Early Interstitial Lung Disease Research Articles

Cyclophosphamide-refractory scleroderma-associated interstitial lung disease: remarkable clinical and radiological response to a single course of rituximab combined with high-dose corticosteroids

We would like to report our experience of using rituximab in cyclophosphamide refractory, rapidly progressive interstitial lung disease (ILD) in a patient with limited scleroderma. A 40-year-old man presented with 10-week history of inflammatory polyarthritis, which responded to a short course of oral corticosteroids. However, 3 weeks later, he developed new onset of exertional dyspnoea. High-resolution CT of the thorax was suggestive of early ILD. Surgical lung biopsy showed features of fibrotic non-specific interstitial pneumonia. He was diagnosed with scleroderma on the basis of: presence of anticentromere antibodies, Raynaud's phenomenon, pulmonary fibrosis, digital oedema and hypomotility along with a dilated oesophagus. He was treated aggressively with pulse doses of corticosteroids and cyclophosphamide; however, his ILD continued to deteriorate. At this stage, he received rituximab (two pulses of 1 g each), which led to a gradual clinical improvement. Now, 12 months since his rituximab infusion, he walks 2 miles daily without any exertional dyspnoea.

Computer-aided detection of early interstitial lung diseases using low-dose CT images

This study aims to develop a new computer-aided detection (CAD) scheme to detect early interstitial lung disease (ILD) using low-dose computed tomography (CT) examinations. The CAD scheme classifies each pixel depicted on the segmented lung areas into positive or negative groups for ILD using a mesh-grid-based region growth method and a multi-feature-based artificial neural network (ANN). A genetic algorithm was applied to select optimal image features and the ANN structure. In testing each CT examination, only pixels selected by the mesh-grid region growth method were analyzed and classified by the ANN to improve computational efficiency. All unselected pixels were classified as negative for ILD. After classifying all pixels into the positive and negative groups, CAD computed a detection score based on the ratio of the number of positive pixels to all pixels in the segmented lung areas, which indicates the likelihood of the test case being positive for ILD. When applying to an independent testing dataset of 15 positive and 15 negative cases, the CAD scheme yielded the area under receiver operating characteristic curve (AUC = 0.884 ± 0.064) and 80.0% sensitivity at 85.7% specificity. The results demonstrated the feasibility of applying the CAD scheme to automatically detect early ILD using low-dose CT examinations.

P64 Early onset interstitial lung disease and JO 1 positivity

P64 Early onset interstitial lung disease and JO 1 positivity

Antisynthetase Syndrome Presenting as Rheumatoid-Like Polyarthritis

The antisynthetase syndrome is a systemic inflammatory disease associated with anti-tRNA synthetase antibodies and consisting of the clinical features of inflammatory myopathy arthritis, interstitial lung disease (ILD), fever, Raynaud syndrome, and rash. It rarely presents with symmetric arthritis as the initial manifestation of the disease. The aim of the study was to describe the clinical, laboratory, and radiographic characteristics of patients with antisynthetase syndrome who presented with symptoms of inflammatory arthritis, mimicking rheumatoid arthritis (RA) at the time of initial evaluation. Six cases derived from a single university-based rheumatology clinic in Wisconsin are presented. The major clinical, laboratory, radiographic, and histopathologic data are described. All 6 patients demonstrated symmetric synovitis involving the hands. Five patients met the American College of Rheumatology classification criteria for RA. Three patients had nail-fold capillary abnormalities, and 4 patients were observed to have Raynaud phenomenon. Three patients demonstrated a cytoplasmic pattern when testing for antinuclear antibodies by immunofluorescent assay, and all had t-RNA synthetase antibodies. Two patients had positive rheumatoid factors, but none had strongly positive cyclic citrullinated peptide antibodies. None of the patients demonstrated radiographic erosions. All patients had evidence of ILD by imaging or pulmonary function testing. Prognosis was generally favorable, although disease severity and treatment varied considerably. In patients who present with features mimicking but atypical for RA, such as early ILD, nail-fold capillary abnormalities, Raynaud phenomenon, cytoplasmic antinuclear antibody pattern, negative cyclic citrullinated peptide antibody status, and nonerosive arthritis, the antisynthetase syndrome should be considered.

