Clinical profiles of SS-ILD compared with SS-NILD in a Chinese population: a retrospective analysis of 735 patients.

BACKGROUND: Interstitial lung disease (ILD) is a serious complication in patients with Sjögren's syndrome (SS). Most studies on primary SS (pSS) with ILD are limited in sample size, and studies on secondary SS (sSS) with ILD are rare. This study aimed to elucidate both primary and secondary SS-associated ILD (SS-ILD) based on a large cohort. METHODS: The medical records of hospitalized patients diagnosed with SS at the Second Xiangya Hospital of Central South University from January 2010 to May 2020 were retrospectively reviewed. Clinical manifestations, medical history, biological results and imaging data were collected. RESULTS: Of the 735 SS patients enrolled in this study, 563 (76.6%) were diagnosed with pSS, 172 (23.4%) were diagnosed with sSS. Additionally, 316 (43.0%) were diagnosed with SS-ILD. No significant difference was found between the pSS and sSS groups concerning the incidence of ILD (p = .718). Factors associated with SS-ILD were older age (p < .001), male sex (p = .032), female sex at menopause (p = .002), Raynaud's phenomenon (p < .001), low levels of albumin (p = .010) and respiratory symptoms (p < .001). The SS-ILD group showed higher counts of platelets (p < .001). The three most frequent high-resolution CT (HRCT) findings of SS-ILD were irregular linear opacities (42.7%), grid shadows (30.7%) and pleural thickening (28.5%). NSIP (56.3%) was the most frequent HRCT pattern. Compared with pSS patients with ILD (pSS-ILD) patients, sSS patients with ILD (sSS-ILD) patients had a higher incidence of proteinuria (p < .001) and hypercreatinaemia (p = .013), a higher level of erythrocyte sedimentation rate (ESR) (p = .003), low levels of complement 3 (C3) (p = .013), lymphocytes (p = .009) and leukocytes (p = .024), and worse DLCO (%Pred) (p = .035). CONCLUSIONS: ILD is a common pulmonary involvement in both pSS patients and sSS patients. Older age, male sex, female sex at menopause, Raynaud's phenomenon, low albumin levels and respiratory symptoms are risk factors associated with SS-ILD. NSIP is important HRCT feature of SS-ILD. sSS-ILD patients showed worse laboratory results and pulmonary function.KEY MESSAGEOlder age, male sex, female sex at menopause, Raynaud's phenomenon, low albumin levels and respiratory symptoms are risk factors associated with SS-ILD.SS-ILD patients show higher counts of platelets and less purpura.sSS-ILD patients have worse laboratory results and pulmonary function.

Efficacy and safety of nintedanib in Asian patients with systemic sclerosis-associated interstitial lung disease: Subgroup analysis of the SENSCIS trial.

BACKGROUND AND OBJECTIVE: In the SENSCIS trial in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), nintedanib reduced the rate of decline in forced vital capacity (FVC) (mL/year) over 52 weeks by 44% in comparison with placebo, with manageable adverse events in most patients. We analyzed the efficacy and safety of nintedanib in patients of Asian race. METHODS: Patients with SSc-ILD were randomized to receive nintedanib or placebo. The outcomes over 52 weeks were analyzed in Asian versus non-Asian patients. RESULTS: Of the 288 patients in each treatment group, 62 (21.5%) in the nintedanib group and 81 (28.1%) in the placebo group were Asian; 90.2% of the Asian patients were enrolled in Asian countries. In the placebo group, the rate of FVC decline over 52 weeks was consistent between Asian and non-Asian patients (-99.9 and -90.6 mL/year, respectively). The effect of nintedanib on reducing the rate of FVC decline over 52 weeks was consistent between Asian (difference, 44.3 mL/year [95% CI: -32.8, 121.4]) and non-Asian patients (difference, 39.0 mL/year [95% CI: -5.1, 83.1]) (treatment-by-time-by-subgroup interaction, p = 0.91). Diarrhea was the most frequent adverse event and was reported in similar proportions of Asian and non-Asian patients in the nintedanib group (80.6% and 74.3%, respectively) and placebo group (28.4% and 32.9%, respectively). CONCLUSIONS: In patients with SSc-ILD, nintedanib had a consistent benefit on slowing the progression of SSc-ILD in Asian and non-Asian patients, with a similar adverse event profile. TRIAL REGISTRATION: ClinicalTrials.gov NCT02597933.

