Safety of immune checkpoint inhibitors in non-small-cell lung cancer patients with idiopathic interstitial pneumonia: a matched case-control study.

PURPOSE: The immune checkpoint inhibitor nivolumab is commonly used for non-small-cell lung cancer treatment. Immune checkpoint inhibitors cause immune-related adverse events, including interstitial pneumonia. However, there are no studies on the risk factors for interstitial pneumonia exacerbation after immune checkpoint inhibitor administration in patients with a history of different types of interstitial pneumonia. Therefore, we aimed to investigate the risk factors for interstitial pneumonia exacerbation in patients with non-small-cell lung cancer and a history of interstitial pneumonia. We also aimed to explore differences in the risk of interstitial pneumonia exacerbation due to various types of interstitial pneumonia-idiopathic interstitial pneumonia, immune-related pneumonitis, and radiation pneumonitis. METHODS: Eleven patients with a history of interstitial pneumonia exacerbation following the administration of immune checkpoint inhibitor were included in the study. We performed 1:2 matching based on age and sex. Twenty-two patients whose interstitial pneumonia did not worsen after immune checkpoint inhibitor administration belonged to the control group. We calculated odds ratios for each factor in the patients and control subjects. RESULTS: The odds ratio of idiopathic interstitial pneumonia in the case group was 0.15 (95% confidence interval: 0.03-0.89) (p = 0.03). There were no significant differences in other factors, such as smoking history, pulmonary emphysema, and chronic obstructive pulmonary disease. CONCLUSION: The administration of immune checkpoint inhibitors in non-small-cell lung cancer patients with a history of idiopathic interstitial pneumonia might be a viable treatment option and have clinical benefits.

Bimodal fibrosis in a novel mouse model of bleomycin-induced usual interstitial pneumonia.

Idiopathic pulmonary fibrosis is pathologically represented by usual interstitial pneumonia (UIP). Conventional bleomycin models used to study pathogenic mechanisms of pulmonary fibrosis display transient inflammation and fibrosis, so their relevance to UIP is limited. We developed a novel chronic induced-UIP (iUIP) model, inducing fibrosis in D1CC×D1BC transgenic mice by intra-tracheal instillation of bleomycin mixed with microbubbles followed by sonoporation (BMS). A bimodal fibrotic lung disease was observed over 14 wk, with an acute phase similar to nonspecific interstitial pneumonia (NSIP), followed by partial remission and a chronic fibrotic phase with honeycombing similar to UIP. In this secondary phase, we observed poor vascularization despite elevated PDGFRß expression. γ2PF- and MMP7-positive epithelial cells, consistent with an invasive phenotype, were predominantly adjacent to fibrotic areas. Most invasive cells were Scgb1a1 and/or Krt5 positive. This iUIP mouse model displays key features of idiopathic pulmonary fibrosis and has identified potential mechanisms contributing to the onset of NSIP and progression to UIP. The model will provide a useful tool for the assessment of therapeutic interventions to oppose acute and chronic fibrosis.

The pathogenesis and pathology of idiopathic pleuroparenchymal fibroelastosis.

Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare subtype of idiopathic interstitial pneumonias that consists of elastofibrosis involving the lung parenchyma and pleural collagenous fibrosis predominantly located in the upper lobes. IPPFE has various distinct clinical and physiological characteristics, including platythorax and a marked decrease of forced vital capacity with an increased residual volume on a respiratory function test. The concept of IPPFE is now widely recognized and some diagnostic criteria have been proposed. In addition, the accumulation of cases has revealed the pathological features of IPPFE. However, little is known about the pathogenesis or the process of disease formation in IPPFE. This review article will provide a summary of the pathological features and previously reported hypotheses on disease formation in IPPFE, to discuss the potential etiologies and pathogenesis of IPPFE.

Clinical significance of minor salivary gland biopsy in patients with idiopathic interstitial pneumonia.

