Serum matrix metalloproteinase levels in polymyositis/dermatomyositis patients with interstitial lung disease.

OBJECTIVE: We aimed to clarify the clinical significance of serum levels of MMPs in interstitial lung disease (ILD) complicated with PM/DM (PM/DM-ILD). METHODS: We retrospectively analysed serum levels of seven subsets of MMPs in 52 PM/DM-ILD patients diagnosed at Kyoto University Hospital or Tenri Hospital from January 2005 to December 2014. The patients were sub-grouped based on the presence of anti-amimoacyl-tRNA synthetase antibody (anti-ARS antibody), anti-melanoma differentiation-associated protein 5 antibody (anti-MDA5 antibody) or lack of the antibodies (ARS-ILD, MDA5-ILD and other-ILD groups, respectively) and independently analysed. Eighteen PM/DM patients without ILD and 55 healthy control were also analysed. Associations between serum levels of MMPs and clinical findings including mortality were analysed. RESULTS: Among the MMPs analysed, MMP-7 serum levels in the ARS-ILD group were significantly higher compared with those in any of the other groups of PM/DM patients or in healthy controls. On the other hand, in the MDA5-ILD group, serum MMP-7 levels >5.08 ng/ml were associated with worse overall survival both in univariate (P = 0.017; odds ratio 18.0; 95% CI 1.69, 192.00) and multivariate (P = 0.027; odds ratio 14.60; 95% CI 1.11, 192.00) analyses. Immunohistochemical analysis suggested that MMP-7 was expressed in type II alveolar epithelial cells adjacent to the fibrotic lesions. CONCLUSION: Serum MMP-7 levels were higher in anti-ARS antibody-positive PM/DM-ILD patients, while higher serum MMP-7 levels among anti-MDA5 antibody-positive PM/DM-ILD patients were associated with a worse prognosis. Fibrotic processes may be associated with the elevation of serum MMP-7 levels.

Clinical significance of radiological pleuroparenchymal fibroelastosis pattern in interstitial lung disease patients registered for lung transplantation: a retrospective cohort study.

BACKGROUND: Radiological pleuroparenchymal fibroelastosis (PPFE) lesion is characterized by pleural thickening with associated signs of subpleural fibrosis on high-resolution computed tomography (HRCT). This study evaluated the clinical significance of radiological PPFE as an isolated finding or associated with other interstitial lung diseases (ILDs) in patients having fibrotic ILDs and registered for cadaveric lung transplantation (LT). METHODS: This retrospective study included 118 fibrotic ILD patients registered for LT. Radiological PPFE on HRCT was assessed. The impact of radiological PPFE on clinical features and transplantation-censored survival were evaluated. RESULTS: Radiological PPFE was observed in 30/118 cases (25%): definite PPFE (PPFE concentrated in the upper lobes, with involvement of lower lobes being less marked) in 12 (10%) and consistent PPFE (PPFE not concentrated in the upper lobes, or PPFE with features of coexistent disease present elsewhere) in 18 (15%). Of these, 12 had late-onset non-infectious pulmonary complications after hematopoietic stem-cell transplantation and/or chemotherapy (LONIPCs), 9 idiopathic PPFE, and 9 other fibrotic ILDs (idiopathic pulmonary fibrosis, IPF; other idiopathic interstitial pneumonias, other IIPs; connective tissue disease-associated ILD, CTD-ILD, and hypersensitivity pneumonia, HP). Radiological PPFE was associated with previous history of pneumothorax, lower body mass index, lower percentage of predicted forced vital capacity (%FVC), higher percentage of predicted diffusion capacity of carbon monoxide, less desaturation on six-minute walk test, and hypercapnia. The median survival time of all study cases was 449 days. Thirty-seven (28%) received LTs: cadaveric in 31 and living-donor lobar in six. Of 93 patients who did not receive LT, 66 (71%) died. Radiological PPFE was marginally associated with better survival after adjustment for age, sex, %FVC, and six-minute walk distance < 250 m (hazard ratio 0.51 [0.25-1.05], p = 0.07). After adjustment for covariates, idiopathic PPFE and LONIPC with radiological PPFE was associated with better survival than fibrotic ILDs without radiological PPFE (hazard ratio 0.38 [0.16-0.90], p = 0.03), and marginally better survival than other fibrotic ILDs with radiological PPFE (hazard ratio, 0.20 [0.04-1.11], p = 0.07). CONCLUSIONS: idiopathic PPFE and LONIPC with radiological PPFE has better survival on the wait list for LT than fibrotic ILDs without radiological PPFE, after adjustment for age, sex, %FVC, and six-minute walk distance.

