Potential clinical utility of 68Ga-DOTATATE PET/CT for detection and response assessment in cardiac sarcoidosis.

BACKGROUND: Somatostatin receptor is expressed in sarcoid granulomas, and preliminary clinical studies have shown that myocardial sarcoidosis can be identified on somatostatin receptor-targeted PET. We examined the potential clinical use of 68Ga-DOTATATE PET/CT for diagnosis and response assessment in cardiac sarcoidosis compared to 18F-FDG PET/CT. METHODS: Eleven cardiac sarcoidosis patients with 18F-FDG PET/CT were prospectively enrolled for cardiac 68Ga-DOTATATE PET/CT. The two PET/CT studies were interpreted independently and were compared for patient-level and segment-level concordance, as well as for the degree of radiotracer uptake. Follow-up 68Ga-DOTATATE PET/CT was performed in eight patients. RESULTS: Patient-level concordance was 91%: ten patients had multifocal DOTATATE uptake (active cardiac sarcoidosis) and one patient showed diffuse DOTATATE uptake. Segment-level agreement was 77.1% (Kappa 0.53 ± 0.07). The SUVmax-to-blood pool ratio was lower on 68Ga-DOTATATE PET/CT (3.2 ± 0.6 vs. 4.9 ± 1.5, P = 0.006 on paired t test). Follow-up 68Ga-DOTATATE PET/CT showed one case of complete response and one case of partial response, while 18F-FDG PET/CT showed four cases of response, including three with complete response. CONCLUSION: Compared to 18F-FDG PET/CT, 68Ga-DOTATATE PET/CT can identify active cardiac sarcoidosis with high patient-level concordance, but with moderate segment-level concordance, low signal-to-background ratio, and underestimation of treatment response.

Analysis of single nucleotide polymorphisms in chronic beryllium disease.

Sarcoidosis and chronic beryllium disease (CBD) are phenocopies, however the latter one has a clear trigger factor that is beryllium exposure. This study analyses single nucleotide polymorphisms (SNPs) in a large cohort for beryllium-exposed persons. SNPs were chosen for their relevance in sarcoidosis. Even though one of largest cohorts of beryllium-exposed persons was analysed, no statistically relevant association between any SNP and CBD could be verified. Notably, some SNPs exhibit inverse OR for beryllium sensitization and CBD with nominally statistical significance, which allows hypothesizing about pathophysiological role of genes for the disease triggering and development.

Microbial Lineages in Sarcoidosis. A Metagenomic Analysis Tailored for Low-Microbial Content Samples.

RATIONALE: The etiology of sarcoidosis is unknown, but microbial agents are suspected as triggers. OBJECTIVES: We sought to identify bacterial, fungal, or viral lineages in specimens from patients with sarcoidosis enriched relative to control subjects using metagenomic DNA sequencing. Because DNA from environmental contamination contributes disproportionately to samples with low authentic microbial content, we developed improved methods for filtering environmental contamination. METHODS: We analyzed specimens from subjects with sarcoidosis (n = 93), control subjects without sarcoidosis (n = 72), and various environmental controls (n = 150). Sarcoidosis specimens consisted of two independent sets of formalin-fixed, paraffin-embedded lymph node biopsies, BAL, Kveim reagent, and fresh granulomatous spleen from a patient with sarcoidosis. All specimens were analyzed by bacterial 16S and fungal internal transcribed spacer ribosomal RNA gene sequencing. In addition, BAL was analyzed by shotgun sequencing of fractions enriched for viral particles, and Kveim and spleen were subjected to whole-genome shotgun sequencing. MEASUREMENTS AND MAIN RESULTS: In one tissue set, fungi in the Cladosporiaceae family were enriched in sarcoidosis compared with nonsarcoidosis tissues; in the other tissue set, we detected enrichment of several bacterial lineages in sarcoidosis but not Cladosporiaceae. BAL showed limited enrichment of Aspergillus fungi. Several microbial lineages were detected in Kveim and spleen, including Cladosporium. No microbial lineage was enriched in more than one sample type after correction for multiple comparisons. CONCLUSIONS: Metagenomic sequencing revealed enrichment of microbes in single types of sarcoidosis samples but limited concordance across sample types. Statistical analysis accounting for environmental contamination was essential to avoiding false positives.

