Interstitial Pneumonia With Autoimmune Features Criteria Research Articles

Radiological and histopathological features and treatment response by subtypes of interstitial pneumonia with autoimmune features: A prospective, multicentre cohort study

BackgroundPatients with idiopathic interstitial pneumonia (IIP) have a favourable prognosis when they have interstitial pneumonia with autoimmune features (IPAF). However, precise IPAF-related findings from high-resolution computed tomography (HRCT) and lung histopathological specimens and the treatment response have not been fully determined. Therefore, this study was conducted to evaluate the relationship between findings on HRCT or lung histopathological specimens and the progression of interstitial pneumonia in patients with IPAF. MethodsThis multicentre cohort study prospectively enrolled consecutive patients with IIP. At the diagnosis of IIP, we systematically evaluated 74 features suggestive of connective tissue diseases and followed them up. HRCT, lung specimens, serum antibodies, and the clinical course were also evaluated. ResultsAmong 222 patients with IIP, 26 (11.7%) fulfilled the IPAF criteria. During a median observation period of 36 months, patients with IPAF showed better survival than those without IPAF (p = 0.034). While histopathological findings were not related to IPAF, nonspecific interstitial pneumonia (NSIP) with organizing pneumonia (OP) overlap was the most prevalent HRCT pattern (p < 0.001) and the consolidation opacity was the most common radiological finding in IPAF (p = 0.017). Furthermore, in patients with IPAF, the diagnosis of COP or NSIP with OP overlap was associated with a higher increase in %FVC in 1 year than in those with idiopathic pulmonary fibrosis, NSIP, or unclassifiable IIP (p = 0.002). ConclusionsThis study shows the presence of consolidation opacity on HRCT and the diagnosis of COP or NSIP with OP overlap are associated with IPAF and its favourable treatment response in patients with IPAF.

Unclassifiable interstitial lung disease and autoimmunity: Towards IPAF in children?

Interstitial pneumonia with autoimmune features (IPAF) has been defined for adults with interstitial lung disease (ILD) and autoimmunity who do not meet the criteria for a specific connective tissue disease (CTD). We aimed to determine whether IPAF criteria could apply to children. We retrospectively studied patients with ILD and autoimmunity followed at Necker Hospital between 2008 and 2019. Children were classified according to specific CTD and IPAF criteria. The epidemiology and course of the disease were studied according to the final diagnosis. Among 27 patients, 6 fulfilled the criteria for IPAF and represented 4.5% of all patients with ILD during the study period. Other diagnoses included juvenile dermatomyositis (30%), overlap syndromes (19%), systemic lupus erythematosus (15%), systemic sclerosis (7%), mixed CTD (4%), and rheumatoid arthritis (4%). IPAF patients were more frequently boys versus CTD-ILD patients (67% vs. 14%, p = .02). Two patients had severe respiratory distress that led to death for one of them. The course was favorable for the others, with a good response to steroids. The course tended to be more favorable for IPAF patients than for those with CTD-ILD (0% lung fibrosis in the IPAF group vs. 43% in the CTD-ILD group, p = .07). We confirmed the existence of IPAF in children. Its prevalence was lower than in adults but comparable to that found for other pediatric series. Boys were more highly represented than in CTD-ILD. The course was favorable for most cases. Larger and more prospective studies are needed to confirm these results.

Performance of GAP and ILD-GAP models in predicting lung transplant or death in interstitial pneumonia with autoimmune features.

To assess the ability of two risk prediction models in interstitial lung disease (ILD) to predict death or lung transplantation in a cohort of patients with interstitial pneumonia with autoimmune features (IPAF). We performed a retrospective cohort study of adults with IPAF at an academic medical centre. The primary outcome was a composite of lung transplantation or death. We applied the patient data to the previously described Gender-Age-Physiology (GAP) and ILD-GAP models to determine the ability of these models to predict the composite outcome. Model discrimination was assessed using the c-index, and model calibration was determined by comparing the incidence ratios of observed vs expected deaths. Ninety-four patients with IPAF were included. Mean (s.d.) age was 58 (13.5) years and the majority were female (62%). The majority met serologic and morphologic criteria for IPAF (94% and 91%, respectively). The GAP model had a c-index of 0.664 (95% CI 0.547-0.781), while the ILD-GAP model had a c-index of 0.569 (95% CI 0.440-0.697). In those with GAP stage 1 or GAP stage 2 disease, calibration of the GAP model was satisfactory at 2 and 3 years for the cumulative end point of lung transplantation or death. In patients with IPAF, the GAP model performed well as a predictor of lung transplantation or death at 2 years and 3 years from ILD diagnosis in patients with GAP stage 1 and GAP stage 2 disease.