The Clinical Significance of Body Weight Loss in Idiopathic Pulmonary Fibrosis Patients.

BACKGROUND: The significance of the nutritional status in idiopathic pulmonary fibrosis (IPF) is largely unknown. Temporal body weight (BW) change, a dynamic index of nutrition status, can detect the malnutrition more accurately than the conventional single-point body mass index evaluation. OBJECTIVE: To investigate how the temporal BW change influences the clinical courses of IPF. METHODS: This multicenter study enrolled IPF patients from four referral hospitals of interstitial lung diseases in Japan (the Japanese cohort, the derivation cohort) and the Royal Brompton Hospital (the UK cohort, the validation cohort). The annual rate of BW change from the initial presentation was evaluated. A > 5% decrease of BW was defined as a significant BW loss. RESULTS: Twenty-seven out of 124 patients in the Japanese cohort and 13 out of 86 patients in the UK cohort showed significant BW loss. Patients with BW loss showed significantly worse survival in both cohorts. Multivariate analyses revealed that BW loss was an independent factor for decreased survival (Japanese cohort: p = 0.047, UK cohort: p = 0.013). A 6.1% loss of BW was chosen as the optimal cutoff value to predict the 2-year mortality from the initial presentation. The stratified analysis revealed that a 6.1% or greater BW loss could predict worse survival specifically in cases without a greater than 10% decline in forced vital capacity (FVC). CONCLUSIONS: BW loss is independently associated with the survival of IPF patients, particularly when a decline in the FVC was not observed. Further studies are needed to understand the mechanisms underlying BW loss in IPF.

Chronic Kidney Disease Predicts Survival in Patients with Idiopathic Pulmonary Fibrosis.

BACKGROUND: The prevalence of chronic kidney disease (CKD) increases with age as with idiopathic pulmonary fibrosis (IPF). OBJECTIVES: We assessed the prevalence of CKD (stages 3-5) and investigated the relationship of CKD to clinical features and outcomes in patients with IPF. METHODS: This study comprised 123 patients with IPF; 61 subjects with chronic obstructive pulmonary disease (COPD), which was reportedly associated with CKD, were also enrolled as a disease control. CKD (stages 3-5) was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. RESULTS: Thirty-seven patients (30%) with IPF and 14 controls (23%) with COPD were diagnosed with CKD, and these frequencies were not significantly different. The patients with IPF and CKD were older (p < 0.01) and had a higher frequency of hypertension (p = 0.048) and ischemic heart disease (p = 0.02) than those with IPF but without CKD. Furthermore, the diffusing capacity of the lung for carbon monoxide (DLCO) and the 6-min walking distance in the patients with CKD were significantly lower (40.0 ± 13.2 vs. 45.9 ± 14.4%, p = 0.04, and 416 ± 129 vs. 474 ± 84 m, p = 0.01, respectively) than in the patients without CKD. The outcome of the patients with CKD showed significantly worse survival compared with the patients without CKD (p = 0.04). Moreover, eGFR remained an independent predictor of survival after adjusting for age and pulmonary function data. CONCLUSION: A substantial percentage of IPF patients have CKD. CKD with a low eGFR was associated with decreased survival in IPF.

Serial perfusion in native lungs in patients with idiopathic pulmonary fibrosis and other interstitial lung diseases after single lung transplantation.

BACKGROUND: Lung perfusions after single lung transplantation (SLT) have not been fully clarified in patients with interstitial lung disease (ILD). The present study aimed to investigate temporal changes in native lung perfusion and their associated clinical factors in patients with ILD who have undergone SLT. METHODS: Eleven patients were enrolled. Perfusion scintigraphy was serially performed up to 12 months after SLT. Correlations between the post-operative perfusion ratio in the native lung and clinical parameters, including pre-operative perfusion ratio and computed tomography (CT) volumetric parameters, were evaluated. RESULTS: On average, the perfusion ratio of the native lung was maintained at approximately 30% until 12 months after SLT. However, the ratio declined more significantly in idiopathic pulmonary fibrosis (IPF) than in other ILDs (p = 0.014). The perfusion ratio before SLT was significantly correlated with that at three months after SLT (ρ = 0.64, p = 0.048). The temporal change of the perfusion ratio in the native lung did not correlate with those of the CT parameters. CONCLUSION: The pre-operative perfusion ratio may predict the post-operative perfusion ratio of the native lung shortly after SLT in ILD. Perfusion of the native lung may decline faster in IPF compared with other ILDs.