Regional Fractional Ventilation by Using Multibreath Wash-in (3)He MR Imaging.

Purpose To assess the feasibility and optimize the accuracy of the multibreath wash-in hyperpolarized helium 3 ((3)He) approach to ventilation measurement by using magnetic resonance (MR) imaging as well as to examine the physiologic differences that this approach reveals among nonsmokers, asymptomatic smokers, and patients with chronic obstructive pulmonary disease (COPD). Materials and Methods All experiments were approved by the local institutional review board and compliant with HIPAA. Informed consent was obtained from all subjects. To measure fractional ventilation, the authors administered a series of identical normoxic hyperpolarized gas breaths to the subject; after each inspiration, an image was acquired during a short breath hold. Signal intensity buildup was fit to a recursive model that regionally solves for fractional ventilation. This measurement was successfully performed in nine subjects: three healthy nonsmokers (one man, two women; mean age, 45 years ± 4), three asymptomatic smokers (three men; mean age, 51 years ± 5), and three patients with COPD (three men; mean age, 59 years ± 5). Repeated measures analysis of variance was performed, followed by post hoc tests with Bonferroni correction, to assess the differences among the three cohorts. Results Whole-lung fractional ventilation as measured with hyperpolarized (3)He in all subjects (mean, 0.24 ± 0.06) showed a strong correlation with global fractional ventilation as measured with a gas delivery device (R(2) = 0.96, P < .001). Significant differences between the means of whole-lung fractional ventilation (F2,10 = 7.144, P = .012) and fractional ventilation heterogeneity (F2,10 = 7.639, P = .010) were detected among cohorts. In patients with COPD, the protocol revealed regions wherein fractional ventilation varied substantially over multiple breaths. Conclusion Multibreath wash-in hyperpolarized (3)He MR imaging of fractional ventilation is feasible in human subjects and demonstrates very good global (whole-lung) precision. Fractional ventilation measurement with this physiologically realistic approach reveals significant differences between patients with COPD and healthy subjects. To minimize error, several sources of potential bias must be corrected when calculating fractional ventilation. (©) RSNA, 2016 Online supplemental material is available for this article.

Multibreath alveolar oxygen tension imaging.

PURPOSE: This study tested the ability of a multibreath hyperpolarized HP (3) He MRI protocol to increase the accuracy of regional alveolar oxygen tension (PA O2 ) measurements by lessening the influence of gas-flow artifacts. Conventional single-breath PA O2 measurement has been susceptible to error induced by intervoxel gas flow, particularly when used to study subjects with moderate-to-severe chronic obstructive pulmonary disease (COPD). METHODS: Both single-breath and multibreath PA O2 imaging schemes were implemented in seven human subjects (one healthy, three asymptomatic smokers, and three COPD). The number and location of voxels with nonphysiologic PA O2 values generated by intervoxel gas flow were compared between the two protocols. RESULTS: The multibreath scheme resulted in a significantly lower total percentage of nonphysiologic PA O2 values (6.0%) than the single-breath scheme (13.7%) (P = 0.006). PA O2 maps showed several patterns of gas-flow artifacts that were present in the single-breath protocol but mitigated by the multibreath approach. Multibreath imaging also allowed for the analysis of slow-filling areas that presented no signal after a single breath. CONCLUSION: A multibreath approach enhances the accuracy and completeness of noninvasive PA O2 measurement by significantly lessening the proportion of nonphysiologic values generated by intervoxel gas flow. Magn Reson Med 76:1092-1101, 2016. © 2015 Wiley Periodicals, Inc.

Oxygen-weighted Hyperpolarized (3)He MR Imaging: A Short-term Reproducibility Study in Human Subjects.