BACKGROUND: Significant overlap may occur between idiopathic interstitial pneumonia (IIP) and connective tissue diseases (CTDs) that do not meet the established classification criteria for any known CTDs (i.e., occult CTD). Performing minor salivary gland biopsy (MSGB) to detect occult primary Sjogren's syndrome (pSS) in IIP patients is not well studied. METHODS: Consecutive IIP patients underwent MSGB to determine the prevalence of positive MSGB findings. Furthermore, we characterised the clinical, physiological and serological profiles of the MSGB-positive patients. Cox regression models were used to identify independent predictors of survival. RESULTS: The data of 155 patients with IIP were available for analysis. Sixty patients (38.7%) had positive MSGB findings. Of them, the mean age was 63.3 years, 51.6% were women, usual interstitial pneumonia (UIP) was the predominant pattern (63.3%), and seronegative antibodies (61.6%) were likely. Patients with positive MSGB findings had significantly greater survival than those with negative MSGB findings (p = 0.041). After stratifying the MSGB cohort based on the presence of a UIP pattern, no significant difference in survival was noted between those with positive MSGB-UIP pattern and those with a negative MSGB-UIP pattern (p = 0.231). Multivariate analysis on all UIP patients showed that higher forced vital capacity (p = 0.010) and smoking status (p = 0.035) were independently associated with survival. CONCLUSIONS: A substantial number of IIP patients had underlying occult CTD, highlighting the importance of performing MSGB to identify the salivary component of pSS when evaluating patients with interstitial lung disease of undetermined aetiology.

Desquamative interstitial pneumonia: a systematic review of its features and outcomes.

BACKGROUND: Desquamative Interstitial Pneumonia (DIP) is a rare form of idiopathic interstitial pneumonia (IIP). Data on clinical features, aetiology, prognosis and effect of treatment strategies are limited. We aimed to collect all published cases to better characterise DIP. METHODS: A systematic literature search was performed for all original cases of adult patients with histopathologically-confirmed DIP. Individual patient data were extracted and summarised. RESULTS: We included 68 individual cases and 13 case series reporting on 294 cases. Most common presenting symptoms were dyspnoea and cough. Pulmonary function showed a restrictive pattern (71%) with decreased diffusion capacity. We found a high incidence (81%) of ever smoking in patients with DIP and 22% of patients had other (occupational) exposures. Characteristic features on high-resolution computed tomography (HRCT) scan were bilateral ground-glass opacities with lower lobe predominance (92%). Treatment and duration of treatment widely varied. Initial response to treatment was generally good, but definitely not uniformly so. A significant proportion of patients died (25% of individual cases) or experienced a relapse (18% of individual cases). CONCLUSION: DIP remains an uncommon disease, frequently but not always related to smoking or other exposures. Furthermore, DIP behaves as a progressive disease more often than generally thought, possibly associated with different underlying aetiology.

Endothelial cell function and endothelial-related disorders following haematopoietic cell transplantation.

Use of haematopoietic cell transplantation (HCT) in the treatment of haematologic and neoplastic diseases may lead to life-threatening complications that cause substantial morbidity and mortality if untreated. In addition to patient- and disease-related factors, toxicity associated with HCT puts patients at risk for complications that share a similar pathophysiology involving endothelial cells (ECs). Normally, the endothelium plays a role in maintaining homeostasis, including regulation of coagulation, vascular tone, permeability and inflammatory processes. When activated, ECs acquire cellular features that may lead to phenotypic changes that induce procoagulant, pro-inflammatory and pro-apoptotic mediators leading to EC dysfunction and damage. Elevated levels of coagulation factors, cytokines and adhesion molecules are indicative of endothelial dysfunction, and endothelial damage may lead to clinical signs and symptoms of pathological post-HCT conditions, including veno-occlusive disease/sinusoidal obstruction syndrome, graft-versus-host disease, transplant-associated thrombotic microangiopathy and idiopathic pneumonia syndrome/diffuse alveolar haemorrhage. The endothelium represents a rational target for preventing and treating HCT complications arising from EC dysfunction and damage. Additionally, markers of endothelial damage may be useful in improving diagnosis of HCT-related complications and monitoring treatment effect. Continued research to effectively manage EC activation, injury and dysfunction may be important in improving patient outcomes after HCT.

