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.

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.

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.

Can the Sarcoidosis Health Questionnaire predict the long-term outcomes in Japanese sarcoidosis patients?

RATIONALE: The Sarcoidosis Health Questionnaire (SHQ) is the first sarcoidosis-specific health status questionnaire ever developed. Worse health status, as evaluated by the SHQ, may indicate higher risk for deterioration in the following 5 years. OBJECTIVES: To evaluate the association between SHQ scores and deterioration defined clinically at 5-year follow-up. METHODS: 122 patients with biopsy-supported sarcoidosis completed the SHQ and underwent evaluation with respect to organ involvement, chest radiograph, electrocardiogram, serum biomarker measurements, pulmonary function tests, and echocardiogram. Of these 122, 88 (72.1%) were available for pulmonary, cardiac, and non-pulmonary, non-cardiac deterioration assessment during the following 5 years. MEASUREMENTS AND MAIN RESULTS: Five-year deterioration was observed in 20 patients (23%). The SHQ total score was significantly associated with 5-year deterioration, after adjusting for cardiac involvement at baseline, with adjusted odds ratio (OR) of 0.54 (95% confidence interval [95% CI], 0.29-0.99). The association of the total SHQ with 5-year outcome was not significant when adjusted for left ventricular ejection fraction (LVEF) at baseline (adjusted OR, 0.61 [0.32-1.16]), whereas LVEF was significantly associated with 5-year outcome (adjusted OR, 0.92 [0.86-0.99]). The association between total SHQ score and 5-year deterioration was marginal when adjusted for baseline usage of systemic corticosteroid (CS)/immunosuppressive (IS) agents (adjusted OR, 0.58 [0.31-1.10]), whereas systemic CS/IS usage significantly predicted 5-year deterioration (adjusted odds ratio [OR], 3.46 [1.12-10.7]). There was a marginal correlation between the total SHQ and LVEF (rho = 0.19, p = 0.07) and a weak association between the total SHQ and systemic CS/IS usage (rho = -0.23, p = 0.03). The Physical Functioning domain scores of the SHQ were significantly associated with 5-year deterioration (adjusted OR, 0.45-0.51). CONCLUSIONS: Worse health status, as assessed by the SHQ score, can be a risk factor for 5-year deterioration of sarcoidosis, although usage of the CS/IS at baseline and lower LVEF at baseline are more predictive of 5-year deterioration.

Asymmetry in acute exacerbation of idiopathic pulmonary fibrosis.

Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) results in poor survival. The objective of the present study was to elucidate the impact of asymmetrical ground-glass opacity (GGO) and/or consolidation on outcomes in patients with AE-IPF. The cases of 59 consecutive patients with AE-IPF were retrospectively reviewed. High-resolution computed tomography (HRCT) at diagnosis of an AE was assessed to determine the disease extent and asymmetry. Asymmetrical AE was defined as a right-to-left ratio of GGO and consolidation ≥2.0 or ≤0.5. The impacts of HRCT indices and other clinical parameters on 180-day mortality were analysed. The overall 180-day mortality rate was 59.2%, and asymmetrical AE was observed in 13 patients (22.0%). A multivariate analysis revealed that asymmetrical AE was a significant predictor of 180-day mortality (hazard ratio=0.36, p=0.047), long-term oxygen therapy before AE and serum lactate dehydrogenase levels. The 180-day mortality of patients with asymmetrical AE was significantly lower than that of patients with symmetrical AE (asymmetrical AE 30.8% versus symmetrical AE 68.2%, p=0.03). An asymmetrical distribution of GGO and/or consolidation is a predictor of survival in patients with AE-IPF.

The long-term outcome of interstitial lung disease with anti-aminoacyl-tRNA synthetase antibodies.