Matrix metalloproteinase-10: a novel biomarker for idiopathic pulmonary fibrosis.

BACKGROUND: Matrix metalloproteinases (MMPs) are believed to be involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF), and MMP-7 has been described as a useful biomarker for IPF. However, little is known regarding the significance of MMP-10 as a biomarker for IPF. METHODS: This observational cohort study included 57 patients with IPF. Serum MMPs were comprehensively measured in all patients, and the relationships between these markers and both disease severity and prognosis were evaluated. Bronchoalveolar lavage fluid (BALF) MMP-7 and -10 levels were measured in 19 patients to investigate the correlation between these markers and their corresponding serum values. Immunohistochemical staining for MMP-10 was also performed in IPF lung tissue. RESULTS: Serum MMP-7 and -10 levels correlated significantly with both the percentage of predicted forced vital capacity (ρ = -0.31, p = 0.02 and ρ = -0.34, p < 0.01, respectively) and the percentage of predicted diffusing capacity of the lung for carbon monoxide (ρ = -0.32, p = 0.02 and ρ = -0.43, p < 0.01, respectively). BALF MMP-7 and -10 levels correlated with their corresponding serum concentrations. Only serum MMP-10 predicted clinical deterioration within 6 months and overall survival. In IPF lungs, the expression of MMP-10 was enhanced and localized to the alveolar epithelial cells, macrophages, and peripheral bronchiolar epithelial cells. CONCLUSIONS: MMP-10 may be a novel biomarker reflecting both disease severity and prognosis in patients with IPF.

Clinical impact of high-attenuation and cystic areas on computed tomography in fibrotic idiopathic interstitial pneumonias.

BACKGROUND: Quantitative computed tomography (CT) analysis has been proposed as a means of objectively assessing fibrotic interstitial pneumonia (IP) including idiopathic pulmonary fibrosis (IPF). We investigated whether percentages of high-attenuation areas (HAA%) and cystic areas (CA%) quantified from CT images were useful as indices of fibrotic IP. METHODS: CT images of 74 patients with fibrotic idiopathic interstitial pneumonias (IPF, 36; non-specific interstitial pneumonia, 9; unclassifiable idiopathic interstitial pneumonia, 29) were analyzed via in-house computer software, which automatically calculated HAA%, CA%, mean lung density (MLD), standard deviation of lung density (SD-LD), kurtosis, and skewness from CT attenuation histograms. These indices were compared in each instance with physiologic measures, visual fibrosis score, clinical diagnosis, radiologic CT pattern, and prognosis. RESULTS: HAA% correlated significantly with physiologic measures and visual fibrosis score to a moderate extent (%forced vital capacity, rs = -0.59; % carbon monoxide diffusion capacity, rs = -0.43; fibrosis score, rs = 0.23). Densitometric parameters (MLD, SD-LD, kurtosis, and skewness) correlated significantly with physiologic measures and fibrosis score (|rs| = 0.28-0.59). CA% showed no association with pulmonary functions but differed significantly between IPF and other interstitial pneumonias (IPs) (1.50 ± 2.41% vs. 0.41 ± 0.80%; P < 0.01) and between the definite usual interstitial pneumonia (UIP) pattern and other patterns (1.48 ± 2.38% vs. 0.55 ± 1.19%; P < 0.01). On univariate analysis, HAA%, MLD, SD-LD, kurtosis, skewness, fibrosis score, and definite UIP pattern all correlated with survival, with kurtosis alone identified as a significant predictor of mortality on multivariate analysis (hazard ratio = 0.67; 95% CI, 0.44-0.96; P = 0.03). CONCLUSION: CA% and HAA% are novel quantitative CT indices with differing properties in fibrotic IP evaluations. HAA% largely reflects physiologic impairments, whereas CA% corresponds with diagnosis and HRCT pattern. Of the CT indices examined, kurtosis constituted the strongest predictor of mortality.

Smoking-related idiopathic interstitial pneumonia.

