Definite Usual Interstitial Pneumonia Pattern Research Articles

Assessment of quality of life in IPF Patients: a multicenter observational study.

This study aimed to examine how dyspnea, cough, sleep disruption, anxiety, depression, and physiological factors affect the quality of life in newly diagnosed, untreated IPF patients. This study is a multicenter observational study. Patients not receiving antifibrotic treatment were included. To assess patients' quality of life, Leicester Cough Questionnaire (LCQ), St. George's Respiratory Questionnaire (SGRQ), Short Form-36 (SF-36), Hospital Anxiety and Depression Scale (HADS), Borg Dyspnea Index (BDI), Modified Medical Research Council Dyspnea Scale (MMRC) score, Composite Physiological Index (CPI), Gender Age and physiology (GAP) score, and Pittsburgh Sleep Quality Index (PSQI) were administered. Among 88 patients (mean age: 67.6±8.5 years), 81.9% were diagnosed with IPF through HRCT, 14.8% through surgery, and 3.4% via cryobiopsy. The average disease duration was 2.2±2.9 years. Over 50% experienced moderate to severe depression, and 40% had moderate to severe anxiety. In the IPF group, 13.6% had possible usual interstitial pneumonia (UIP), and 81.8% had definite UIP pattern. No significant differences were found between UIP groups in various scores. Anxiety and depression correlated negatively with respiratory function and positively with MMRC score and BDI. Sleep quality scores had similar correlations. Patients with good sleep quality had better respiratory parameters (p=0.013), lower MMRC (p=0.004), BDI (p=0.026), and CPI (p=0.047). -Conclusion: A notable number of IPF patients in follow-up show symptoms of anxiety and depression. Moreover, declining respiratory function not only diminishes sleep quality but also elevates dyspnea scores.

Factors influencing long-term outcomes in fibrotic interstitial lung disease (F-ILD) diagnosed through multidisciplinary discussion (MDD): a prospective cohort study

BackgroundThe diagnostic process for fibrotic interstitial lung disease (F-ILD) is notably intricate, necessitating a multidisciplinary discussion to achieve consensus based on both clinical and radiological features. This study investigated the shared and distinctive long-term mortality predictors among the two primary phenotypes of F-ILD, namely idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD).MethodsWe included patients with F-ILD diagnosed from December 2018 to December 2019 and conducted follow-up assessments until February 2023. Age, gender, usual interstitial pneumonia (UIP) pattern, gender–age–physiology (GAP) score, modified Medical Research Council (mMRC) dyspnea score, antifibrotic agent use, pulmonary function test parameters, and six-minute walking test (6MWT) parameters were recorded at baseline and used as mortality predictors in a multivariate Cox regression model.ResultsWe enrolled 104 ILD patients. The survival rate of non-IPF patients was more than twice that of IPF patients (78.9% vs. 34%, p < 0.001), and the survival rate of patients with a GAP score of 0–2 was more than twice that of patients with a score of > 2 (93.2% vs. 36.6%, p < 0.001). Older age, male gender, definite UIP pattern, higher GAP score, higher mMRC dyspnea score, lower forced expiratory volume in one second/forced vital capacity (FEV1/FVC), shorter 6MWT distance, and lower initial and final SpO2 were also associated with higher long-term mortality (p < 0.05). In multivariable analysis, only a GAP score of > 2 (hazard ratio [HR]:16.7; 95% confidence interval [CI] 3.28–85.14; p = 0.001) and definite UIP pattern (HR: 4.08; 95% CI 1.07–15.5; p = 0.039) were significantly associated with overall mortality.ConclusionThe long-term mortality rate of IPF patients was higher than that of CTD-ILD patients. The GAP score and UIP patterns were significant mortality predictors for both IPF and CTD-ILD patients.

Periostin Is a Biomarker of Rheumatoid Arthritis-Associated Interstitial Lung Disease.

Periostin was investigated as a biomarker for rheumatoid arthritis-associated interstitial lung disease (RA-ILD). This prospective study measured serum monomeric and total periostin, Klebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), and lactate dehydrogenase (LDH) in 19 patients with RA-ILD, 20 RA without ILD, and 137 healthy controls (HC). All biomarkers were higher in RA-ILD than HC or RA without ILD. KL-6 accurately detected ILD in RA patients (area under curve [AUC] = 0.939) and moderately detected SP-D and monomeric and total periostin (AUC = 0.803, =0.767, =0.767, respectively). Monomeric and total periostin were negatively correlated with normal lung area and positively correlated with honeycombing, reticulation, fibrosis score, and the traction bronchiectasis grade but not inflammatory areas. Serum levels of SP-D, KL-6, and LDH did not correlate with the extent of those fibrotic areas on high-resolution CT. Serum monomeric and total periostin were higher in patients with RA-ILD with definite usual interstitial pneumonia pattern compared with other ILD patterns. Immunohistochemical analyses of biopsy or autopsy lung tissues from RA-ILD during the chronic phase and acute exacerbation showed that periostin was expressed in fibroblastic foci but not inflammatory or dense fibrosis lesions. Periostin is a potential biomarker for diagnosis, evaluating fibrosis, and deciding therapeutic strategies for patients with RA-ILD.