RATIONALE: Anti-aminoacyl transfer RNA synthetase antibodies (anti-ARS) are a group of myositis-specific autoantibodies that are detected in the sera of patients with polymyositis and dermatomyositis (PM/DM) and also in those of patients with idiopathic interstitial pneumonias without any connective tissue disease (CTD), including PM/DM. Although we reported the clinical characteristics of interstitial lung disease with anti-ARS antibodies (ARS-ILD) with and without PM/DM, the long-term prognosis of ARS-ILD remains undetermined. As our previous studies revealed that ARS-ILD without PM/DM was similar to CTD-associated ILD, and that ARS-ILD with PM/DM was radiologically suggestive of a nonspecific interstitial pneumonia (NSIP) pathological pattern, we hypothesized that the prognosis of ARS-ILD might be distinct from that of idiopathic pulmonary fibrosis (IPF) without anti-ARS. OBJECTIVES: To elucidate the long-term outcome of ARS-ILD with and without PM/DM and compare it to that of IPF. METHODS: A two-center retrospective study was conducted. The study population comprised 36 patients with ARS-ILD (8 with PM, 12 with DM, and 16 without myositis throughout the course), 100 patients with IPF without anti-ARS, and 7 patients with NSIP without anti-ARS. The presence of anti-ARS was determined by RNA immunoprecipitation using the sera obtained at the time of diagnosis before specific treatment. MEASUREMENTS AND MAIN RESULTS: During the observational period (median 49 months; range, 1-114 months), 7 patients with ARS-ILD (19%; 3 with PM, 1 with DM, and 3 without PM/DM) and 51 patients with IPF (51%) died. Patients with ARS-ILD had better overall survival than those with IPF (log-rank test, P < 0.001) and similar survival compared to those with NSIP (log-rank test, P = 0.59). The prognosis for patients with ARS-ILD was similar between those with and without myositis (log-rank test, P = 0.91). At the median follow-up time of 76.5 months, 14 of the 36 patients with ARS-ILD had deteriorated. Both a decline in forced vital capacity or an initiation of long-term oxygen therapy during the course (odds ratio [OR], 5.34) and acute exacerbation (OR, 28.4) significantly increased the mortality risk. CONCLUSIONS: The long-term outcome of ARS-ILD was significantly better than that of IPF regardless of the presence or absence of myositis.

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.

Treatment with methotrexate and low-dose corticosteroids in sarcoidosis patients with cardiac lesions.

OBJECTIVE: Our objective was to evaluate the effectiveness of combination therapy consisting of low-dose corticosteroids with weekly methotrexate in patients with cardiac sarcoidosis in whom long-term therapy is required. Combination therapy was selected because long-term standard corticosteroid therapy tends to result in various adverse effects and the steroid-sparing effects of methotrexate have been reported. METHODS: This study was a small open-label study comparing long-term functional changes between patients who received combination therapy (5-15 mg/day of prednisolone and 6 mg/week of methotrexate) and patients who received corticosteroids alone. The comparative analysis was based on the following therapeutic indexes: ejection fraction (EF), left ventricular end-diastolic diameter (LVDd) on echocardiography, serum N-terminal fragment pro-brain natriuretic peptide (NT-proBNP) and cardiothoracic ratio (CTR) on plain chest radiographs. PATIENTS: Seventeen patients with cardiac sarcoidosis were examined in the sarcoidosis clinic. Cardiac sarcoidosis was diagnosed based on the Japanese diagnostic guidelines published in 2006. RESULTS: The EF was significantly stabilized in the combination therapy group but not in the corticosteroids alone group at three years after the first treatment. The CTR and NT-proBNP levels were significantly stabilized in the combination therapy group compared with those observed in the corticosteroids alone group at both three and five years after the first treatment. The LVDd values tended to be stable in the combination therapy group compared with those observed in the corticosteroids alone group. The combination therapy was associated with few adverse effects. CONCLUSION: Weekly methotrexate therapy with daily small doses of corticosteroids stabilized the EF, CTR and NT-proBNP levels in the serum without eliciting adverse effects longitudinally.

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.

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.

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.

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.

Outcome of sarcoidosis.

Sarcoidosis is a chronic granulomatous inflammatory disease of unknown etiology with heterogeneous outcome. Based on the natural history or clinical treatment course, the outcomes of cases can be divided into two wings: spontaneous regression (self-limited disease) or progression of extensive fibrotic lesions as a postgranulomatous fibrosis. In addition to examining these outcomes, this article focuses on several related concepts, including chronicity (persistence of the lesions), relapse/recurrence, deterioration, and mortality. It also reviews the outcomes from the point of view of relevant clinical phenotypes, the natural disease course, the effects of treatment, and the effects of lung transplantation. Finally, it considers the effects of pulmonary hypertension, various genetic factors on the outcomes, and the efficacy of several novel therapeutic drugs in treating sarcoidosis.

Bronchoalveolar lavage in idiopathic interstitial lung diseases.

