDNA in sarcoidosis are associated with extrapulmonary disease and African American descent. Further study into the mechanistic basis of these clinical findings may lead to novel pathophysiologic and therapeutic insights.

Paediatric sarcoidosis.

Paediatric sarcoidosis is an extremely rare disease characterized by a granulomatous inflammation. The estimated incidence is 0.6-1.02/100,000 children, but in the absence of international registers, the disease is probably under-reported. Its pathophysiologic basis is not clearly understood but the current hypothesis is a combination of a genetic predisposition and an environmental exposure that could be either organic or mineral. Contrary to adult forms of the disease, general symptoms are often at the forefront at diagnosis. In its most frequent form, paediatric sarcoidosis is a multi-organ disorder affecting preferentially the lungs, the lymphatic system and the liver, but all organs can be affected. This review aims to provide an overview of current knowledge on sarcoidosis in children, providing a summary of the data available from cohort studies on the presentation, the management and the evolution of the disease in this specific population.

Physical Inactivity in Pulmonary Sarcoidosis.

PURPOSE: Reduced physical activity in many chronic diseases is consistently associated with increased morbidity. Little is known about physical activity in sarcoidosis. The aim of this study was to objectively assess physical activity in patients with pulmonary sarcoidosis and investigate its relationship with lung function, exercise capacity, symptom burden, and health status. METHODS: Physical activity was assessed over one week in 15 patients with pulmonary sarcoidosis and 14 age-matched healthy controls with a tri-axial accelerometer (ActivPal™) and the International Physical Activity Questionnaire (IPAQ). All participants underwent pulmonary function tests, 6-min walk test (6MWT) and completed the Fatigue Assessment Scale (FAS), Medical Research Council (MRC) Dyspnoea Scale and the King's Sarcoidosis Questionnaire (KSQ). RESULTS: Patients with sarcoidosis had significantly lower daily step counts than healthy controls; mean (SD) 5624 (1875) versus 10,429 (2942) steps (p < 0.01) and a trend towards fewer sit-to-stand transitions each day (p = 0.095). Only two patients (13%) self-reported undertaking vigorous physical activity (IPAQ) compared to half of healthy individuals (p < 0.01). Daily step count was significantly associated with 6MWT distance in sarcoidosis (r = 0.634, p = 0.01), but not with forced vital capacity (r = 0.290), fatigue (r = 0.041), dyspnoea (r = -0.466) or KSQ health status (r = 0.099-0.484). Time spent upright was associated with fatigue (r = -0.630, p = 0.012) and health status (KSQ Lung scores r = 0.524, p = 0.045), and there was a significant correlation between the number of sit-to-stand transitions and MRC dyspnoea score (r = -0.527, p = 0.044). CONCLUSION: Physical activity is significantly reduced in sarcoidosis and is associated with reduced functional exercise capacity (6MWD). Fatigue, exertional symptoms and health status were more closely associated with time spent upright and the number of bouts of physical activity, as compared to step counts. Further studies are warranted to identify the factors that determine different physical activity profiles in sarcoidosis.

Sarcoidosis and Work Participation: The Need to Develop a Disease-Specific Core Set for Assessment of Work Ability.

OBJECTIVE: Sarcoidosis, an inflammatory multi-organ disease with a wide variety of clinical manifestations, affecting people of working age. Patients suffer from a broad spectrum of physical symptoms of varying severity that impact function including cognitive impairment and disabling fatigue. The Dutch Sarcoidosis Society identified a knowledge gap in various facets related to work ability. The aim of this study was to assess sarcoidosis patients' perceived problems related to work performance, employer, and disability evaluations. METHODS: A cross-sectional web-based anonymous survey was conducted among Dutch sarcoidosis patients recruited through sarcoidosis patient societies and outpatient sarcoidosis clinics. This investigation queried work performance, employer support, and disability evaluations. RESULTS: The study sample included 755 patients of whom 43% (n = 328) had undergone disability evaluation and were significantly more likely to experience extrapulmonary symptoms, severe fatigue, reduced exercise capacity along with memory problems and concentration problems with higher mean FAS and SFNSL-scores. Of these 328, 37% (n = 121) perceived they had not been listened to or taken seriously at assessments, and 38% (n = 124) disagreed with the outcome of disability assessments by benefits authorities; 75% (n = 93) appealed or requested re-assessment. DISCUSSION: A better understanding of sarcoidosis-related impact on work ability and quantification of disease burden is needed. Education for medical examiners and employers on sarcoidosis may improve quality of assessments and work accommodations. Development of guidelines for benefit authorities, which consider the broad impact of sarcoidosis beyond that of reduced pulmonary function, including extra-pulmonary assessment like fatigue, cognitive difficulties, as well as other organ involvement are needed.

Sarcoidosis and calcium homeostasis disturbances-Do we know where we stand?

