Predictive Factors for the Long-Term Deterioration of Pulmonary Function in Interstitial Lung Disease Associated with Anti-Aminoacyl-tRNA Synthetase Antibodies.

BACKGROUND: Little has been reported on long-term pulmonary function trends among patients with interstitial lung disease associated with anti-aminoacyl-tRNA synthetase antibodies (ARS-ILD). OBJECTIVES: To clarify the factors predictive of progression in ARS-ILD based on patients' initial clinical and radiological features. METHODS: The clinical courses of 88 patients with > 1 year of follow-up data on pulmonary function tests (PFTs) were retrospectively analyzed. Disease behavior was categorized into three groups: (1) improved or (2) worsened (defined as increases or decreases, respectively, of > 10% in forced vital capacity and > 15% in %diffusing capacity of lung carbon monoxide) or (3) stable based on PFT changes compared between 1-year results as the initial data and results at 3 years to assess the long-term course. RESULTS: In the initial course of 75 patients with ARS-ILD who received anti-inflammatory therapy within 6 months after diagnosis, 48 patients (64.0%) improved and 6 patients (8.0%) worsened. The radiological patterns in the patients with ARS-ILD included nonspecific interstitial pneumonia (NSIP) in 46.7% and NSIP with organizing pneumonia overlap in 52.0% of the cases. One-third of the initially improved patients who worsened over the long-term course were assigned to the unstable group. By multivariate logistic analysis, middle lobe traction bronchiectasis was a significant predictive factor for the patients in the unstable group. CONCLUSIONS: Most patients with ARS-ILD receiving anti-inflammatory therapy had improved or remained stable in the first year. However, over the long-term course, some patients worsened despite their initial improvement. Even though the extent of the disease is limited, middle lobe traction bronchiectasis in ARS-ILD may be a useful predictor of poor long-term disease behavior.

Emphysematous change with scleroderma-associated interstitial lung disease: the potential contribution of vasculopathy?

BACKGROUND: Pulmonary emphysema combined with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) occurs more often in smokers but also in never-smokers. This study aimed to describe a new finding characterized by peculiar emphysematous change with SSc-associated ILD (SSc-ILD). METHODS: We conducted a retrospective review of 21 consecutive patients with SSc-ILD diagnosed by surgical lung biopsy and focused on the radio-pathological correlation of the emphysematous change. RESULTS: Pathological pulmonary emphysema (p-PE) with SSc-ILD was the predominant complication in 16 patients (76.2%) with/without a smoking history, of whom 62.5% were never-smokers. A low attenuation area (LAA) within interstitial abnormality on high-resolution computed tomography (HRCT) was present in 31.3%. Diffusing capacity of the lung for carbon monoxide (DLCO) was lower, disease extent on HRCT higher, and intimal/medial thickening in muscular pulmonary arteries more common in the patients with p-PE with SSc-ILD. However, forced vital capacity (FVC) was well preserved regardless of whether p-PE was observed. Most SSc-ILD patients had pulmonary microvasculature changes in arterioles (90.5%), venules (85.7%), and interlobular veins (81.0%). CONCLUSIONS: Pulmonary emphysematous changes (LAA within interstitial abnormalities on HRCT and destruction of fibrously thickened alveolar walls) are specific and novel radio-pathological features of SSc-ILD. Peripheral vasculopathy may help to destroy the fibrously thickened alveolar walls, resulting in emphysematous change in SSc-ILD.

Long-term clinical course of anti-glycyl tRNA synthetase (anti-EJ) antibody-related interstitial lung disease pathologically proven by surgical lung biopsy.

BACKGROUND: Anti-glycyl-tRNA synthetase (anti-EJ) antibody is occasionally positive in patients with interstitial lung disease (ILD). We aimed to define the clinical, radiological and pathological features of patients with anti-EJ antibody-positive ILD (EJ-ILD). METHODS: We retrospectively analyzed the medical records of 12 consecutive patients with EJ-ILD who underwent surgical lung biopsy. RESULTS: The median follow-up time was 74 months (range, 17-115 months). The median age was 62 years (range, 47-75 years). Seven of 12 patients were female. Eight patients presented with acute onset. Six patients eventually developed polymyositis/dermatomyositis. On high-resolution computed tomography, consolidation and volume loss were predominantly observed in the middle or lower lung zone. Nine patients presented pathologically nonspecific interstitial pneumonia with organizing pneumonia, alveolar epithelial injury and prominent interstitial cellular infiltrations whereas the other three patients were diagnosed with unclassifiable interstitial pneumonia. Although all patients but one improved with the initial immunosuppressive therapy, five patients relapsed. When ILD relapsed, four of the five patients were treated with corticosteroid monotherapy. Four of the six patients without relapse have been continuously treated with combination therapy of corticosteroid and immunosuppressant. CONCLUSIONS: Patients with EJ-ILD often had acute onset of ILD with lower lung-predominant shadows and pathologically nonspecific interstitial pneumonia or unclassifiable interstitial pneumonia with acute inflammatory findings. Although the disease responded well to the initial treatment, relapse was frequent. Because of the diversity of the clinical courses, combination therapy of corticosteroid and immunosuppressant should be on the list of options to prevent relapse of EJ-ILD.