Demographic and clinical predictors of progression and mortality in connective tissue disease-associated interstitial lung disease: a retrospective cohort study.

BACKGROUND: Connective tissue disease-associated interstitial lung disease (CTD-ILD) is associated with reduced quality of life and poor prognosis. Prior studies have not identified a consistent combination of variables that accurately predict prognosis in CTD-ILD. The objective of this study was to identify baseline demographic and clinical characteristics that are associated with progression and mortality in CTD-ILD. METHODS: Patients were retrospectively identified from an adult CTD-ILD clinic. The predictive significance of baseline variables on serial forced vital capacity (FVC), diffusion capacity (DLCO), and six-minute walk distance (6MWD) was assessed using linear mixed effects models, and Cox regression analysis was performed to assess impact on mortality. RESULTS: 359 patients were included in the study. Median follow-up time was 4.0 (IQR 1.5-7.6) years. On both unadjusted and multivariable analysis, male sex and South Asian ethnicity were associated with decline in FVC. Male sex, positive smoking history, and diagnosis of systemic sclerosis (SSc) vs. other CTD were associated with decline in DLCO. Male sex and usual interstitial pneumonia (UIP) pattern predicted decline in 6MWD. There were 85 (23.7%) deaths. Male sex, older age, First Nations ethnicity, and a diagnosis of systemic sclerosis vs. rheumatoid arthritis were predictors of mortality on unadjusted and multivariable analysis. CONCLUSION: Male sex, older age, smoking, South Asian or First Nations ethnicity, and UIP pattern predicted decline in lung function and/or mortality in CTD-ILD. Further longitudinal studies may add to current clinical prediction models for prognostication in CTD-ILD.

Family-based case-control study of exposure to household humidifier disinfectants and risk of idiopathic interstitial pneumonia.

BACKGROUND: In Korea, several household humidifier disinfectants (HDs) were clinically confirmed to cause HD-associated lung injury (HDLI). Polyhexamethylene guanidine (PHMG) phosphate is the main ingredient of the HDs found to be associated with lung disease. However, the association of HDs with other interstitial lung disease including idiopathic interstitial pneumonia (IIP) is not clear. We examined the relationship between HD exposure and IIP in a family-based study. METHODS: This case-control study included 244 IIP cases and 244 family controls who lived with the IIP patients. The IIP cases were divided into two groups, HDLI and other IIP, and were matched to family controls based on age and gender. Information on exposure to HDs was obtained from a structured questionnaire and field investigations. Conditional logistic regression was used to estimate odds ratio (ORs) and their corresponding 95% confidence interval (CI), investigating the association of HD-related exposure characteristics with IIP risk. RESULTS: The risks of IIP increased two-fold or more in the highest compared with the lowest quartile of several HD use characteristics, including average total use hours per day, cumulative sleep hours, use of HD during sleep, and cumulative exposure level. In analyses separated by HDLI and other IIP, the risks of HDLI were associated with airborne HD concentrations (adjusted OR = 3.01, 95% CI = 1.34-6.76; Q4 versus Q1) and cumulative exposure level (adjusted OR = 3.57, 95% CI = 1.59-8.01; Q4 versus Q1), but this relationship was not significant in the patients with other IIP. In comparison between HDLI and other IIP, the odds ratios of average total use hours, cumulative use hours, and cumulative sleeps hours was higher for other IIP. CONCLUSION: The use of household HDs is associated not only with HDLI but also with other IIP.

Idiopathic pulmonary fibrosis in small cell lung cancer as a predictive factor for poor clinical outcome and risk of its exacerbation.