Clinical and Serological Characteristics of a Monocentric Cohort of Patients Affected by Interstitial Pneumonia with Autoimmune Features (IPAF).

Interstitial lung diseases (ILDs) are diseases characterised by excessive deposition of collagen matrices in the pulmonary interstitium. Some of them are considered idiopathic (idiopathic pulmonary fibrosis - IPF), others are related to known pathologies such as connective tissue diseases (CTDs-ILD). Patient affected by ILD and features referable to CTD, not satisfying CTD criteria, are called Interstitial pneumonia with autoimmune features (IPAF) patients. The aim of this report was to investigate clinical and serologic features of a monocentric cohort of patients with IPAF. Another objective was to describe the autoantibody profile, clinical features, High Resolution Computerised Tomography (HRCT) and Nailfold Video Capillaroscopy (NVC) patterns. 36 IPAF patients were consecutively enrolled. Clinical, serological, and morphological features were collected. 36 consecutive IPAF patients were enrolled from January 2021 to January 2022. Raynaud's phenomenon was the most frequent symptom identified. We also described other signs and symptoms not included in IPAF criteria. 36,1% of patients demonstrated a Usual Interstitial Pneumonia (UIP) pattern by HRCT. Pulmonary arterial pressure estimation (PAPs) resulted elevated (≥ 25 mmHg) in 6 patients. Antinuclear antibodies (ANA) ≥ 1/80 was the most frequent autoantibody, followed by anti-Ro, in patients with UIP pattern and Non-Specific Interstitial Pneumonia (NSIP) pattern at HRCT. NVC highlighted non-specific microangiopathy as the most common pattern especially in UIP patients. This paper may contribute to stimulate the interest in better characterisation of clinical, serologic, and instrumental features for IPAF patients by redefining IPAF classification criteria in order to treat them as best as possible.

Fine-tuning characterization of patients with interstitial pneumonia and an underlying autoimmune disease in real-world practice: We get closer with Nailfold videocapillaroscopy.

To assess performance of interstitial pneumonia (IP) with autoimmune features (IPAF) criteria in clinical practice and describe the utility of additional workup in identifying patients with underlying connective tissue diseases (CTD). We set a retrospective study of our patients with autoimmune IP, who were allocated to CTD-IP, IPAF or undifferentiated autoimmune IP (uAIP) subgroups according to the updated classification criteria. Presence of the process-related variables comprising IPAF defining domains was scrutinized in all patients, and, when available, the results of nailfold videocapillaroscopy (NVC) were recorded. Thirty nine out of 118 patients, accounting for 71% of former undifferentiated cases, fulfilled IPAF criteria. Arthritis and Raynaud's phenomenon were prevalent in this subgroup. While systemic sclerosis-specific autoantibodies were restricted to CTD-IP patients, anti-tRNA synthetase antibodies were also present in IPAF. In contrast, rheumatoid factor, anti-Ro antibodies and ANA nucleolar patterns could be found in all subgroups. Usual interstitial pneumonia (UIP) / possible UIP were the most frequently observed radiographic patterns Therefore, the presence of thoracic multicompartimental findings as also performance of open lung biopsies were useful in characterizing as IPAF those UIP cases lacking a clinical domain. Interestingly, we could observe NVC abnormalities in 54% of IPAF and 36% of uAIP tested patients, even though many of them did not report Raynaud's phenomenon. Besides application of IPAF criteria, distribution of IPAF defining variables along with NVC exams help identify more homogeneous phenotypic subgroups of autoimmune IP of potential relevance beyond clinical diagnosis.

Interstitial Pneumonia with Autoimmune Features: What the Rheumatologist Needs to Know.