Cigarette smoking is a key factor in the development of numerous pulmonary diseases. An international group of clinicians, radiologists and pathologists evaluated patients with previously identified idiopathic interstitial pneumonia (IIP) to determine unique features of cigarette smoking. Phase 1 (derivation group) identified smoking-related features in patients with a history of smoking (n=41). Phase 2 (validation group) determined if these features correctly predicted the smoking status of IIP patients (n=100) to participants blinded to smoking history. Finally, the investigators sought to determine if a new smoking-related interstitial lung disease phenotype could be defined. Phase 1 suggested that preserved forced vital capacity with disproportionately reduced diffusing capacity of the lung for carbon monoxide, and various radiographic and histopathological findings were smoking-related features. In phase 2, the kappa coefficient among clinicians was 0.16 (95% CI 0.11-0.21), among the pathologists 0.36 (95% CI 0.32-0.40) and among the radiologists 0.43 (95% CI 0.35-0.52) for smoking-related features. Eight of the 100 cases were felt to represent a potential smoking-related interstitial lung disease. Smoking-related features of interstitial lung disease were identified in a minority of smokers and were not specific for smoking. This study is limited by its retrospective design, the potential for recall bias in smoking history and lack of information on second-hand smoke exposure. Further research is needed to understand the relationship between smoking and interstitial lung disease.

One-year lung function decline in sarcoidosis.

BACKGROUND: The definition of progressive pulmonary fibrosis is based on a 1-year lung function decline. OBJECTIVES: To evaluate the epidemiology and clinical relevance of 1-year lung function decline in sarcoidosis. METHODS: A retrospective observational study at a general sarcoidosis clinic. RESULTS: Of the 198 patients, 42 (18.4 %) had a 1-year lung function decline (absolute 12-month decline in percentage predicted forced vital capacity [%FVC] of ≥5 % or percentage predicted diffusion capacity for carbon monoxide [%DLCO] of ≥10 %). A 1-year lung function decline was associated with a 2-year lung function decline (a relative 24-month decline in %FVC of ≥10 % or %DLCO of ≥15 %), which occurred in 13 (7.4 %) of the 175 patients with 24-month follow-up results. A 1-year lung function decline was not associated with survival; a 2-year lung function decline predicted mortality. CONCLUSIONS: Compared with a 24-month decline, a 12-month decline in lung function did not predict worse survival in sarcoidosis.

An official American Thoracic Society clinical practice guideline: the clinical utility of bronchoalveolar lavage cellular analysis in interstitial lung disease.

BACKGROUND: The clinical utility of bronchoalveolar lavage fluid (BAL) cell analysis for the diagnosis and management of patients with interstitial lung disease (ILD) has been a subject of debate and controversy. The American Thoracic Society (ATS) sponsored a committee of international experts to examine all relevant literature on BAL in ILD and provide recommendations concerning the use of BAL in the diagnosis and management of patients with suspected ILD. PURPOSE: To provide recommendations for (1) the performance and processing of BAL and (2) the interpretation of BAL nucleated immune cell patterns and other BAL characteristics in patients with suspected ILD. METHODS: A pragmatic systematic review was performed to identify unique citations related to BAL in patients with ILD that were published between 1970 and 2006. The search was updated during the guideline development process to include published literature through March 2011. This is the evidence upon which the committee's conclusions and recommendations are based. RESULTS: Recommendations for the performance and processing of BAL, as well as the interpretation of BAL findings, were formulated by the committee. CONCLUSIONS: When used in conjunction with comprehensive clinical information and adequate thoracic imaging such as high-resolution computed tomography of the thorax, BAL cell patterns and other characteristics frequently provide useful information for the diagnostic evaluation of patients with suspected ILD.

Interferon regulatory factor 5 polymorphisms in sarcoidosis.