The majority of cases involving hypercalcemia in the setting of sarcoidosis are explained by the overproduction of calcitriol by activated macrophages. Vitamin D takes part in the regulation of granuloma formation. However, using vitamin D metabolites to assess the activity of the disease is still problematic, and its usefulness is disputable. In some cases, though, a calcium metabolism disorder could be a valuable tool (i.e. as a marker of extrathoracic sarcoidosis). Although sarcoidosis does not cause a decrease in bone mineral density, increased incidence of vertebral deformities is noted. Despite increasing knowledge about calcium homeostasis disorders in patients with sarcoidosis, there is still a need for clear guidelines regarding calcium and vitamin D supplementation in these patients.

Why do people die from pulmonary sarcoidosis?

PURPOSE OF REVIEW: In sarcoidosis, the design and validation of an appropriate risk stratification strategy is hampered by the considerable variability in initial presentation, disease evolution, and outcome. Although spontaneous resolution of the disease is described in a large proportion of patients, approximately 20-30% would present with chronic or progressive lung disease that has been associated with morbidity and mortality. Higher morbidity and mortality can be related to both the disease severity and extent as well as its treatments. We review the utility of integration of clinical, pathological, and radiological features of pulmonary sarcoidosis to detect pulmonary sarcoidosis patient at risk of developing severe, fibrotic lung disease. RECENT FINDINGS: Recently published studies suggested a mortality rate of 11-14 per 1000 person-years. Demographic characteristics such as age, sex, and race may play a role but conflicting evidence are reported depending on the origin of the population. To date, there are no tools that can reliably predict the exact group of pulmonary sarcoidosis patients to progress to fibrosis. Imaging contributes significantly to the diagnosis and management of patients with sarcoidosis as it can provide useful information regarding the discrimination between reversible and irreversible disease, the extent of the parenchymal damage and the presence of possible complications. Symptoms and lung function tests are the rest of the key determinants and their change over time should be considered. SUMMARY: This review concentrates on the definition of advanced pulmonary sarcoidosis and determinants of mortality in the pulmonary sarcoidosis group of patients.

Physical Activity and Fatigue in Patients with Sarcoidosis.

BACKGROUND: Little is known about physical activity in daily life among patients with sarcoidosis. Fatigue is a frequent and disabling symptom that might negatively affect physical activity levels. METHODS: In patients with sarcoidosis, we measured physical activity (steps per day) by accelerometry (SenseWear Armband) for 1 week. We assessed lung function (DLCO, FVC), exercise capacity (6-min walking distance [6MWD]), health-related quality of life (St George's Respiratory Questionnaire [SGRQ]), generic quality of life (12-Item Short-Form Health Survey [SF-12]), and fatigue (Multidimensional Fatigue Inventory [MFI-20]). RESULTS: We investigated 57 patients with sarcoidosis (mean age 50 years, 56% male, mean DLCO 73% predicted, mean FVC 91% predicted, mean 6MWD 525 m, mean steps per day 7,490), of whom n = 14 (25%) had severe fatigue. The MFI-20 subscales "reduced activity" and "physical fatigue" were weakly associated with steps per day on a bivariate level (Spearman ρ = -0.274 and ρ = -0.277, respectively; p < 0.05), while the other subscales and the total score were not. 6MWD, SGRQ score, and SF-12 (physical health) score showed stronger associations with steps per day in bivariate analyses (Pearson r = 0.499, r = -0.386, and r = 0.467, respectively; p < 0.01), and were independent predictors of steps per day in multivariate linear regression analyses adjusting for confounders (p < 0.05). In ROC curve analyses, 6MWD, SGRQ score, and SF-12 (physical health) score properly identified sedentary patients (steps per day <5,000; AUROC 0.90, 0.81, and 0.80, respectively; p < 0.01). Fatigue was less predictive (MFI-20 subscale "general fatigue," AUROC 0.70; p = 0.03). CONCLUSION: While exercise capacity and quality of life measurements were robust predictors of physical activity in patients with sarcoidosis, associations of objectively measured physical activity with fatigue were surprisingly weak. In sarcoidosis, fatigue might not preclude affected patients from being physically active, although this symptom is subjectively perceived as highly disabling.

[Differentiation of dyspnea in patients with asthma and lung sarcoidosis]. / Differentiation of dyspnea in patients with asthma and lung sarcoidosis.

Dyspnea as a subjective feeling of lack of air is the patients with the pathology of the respiratory system. Objectivization of this phenomenon is difficult, despite the introduction of questionnaires about the degree of dyspnoea. The results of these assessments do not always correlate with the results of spirometric tests. In patients with asthma, dyspnoea is caused by airway obstruction. In the case of patients with lung sarcoidosis, the complexity of the phenomenon causes that many mechanisms and factors are responsible for the dyspnea symptoms in these patients. Dyspnea in patients with sarcoidosis is progressive and is closely related to the extent of interstitial exchanges. The diffusion capacity for carbon monoxide (DLco) determined in these patients reflects the degree of respiratory distress. Therapeutic procedures are also dependent on this parameter.