PURPOSE: To determine whether hyperpolarized helium 3 magnetic resonance (MR) imaging to measure alveolar partial pressure of oxygen (Pao2) shows sufficient test-retest repeatability and between-cohort differences to be used as a reliable technique for detection of alterations in gas exchange in asymptomatic smokers. MATERIALS AND METHODS: The protocol was approved by the local institutional review board and was HIPAA compliant. Informed consent was obtained from all subjects. Two sets of MR images were obtained 10 minutes apart in 25 subjects: 10 nonsmokers (five men, five women; mean ± standard deviation age, 50 years ± 6) and 15 smokers (seven women, eight men; mean age, 50 years ± 8). A mixed-effects model was developed to identify the regional repeatability of Pao2 measurements as an intraclass correlation coefficient. Ten smokers were matched with the 10 nonsmokers on the basis of signal-to-noise ratio (SNR). Three separate models were generated: one for nonsmokers, one for the SNR-matched smokers, and one for the five remaining smokers, who were imaged with a significantly higher SNR. RESULTS: Short-term back-to-back regional reproducibility was assessed by using intraclass correlation coefficients, which were 0.67 and 0.65 for SNR case-matched nonsmokers and smokers, respectively. Repeatability was a strong function of SNR; a 50% increase in SNR in the remaining smokers improved the intraclass correlation coefficient to 0.82. Although repeatability was not significantly different between the SNR-matched cohorts (P = .44), the smoker group showed higher spatial and temporal variability in Pao2. CONCLUSION: The short-term test-retest repeatability of hyperpolarized gas MR imaging of regional Pao2 was good. Asymptomatic smokers exhibited greater spatial and temporal variability in Pao2 than did the nonsmokers, which suggests that this parameter allows detection of small functional alterations associated with smoking.

Alterations of regional alveolar oxygen tension in asymptomatic current smokers: assessment with hyperpolarized (3)He MR imaging.

PURPOSE: To assess the ability of helium 3 ((3)He) magnetic resonance (MR) imaging of regional alveolar partial pressure of oxygen (Pao2) to depict smoking-induced functional alterations and to compare its efficacy to that of current diagnostic techniques. MATERIALS AND METHODS: This study was approved by the local institutional review board and was compliant with HIPAA. All subjects provided informed consent. A total of 43 subjects were separated into three groups: nonsmokers, asymptomatic smokers, and symptomatic smokers. All subjects underwent a Pao2 imaging session followed by clinically standard pulmonary function tests (PFTs), the 6-minute walk test, and St George Respiratory Questionnaire (SGRQ). The whole-lung mean and standard deviation of Pao2 were compared with metrics derived from PFTs, the 6-minute walk test, and the SGRQ. A logistic regression model was developed to identify the predictors of alterations to the lungs of asymptomatic smokers. RESULTS: The whole-lung standard deviation of Pao2 correlated with PFT metrics (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC], Pearson r = -0.69, P < .001; percentage predicted FEV1, Pearson r = -0.67, P < .001; diffusing capacity of lung for carbon monoxide [Dlco], Pearson r = -0.45, P = .003), SGRQ score (Pearson r = 0.67, P < .001), and distance walked in 6 minutes (Pearson r = -0.47, P = .002). The standard deviation of Pao2 was significantly higher in asymptomatic smokers than in nonsmokers (change in the standard deviation of Pao2 = 7.59 mm Hg, P = .041) and lower when compared with symptomatic smokers (change in the standard deviation of Pao2 = 10.72 mm Hg, P = .001). A multivariate prediction model containing FEV1/FVC and the standard deviation of Pao2 (as significant predictors of subclinical changes in smokers) and Dlco (as a confounding variable) was formulated. This model resulted in an area under the receiver operating characteristic curve with a significant increase of 29.2% when compared with a prediction model based solely on nonimaging clinical tests. CONCLUSION: The (3)He MR imaging heterogeneity metric (standard deviation of Pao2) enabled the differentiation of all three study cohorts, which indicates that it can depict smoking-related functional alterations in asymptomatic current smokers.

Recent chronic beryllium disease in residents surrounding a beryllium facility.