Collagen biomarkers and subclinical interstitial lung disease: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Lung fibrosis is attributed to derangements in extracellular matrix remodeling, a process driven by collagen turnover. We examined the association of two collagen biomarkers, carboxy-terminal telopeptide of collagen type I (ICTP) and amino-terminal propeptide of type III procollagen (PIIINP), with subclinical interstitial lung disease (ILD) in adults. METHODS: We performed a cross-sectional analysis of 3244 participants age 45-84 years in the Multi-Ethnic Study of Atherosclerosis. Serum ICTP and PIIINP levels were measured at baseline by radioimmunoassay. Subclinical ILD was defined as high attenuation areas (HAA) in the lung fields on baseline cardiac CT scans. Interstitial lung abnormalities (ILA) were measured in 1082 full-lung CT scans at 9.5 years median follow-up. We used generalized linear models to examine the associations of collagen biomarkers with HAA and ILA. RESULTS: Median (IQR) for ICTP was 3.2 µg/L (2.6-3.9 µg/L) and for PIIINP was 5.3 µg/L (4.5-6.2 µg/L). In fully adjusted models, each SD increment in ICTP was associated with a 1.3% increment in HAA (95% CI 0.2-2.4%, p = 0.02) and each SD increment in PIIINP was associated with a 0.96% increment in HAA (95% CI 0.06-1.9%, p = 0.04). There was no association between ICTP or PIIINP and ILA. There was no evidence of effect modification by gender, race, smoking status or eGFR. CONCLUSIONS: Higher levels of collagen biomarkers are associated with greater HAA independent of gender, race and smoking status. This suggests that extracellular matrix remodeling may accompany subclinical ILD prior to the onset of clinically evident disease.

African-American race and mortality in interstitial lung disease: a multicentre propensity-matched analysis.

We studied whether African-American race is associated with younger age and decreased survival time at diagnosis of interstitial lung disease (ILD).We performed a multicentre, propensity score-matched analysis of patients with an ILD diagnosis followed at five US hospitals between 2006 and 2016. African-Americans were matched with patients of other races based on a time-dependent propensity score calculated from multiple patient, physiological, diagnostic and hospital characteristics. Multivariable logistic regression models were used. All-cause mortality and hospitalisations were compared between race-stratified patient cohorts with ILD, and sensitivity analyses were performed.The study included 1640 patients with ILD, 13% of whom were African-American, followed over 5041 person-years. When compared with patients of other races, African-Americans with ILD were younger at diagnosis (56 years versus 67 years), but in the propensity-matched analyses had greater survival (hazard ratio 0.46, 95% CI 0.28-0.77; p=0.003) despite similar risk of respiratory hospitalisations (relative risk 1.04, 95% CI 0.83-1.31; p=0.709), and similar GAP-ILD (gender-age-physiology-ILD) scores at study entry. Sensitivity analyses in a separate cohort of 9503 patients with code-based ILD diagnosis demonstrated a similar association of baseline demographic characteristics with all-cause mortality.We conclude that African-Americans demonstrate a unique phenotype associated with younger age at ILD diagnosis and perhaps longer survival time.

FOXP3 polymorphisms in interstitial lung disease among Chinese Han population: A genetic association study.

INTRODUCTION: Both genetic and environmental factors are implicated in the pathogenesis of interstitial lung disease (ILD). Single-nucleotide polymorphisms (SNPs) in FOXP3 genes were implicated in the causation of some autoimmune diseases; however, association of these genes and ILD has not been reported. OBJECTIVES: To investigate whether FOXP3 polymorphisms are associated with ILD in a representative Chinese population. METHODS: One hundred and fifty-seven ILD patients and 170 healthy controls were recruited; SNPs were genotyped by the Sequenom MassARRAY platform and SHEsis was used to estimate the haplotype frequencies of SNPs. RESULTS: The CC and TC genotypes of FOXP3 rs2280883 were associated with a significantly higher risk of connective tissue disease-associated ILD (CTP-ILD) than the TT genotype (P = .006). Patients with idiopathic interstitial pneumonia (IIP) showed a significantly higher frequency of rs3761547 (GG genotype) and rs3761549 (CC genotype) polymorphisms of FOXP3 as compared to that in controls (P = .038 and P = .026, respectively). The rs2294021 (TC genotype) was less frequently observed among IIP patients as compared to that in controls (P = 0.029). In addition, the FOXP3 CAATC haplotype was associated with a greater risk for CTD-ILD (P =.048) as compared to controls, and the FOXP3 TCCCC haplotype showed an increased IIP risk (P = .001); however, patients with the FOXP3 TACTT haplotype showed a significant protective effect against IIP (P = .036). CONCLUSION: FOXP3 polymorphisms may be important markers to determine susceptibility to IIP or CTP-ILD in Chinese population.