Incidence, risk factors, and prognosis of acute exacerbation of rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis

IntroductionAcute exacerbation (AE) is a devastating complication of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and leads to high mortality. This study aimed to investigate the incidence, risk factors, and prognosis of acute exacerbation of rheumatoid arthritis-associated interstitial lung disease (AE-RA-ILD).MethodsPubMed, EMBASE, Web of Science, and Medline were searched through 8 February 2023. Two independent researchers selected eligible articles and extracted available data. The Newcastle Ottawa Scale was used to assess the methodological quality of studies used for meta-analysis. The incidence and prognosis of AE-RA-ILD were investigated. Weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) and pooled odds ratios (ORs) with 95% CIs were calculated to explore the risk factors of AE in RA-ILD.ResultsTwenty-one of 1,589 articles were eligible. A total of 385 patients with AE-RA-ILD, of whom 53.5% were male, were included. The frequency of AE in patients with RA-ILD ranged from 6.3 to 55.6%. The 1-year and 5-year AE incidences were 2.6–11.1% and 11–29.4%, respectively. The all-cause mortality rate of AE-RA-ILD was 12.6–27.9% at 30 days and 16.7–48.3% at 90 days. Age at RA diagnosis (WMD: 3.61, 95% CI: 0.22–7.01), male sex (OR: 1.60, 95% CI:1.16–2.21), smoking (OR: 1.50, 95% CI: 1.08–2.08), lower forced vital capacity predicted (FVC%; WMD: −8.63, 95% CI: −14.68 to − 2.58), and definite usual interstitial pneumonia (UIP) pattern (OR: 1.92, 95% CI: 1.15–3.22) were the risk factors of AE-RA-ILD. Moreover, the use of corticosteroids, methotrexate, and biological disease-modifying anti-rheumatic drugs, was not associated with AE-RA-ILD.ConclusionAE-RA-ILD was not rare and had a poor prognosis. Age at RA diagnosis, male sex, smoking, lower FVC%, and definite UIP pattern increased the risk of AE-RA-ILD. The use of medications, especially methotrexate and biological disease-modifying anti-rheumatic drugs, may not be related to AE-RA-ILD.RegistrationCRD42023396772.

Predictors of progression in rheumatoid arthritis-associated interstitial lung disease: A single-center retrospective study from China.

Interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA) and is associated with high mortality, especially in progressive ILD. We aimed to identify predictors of disease progression in the early stages of ILD in a large sample of patients with RA. The medical records of 201 RA-ILD patients were retrospectively analyzed. According to changes in their pulmonary function tests, patients were divided into progressive disease and stable disease groups. Data were collected on clinical characteristics, laboratory findings, chest high-resolution computed tomography, and therapeutic agents. Univariate and multivariate analyses were performed to identify predictors of ILD progression. During a median follow up of 38 months, 105 (52.5%) patients were diagnosed with progressive ILD. These patients were mostly male, past or present smokers (P=0.028, P=0.021, respectively). Higher Health Assessment Questionnaire-Disability Index score and higher Disease Activity Score in 28 joints with erythrocyte sedimentation rate (DAS28-ESR) were observed in the ILD progression group (P=0.003, P < 0.001, respectively). There were no significant differences in baseline respiratory symptoms, pulmonary function, or laboratory features. Multivariate analysis indicated that high DAS28-ESR, definite usual interstitial pneumonia pattern, fibrosis score, and less use of cyclophosphamide were independent risk factors for RA-ILD progression. Fifteen (7.46%) patients died during the follow up, and the most frequent cause of death was lung infection. Our results suggested that high disease activity, definite usual interstitial pneumonia pattern, fibrosis score, and less use of cyclophosphamide at the onset of ILD may indicate the progression of ILD in RA patients.

Transbronchial lung cryobiopsy for the diagnosis of interstitial lung diseases.