OBJECTIVE: Interferon regulatory factor 5 (IRF5) gene polymorphisms are associated with susceptibility to autoimmune diseases. The aim of this study is to determine the roles of IRF5 single-nucleotide polymorphisms (SNPs) in sarcoidosis. METHODS: A total of 175 Japanese patients with biopsy-proven sarcoidosis and 150 sex-matched controls were genotyped for four IRF5 SNPs: rs729302A/C, rs2004640G/T, rs10954213A/G, and rs2280714G/A. The associations of these SNPs with susceptibility to sarcoidosis were examined. RESULTS: Carriage of rs10954213A and rs2280714A conferred significant risks for sarcoidosis [carriage of rs10954213A: odds ratio (OR) = 1.96, 95% confidence interval (CI) = 1.15-3.33, P = 0.01, corrected P = 0.04; carriage of rs2280714A: OR = 1.97, 95% CI = 1.22-3.16, P = 0.005, corrected P = 0.02]. The haplotype carrying rs10954213A and rs2280714A (haplotype 2) was significantly associated with susceptibility to sarcoidosis (OR = 2.00, 95% CI = 1.24-3.24, P = 0.004, corrected P = 0.01). rs729302 and rs2004640 were not associated with susceptibility to sarcoidosis, whereas carriage of rs2004640G was protective against pulmonary hypertension (OR = 0.017, 95% CI = 0.002-0.15, P < 0.001, corrected P < 0.001). CONCLUSION: A haplotype carrying two functional SNPs of IRF5, rs10954213A and rs2280714A, was associated with the risk of sarcoidosis in the Japanese population.

Sarcoidosis HLA class II genotyping distinguishes differences of clinical phenotype across ethnic groups.

The HLA class II (DRB1 and DQB1) associations with sarcoidosis have been studied by several groups but often without consistent results. In this paper, we consider the hypothesis that observed inconsistencies relate to distinct, genetically encoded disease phenotypes which differ in prevalence between centres. We therefore typed HLA-DRB1 and DQB1 in 340 UK, 139 Dutch and 163 Japanese sarcoidosis patients and, respectively, 354, 218 and 168 healthy controls from these populations. We applied consistent phenotyping and genotyping and investigated associations between HLA class II alleles and distinct disease phenotypes within and between ethnic groups. DRB1*01 and DQB1*0501 are protective against all manifestations of sarcoidosis. Lung-predominant sarcoidosis is associated with DRB1*12 and *14. Löfgren's syndrome is a common sarcoidosis phenotype in the Dutch and is strongly associated with the DRB1*0301 allele. This phenotype is not seen among the Japanese in whom DRB1*0301 is absent. The same allele is protective for UK uveitis. Sarcoid uveitis is common in Japan. The DRB1*04-DQB1*0301 haplotype is a risk factor for this disease manifestation in Japanese and UK subjects but protective for sarcoidosis overall. We show that distinct sarcoidosis phenotypes have similar genetic associations across ethnic groups. The disease case mix differs between centres and may be explained by different ethnic allelic frequencies.

Desquamative interstitial pneumonia may progress to lung fibrosis as characterized radiologically.

BACKGROUND AND OBJECTIVE: In some patients, desquamative interstitial pneumonia may progress to lung fibrosis. The aim of this study was to assess the long-term radiological follow-up results in patients with desquamative interstitial pneumonia. METHODS: Among 75 patients suspected of having desquamative interstitial pneumonia, 31 who fulfilled the criteria were included in this study. Clinical characteristics at presentation, responses to treatment and long-term follow-up were evaluated. RESULTS: The 31 patients were predominantly males (94%), and the mean age was 55 years; 93% (28/30) had a history of smoking. The clinical findings included high serum levels of lactate dehydrogenase and immunoglobulin G. Bronchoalveolar lavage (26 patients, 84% of cases) frequently showed an increased percentage of eosinophils (mean 17%). Computed tomography (CT) or high resolution (HR) CT at presentation showed ground glass opacities and/or consolidation in all patients, with one third of patients also showing thin-walled cysts within the ground glass opacities. There was no honeycombing on CT or HRCT scans at presentation. Corticosteroid therapy was effective early in the course of the disease; long-term follow-up (mean 99 months) of 31 patients showed only one death due to progression of the disease, but long-term follow-up of 14 patients (mean 125 months) by HRCT showed the development of new thin-walled cysts and honeycombing in five and lung cancer in four patients, respectively. CONCLUSIONS: In a proportion of patients, desquamative interstitial pneumonia may progress to lung fibrosis with honeycombing on HRCT, despite therapy.

Basal interventricular septum thinning and long-term left ventricular function in patients with sarcoidosis.