A longitudinal cohort study of the anti-synthetase syndrome: increased severity of interstitial lung disease in black patients and patients with anti-PL7 and anti-PL12 autoantibodies.

Objective: The aim was to study the prevalence, rate of appearance and severity of clinical features in patients with different anti-synthetase syndrome (ASyS) autoantibodies. Methods: All Johns Hopkins Myositis Longitudinal Cohort subjects positive for any ASyS autoantibodies were included. Clinical information, including symptoms, signs, strength, creatine kinase concentrations and pulmonary function tests, were prospectively collected. The standardized mortality and cancer rates and the rate of appearance and intensity of the different organ manifestations were assessed using univariate and multivariate analysis and compared between ASyS autoantibodies. Results: One hundred and twenty-four (73.4%) patients were positive for anti-Jo1, 23 (13.6%) for anti-PL12, 16 for anti-PL7 (9.5%) and 3 (1.8%) for anti-EJ or anti-OJ, respectively. The mean length of follow-up was 4.1 years. Anti-PL12 was more frequent in black subjects. Anti-PL12 and anti-PL7 were associated with more prevalent and severe lung involvement, often without muscle involvement. Anti-Jo1 displayed more severe muscle involvement compared with anti-PL12 patients. Concurrent anti-Ro52 was more prevalent in anti-Jo1 patients and was associated with earlier development of mechanic's hands, DM-specific skin findings and arthritis. Independent of ASyS antibody status, black patients demonstrated more severe lung involvement than white patients. There was no significant increase in mortality or cancer risk in ASyS patients compared with the general US population. Conclusion: Different ASyS autoantibodies are associated with phenotypically distinct subgroups within the ASyS spectrum. Anti-PL7 and anti-PL12 are characterized by more severe lung involvement, whereas anti-Jo1 is associated with more severe muscle involvement. Black race is a major prognostic factor associated with lung disease severity.

A single-nucleotide polymorphism of CCL21 rs951005 T>C is associated with susceptibility of polymyositis and such patients with interstitial lung disease in a Chinese Han population.

OBJECTIVES: Our objective was to better understand the roles of single nucleotide polymorphisms (SNPs) in the CCL21, ERBB3, and TERT genes region in the development of idiopathic inflammatory myopathies (IIMs), we explored the associations between SNPs in the mentioned three genes and IIMs susceptibility in a Chinese Han population. METHODS: Chinese polymyositis (PM) patients (n =291), dermatomyositis (DM) patients (n=526) and ethnically-matched healthy controls (n =968) were genotyped for the CCL21 region SNPs (rs951005 and rs2492358), ERBB3 (rs2292239 and rs11171739), and TERT (rs2853676 and rs10069690), by using the Sequenom MassArray system. RESULTS: Our study indicated strong allele and genotype associations between rs951005 (OR: 1.65, 95%CI: 1.18-2.30, Pc=0.015; Pc=0.041, respectively) in CCL21 gene and PM patients. Additionally, rs951005 was associated with interstitial lung disease (ILD) in PM patients (Pc =0.01), and was associated with PM patients in additive model. However, the Chinese Han PM/DM patients and controls had statistically similar frequencies of alleles, genotypes and different genetic models (additive, dominant, and recessive) of ERBB3 and TERT polymorphisms. CONCLUSIONS: This was the first study to demonstrate that the CCL21 gene SNP (rs951005) might confer genetic predisposition to PM patients or such patients with ILD in a Chinese Han population.