Transbronchial lung cryobiopsy has shown promise in several studies in providing meaningful histological information in the multidisciplinary team diagnosis of fibrotic interstitial lung diseases. The purpose of this review is to describe recent literature providing support for the formal integration of cryobiopsy into the algorithm for interstitial lung disease diagnosis. Histopathological concordance between cryobiopsy and surgical biopsy and diagnostic agreement at multidisciplinary discussion have been reported good; furthermore, cryobiopsy may provide an increased diagnostic confidence to a level likely to influence management. Finally, although cryobiopsy is more likely to provide a probable usual interstitial pneumonia (UIP) pattern than a definite UIP pattern, given the limited sampling of sub-pleural lung parenchyma in most cases, finding of a probable UIP pattern at cryobiopsy samples is strongly predictive of a definite UIP pattern in the corresponding surgical biopsy and when a UIP pattern is found on cryobiopsy sample, this is associated with higher mortality compared with other histological patterns. Cryobiopsy is becoming a valid alternative to surgical lung biopsy for making histopathological diagnosis in patients with interstitial lung diseases of undetermined type in experienced centres, with standardized protocols, in order to have the best risks/diagnostic yields ratio.

Impact of Lung Biopsy Information on Treatment Strategy of Patients with Interstitial Lung Diseases.

Rationale: Lung biopsy (LBx) has a relevant role in the prediction of prognosis of interstitial lung diseases (ILDs), but its impact on the clinical management of patients remains unexplored. Objectives: This study evaluates whether LBx may change the therapeutic strategy and assesses the effect of diagnostic reclassification after LBx on long-term prognosis. Methods: We evaluated the LBx of 426 consecutive patients with ILDs, without a definite usual interstitial pneumonia pattern on high-resolution computed tomographic imaging. A total of 266 patients underwent transbronchial lung cryobiopsy (TBLC), and 160 patients underwent surgical lung biopsy (SLB). The multidisciplinary team (MDT) determined a diagnosis with high or low confidence, and a management strategy, both before and after the LBx data. Results: Final MDT diagnoses were 189 idiopathic pulmonary fibrosis (IPF), 143 non-IPF fibrotic ILDs, and 94 nonfibrotic ILDs. LBx data changed the management strategy in 145 cases (34%), with similar results for TBLC and SLB (the treatment strategy changed in 31.5% of TBLC cases, 84/266, P < 0.001, and in 38% of SLB, 61/160, P < 0.001). After LBx, the MDT was less inclined to "wait and see" (from 15% to 4% of cases, P < 0.001) or to prescribe steroids only (from 54% to 37%, P < 0.001) and was more confident to treat with antifibrotics (from 23% to 44%, P < 0.001) or immunosuppressive drugs (from 7% to 14%, P < 0.001). The therapeutic strategy changed in 70% of reclassified cases (60/85) and in 59% of cases in which LBx increased the MDT confidence (84/142). Reclassification significantly impacted the outcome. The cases classified as non-IPF by clinician and radiologist and then reclassified to be IPF after LBx showed a significantly worse survival compared with non-IPF confirmed cases (adjusted hazard ratio [HR], 3.8; 95% confidence interval [CI], 1.75-8.3); P = 0.001. Cases initially classified as IPF and then reclassified as non-IPF after LBx showed a better prognosis compared with IPF confirmed cases (HR, 0.41; 95% CI, 0.18-0.94; P = 0.03). Conclusions: Reclassification of cases with LBx data increased diagnostic confidence and changed the therapeutic strategy in one-third of cases. Pathologic reclassification of cases refined prognosis prediction. Patients classified as non-IPF by clinician and radiologist and then reclassified IPF after LBx had worse prognosis compared with the non-IPF confirmed cases.

Title: THE IMPACT OF THE ENVISIA GENOMIC CLASSIFIER IN THE DIAGNOSIS AND MANAGEMENT OF PATIENTS WITH INTERSTITIAL LUNG DISEASE