Low-normal lung volume correlates with pulmonary hypertension in fibrotic idiopathic interstitial pneumonia: computer-aided 3D quantitative analysis of chest CT.

OBJECTIVE: We investigated whether the lung volume determined on CT, especially the volume of the normal lung, is correlated with mean pulmonary artery pressure (PAP) in patients with chronic fibrosing idiopathic interstitial pneumonia (IIP). MATERIALS AND METHODS: The subjects were 40 patients with IIP who underwent right heart catheterization (RHC) and chest CT. Thirty-three patients (82.5%) were smokers or former smokers. Using a computer-aided system, the lungs in the 3D CT images were automatically categorized pixel-by-pixel with gaussian histogramnormalized correlations, and the relative volume of each lesion to the CT lung volume was calculated as "normal(%)," "ground-glass opacities(%)," "consolidation(%)," "emphysema(%)," and "fibrosis(%)." The relationship between each "volume(%)" and pulmonary hypertension was evaluated using logistic regression analysis. ROC curves were constructed to assess the predictive value of these CT-based volumes in the identification of pulmonary hypertension. RESULTS: Sixteen patients had pulmonary hypertension at rest (mean PAP > 25 mm Hg on RHC). Emphysema constituted more than 10% of the CT lung volume in 13 patients. On multivariate analysis of each volume(%), normal(%) was significant for detecting pulmonary hypertension (odds ratio, 0.92; 95% CI, 0.86-0.96; p = 0.02). On ROC analysis, the AUC of normal(%) was 0.849 (0.731-0.967). CONCLUSION: The relative CT volume of any single lesion was of limited value in predicting pulmonary hypertension in patients with pulmonary fibrosis and emphysema. In these patients, normal(%), measured by a 3D computer-aided system, was correlated with pulmonary hypertension measured by RHC.

Clinical, radiological, and pathological features of anti-asparaginyl tRNA synthetase antibody-related interstitial lung disease.

BACKGROUND: Myositis and interstitial lung disease (ILD) frequently occur in patients with anti-aminoacyl-tRNA synthetase (ARS) antibodies. Nearly half of ARS-ILD patients have the acute or subacute form of the disease, and one-third of these patients show a deterioration in pulmonary function over the long-term course because of frequent recurrences and refractoriness to therapy. Several reports recently described different characteristics depending on the individual anti-ARS antibodies, and the anti-asparaginyl tRNA synthetase (KS) antibody was strongly linked to ILD rather than to myositis. We therefore hypothesized that KS-ILD may have clinical characteristics that differ from those of other ARS-ILDs. The aim of this study was to clarify the clinical, radiological, and pathological features of KS antibody-positive ILD. METHODS: We retrospectively analyzed 19 consecutive patients with KS-ILD who underwent initial clinical measurements and high-resolution computed tomography and pathological assessments. We also analyzed disease behavior based on pulmonary function test results during the follow-up period. RESULTS: Our KS-ILD cohort included patients with dermatomyositis (10.5%), primary Sjögren syndrome (5.3%), and idiopathic ILD (84.2%). Most patients presented with chronic onset (89.5%) and a nonspecific pattern of interstitial pneumonia at each radiological and pathological assessment (89.4% and 85.7%, respectively). The pulmonary function test results showed that the mean changes from the initial %forced vital capacity and %diffusing capacity of the lung for carbon monoxide at 3 years were 3.7% ± 2.9% and 9.35% ± 3.0%, respectively. CONCLUSIONS: Most KS-ILD patients showed a tendency for chronic disease onset and long-term stabilization of pulmonary function.

Evaluation of changes in the serum levels of Krebs von den Lungen-6 and surfactant protein-D over time as important biomarkers in idiopathic fibrotic nonspecific interstitial pneumonia.