Purpose of ReviewThis narrative review will focus on the role of the rheumatologist in evaluating patients with interstitial lung disease (ILD) without a defined rheumatic disease and will outline the current classification criteria for interstitial pneumonia with autoimmune features (IPAF) and describe what is known regarding IPAF pathobiology, natural history, prognosis, and treatment. Lastly, knowledge gaps and opportunities for future research will be discussed.Recent FindingsIPAF is a recently defined classification of ILD patients who have features suggesting an autoimmune-mediated process, but do not fulfill current rheumatic disease criteria. The goal of the IPAF criteria is to provide a uniform case definition for the study of autoimmune ILD patients who do not currently fit within standard ILD diagnostic categories, ultimately improving diagnosis and therapy. Many of these patients are referred for rheumatologic evaluation to aid the diagnostic process.SummaryThe care of the IPAF patient is complex and is multidisciplinary with pulmonology, rheumatology, pathology, radiology, physical therapy, primary care, pulmonary transplant providers all serving vital roles. The rheumatologist has several roles which include classification, disease monitoring, and management.

The role of pirfenidone in the treatment of interstitial pneumonia with autoimmune features.

No approved pharmacotherapies are available for patients with interstitial pneumonia with autoimmune features (IPAF). In the present work, we aimed to evaluate the efficacy and safety of pirfenidone for the treatment of IPAF. A retrospective cohort study consisting of patients who met diagnostic criteria for IPAF was performed after a multidisciplinary review, and the patients receiving pirfenidone were compared with those in the non-pirfenidone group. The baseline data and diagnostic characteristics of patients were assessed. Pulmonary function and prednisone dose were analysed by a mix-effects model. A total of 184 patients, who met the diagnostic criteria of IPAF, were divided into two groups: pirfenidone group (n=81) and non-pirfenidone group (n=103). Patients in the pirfenidone group had a lower forced vital capacity (FVC%, p<0.001) and a lower diffusion capacity for carbon monoxide (DLCO%, p=0.003). The pirfenidone group exhibited a greater increase of FVC% at 6 (p=0.003), 12 (p=0.013), and 24 (p=0.003) months. After adjustment for sex, age, UIP pattern, baseline FVC% and DLCO%, patients in the pirfenidone group continued to show a greater improvement in FVC% (χ2(1)=4.59, p=0.032). Subgroup analysis identified superior therapeutic effects of pirfenidone in patients with dosage >600 mg/day (p=0.010) and medication course >12 months (p=0.007). Besides, the pirfenidone group had a lower prednisone dose than the non-pirfenidone group after 12 months of treatment (p=0.002). Moreover, 17 patients (19.32%) experienced side effects after taking pirfenidone, including one case of anaphylactic shock. Pirfenidone (600-1,800 mg/day) might help improve FVC, with an acceptable safety and tolerability profile in IPAF patients.

Interstitial pneumonia with autoimmune features: challenges and controversies.

The presence of clinical, serological and/or radiological features suggestive, but not confirmatory, of a defined connective tissue disease in patients with interstitial lung disease is a relatively frequent occurrence. In 2015, the European Respiratory Society and the American Thoracic Society proposed classification criteria for the interstitial pneumonia with autoimmune features (IPAF) research entity to capture such patients in a standardised manner, with the intention of nurturing clinical research. This initiative resulted in the publication of several series of IPAF patients, with significant variation between cohorts in clinical characteristics, outcome and the application of IPAF criteria in patient selection. From this increasing body of published work, it has become apparent that revision of IPAF criteria is now required in order to justify the eventual designation of IPAF as a standalone diagnostic term, as opposed to a provisional entity put forward as a basis for clinical research. This review covers the current state of IPAF, conclusions that can and cannot be drawn from the IPAF evidence base, and ongoing uncertainties that require further expert group consideration.

Long-term evaluation of pulmonary function and survival of patients with interstitial pneumonia with autoimmunefeatures.