TOPIC: Diffuse Lung Disease TYPE: Original Investigations PURPOSE: The diagnosis of idiopathic pulmonary fibrosis (IPF), a progressive fibrosing ILD, remains challenging and often results in prolonged misdiagnosis associated with treatment delays and ultimately, poor outcomes. The diagnosis of IPF is based upon the presence of either a radiographic or histologic Usual Interstitial Pneumonia (UIP) pattern. The Envisia Genomic Classifier (EGC), a clinically validated molecular diagnostic test for UIP in transbronchial biopsies, was developed as a “rule in” test for UIP with high specificity. Here, we evaluate the impact of the EGC on physicians’ clinical decision-making for patients undergoing evaluation of ILD. METHODS: This prospective randomized decision impact survey included 11 patient ILD case studies from the BRAVE clinical sample collection study. Patient cases were included if they had an HRCT scan without a definite UIP pattern, an EGC UIP+ result, and underwent a multidisciplinary team discussion that resulted in a final diagnosis of IPF. HRCT patterns included 67 (43%) classified as probable UIP, 51 (33%) indeterminate for UIP and 37 (24%) inconsistent with UIP. A physician survey was designed to test the hypothesis that including an EGC UIP+ result will increase their number of correct IPF diagnoses, their associated confidence of this diagnosis and increase their recommendation to initiate anti-fibrotic therapy without obtaining a surgical lung biopsy (SLB) or cryobiopsy (Cryo). Physicians were first presented with the patients’ clinical information without Envisia (pre) and then with Envisia (post). RESULTS: 81 US-based pulmonologists provided survey responses. Overall, IPF diagnoses increased from 47 (30%) pre-Envisia to 107 (69%) post-Envisia. When stratified by HRCT pattern to include only those that were indeterminate or inconsistent for UIP, the number of IPF diagnoses increased from 4 (4.5%) pre-Envisia to 48 (54.5%) post-Envisia (Odds Ratio (OR)= 30.4, p < 0.001). Similarly, in cases with a probable UIP HRCT pattern, there was an increase in IPF diagnoses with Envisia (OR= 7.24, p < 0.001). High confidence (≥ 90%) of ILD diagnoses also increased from 5.8% to 42% with Envisia (p < 0.001). Recommendation for antifibrotic treatment increased from 15 (10%) pre-Envisia to 72 (46.4%) post-Envisia, while the recommendation for SLB or Cryo decreased with Envisia (OR = 0.48, p= 0.03). CONCLUSIONS: The Envisia Genomic Classifier had a significant impact on physicians’ decision-making for patients undergoing ILD evaluation by increasing the number of correct IPF diagnoses that were made with high confidence as well as increasing the recommendation for antifibrotic therapy. CLINICAL IMPLICATIONS: The Envisia Genomic Classifier has the potential to improve the outcome of IPF patients by facilitating an accurate IPF diagnosis and advancing earlier antifibrotic therapy. 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Several specific high-resolution computed tomography patterns correlate with survival in patients with idiopathic pulmonary fibrosis.

BackgroundEvidence of honeycombing in high-resolution computed tomography (HRCT) is a recognized risk factor for shortened survival in patients with idiopathic pulmonary fibrosis (IPF), but few studies have evaluated the feasibility of exploiting other specific patterns for predicting survival. The aim of this study was to examine the extent of specific HRCT patterns in IPF and determine whether they correlate with clinical features, pulmonary function tests (PFT), and survival.MethodsBoth the presence and extent of specific HRCT patterns, such as traction bronchiectasis, honeycombing, architectural distortion, reticulation, emphysema, and ground glass opacity, in 129 HRCT examinations were scored semi-quantitatively in three zones of each lung. HRCT examinations were also re-classified according to the 2011 and 2018 international statements. Correlations were calculated between the scores of specific HRCT patterns, clinical features, PFT, and patient survival.ResultsThe extent of traction bronchiectasis was found to be an independent risk factor of shortened survival (HR 1.227, P=0.001). Patients with a possible usual interstitial pneumonia (UIP) pattern had a better median survival than the patients with a definite UIP pattern (61 vs. 37 months, P=0.026). The extents of traction bronchiectasis, honeycombing, and architectural distortion displayed an inverse correlation with all PFT values at the time of diagnosis. There were few differences between the radiological classifications of the 2011 and 2018 international statements.ConclusionsWe conclude that several specific HRCT patterns displayed a correlation with shortened survival in IPF; these may help in evaluating the risk of death in IPF patients.

Prognostic value of transbronchial lung cryobiopsy for the multidisciplinary diagnosis of idiopathic pulmonary fibrosis: a retrospective validation study

Transbronchial lung cryobiopsy (TBLC) has been introduced recently in the diagnosis of interstitial lung diseases. We aimed to evaluate the prognostic significance of the distinction between idiopathic pulmonary fibrosis and other interstitial lung diseases with the use of TBLC data in multidisciplinary team (MDT) diagnosis. In this single-centre, retrospective, investigator-initiated comparative study, we evaluated consecutive patients without a definite usual interstitial pneumonia pattern on high-resolution CT, who presented to the GB Morgagni Hospital (Forlì, Italy), and who underwent TBLC (Jan 1, 2011, to Dec 31, 2014) or surgical lung biopsy (SLB; Jan 1, 2002, to Dec 31, 2016). Three pathologists reviewed the specimens, masked to clinical information. MDT evaluation was done before and after biopsy. The primary endpoint was the prognostic significance of the MDT diagnostic separation between idiopathic pulmonary fibrosis and other interstitial lung diseases in patients undergoing TBLC. Mortality was evaluated by means of Cox regression analysis. We evaluated 500 consecutive cases, 426 of which were included: 266 had TBLC and 160 had SLB. 189 patients had idiopathic pulmonary fibrosis, 143 had other fibrotic interstitial lung diseases, and 94 had non-fibrotic interstitial lung diseases. Patients undergoing TBLC had more comorbidities and better preserved lung function compared with those undergoing SLB; among patients with a final MDT diagnosis of idiopathic pulmonary fibrosis, patients undergoing TBLC were older, had more comorbidities, and had a different post-biopsy treatment profile than those who received SLB. The distinction between idiopathic pulmonary fibrosis and other interstitial lung diseases made by MDT diagnosis on the basis of TBLC biopsy had clear prognostic significance, with a 5-year transplant-free survival of 68% (95% CI 57-76) in patients with an MDT idiopathic pulmonary fibrosis diagnosis based on TBLC compared with 93% (87-96) in patients without an idiopathic pulmonary fibrosis diagnosis based on TBLC (hazard ratio 5·28, 95% CI 2·72-10·04; p<0·0001). This distinction remained statistically significant in a multivariate analysis controlling for age, sex, smoking status, comorbidities, pulmonary function, and high-resolution CT patterns (p=0·02). TBLC makes an important diagnostic contribution in interstitial lung disease, on the basis of the prognostic distinction between idiopathic pulmonary fibrosis and other interstitial lung diseases when TBLC findings are included in multidisciplinary diagnosis. None.