Interstitial Lung Disease in Classic and Skin-Predominant Dermatomyositis

(1) To determine the prevalence of interstitial lung disease (ILD) and isolated low diffusing capacity for carbon monoxide (DLCO) in a large cohort of outpatients with dermatomyositis. (2) To compare the pulmonary abnormalities of patients with classic dermatomyositis and those with skin-predominant dermatomyositis. Retrospective cohort study. University hospital outpatient dermatology referral center. Patients Medical records of 91 outpatients with adult-onset dermatomyositis seen between May 26, 2006, and May 25, 2009, were reviewed. Presence of ILD on thin-slice chest computed tomographic (CT) scans and DLCO. Of the 71 patients with dermatomyositis who had CT or DLCO data, 16 (23%; 95% confidence interval [CI], 13%-33%) had ILD as defined by CT results [corrected]. All patients with ILD had a reduced DLCO, and the ILD prevalence was not different between patients with skin-predominant dermatomyositis (10 of 35 [29% ]) and those with classic dermatomyositis (6 of 36 [17% ]) (P = .27). Eighteen of 71 patients with dermatomyositis (25%; 95% CI, 15%-36%) (7 of 35 [20%] with skin-predominant dermatomyositis; 11 of 36 [31%] with classic dermatomyositis; P = .41) had a low DLCO in the absence of CT findings showing ILD. The prevalence of malignant disease was higher in patients with classic dermatomyositis than in those with skin-predominant dermatomyositis (P = .02), and no patients with skin-predominant dermatomyositis had internal malignant disease. Radiologic ILD and isolated DLCO reductions, which may signify early ILD or pulmonary hypertension, are common in dermatology outpatients with both classic and skin-predominant dermatomyositis. Because DLCO testing is both inexpensive and sensitive for pulmonary disease, it may be appropriate to screen all patients with dermatomyositis with serial DLCO measurements and base further testing on DLCO results.

Identification of Early Interstitial Lung Disease in an Individual With Genetic Variations in ABCA3 and SFTPC

A man with usual interstitial pneumonia (age of onset 58 years) was previously found to have an Ile73Thr (I73T) surfactant protein C (SFTPC) mutation. Genomic DNA from the individual and two daughters (aged 39 and 43 years) was sequenced for the I73T mutation and variations in ATP-binding cassette A3 (ABCA3). All three had the I73T SFTPC mutation. The father and one daughter (aged 39 years) also had a transversion encoding an Asp123Asn (D123N) substitution in ABCA3. The daughters were evaluated by pulmonary function testing and high-resolution CT (HRCT). Neither daughter had evidence of disease, except for focal subpleural septal thickening on HRCT scan in one daughter (aged 39 years). This daughter underwent bronchoscopy with transbronchial biopsies revealing interstitial fibrotic remodeling. These findings demonstrate that subclinical fibrotic changes may be present in family members of patients with SFTPC mutation-associated interstitial lung disease and suggest that ABCA3 variants could affect disease pathogenesis.

Identification of Early Interstitial Lung Disease in Smokers from the COPDGene Study

The aim of this study is to compare two subjective methods for the identification of changes suggestive of early interstitial lung disease (ILD) on chest computed tomographic (CT) scans. The CT scans of the first 100 subjects enrolled in the COPDGene Study from a single institution were examined using a sequential reader and a group consensus interpretation scheme. CT scans were evaluated for the presence of parenchymal changes consistent with ILD using the following scoring system: 0 = normal, 1 = equivocal for the presence of ILD, 2 = highly suspicious for ILD, and 3 = classic ILD changes. A statistical comparison of patients with early ILD to normal subjects was performed. There was a high degree of agreement between methods (kappa = 0.84; 95% confidence interval, 0.73-0.94; P < .0001 for the sequential and consensus methods). The sequential reading method had both high positive (1.0) and negative (0.97) predictive values for a consensus read despite a 58% reduction in the number of chest CT evaluations. Regardless of interpretation method, the prevalence of chest CT changes consistent with early ILD in this subset of smokers from COPDGene varied between 5% and 10%. Subjects with early ILD tended to have greater tobacco smoke exposure than subjects without early ILD (P = .053). A sequential CT interpretation scheme is an efficient method for the visual interpretation of CT data. Further investigation is required to independently confirm our findings and further characterize early ILD in smokers.