Interstitial pneumonia with autoimmune features (IPAF) includes patients with interstitial lung disease with autoimmune features who do not meet criteria for a connective tissue disease (CTD). Previous studies showed a wide variation in the radiologic pattern, pulmonary function and prognosis but there is still limited data on longitudinal outcomes. We aim to describe the long-term pulmonary function, radiological patterns, and survival of IPAF patients and explore a classification based on CTD-like subgroups by using clinical/serologic data. Retrospective analysis of IPAF patients who were sub-classified into six CTD-(like) subgroups: systemic lupus erythematosus-like, rheumatoid arthritis-like, Sjögren's syndrome-like, scleroderma, myositis-like, and unclassifiable. Linear mixed-effect models were used to compare the change in percent-predicted forced vital capacity (FVC%), percent-predicted diffusion capacity (DLCO%), and six-minute walk distance (SMWD) over time; and survival in the entire cohort and according to CTD-like subgroups and radiological patterns. Fifty-nine patients fulfilled IPAF criteria. FVC%, DLCO%, and SMWD remained stable over time. There was no difference between usual interstitial pneumonia (UIP) versus non-UIP radiologic patterns. Thirty-five patients were sub-classified into CTD-like subgroups. Survival decreased from 79% at 60 months to 53% at 120 months in the entire cohort but was similar among CTD-like subgroups and radiological patterns. Long-term pulmonary function and six-minute walk test remained stable over 36 months in our IPAF cohort. Prognosis and pulmonary function in UIP had similar outcomes compared to non-UIP. Although 40% of IPAF patients could not be sub-classified, our exploratory subclassification stratified 60% of patients into a CTD-like subgroup.

Variables Associated With Response to Therapy in Patients With Interstitial Pneumonia With Autoimmune Features.

Background/ObjectiveWe have limited knowledge regarding characteristics of patients with interstitial pneumonia with autoimmune features (IPAF) that are associated with response to immunosuppression. In this study, we used published IPAF criteria to characterize features associated with response to treatment.MethodsWe conducted a single-center medical records review study of 63 IPAF patients to evaluate for serological, clinical, and morphological characteristics that are associated with response to immunosuppression. Response was defined as % relative functional vital capacity decline of less than 10% and absence of death or lung transplant within the first year of continuous immunosuppressive therapy. Nonparametric measures of association and multivariate logistic regression were used to evaluate the relationship between baseline characteristics and immunosuppressive response.ResultsThere was a trend of greater progression among men, ever smokers, those negative for antisynthetase antibodies, and those with usual interstitial pneumonia radiographic pattern, but no statistically significant relationship was found between baseline serological, clinical, or morphological features and response to immunosuppression. Patients on combination therapy with mycophenolate mofetil and prednisone had less disease progression (p = 0.018) than those on regimens that did not include both of these medications.ConclusionsIn our cohort, baseline clinical assessment did not identify which patients with IPAF will respond to immunosuppressive therapy. Combination therapy with mycophenolate mofetil and prednisone was associated with lack of disease progression in our IPAF patients, including in IPAF–usual interstitial pneumonia. Further studies are needed to evaluate which IPAF patients would benefit from immunosuppressive therapy, antifibrotic therapy, or a combination of both.

Rituximab for interstitial pneumonia with autoimmune features at two medical centres.

ObjectivesMany patients with interstitial lung disease (ILD) have autoimmune manifestations but do not meet criteria for a systemic rheumatic disease. A subset meets criteria for interstitial pneumonia with autoimmune features (IPAF) and have ILD requiring therapy. We conducted a multicentre observational study to examine the use of rituximab (RTX) in IPAF.MethodsPatients from Mass General Brigham (MGB) and University of Chicago Medicine (UCM) were included if they were ≥18 years old, met the 2015 classification criteria for IPAF and were treated with RTX. Clinical improvement was defined as improvement in four out of four domains at 1 year after RTX initiation: documented clinician global assessment; oxygen requirement; need for respiratory-related hospitalization; and survival.ResultsAt MGB, 36 IPAF patients (mean age 61 years, 44% female) were treated with RTX. At 1 year, 18 (50%) were clinically improved, 12 (33%) were stable, and 6 (17%) died from progressive respiratory failure. At UCM, 14 IPAF patients (mean age 53 years, 71% female) were treated with RTX. At 1 year, eight (57%) were improved, two (14%) were stable, three (21%) died from progressive respiratory failure, and one (7%) was lost to follow-up. Two patients experienced minor infusion reactions, and two patients discontinued therapy owing to adverse events (infections).ConclusionIn patients with IPAF treated with RTX at two medical centres, the majority (40 [80%]) demonstrated improvement/stability at 1 year. These findings call for prospective studies, including randomized clinical trials, to determine the risks, benefits and cost effectiveness of RTX in IPAF.