Quantitative CT analysis of honeycombing area predicts mortality in idiopathic pulmonary fibrosis with definite usual interstitial pneumonia pattern: A retrospective cohort study.

BackgroundHoneycombing on high-resolution computed tomography (HRCT) images is a key finding in idiopathic pulmonary fibrosis (IPF). In IPF, honeycombing area determined by quantitative CT analysis is correlated with pulmonary function test findings. We hypothesized that quantitative CT-derived honeycombing area (HA) might predict mortality in patients with IPF.Materials and methodsChest HRCT images of 52 IPF patients with definite usual interstitial pneumonia (UIP) pattern were retrospectively evaluated. Mortality data up to July 31, 2016, were recorded. Using a computer-aided system, HA and percentage of HA (%HA) were measured quantitatively. Predictors of 3-year mortality were evaluated using logistic regression models.ResultsThe median %HA, %predicted forced vital capacity (FVC) and composite physiologic index (CPI) were 3.8%, 83.6%, and 33.6, respectively. According to GAP (gender, age, and physiology) stage, 20, 14, and 5 patients were classified under stages I-II-III, respectively. Percentage of HA was significantly correlated with %FVC, CPI, and GAP stage (all, p < 0.001). In univariate analysis, %HA, %FVC, and CPI were statistically significant predictors of mortality. In multivariate analysis using the stepwise regression method, only %HA (odds ratio [OR], 1.27; p = 0.011) was a significant independent predictors of mortality. Patients with %HA ≥ 4.8% had significantly lower survival rates than those with lesser %HA (median survival time, 1.3 vs 5.0 years; log-rank test; p < 0.001).ConclusionQuantitative CT-derived HA might be an important and independent predictor of mortality in IPF patients with definite UIP pattern.

Spectrum of interstitial lung diseases at a tertiary center in a developing country: A study of 803 subjects.

BackgroundThe spectrum of interstitial lung diseases (ILDs) have mainly been reported from the developed countries; data from developing countries is sparse and conflicting. The aim of this study is to describe the distribution of various ILDs from a developing country.MethodsThis is an analysis of prospectively collected clinical, radiological and histological data of consecutive subjects (age >12 years) with ILDs from a single tertiary care medical center. The diagnosis of the specific subtype of ILD was made according to standard criteria for various ILDs.ResultsA total of 803 subjects (mean age, 50.6 years; 50.2% women) were enrolled between March 2015 to February 2017 of which 566 (70.5%) were diagnosed during the study period (incident cases). Sarcoidosis (42.2%), idiopathic pulmonary fibrosis (IPF, 21.2%), connective tissue disease (CTD)-related ILDs (12.7%), hypersensitivity pneumonitis (10.7%), and non-IPF idiopathic interstitial pneumonias (9.2%) were the most common ILDs. The spectrum of ILDs was not significantly different (p = 0.87) between incident and prevalent cases. A histopathological specimen was obtained in 49.9% of the subjects yielding a histologically confirmed diagnosis in 40.6%. A diagnostic procedure was not performed in 402 subjects; the most common reasons were presence of definite usual interstitial pneumonia pattern on high resolution computed tomography and patients’ unwillingness to undergo the procedure.ConclusionSarcoidosis, IPF and CTD-ILDs were the most common ILDs seen at a tertiary center in northern India similar to the spectrum reported from developed countries. More studies are required from developing countries to ascertain the spectrum of ILDs in different geographic locales.