Bronchoalveolar lavage (BAL) is useful for diagnosing various interstitial lung diseases (ILDs) and monitoring ILD during treatment. The ability to detect specific agents or substances by using BAL is especially helpful in determining whether idiopathic ILD has a background causality. BAL in combination with other intensive examinations may enable the definitive diagnosis of an idiopathic ILD. Among the idiopathic ILDs of concern, this article focuses on idiopathic interstitial pneumonia (IIP) and cryptogenic organizing pneumonia (COP). IIP and COP are classified together as idiopathic interstitial pneumonia (IIP), an integrated clinicoradiographic pathological disease entity. BAL has identified two points important for differentiating the disease entity: a paucity of lymphocytes appears in the BAL fluid of patients with idiopathic pulmonary fibrosis (IPF), and lymphocytosis with a decreased CD4:CD8 ratio appears in patients with COP. These findings can be useful, in combination with high-resolution computed tomographic (HRCT) data, for selecting a favorable treatment option. On the other hand, these rules cannot be applied to IP associated with collagen vascular disease (CVD). Furthermore, some IIP patients may manifest features of CVD during the clinical course after the detection of IP (interstitial pneumonia). Thus the definite role of BAL cell profiles remains to be determined.

Incidence of pulmonary hypertension and its clinical relevance in patients with interstitial pneumonias: comparison between idiopathic and collagen vascular disease associated interstitial pneumonias.

OBJECT: This study was undertaken to investigate the frequency of pulmonary hypertension (PH), and clinical parameters associated with PH in patients with idiopathic interstitial pneumonias (IIPs) and collagen vascular disease-associated interstitial pneumonias (CVD-IPs). PATIENTS AND METHODS: Retrospective analyses were performed in 163 consecutively enrolled patients (78 IIPs and 85 CVD-IPs) who were being evaluated for PH by Doppler echocardiography. PH was defined as an estimated systolic pulmonary artery pressure (sPAP) of > or = 40 mmHg. The frequency of PH was evaluated and clinical parameters were compared between patients with PH and those without PH. RESULTS: Among patients successfully evaluated for sPAP by echocardiography, 20 of 70 (28%) patients with IIPs and 17 of 80 (21%) patients with CVD-IPs had PH. Among patients with IIP and CVD-IP, those with PH were more frequently treated with supplemental oxygen. Patients with IIP who had PH tended to be older and had decreased % diffusion capacity of carbon monoxide (%DLCO). Additionally, in patients with IIP, sPAP was negatively correlated with %DLCO. However, this association was not found in patients with CVD-IP. Patients with CVD-IP who had PH were predominantly male. CONCLUSION: PH was frequently observed in patients with both IIPs (28%) and CVD-IPs (21%) in the chronic phase of the disease. PH should be evaluated in patients with IPs who need supplemental oxygen, IIP patients with decreased diffusing capacity, and in patients with CVD-IP.

Significance of pulmonary arterial pressure and diffusion capacity of the lung as prognosticator in patients with idiopathic pulmonary fibrosis.

STUDY OBJECTIVES: To evaluate the long-term clinical course of patients with idiopathic pulmonary fibrosis (IPF) complicated with pulmonary arterial hypertension. DESIGN: Prospective analysis of consecutive IPF patients undergoing initial workup with right-heart catheterization (RHC) and pulmonary function testing (PFT). Pulmonary arterial pressure (PAP) and diffusion capacity of the lung for carbon monoxide (Dlco) were focused on. SETTING: University hospital. PATIENTS: Seventy-eight patients with IPF (67 men, 11 women; diagnosis by pathology, n = 59; clinical diagnosis, n = 19) had been followed up after initial workup for a maximum of 14 years. MEASUREMENTS AND RESULTS: RHC data on 61 patients and PFT data on 52 patients were available. Five-year survival rates were 62.2% in the normal-PAP group (mean PAP < 17 mm Hg, n = 37) and 16.7% in the high-PAP group (mean PAP > 17 mm Hg, n = 24) [p < 0.001]; 70.4% in the preserved-Dlco group (percentage of predicted > 40%, n = 27) and 20.0% in the low-Dlco group (percentage of predicted < 40%, n = 25) [p < 0.001]; and 82.6% in group 1 (normal PAP and preserved Dlco, n = 23) and 15.6% in group 2 (high PAP, low Dlco, or both, n = 32) [p < 0.0001]. The relative risks of mortality within 5 years after RHC were 2.20 (95% confidence interval [CI], 1.40 to 3.45) in the high-PAP group, 2.70 (95% CI, 1.46 to 4.99) in the low-Dlco group, and 4.85 (95% CI, 1.97 to 11.97) in group 2. CONCLUSION: Dlco was a critical factor for evaluating disease status and prognosis, and PAP status provided feasible information in the initial workup of IPF patients.

Clinical and radiographic indices associated with airflow limitation in patients with sarcoidosis.