RATIONALE: Between 1948 and 1969, cases of community-acquired chronic beryllium disease (CA-CBD) were reported in neighborhoods surrounding beryllium facilities. Further surveillance was not performed in these communities, and additional cases have not been reported. OBJECTIVES: To increase awareness of recently diagnosed cases of CA-CBD in residents surrounding a beryllium facility. METHODS: Medical records were reviewed from individuals in a community surrounding a beryllium manufacturing facility in Reading, Pennsylvania. Definite cases of CBD required (1) an abnormal beryllium lymphocyte proliferation test in blood or bronchoalveolar lavage and (2) biopsy evidence of granulomatous inflammation. Probable cases of CBD either displayed an abnormal blood test to beryllium and radiographic evidence consistent with disease, or met epidemiologic criteria for CBD based on the Beryllium Case Registry criteria. Cases with occupational or potential paraoccupational exposure were excluded. MEASUREMENTS AND MAIN RESULTS: Sixteen cases of potential community-acquired CBD were evaluated. From these, eight cases of community-acquired CBD were identified (five definite and three probable). The cases' initial year of residence began between 1943 and 1953 and continued until 1956-2001. Six of the eight cases required medical treatment and three of the cases died since diagnosis. CONCLUSIONS: Cases of CBD meeting current immunologic diagnostic criteria and attributable to industry-associated environmental exposure were detected among residents of a community surrounding a beryllium manufacturing facility. Most were diagnosed years after exposure cessation. The frequency and extent of beryllium disease in this community are unknown. We anticipate that not only have cases been misdiagnosed in this community but that more cases of CBD will be diagnosed in the future.

Role of imaging in progressive-fibrosing interstitial lung diseases.

Imaging techniques are an essential component of the diagnostic process for interstitial lung diseases (ILDs). Chest radiography is frequently the initial indicator of an ILD, and comparison of radiographs taken at different time points can show the rate of disease progression. However, radiography provides only limited specificity and sensitivity and is primarily used to rule out other diseases, such as left heart failure. High-resolution computed tomography (HRCT) is a more sensitive method and is considered central in the diagnosis of ILDs. Abnormalities observed on HRCT can help identify specific ILDs. HRCT also can be used to evaluate the patient's prognosis, while disease progression can be assessed through serial imaging. Other imaging techniques such as positron emission tomography-computed tomography and magnetic resonance imaging have been investigated, but they are not commonly used to assess patients with ILDs. Disease severity may potentially be estimated using quantitative methods, as well as visual analysis of images. For example, comprehensive assessment of disease staging and progression in patients with ILDs requires visual analysis of pulmonary features that can be performed in parallel with quantitative analysis of the extent of fibrosis. New approaches to image analysis, including the application of machine learning, are being developed.

Pulmonary Tuberculosis.

This review on pulmonary tuberculosis includes an introduction that describes how the lung is the portal of entry for the tuberculosis bacilli to enter the body and then spread to the rest of the body. The symptoms and signs of both primary and reactivation tuberculosis are described. Routine laboratory tests are rarely helpful for making the diagnosis of tuberculosis. The differences between the chest X ray in primary and reactivation tuberculosis is also described. The chest computed tomography appearance in primary and reactivation tuberculosis is also described. The criteria for the diagnosis of pulmonary tuberculosis are described, and the differential is discussed. The pulmonary findings of tuberculosis in HIV infection are described and differentiated from those in patients without HIV infection. The occurrence of tuberculosis in the elderly and in those patients on anti-tumor necrosis factor alpha inhibitors is described. Pleural tuberculosis and its diagnosis are described. Efforts to define the activity of tuberculosis and the need for respiratory isolation are discussed. The complications of pulmonary tuberculosis are also described.

Interstitial Lung Disease in the Elderly.

BACKGROUND: Despite the relationship between idiopathic pulmonary fibrosis (IPF) and advancing age, little is known about the epidemiology of interstitial lung disease (ILD) in the elderly. We describe the diagnoses, clinical characteristics, and outcomes of patients who were elderly at the time of ILD diagnosis. METHODS: Among subjects from a prospective cohort study of ILD, elderly was defined as age ≥ 70 years. Diagnoses were derived from a multidisciplinary review. Differences between elderly and nonelderly groups were determined using the χ2 test and analysis of variance. RESULTS: Of the 327 subjects enrolled, 80 (24%) were elderly. The majority of elderly subjects were white men. The most common diagnoses were unclassifiable ILD (45%), IPF (34%), connective tissue disease (CTD)-ILD (11%), and hypersensitivity pneumonitis (8%). Most elderly subjects (74%) with unclassifiable ILD had an imaging pattern inconsistent with usual interstitial pneumonia (UIP). There were no significant differences in pulmonary function or 3-year mortality between nonelderly and elderly subjects combined or in a subgroup analysis of those with IPF. CONCLUSIONS: Although IPF was the single most common diagnosis, the majority of elderly subjects had non-IPF ILD. Our findings highlight the need for every patient with new-onset ILD, regardless of age, to be surveyed for exposures and findings of CTD. Unclassifiable ILD was common among the elderly, but for most, the radiographic pattern was inconsistent with UIP. Although the effect of ILD may be more pronounced in the elderly due to reduced global functionality, ILD was not more severe or aggressive in this group.