BACKGROUND: Basal interventricular septum (IVS) thinning on transthoracic echocardiography (TTE) is highly specific to cardiac sarcoidosis. Although basal IVS thinning is listed as one of the five major diagnostic criteria for cardiac sarcoidosis, its association with long-term cardiac function has not been investigated. This study aimed to evaluate the epidemiology and clinical relevance of basal IVS thinning in a clinic-based cohort of patients with sarcoidosis. METHODS: This retrospective observational study was conducted at a general sarcoidosis clinic. The incidence of basal IVS thinning and associations with variables at baseline and a delayed onset of left ventricular (LV) dysfunction (LV ejection fraction [LVEF] < 50%) were analyzed. RESULTS: Of the 1009 patients, 23 (2.3%) had basal IVS thinning. Basal IVS thinning was associated with cardiac pacemaker (PM) implantation at baseline (adjusted odds ratio = 20.5; 95% confidence interval [CI] = 7.9-53.2; P < 0.01). Of the 768 patients with an LVEF of ≥50% at baseline who underwent one or more longitudinal TTEs after baseline, 36 (4.7%) developed LV dysfunction over a median observation period of 88.9 months. Basal IVS thinning and PM implantation at baseline were the independent predictors of a delayed onset of LV dysfunction (basal IVS thinning, adjusted hazard ratio [HR] = 3.7; 95% CI = 1.5-9.6; PM implantation, adjusted HR = 15.7; 95% CI = 7.4-33.3). CONCLUSIONS: Basal IVS thinning in patients with sarcoidosis can predict a delayed onset of LV dysfunction even when the LV function is preserved at the time of detection.

Lung function decline in sarcoidosis.

BACKGROUND: A decline in lung function is the basis of the definition of progressive fibrosing interstitial lung disease. This study aimed to evaluate the epidemiology and clinical relevance of lung function decline in sarcoidosis. METHODS: This retrospective observational study was conducted at a general sarcoidosis clinic. Lung function decline was defined as a relative 24-month decline in the percentage of predicted forced vital capacity (%FVC) of ≥10% or the percentage of predicted diffusion capacity for carbon monoxide (%DLco) of ≥15%. The frequency of lung function decline and its associations with the subsequent 24-month change in lung function and survival time were analyzed. RESULTS: Of the 201 patients, 14 (7.0%) exhibited a 24-month decline in %FVC of ≥10% and 28 (16.6%) exhibited a 24-month decline in %DLco of ≥15%. A 24-month decline in lung function was not associated with a subsequent 24-month lung function decline. Eleven patients died during the median observational time of 148.3 months; 4 of the 11 deaths were associated with sarcoidosis. A 24-month decline in lung function was associated with worse survival even after the adjustment for composite physiological index (CPI) and pulmonary hypertension (PH): 24-month decline in %FVC ≥10%, hazard ratio (HR) adjusted for CPI = 21.8, HR adjusted for PH = 19.3 and 24-month decline in %DLco ≥15%, HR adjusted for PH = 6.74. CONCLUSIONS: A 24-month decline in lung function can be a risk factor for mortality in sarcoidosis irrespective of CPI and PH.

Validation of the Japanese version of the Sarcoidosis Health Questionnaire: a cross-sectional study.

BACKGROUND: Although impaired health-related quality of life (HRQOL) has been reported in patients with sarcoidosis, there is currently no sarcoidosis-specific questionnaire in Japan. The 29-item Sarcoidosis Health Questionnaire (SHQ), originally developed in the United States, is the only sarcoidosis-specific HRQOL questionnaire currently available. The primary aim of this study was to develop and validate a Japanese version of the SHQ. FINDINGS: The SHQ was translated into Japanese following the forward-backward procedure. The reliability and validity of the Japanese version of the SHQ were examined. One hundred twenty-two Japanese patients with biopsy-proven sarcoidosis were evaluated by the SHQ, the Medical Outcomes Study 36-item short form (SF-36), the St. George's Respiratory Questionnaire (SGRQ), chest radiography, an electrocardiogram, laboratory blood tests, pulmonary function tests, an echocardiogram, and assessments of dyspnea and depressive symptoms. The SHQ was found to have acceptable levels of internal consistency (Cronbach's coefficient α values = 0.68 to 0.91). SHQ scores correlated significantly with scores on the SF-36 and SGRQ. The domain or total scores on the SHQ also significantly correlated with serum levels of the soluble interleukin-2 receptor, the percentage of the predicted forced vital capacity, pulmonary arterial systolic pressure, dyspnea, and depressive symptoms. Also, the SHQ scores of patients who had one or two organ systems affected by sarcoidosis were significantly different from those of patients who had three or more organ systems involvement. CONCLUSIONS: The Japanese version of the SHQ can be used to assess the HRQOL of patients with sarcoidosis.