BACKGROUND: Airflow limitation is found in some patients with sarcoidosis, and it is associated with a poor prognosis. The aim of this study was to investigate clinical and radiographic indices associated with airflow limitation in patients with sarcoidosis. METHODS: A prospective, observational study was performed on 228 consecutive sarcoidosis patients followed up at our patient clinic at the Central Clinic of Kyoto. Patients underwent pulmonary function tests, and high-resolution CT (HRCT) of the lung was evaluated for the presence of lymph node enlargement, lung opacity, reticular shadow, and thickening of bronchovascular bundles (BVB). Airflow limitation was defined as FEV(1)/FVC < 70%. Airway reversibility was tested in subjects with airflow limitation. The frequency of airflow limitation was evaluated, and clinical and radiographic parameters were compared between patients with and without airflow limitation. RESULTS: Among all 228 subjects, 20 subjects (8.8%) had airflow limitation, and none showed airway reversibility. Patients with airflow limitation were predominantly male, smokers, and had advanced chest radiographic stage, increased frequency of lung opacities, reticular shadows, and thickened BVB on HRCT. Stepwise regression analysis showed that chest radiographic stage IV, higher age, smoking, and thickened BVB were independently associated with lower FEV(1)/FVC. CONCLUSION: The frequency of airflow limitation was 8.8% in Japanese sarcoidosis patients. Chest radiographic stage IV, higher age, smoking, and thickened BVB were associated with airflow limitation in patients with sarcoidosis.

Incidence of pulmonary hypertension and its clinical relevance in patients with sarcoidosis.

OBJECTIVE: To investigate the frequency of pulmonary hypertension (PH) and clinical parameters associated with PH in sarcoidosis patients. METHODS: A prospective, observational study was performed on 246 consecutive Japanese sarcoidosis patients followed up at the outpatient sarcoidosis clinic in the Central Clinic of Kyoto. The patients were evaluated for PH by Doppler echocardiography. Among these patients, 192 underwent pulmonary function tests. In addition, high-resolution CT of the lung was evaluated for the presence of lymph node enlargement, lung opacity, and thickening of bronchovascular bundles in 122 patients. PH was defined as estimated systolic pulmonary artery pressure (sPAP) > or = 40 mm Hg. The frequency of PH was evaluated, and clinical parameters were compared between patients with PH and those without PH. RESULTS: Among 212 patients who were successfully evaluated for sPAP, 12 patients (5.7%) had PH. Patients with PH had the following clinical characteristics: advanced chest radiographic stage, decreased oxygen saturation, predominantly male gender, and decreased percentage of predicted vital capacity, percentage of predicted FVC, percentage of predicted FEV1, percentage of predicted functional residual capacity, and percentage of predicted total lung capacity (%TLC). Multivariate logistic regression analysis showed that decreased %TLC was independently associated with PH. There was a weak negative correlation between sPAP and %TLC (p < 0.05). CONCLUSIONS: The frequency of PH in Japanese sarcoidosis patients was 5.7% evaluated with Doppler echocardiography. Decreased lung volume increases the risk of PH developing in patients with sarcoidosis.

Chymase gene (CMA1) polymorphisms in Dutch and Japanese sarcoidosis patients.

BACKGROUND: Chymase is released from mast cells following activation. Evidence suggests that chymase plays an important role in tissue injury and remodeling of the lungs, heart and skin. OBJECTIVE: We postulated that chymase gene (CMA1) polymorphisms are associated with pulmonary fibrosis in Dutch and with cardiac and skin involvement in Japanese sarcoidosis patients. PATIENTS AND METHODS: Dutch (n = 153) and Japanese (n = 122) sarcoidosis patients with controls (Dutch, n = 309; Japanese, n = 111) were studied. Pulmonary involvement in Dutch patients as well as clinical manifestations in Japanese patients was evaluated for association with five CMA1 polymorphisms. RESULTS: The CMA1 polymorphisms were not associated with disease susceptibility in either population, or with radiographic evolution in the Dutch or with cardiac or skin involvement in the Japanese patients. The -526 T allele was associated with a lower iVC in Dutch patients. CONCLUSIONS: The CMA1 polymorphisms studied do not contribute to disease susceptibility in Japanese or Dutch sarcoidosis patients. CMA1 polymorphisms do not influence radiographic evolution in Dutch sarcoidosis patients, nor do they predispose to cardiac or skin involvement in Japanese patients. However, the association between CMA1 -526 C/T and iVC in the Dutch patients suggests that chymase may modify the functional outcome of pulmonary sarcoidosis.