Comparison of sarcoidosis phenotypes among affected African-American siblings.

STUDY OBJECTIVE: To test the hypothesis that sibling pairs, who share genes and environmental exposures, might have similar phenotypic expressions of sarcoidosis beyond what would be expected by chance alone. DESIGN: Multicenter family study with study subjects recruited from 11 clinical centers. SUBJECTS: Subjects were African-American sibling pairs with sarcoidosis. Sarcoidosis and organ pattern involvement were defined according to specific criteria. Fifteen different organ systems were evaluated. RESULTS: For full-sibling pairs, ocular involvement was found in both siblings more often than expected by chance alone (p < 0.05), but the concordance was weak (kappa = 0.18). When analyzing full-sibling and half-sibling pairs, ocular and liver involvement showed a significant concordance between sibling pairs (p < 0.05), but again the agreement was poor (kappa = 0.16 for both). Concordance in pulmonary function change over time was also weak. Clinical outcomes of sibling pairs were not significantly correlated except for whether treatment was prescribed, and this level of agreement was poor (kappa = 0.14 for full-sibling and half-sibling pairs; kappa = 0.15 for full-sibling pairs only). Modeling phenotypic expression in sibling pairs using logistic regression did show that the presence of ocular and liver sarcoidosis in the first affected sibling conferred a statistically significant increased risk to the second affected sibling for having those organs involved (odds ratio [OR], 3; 95% confidence interval [CI], 1.7 to 5.4 for ocular; OR, 3.3; 95% CI, 1.5 to 7.4 for liver). CONCLUSIONS: The phenotypic features and clinical outcomes of sarcoidosis in sibling pairs show minimal concordance, with the possible exception that the presence of ocular or liver involvement in the first sibling with a diagnosis of sarcoidosis makes involvement of these organs more likely in other affected siblings.

A double-blinded, randomized, placebo-controlled trial of infliximab in subjects with active pulmonary sarcoidosis.

STUDY OBJECTIVES: To evaluate the safety and tolerability of infliximab in the treatment of active pulmonary sarcoidosis, and to provide an initial assessment of the efficacy of infliximab in the treatment of active pulmonary sarcoidosis. DESIGN: Double-blind, randomized, placebo-controlled phase II study. SETTING: Multicenter. PATIENTS: Active Radiographic Stage II, III, and IV active pulmonary sarcoidosis despite corticosteroids or previous intolerance to corticosteroids. INTERVENTION: Infliximab 5mg/kg (group I) or placebo (group II) at weeks 0 and 2 and open-label infliximab 5mg/kg for all subjects at weeks 6 and 14. MEASUREMENTS: Pulmonary function, chest radiographs, dyspnea stage, SF-36. RESULTS: Mean vital capacity (VC) at wk 0 was 2.47 +/- 0.2 (group I) and 2.37 +/- 0.31 (group II). At 6 weeks the mean +/- SD relative change in VC compared to baseline was 15.22 +/- 9.91% for group I (n=13) and 8.39 +/- 3.33% for group II (n=6) (p=0.65). Four patients had serious adverse events, including decreased WBC and elevated CPK (1 patient), pneumonia (1 patient), cellulitis, acute renal failure, pulmonary embolus and death (1 patient), and visual field defect (1 patient). CONCLUSIONS: Infliximab may improve VC in patients with active PS resistant to steroids. Larger scale, longer term studies will be needed to assess both safety and efficacy.

Relationship of environmental exposures to the clinical phenotype of sarcoidosis.