Possible UIP pattern on high-resolution computed tomography is associated with better survival than definite UIP in IPF patients.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing lung disease of unknown etiology. Inter-society consensus guidelines on IPF diagnosis and management outline radiologic patterns including definite usual interstitial pneumonia (UIP), possible UIP, and inconsistent with UIP. We evaluate these diagnostic categories as prognostic markers among patients with IPF. Included subjects had biopsy-proven UIP, a multidisciplinary team diagnosis of IPF, and a baseline high-resolution computed tomography (HRCT). Thoracic radiologists assigned the radiologic pattern and documented the presence and extent of specific radiologic findings. The outcome of interest was lung transplant-free survival. IPF patients with a possible UIP pattern on HRCT had significantly longer Kaplan-Meier event-free survival compared to those with definite UIP pattern (5.21 and 3.57 years, respectively, p=0.002). In a multivariable Cox proportional hazards model adjusted for baseline age, gender, %-predicted FVC, and %-predicted DLCO via the GAP Stage, extent of fibrosis (via the traction bronchiectasis score) and ever-smoker status, possible UIP pattern on HRCT (versus definite UIP) was associated with reduced hazard of death or lung transplant (HR=0.42, CI 95% 0.23-0.78, p=0.006). Radiologic diagnosis categories outlined by inter-society consensus guidelines is a widely-reported and potentially useful prognostic marker in IPF patients, with possible UIP pattern on HRCT associated with a favorable prognosis compared to definite UIP pattern, after adjusting for relevant covariates.

The performance of the GAP model in patients with rheumatoid arthritis associated interstitial lung disease

BackgroundRheumatoid arthritis-associated interstitial lung disease (RA-ILD) is associated with significant morbidity and mortality. Similarities have been observed between patients with idiopathic pulmonary fibrosis (IPF) and the UIP (usual interstitial pneumonia) form of RA-ILD. The GAP (gender, age, physiology) model has been shown to predict mortality in patients with IPF, but its ability to predict mortality in RA-ILD is not known. MethodsWe identified 309 patients with RA-ILD at 4 academic centers with ongoing longitudinal cohorts of patients with ILD. The primary endpoint was mortality. To handle missing data (n = 219 subjects with complete dataset), multiple imputation by iterative chained equations was used. Using the GAP model as a baseline, we assessed improvements in mortality risk prediction achieved by incorporating additional variables. Model discrimination was assessed using the c-index, and calibration was checked by comparing observed and expected incidence of death. ResultsPatients had a mean age of 65 years and were predominantly female (54%). The mean forced vital capacity (FVC) % predicted was 73 and the mean diffusing capacity for carbon monoxide (DLCO) % predicted was 55. Twenty-four percent of the 236 patients with a high-resolution computed tomography scan available for review had a definite UIP pattern. The original GAP model, including gender, age, FVC%, and DLCO%, had a c-index of 0.746 in our cohort. Calibration of this model was satisfactory at 1, 2 and 3 years. Model discrimination was not meaningfully improved by adding other clinical variables. ConclusionThe GAP model that was derived for IPF performs similarly as a mortality risk prediction tool in RA-ILD.

Prevalence and characterization of non-sicca onset primary Sjögren syndrome with interstitial lung involvement.

Primary Sjögren syndrome (pSS)-related interstitial lung disease (ILD) involved about 10-20% of patients. In 20% of cases, ILD can be diagnosed before pSS; anyway, few studies have investigated the frequency of ILD as the first clinically relevant manifestation of pSS, generally referred to retrospective studies. Aim of our prospective study was to describe prevalence, clinical, serological, and instrumental features of non-sicca onset pSS patients with interstitial lung involvement. During a period of 48months, all consecutive patients diagnosed as pSS were enrolled. For all patients, the reason for the first visit was recorded. When present, ILD was categorized as definite, possible, or inconsistent with usual interstitial pneumonia (UIP) pattern, according to the current criteria. ILD was the main presenting symptom in 13/77 new diagnoses of pSS patients; in particular, 6/13 patients were initially diagnosed as idiopathic ILD, and only later developed clinical manifestations suggestive for pSS; ILD-pSS patients were older than others and showed a higher EULAR primary Sjögren's syndrome disease activity index. A radiologic definite or possible UIP pattern was detected in 12/13 pSS. For the first time, we prospectively observed a prevalence of 16.8% of non-sicca onset pSS patients with ILD. Interestingly, UIP pattern was the most frequently detected, while typical autoantibodies were often absent. These features stressed the importance of differential diagnosis in the first stage of the disease, considering the possible poorer prognosis in this subgroup of patients. Multidisciplinary approach is crucial for a correct and early diagnosis, at both onset and follow-up.