OBJECTIVE: Lung cancer frequently co-exists with idiopathic interstitial pneumonia (IIP), which can be subdivided into idiopathic pulmonary fibrosis (IPF) and IIP other than IPF (other IIP). Although chemotherapy in small cell lung cancer (SCLC) patients with IIP may result in the exacerbation of IIP, these patients commonly receive chemotherapy. This study aimed to assess the risks and benefits of chemotherapy in SCLC patients with IIP. METHODS: We retrospectively analyzed the medical records of 122 patients with SCLC who received chemotherapy. Patients with secondary interstitial lung disease (ILD) of known etiology were excluded. Eligible patients were divided into two groups: SCLC with and without IIP. The former group was subdivided into those with IPF and other IIP. RESULTS: Of the 47 (39.2%) SCLC patients with IIP, 20 had IPF and 27 had other IIP. The frequency of chemotherapy-induced ILD development or IIP exacerbation was higher in patients with IPF (40.0%) than in those with other IIP (3.7%) and non-IIP (1.4%). Logistic regression analysis demonstrated that ILD development or IIP exacerbation was independently associated with IPF (P = 0.007). Time to treatment failure (P < 0.001) and overall survival (P = 0.001) were different among the groups., Cox proportional hazard model revealed that IPF was independently associated with time to treatment failure (P = 0,017) and overall survival (P = 0.006). Other IIP had no impact on time to treatment failure or overall survival. Development of ILD or exacerbation of IIP independently reduced time to treatment failure and overall survival. CONCLUSIONS: Comorbid IPF can be an independent, negative prognostic indicator and at high risk of ILD development or IIP exacerbation in SCLC patients. Early diagnosis and intervention for chemotherapy-induced IIP exacerbation will be beneficial for SCLC patients with IPF, who need close monitoring for its onset.

Weekly paclitaxel in combination with carboplatin for advanced non-small-cell lung cancer complicated by idiopathic interstitial pneumonias: a single-arm phase II study.

BACKGROUND: Idiopathic interstitial pneumonias (IIPs) are associated with increased risk of lung cancer. In Japan, acute exaberation of IIPs induced by anticancer treatment is a critical issue. For this reason, there is limited available evidence regarding the optimal treatment approach for lung cancer patients complicated with IIPs. Our previous prospective pilot study demonstrated the safety and efficacy of weekly paclitaxel in combination with carboplatin for advanced non-small-cell lung cancer (NSCLC) with IIPs. The current study was conducted to confirm the results of the same combination therapy used in a larger patient population. METHODS: Chemotherapy-naïve patients with advanced stage or post-operative recurrent NSCLC patients complicated by IIPs were enrolled. Patients received paclitaxel (100 mg/m2) on days 1, 8, and 15, and carboplatin (AUC 5.0) once every 4 weeks. RESULTS: Thirty-three of 35 enrolled patients were evaluable for analysis and received a median of four treatment cycles (range 1-6). Four patients (12.1%; 95% confidence interval 3.4-28.2%) had acute exacerbation (AEx)-related IIPs to the study treatment. However, no fatalities due to AEx were observed. The overall response was 69.7%. The median progression-free survival, median survival time, and 1-year survival were 6.3 months, 19.8 months, and 55.4%, respectively. CONCLUSIONS: The efficacy of carboplatin plus weekly paclitaxel treatment for advanced NSCLC patients with IIPs was comparable to that of conventional chemotherapy in advanced NSCLC patients without IIPs. Moreover, the primary endpoint was set to the frequency of treatment-related acute exacerbation, and the primary endpoint was met. These results suggest that patients with advanced NSCLC complicated by IIPs may benefit from this combination chemotherapy.

Utility of Anti-DSF70 Antibodies to Predict Connective Tissue Disease in Patients Originally Presenting with Idiopathic Interstitial Pneumonia.