The Risk Factors of Exacerbation in Interstitial Pneumonia With Autoimmune Features: A Single-Center Observational Cohort Study.

ObjectivesTo investigate the long-term outcomes, including risk factors, for exacerbation between monotherapy and combination therapy in patients with interstitial pneumonia with autoimmune features (IPAF).MethodsWe assessed 672 patients between April 2009 and March 2019 who were evaluated using high-resolution computed tomography (HRCT) of the chest. We applied the IPAF criteria. Fifty-two patients who visited our department for at least 6 months were diagnosed with IPAF. Clinical, laboratory, and imaging data were collected from medical records and statistically analyzed.ResultsAmong the 52 cases of IPAF, we compared the characteristics at diagnosis between treated (n = 28) and untreated patients (n = 24). The exacerbation rates were 42.9% (n = 12) and 8.3% (n = 2) (P = 0.0051), respectively. Among the treated patients, smoking history, high titer of KL-6, and the duration from diagnosis to the start of treatment were significant risk factors for exacerbation (P = 0.0062, 0.011, and 0.019, respectively). The number of risk factors was significantly and positively associated with exacerbation rate (P = 0.0053). Among the treated patients, glucocorticoid (GC) monotherapy was used in 13 cases, and GC and immunosuppressant (IS) combination therapy was used in 14 patients. There was no significant difference in the treatment methods between patients with and without risk factors (P = 0.47). When comparing the long-term outcomes between the monotherapy and combination therapy groups, the 3-year non-exacerbation rates were 72.9 and 45.9% (P = 0.020), respectively.ConclusionsIPAF patients with risk factors had a high exacerbation rate, regardless of the type of treatment. New interventions aimed at preventing exacerbations in these patients are required.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00371-3.

Prospective nationwide multicentre cohort study of the clinical significance of autoimmune features in idiopathic interstitial pneumonias

BackgroundSome patients with idiopathic interstitial pneumonia (IIP) show autoimmune features. Interstitial pneumonia with autoimmune features (IPAF) was recently proposed as a research concept in these patients. However, retrospective studies reported...

Interstitial pneumonia with autoimmune features: from research classification to diagnosis

The term interstitial pneumonia with autoimmune features (IPAF) was first proposed by an international task force in 2015 as a research classification to standardise nomenclature regarding patients with idiopathic interstitial pneumonia and features of connective tissue disease. However, how the use of this term and its proposed definition translates to clinical practice remains uncertain. This review will provide a comprehensive overview of studies of IPAF cohorts to date, discuss the consideration of IPAF as a distinct diagnostic entity and outline a suggested approach to patient management. Considerable heterogeneity exists between published IPAF cohorts, with some cohorts exhibiting similarities to those with connective tissue disease-associated interstitial lung disease (CTD-ILD), and others more similar to idiopathic interstitial pneumonias including idiopathic pulmonary fibrosis (IPF). Little data exist to inform the management of patients who fulfil the IPAF criteria. Preliminary data supports pragmatic management of these patients as having a working clinical diagnosis of either idiopathic interstitial pneumonia or CTD-ILD. Future research studies into this approach are required. The term IPAF, and its definition, have been of fundamental benefit to facilitating research in this diverse patient group. However, to date, there remain many unanswered questions regarding their natural histories and response to treatment.

Clinical, radiologic and serologic profile of patients with interstitial pneumonia with autoimmune features: a cross-sectional study.

The current study aimed to characterize patients from a rheumatology referral center in north India, who satisfied the definition of interstitial pneumonia with autoimmune features (IPAF) as given by the American Thoracic Society and European Respiratory Society (ATS/ERS) consensus committee in 2015. Thirty-five adult patients aged 18 years and above, fulfilling the 2015 ATS/ERS criteria for IPAF were included in the study. The clinical and immunological profile, and radiologic findings on high-resolution computerized tomography thorax were noted. Antinuclear antibody (ANA) by indirect immunofluorescence at 1:320 titer and myositis-specific antibody (MSA) assays were performed. Non-parametric tests were used to compare variables between groups. The study cohort included predominantly female patients with a mean age of 50.6 ± 13 years and mean duration of disease of 38.8 ± 28.4 months. Majority of patients (49%) fulfilled the morphologic and serologic domains as per the IPAF consensus criteria and 31% patients had features in all three domains. Non-specific interstitial pneumonia was the most common pattern observed in 77% patients. Raynaud’s phenomenon and inflammatory arthritis were the predominant autoimmune features. Pulmonary arterial hypertension was documented in 60% of patients on echocardiography. Positive ANA at 1:320 dilution was present in all 26 patients tested, whereas extractable nuclear antigen and MSA assays detected autoantibodies in 49% and 51% of patients respectively. IPAF predominantly affected females in the age group of 50 years and above, with varied autoimmune manifestations and autoantibody profile.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00296-021-04883-7.