Agreement in the Diagnosis of an Usual Interstitial Pneumonia (UIP) Pattern on High Resolution Chest CT Between Chest Radiologists

SESSION TITLE: Imaging SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 26, 2016 at 01:30 PM - 02:30 PM PURPOSE: Current guidelines have proposed criteria to diagnose a Usual Interstitial Pneumonia (UIP) pattern on a High Resolution Computed Tomography (HRCT) of the chest and recommend that a definite UIP pattern on chest HRCT obviates the need of a biopsy. However, the criteria have not been prospectively validated. To our knowledge there has been no assessment of the agreement of a UIP pattern amongst chest radiologists. Our objective was to assess the agreement in the diagnosis of UIP between chest radiologists. METHODS: Two Chest Radiologists at a tertiary academic center in Canada (Kingston General Hospital) reviewed 117 good quality chest CT scans of patients with Interstitial Lung Diseases to determine the presence of a UIP pattern. As per the guidelines, Chest Radiologists diagnosed: 1) definite UIP; 2) possible UIP or 3) inconsistent UIP pattern. In addition, we assessed the agreement between them in the presence of reticulation and honeycombing. RESULTS: Agreement between chest radiologists in the diagnosis of definite UIP was 65% to 77%; for possible UIP was 31% to 60% and for inconsistent UIP pattern was 56% to 82% (Kappa 0.36; fair agreement). Agreement in the diagnosis of Reticulation was 50% to 96% (Kappa 0.65; substantial agreement) and in the diagnosis of Honeycombing was 71% to 91% (Kappa 0.64; substantial agreement. Agreement on the subpleural predominance of abnormalities was 46% to 94% (Kappa 0.04; slight agreement) and in the lower predominance of abnormalities was only 49% to 79% (Kappa 0.44; moderate agreement). CONCLUSIONS: The agreement in the diagnosis of UIP by chest radiologists using the criteria proposed by current guidelines is unsatisfactory in the real clinical setting. CLINICAL IMPLICATIONS: In clinical practice and using current guidelines, the diagnosis of a UIP pattern could vary considerably between chest radiologists. This could result in a significant variation on the number of patients “requiring” surgical biopsy to confirm the diagnosis of UIP. DISCLOSURE: The following authors have nothing to disclose: Katarina Janic, Robert Nolan, Rob Dhillion, Justin Flood, Muhannad Hawari, Angel Moran No Product/Research Disclosure Information

Clinical impact of high-attenuation and cystic areas on computed tomography in fibrotic idiopathic interstitial pneumonias.

BackgroundQuantitative computed tomography (CT) analysis has been proposed as a means of objectively assessing fibrotic interstitial pneumonia (IP) including idiopathic pulmonary fibrosis (IPF). We investigated whether percentages of high-attenuation areas (HAA%) and cystic areas (CA%) quantified from CT images were useful as indices of fibrotic IP.MethodsCT images of 74 patients with fibrotic idiopathic interstitial pneumonias (IPF, 36; non-specific interstitial pneumonia, 9; unclassifiable idiopathic interstitial pneumonia, 29) were analyzed via in-house computer software, which automatically calculated HAA%, CA%, mean lung density (MLD), standard deviation of lung density (SD-LD), kurtosis, and skewness from CT attenuation histograms. These indices were compared in each instance with physiologic measures, visual fibrosis score, clinical diagnosis, radiologic CT pattern, and prognosis.ResultsHAA% correlated significantly with physiologic measures and visual fibrosis score to a moderate extent (%forced vital capacity, rs = −0.59; % carbon monoxide diffusion capacity, rs = −0.43; fibrosis score, rs = 0.23). Densitometric parameters (MLD, SD-LD, kurtosis, and skewness) correlated significantly with physiologic measures and fibrosis score (|rs| = 0.28-0.59). CA% showed no association with pulmonary functions but differed significantly between IPF and other interstitial pneumonias (IPs) (1.50 ± 2.41 % vs. 0.41 ± 0.80 %; P < 0.01) and between the definite usual interstitial pneumonia (UIP) pattern and other patterns (1.48 ± 2.38 % vs. 0.55 ± 1.19 %; P < 0.01). On univariate analysis, HAA%, MLD, SD-LD, kurtosis, skewness, fibrosis score, and definite UIP pattern all correlated with survival, with kurtosis alone identified as a significant predictor of mortality on multivariate analysis (hazard ratio = 0.67; 95 % CI, 0.44-0.96; P = 0.03).ConclusionCA% and HAA% are novel quantitative CT indices with differing properties in fibrotic IP evaluations. HAA% largely reflects physiologic impairments, whereas CA% corresponds with diagnosis and HRCT pattern. Of the CT indices examined, kurtosis constituted the strongest predictor of mortality.

Early Experience of Pirfenidone in Daily Clinical Practice in Belgium and The Netherlands: a Retrospective Cohort Analysis.