Small airways obstruction syndrome in clinical practice

Small airways obstruction syndrome (SAOS) is a particular pulmonary function test (PFT) pattern showing decreased VC and FEV(1) but a normal FEV(1)/VC ratio and TLC. The significance of this syndrome in clinical practice has not been comprehensively investigated. This study retrospectively identified all patients who had performed PFT that showed a SAOS pattern at a university teaching hospital over 1 year. A simple algorithm for differential diagnosis was developed and validated. Of the 3207 PFT performed, 153 (4.8%) showed a pattern indicating SAOS. Among these, a final diagnosis was confirmed for 85 (63.4%) of the patients. The causes of SAOS included both restrictive and obstructive lung diseases with the leading causes being early interstitial lung disease (n = 20; 23.3%), chest wall deformity (n = 12; 14.1%) and asthma (n = 10; 11.6%). Using a cut-off point of TLC of <95% predicted value to identify restrictive ventilatory defects (P = 0.002) and of > or =95% predicted combined with RV/TLC > or =55% to identify obstructive ventilatory defects (P < 0.001), a simplified algorithm with good accuracy (86.6%) was identified. Validation in an independent group showed accuracy of 91%. The PFT pattern called SAOS is not uncommon. The most common causes of SAOS were early interstitial lung disease, chest wall deformity and asthma. A diagnostic algorithm was proposed, which may help physicians' decision-making in their daily practice.

Additional computed tomography scans in the prone position to distinguish early interstitial lung disease from dependent density on helical computed tomography screening patient characteristics

The purpose of this study was to evaluate the benefit of additional prone CT scanning to helical CT screening to detect early interstitial lung disease (ILD). Helical CT screening was performed as an optional test in 1098 subjects during their annual health examination. Subjects with parenchymal abnormalities in the posterior subpleural aspect of the lung were advised to receive additional CT scans in the prone position. The CT images were assessed independently by both a radiologist and a chest specialist without reference to clinical data. Ninety-three subjects (8%) had parenchymal abnormalities in the posterior subpleural aspect of the lung and 75 subjects (7%) received additional CT scans. These revealed 72 dependent densities and three early ILD (0.3%). By multivariate analysis, subjects aged over 70 years, with obesity (BMI >or= 25) and currently smoking (pack years >or= 20) had a tendency to have dependent density on helical CT, the predominant distribution of which was in the middle lung fields. Additional CT scans were performed in 7% of subjects after abnormal CT screening and three early ILD were detected. Therefore, we recommend that additional CT scans in prone position be performed to detect early ILD after abnormal helical CT screening.

Characteristics and Disease Activity of Early Interstitial Lung Disease in Subjects With True Parenchymal Abnormalities in the Posterior Subpleural Aspect of the Lung

To evaluate characteristics or disease activity of early interstitial lung disease (ILD) in subjects with true parenchymal abnormalities in the posterior subpleural aspect of the lung. This study enrolled 14 subjects with dependent densities that disappeared on helical CT obtained with the subject prone (control group) and 7 subjects with true parenchymal abnormalities that remained unchanged on prone CT image but were not detectable on chest radiographs (true abnormalities group). Pulmonary function tests and serum markers for idiopathic lung fibrosis as KL-6, surfactant protein D (SP-D), and surfactant protein A (SP-A) in the two groups were evaluated. In the true abnormalities group, curvilinear subpleural lines or thickened interlobular and intralobular lines were observed more frequently in the lower lung fields. Diffusing capacities of the lung for carbon monoxide (15.3 +/- 3.5 mL/min/mm Hg vs 18.8 +/- 3.7 mL/min/mm Hg, p = 0.0493) were lower, and KL-6 (607 +/- 297 U/mL vs 318 +/- 143 U/mL, p = 0.0090), SP-A (59 +/- 24 ng/mL vs 34 +/- 12 ng/mL, p = 0.0207), and SP-D (112 +/- 54 ng/mL vs 42 +/- 24 ng/mL, p = 0.0028) were higher in the true abnormalities group than in the control group (+/- SD). True parenchymal abnormalities in the posterior subpleural aspect of the lung may indicate early ILD activity.