"Usual" interstitial pneumonia with autoimmune features: a prospective study on a cohort of idiopathic pulmonary fibrosis patients.

The classification interstitial pneumonia with autoimmune features (IPAF) includes patients with interstitial lung disease (ILD) associated with autoimmune characteristics insufficient to reach classification criteria for a specific autoimmune disease (SAD). These criteria are divided into three domains: clinical, serological and morphological. The latter domain does not include the usual interstitial pneumonia (UIP) pattern, which is deemed not to be significantly associated with SAD. Therefore, the enrolment of these patients is more difficult, requiring at least one item from both of the other domains. The objective of this study is to evaluate the rate of progression towards SAD of a cohort of UIP patients satisfying only one IPAF domain (we called this group "UIPAF") compared with classic idiopathic pulmonary fibrosis (IPF). We prospectively enrolled IPF patients with radiologic and/or histologic UIP pattern, followed jointly by rheumatologists and pulmonologists from January 2017 to January 2021, with a minimum follow-up of 12 months. We enrolled 190 IPF patients, 38 (20%) of whom were classified as UIPAF. IPF and UIPAF patients were similar for general characteristics, severity and prognosis, at presentation and at annual check-up. However, 28.9% of UIPAF patients progressed towards SAD, compared with 2% of IPF patients (χ2=30.4, p≤0.0001). The association between a single clinical or serological domain of IPAF and UIP pattern is predictive for the development of a SAD if compared with isolated UIP. ILD can be the first manifestation of SAD, even with a UIP pattern, therefore, the morphological domain of IPAF criteria could be removed.

Occult primary Sjögren Syndrome in patients with interstitial pneumonia with autoimmune features

Introduction/ObjectivesTo define the performance of Minor Salivary Gland Biopsy (MSGB) and Dry Eye Tests (DET) to detect occult Sjögren Syndrome (SS) among Interstitial Pneumonia with Autoimmune Features (IPAF) patients. MethodsProspective study. Interstitial Lung Disease (ILD) patients without defined Connective Tissue Disease and one or more IPAF classification domains or xerophthalmia were included. MSGB, Schirmer's test (ST) and Ocular Staining Score (OSS) were performed in a blinded manner by experienced specialists. MSGB with ≥1 focus of lymphocytes and Dry Eye Test (DET) with OSS ≥ 5 and/or ST < 5 s were considered positive. SS was diagnosed according to the ACR 2016 criteria. Results534 patients on the first consult were screened. 67 patients had at least one IPAF criteria, 53 (79.1%) female, mean age (SD) 64.2 years old (10.8). Positive ST in 36 (53.7%), positive OSS in 29 (43.3%) and positive MSGB in 36 (53.7%) were found. Finally, 27 (40.3%) met SS diagnostic criteria. 25 (37.3%) and 18 (26.8%) of them did not report dry eyes or dry mouth, respectively. 53 (79.1%) had negative anti SSA/Ro, 57 (85.1%) had negative anti LA/SSB, 30 (44.7%) had negative ANA, and 52 (77.6%) had negative RF, respectively. A significantly higher proportion of ANA (+), anti-SSA/Ro (+), anti-SSB/La (+), positive DET and positive MSGB were found in the SS population. ConclusionsA significant proportion of patients with occult SS were found in our study. MSGB and DET may be considered in the evaluation of IPAF patients.

Recent advances in the diagnosis and management of interstitial pneumonia with autoimmune features: the perspective of rheumatologists.