BACKGROUND: Anti-DFS70 antibodies, corresponding to the dense fine speckled antinuclear antibody (ANA) pattern in HEp-2 substrates, have been observed in chronic inflammatory conditions, cancer and in healthy individuals but in only a small percentage of patients with connective tissue diseases (CTD). OBJECTIVES: The study was aimed to investigate the possible role of Anti-DFS70 antibodies to distinguish CTD associated interstitial lung disease (CTD-ILD) from idiopathic interstitial pneumonia (IIP) and to explore potential correlations between anti-DFS70 antibodies and clinical parameters. METHODS: Serum samples were collected from 49 healthy controls (HC), 35 scleroderma-ILD (SSc-ILD) patients as negative controls for anti-DFS70 antibody, and 260 patients with the initial diagnosis IIP including 100 nonspecific interstitial pneumonia (NSIP) and 160 idiopathic pulmonary fibrosis (IPF) patients. ANA pattern was identified by indirect immunofluorescence on HEp-2 cells and anti-DFS70 antibodies were measured in serum by ELISA. RESULTS: Serum anti-DFS70 antibodies were less frequently seen in ILD and SSc-ILD patients compared to HCs. Thirty-seven patients (34 initial idiopathic NSIP and 3 initial IPF patients) developed CTD during 24 months of follow-up, most of them combined with ANA positivity and anti-DFS70 antibody negativity. Anti-DFS70 antibody positivity was not significantly different between CTD-ILD and idiopathic ILD. CONCLUSIONS: The frequency of serum anti-DFS70 antibody is markedly decreased in patients with ILDs. Anti-DFS70 antibodies may be useful to predict CTD development in ILD patients.

Clinico-radiologic features of pleuroparenchymal fibroelastosis in children.

BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) may be underdiagnosed clinically and radiographically in children with a remote history of cancer, leading to a delay in care and unnecessary lung biopsies. OBJECTIVE: To describe the characteristic clinical and radiologic findings of PPFE in a cohort of children to facilitate recognition and noninvasive diagnosis. MATERIALS AND METHODS: Clinical presentation, history of chemotherapy or radiation therapy, lung or bone marrow transplantation, and lung function testing and outcome were retrospectively extracted from the electronic medical records of eight children treated at our institution's pulmonary medicine clinic with histopathology confirmation of PPFE from 2008 to 2018. Two pediatric radiologists evaluated the chest imaging studies for the presence or absence of published radiologic findings of PPFE in adults, including platythorax, pneumothorax, upper lobe predominant pleural and septal thickening, and bronchiectasis. Platythorax indices were calculated from the normal chest CT exams of eight age- and gender-matched individuals obtained via the radiology search engine. RESULTS: The mean presentation age was 12.9 years (range: 7-16 years). Seven of the eight had a history of chemotherapy and radiation therapy for cancer. Three of the eight had undergone bone marrow transplantation and none had undergone lung transplantation. The mean time between chemotherapy, radiation therapy, and/or bone marrow transplantation and the presentation of PPFE was 8.4 years (range: 5.6-12.1 years). Most of the patients presented with dyspnea (63%), cough (50%) and/or pneumothorax (38%). The mean percentage of predicted FEV1 (forced expiratory volume in one second) was 14.1 (range: 7.7-27.5). All eight patients demonstrated platythorax, bronchiectasis, pleural and septal thickening (upper lobes in four, upper and lower lobes in four) and six had pneumothorax. Five underwent lung biopsies, four of whom developed pneumothoraces. CONCLUSION: Clinical and radiologic findings of pediatric PPFE are similar to those in adults, although a majority of the former have a history of treated cancer. Clinical presentation of restrictive lung disease, dyspnea, cough or spontaneous pneumothorax years after treatment for childhood cancer combined with platythorax, upper lobe pleural and septal thickening and traction bronchiectasis on chest CT establishes a presumptive diagnosis of PPFE.

Rituximab in connective tissue disease-associated interstitial lung disease.