Cutaneous ulceration in dermatomyositis: association with anti-melanoma differentiation-associated gene 5 antibodies and interstitial lung disease.

OBJECTIVE: To identify clinical and serologic correlates of cutaneous ulcers in dermatomyositis (DM). METHODS: We retrospectively examined a cohort of 152 DM patients. We compared the features of patients with ulcers to those without ulcers using chi-square or Fisher's exact tests and used univariate and multivariate logistic regression models to assess the association between ulcers and clinical features such as malignancy, interstitial lung disease (ILD), and amyopathic disease. RESULTS: Forty-three patients (28%) had cutaneous ulcers. Nearly half the patients had ulcers present in more than 1 location: 24 (56%) had ulcers over the extensor surfaces of joints, 18 (42%) at the digital pulp or periungual areas, and 25 (58%) had ulcers located elsewhere. In univariate analysis ulcers were associated with Asian race, but not with other clinical and demographic features, including malignancy or ILD. In multivariate analysis ulcers were significantly associated with anti-melanoma differentiation gene 5 (anti-MDA5) antibodies (odds ratio 10.14, 95% confidence interval 1.95-52.78; P = 0.0059) and this was greatest for ulcers located at the digital pulp. In patients with cutaneous ulcers, ILD risk was specifically increased only in patients with anti-MDA5-positive antibodies. CONCLUSION: We confirmed the strong association between anti-MDA5 antibodies and cutaneous ulcers, with the novel finding that the association of cutaneous ulcers with ILD depends upon the presence of anti-MDA5 antibodies. DM patients who display this cutaneous phenotype should undergo appropriate evaluation for ILD.

Genetic association study of TNFAIP3, IFIH1, IRF5 polymorphisms with polymyositis/dermatomyositis in Chinese Han population.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in the TNFAIP3, IFIH1, and IRF5 genes have been associated with several auto-inflammation diseases, while the susceptibility between these genes and idiopathic inflammatory myopathies (IIMs) were not reported. This study aimed to investigate whether TNFAIP3, IFIH1, and IRF5 gene polymorphisms confer susceptibility for the IIMs in Chinese Han population. METHODS: A large case-control study of Chinese subjects with polymyositis (PM) (n = 298) and dermatomyositis (DM) (n = 530) was accomplished. 968 healthy and ethnically matched controls were available for comparison. Six SNPs in the TNFAIP3 region (rs2230926 and rs5029939), the IFIH1 gene (rs1990760 and rs3747517) and the IRF5 region (rs4728142 and rs729302) were assessed and genotyped using the Sequenom MassArray iPLEX platform. RESULTS: Our study indicated a strong allele association was observed in PM/DM and PM patients for rs2230926 (OR: 1.61, 95%CI: 1.20-2.16, P(c) = 7.5×10(-3); OR: 1.88, 95%CI: 1.30-2.74, P(c) = 4.0×10(-3), respectively) and rs5029939 (OR: 1.64, 95%CI: 1.21-2.21, P(c) = 6.0×10(-3); OR: 1.88, 95%CI: 1.28-2.76, P(c) = 5.5×10(-3), respectively). And rs2230926 and rs5029939 were significantly associated with interstitial lung disease (ILD) in PM/DM and PM patients (P(c) = 0.04 and P(c) = 0.016; P(c) = 0.02 and P(c) = 0.03, respectively). In addition, rs4728142 allele and genotype had significant association with PM/DM patients (P(c) = 0.026 and P(c) = 0.048, respectively). Further analysis with three logistic regression genetic models revealed statistically significant difference in the genotypic distribution in the PM/DM, PM or DM patients when the additive and dominant models were used. CONCLUSIONS: This was the first study to reveal TNFAIP3 and IRF5 polymorphisms were associated with PM/DM patients or these patients with ILD, indicating that TNFAIP3 and IRF5 might be the susceptibility gene for PM/DM patients in Chinese Han population.

Hereditary interstitial lung diseases manifesting in early childhood in Japan.