STUDY OBJECTIVES: Sarcoidosis is a granulomatous disorder with heterogeneous clinical manifestations, which are potentially reflective of a syndrome with different etiologies leading to similar histologic findings. We examined the relationship between environmental and occupational exposures, and the clinical phenotype of sarcoidosis. DESIGN: We performed a cross-sectional study of incident sarcoidosis cases that had been identified by A Case Control Etiologic Study of Sarcoidosis. Subjects were categorized into the following two groups: (1) pulmonary-only disease; and (2) systemic disease (with or without pulmonary involvement). Logistic regression was used to examine the associations of candidate exposures with clinical phenotype. SETTING: Ten academic medical centers across the United States. PATIENTS: The current study included 718 subjects in whom sarcoidosis had been diagnosed within 6 months of study enrollment. Patients met the following criteria prior to enrollment: (1) tissue confirmation of noncaseating granulomas on tissue biopsy on one or more organs within 6 months of study enrollment with negative stains for acid-fast bacilli and fungus; (2) clinical signs or symptoms that were consistent with sarcoidosis; (3) no other obvious explanation for the granulomatous disease; and (4) age > 18 years. MEASUREMENTS AND RESULTS: Several exposures were associated with significantly less likelihood of having extrapulmonary disease in multivariate analysis, including agricultural organic dusts and wood burning. The effects of many of these exposures were significantly different in patients of different self-defined race. CONCLUSIONS: The differentiation of sarcoidosis subjects on the basis of clinical phenotypes suggests that these subgroups may have unique environmental exposure associations. Self-defined race may play a role in the determination of the effect of certain exposures on disease phenotypes.

The spectrum of biopsy sites for the diagnosis of sarcoidosis.

BACKGROUND: The diagnosis of sarcoidosis is most secure when supported by a tissue biopsy exhibiting noncaseating epithelioid granulomas with absence of known granulomagenic agents in a patient with multi-organ disease. Clinicians must decide which site offers the best chance of achieving a diagnostic biopsy with the least patient risk and discomfort. METHODS: 736 cases were enrolled in the NHLBI supported A Case Controlled Etiologic Study of Sarcoidosis (ACCESS) from November 1996 to June 1999. All cases required diagnostic organ biopsy (Bx) exhibiting non-caseating epithelioid granulomas without identifiable granulomagenic agent, within six months of recruitment. Positive Kveim-Siltzbach test was accepted in patients with Löfgren's syndrome. Bx sites were correlated with demographic data, chest radiographic stages, symptoms, pulmonary function and associated organ involvement. RESULTS: Seven hundred and seventy-six diagnostic biopsies were performed. Five hundred and sixty-seven were intrathoracic, 198 extrathoracic. Eleven Kveim tests were positive. When cutaneous sarcoidosis or an enlarged extrathoracic lymph node was present, skin or lymph node Bx was the preferred procedure. Twenty-three different organs yielded diagnostic biopsies. CONCLUSIONS: Biopsy diagnosis in sarcoidosis is almost always easily obtained. As shown by ACCESS, sarcoidosis offers a wide spectrum of diagnostic biopsy sites. The choice for biopsy is influenced by the presenting clinical constellation of organ involvement and the ease and safety of the biopsy procedure.

A sarcoidosis genetic linkage consortium: the sarcoidosis genetic analysis (SAGA) study.

BACKGROUND: Sarcoidosis, a systemic granulomatous disease of unknown etiology, likely results from an environmental insult in a genetically susceptible host. In the United States of America, African Americans have a higher sarcoidosis incidence and suffer greater morbidity than Caucasians. METHODS: A sarcoidosis genetic linkage study consortium was established to recruit African-American affected sib pair (ASP) families to identify chromosomal regions that may harbor sarcoidosis susceptibility genes and to determine if environmental factors modify any genetic effects. RESULTS: We successfully met our goal of enrolling 359 ASPs using a multifaceted recruitment approach. In the total 559 sib pairs that were enrolled, genetic analyses revealed incorrectly specified relationships that required reclassification or removal from the analysis dataset of 10.4% of reported full and 1.4% of reported half sib pairs. The final study sample comprised 415 full and 104 half sib pairs with complete data. This included 338 ASPs. Within sib pairs, affection status was not associated with sex. Only 15 per cent of the 229 families had three or more affected sibs, but they contributed 42 per cent of the ASP total. CONCLUSIONS: The SAGA study experience should provide useful lessons and information to serve others in conducting genetic studies of complex diseases in African-American families.