INTRODUCTION/OBJECTIVES: To evaluate rituximab (RTX) effectiveness and safety in patients with interstitial lung disease (ILD) related to connective tissue diseases (CTD). METHODS: Retrospective multicenter cohort study, including patients with CTD-ILD, followed in six Portuguese rheumatology departments until November 2018. ILD diagnosis was based on high-resolution CT (HRCT) and/or lung biopsy. Results of HRCT, pulmonary function tests, and 6-min walking test before and after RTX were compared using the Wilcoxon matched pair test. Safety, including adverse events during treatment and reasons for RTX discontinuation, was also analyzed. RESULTS: A total of 49 patients were included, with rheumatoid arthritis being the commonest CTD (61.2%). The median interval between CTD onset and ILD diagnosis was 4 years (IQR 1-9.5) and median ILD duration at first RTX administration was 1 year (IQR 0-4). The median RTX treatment duration until the last follow-up was 3 years (IQR 1-6). Usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP) were the commonest patterns, occurring in 20 and 18 patients, respectively. One year after RTX first administration, there was a stabilization in carbon monoxide diffusing capacity (DLCO; mean + 5.4%, p = 0.12) and improvement in forced vital capacity (FVC; mean + 4.3%, p = 0.03), particularly in patients with NSIP. Patients with UIP had less promising results, but at 1 year, pulmonary function tests remained stable (DLCO + 2.5%, p = 0.77; FVC + 4.2%, p = 0.16). Infection was the main reason for RTX discontinuation and led to two deaths. CONCLUSIONS: RTX seems to be a promising treatment for CTD-ILD patients, particularly when NSIP pattern is present. Key points • The use of rituximab in patients with interstitial lung disease related to connective tissue disease is associated with long-standing disease stability in a wide range of systemic rheumatic diseases. • Efficacy results were particularly impressive in patients with non-specific interstitial pneumonia pattern, although in a subgroup of patients with usual interstitial pneumonia pattern, disease progression was also hold with this treatment. • In a large number of patients, rituximab was used in monotherapy and as first-line treatment.

The surgical outcomes of lung cancer combined with interstitial pneumonia: a single-institution report.

PURPOSE: Several studies have reported that an acute exacerbation (AE) of idiopathic interstitial pneumonia (IIP) can occur after lung resection in patients with non-small cell lung cancer (NSCLC); however, the perioperative management strategy is controversial. METHODS: The data of lung cancer patients at Nagasaki University Hospital from June 1994 to October 2013 were retrospectively reviewed. RESULTS: Among all 1701 NSCLC patients who underwent lung resection, 59 (3.5%) had IIP. Five patients (8.5%) had an AE of IIP following lung resection, three (60%) of whom died in hospital. Univariate and multivariate analyses were performed to identify possible risk factors for AE. The univariate analyses identified LDH and the volume of blood loss as risk factors. The multivariate analysis identified no factors. The treatment for an AE included steroid pulse therapy and neutrophil elastase inhibitor therapy. Direct hemoperfusion with polymyxin B immobilized the fiber column and immunosuppressant therapy was attempted in some of the patients who did not respond to these treatments. CONCLUSION: Patients with lung cancer and IIP have a higher risk of chest surgery and a poor prognosis. Very careful surgery and perioperative management are needed, because AEs are often difficult to AE predict.

Nonspecific interstitial pneumonia: time to be more specific?

PURPOSE OF REVIEW: There is growing speculation that idiopathic nonspecific interstitial pneumonia (NSIP) is, in reality, a grouping of separate disorders with a common histologic pattern. In this review, distinct clinical, imaging, and serologic features providing support for this premise are detailed and discussed. RECENT FINDINGS: The diagnosis of idiopathic NSIP is often uncertain because of its clinical and imaging diversity. In a landmark study of inter-multidisciplinary group diagnostic variation, there were striking discrepancies between seven expert groups (κ = 0.24) in diagnoses of idiopathic NSIP. Recent histologic observations provide support for the concept of an NSIP/organizing pneumonia overlap, distinct from isolated NSIP. An important group of NSIP patients with features of 'undifferentiated connective disease', historically classified as an idiopathic NSIP subgroup, have been shown to have a lower mortality than idiopathic NSIP patients without features of autoimmune disease. The recently proposed entity of 'interstitial pneumonia with autoimmune features' includes many patients with a histologic or imaging pattern of NSIP, shown by Oldham and colleagues to have a similar survival to patients with connective tissue disease-related NSIP. SUMMARY: The concept of idiopathic NSIP as a grouping of separate disorders with a common histologic pattern provides a template for potentially important pathogenetic insights.

Postoperative pyothorax a risk factor for acute exacerbation of idiopathic interstitial pneumonia following lung cancer resection.