BACKGROUND: Genetic variations associated with interstitial lung diseases (ILD) have not been extensively studied in Japanese infants. METHODS: Forty-three infants with unexplained lung dysfunction were studied. All 43, 22, and 17 infants underwent analyses of surfactant protein (SP)-C gene (SFTPC) and ATP-binding cassette A3 gene (ABCA3), SP-B gene (SFTPB), and SP-B western blotting, respectively. Two and four underwent assessment of granulocyte macrophage colony-stimulating factor-stimulating phosphorylation of signal transducer and activator of transcription-5 (pSTAT-5) and analyses of FOXF1 gene (FOXF1), respectively. RESULTS: ILD were diagnosed clinically in nine infants: four, three, and two had interstitial pneumonitis, hereditary pulmonary alveolar proteinosis (hPAP), and alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), respectively. Genetic variations considered responsible were detected in six (67%) of the nine infants with ILD: three with hPAP (SFTPC p.Leu45Arg and p.Gln145fs, and ABCA3 p.Arg1583Trp/p.Val1495CysfsX21), two with interstitial pneumonitis (SFTPC p.Lys63Glu and p.Ser72Asn/p.Gly100Ala), and one with ACD/MPV (FOXF1 p.Leu300ArgfsX79). None showed SFTPB mutations or defects in pSTAT-5. The 17 bronchoalveolar lavage or tracheal aspirates contained enough SP-B protein. CONCLUSION: The SP-C abnormality was most prevalent, and SP-B deficiency was rare in Japanese infants with hereditary ILD.

Caveolin-1 deficiency may predispose African Americans to systemic sclerosis-related interstitial lung disease.

OBJECTIVE: Interstitial lung disease (ILD) is the leading cause of death in patients with systemic sclerosis (SSc; scleroderma). Although SSc-related ILD is more common and severe in African Americans than in Caucasians, little is known about factors underlying this significant health disparity. The aim of this study was to examine the role that low expression of caveolin-1 might play in susceptibility to ILD among African Americans. METHODS: Assays of monocyte migration toward stromal cell-derived factor 1 (SDF-1) were performed using monocytes from Caucasian and African American healthy donors and patients with SSc. For fibrocyte differentiation studies, total peripheral blood mononuclear cells were incubated on fibronectin-coated plates. Protein expression was evaluated by immunohistochemistry and Western blotting. RESULTS: Monocytes from healthy African American donors and those from patients with SSc had low caveolin-1 levels, enhanced migration toward the CXCR4 ligand SDF-1, and enhanced differentiation to fibrocytes. Enhanced migration and differentiation of monocytes from African Americans and patients with SSc appeared to be attributable to the lack of caveolin-1, because restoring caveolin-1 function using a caveolin-1 scaffolding domain peptide inhibited these processes. Although they differed from monocytes from Caucasians, monocytes from both African Americans and patients with SSc were not identical, because SSc monocytes showed major increases from baseline in ERK, JNK, p38, and Smad2/3 activation, while monocytes from African Americans showed only limited ERK activation and no activation of JNK, p38, or Smad2/3. In contrast, SDF-1 exposure caused no additional ERK activation in SSc monocytes but did cause significant additional activation in monocytes from African Americans. CONCLUSION: African Americans may be predisposed to SSc-related ILD due to low baseline caveolin-1 levels in their monocytes, potentially affecting signaling, migration, and fibrocyte differentiation. The monocytes of African Americans may lack caveolin-1 due to high levels of transforming growth factor ß in their blood.

Preliminary characterizations of a serum biomarker for sarcoidosis by comparative proteomic approach with tandem-mass spectrometry in ethnic Han Chinese patients.