IntroductionThis analysis aimed to investigate the effectiveness and safety profile of pirfenidone for the treatment of idiopathic pulmonary fibrosis (IPF) in clinical practice.MethodsClinical records of patients diagnosed with mild-to-moderate IPF (as per European Medicines Agency indication) and receiving pirfenidone treatment across three centers in Belgium and the Netherlands between April 2011 and October 2013 were retrospectively collected from patient notes at 3-month intervals. Pulmonary function measurements, including % predicted forced vital capacity (%FVC) and % predicted diffusing capacity of the lungs for carbon monoxide (%DLCO), were analyzed from 6 months prior to pirfenidone treatment up to 12 months of treatment. Decline in lung function, defined as an absolute ≥10% decline in FVC from baseline or death at 12 months, was also analyzed. Safety data were included for all follow-up visits.ResultsIn the pooled cohort (n = 63), patients were mostly men (84.1%) and current or former smokers (79.4%). Average baseline %FVC and %DLCO were 75.0% and 47.9%, respectively. 69.8% of patients had a high-resolution computed tomography scan with a definite usual interstitial pneumonia pattern, and 46% had a surgical lung biopsy. The mean decline in %FVC for 32 patients with available data was 4.8% from −6 months to baseline (p = 0.002) and 0.8% from baseline to 6 months (p = 0.516). Across these time intervals, a lesser decline in DLCO was similarly observed during therapy. At 12 months, ten patients had an %FVC decline ≥10% or died. Loss of appetite (25.3%) and nausea (11.1%) were the most frequent gastrointestinal side effects. Nausea was the most highly cited reason for discontinuation (7.9%).ConclusionsIn this clinical practice cohort, pirfenidone showed effectiveness and safety profiles consistent with those seen in the Phase III clinical study ASCEND (ClinicalTrials.gov #NCT01366209). These results highlight the challenges and benefits associated with pirfenidone treatment in clinical practice.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-015-0225-1) contains supplementary material, which is available to authorized users.

Reproducibility of the ATS/ERS classification of idiopathic interstitial pneumonias

Histopathological diagnosis of interstitial pneumonia (IP) requires experiences and is often challenging for general surgical pathologists. In its context, accurate recognition of histopathological usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP) patterns along with separation of idiopathic IPs from ones associated with hypersensitivity pneumonia and systemic connective tissue disease are the critical points. Several reports had indicated insufficient interobserver agreement of IP diagnosis, and we also have investigated the interobserver agreement of chronic interstitial pneumonia in various conditions showing that reproducibility of pathological judgment of above points was not greatest. To improve the reproducibility of diagnosis, recent publication of IPF guidelines set criteria of pathological UIP. It indeed helps pathologists to evaluate definite UIP pattern and works well for pulmonary pathologists, however, it still have some confusions and difficulties to the general surgical pathologists. In the course, summary of interobserver agreement along with our own data among pulmonary and general pathologists before and after the new guidelines will be shown. I will also share possible causes of confusion with audience and suggest a few tips for the improved histological assessment.

Rheumatoid Arthritis–associated Interstitial Lung Disease: Radiologic Identification of Usual Interstitial Pneumonia Pattern

To determine the accuracy of computed tomography (CT) in identifying the histopathologic usual interstitial pneumonia (UIP) pattern in rheumatoid arthritis-associated interstitial lung disease (RA-ILD). All patients were enrolled into institutional review board-approved longitudinal cohorts at their respective institution, and informed consent was obtained at the time of enrollment. Images of patients with surgical lung biopsy-proved RA-ILD (n = 69) were collected from three tertiary care centers. Two experienced thoracic radiologists independently reviewed the CT scans. The CT pattern was categorized as definite UIP, possible UIP, or inconsistent with UIP in accordance with published criteria. Findings of biopsies were reviewed by an experienced lung pathologist. The sensitivity and specificity of definite CT UIP pattern to histopathologic UIP pattern were determined. The agreement between radiologists was assessed by calculating a κ score. The histopathologic UIP pattern was present in 42 of 69 (61%) patients. Men were more likely than women to have a histopathologic UIP pattern (P = .02). Twenty patients (29%, 20 of 69) had a definite UIP pattern on CT scans. The specificity of CT UIP pattern was 96% (26 of 27; 95% confidence interval [CI]: 81%, 100%), with a negative predictive value of 53% (26 of 49). The sensitivity of CT UIP pattern was 45% (19 of 42; 95% CI: 30%, 61%), with a positive predictive value of 95% (19 of 20). The agreement between radiologists for definite UIP pattern versus not was 87% (κ = 0.67, P < .0001). Definite UIP pattern on a CT scan in RA-ILD is highly specific and moderately sensitive for histopathologic UIP pattern. CT can therefore help accurately identify the UIP pattern in RA-ILD.