OBJECTIVE: Acute exacerbation (AE) of idiopathic interstitial pneumonia (IP) is a potentially fatal postoperative complication following lung cancer resection. Postoperative pyothorax (PP) following development of a bronchopleural fistula (BPF) after lung surgery induces continuous inflammation and may affect the occurrence of AE. We investigated the relationship between AE and PP in patients who underwent pulmonary resection for lung cancer. METHODS: A total of 941 patients who underwent lung resection due to primary lung cancer from 2006 to 2015 at our hospital were investigated. RESULTS: Of the 941 enrolled patients, 137 (14.6 %) had idiopathic IP and were predominantly male (p < 0.01). Pathological stage Ia and adenocarcinoma were observed at significantly high rates in the non-IP group (p < 0.01). Patients with IP showed a tendency for a higher percentage of PP (p = 0.054). Of the 137 patients with IP, 17 (12.4 %) showed postoperative AE. Furthermore, PP was observed in three cases in the AE(+) group and two in the AE(-) group. PP had a correlation with a significantly higher incidence of AE (p = 0.007). CONCLUSION: PP was found to be a significant risk factor for postoperative AE in lung cancer patients undergoing a pulmonary resection. Since IP itself is likely a risk factor for PP, prevention of BPF is important for patients with IP, as it can lead to PP.

A Multidisciplinary Evaluation Helps Identify the Antisynthetase Syndrome in Patients Presenting as Idiopathic Interstitial Pneumonia.

INTRODUCTION: Interstitial lung disease (ILD) is 1 possible manifestation of the idiopathic inflammatory myopathies (IIM). Occasionally, patients presenting with ILD are mistakenly diagnosed with idiopathic interstitial pneumonia (IIP), but after multidisciplinary evaluation, their ILD is determined to be because of antisynthetase syndrome (SynS) or myositis spectrum of disease. METHODS: We used retrospective analytic methods to identify patients with ILD evaluated at the National Jewish Health between February 2008 and August 2014 and believed initially to have IIP but ultimately diagnosed with SynS or myositis spectrum of disease. RESULTS: The cohort included 33 patients; most were white women with a mean age at presentation of 55 years. Their pulmonary physiologic impairment was moderate. In 31 cases, the ILD pattern by thoracic high-resolution computed tomography scan was nonspecific interstitial pneumonia (NSIP), organizing pneumonia (OP), or a combination of the 2. Surgical lung biopsy was performed in 21 patients; NSIP was the most common pattern. Less than one-third of the cohort had positive antinuclear antibodies. Two-thirds had positive SSA. All patients had either myositis-specific or myositis-associated autoantibody. Most had subtle extrathoracic symptoms or signs of SynS; 12 had an elevated serum creatine phosphokinase, but none had clinical evidence of myositis. None met the Peter and Bohan classification criteria for polymyositis/dermatomyositis. CONCLUSION: Among patients who present with presumed IIP, a multidisciplinary evaluation that includes the integration of clinical evaluations by rheumatologists and pulmonologists, morphologic (both histopathologic and radiographic) data, and serologic features is helpful in the detection of occult SynS or the myositis spectrum of disease.

Coexistence of Autoantibodies against the Golgi Complex and Ro52 Antigen in a Patient with Nonspecific Interstitial Pneumonia.

Nonspecific interstitial pneumonia (NSIP) is often associated with connective tissue diseases (CTD). The diagnosis of NSIP was confirmed in a 63-year-old man by high-resolution computed tomography and an open lung biopsy. Anti-Golgi complex autoantibodies (AGA) and anti-Ro52 antibodies were simultaneously detected at high concentrations. Autoantibodies to aminoacyl-tRNA synthetases (ARS) were negative. The patient was treated with corticosteroids for six months. During the seven-year follow-up, NSIP had a slow progression and patient had not developed the clinical features of CTD. The present study potentially demonstrates that the autoimmune process elicited by AGA and/or Ro/SSA may play a role in promoting idiopathic NSIP independently of the typical ARS routes, which has not been reported thus far.