BACKGROUND: The diagnosis of sarcoidosis is still a significant challenge in China because of the need to exclude other diseases including granulomatous infections and malignancies that may be clinically and radiographically similar. The specific aim of the study is to search for serum protein biomarkers of sarcoidosis and to validate their clinical usefulness in differential diagnosis. METHODS: Serum samples were collected from patients with sarcoidosis (n = 37), and compared to those from patients with tuberculosis (n = 20), other pulmonary diseases (n = 20), and healthy volunteers (n = 20) for determination of sarcoidosis-specific or -associated protein expression profiles. The first part of this study focused on proteomic analysis of serum from patients with sarcoidosis to identify a pattern of peptides capable of differentiating the studied populations using the ClinProt profiling technology based on mass spectrometry. Enzyme Linked Immunosorbent Assay (ELISA) was then used to verify corresponding elevation of the serum protein concentration of the potential biomarkers in the same patients sets. Receiver operating characteristic curve (ROC) analyses was performed to determine the optimal cutoff value for diagnosis. Immunohistochemistry was carried out to further confirm the protein expression patterns of the biomarkers in lung tissue. RESULTS: An unique protein peak of M/Z 3,210 Daltons (Da) was found to be differentially expressed between the sarcoidosis and control groups and was identified as the N-terminal peptide of 29 amino acids (94-122) of serum amyloid A (SAA). ELISA confirmed that the serum SAA level was significantly higher in the sarcoidosis group than that of the other 3 control groups (p < 0.05). The cutoff for serum SAA concentration determined by ROC analysis was 101.98 ng/ml, with the sensitivity and specificity of 96.3% and 52.5%, respectively. Immunohistochemical staining showed that the SAA depositions in lung tissue of the sarcoidosis patients were also significantly more intense than in non-sarcoid lung tissue (p < 0.05). CONCLUSION: This is the first study to investigate serum protein markers in Chinese subjects with sarcoidosis. This study shows that the serum SAA expression profiles were different between the sarcoidosis and non-sarcoidosis groups. SAA may be a potential serum biomarker for ruling-out the diagnosis of sarcoidosis in Chinese subjects.

Interstitial lung disease in clinically amyopathic dermatomyositis (CADM) patients: a retrospective study of 41 Chinese Han patients.

To study the clinical features and associated risk factors of interstitial lung disease (ILD) in clinically amyopathic dermatomyositis (CADM) in Chinese patients. Forty-one Chinese Han patients with a diagnosis of CADM in West China Hospital from August 2008 to 2011 were retrospectively analyzed. The prevalence of ILD in CADM patients is 60.98 %, in which 26.83 % for acute/subacute interstitial pneumonia (A/SIP) and 34.15 % for chronic interstitial pneumonia (CIP). Mortality of A/SIP is 63.64 %, with a 6-month survival rate of 54.50 %. Levels of erythrocyte sedimentation rate, serum ferritin, alanine aminotransferase, aspartate aminotransferase, creatine kinase, lactate dehydrogenase, hydroxybutyric dehydrogenase, and immunoglobulin A (IgA) are higher in CADM-ILD patients than CADM patients without ILD. Levels of serum ALB and lymphocyte count in peripheral blood are significant lower in A/SIP than in CIP group. Sign of ground glass opacities in high-resolution computed tomography (HRCT) images is more common in A/SIP group, and diffusion function is worse in these patients compared with CIP group. The prevalence of ILD in Chinese CADM patients is strikingly high, and A/SIP is a major cause of death in CADM patients. Laboratory findings combined with HRCT examination and pulmonary function tests can provide valuable predictive information of ILD or A/SIP in CADM patients.

Idiopathic inflammatory myositis-associated interstitial lung disease: ethnicity differences and lung function trends in a British cohort.

OBJECTIVE: Interstitial lung disease (ILD) is an important feature of idiopathic inflammatory myositis (IIM). Factors associated with its development and progression remain incompletely understood. The authors report ethnicity differences and lung function trends that characterize the predilection for and natural history of ILD in a group of British patients with IIM. METHODS: A 10-year retrospective analysis of patients with IIM at two hospitals was conducted. Demographic, clinico-radiological and laboratory features of cases with and without ILD were compared. Serial pulmonary function tests, including measurements of forced vital capacity, volume and diffusing capacity for carbon monoxide, were used to identify longitudinal patterns of lung disease. RESULTS: A total of 107 patients with IIM were identified. ILD was present in 37.4%, with non-specific interstitial pneumonia being the most common radiological pattern (75%). ILD was more common in IIM patients of Black ethnicity (OR 3.42), and in cases where ANA (OR 3.06) and anti-histidyl-tRNA synthetase (OR 3.2) antibodies were detected. In the ILD cohort, 50% deteriorated, defined as a drop in diffusing capacity of the lung for carbon monoxide by <15% or forced vital capacity <10% during the study period, occurring in all within a year of onset of ILD and significantly more frequently in those with a synchronous onset of IIM and ILD. Black ethnicity was not associated with poor lung function outcome. CONCLUSION: In IIM, the risk of developing ILD is significantly higher in patients of Black ethnicity. Progressive lung damage occurs in an appreciable subgroup of patients with IIM-ILD, heralded by functional lung decline at 1 year despite systemic immunomodulatory treatment.