The impact of demographic disparities in the presentation of sarcoidosis: A multicenter prospective study.

OBJECTIVE: To study how demographic differences impact disease manifestation of sarcoidosis using the WASOG tool in a large multicentric study. METHODS: Clinical data regarding 1445 patients with sarcoidosis from 14 clinical sites in 10 countries were prospectively reviewed from Feb 1, 2020 to Sep 30, 2020. Organ involvement was evaluated for the whole group and for subgroups differentiated by sex, race, and age. RESULTS: The median age of the patients at diagnosis was 46 years old; 60.8% of the patients were female. The most commonly involved organ was lung (96%), followed by skin (24%) and eye (22%). Black patients had more multiple organ involvement than White patients (OR = 3.227, 95% CI: 2.243-4.643) and females had more multiple organ involvement than males (OR = 1.238, 95% CI: 1.083-1.415). Black patients had more frequent involvement of neurologic, skin, eye, extra thoracic lymph node, liver and spleen than White and Asian patients. Women were more likely to have eye (OR = 1.522, 95%CI: 1.259-1.838) or skin involvement (OR = 1.369, 95%CI: 1.152-1.628). Men were more likely to have cardiac involvement (OR = 1.326, 95%CI: 1.096-1.605). A total of 262 (18.1%) patients did not receive systemic treatment for sarcoidosis. Therapy was more common in Black patients than in other races. CONCLUSION: The initial presentation and treatment of sarcoidosis was related to sex, race, and age. Black and female individuals are found to have multiple organ involvement more frequently. Age at diagnosis<45, Black patients and multiple organ involvement were independent predictors of treatment.

Genetic control of CCL24, POR, and IL23R contributes to the pathogenesis of sarcoidosis.

Sarcoidosis is a genetically complex systemic inflammatory disease that affects multiple organs. We present a GWAS of a Japanese cohort (700 sarcoidosis cases and 886 controls) with replication in independent samples from Japan (931 cases and 1,042 controls) and the Czech Republic (265 cases and 264 controls). We identified three loci outside the HLA complex, CCL24, STYXL1-SRRM3, and C1orf141-IL23R, which showed genome-wide significant associations (P < 5.0 × 10-8) with sarcoidosis; CCL24 and STYXL1-SRRM3 were novel. The disease-risk alleles in CCL24 and IL23R were associated with reduced CCL24 and IL23R expression, respectively. The disease-risk allele in STYXL1-SRRM3 was associated with elevated POR expression. These results suggest that genetic control of CCL24, POR, and IL23R expression contribute to the pathogenesis of sarcoidosis. We speculate that the CCL24 risk allele might be involved in a polarized Th1 response in sarcoidosis, and that POR and IL23R risk alleles may lead to diminished host defense against sarcoidosis pathogens.

Computed tomography analysis of airway dimensions and lung density in patients with sarcoidosis.

BACKGROUND: It was previously reported that visual scores of the lung opacities were associated with lung function in patients with sarcoidosis. However, there are no reports on the evaluation of airway dimensions or lung density by computed tomography (CT) in sarcoidosis patients. OBJECTIVES: The aim of this study was to investigate whether airway dimensions and lung densities assessed by CT associate with pulmonary function in patients with sarcoidosis. METHODS: CT scanning was performed in 43 sarcoidosis patients and lung densities were measured using in-house software. Means and standard deviations of lung density, kurtosis and skewness of lung density histograms were calculated. Tracheal area and airway wall area/total airway area (WA%) of the right apical bronchus were also measured. Pulmonary function tests were performed on the same day. RESULTS: Increased standard deviation of lung density and decreased kurtosis and skewness of lung density histograms were all associated with decreased total lung capacity, vital capacity and diffusion capacity. Increased standard deviation of lung density was also associated with decreased percentages of forced expiratory volume in 1 s and peak expiratory flow (%PEF). There was a positive correlation between tracheal area corrected by body surface area and %PEF, and negative correlation between WA% and %PEF. Stepwise regression analysis showed that increased standard deviation of lung density and decreased tracheal area were independently associated with lower %PEF. CONCLUSIONS: Thus, in sarcoidosis, densitometric parameters reflect restrictive lung function impairment. In addition to parenchymal lesions, it is concluded that the luminal area of the central airways also affects PEF.