Pulmonary and psychosocial findings at enrollment in the ACCESS study.

AIM: To assess lung involvement and the association of demographic and psychosocial factors with respiratory health in 736 persons with sarcoidosis at enrollment in A Case Control Etiologic Study of Sarcoidosis (ACCESS). METHODS: 736 patients with biopsy diagnosis of sarcoidosis within 6 months of enrollment were studied at 10 US centers. Lung involvement was evaluated by chest radiography, spirometry and dyspnea questionnaire. Demographics, number of involved extrathoracic organ systems, comorbidities, and health-related quality of life (HRQL) were assessed. RESULTS: 95% of patients had lung involvement. 8% were Scadding Stage 0, 40% I, 37% II, 10% III, and 5% IV 51% reported dyspnea. Increasing radiographic lung stage was associated with decreasing Forced Vital Capacity (FVC) (p < 0.01). Patients with higher stages had more airways obstruction and dyspnea. 46% of cases and 27% of controls had Center for Epidemiologic Studies Depression Scale (CES-D) scores of 9 or greater, (p < 0.001). Age > or = 40, African-American race, body mass index > or = 30kg/m2, and CES-D scores > 9 were associated with decreased FVC and greater dyspnea. Impaired spirometry and greater dyspnea were associated with poorer quality of life. CONCLUSION: A "global" approach to the sarcoidosis patient, including careful assessment of dyspnea and health related quality of life, as well as of lung function and radiographic changes, and any extrathoracic involvement, is important, not only in management of the individual patient, but should also prove beneficial in assessing outcomes in clinical trials in the future.

Reliability and Validity of Cutaneous Sarcoidosis Outcome Instruments Among Dermatologists, Pulmonologists, and Rheumatologists.

IMPORTANCE: Dermatologists, pulmonologists, and rheumatologists study and treat patients with sarcoidosis with cutaneous manifestations. The validity of cutaneous sarcoidosis outcome instruments for use across medical specialties remains unknown. OBJECTIVE: To assess the reliability and validity of cutaneous sarcoidosis outcome instruments for use by dermatologists and nondermatologists treating sarcoidosis. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional study evaluating the use of the Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) and Sarcoidosis Activity and Severity Index (SASI) to assess cutaneous sarcoidosis disease severity and the Physician's Global Assessment (PGA) as a reference instrument. Four dermatologists, 3 pulmonologists, and 4 rheumatologists evaluated facial cutaneous sarcoidosis in 13 patients treated at a cutaneous sarcoidosis clinic in a 1-day study on October 24, 2014; data analysis was performed from November through December 2014. MAIN OUTCOMES AND MEASURES: Interrater and intrarater reliability and convergent validity, with correlation with quality-of-life measures as the secondary outcome. RESULTS: All instruments demonstrated excellent intrarater reliability. Interrater reliability (reported as intraclass correlation coefficient [95% CI]) was good for the CSAMI Activity scale (0.69 [0.51-0.87]) and PGA (0.66 [0.47-0.85]), weak for the CSAMI Damage scale (0.26 [0.11-0.52]), and excellent for the modified Facial SASI (0.78 [0.63-0.91]). The CSAMI Activity scale and modified Facial SASI showed moderate correlations (95% CI) with the PGA (0.67 [0.57-0.75] and 0.57 [0.45-0.66], respectively). The CSAMI Activity scale but not the modified Facial SASI showed significant correlations (95% CI) with quality-of-life instruments, such as the Dermatology Life Quality Index (Spearman rank correlation, 0.70 [0.25-0.90]) and the Skin Stigma raw score of the Sarcoidosis Assessment Tool (Pearson product moment correlation, 0.56 [0.01-0.85]). CONCLUSIONS AND RELEVANCE: The CSAMI and SASI were reliable and valid in assessing cutaneous sarcoidosis among our diverse group of specialists. The CSAMI Activity score also correlated with quality-of-life measures and suggested construct validity. These results lend credibility to expand the use of the CSAMI and SASI by dermatologists and nondermatologists in assessing cutaneous sarcoidosis disease activity.