BACKGROUND: Some cases of idiopathic fibrotic nonspecific interstitial pneumonia (f-NSIP) show a progressive course that is similar to that of idiopathic pulmonary fibrosis. However, it is difficult to predict poor patient outcomes. This study aimed to evaluate whether serial changes in serum levels of Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) can predict disease progression. METHODS: We retrospectively analyzed the medical records of 75 patients with idiopathic f-NSIP. Disease behavior was categorized into two groups depending on long-term change of pulmonary function: progressive type (≥5%/year relative decline in the slope of forced vital capacity [FVC] and/or ≥7.5%/year relative decline in the slope of %diffusing capacity of the lung for carbon monoxide [%DLCO]) and stable type. Levels of KL-6 and SP-D and results of pulmonary function tests, which were performed parallelly, were reviewed and analyzed using a linear mixed-effects model. RESULTS: The study subjects comprised 62 patients with stable type and 13 patients with progressive type disease behavior. Among these subjects, 50 patients fulfilled the diagnostic criteria of interstitial pneumonia with autoimmune features (IPAF). Serum levels of both KL-6 and SP-D at baseline showed a negative correlation with %DLCO, but not with FVC, and these biomarkers were not related to disease progression. Persistently high levels of KL-6 and SP-D correlated with progressive type disease behavior in idiopathic (non-IPAF) f-NSIP. CONCLUSIONS: Changes in serum KL-6 and SP-D levels over time may provide useful predictive information on disease behavior during treatment in patients with idiopathic f-NSIP and especially in those with non-IPAF f-NSIP.

Interstitial lung disease associated with anti-citrullinated peptide/protein antibody-positive anti-synthetase syndrome.

Little has been reported on the characteristics of interstitial lung disease (ILD) associated with anti-citrullinated peptide/protein antibody (ACPA)-positive anti-synthetase syndrome (ASS). We sought to investigate the clinical, radiologic, and pathologic features of patients with ILD associated with ACPA-positive ASS. Medical records of seven ILD patients with positive results of both ACPA and anti-aminoacyl-tRNA synthetase antibody were retrospectively reviewed. Five patients had clinical symptoms associated with ASS other than ILD. On high-resolution computed tomography (HRCT) analysis, a nonspecific interstitial pneumonia (NSIP) pattern was shown in 3 patients and NSIP with organizing pneumonia (OP) overlap in 2 patients. Coronal slices of these 5 patients showed lower lung disease predominance with traction caudally on major fissures due to lower lobe volume loss. These were features that could commonly be observed in ASS-associated ILD. Pathological findings available for 3 patients showed NSIP. The characteristics of ILD associated with ACPA-positive ASS appear to be similar to those of ILD associated with ASS, but not to rheumatoid arthritis (RA) or ACPA, especially in terms of the radiological findings.

Clinical Features of Idiopathic Interstitial Pneumonia with Systemic Sclerosis-Related Autoantibody in Comparison with Interstitial Pneumonia with Systemic Sclerosis.

BACKGROUND: Patients with idiopathic interstitial pneumonias sometimes have a few features of connective tissue disease (CTD) and yet do not fulfil the diagnostic criteria for any specific CTD. OBJECTIVE: This study was conducted to elucidate the characteristics, prognosis, and disease behavior in patients with interstitial lung disease (ILD) associated with systemic sclerosis (SSc)-related autoantibodies. METHODS: We retrospectively analyzed medical records of 72 ILD patients: 40 patients with SSc (SSc-ILD) and 32 patients with SSc-related autoantibody-positive ILD but not with CTD (ScAb-ILD), indicating lung-dominant CTD with SSc-related autoantibody. RESULTS: Patients with SSc-ILD were predominantly females and non-smokers, and most had nonspecific interstitial pneumonia confirmed by high-resolution computed tomography (HRCT) and pathological analysis. However, about half of the patients with ScAb-ILD were male and current or ex-smokers. On HRCT analysis, honeycombing was more predominant in patients with ScAb-ILD than with SSc-ILD. Pathological analysis showed the severity of vascular intimal or medial thickening in the SSc-ILD patients to be significantly higher than that in the ScAb-ILD patients. Survival curves showed that the patients with ScAb-ILD had a significantly poorer outcome than those with SSc-ILD. CONCLUSION: Data from this study suggest that lung-dominant CTD with SSc-related autoantibody is a different disease entity from SSc-ILD.