Interstitial pneumonia with autoimmune feature (IPAF) is a recently established disease entity that is comprised of interstitial lung diseases with evidence of autoimmune features but that does not fulfill the criteria for definite autoimmune rheumatic diseases. The classification criteria for IPAF were defined by the European Respiratory Society and American Thoracic Society in 2015. However, further studies to establish IPAF subgroups and treatment modalities for each subgroup are still needed. In this review, we discuss recent advances regarding IPAF and raise critical points for the diagnosis and management of patients with IPAF from the perspective of rheumatologists.

Clinical, radiological, and pathological evaluation of “NSIP with OP overlap” pattern compared with NSIP in patients with idiopathic interstitial pneumonias

BackgroundNonspecific interstitial pneumonia (NSIP) and organizing pneumonia (OP) are major subtypes of idiopathic interstitial pneumonias (IIPs) and closely related to connective tissue diseases (CTDs). “NSIP with OP overlap” is a controversial finding that has recently appeared in the criteria of interstitial pneumonia with autoimmune features (IPAF). However, details of this controversial entity are not well known. ObjectiveTo determine the frequency of “NSIP with OP overlap” pattern in IIPs and to identify differences from idiopathic NSIP (iNSIP). MethodsIn 524 patients with interstitial pneumonia from 39 institutes who underwent surgical lung biopsy, 444 were diagnosed as IIPs by a multidisciplinary discussion meeting via a cloud-based integrated database. Among these patients, 44 (9.9%) who had iNSIP and 21 (4.7%) with histopathologically-defined “NSIP with OP overlap” pattern (a pathological NSIP and OP pattern, but without a UIP pattern) were retrospectively studied. ResultsPatients with “NSIP with OP overlap” pattern showed a significantly greater extent of consolidation (p < 0.001), more subpleural ground glass attenuation (p = 0.036), and more peripheral + bronchovascular distribution (p = 0.009) on high-resolution computed tomography than those with iNSIP. The incidences of newly-developed CTDs during follow-up was similar between the groups and polymyositis/dermatomyositis was the most frequent CTD in both groups. Nearly half of the patients fulfilled IPAF criteria, but no significant difference was found between iNSIP and “NSIP with OP overlap” pattern (47.7% vs. 42.9, p = 0.712). The incidence of acute exacerbation and the survival rates were similar between the groups. ConclusionsThe incidence of “NSIP with OP overlap” pattern is 4.7% in IIPs. The frequency of newly-developed CTDs during follow-up, mainly polymyositis/dermatomyositis, the frequency of acute exacerbation, and the survival rate in “NSIP with OP overlap” pattern are similar to those of iNSIP.

Myositis-specific Antibodies Identify A Distinct Interstitial Pneumonia with Autoimmune Features Phenotype.

Interstitial pneumonia with autoimmune features (IPAF) characterises individuals with interstitial lung disease (ILD) and features of connective tissue disease (CTD) who fail to satisfy CTD criteria. Inclusion of myositis-specific antibodies (MSAs) in the IPAF criteria has generated controversy, as these patients also meet proposed criteria for an anti-synthetase syndrome. Whether MSAs and myositis associated antibodies (MAA) identify phenotypically distinct IPAF subgroups remains unclear.A multi-center, retrospective investigation was conducted to assess clinical features and outcomes in patients meeting IPAF criteria stratified by the presence of MSAs and MAAs. IPAF subgroups were compared to cohorts of patients with idiopathic inflammatory myopathy-ILD (IIM-ILD), idiopathic pulmonary fibrosis (IPF) and non-IIM CTD-ILDs. The primary endpoint assessed was three-year transplant-free survival. Two hundred sixty-nine patients met IPAF criteria, including 35 (13%) with MSAs and 65 (24.2%) with MAAs. Survival was highest among patients with IPAF-MSA and closely approximated those with IIM-ILD. Survival did not differ between IPAF-MAA and IPAF without MSA/MAA cohorts. Usual interstitial pneumonia (UIP) morphology was associated with differential outcome risk, with IPAF patients with non-UIP morphology approximating survival observed in non-IIM CTD-ILDs. MSAs, but not MAAs identified a unique IPAF phenotype characterised by clinical features and outcomes similar to IIM-ILD. UIP morphology was a strong predictor of outcome in others meeting IPAF criteria. Because IPAF is a research classification without clear treatment approach, these findings suggest MSAs should be removed from the IPAF criteria and such patients should be managed as an IIM-ILD.