Gefitinib-induced interstitial lung disease-addition of intravenous cyclophosphamide to corticosteroids is a valuable treatment option: A case report.

A 77-year-old woman was diagnosed as having advanced non-small cell lung cancer, and was started on treatment with gefitinib. Fifty days after the start of treatment, the patient was admitted to the hospital with complaints of dry cough, fever, and shortness of breath. A diagnosis of gefitinib-induced interstitial lung disease was made, and administration of high-dose prednisolone (1 g/day of intravenous methylprednisolone for three consecutive days, followed by oral prednisolone at 50 mg/day) was started. Although progression to respiratory failure could be stopped by the corticosteroid treatment, there was still no improvement in either the lung opacities seen on radiologic imaging, or in the symptoms; moreover, the patient developed corticosteroid-induced myopathy. Therefore, in order to allow reduction of the daily steroid dose, the patient was started on intravenous cyclophosphamide (500 mg/day). This additional treatment allowed the daily dose of oral prednisolone to be reduced to 15 mg/day. Thus, it is considered that intravenous cyclophosphamide may be a valid treatment option for gefitinib-induced lung injury.

Clinical and high resolution computed tomography characteristics of patients with rheumatoid arthritis lung disease.

INTRODUCTION: Rheumatoid arthritis (RA) is a systemic disease of unknown cause. A variety of pulmonary disorders have been described in association with RA. Among the most common are interstitial lung disease (ILD) and bronchiectasis. OBJECTIVES: This study aims to determine the characteristics of RA patients with lung disease in relation to clinical characteristics, pulmonary function test (PFT) and high resolution computed tomography (HRCT) thorax. METHOD: This is a 6-months cross-sectional study involving 63 consecutive RA patients in an outpatient rheumatology clinic. Patients had a mean disease duration of 5 years and above. Disease activity and severity was assessed by Disease Activity Score 28 (DAS28), Health Assessment Questionnaire (HAQ) and Rheumatoid Arthritis Articular Damage (RAAD) score. Full pulmonary function test (PFT) and HRCT of thorax were performed. CONCLUSIONS: The prevalence of RA-ILD is 44% and 67% of patients are asymptomatic. There was significant higher proportion (68%) in patients of Chinese ethnicity who have ILD. Diffusion capacity of carbon monoxide was abnormal in all patients and forced expiratory flow (FEF)(25-75%) was low in 16%. Restrictive pattern was 66.7% by PFT. The most common HRCT findings were reticulation (46%) followed by ground glass opacities (38.1%) and bronchiectasis (28.6%). There was no association between ILD and male gender, duration of the disease, smoking, rheumatoid factor, extra-articular manifestations, disease activity or severity.

Clinical characteristics of Japanese patients with anti-PL-7 (anti-threonyl-tRNA synthetase) autoantibodies.

OBJECTIVE: The clinical and laboratory features of seven Japanese patients with anti-aminoacyl-tRNA synthetase (ARS) autoantibodies against PL-7 (anti-threonyl-tRNA synthetase) were analyzed and compared with previously published findings. METHODS: Serum samples from 1,135 Japanese patients with various autoimmune diseases were screened for anti-PL-7 antibodies using RNA and protein immunoprecipitation assays. The patients whose sera contained anti-PL-7 antibodies were assessed regarding clinical symptoms and clinical course. RESULTS: Sera from seven patients were found to have anti-PL-7 antibodies. These autoantibodies were associated with polymyositis/dermatomyositis (PM/DM) and/or interstitial lung disease (ILD). The clinical diagnoses of these seven patients were PM - systemic sclerosis (SSc) overlap (5 patients), DM (1 patient) and idiopathic pulmonary fibrosis (IPF) (1 patient). All patients had ILD with a chronic course and six also had arthritis (85%) and five sclerodactyly (71%). CONCLUSIONS: These results indicate that anti-PL-7 autoantibodies are closely associated with PM-SSc overlap as well as ILD, arthritis and sclerodactyly in our series of Japanese patients.